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PUBMED

Biophysical chemistry

9652088

Calcium waves and oscillations driven by an intercellular gradient of inositol (1,4,5)-trisphosphate.

In response to a local mechanical stimulus, mixed glial cells initially exhibit a propagating intercellular Ca2+ wave. Subsequently, cells within a zone, at a specific distance from the stimulated cell, display asynchronous intracellular Ca2+ oscillations. The experimental hypothesis that the initial Ca2+ wave could be mediated by the passive diffusion of inositol (1,4,5)-trisphosphate (IP3) from the stimulated cell has been verified by model simulations. Further simulations with the same model also show that Ca2+ oscillations can only occur within model cells when the IP3 concentration is within a specific range. Thus, this passive diffusion model predicts (a) that the IP3 concentration gradient established in the cells following mechanical stimulation will initiate Ca2+ oscillations in cells in a specific zone along this gradient and (b) that different Ca2+ oscillatory patterns will occur within a specified oscillatory zone. Both of these predictions have been confirmed by experimental data. The failure of experimentally observed Ca2+ oscillations to approach synchrony or entrain indicates a low intercellular calcium permeability of about 0.1 micron/s, and further suggests that Ca2+ does not appear to act as a significant messenger in the initiation of these intercellular Ca2+ waves or oscillations. In conclusion a passive diffusion of IP3, but not Ca2+, through gap junctions remains the preferred hypothesis for the mechanism underlying mechanically-stimulated intercellular calcium waves and Ca2+ oscillations.

Sneyd J J; Wilkins M M; Strahonja A A; Sanderson M J MJ

1998-05-05

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Anatomia, histologia, embryologia

9652141

Histochemistry of complex carbohydrate in the major salivary glands of hoary bamboo rats (Rhizomys purinosus).

The major salivary glands (parotid glands, monostomatic sublingual glands and submandibular glands) were obtained from hoary bamboo rats (Rhizomys purinosus) and fixed in Bouin's solution. Paraffin sections were subjected to a battery of staining methods including lectin staining for demonstration of complex carbohydrates. Among the three major salivary glands, unique histochemical features were observed in the submandibular gland. Different from most myomorpha species, submandibular glands of the hoary bamboo rats have two types of secretory cells in the secretory endpieces. One type of cells showed positive reactions with Alcian blue (AB)(pH2.5), periodic acid-Schiff (PAS) and some lectins (peanuts agglutinin, Griffonia simplicifolia I, Maclura pomifera agglutinin). The granular ducts, which exist in animals belonging to suborder myomorpha, were not observed in the submandibular glands of this animal.

Kimura J J; Habata I I; Endo H H; Rerkamnuaychoke W W; Kurohmaru M M; Yamada J J; Nishida T T; Tsukise A A

1998-06-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Anatomia, histologia, embryologia

9652149

Distention of the lateral intercellular spaces (LIS) in the proximal tubule cells of the non-stenosed kidney of the 2K-1C Goldblatt model of hypertension as evidence of pressure diuresis.

This study shows the development of two major deformities in the non-stenosed kidney of the 2K-1C Goldblatt model; namely the widening of the LIS and the enlargement of the basilar interdigitations of the proximal tubule cells. These deformities were much less in the 2K-1C animals treated with the angiotensin I converting enzyme inhibitor (AICEI) cilazapril. From these findings it is suggested that the non-stenosed kidney is operating under the diuretic effect of the elevated systemic blood pressure (SBP) via an increase in the renal interstitial hydrostatic pressure (RIHP). Therefore, the AII antidiuretic effect is masked by the diuretic effect of the elevated SBP. The suggested rise in urine output fits well with the idea that kidneys lose water and sodium when SBP increases enormously. Therefore, in this model of hypertension, the non-stenosed kidney tries to lower SBP by losing water and sodium, an excretion behavior which is opposite to that of the stenosed kidney. Thus, the rise in SBP in this model is probably due to an increase in the vascular peripheral resistance rather than fluid accumulation.

al-Qattan K K KK; Safer A M AM; al-Hajri D K DK

1998-06-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Anatomia, histologia, embryologia

9652150

Regional peripheral vascular supply based on the superficial temporal artery in dogs and cats.

Cutaneous arterial blood supply to the temporal region was evaluated in 8 dogs and 8 cats. Subtraction radiography and angiography of the carotid and superficial temporal arteries were used in 4 dogs and 4 cats to determine arterial blood supply to the temporal region and frontalis muscle. A myocutaneous axial pattern flap based on the superficial temporal artery and frontalis muscle may be indicated for cosmetic reconstruction in dogs and cats following surgical resection of neoplastic lesions or traumatic wounds in the maxillofacial region. The frontalis muscle was identified as the thin subcutaneous continuation of the platysma muscle extending cranially and rostrally. Dissection of the temporal region in 4 dogs and 4 cats revealed the subcutaneous location of the superficial temporal artery as it continues rostrally from the caudal aspect of the zygomatic arch.

Fahie M A MA; Smith B J BJ; Ballard J B JB; Moon M L ML; Smith M M MM

1998-06-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

The Netherlands journal of medicine

9652156

The newly developed sulfonylurea glimepiride: a new ingredient, an old recipe.

Disturbances in insulin secretion and insulin action are both involved in the pathophysiology of type 2 (or non-insulin-dependent) diabetes mellitus. The newly developed sulfonylurea (SU) derivative glimepiride has a marked insulin secretory effect both in vitro and in vivo, and is capable of increasing plasma insulin levels with approximately 50% in type 2 diabetes subjects. Glimepiride improves metabolic control comparable but not superior to other (second generation) SU derivatives. Although it has been advocated for once-daily use, maximum effect is presumably achieved by twice-daily dosing. One of the most important side-effects of SU remains hypoglycemia in some patients, which may last for several hours. Although there is some indication that the use of glimepiride leads to fewer hypoglycemic episodes than glibenclamide, the differences reported sofar are not statistically significant.

Veneman T F TF; Tack C J CJ; van Haeften T W TW

1998-05-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Trends in pharmacological sciences

9652191

Adenosine A3 receptors: novel ligands and paradoxical effects.

The physiological role of the adenosine A3 receptor is being investigated using newly synthesized, selective ligands. Recently, in addition to agonists, selective antagonists have been developed that belong to three distinct, non-purine chemical classes: flavonoids, 1,4-dihydropyridine derivatives and the triazoloquinazolines. The A3 receptor has proven enigmatic in terms of antagonist ligand specificity, coupling to second messengers, and biological effects in the CNS, inflammatory system and cardiovascular system. A3 receptors are also potentially involved in apoptosis. It appears that intense, acute activation of A3 receptors acts as a lethal input to cells, while low concentrations of A3 receptor agonists protect against apoptosis. Here, Kenneth Jacobson describes how A3 receptor agonists might be useful in treating inflammatory conditions, possibly through their inhibition of tumour necrosis factor alpha (TNF-alpha) release, which has been shown in macrophages. A3 receptor antagonists might be useful in treating asthma or acute brain ischaemia. Recently, the versatility of A3 receptor agonists, administered either before or during ischaemia, in eliciting potent cardioprotection has been shown.

Jacobson K A KA

1998-05-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

International archives of allergy and immunology

9652308

Inhibition of neurotensin-stimulated mast cell secretion and carboxypeptidase A activity by the peptide inhibitor of carboxypeptidase A and neurotensin-receptor antagonist SR 48692.

BACKGROUND: Neurotensin. In the experiments described here, we tested for the involvement of CPA activity in the activation of mast cell secretion by the peptide, NT. METHODS: Mast cells were isolated from the peritoneal and pleural cavities of rats, purified over metrizamide gradients and incubated at 37 degrees C in Locke solution or Locke containing the appropriate inhibitors. For some experiments, media derived from mast cells stimulated by compound 48/80 were used as a source of mast cell CPA activity. RESULTS: Treatment of mast cells with the highly specific peptide inhibitor of CPA derived from potato (PCI) inhibited histamine release in response to NT and NT8-13 (the biologically active region of NT). This inhibition required some 20 min to develop and was only partially reversed by a 20-min wash period. PCI (10 microM) did not inhibit histamine release in response to NT1-12, bradykinin, compound 48/80, the calcium ionophore, A23187, or anti-IgE serum. PCI also inhibited mast cell CPA activity. SR 48692, a highly selective antagonist of the brain NT receptor and of NT-stimulated mast cell secretion, also inhibited mast cell CPA activity as well as bovine pancreatic CPA activity in a concentration-dependent manner. DISCUSSION: It is suggested that the mast cell binding site for NT and the active site for CPA may share similar characteristics. The results are discussed in terms of NT mechanism of action on the mast cell.

Miller L A LA; Cochrane D E DE; Feldberg R S RS; Carraway R E RE

1998-06-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Japanese circulation journal

9652319

Validity of a self-administered diet history questionnaire for assessment of sodium and potassium: comparison with single 24-hour urinary excretion.

We developed a self-administered diet history questionnaire (DHQ) for use in prevention and control of cardiovascular diseases and cancer, and validated it by comparison with single 24-h urinary excretion of sodium (Na) and potassium (K). The subjects were 154 male and 69 female freshmen university students. Mean intakes (mmol/day) assessed by DHQ and the urinary excretion of Na were 196 and 165 respectively for men and 179 and 136 respectively for women. Those of K were 61.5 and 43.9 respectively for men and 56.8 and 41.6 respectively for women. The ratios of urinary excretion to dietary intake of Na were 0.97 in men and 0.84 in women. Those of K were 0.78 in men and 0.80 in women. The results for both Na and K were reasonable, except for Na in men. When Pearson correlation was examined between dietary and urinary Na and K, no significant correlations for Na in men (r=0.14) or women (r=0.23, p=0.06), or significant correlations for K in men (r=0.34, p<0.001) or women (r=0.40, p<0.001) were observed. The results suggest a reasonable ability to estimate a subject mean for Na in women, K in both sexes, and individual level for K for both sexes. The validity for individual level for Na intake is not conclusive because the duration of urine collection was too short.

Sasaki S S; Yanagibori R R; Amano K K

1998-06-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Japanese circulation journal

9652321

Postrest shortening of the action potential duration in rabbits: in vitro and in vivo correlation.

Previous evidence has shown that the action potential duration of rabbit ventricular muscle cells shortens after a rest period (postrest shortening). However, there has not been much research on postrest shortening in the intact heart. We recorded transmembrane action potentials (TAPs) of isolated papillary muscle from rabbit ventricle with glass microelectrodes and monophasic action potentials (MAPs) of the rabbit left ventricular endocardium with contact electrodes. In the in vitro experiments, repetitive regular stimuli (S1) at a cycle length of 1 sec were followed by a single extrastimulus (S2) at coupling intervals (S1S2) ranging between 0.5 sec and 8 sec. The increase in the S1S2 interval resulted in a progressive shortening of the duration of TAP elicited by the S2, which was abolished by the simultaneous application of 1 mmol/L 4-aminopyridine and 2 micromol/L ryanodine. In the in vivo experiments, regular right ventricular pacing (S1) at a cycle length of 0.35 sec was followed by a single extrastimulus (S2) with coupling intervals (S1S2) ranging between 0.25 sec and 3 sec. The increase in the S1S2 interval also resulted in a progressive shortening of the duration of MAP elicited by the S2. This is the first report to demonstrate postrest shortening in the intact heart, which probably occurs because of a mechanism analogous to that observed in the isolated ventricular muscle.

Ishida S S; Takahashi N N; Saikawa T T; Iwao T T; Fujino T T; Nakagawa M M; Yonemochi H H; Ito M M

1998-06-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Japanese circulation journal

9652320

Doppler echocardiographic assessment and cardiac gene expression analysis of the left ventricle in myocardial infarcted rats.

The purpose of this study was to examine cardiac geometry and function by Doppler echocardiography and to analyze mRNA expression of cardiac phenotype and extracellular matrix in myocardial infarcted rats. Doppler echocardiograms and hemodynamics were measured 2 weeks after myocardial infarction (MI). mRNA levels in the non-infarcted left ventricle (LV) and infarct site were measured by Northern blot analysis. LV internal diastolic dimension was greater in infarcted (MI) than in sham-operated rats (control) (MI 7.2+/-0.3 mm vs control 4.6+0.3 mm, p<0.01). The fractional shortening decreased in MI rats (MI 32+4% vs control 61+/-3%, p<0.01). Peak early filling velocity increased in MI rats (MI 91+/-5 cm/sec vs control 72+/-4 cm/sec, p<0.05), and deceleration rate of the early filling wave was more rapid in rats with MI (MI 25.1+/-2.8 m/sec2 vs control 12.4+/-1.7 m/sec2, p < 0.01). Late filling velocity decreased (MI 16+/-3 cm/sec vs control 35+/-6 cm/sec, p <0.05), resulting in a marked increase in the ratio of early filling to late filling (MI 7.1+/-1.2 vs control 2.5+/-0.4, p<0.01). mRNA levels for beta-myosin heavy chain (beta-MHC), a-skeletal actin, atrial natriuretic polypeptide (ANP), collagen types I and III, and matrix metalloproteinase 2 (MMP-2) in the non-infarcted LV increased significantly by 1.8-, 2.4-, 4.7-, 2.6-, 2.1- (all p<0.01) and 1.4-fold (p<0.05), respectively, compared with sham-operated myocardium. In the infarct site, mRNA levels for transforming growth factor (TGF)-beta1, collagen types I and III, and MMP-2 significantly increased by 3.2-, 11.0-, 9.7-, and 6.3-fold (all p<0.01), respectively, compared with sham-operated myocardium. Myocardial infarcted rat was characterized by cavity dilation and marked abnormalities of systolic and diastolic function, accompanied by a shift of myocytes to fetal phenotype and activation of collagen genes in the non-infarcted myocardium.

Shimizu N N; Yoshiyama M M; Takeuchi K K; Hanatani A A; Kim S S; Omura T T; Iwao H H; Yoshikawa J J

1998-06-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Japanese circulation journal

9652322

Alterations in sarcoplasmic reticulum and angiotensin II type 1 receptor gene expression after myocardial infarction in rats.

The purpose of this study was to investigate the function of sarcoplasmic reticulum (SR) and the role of angiotensin II type 1 receptor (AT1) in ventricular remodeling in non-infarcted areas after myocardial infarction (MI). MI was produced in anesthetized Sprague-Dawley rats (10-12-weeks old) by ligation of the left anterior descending coronary artery. Four weeks after MI, hemodynamic measurements were performed. SR Ca2+-ATPase activity and mRNA (SERCA2a) and AT1 mRNA (AT1a, AT1b) were analyzed. Left ventricular end-diastolic pressure was higher and left ventricular dp/dt was significantly lower in the MI group. In non-infarcted areas in the MI group, myocardial transverse diameter was significantly greater and both Ca2+-ATPase activity in the SR and SERCA2a level decreased. The AT1a level was higher in non-infarcted areas than in controls, whereas the AT1b mRNA expression level was unchanged. These results suggest that, in the ventricular remodeling after MI, alterations in SR protein and its mRNA in non-infarcted myocardium help initiate heart failure and that Ca overload caused by the up-regulation of AT1a mRNA is an important cause of alteration in SR function.

Iijima K K; Geshi E E; Nomizo A A; Arata Y Y; Katagiri T T

1998-06-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652329

Tachykinin NK1 receptor antagonists enhance stress-induced c-fos in rat locus coeruleus.

These experiments tested the hypothesis that substance P neurotransmission at tachykinin NK1 receptors in the locus coeruleus is involved in stress-induced activation of the locus coeruleus, using c-fos as an index of activation. Selective tachykinin NK1 receptor antagonists administered systemically did not result in substantial locus coeruleus c-fos expression. Restraint stress resulted in a large number of locus coeruleus c-fos expressing cells. Administration of two selective tachykinin NK1 receptor antagonists prior to restraint resulted in an increase in the number of locus coeruleus c-fos expressing cells, compared to restraint alone. These results suggest that the enhanced c-fos expression observed in response to tachykinin NK1 receptor antagonists combined with stress, could be due to the blockade of tachykinin NK1 receptor-mediated activity at sites other than the locus coeruleus, resulting in an overall activation of the locus coeruleus.

Hahn M K MK; Bannon M J MJ

1998-05-08

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652331

Tension generation and increase in voltage-activated Na+ current by crotamine.

We performed the present experiments to study the action of crotamine, a toxin isolated from the venom of the South American rattlesnake, Crotalus durissus terrificus, on macroscopic Na+ currents in frog skeletal muscle by using the loose patch clamp technique. Crotamine at 50 microM increased the peak Na+ current by 50% (P < 0.05). In addition, the voltage dependence of inactivation was shifted by +8 mV. Other parameters of Na+ currents (reversal potential, voltage-dependence of activation and time courses of inactivation, of activation and of removal of inactivation) were not significantly affected. We suggest that crotamine inhibits the direct transition of channels from closed to inactivated states, thereby forcing their transition through the open states.

Matavel A C AC; Ferreira-Alves D L DL; Beirão P S PS; Cruz J S JS

1998-05-08

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652332

Bradykinin B2 receptors in nodose ganglia of rat and human.

The present study has employed in vitro electrophysiology to characterise the ability of bradykinin to depolarise the rat isolated nodose ganglion preparation, containing the perikarya of vagal afferent neurons. Both bradykinin and kallidin elicited a concentration-dependent (1-100 nM) depolarisation when applied to the superfusate bathing the nodose ganglia, whereas the bradykinin B1 receptor agonist, des-Arg9-bradykinin, was only effective in the micromolar range. Furthermore, the electrophysiological response to bradykinin was antagonised by the bradykinin B2 receptor antagonist, D-arginyl-L-arginyl-L-prolyl-trans-4-hydroxy-L-prolylglycyl-3-(2-t hienyl)-L-alanyl-L-seryl-D-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl+ ++-L-(2alpha,3beta,7abeta)-octahydro-1H-indole-2-carbonyl-L- arginine (Hoe 140), in a concentration-related manner. To determine the anatomical location of functional bradykinin B2 receptors, in vitro autoradiography withpara-iodophenyl Hoe 140 was performed on sections of rat and human inferior vagal (nodose) ganglia and confirmed the presence of binding over vagal perikarya. Collectively, these data provide evidence for functionally relevant bradykinin B2 receptors on vagal afferent neurons, which are apparently also present on human vagal perikarya.

Krstew E E; Jarrott B B; Lawrence A J AJ

1998-05-08

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652333

Effects of chylomicrons and chylomicron remnants on endothelium-dependent relaxation of rat aorta.

The effects of chylomicrons and chylomicron remnants on endothelium-dependent relaxation of rat aorta were studied in vitro. Chylomicrons and chylomicron remnants were prepared in vivo. Aortic rings were incubated with the lipoproteins for 45 min before the vessels were constricted with phenylephrine and concentration relaxation response curves constructed to carbachol, ATP, A23187 and S-nitroso-N-acetylpenicillamine. Maximum % relaxations to carbachol were significantly reduced by both chylomicrons and chylomicron remnants but responses to ATP and S-nitroso-N-acetylpenicillamine were unaffected. In addition, chylomicrons significantly inhibited A23187-induced relaxation, causing an increase in the EC50 value. Chylomicron remnants cause selective inhibition of carbachol-induced relaxation suggesting an action at the receptor or G protein-coupled component of the receptor-mediated activation of the L-arginine-nitric oxide pathway. Chylomicrons appear to be less selective in their inhibition of the endothelium-dependent relaxation. This study demonstrates that lipoprotein particles of dietary origin may cause endothelial cell dysfunction.

Grieve D J DJ; Avella M A MA; Botham K M KM; Elliott J J

1998-05-08

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652334

Central cardiovascular effects of tacrine in the conscious dog: a role for catecholamines and vasopressin release.

Centrally acting cholinergic agents are currently reported to increase blood pressure in various species through the stimulation of muscarinic cholinoceptors. Moreover, several cardiovascular adverse effects have been reported from clinical studies. The aim of this study was to investigate the effects of tacrine, an acetylcholinesterase inhibitor which has been reported to have therapeutic potential in Alzheimer's disease, on blood pressure and two vasopressor systems (sympathetic and vasopressinergic) in Beagle dogs. Intravenous (i.v.) tacrine (2 mg kg(-1)) induced, in conscious and anesthetized dogs, an increase in systolic and diastolic blood pressure, accompanied by bradycardia. This increase was dose-dependent with a peak effect at 1.5 min following administration. Tacrine also induced an increase in noradrenaline, adrenaline and vasopressin plasma levels. Pretreatment with the muscarinic receptor antagonist, atropine (2 mg kg(-1), i.v.), abolished the pressor response to i.v. injection of tacrine while pretreatment with the peripheral muscarinic receptor antagonist, methylscopolamine (0.2 mg kg(-1), i.v.), did not alter the increase in blood pressure. Similarly, noradrenaline and adrenaline changes in plasma levels were not modified by methylscopolamine but were abolished by atropine pretreatment. A similar tendency although not significant was observed for vasopressin plasma levels. The present results demonstrate that in dogs, tacrine (2 mg kg(-1), i.v.) stimulates central muscarinic cholinoceptors to increase blood pressure through activation of the two components of the sympathetic nervous system (that is, neuroneuronal noradrenergic and the neurohormonal adrenergic pathways) as well as through increasing noradrenaline, adrenaline and vasopressin plasma levels.

Allal C C; Lazartigues E E; Tran M A MA; Brefel-Courbon C C; Gharib C C; Montastruc J L JL; Rascol O O

1998-05-08

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652335

In vivo and in vitro action of endothelin-1 on goat cerebrovascular bed.

This study concerned the effects and mechanisms of action of endothelin-1 on the cerebral circulation. Cerebral blood flow was electromagnetically measured in awake goats. Endothelin-1, agonist for endothelin ET receptors, BQ-123-10, whereas IRL 1620 endothelin-1 produces cerebral vasoconstriction by activating endothelin ET(A) receptors probably located in smooth muscle; (2) endothelin ET(B) receptors, nitric oxide and prostanoids might be not involved in the cerebrovascular action of endothelin-1, and (3) endothelium removal may increase cerebrovascular reactivity by increasing sensitivity of endothelin ET(A) receptors to endothelin-1.

Fernández N N; Monge L L; García J L JL; García-Villalón A L AL; Gómez B B; Diéguez G G

1998-05-08

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652336

Cardiovascular effects of verapamil enantiomer combinations in conscious dogs.

We examined the systemic and coronary hemodynamic effects of five combinations of R- and S-verapamil enantiomers (R/S; 100/0, 90/10, 80/20, 50/50, and 20/80%, respectively) in conscious dogs chronically instrumented for measurement of aortic and LV pressure, +dP/dt, subendocardial segment length, coronary blood flow velocity, and aortic blood flow. Dogs received escalating doses (0.1, 0.2, and 0.4 mg kg(-1)) of each verapamil combination over 2 min at 30 min intervals on different experimental days and peak changes in hemodynamics were recorded 2 min after each dose. All verapamil combinations increased heart rate, mean aortic blood flow, and coronary blood flow velocity and decreased calculated systemic and coronary vascular resistance. Alterations in coronary hemodynamics were most pronounced with 20/80 R/S verapamil. Racemic and 20/80 R/S verapamil decreased mean arterial and left ventricular systolic pressure, in contrast to combinations with greater concentrations of the R enantiomer. Left ventricular function was unchanged during administration of 100/0, 90/10, and 80/20 R/S verapamil. Direct negative inotropic and lusitropic effects occurred with 50/50 and 20/80 R/S verapamil. The high dose of 20/80 R/S verapamil also increased left ventricular end-diastolic pressure and the regional chamber stiffness constant, consistent with diastolic dysfunction. The results indicate that combinations of R- and S-verapamil produce differential hemodynamic and left ventricular functional effects in conscious, unsedated dogs that are dependent on the relative ratio of these enantiomers.

Pagel P S PS; Hettrick D A DA; Lowe D D; Gowrie P W PW; Kersten J R JR; Bosnjak Z J ZJ; Warltier D C DC

1998-05-08

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652338

Cardioprotective effects of quinapril after myocardial infarction in hypertensive rats.

Although angiotensin-converting enzyme inhibitors are beneficial for patients with congestive heart failure, the appropriate timing and dosage in acute myocardial infarction are still controversial. We examined the hemodynamic effects of quinapril administered before acute myocardial infarction in spontaneously hypertensive rats (SHR). Quinapril (10 mg/kg per day in drinking water) was started 1 week before infarction and continued for 4 weeks after infarction (total duration 5 weeks). The hemodynamic parameters were evaluated by cardiac catheterization 4 weeks after coronary ligation. Sham-operated SHR served as controls. After infarction, left ventricular end-diastolic and right atrial pressures were increased (P < 0.01) and blood pressure and cardiac index were decreased (P < 0.01); the magnitude of blood pressure reduction was similar in the treated and untreated rats with infarction. Quinapril improved these hemodynamic parameters significantly and decreased left and right ventricular weight. These results suggest that a prior treatment with quinapril in SHR with acute myocardial infarction is hemodynamically beneficial.

Mori T T; Nishimura H H; Okabe M M; Ueyama M M; Kubota J J; Kawamura K K

1998-05-08

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652340

Nitric oxide enhances prostaglandin production in ethanol-induced gastric mucosal injury in rats.

The interaction between endogenous nitric oxide (NO), elicited by administration of Escherichia coli lipopolysaccharide, and cyclooxygenase system, in ethanol-induced injury in rat gastric mucosa, was investigated. Administration of graded doses of lipopolysaccharide reduced the gastric mucosal injury in response to ethanol. The ex vivo production of both nitrite and prostaglandin E2 was increased in dose-related manner by lipopolysaccharide. Pretreatment with dexamethasone, L-N6-(1-Iminoethyl)lysine(dihydrochloride) and L-NG-nitro arginine methyl ester inhibited the protection associated with lipopolysaccharide treatment and the ex vivo production of both, nitrite and prostaglandin E2. The pretreatment with L-arginine counteracted the decrease of nitrite and prostaglandin E2 production in lipopolysaccharide-treated rats in which nitric oxide synthesis was blocked by L-N6-(1-Iminoethyl)lysine(dihydrochloride). Administration of sodium nitroprusside and S-nitroso-N-acetyl-D,L-penicillamine caused a dose related enhancement in the accumulation of prostaglandin E2. Indomethacin administration and N-(2-Cyclohexyloxy-4-nitrophenyl)methanesulfonamide were ineffective in suppressing lipopolysaccharide-mediated protection against ethanol-induced damage, and in suppressing ex vivo increase of nitrite whereas the ex vivo increase of prostaglandin E2 was prevented in a dose-related fashion. These results indicate that in ethanol-induced rat gastric injury, endogenous NO elicited by lipopolysaccharide or released by NO donors is able to activate the cyclooxygenase pathway, and the protective effect of lipopolysaccharide is dependent upon NO formation.

Franco L L; Doria D D

1998-05-08

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652342

Pancreatic islet responsiveness to D-glucose after repeated administration of repaglinide.

The influence of three daily oral doses of repaglinide (1.0 microg/g body wt.) on plasma insulin and glucose concentrations, pancreatic islet insulin content and both protein biosynthesis and insulin release in isolated islets incubated for 90 min in the presence of either 2.8 or 16.7 mM D-glucose was examined in both control and hereditary diabetic Goto-Kakizaki (GK) rats. In the control rats, repaglinide lowered the plasma glucose concentration, whilst failing to affect significantly the plasma insulin concentration or insulin/glucose ratio, 24 h after the last administration of the antidiabetic agent. Despite a severe decrease of islet insulin content, the ratio between insulin release and content was not altered in islets obtained from repaglinide-treated control rats and incubated in the presence of 16.7 mM D-glucose. Also the biosynthesis of islet peptides was increased at both low and high hexose concentrations. In GK rats, repaglinide administration affected neither plasma glucose nor insulin concentration, restored a normal value for the otherwise abnormally high basal insulin output, increased the 16.7 mM/2.8 mM ratio for insulin release, and again augmented protein biosynthesis at both low and high hexose concentrations. In both control and GK rats, the stress induced by bleeding and decapitation augmented plasma glucose concentration. This effect was more pronounced in GK than in control rats and, in the diabetic animals, coincided with a severe lowering of the plasma insulin/glucose ratio, suggesting a higher adrenergic sensitivity of islet cells in the GK than in control rats. The increased secretory responsiveness to glucose and increased biosynthetic activity found in islets from GK rats after repaglinide administration, are considered favourable attributes of this meglitinide analogue in the perspective of its use as an insulinotropic agent in noninsulin-dependent diabetes.

Laghmich A A; Ladrière L L; Malaisse-Lagae F F; Malaisse W J WJ

1998-05-08

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652345

Characterization of specific binding ofL-762,459, a selective alpha1A-adrenoceptor radioligand to rat and human tissues.

L-762,459-2-((2-aminoethyl)oxy)methyl-5-carboxamido-6-ethyl-4-(4-nitropheny l)-3-N-(3-(4,4-diphenylpiperidin-1-yl)propyl)carboxamido-1,4-dihyd ropyridine hydrate (0.5-4.8)]. The results were consistent with the selective binding ofL-762,459 to the alpha1A-adrenoceptor. The specific labeling of the alpha1A-adrenoceptor subtype byL-762,459 may make it a useful tool to localize the distribution of the alpha1A-adrenoceptor.

O'Malley S S SS; Chen T B TB; Francis B E BE; Gibson R E RE; Burns H D HD; DiSalvo J J; Bayne M L ML; Wetzel J M JM; Nagarathnam D D; Marzabadi M M; Gluchowski C C; Chang R S RS

1998-05-08

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652347

Endothelin-1-(1-31), a novel vasoactive peptide, increasesi in human coronary artery smooth muscle cells.

We have previously found that human chymase cleaves big endothelins at the Tyr31-Gly32 bond and produces 31-amino acid long endothelins-(1-31), without any further degradation products. In this study, we investigated the effect of synthetic endothelin-1-(1-31) on the intracellular free Ca2+ concentration (i) in cultured human coronary artery smooth muscle cells. Endothelin-1-(1-31) increasedi in a concentration-dependent manner (10(-14) to 10(-10) M). This endothelin-1-(1-31)-inducedi increase was not affected by phosphoramidon (N-(alpha-Rhamnopyranosyloxyhydroxyphosphinyl)-L-Leucyl-L-Tryptoph an), an inhibitor of endothelin-converting enzyme. It was, however, inhibited by 10(-10) M BQ123 (Cyclo-(-D-Trp-D-Asp(ONa)-Pro-D-Val-Leu-)), an endothelin ET(A) receptor antagonist, but not by 10(-10) M BQ788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-yMeLeu-D-Trp(COOM e)-D-Nle-ONa), an endothelin ET(B) receptor antagonist. These results suggest that endothelin-1-(1-31) by itself exhibits vasoactive properties probably through endothelin ET(A) receptors. Since human chymase has been reported to play a role in atherosclerosis, endothelin-1-(1-31) may be one of the candidate substances for its cause.

Yoshizumi M M; Inui D D; Okishima N N; Houchi H H; Tsuchiya K K; Wakabayashi H H; Kido H H; Tamaki T T

1998-05-08

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652350

Identification of adenylyl cyclase isoenzymes in CHO and B82 cells.

The identification of adenylyl cyclase isoenzymes in mammalian host cells is important for the interpretation of data obtained from cell lines heterologously expressing G-protein coupled receptors. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to amplify adenylyl cyclase cDNAs from Chinese hamster ovary (CHO) and mouse fibroblast (B82) cells. The isolated fragments were identified by restriction analyses and by sequencing. We found mRNAs for adenylyl cyclases VI and VII in CHO and adenylyl cyclases IX and VII in B82 cells.

Varga E V EV; Stropova D D; Rubenzik M M; Wang M M; Landsman R S RS; Roeske W R WR; Yamamura H I HI

1998-05-08

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652354

Temporal dependent neuroprotection with propentofylline (HWA 285) in a temporary focal ischemia model.

Propentofylline (HWA 285, 3-methyl-1-(5-oxo-hexyl)-7-propylxanthine) is an adenosine uptake and phosphodiesterase inhibitor that has been shown to be neuroprotective in both global and permanent focal ischemia animal models. However, to date, the efficacy of propentofylline has never been examined in an animal model of temporary focal ischemia or the 'therapeutic window' systematically examined in a focal ischemia model. The present experiments were designed to investigate these. Temporary (3 h) middle cerebral artery occlusion was accomplished by the monofilament method. Infarct volumes were determined at 24 h from 2,3,5-triphenyltetrazolieum chloride (TTC) stained coronal slices. Animals were dosed with vehicle or propentofylline at 3 mg/kg bolus and/or a 6 mg/kg per h infusion (24 h infusion) at 30 min, 1 h or 3 h post ischemia onset. Physiological monitoring on a subset of animals indicated no changes in mean arterial pressure, blood gases, blood pH, and glucose levels with either ischemia or drug treatment. Propentofylline treatment resulted in a statistically significant decrease in infarct volume when an infusion dose of 6 mg/kg per h was initiated at 30 min or when a bolus of 3 mg/kg plus an infusion dose was initiated at 1 h but not 3 h post ischemia. Therefore, propentofylline is neuroprotective in a model of temporary focal ischemia. This suggests that combination therapy with propentofylline might lead to clinical improvement beyond that which would occur with thrombolytics alone. The apparent short window of opportunity for effective dosing is consistent with the proposed mechanism of action for propentofylline.

Johnson M P MP; McCarty D R DR; Chmielewski P A PA

1998-04-10

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652356

Modulatory effect of bradykinin on noradrenaline release in isolated atria from normal and B2 knockout transgenic mice.

The modulatory effect of bradykinin on electrically-induced noradrenaline release was assessed in isolated atria from normal and B2 knockout transgenic mice preincubated withnoradrenaline. Concentrations of 1, 3 and 10 nM of bradykinin did not significantly alter the outflow of radioactivity whereas higher concentrations of bradykinin (30 and 100 nM) enhanced it. The facilitatory effect of 30 nM bradykinin was inhibited by a selective bradykinin B2 receptor antagonist. Hoe 140 (D-Arg-bradykinin, 30 nM), and by a protein kinase C inhibitor, bisindolylmaleimide (1 microM). The co-administration of bradykinin (1 to 100 nM) with eitherdes-Arg9-bradykinin (100 nM), AcLysdes-Arg9-bradykinin (30 nM) (bradykinin B1 receptor antagonists) or diclofenac (1 microM) (a cyclooxygenase inhibitor), shifted the facilitatory effect of bradykinin to lower concentrations. The facilitatory effect of bradykinin also was enhanced by enalaprilat (1 microM) and mergetpa (1 microM), inhibitors of angiotensin-converting enzyme (kininase II) and kininase I, respectively. In contrast, selective bradykinin B1 receptor agonists, des-Arg9-bradykinin (1 to 100 nM) and Sardes-Arg7-bradykinin (1 to 100 nM), did not significantly affect the stimulation-induced outflow of radioactivity. Neither bradykinin (100 nM) nor des-Arg9-bradykinin (100 nM) had any modulatory effect in B2 knockout transgenic mice. These findings suggest that the facilitatory effect of bradykinin on noradrenaline release in the mouse atria is mediated exclusively by presynaptic bradykinin B2 receptors which are linked to protein kinase C. The greater release of noradrenaline with bradykinin under inhibition of prostaglandins production and kininases I and II activity might be of importance in pharmacotherapies.

Chulak C C; Couture R R; Foucart S S

1998-04-10

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652363

The role of P-selectin, sialyl Lewis X and sulfatide in myocardial ischemia and reperfusion injury.

The role of P-selectin and the ligands of selectins such as sialyl Lewis X and sulfatide was studied in a myocardial ischemia and reperfusion injury model. Anesthetized rabbits underwent the occlusion of coronary artery (30 min) followed by reperfusion (5 h). The inhibitory effect on myocardial ischemia and reperfusion injury was examined with infarct size normalized by area-at-risk. Intravenous administration of an anti-P-selectin monoclonal antibody, PB1.3 (2 mg/kg), reduced infarct size by 38%. Similarly, the administration of sialyl Lewis X-oligosaccharide (10 mg/kg) reduced infarct size by 53% significantly. Finally, the infarct size was significantly reduced bv 39% in sulfatide-treated group (10 mg/kg). These results suggest that P-selectin plays an important role in myocardial ischemia and reperfusion injury and that the ligands of selectins, such as sialyl Lewis X-oligosaccharide and sulfatide, have cardioprotective effect on myocardial ischemia and reperfusion injury.

Yamada K K; Tojo S J SJ; Hayashi M M; Morooka S S

1998-04-10

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652365

Effects of 2,5-di-t-butyl-1,4-benzohydroquinone (BHQ) on rat aorta smooth muscle.

To characterise the pharmacological activity of 2,5-di-t-butyl-1,4-benzohydroquinone or by increasing extracellular Ca2+ concentration. In the presence of nifedipine and Ni2+, depolarised rings (80 mM K+) contracted in response to addition of 1 microM phenylephrine; this response was fast and then slowly decreased. When the preparations were preincubated with BHQ, the phenylephrine-induced contraction was transient and antagonised in a concentration-dependent manner by BHQ. These results indicate that the myotonic effect of BHQ on rat aortic rings depends on activation of Ca2+ influx via a Ni2+-sensitive pathway, whereas its myolytic activity is due either to antagonism of Ca2+ entry via L-type Ca2+ channels or depletion of intracellular Ca2+ stores.

Fusi F F; Gorelli B B; Valoti M M; Marazova K K; Sgaragli G P GP

1998-04-10

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652367

Effects of K+ channel inhibitors on the basal tone and KCl- or methacholine-induced contraction of mouse trachea.

The present study examined the effects of K+ channel inhibitors on the basal tone and on KCl- or methacholine-induced contraction of the mouse-isolated trachea. Glibenclamide and iberiotoxin, procaine, quinine and tetraethylammonium did not induce any contraction of the indomethacin-treated mouse trachea. 4-Aminopyridine induced concentration-dependent contraction. This action of 4-aminopyridine was abolished by atropine and reduced by tetrodotoxin and nifedipine. Glibenclamide failed to modify KCl- or methacholine-induced contraction. Iberiotoxin and 4-aminopyridine potentiated KCl- and methacholine-induced contractions. Nifedipine, procaine, quinine and tetraethylammonium inhibited KCl- and methacholine-induced contractions. These data suggest that the closure of large Ca2+-dependent K+ channels can potentiate KCI- and methacholine-induced contraction. The effects of 4-aminopyridine on the mouse trachea reflect chiefly activation of muscarinic receptors. Procaine, quinine and tetraethylammonium inhibit depolarization-induced and receptor-mediated contractions of the mouse-isolated trachea.

Li L L; Paakkari I I; Vapaatalo H H

1998-04-10

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652372

Cloning, sequencing and functional expression of a guinea pig lung bradykinin B2 receptor.

Kinin receptors are classified as B1 and B2 based upon agonist and antagonist potencies and cloning and expression studies. Using sequences from human and rat bradykinin B2 receptors, polymerase chain reaction (PCR) was utilized to isolate cDNA from guinea pig lung. The receptor obtained is predicted to have 372 amino acids and shares > 80% sequence homology with human, rat, rabbit and mouse B2 receptors. In competition binding experiments in Chinese hamster ovary (CHO-K1) cells in which the guinea pig cDNA was expressed,bradykinin was displaced by kinin receptor ligands with an order of potency consistent with a B2 subtype. In CHO cells expressing the guinea pig receptor, bradykinin caused a concentration 45Ca2+ efflux. A B1 receptor agonist, desArg9-bradykinin, also caused 45Ca2+ efflux but with a potency several orders of magnitude lower than bradykinin. Curiously, several B1 and B2 receptor antagonists induced 45Ca2+ efflux, indicating that this receptor may be coupled differently in CHO cells than in native tissues.

Farmer S G SG; Powell S J SJ; Wilkins D E DE; Graham A A

1998-04-10

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652370

L-arginine and NG-nitro-L-arginine methyl ester cause macromolecule extravasation in the microcirculation of awake hamsters.

We investigated the effects of L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) on macromolecule extravasation in the microcirculation of awake hamsters by computer-assisted image analysis of the distribution of FITC (fluorescein isothiocyanate)-dextran fluorescence in dorsal fold skin preparations. This analysis made it possible to simultaneously study the time course of local (skin) and general (all irrigated organs) extravasation in 180-min experiments. Bolus injection of 30 or 150 mg/kg (i.v.) L-arginine induced immediate local and general macromolecule leakage and delayed venule dilation beginning 1 h later. Injection of 20 or 100 mg/kg (i.v.) L-NAME caused rapid venule constriction followed by local and general extravasation beginning 45-60 min later. These effects of L-arginine and L-NAME were not mimicked by their biologically inactive isomers, D-arginine and D-NAME. Simultaneous bolus injection of 20 mg/kg L-NAME and 150 mg/kg L-arginine caused no significant change in fluorescence distribution or venule diameter. L-arginine effects on macromolecule extravasation were mimicked by sodium nitroprusside (10 microg/kg, i.v.) and by 8-bromo-cGMP (1 mg/kg, i.v.). Sodium nitroprusside was ineffective on venule diameter. The effects of both L-arginine and sodium nitroprusside on FITC-dextran extravasation were prevented by simultaneous injection (10 microg/kg, i.v.) of the specific inhibitor of the soluble guanylate cyclase, 1H-oxadiazoloquinoxalin-1-one (ODQ). This dose of ODQ mimicked the effects of L-NAME on macromolecule extravasation and venule diameter. Taken together, these results suggest that activation or inhibition of basal NO synthesis might induce macromolecule leakage in the microcirculation of awake hamsters via temporally distinct cGMP-dependent mechanisms.

Gimeno G G; Carpentier P H PH; Desquand-Billiald S S; Hanf R R; Finet M M

1998-04-10

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652374

Inhibition by taurine of the inwardly rectifying K+ current in guinea pig ventricular cardiomyocytes.

Effects of taurine on the inwardly rectifying K+ current (IK1) in isolated guinea pig ventricular cardiomyocytes were examined using patch voltage-clamp methods. All experiments were performed at 36 degrees C. Taurine (10-20 mM) increased the action potential duration, but failed to affect the resting potential. Holding potential was maintained at -30 mV. The current was activated with an inwardly going rectification, and was completely blocked by Ba2+ (2 mM). Taurine inhibited IK1 at - 120 mV by 28.3+/-1.1% (n=6, P < 0.05) at 10 mM and by 36.0+/-2.1% (n=6, P < 0.01) at 20 mM. The reversal potential was shifted in the hyperpolarizing direction by 3.7+/-0.6 mV (n=6) at 20 mM. In inside-out patch-clamp experiments, the amplitude of unitary channels was -2.7+/-0.3 pA (n=21) at -90 mV. Symmetrical high-K+ (150 mM) solutions in both bath and pipette were used. The channel conductance was 32+/-2 pS (n=9). Taurine did not affect channel conductance, but markedly decreased the open probability at - 120 mV of channel by 21.5+/-2.4% (n=8, P < 0.01) at 10 mM, and by 56.7+/-3.8% (n=8, P < 0.001) at 20 mM. These responses were almost reversible. These results suggest that taurine directly modulates the open probability of the inwardly rectifying K+ current, resulting in regulation of the functions of heart cells.

Satoh H H

1998-04-10

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652376

Muscarinic cation current and suppression of Ca2+ current in guinea pig ileal smooth muscle cells.

Cationic current (Icat) and inhibition of the voltage-dependent Ca2+ current (ICa) evoked by muscarinic receptor activation with carbachol were studied using whole-cell patch clamp technique in smooth muscle cells isolated from longitudinal muscle of guinea pig small intestine. With low buffering ofi (0.1 mM BAPTA in pipette solution) Icat and ICa inhibitory responses had a rapid onset to an initial peak followed by a sustained phase. The sustained phase of ICa suppression was bigger than in the case wheni was clamped to 100 nM, but decreased with repeated stimulation. Upon repeated stimulation with 50 microM carbachol in cells wherei was clamped to 100 nM and when GTP was absent, Icat amplitude decreased strongly and more substantially compared to ICa inhibition, but both responses declined only slightly when 1 mM GTP was present in the pipette solution. GDP-betaS (1 or 5 mM) in pipette solution or pre-treatment of cells with pertussis toxin (6 microg/ml, for 4 h or longer) blocked Icat more than ICa suppression by carbachol, whereas L-NAME (N-omega-nitro-L-arginine methyl ester hydrochloride) (100 microM in pipette solution) affected neither of them significantly. We conclude that the cationic current and the suppression of the voltage-dependent Ca2+ current evoked by muscarinic receptor activation are mediated by pertussis toxin-sensitive G-protein(s) but the latter response was less sensitive to blockade by GDP-betaS and to GTP deficiency in the cell.

Pucovský V V; Zholos A V AV; Bolton T B TB

1998-04-10

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of pharmacology

9652378

Effect of adenosine receptor agonists on release of the nucleoside analogueformycin B from cultured smooth muscle DDT1 MF-2 cells.

Adenosine has receptor-mediated effects in a variety of cell types and is predominantly formed from ATP by a series of nucleotidase reactions. Adenosine formed intracellularly can be released by bidirectional nucleoside transport processes to activate cell surface receptors. We examined whether stimulation of adenosine receptors has a regulatory effect on transporter-mediated nucleoside release. DDT1 MF-2 smooth muscle cells, which possess nitrobenzylthioinosine-sensitive (ES) transporters as well as both adenosine A1 and A2 receptors, were loaded with the metabolically stable nucleoside analogueformycin B. N6-cyclohexyladenosine (CHA), a selective adenosine A1 receptor agonist, produced a concentration-dependent inhibition offormycin B release with an IC50 value of 2.7 microM. Further investigation revealed CHA interacts directly with nucleoside transporters with a Ki value of 3.3 microM. Neither 5'-N-ethylcarboxamidoadenosine (NECA), a mixed adenosine A1 and A2 receptor agonist, nor CGS 21680, a selective adenosine A2A receptor agonist, affected nucleoside release. We conclude that release of the nucleoside formycin B from DDT1 MF-2 cells is not regulated by adenosine A1 or A2 receptor activation.

Borgland S L SL; Parkinson F E FE

1998-04-10

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of biochemistry

9652388

The Ulip family phosphoproteins--common and specific properties.

The search for intracellular phosphoproteins implicated in the regulation of neuronal differentiation led to the identification of Ulip1, a mammalian protein related to the Caenorhabditis elegans unc-33 gene product. The expression level and phosphorylation pattern of Ulip1 were shown to be strongly regulated during development and neuronal differentiation. We have isolated three additional complete coding sequences for members of the Ulip family in the mouse, Ulips 2-4, all preferentially expressed in the nervous system. Furthermore, two Ulip sequences, Ulips A and Ulips B, could be identified in C. elegans. The Ulip family is highly conserved throughout evolution (more than 96 % for Ulips 1-3 and 92.5 % for Ulip4 between mouse and human) and the various members of the family within a single species display about 75% similarity. Sequence comparisons further reveal several highly similar domains and subdomains, including a 32-amino-acid region highly conserved from a bacterial hydantoinase to human Ulips. Two-dimensional immunoblot analysis of in vitro translated Ulips 1-4 demonstrates the existence, for each Ulip protein, of several, most probably differentially phosphorylated forms, in agreement with the presence of conserved phosphorylation consensus sites within their sequences. The expression of Ulips 1-4 mRNAs is differentially regulated during development and nerve-growth-factor-induced neuronal differentiation of PC12 cells. Our results indicate a differential, possibly complementary role of phosphoproteins of the highly conserved Ulip family in the control of neuronal differentiation, in relation with the development and plasticity of the nervous system.

Byk T T; Ozon S S; Sobel A A

1998-05-15

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of biochemistry

9652395

A pancreas-specific glycosylated protein disulphide-isomerase binds to misfolded proteins and peptides with an interaction inhibited by oestrogens.

Using a cross-linking approach, we have demonstrated that radiolabeled model peptides or misfolded proteins specifically interact in vitro with two different luminal proteins in a crude extract from sheep pancreas microsomes. One of the proteins was identified as protein disulphide-isomerase (PDI), the other one was a related protein (PDIp). We have shown that PDIp was expressed exclusively in the pancreas. Interspecies conservation of PDIp was confirmed and, unlike other members of the PDI family, PDIp from various sources was found to be a glycoprotein. PDIp interacted with peptides and also a misfolded protein, but not with native proteins, suggesting that it might act as a molecular chaperone. The initial binding process was independent of the presence of Cys residues in the probed peptides. Certain oestrogens strongly inhibited the interaction between peptides and PDIp, with 17beta-oestradiol being the most potent inhibitor.

Klappa P P; Stromer T T; Zimmermann R R; Ruddock L W LW; Freedman R B RB

1998-05-15

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of biochemistry

9652401

Sequence and structure of the human 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase heart isoform gene (PFKFB2).

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) is a bifunctional enzyme that catalyzes the synthesis and degradation of Fru-2,6-P2, a key regulator of glycolysis. In mammals, several genes have been found to code for different PFK-2/FBPase-2 isoforms that differ in tissue distribution and enzymatic activities. In the present study, we report the characterization of the PFK-2/FBPase-2 heart isoform gene in humans (PFKFB2), including a full analysis of repetitive sequences and potential transcription binding sites. The genomic sequence of the PFKFB2 gene spans 22,485 bp and contains 15 exons. Heart cDNA analysis shows that PFKFB2 codes for a protein of 505 amino acids with a deduced molecular mass of 58,849 Da. Comparison of the human PFKFB2 gene to the homologous genes in rat and ox outlines a significant conservation of the intron-exon structure, sequence of 5' and 3' flanking regions, and simple sequence repetitive element positions. Most important, the human heart PFK-2/ FBPase-2 protein was found to retain all the important regulatory sites, as well as the catalytic and substrate binding sites identified in the rat and bovine heart isoforms, suggesting that the human enzyme is regulated in a manner similar to that observed in these organisms.

Heine-Suñer D D; Díaz-Guillén M A MA; Lange A J AJ; Rodríguez de Córdoba S S

1998-05-15

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of biochemistry

9652404

Primary structure and high expression of human agrin in basement membranes of adult lung and kidney.

Agrin is a heparan sulfate proteoglycan involved in the development of the neuromuscular junction during embryogenesis. In addition to this well-characterized function, agrin may have additional functions in other tissues and during other stages in development. In this study we present the cDNA sequence of human agrin, and demonstrate a high agrin content in adult basement membranes. The N-terminal domain of human agrin is highly similar to that of chick agrin, suggesting a similar function in laminin binding. The presence of three SGXG sequences supports serine-linked glycosylation of the core protein, two sites being particularly favorable for heparan sulfate attachment. Comparison of levels of agrin mRNA in fetal and adult human tissues showed a remarkable upregulation in adult kidney and lung. In both tissues truncated agrin transcripts were detected, lacking the region that encodes the laminin-binding domain. The high transcription levels in lung and kidney corresponded with the accumulation of agrin in the alveolar and glomerular basement membranes, suggesting a filtration-associated function. These data provide new directions for investigating the role of agrin in its different physiological environments, including the basement membranes of the neuromuscular junction, kidney and lung.

Groffen A J AJ; Buskens C A CA; van Kuppevelt T H TH; Veerkamp J H JH; Monnens L A LA; van den Heuvel L P LP

1998-05-15

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

European journal of biochemistry

9652411

Dextran strongly increases the Michaelis constants of oxidative phosphorylation and of mitochondrial creatine kinase in heart mitochondria.

Macromolecules restore the morphological changes which occur upon isolation of mitochondria in normally used isolation media. It was shown that in the presence of dextrans the permeability of mitochondrial outer membrane for adenine nucleotides decreases which may have considerable implications for the transport of ADP into the mitochondria. In this study the effect of dextran on the apparent Michaelis constants of oxidative phosphorylation and mitochondrial creatine kinase (mi-CK) of rat heart mitochondria was investigated. Mitochondria were isolated either in normally used isolation media or in the additional presence of 15% dextran 20 in order to avoid changes in the oncotic conditions on the mitochondria during preparation and investigation. Except for an increased contamination with extramitochondrial ATPases the basic functional properties of these mitochondria were normal. With oxygraphic measurements it was found that Km(ADP) of oxidative phosphorylation increased from 16 +/- 4 microM ADP (without dextran) to 50 +/- 15 microM (15% dextran 20) and to 122 +/- 62 microM (25% dextran 20) irrespective of the mode of preparation of the mitochondria. Using spectrophotometric measurements the effect of dextran on the Km(ATP) of mi-CK was investigated in three systems (a) as soluble enzyme, (b) bound to mitoplasts, (c) and in intact rat heart mitochondria. The addition of 10% dextran had no effect on kinetic properties of solubilized mi-CK. In intact heart mitochondria, however, the addition of dextran caused an augmentation of Km(ATP) from 332 +/- 91 microM (control) to 525 +/- 150 microM ATP (10% dextran) and 641 +/- 160 microM ATP (30% dextran). In mitoplasts the effect of dextran disappeared (control, 230 +/- 19 microM ATP; 10% dextran, 238 +/- 28 microM ATP) indicating that the outer mitochondrial membrane is a prerequisite for the modulation of the transport of adenine nucleotides into the intermembrane space by macromolecules. To investigate the effects of viscosity of dextran solutions on the diffusion of adenine nucleotides across the outer membrane, dextrans with different molecular size (20, 40 70 and 500 kDa) were used. The viscosity of the 10% solutions drastically increased with the molecular size of the dextrans used, but the effects of different dextran solutions on the kinetic constants were the same. From these results it was concluded that neither the viscosity nor the molar concentration but the content of macromolecules (mass/vol.) correlates with restrictions of diffusion into the intermembrane space of mitochondria with intact outer membranes. Assuming that a dextran concentration of 15% mimicks the intracellular oncotic pressure on mitochondria in vivo, the apparent Km(ATP) of oxidative phosphorylation within the intact cell seems to be about 50 microM ADP which is somewhat higher than the cytoplasmic free ADP concentration as reported for the intact heart.

Gellerich F N FN; Laterveer F D FD; Korzeniewski B B; Zierz S S; Nicolay K K

1998-05-15

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Lancet (London, England)

9652560

Randomised placebo-controlled trial of human recombinant insulin-like growth factor I plus intensive insulin therapy in adolescents with insulin-dependent diabetes mellitus.

BACKGROUND: Good glycaemic control in insulin-dependent diabetes mellitus. Retinal photographs, renal function (glomerular filtration rate and urinary albumin excretion), and routine biochemistry showed no adverse events. INTERPRETATION: Our data confirm that rhIGF-I as an adjunct to insulin therapy can improve HbA1c values in adolescents with IDDM without overt toxic effects, but they raise questions about whether these effects can be sustained in cases of poor compliance or reduced bioefficacy.

Acerini C L CL; Patton C M CM; Savage M O MO; Kernell A A; Westphal O O; Dunger D B DB

1997-10-25

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Cancer letters

9652787

Changes in liver fatty acid-binding protein in rat enzyme-altered foci.

The level of liver fatty acid-binding protein (L-FABP) was analyzed in enzyme-altered foci (EAF) positive for GST-P, or after classification of foci into different subclasses by haematoxylin and eosin staining. Rats were treated with either an initiating single dose of diethylnitrosamine (DEN) followed by no treatment, treatment with phenobarbital, PCB, nafenopin or repeated injections of DEN, or alternatively non-treated or treated with nafenopin alone. Changes in the level of L-FABP were detected in the majority of EAF and both L-FABP-positive and -negative foci were seen. However, in rats initiated with DEN, EAF were almost exclusively L-FABP-negative. The fraction of L-FABP-negative foci increased with increasing foci size, while the time of treatment or the dose of the promoter did not seem to have any effect. It was also found that treatment with DEN gave a higher fraction of L-FABP-negative foci as compared to treatment with phenobarbital or PCB, indicating a specific effect of DEN. These data together with previously published findings suggest that L-FABP expression in EAF is determined by the initiating carcinogenic regimen and that it might be possible to use the expression of L-FABP in tumours to differentiate initiating chemicals.

Thullberg M M; Grasl-Kraupp B B; Högberg J J; Garberg P P

1998-06-05

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

International journal of radiation oncology, biology, physics

9652855

Increased induction of Ca2+-mediated differentiation by gamma ray is mediated by endogenous activation of the protein kinase C signaling pathways in mouse epidermal cells.

PURPOSE: The aim of this study was to determine whether gamma-rays can affect Ca2+-induced differentiation in normal and neoplastic mouse epidermal cells. METHODS AND MATERIALS: After gamma-ray irradiation, primary and v-rasHa transformed mouse keratinocytes were cultured for 48 h in 0.12 mM Ca2+-containing media, and cellular translocation from cytosolic to particulated fraction of each PKC isozyme and expressions of differentiation markers were examined. RESULTS: Morphological difference was seen at 48 h after irradiation in both Ca2+-shifted normal and v-rasHa transformed cells; v-rasHa cells were more resistant to the radiation than normal cells. Radiation potentiated granular cell-differentiation marker expressions (filaggrin, loricrin, and SPR-1) in both normal and v-rasHa transformed cells. In the case of spinous cell markers, the expression of keratins K1 and K10, which are usually blocked in v-rasHa cells was increased after irradiation. However, there was no change of K8 expression level, which can be seen only after v-rasHa transfection. Cellular fractionation and immunoblot analysis with antibodies against PKCalpha, delta, epsilon, eta, and xi revealed that PKCalpha was responsible for the differentiation marker expression. CONCLUSIONS: These findings suggest that PKCalpha is an important component of the signaling pathway regulating radiation-induced differentiation in both normal and neoplastic epidermal cells.

Song H J HJ; Cho C K CK; Yoo S Y SY; Park K S KS; Lee Y S YS

1998-07-01

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Cardiovascular drugs and therapy

9652874

Calcium channel blockers and the risk of cancer: a preclinical assessment.

The preclinical evidence for a potential influence of calcium channel blockers (CCBs) on carcinogenesis is discussed in the light of a broad database from rodent carcinogenicity studies as well as literature data. In all bioassays performed in rats and mice on the dihydropyridine CCBs--nifedipine, nimodipine, nisoldipine, and nitrendipine--no evidence was found for a carcinogenic potential of these compounds. Calcium is an essential intracellular signal for cell proliferation and apoptosis. The crucial role of increased cell proliferation in all stages of carcinogenesis is well documented. Some indirect experimental evidence also points to a role of defective apoptosis in tumor promotion. CCBs uniformly inhibit cell proliferation, whereas the influence of CCBs on apoptosis is inconsistent, resulting in an inhibition or increase in apoptosis dependent on cell type. Accordingly, antitumorigenic effects of CCBs have been reported based on their antiproliferative action. A tumor-promoting effect of CCBs based on inhibition of apoptosis, however, remains purely speculative and, in fact, can be denied based on the results of in vivo bioassays. It is therefore concluded that there is no preclinical evidence that should give rise to concern over the carcinogenic potential of dihydropyridine-type CCBs.

Ahr H J HJ; Bomhard E E; Enzmann H H; Karbe E E; Mager H H; Sander E E; Schlüter G G

1998-05-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Cardiovascular drugs and therapy

9652877

Acute myocardial infarction mortality related to use of calcium antagonists before admission to hospital.

We investigated whether prior use of calcium antagonists in 80 (16.8%) out of 477 patients (64% males) admitted with acute myocardial infarction (MI) had any impact on in-hospital mortality. Patients using calcium antagonists were slightly older (74 years versus 72 years, 2P = 0.039) than those not taking them and fewer were male patients. Previous MI, diabetes mellitus, and prior use of aspirin, beta-blockers, and long-acting nitrates were more frequent in patients on calcium antagonists. In contrast, fewer patients on calcium antagonists prior to symptoms received thrombolytic treatment (21.3% versus 34.8%, 2P = 0.018). The study had an observational exposed/nonexposed design, and we looked for both crude and adjusted effects. Of the 83 patients (17.4%) who died during hospitalization, 18 patients were in the calcium antagonist group (22.5%). The odds ratio (OR) for these patients to die in the hospital was 1.48 and the 95% confidence interval (CI) 0.78-2.78; 2P = 0.19. When adjusting for confounders (gender, age, smoking habit, previous MI, and diabetes mellitus, as well as prior use of aspirin, beta-blockers, long-acting nitrates, and thrombolytic treatment at entry) OR was 1.08 and 95% CI 0.57-2.05; 2P = 0.85. Thus, we found no excess in-hospital mortality in patients with acute MI using calcium antagonists prior to the onset of symptoms.

Landmark K K; Reikvam A A; Abdelnoor M M; Sivertssen E E; Aursnes I I

1998-05-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Cardiovascular drugs and therapy

9652880

Safety, tolerability, and neurohormonal changes of the combination captopril plus losartan in the early postinfarction period: a pilot study.

Suppression of formation of angiotensin II (A-II) is thought to be a major contributor to the hemodynamic response to angiotensin-converting enzyme inhibition (ACE-in) therapy. However, angiotensin II (A-II) plasma levels may rebound during ACE-in treatment. The study sought to verify the feasibility, safety, and tolerability of the combination of captopril (75 mg/d) plus losartan (25 mg/d). We also wished to establish whether the combination was able to avoid the increase of angiotensin II resulting from losartan treatment in early postinfarction phases of reperfused anterior acute myocardial infarction (AMI). Forty-four patients, hospitalized for suspected anterior AMI within 4 hours from the onset of symptoms, suitable for thrombolysis (first episode), Killip class I-II and reperfused, receiving 75 mg/d of captopril within 3 days from admission, and with systolic blood pressure (BP) >120 mmHg were randomized (single-blind) into two groups: Group A included 22 patients (6 women and 16 men) and received captopril 75 mg/d and placebo. Group B included 22 patients (5 women and 17 men) and received captopril 75 mg/d within 3 days from admission plus losartan 12.5 mg, as the first dose, and 25 mg/d (BP >110 mmHg) successively. Norepinephrine (NE) and A-II levels were measured on the 3rd and 10th days after admission. The two groups were similar with regard to age, sex, creatinine kinase peak, ejection fraction, end-systolic volume, and risk factors. Group B (captopril plus losartan) showed a significant reduction of BP, from 124 +/- 8.5 mmHg to 108 +/- 6.4 mmHg, P < 0.001, at 10 days after admission. In group A, BP was 122 +/- 9 mmHg, and 10 days after admission BP was 118 +/- 11 mmHg. NE and A-II values did not show significant differences in basal samples. At 10 days after admission values were NE 298 +/- 90 versus 272 +/- 86 pg/mL and A-II 6.07 +/- 2.97 versus 5.29 +/- 2.05 pg/mL for the two groups. Our data suggest, for the first time, that the combination of captopril plus losartan is feasible and does not produce serious side effects. When losartan was added to ACE-in treatment, there was no significant increase in A-II.

Di Pasquale P P; Bucca V V; Scalzo S S; Paterna S S

1998-05-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Cardiovascular drugs and therapy

9652881

Increasing nitroglycerin release from patches enables circumvention of early nitrate tolerance.

Continuous treatment with transdermal nitroglycerin leads to tolerance development within the first day of application. Effective long-term therapy can be provided by interval treatment with nightly patch removal, but even during the hours of intermittent patch application there is rapid attenuation of initial effects. To assess whether an unattenuated antiischemic and antianginal efficacy during the hours of intermittent dosing can be maintained, a modified drug-release profile with increasing plasma concentrations was evaluated using a double-blind, placebo-controlled crossover protocol. Eleven patients with documented coronary artery disease received, in a randomized order, a total of four low-dose nitroglycerin patches (5 mg/24 h each) or placebo, respectively, at intervals of 3 hours. After a treatment interval of 12 hours, all patches were removed for an equally long patch-free interval prior to renewed application of one patch the next morning. At a comparable workload, reductions of ST-segment depression of 65%, 63%, and 56% were found at 2.5 hours, 8 hours, and 12 hours after application of the first patch on day 1, respectively (all significant versus placebo; 2.5 hours versus 12 hours, n.s.). On day 2, the comparable reduction of 63% at 2.5 hours after renewed application indicates prevention of tolerance development during subchronic treatment. Effects on exercise capacity and angina pectoris paralleled those on exercise-induced ST-segment depression. Plasma concentrations of nitroglycerin increased from 223 pg/mL to 558 and 803 pg/mL on day 1 and amounted to 205 ng/mL at 2.5 hours on day 2. Thus, interval therapy with increasing nitroglycerin concentrations provides unattenuated antiischemic and antianginal efficacy during the hours of treatment and circumvention of early tolerance during subchronic application. This modified pharmacokinetic profile can be regarded as a model for an improved dosage regimen in nitrate interval therapy.

Reiniger G G; Lehmann G G

1998-05-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Internal medicine (Tokyo, Japan)

9652900

Diabetes mellitus accompanied by nonocclusive colonic ischemia.

A 70-year-old man with diabetic triopathy was hospitalized with left lower quadrant abdominal pain and tenderness, muscle guarding and absent bowel sounds. Three hours after admission, creatine phosphokinase (CPK) was elevated and an abdominal plain film X-ray showed intestinal gas retention, indicating paralytic ileus due to inferior mesenteric artery occlusion. Urokinase (60,000 units/day) and heparin (10,000 units/day) were administered. Angiography showed no occlusion in the mesenteric artery. On the 16th day, the abdominal signs had disappeared and CPK was normalized. We diagnosed this case as nonocclusive colonic ischemia because of the hemorheological abnormalities due to diabetic triopathy and the hypercoagulable state.

Nagai T T; Tomizawa T T; Monden T T; Mori M M

1998-05-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Internal medicine (Tokyo, Japan)

9652905

Malignant insulinoma with extensive liver metastases presenting as disturbance of consciousness.

A 56-year-old man was referred to our hospital for evaluation of episodic disturbance of consciousness. Hypoglycemic symptoms were noted and Whipple's triad was satisfied. The 75 g OGTT and the glucagon test revealed a high baseline insulin level and hyperreactivity to glucagon. A pancreatic tumor and liver metastases were found by abdominal computed tomography (CT). Based on the finding of liver biopsy, the final diagnosis was malignant insulinoma with liver metastasis. He selected conservative treatment and no hypoglycemic crisis has occurred for one year since discharge. Early diagnosis and long-term follow-up is necessary since this tumor is slow growing.

Toyoda C C; Hosokawa K K; Atsumi Y Y; Asahina S S; Shimada A A; Mokubo A A; Matsuoka K K; Morinaga S S; Hayashi F F; Hikita M M; Tomonari H H; Kuriyama S S; Inoue K K; Hosoya T T

1998-05-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Regulatory peptides

9652972

Endogenous CCK inhibits colonic contractions in unrestrained conscious rats.

As cholecystokinin octapeptide, prior to clinimeal blocked the inhibitory action of CCK on the motor activity in a concentration-dependent manner. These data suggest that endogenous CCK released by a residual diet is involved in the mechanism of inhibition of motor activity in the proximal colon.

Hayashi K K; Kishimoto S S; Kannbe M M

1997-10-31

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Regulatory peptides

9652970

Pharmacological characterization and selectivity of the NPY antagonist GR231118 for different NPY receptors.

Neuropeptide Y (NPY) is widely distributed throughout the central and peripheral nervous system and exerts a wide range of physiological responses by activating specific receptors. In this study we have characterized the potency of the high affinity peptide dimer antagonist, GR231118, to displace radiolabeled NPY/PYY from different tissues and cell lines expressing Y1 or Y2 receptors and from CHO cells stably transfected with human cDNA encoding for Y1, Y2 and Y4 receptors. GR231118 displays high affinity for Y1 and Y4 receptors, equal or better than that of NPY itself, while its activity is several fold weaker for Y2 receptors. Displacement of radiolabeled PYY from rat hypothalamic membranes by GR231118, reveals the existence of high and low affinity binding sites which may be equated to Y1 and Y2 receptors respectively suggesting that the compound maybe used as a tool to dissect central NPY receptors.

Matthews J E JE; Jansen M M; Lyerly D D; Cox R R; Chen W J WJ; Koller K J KJ; Daniels A J AJ

1997-10-31

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Regulatory peptides

9652973

Angiotensin receptors and norepinephrine neuromodulation: implications of functional coupling.

The objective of this review is to examine the role of neuronal angiotensin II (Ang II) receptors in vitro. Two types of G protein-coupled Ang II receptors have been identified in cardiovascularly relevant areas of the brain: the AT1 and the AT2. We have utilized neurons in culture to study the signaling mechanisms of AT1 and AT2 receptors. Neuronal AT1 receptors are involved in norepinephrine (NE) neuromodulation. NE neuromodulation can be either evoked or enhanced. Evoked NE neuromodulation involves AT1 receptor-mediated, losartan-dependent, rapid NE release, inhibition of K+ channels and stimulation of Ca2+ channels. AT1 receptor-mediated enhanced NE neuromodulation involves the Ras-Raf-MAP kinase cascade and ultimately leads to an increase in NE transporter, tyrosine hydroxylase and dopamine beta-hydroxylase mRNA transcription. Neuronal AT2 receptors signal via a Gi protein and are coupled to activation of PP2A and PLA2 and stimulation of K+ channels. Finally, putative cross-talk pathways between AT1 and AT2 receptors will be discussed.

Gelband C H CH; Sumners C C; Lu D D; Raizada M K MK

1997-10-31

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Regulatory peptides

9652975

Renal aminopeptidase activities in animal models of hypertension.

Aminopeptidase activity (AP) has been implicated in the metabolism of renal and circulating vasoactive peptides. This activity is involved in the pathogenia of hypertension, essentially in spontaneously hypertensive rats. However, no other animal models, which develop hypertension by other different ways, have been used to study the possible role of aminopeptidase activity. To investigate the role of this activity in the pathogenesis of hypertension, angiotensinase A activity (glutamyl-AP and aspartyl-AP), aminopeptidase M activity (alanyl-AP), aminopeptidase B activity (arginyl-AP), pyroglutamyl-AP, and cystinyl-AP were measured in the serum and kidney of two experimental animal models of renovascular hypertension: Goldblatt two-kidney one clip (G2K-1C) and low renal mass rats (LRM). No differences were found in serum levels of AP in LRM or G2K-1C in comparison with their respective controls. In LRM rats there was a significant decrease in membrane-bound angiotensinase A (glutamyl-AP), arginyl-AP and alanyl-AP activities. In G2K-1C rats there was a significant decrease in soluble and membrane-bound angiotensinase A activity (aspartyl-AP). Our results suggest that AP activities play a role in the regulation of renal vasoactive peptides, and respond differently depending on the cause of hypertension.

Ramírez M M; Prieto I I; Martinez J M JM; Vargas F F; Alba F F

1997-10-31

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Regulatory peptides

9652974

PACAP stimulates pancreatic exocrine secretion via the vagal cholinergic nerves in sheep.

The present study evaluates the possible role of the vagus nerves in mediating the stimulatory effect of PACAP-27, PACAP-38 and VIP on the exocrine pancreas, especially on enzyme secretion which is atropine sensitive in sheep. The animals were equipped with two cannulae into the common bile duct, a duodenal cannula, and a ruminal cannula under anesthesia. The bilateral cervical vagus nerves were coiled with a cooling device. In conscious animals, the peptides were infused intravenously for 10 min at 10 pmol kg(-1)min(-1) in phase II of the duodenal migrating motor complexes and the same peptide infusion was repeated in the reversible cooling blockade of the vagus nerves. Increment in fluid secretion was not significantly altered by the vagal blockade in all the peptide infusions, while increment in bicarbonate ion by only PACAP-27 was inhibited by the vagal blockade. Increments in protein and amylase output decreased significantly to 32.0+/-5.0 and 23.2+/-2.6% in PACAP27, and to 26.1+/-7.7 and 20.8+/-6.4% in PACAP-38 in the vagal blockade, but the increments by VIP did not decrease. These results demonstrate that circulating PACAP stimulates pancreatic enzyme secretion via the vagal cholinergic preganglionic neurons in sheep, suggesting the central action of PACAP.

Onaga T T; Okamoto K K; Harada Y Y; Mineo H H; Kato S S

1997-10-31

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Regulatory peptides

9652978

Urinary excretion of epidermal growth factor and Tamm-Horsfall protein in three rat models with increased renal excretion of urine.

Epidermal growth factor (EGF) and Tamm-Horsfall protein (THP) are synthesized in the kidneys by the distal tubular cells and excreted into urine. The urinary excretion of these peptides has been suggested as a potential index for distal tubular function. The urinary excretion rates of EGF and THP were examined in three groups of rats with increased renal excretion of urine: uninephrectomy, non-osmotic polyuria and diabetic osmotic polyuria. Twenty-four hour urine samples were obtained after 7, 14 and 21 days. The urinary volume per kidney was doubled in uninephrectomy when compared to controls. There was a seven-fold increase in urinary volume in rats with non-osmotic polyuria and diabetic osmotic polyuria, as compared to controls. Uninephrectomy, non-osmotic polyuria and diabetes all affected the urinary excretion of EGF and THP differently. The EGF excretion in uninephrectomized rats was 60-80% of that of the controls, whereas THP excretion was unchanged, indicating that EGF excretion varied with renal tissue mass. Non-osmotic polyuria caused a five-fold increase in THP excretion but no change in EGF excretion. THP excretion in the diabetic rats was increased three-fold after 21 days when compared to controls, whereas EGF excretion was decreased when expressed per kidney weight. Immunohistochemistry demonstrated that EGF and THP were colocalized in the thick ascending limbs of Henle's loops and distal tubules in all five groups of rats. In conclusion, the EGF excretion appears to follow renal tissue mass and seems independent of urinary volume, whereas THP excretion is dependent mainly on urinary volume. This has implications for the use of EGF and/or THP excretion rates as an indicator for distal tubular function.

Thulesen J J; Jørgensen P E PE; Torffvit O O; Nexø E E; Poulsen S S SS

1997-10-31

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Regulatory peptides

9652981

Effects of OPC-21268, a vasopressin V1-receptor antagonist, on expression of growth factors from glomeruli in spontaneously hypertensive rats.

To assess the chronic in vivo effects of OPC-21268, a vasopressin-V1 receptor antagonist, on renal injury, we investigated the mRNA expressions of platelet-derived growth factor excretion between the two groups. Serum electrolytes, protein and creatinine levels also did not differ between the groups. The mRNA expressions of PDGF B-chain, TGF-beta1 and PCNA in the glomerulus were examined using reverse transcriptase-polymerase chain reaction (RT-PCR) methods. The mRNA expressions of PDGF B-chain and PCNA among these were significantly suppressed in the OPC group. No significant differences in renal histology including the organ weights were found between the two groups; however, the glomerular size tended to be enlarged in the OPC group. These findings suggest that chronic V1-receptor blockade directly inhibits the glomerular proliferative injury of salt-loaded SHR at the established hypertension stage.

Otsuka F F; Ogura T T; Yamauchi T T; Oishi T T; Hashimoto M M; Mimura Y Y; Makino H H

1997-10-31

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Regulatory peptides

9652982

Mutational analysis of the angiotensin II type 2 receptor: contribution of conserved extracellular amino acids.

While much work has been done examining the ligand-binding characteristics of the AT1 receptor, very little attention has been focused on the AT2 receptor. Both receptors bind angiotensin II (AngII) with identical affinities, but share only 34% homology. Although it is tempting to assume that conserved residues between the two subtypes are responsible for the binding of AngII, there is little data to support this view. To determine the commonalities in ligand binding of the AT1 and AT2 receptors, we have chosen several conserved extracellular amino acids which have been shown to be important in AngII binding to the AT1 receptor for mutational studies of the AT2 receptor. Specifically, we have mutated tyrosine108 in extracellular loop 1 (ECL1), arginine182 in ECL2, and aspartate297 in ECL3 of the AT2 receptor in order to determine their contribution to AngII binding. In the AT2 receptor, mutation of tyrosine108 to an alanine resulted in a receptor with wild-type binding for AngII, while mutation of either arginine182 or aspartate297 drastically impaired AngII binding ( > 100 nM). These results demonstrate both similarities as well as clear differences between receptor subtypes in the contributions to AngII binding of several conserved extracellular amino acid residues.

Heerding J N JN; Yee D K DK; Jacobs S L SL; Fluharty S J SJ

1997-10-31

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

General and comparative endocrinology

9653016

Characterisation of glucocorticoid receptors in peripheral blood leukocytes of Carp, Cyprinus carpio L.

Binding studies withcortisol revealed the presence of a single class of cortisol-binding sites on carp peripheral blood leukocytes (PBL). These binding sites showed high affinity (Kd of 3.8 nM) and low capacity (490 binding sites per cell), indicative of receptor binding. Affinity for cortisone was 254-fold lower than for cortisol. Affinity for the two synthetic glucocorticoids dexamethasone and triamcinolone acetonide (TA) was 4- and 10-fold higher than for cortisol, respectively. Further evidence for the GR character of the receptor came from results showing that cortisol induced apoptosis, which could be blocked by the glucocorticoid analogue RU486. A single meal of cortisol-containing food elevated plasma cortisol concentrations and decreased GR density in PBL, as measured 3 h later. The percentage of circulating B lymphocytes also decreased. Cortisol-induced redistribution of B lymphocytes from the blood, due to cortisol treatment, may explain the decrease of GR numbers in PBL, although downregulation of available GR remains possible.

Weyts F A FA; Verburg-van Kemenade B M BM; Flik G G

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

General and comparative endocrinology

9653017

Loss of glucose transporter-2 precedes insulin loss in the nonobese diabetic and the low-dose streptozotocin mouse models: a comparative immunohistochemical study by light and confocal microscopy.

Glucose transporter-2 (glut2) is underexpressed in beta cells of several rodent models of non-insulin-dependent diabetes mellitus (NIDDM). This may also be true for rodent models of insulin-dependent diabetes mellitus (IDDM). The present study examines two murine models of autoimmune IDDM, the nonobese diabetic (NOD) and the low-dose streptozotocin (stz) murine models for changes in the expression of glut2 by double-label light and confocal microscopy during various stages of the disease. The spatial distribution of glut2 cells was also examined in relation to insulin immunoreactive cells and the islet inflammatory cells during these stages. In both the female NOD mouse and the female Swiss mouse without stz treatment, glut2 colocalized with insulin in virtually all the beta cells. In the NOD mouse, islets with moderate to advanced insulitis showed either an absence or considerably reduce expression of glut2 in insulin-containing beta cells. Cells with reduced glut2 expression were usually located adjacent to the region of insulitis. At onset of diabetes, glut2 immunolabeling was reduced despite the preservation of weak insulin immunoreactivity. In Swiss mice treated repeatedly with stz, glut2 labeling began to decline in select Beta cells after the fourth injection in approximately 50% of the islets, despite the lack of insulitis. At this stage expression of glut2 fell in a small number of islets with evidence of early macrophage infiltration. Loss of glut2 became more pronounced in nondiabetic Swiss mice after the fifth injection. At this stage glut2 labeling in the plasma membrane appeared diffuse and variable. At onset of stz-induced diabetes, glut2 expression significantly fell, despite weak immunoreactivity for insulin. This loss was associated with an enhanced influx of both macrophages and T lymphocytes within the islets of diabetes mice. In both the NOD and the low-dose stz mouse models, loss of glut2 thus occurs from an early stage and precedes hyperglycaemia. This loss may be mediated by immune and nonimmune mechanisms.

Reddy S S; Young M M; Poole C A CA; Ross J M JM

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Toxicology and applied pharmacology

9653067

Methanol-induced contraction of canine cerebral artery and its possible mechanism of action.

In the present report, we investigated the effects of methanol on canine basilar cerebral arterial rings. Our data indicate that acute methanol exposure (5-675 mM) induces potent contractile responses of cerebral arteries in a concentration-dependent manner. Pharmacological antagonists, such as propranolol, phentolamine, haloperidol, methysergide, naloxone, diphenhydramine, and cimetidine, did not exert any effects on these methanol-induced contractions. Likewise, a potent antagonist of cyclo-oxygenase, and subsequent synthesis of prostanoids (that is, indomethacin), failed to exert any effect on methanol-induced contractions. No differences in responsiveness to methanol in canine cerebral arteries were found in vessel segments with or without endothelial cells. Removal of extracellular Ca2+ (o) partially attenuated methanol-induced contractions, while withdrawal of extracellular Mg2+ (o) potentiated the contractions. In the complete absence ofo, 10 mM caffeine and 400 mM methanol induced similar, transient contractions followed by relaxation in K(+)-depolarized cerebral vascular tissues. Methanol-induced contractions were, however, completely abolished by pretreatment of tissue with 10 mM caffeine. Our results indicate that (1) methanol causes contractile responses of cerebral arterial smooth muscle (independent of amine, prostanoid, or opioid mediation; (2) in addition to a need foro, an intracellular release of Ca2+ is required for methanol-induced contractions; and (3) Mg deficiency potentiates the contractile responses of methanol on these brain vessels. The data presented in the study suggest that methanol-induced contractions occur via an sarcoplasmic reticulum-releasable store ofi; via mediation of either ryanodine-caffeine type receptors or a caffeine-releasable intracellular store of CA2+.

Li W W; Altura B T BT; Altura B M BM

1998-06-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Proceedings of the National Academy of Sciences of the United States of America

9653138

Nature of PEVK-titin elasticity in skeletal muscle.

A unique sequence within the giant titin molecule, the PEVK domain, has been suggested to greatly contribute to passive force development of relaxed skeletal muscle during stretch. To explore the nature of PEVK elasticity, we used titin-specific antibodies to stain both ends of the PEVK region in rat psoas myofibrils and determined the region's force-extension relation by combining immunofluorescence and immunoelectron microscopy with isolated myofibril mechanics. We then tried to fit the results with recent models of polymer elasticity. The PEVK segment elongated substantially at sarcomere lengths above 2.4 micro(m) and reached its estimated contour length at approximately 3.5 micro(m). In immunofluorescently labeled sarcomeres stretched and released repeatedly above 3 micro(m), reversible PEVK lengthening could be readily visualized. At extensions near the contour length, the average force per titin molecule was calculated to be approximately 45 pN. Attempts to fit the force-extension curve of the PEVK segment with a standard wormlike chain model of entropic elasticity were successful only for low to moderate extensions. In contrast, the experimental data also could be correctly fitted at high extensions with a modified wormlike chain model that incorporates enthalpic elasticity. Enthalpic contributions are likely to arise from electrostatic stiffening, as evidenced by the ionic-strength dependency of titin-based myofibril stiffness; at high stretch, hydrophobic effects also might become relevant. Thus, at physiological muscle lengths, the PEVK region does not function as a pure entropic spring. Rather, PEVK elasticity may have both entropic and enthalpic origins characterizable by a polymer persistence length and a stretch modulus.

Linke W A WA; Ivemeyer M M; Mundel P P; Stockmeier M R MR; Kolmerer B B

1998-07-07

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Proceedings of the National Academy of Sciences of the United States of America

9653142

ClC-5, the chloride channel mutated in Dent's disease, colocalizes with the proton pump in endocytotically active kidney cells.

Loss-of-function mutations of the ClC-5 chloride channel lead to Dent's disease, a syndrome characterized by low molecular weight proteinuria, hypercalciuria, and kidney stones. We show that ClC-5 is expressed in renal proximal tubule cells, which normally endocytose proteins passing the glomerular filter. Expression is highest below the brush border in a region densely packed with endocytotic vesicles, where ClC-5 colocalizes with the H+-ATPase and with internalized proteins early after uptake. In intercalated cells of the collecting duct it again localizes to apical intracellular vesicles and colocalizes with the proton pump in alpha-intercalated cells. In transfected cells, ClC-5 colocalizes with endocytosed alpha2-macroglobulin. Cotransfection with a GTPase-deficient rab5 mutant leads to enlarged early endosomes that stain for ClC-5. We suggest that ClC-5 may be essential for proximal tubular endocytosis by providing an electrical shunt necessary for the efficient acidification of vesicles in the endocytotic pathway, explaining the proteinuria observed in Dent's disease.

Günther W W; Lüchow A A; Cluzeaud F F; Vandewalle A A; Jentsch T J TJ

1998-07-07

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Proceedings of the National Academy of Sciences of the United States of America

9653146

Phospholipase A2-mediated activation of mitogen-activated protein kinase by angiotensin II.

In renal proximal tubule epithelial cells, a membrane-associated phospholipase A2 (PLA2) is a major signaling pathway linked to angiotensin II (Ang II) type 2 receptor (AT2). The current studies were designed to test the hypothesis that membrane-associated PLA2-induced release of arachidonic acid (AA) and/or its metabolites may serve as an upstream mediator of Ang II-induced mitogen-activated protein kinase (MAPK) activation. Ang II stimulated transient dose-dependent phosphorylation of MAPK with a maximum at 1 microM (10 min). Inhibition of PLA2 by mepacrine diminished both AA release and MAPK phosphorylation, induced by Ang II. Furthermore, AA itself induced time- and dose-dependent phosphorylation of MAPK, supporting the importance of PLA2 as a mediator of Ang II signaling. The effects of both Ang II and AA on MAPK phosphorylation were protein kinase C independent and abolished by the inhibitor of cytochrome P450 isoenzyme, ketoconazole. Moreover, 5,6-epoxyeicosatrienoic acid and 14,15-epoxyeicosatrienoic acid, the cytochrome P450-dependent metabolites of AA, significantly stimulated MAPK activity in renal proximal tubule epithelial cells. These observations document a mechanism of Ang II-induced MAPK phosphorylation, mediated by PLA2-dependent release of AA and cytochrome P450-dependent production of epoxy derivatives of AA.

Dulin N O NO; Alexander L D LD; Harwalkar S S; Falck J R JR; Douglas J G JG

1998-07-07

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Proceedings of the National Academy of Sciences of the United States of America

9653178

Depletion of intracellular Ca2+ stores, phosphorylation of eIF2alpha, and sustained inhibition of translation initiation mediate the anticancer effects of clotrimazole.

Regulation of translation initiation plays a critical role in the control of cell growth and division in eukaryotic cells. Translation of many growth regulatory proteins including cyclins depends critically on translation initiation factors because their mRNAs are translated inefficiently. We report that clotrimazole, a potent antiproliferative agent both in vitro and in vivo, inhibits cell growth by interfering with translation initiation. In particular, clotrimazole causes a sustained depletion of intracellular Ca2+ stores, which results in activation of PKR, phosphorylation of eIF2alpha, and thereby in inhibition of protein synthesis at the level of translation initiation. Consequently, clotrimazole preferentially decreases the expression of the growth promoting proteins cyclin A, E and D1, resulting in inhibition of cyclin-dependent kinase activity and blockage of cell cycle in G1.

Aktas H H; Flückiger R R; Acosta J A JA; Savage J M JM; Palakurthi S S SS; Halperin J A JA

1998-07-07

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Proceedings of the National Academy of Sciences of the United States of America

9653196

Human alpha-endosulfine, a possible regulator of sulfonylurea-sensitive KATP channel: molecular cloning, expression and biological properties.

Sulfonylureas are a class of drugs commonly used in the management of non-insulin-dependent diabetes mellitus. Their therapeutic action results primarily from their ability to inhibit ATP-sensitive potassium (KATP) channels in the plasma membrane of pancreatic beta cells and thereby stimulate insulin release. A key question is whether an endogenous ligand for the KATP channel exists that is able to mimic the inhibitory effects of sulfonylureas. We describe here the cloning of the cDNA encoding human alpha-endosulfine, a 13-kDa peptide that is a putative candidate for such a role. alpha-Endosulfine is expressed in a wide range of tissues including muscle, brain, and endocrine tissues. The recombinant protein displaces binding of the sulfonylureaglibenclamide to beta cell membranes, inhibits cloned KATP channel currents, and stimulates insulin secretion. We propose that endosulfine is an endogenous regulator of the KATP channel, which has a key role in the control of insulin release and, more generally, couples cell metabolism to electrical activity.

Heron L L; Virsolvy A A; Peyrollier K K; Gribble F M FM; Le Cam A A; Ashcroft F M FM; Bataille D D

1998-07-07

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Professional nurse (London, England)

9653276

Beliefs about diabetes and diabetic complications.

A study of people with non-insulin dependent diabetes found that, generally, they had a good understanding of its complications although over half believed they personally were not vulnerable. Non-diabetic subjects had limited knowledge in this area.

Dunning P P; Martin M M

1998-04-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

American journal of rhinology

9653479

Muscarinic ciliostimulation requires endogenous prostaglandin production.

Prostaglandin E2 (PGE2) is a known modulator in upper airway ciliary activity and may be involved in the transduction of the muscarinic acetylcholine receptor signal. We studied the in vitro effects of muscarinic ciliostimulation on ciliary beat frequency (CBF) and PGE2 in human adenoid explants to determine whether PGE2 production is an essential step in the signal transduction mechanism. Methacholine applied to adenoid explants significantly increased ciliary beat frequency. This effect was blocked by the application of diclofenac, a cyclooxygenase inhibitor. Using radioimmunoassay, PGE2 production was measured during ciliostimulation with methacholine. Methacholine produced a significant increase in production in PGE2 during ciliostimulation. The roles of phospholipase C and phospholipase A2 in prostaglandin production were investigated by inhibiting these enzymes. D609, a phospholipase C inhibitor, significantly inhibited ciliary beat frequency increase and PGE2 production during methacholine stimulation. However, PACOCF3, a phospholipase A2 inhibitor, did not block ciliary beat frequency increase or PGE2 production in response to methacholine. These data show that phospholipase C is required for PGE2 production and ciliostimulation.

Gayner S M SM; McCaffrey T V TV

1998-07-08

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Bioscience reports

9653513

Ouabain induces apoptosis on PHA-activated lymphocytes.

Apoptotic cell death plays a critical role in immune system homeostasis, and c-myc protooncogene deregulated expression is a component of this programmed genomic response. Pharmacological intervention and modulation of peripheral lymphocytes apoptosis would have important implications. The present results indicate that ouabain, a specific inhibitor of Na+K(+)-ATPase, promotes an increased expression of c-myc mRNA, and induces apoptosis in PHA-stimulated lymphocytes. Furthermore, this ouabain-induced apoptosis cannot be counteracted by the addition of exogenous IL-2.

Olej B B; dos Santos N F NF; Leal L L; Rumjanek V M VM

1998-02-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Bioscience reports

9653514

Folate transport by prawn hepatopancreas brush-border membrane vesicles.

The transport system of folic acid (Pte-Glu) by brush-border membrane vesicles (BBMV) isolated from prawn (Penaeus japonicus) hepatopancreas, was studied by measuring the uptake of Pte-Glu. This uptake was found to have two components, intravesicular transport and membrane binding. Membrane binding was not affected by the presence of a transmembrane pH-gradient at a short incubation period. However, a transmembrane pH-gradient increased membrane binding at 60 min. The transport of Pte-Glu appeared to be carrier-mediated, was stimulated by an inwardly proton gradient (pH 5.5 outside, 7.4 inside) and was unaffected by a sodium-gradient. The relationship between pH gradient-driven Pte-Glu uptake and medium Pte-Glu concentration followed saturating Michaelis-Menten kinetics. Eadie-Hofstee representation of the pH gradient-driven Pte-Glu uptake indicated a single transport system with a Km of 0.37 microM and Vmax of 1.06 pmol/mg protein/15 s. These findings indicate that BBMV isolated from prawn hepatopancreas possesses a Pte-Glu transport system similar to that described in mammalian intestine.

Blaya J A JA; Muriana F J FJ; Ruiz-Gutierrez V V; Vazquez C M CM; Bolufer J J

1998-02-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Bioscience reports

9653515

The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester potentiates insulin secretion stimulated by glucose and L-arginine independently of its action on ATP-sensitive K+ channels.

The nature of the action of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on hormone release from isolated islets was investigated. We found that glucose-induced insulin release was potentiated by L-NAME in the absence or presence of diazoxide, a potent K+ATP channel opener, as well as in the presence of diazoxide plus a depolarizing concentration of K+. At a low, physiological glucose concentration L-NAME did not influence insulin secretion induced by K+ but inhibited glucagon secretion. L-arginine-induced insulin release was potentiated by L-NAME. This potentiation was observed also in the presence of K+ plus diazoxide. Further, glucagon release induced by L-arginine as well as by L-arginine plus K+ and diazoxide was suppressed by L-NAME. The results strongly suggest that the L-NAME-induced potentiation of insulin secretion in response to glucose or L-arginine as well as the inhibitory effects on glucagon secretion are largely mediated by L-NAME directly suppressing islet NOS activity. Hence NO apparently affects insulin and glucagon secretion independently of membrane depolarization events.

Salehi A A; Parandeh F F; Lundquist I I

1998-02-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Bioscience reports

9653517

Computational observation of an ion permeation through a channel protein.

The ion permeation process, driven by a membrane potential through an outer membrane protein, OmpF porin of Escherichia coli, was simulated by molecular dynamics. A Na+ ion, initially placed in the solvent region at the outer side of the porin channel, moved along the electric field passing through the porin channel in a 1.3 nsec simulation; the permeation rate was consistent with the experimentally estimated channel activity (10(8)-10(9)/sec). It this simulation, it was indicated that the ion permeation through the porin channel proceeds by a "push-out" mechanism, and that Asp113 is an important residue for the channel activity.

Suenaga A A; Komeiji Y Y; Uebayasi M M; Meguro T T; Saito M M; Yamato I I

1998-02-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Clinical hemorheology and microcirculation

9653588

Red blood cell aging and risk of cardiovascular diseases.

We hypothesized that due to monthly bloodloss, the mechanical properties of blood of premenopausal women are superior to men, and place them at less risk for cardiovascular diseases than men in any age group. Rheological properties of blood of premenopausal women and age-matched men were compared. It was found that male blood possesses an increased viscosity, RBC aggregability and RBC rigidity. Additionally, male RBCs were found to have higher mechanical fragility. Since women in reproductive age have almost half as many old RBCs and almost twice as many young RBCs as men, we investigated the effect of in vivo aging of RBCs on their mechanical properties. Old RBCs were shown to have an increased mechanical fragility and aggregability, and decreased deformability as compared to young RBCs. Decreased deformability and increased aggregability of RBCs cause an increase in blood viscosity and are known as risk factors of cardiovascular diseases. Since men possess a higher number of old RBCs with suboptimum mechanical properties than premenopausal women, who due to monthly bloodloss have a higher number of young cells and a lower number of old RBCs than their male counterparts, our results suggest that an elevated hemorheological risk for males is associated with the age distribution of RBCs. This, in addition to significantly higher hematocrit, may be the reason for the increased risk of morbidity and mortality from cardiovascular diseases of men as compared to women of reproductive age.

Kameneva M V MV; Garrett K O KO; Watach M J MJ; Borovetz H S HS

1998-04-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653592

Successful treatment with insulin analog lispro in IDDM with delayed absorption of subcutaneously applied human regular insulin and complicated intraperitoneal insulin infusion. A case report.

OBJECTIVE: To subcutaneously administer the insulin analog lispro in a patient with delayed absorption of subcutaneously applied human regular insulin whose continuous intraperitoneal insulin infusion (CIPII) with a percutaneous access device had required multiple surgical interventions because of complications. RESEARCH DESIGN AND METHODS: In a 35-year-old woman with long-term IDDM and delayed absorption of subcutaneously applied human regular insulin, a 3-year CIPII with human regular insulin via a percutaneous access device was complicated by three catheter obstructions and one subcutaneous abscess. Each complication required the implantation of a new percutaneous access device. During a 2-day trial with continuous subcutaneous insulin infusion (CSII) of the insulin analog lispro at basal infusion rates of 0.5-1.1 U/h, stable metabolic control was achieved. A 5-h intermediate attempt with human regular insulin in CSII, however, increased blood glucose concentrations from 6.0 to 28.8 mmol/l, despite identical basal rates and additional injection of 16 U of human regular insulin. Restarting with CSII of the insulin analog lispro reinforced stable metabolic control. CONCLUSIONS: It is suggested that the insulin analog lispro is a promising approach in the treatment of IDDM with delayed absorption of subcutaneously applied human regular insulin and a suitable alternative therapy for patients with complications attributed to percutaneous access devices for CIPII.

Meier M M; Brand J J; Standl E E; Schnell O O

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653591

Application of a diabetes managed care program. The feasibility of using nurses and a computer system to provide effective care.

OBJECTIVE: Treatment of patients with diabetes often falls short of recommended process and outcome guidelines. To improve the quality of the provided diabetes care, a program (the Comprehensive Diabetes Care Service [CDCS]) using a computerizing tracking and recall system in conjunction with nurses following protocols was implemented in a managed care setting. The impact of this program was studied and compared to the care provided to patients in another managed care setting. RESEARCH DESIGN AND METHODS: Patients followed in the CDCS who completed a diabetes education course were compared with patients followed in a group model health maintenance organization (GMH) who also completed a diabetes education course. CDCS patients received routine care in the program. GMH patients came to the CDCS yearly to have a diabetes evaluation. A chart review was also performed on their GMH outpatient records. RESULTS: Initial HbA1c levels were higher in the CDCS group than in the GMH group (median of 11.9 versus 10.0%). In the CDCS patients, HbA1c levels not only fell significantly but were also significantly lower (P < 0.05) than in the GMH patients during the 2nd and 3rd year of follow-up care. There were no significant changes in HbA1c levels in the GMH patients. When CDCS patients were divided into compliant and noncompliant patients, the median HbA1c levels in compliant patients was 8.2%, compared with 11.5% in the noncompliant group. The CDCS patients who needed treatment for hypercholesterolemia were more likely to have a lowering of their cholesterol levels than the GMH patients. All process measures, such as yearly measurement of HbA1c levels, lipid levels, and foot and retinal exams, occurred much more frequently in the CDCS patients. CONCLUSIONS: The system developed and implemented for managing diabetes improved both outcome and process measures. The comparison group, followed at another managed care setting, received the care consistent with the average (suboptimal) quality of care provided to patients with diabetes in the U.S. Therefore, by using innovative systems of management, the treatment of patients with diabetes can be greatly improved.

Peters A L AL; Davidson M B MB

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653593

Development of a scale to measure adherence to self-monitoring of blood glucose with latent variable measurement.

OBJECTIVE: Adherence to self-monitoring of blood glucose (SMBG) is problematic for many people with diabetes. Self-reports of adherence have been found to be unreliable, and existing paper-and-pencil measures have limitations. This study developed a brief measure of SMBG adherence with good psychometric properties and a useful factor structure that can be used in research and in practice. RESEARCH DESIGN AND METHODS: A total of 216 adults with diabetes responded to 30 items rated on a 9-point Likert scale that asked about blood monitoring habits. In part I of the study, items were evaluated and retained based on their psychometric properties. The sample was divided into exploratory and confirmatory halves. Using the exploratory half, items with acceptable psychometric properties were subjected to a principal components analysis. In part II of the study, structural equation modeling was used to confirm the component solution with the entire sample. Structural modeling was also used to test the relationship between these components. It was hypothesized that the scale would produce four correlated factors. RESULTS: Principal components analysis suggested a two-component solution, and confirmatory factor analysis confirmed this solution. The first factor measures the degree to which patients rely on others to help them test and thus was named "social influence." The second component measures the degree to which patients use physical symptoms of blood glucose levels to help them test and thus was named "physical influence." Results of the structural model show that the components are correlated and make up the higher-order latent variable adherence. CONCLUSIONS: The resulting 15-item scale provides a short, reliable way to assess patient adherence to SMBG. Despite the existence of several aspects of adherence, this study indicates that the construct consists of only two components. This scale is an improvement on previous measures of adherence because of its good psychometric properties, its interpretable factor structure, and its rigorous empirical development.

Wagner J A JA; Schnoll R A RA; Gipson M T MT

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653594

Beginning insulin treatment of obese patients with evening 70/30 insulin plus glimepiride versus insulin alone. Glimepiride Combination Group.

OBJECTIVE: This study tested a simple algorithm for beginning insulin for obese patients with type 2 diabetes after sulfonylurea failure, comparing suppertime 70/30 insulin plus continued glimepiride with insulin alone. RESEARCH DESIGN AND METHODS: This was a multicenter ambulatory randomized double-masked parallel comparison. There were 208 subjects with secondary failure to sulfonylureas who took glimepiride titrated to 8 mg b.i.d. for 8 weeks; 145 subjects with fasting plasma glucose (FPG) 180-300 mg/dl (10-16.7 mmol/l) on this treatment were randomized to placebo plus insulin (PI) or glimepiride plus insulin (GI) for 24 weeks. A dosage of 70/30 insulin before supper was titrated, seeking fasting capillary blood glucose (FBG) 120 mg/dl (6.7 mmol/l), equivalent to FPG 140 mg/dl (7.8 mmol/l). Outcome measures included FPG, HbA1c, insulin dosage, weight, serum insulin and lipids, and adverse events. RESULTS: FPG and HbA1c were equivalent at baseline: 261 versus 250 mg/dl (14.5 versus 13.9 mmol/l), and 9.9 versus 9.7%. At 24 weeks, the FPG target was achieved in both groups (136 versus 138 mg/dl, 7.6 versus 7.6 mmol/l), and HbA1c values were equal (7.7 versus 7.6%). However, with GI, control improved faster and fewer subjects dropped out (3 versus 15%, P < 0.01), and less insulin was needed (49 versus 78 U/d, P < 0.001). The outcomes were alike in other respects. No subject had severe hypoglycemia. CONCLUSIONS: Injection of 70/30 insulin before supper safely restored glycemic control of type 2 diabetes not controlled by glimepiride alone. Control was restored more rapidly and with less injected insulin when glimepiride was continued.

Riddle M C MC; Schneider J J

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653595

An Asian multicenter clinical trial to assess the efficacy and tolerability of acarbose compared with placebo in type 2 diabetic patients previously treated with diet. Asian Acarbose Study Group.

OBJECTIVE: To assess the efficacy, safety, and tolerability of acarbose versus placebo during a 24-week treatment period in Asian type 2 diabetic patients with dietary failure. RESEARCH DESIGN AND METHODS: After a 6-week screening period, 126 multiethnic Asian type 2 diabetic patients (64 men, 62 women; mean age +/- SD, 53.4 +/- 10 years) were randomized to receive acarbose (n = 63) or placebo (n = 63). The dosage was increased from 50 mg t.i.d. at week 0 to 100 mg t.i.d. at week 4. Patients were then followed up at weeks 10, 16, and 24. At each visit, body weight, blood pressure, and metabolic indexes were measured. At weeks 0 and 24, fasting plasma glucose and insulin were measured before and 1 h after the administration of an individually tailored breakfast. RESULTS: Using the intention-to-treat analysis, there were greater reductions in (mean) HbA1c (-0.70 versus -0.27%; P = 0.04), fasting plasma glucose (-0.37 versus 0.41 mmol/l; P = 0.017) and 1-h plasma glucose (-0.77 versus 0.65 mmol/l; P = 0.05) in the acarbose group compared with the placebo group. With acarbose treatment, 78% of patients achieved an HbAlc < 8% compared with 56% in the placebo group (P = 0.003). There was a greater reduction in body weight (-1.31 versus 0.16 kg; P = 0.02) and higher incidence of flatulence (56 versus 37%; P = 0.032) in the acarbose than in the placebo group. Using baseline HbA1c and race as covariates, there were no significant interethnic differences in treatment responses (P = 0.232 for treatment-race interaction; P < 0.001 for treatment effect). The dropout rates were similar between the two groups (acarbose, 11 of 63; placebo, 6 of 63). There were no significant laboratory adverse events in either group. CONCLUSIONS: In this multicenter study involving six ethnic groups, acarbose 100 mg t.i.d. was an effective, safe, and generally well-tolerated therapy in Asian type 2 diabetic patients with dietary failure. In some patients with troublesome gastrointestinal symptoms, a lower dosage may be necessary.

Chan J C JC; Chan K W KW; Ho L L LL; Fuh M M MM; Horn L C LC; Sheaves R R; Panelo A A AA; Kim D K DK; Embong M M

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653598

Proteinuria is still useful for the screening and diagnosis of overt diabetic nephropathy.

OBJECTIVE: To assess the performance of urinary total protein measurements in timed 24-h urine collection for 24-h UP, 431 mg/l (92.9% specificity) for UPC, and 0.2 (76.2% specificity) for UPCR. CONCLUSIONS: Measurements of proteinuria presented almost perfect accuracy for the screening and diagnosis of overt diabetic nephropathy. Protein measurement in spot urine is a reliable and simple method for the screening and diagnosis of overt diabetic nephropathy.

Zelmanovitz T T; Gross J L JL; Oliveira J J; de Azevedo M J MJ

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653601

Diabetes in the African-American Medicare population. Morbidity, quality of care, and resource utilization.

OBJECTIVE: To determine whether African-American Medicare recipients with diabetes are at increased risk for morbidity, poor quality of care, and high resource utilization. RESEARCH DESIGN AND METHODS: We analyzed 1,376 patients with diabetes who were > or = 65 years of age and in the 1993 Medicare Current Beneficiary Survey. Morbidity measures were the Katz Index of Activities of Daily Living, Instrumental Activities of Daily Living, overall health perception, Charlson Comorbidity Index score, and diabetic complications. Quality of care standards were glycosylated hemoglobin measurements, ophthalmological visits, lipid testing, mammography, influenza vaccination, readmission within 30 days of hospital discharge, and outpatient visits within 4 weeks of hospital discharge. We stratified Medicare reimbursement by type of service and adjusted for sex, education, and age in multivariable analyses. RESULTS: Compared with white patients, African-American patients had worse health perception and lower quality of care. They were more likely to visit the emergency department and had fewer physician visits per year. African-Americans had higher reimbursement for home health services, but total reimbursement was similar after case-mix adjustment. CONCLUSIONS: Improved access to preventive care for older African-Americans with diabetes may improve health perception and use of the emergency department. The potential effect on total reimbursement is unclear. Future policy interventions to improve quality of care among Medicare patients with diabetes should especially target African-Americans.

Chin M H MH; Zhang J X JX; Merrell K K

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653599

High incidence of diabetic nephropathy in early-onset Japanese NIDDM patients. Risk analysis.

OBJECTIVE: Because early-onset Japanese NIDDM patients. Diastolic blood pressure and duration of diabetes at entry had significant predictive effects independent of metabolic control. CONCLUSIONS: The incidence rate of diabetic nephropathy in early-onset Japanese NIDDM patients is potentially high, similar to or higher than that in Pima Indian NIDDM or Caucasian IDDM patients of comparable age. Diabetic nephropathy in NIDDM patients aged in their thirties or forties is likely to be an early feature that leads to ESRF, and this would contribute to the marked increase in the number of new patients with diabetic ESRF in Japan. NIDDM is a serious disease if near-normal glycemia is not achieved.

Yokoyama H H; Okudaira M M; Otani T T; Watanabe C C; Takaike H H; Miuira J J; Yamada H H; Mutou K K; Satou A A; Uchigata Y Y; Iwamoto Y Y

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653602

Use of the Physician Insurers Association of America database as a surveillance tool for diabetes-related malpractice claims in the U.S.

OBJECTIVE: To examine the available national surveillance data on malpractice claims associated with diabetes and to determine the medical specialties having the highest number of claims and the classes and costs of filed claims relating to diabetes. RESEARCH DESIGN AND METHODS: Data was abstracted from the Data Sharing Reports was noted for the period between 1993 and 1996. Diabetes claimants were older and predominantly male, relative to all claimants. Ophthalmology, internal medicine, and general and family practice had the highest rates of reported claims at 16.5, 13.6, and 13.4 diabetes claims per 1,000 claims, respectively. Of the diabetes-related injuries, 44% occurred in the practitioners office, as compared with 27% for all claims. A greater proportion of diabetes claims were associated with the highest level of severity of injury with respect to all claims compiled by the PIAA. CONCLUSIONS: The database of the PIAA can be a useful resource to monitor trends in diabetes-related malpractice. Further study into whether claims result from lack of adherence to practice guidelines is needed. Prevention programs designed to reduce the liability among high-risk specialties may also lead to improved care for the patient with diabetes.

Meredith V V; Cook C B CB; Penman A A

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653604

Comorbidity of diabetes and eating disorders. Does diabetes control reflect disturbed eating behavior?

OBJECTIVE: This multicenter study was designed to explore the prevalence of clinical and subclinical eating disorders (EDs), the extent of intentional omission of insulin and oral antidiabetic agents, and its relationship to glycemic control in an inpatient and outpatient population of men and women with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Data have been collected from 12 diabetes medical centers in two German cities. In a questionnaire and interview-based study, a sample of male and female patients (n = 341 type 1, n = 322 type 2) was assessed for the following eating disorders: anorexia nervosa, bulimia nervosa, binge eating disorder, and eating disorder not otherwise specified. For lack of interview data of several patients meeting the screening criteria, prevalence ranges were calculated. RESULTS: The overall prevalence range of current EDs was 5.9-8.0% (lifetime prevalence 10.3-14.0%). When patients were stratified according to type 1 and type 2 diabetes, there was no difference in prevalence of EDs. However, the distribution of the EDs was different in both types of diabetes, with a predominance of binge eating disorder in the type 2 diabetes sample. Type 1 (5.9%) and type 2 (2.2%) diabetic patients reported deliberate omission of hyperglycemic drugs (insulin or oral agents) in order to lose weight. Compared with control subjects, neither the presence of EDs nor insulin omission influenced diabetic control. CONCLUSIONS: There seems to be no difference in prevalence rates of EDs in both types of diabetes; however, distribution of EDs is different. The findings suggest that neither EDs nor insulin omission are necessarily associated with poor control of glycemia. Binge eating disorder seems to precede type 2 diabetes in most patients and could be one of the causes of obesity that often precedes type 2 diabetes.

Herpertz S S; Albus C C; Wagener R R; Kocnar M M; Wagner R R; Henning A A; Best F F; Foerster H H; Schulze Schleppinghoff B B; Thomas W W; Köhle K K; Mann K K; Senf W W

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653607

Association of Helicobacter pylori infection with cardiovascular and cerebrovascular disease in diabetic patients.

OBJECTIVE: Infection by Helicobacter pylori has been epidemiologically linked to some extradigestive conditions, including ischemic heart disease. Diabetic patients are an at-risk population for cardiovascular and thrombo-occlusive cerebral disease. The aim of the study was to examine a possible relationship between H. pylori infection and cardiovascular or cerebrovascular disease in diabetic patients. RESEARCH DESIGN AND METHODS: This was a cross-sectional case-control study with 127 diabetic patients (both IDDM and NIDDM). Special emphasis was placed on the detection of clinical macro- and microvascular complications, cardiovascular risk factors, acute phase reactants, and serological markers of increased cardiovascular disease risk. H. pylori infection was assessed through the determination of specific Ig-G titers, measured by a commercial enzyme-linked immunosorbent assay. RESULTS: Coronary heart disease was more prevalent in diabetic patients with than without H. pylori (odds ratio [OR] 4.07; 95% CI 1.21-13.6; P < 0.05). A history of thrombo-occlusive cerebral disease was also more frequent in H. pylori-positive diabetic patients (OR 4.8; 95% CI 1.24-18.51; P < 0.05). Other complications such as peripheral arteriopathy, advanced nephropathy, neuropathy, or retinopathy were no differently distributed according to serological status. Alterations in the levels of the following acute-phase reactants and blood chemistry determinations were significantly more profound in H. pylori-positive diabetic patients: high fibrinogen (P < 0.05), high erythrocyte sedimentation rate (P < 0.001), high triglycerides (P < 0.001), and low HDL cholesterol (P < 0.001). There values were also more deeply altered in H. pylori-positive diabetic patients with a history of coronary heart disease, thrombo-occlusive cerebral disease, or both, when compared with H. pylori-positive diabetic patients without those complications. CONCLUSIONS: Our data indicate a possible association of H. pylori infection and the development of coronary heart disease, thrombo-occlusive cerebral disease, or both, in diabetic patients. The importance of this link is highlighted by the possibility of an effective intervention against H. pylori infection.

de Luis D A DA; Lahera M M; Cantón R R; Boixeda D D; San Román A L AL; Aller R R; de La Calle H H

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653606

Direct medical costs of complications resulting from type 2 diabetes in the U.S.

OBJECTIVE: To estimate direct medical costs of managing the complications of type 2 diabetes. RESEARCH DESIGN AND METHODS: Costs were estimated for 15 diabetic complications by applying unit costs to typical resource-use profiles. Resource used and unit costs were estimated from many sources, including acute care discharge databases, clinical guidelines, government reports, fee schedules, and peer-reviewed literature. For each complication, the event costs are those associated with resource use that is specific to the acute episode and any subsequent care occurring in the 1st year. State costs are the annual costs of continued management. All costs are expressed in 1996 U.S. dollars. RESULTS: As expected, the more severe or debilitating events, such as acute myocardial infarction ($27,630 event cost; $2,185 state cost), generate a greater financial burden than do early-stage complications, such as microalbuminuria ($62 event cost; $14 state cost). Yet, complications that are initially relatively low in cost (for example, microalbuminuria) can progress to more costly advanced stages (for example, end-stage renal disease, $53,659 state cost); therefore, minor complications should also be considered in any economic analysis of diabetes. CONCLUSIONS: The recent literature has lacked cost estimates that may be readily translated into patient-level cost inputs for an economic model. Emerging therapies that may reduce the incidence of some diabetic complications will need to be scrutinized economically in today's cost-conscious environment. The cost estimates from this study provide one piece of the economic analysis needed to evaluate these new interventional therapies.

O'Brien J A JA; Shomphe L A LA; Kavanagh P L PL; Raggio G G; Caro J J JJ

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653608

Usefulness of revised fasting plasma glucose criterion and characteristics of the insulin response to an oral glucose load in newly diagnosed Japanese diabetic subjects.

OBJECTIVE: To examine the usefulness of the revised criterion for fasting plasma glucose (FPG) in the diagnosis of diabetes recommended by the American Diabetic Association (ADA) (126 mg/dl, 7 mmol/l), and to characterize insulin response during the 75-g oral glucose tolerance test (OGTT) in newly diagnosed Japanese diabetic subjects. RESEARCH DESIGN AND METHODS: A series of 2,121 Japanese subjects underwent a 75-g OGTT (0-3 h) and were divided into three groups (normal glucose tolerance [NGT], impaired glucose tolerance [IGT], and diabetes mellitus [DM] according to the current World Health Organization criteria. After the cutoff values of FPG that distinguish NGT and IGT from diabetes were analyzed, the usefulness of the ADA criterion for FPG was examined by comparing diagnostic parameters (sensitivity, specificity, and accuracy) with those for the cutoff value of 140 mg/dl. To assess insulin response, both the insulinogenic index (IsIx), a marker of early secretion, and the area under the insulin response curve (AUCins), a marker of total secretion, were compared between the DM, NGT, and IGT groups. RESULTS: First, the FPG cutoff value distinguishing NGT from diabetes was 109 mg/dl. An FPG of 126 mg/dl showed a higher sensitivity (0.52 versus 0.31), the same specificity (1.00), and a higher accuracy (0.82 versus 0.74) than an FPG of 140 mg/dl, and it had a higher specificity (1.00 versus 0.86) with a slightly lower accuracy (0.82 versus 0.85) than an FPG of 109 mg/dl. Second, the FPG cutoff value differentiating IGT from diabetes was 113 mg/dl. An FPG of 126 mg/dl showed a higher sensitivity (0.52 versus 0.31) and accuracy (0.80 versus 0.74) and a similar specificity (0.97 versus 1.00) compared with an FPG of 140 mg/dl, and it had a higher specificity (0.97 versus 0.82) with the same accuracy (0.80) as an FPG of 113 mg/dl. Third, the DM group showed the lowest IsIx among the three groups at all FPG values. The AUCIns in the DM group increased along with FPG, reached the maximum level at an FPG of 110 mg/dl, and declined thereafter. AUCIns was higher in the DM group than in the NGT group at FPG values > or = 100 mg/dl. CONCLUSIONS: The revised ADA criterion for FPG of 126 mg/dl may improve diagnostic sensitivity without loss of specificity in Japanese diabetic subjects when compared with an FPG criterion of 140 mg/dl. Although early insulin secretion was impaired, total insulin secretion did not seem to be reduced in newly diagnosed Japanese diabetic subjects.

Tanaka Y Y; Atsumi Y Y; Asahina T T; Hosokawa K K; Matsuoka K K; Kinoshita J J; Onuma T T; Kawamori R R

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653609

Mortality in adults with and without diabetes in a national cohort of the U.S. population, 1971-1993.

OBJECTIVE: To examine 22-year mortality, causes of death, life expectancy, and survival in a national sample of diabetic and nondiabetic adults according to age, sex, and race. RESEARCH DESIGN AND METHODS: A representative national cohort of 14,374 adults aged 25-74 years was identified in 1971-1975 in the First National Health and Nutrition Examination Survey. Causes of death were determined from death certificates. RESULTS: Diabetic subjects comprised 5.1% of the cohort and accounted for 10.6% of the deaths. Mortality for diabetic subjects increased from 12.4 per 1,000 person-years for those aged 25-44 years at baseline to 89.7 per 1,000 person-years for those aged 65-74 years. The age-adjusted mortality rate was 57% higher for diabetic men than for diabetic women; the rate was 27% higher for diabetic non-Hispanic blacks than for diabetic non-Hispanic whites. Mortality rates were highest for insulin-treated subjects and for those with > or = 15 years' duration of diabetes. Diabetes was listed on the death certificate as the underlying cause of death for only 7.7% of diabetic men and 13.4% of diabetic women. Considering multiple causes of death, heart disease was listed the most frequently and was present on 69.5% of death certificates of people with diabetes. Death rates were higher for diabetic than for nondiabetic subjects in all age, sex, and race groups. The relative risk of death (diabetic versus nondiabetic subjects) declined with age from a value of 3.6 for those aged 25-44 years at baseline to 1.5 for those aged 65-74 years. The relative risk was elevated in diabetic subjects for all major causes of death except malignant neoplasms. Survival of diabetic subjects was lower than that of nondiabetic subjects in all age, sex, and race groups. Median life expectancy was 8 years lower for diabetic adults aged 55-64 years and 4 years lower for those aged 65-74 years. CONCLUSIONS: In this representative national sample of adults, mortality rates were higher for diabetic men than for diabetic women and for diabetic blacks than for diabetic whites. The study confirms the substantially higher risk of death, lower survival, and lower life expectancy of diabetic adults compared with nondiabetic adults.

Gu K K; Cowie C C CC; Harris M I MI

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653610

Factors associated with glycemic control. A cross-sectional nationwide study in 2,579 French children with type 1 diabetes. The French Pediatric Diabetes Group.

OBJECTIVE: To determine on a large scale the multiple medical and nonmedical factors that influence glycemic control in the general population of children with diabetes, we performed a nationwide French cross-sectional study. RESEARCH DESIGN AND METHODS: We enrolled 2,579 patients aged 1-19 years with type 1 diabetes of > 1 year's duration. The study was center based: 270 centers were identified, 206 agreed to participate, and 147 included at least 90% of their patients. Questionnaires were completed by physicians interviewing patients and family, and HbA1c measurements were centralized. To identify explanatory variables for HbA1c level and frequency of severe hypoglycemia, we performed multiple regression analysis using all the quantitative variables collected and stepwise logistic regression for the qualitative variables. RESULTS: Mean HbA1c value for the whole population was 8.97 +/- 1.98%, then with daily insulin dosage per kilogram, mother's age, frequency of glucose measurements, and diabetes duration. Logistic regression identified quality of family support and dietary compliance, two related qualitative and possibly subjective variables, as additional explanatory determinants of HbA1c. The frequency of severe hypoglycemia was 45 per 100 patient-years and correlated with diabetes duration, but not with HbA1c levels or other variables. CONCLUSIONS: Although overall results remain unsatisfactory, 33% of studied French children with type 1 diabetes had HbA1c < 8%, the value obtained in Diabetes Control and Complications Trial adolescents treated intensively. Diabetes management in specialized centers should be encouraged.

Rosilio M M; Cotton J B JB; Wieliczko M C MC; Gendrault B B; Carel J C JC; Couvaras O O; Ser N N; Gillet P P; Soskin S S; Garandeau P P; Stuckens C C; Le Luyer B B; Jos J J; Bony-Trifunovic H H; Bertrand A M AM; Leturcq F F; Lafuma A A; French Pediatric Diabetes Group; Bougnères P F PF

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653614

Effects of diabetes and level of glycemia on all-cause and cardiovascular mortality. The San Antonio Heart Study.

OBJECTIVE: Although the level of hyperglycemia is clearly a risk factor for microvascular complications in diabetic patients, its role in macrovascular complications remains controversial. We followed 4,875 subjects (65% Mexican-American) for 7-8 years to investigate the effects of diabetes and hyperglycemia on all-cause and cardiovascular disease (CVD) mortality. These end points were also analyzed according to quartiles of baseline fasting plasma glucose among diabetic participants. RESEARCH DESIGN AND METHODS: The Cox proportional hazards model was used to estimate the relative risks (RRs) for all-cause and CVD mortality. RESULTS: Diabetes was significantly associated with increased all-cause mortality (RR = 2.1 in men; 3.2 in women) and increased CVD mortality (3.2 in men; 8.5 in women). Among diabetic subjects, those in quartile 4 had a 4.2-fold greater risk of all-cause mortality (P < 0.001) and a 4.7-fold greater risk of CVD mortality (P = 0.01) than those in quartiles 1 and 2 combined. After further adjustment for other potential risk factors, subjects in quartile 4 had a 4.9-fold greater risk of all-cause mortality and a 4.9-fold greater risk of CVD mortality than those in quartiles 1 and 2. In addition, hypertension, current smoking, and cholesterol > 6.2 mmol/l were significant predictors of CVD mortality using Cox models. CONCLUSIONS: We conclude that diabetes is a predictor of both all-cause and CVD mortality in the general population and that both hyperglycemia and common CVD risk factors are important predictors of all-cause and CVD mortality in diabetic subjects.

Wei M M; Gaskill S P SP; Haffner S M SM; Stern M P MP

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653613

Optimization of evening insulin dose in patients using the short-acting insulin analog lispro.

OBJECTIVE: A three-way, crossover, open-label, randomized study was designed to compare the evening and night glycemic control when the evening premeal lispro dose was reduced by 20% and the bedtime basal NPH dose increased by 25%, or when the basal NPH dose was moved to before dinner at 1800, compared with the control arm on standard premeal human regular insulin and pre-bedtime NPH insulin. RESEARCH DESIGN AND METHODS: A total of 13 type 1 diabetic patients who use a premeal plus basal insulin regimen were studied on three separate days, with identical meals and snacks at the same times on each study day. On the control study day, patients received human regular insulin before dinner and NPH at bedtime in their usual doses. On another day, lispro was given before dinner with a dose reduction of 20%, and NPH at bedtime at 125% of usual dose. In the third regimen, the lispro and NPH were administered together in their usual dose before the evening meal by separate injections. The three regimens were tested in random order. RESULTS: Postprandial blood glucose concentrations were lower after reduced-dose lispro compared with human regular insulin blood glucose concentrations were not different (8.6 +/- 0.3 versus 9.2 +/- 0.3 mmol/l, NS), and prebreakfast concentrations were also unchanged (7.7 +/- 0.9 versus 8.7 +/- 0.8 mmol/l) after lispro with increased-dose NPH compared with standard insulin. By contrast, both nighttime (10.0 +/- 0.3 mmol/l, P < 0.05) and fasting glucose concentrations (10.8 +/- 0.6 mmol/l, P < 0.05) were significantly higher with dinnertime usual-dose lispro plus dinnertime usual-dose NPH compared with standard human insulin. Hypoglycemia at night (blood glucose < 3.0 mmol/l) did not differ between study days, but it was more frequent postprandially after dinner usual-dose lispro plus early NPH (2 versus 7 patients, P = 0.062). CONCLUSIONS: With lower mealtime and higher basal bedtime insulin doses, patients using insulin lispro may be able to gain an overall improvement in evening blood glucose control without deteriorated nighttime glucose levels. Earlier basal NPH dosage alone does not ameliorate the nighttime hyperglycemia of short-acting insulin analog regimens.

Ahmed A B AB; Mallias J J; Home P D PD

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653617

Progression to type 2 diabetes among high-risk groups in Kin-Chen, Kinmen. Exploring the natural history of type 2 diabetes.

OBJECTIVE: To examine the natural history of 654 high-risk subjects were followed up. Of these, 8.1% had progressed to diabetes (4.1% progression/year, 95% CI 2.3-5.9). Of 131 baseline IGT subjects, 17.6% progressed to diabetes (8.8% progression/year, 6.3-11.3), but only 7.4% of 95 PFH subjects (3.7% progression/year, 2.0-5.4) and 3.5% of 255 NGT subjects (1.8% progression/year, 0.1-3.0) progressed to diabetes. CONCLUSIONS: The rates of progression to type 2 diabetes were lowest from the NGT subgroup, highest from the IGT group, with the PFH group in the middle, suggesting that PFH might be a transitional condition that precedes IGT and diabetes. Other significant predictors of subsequent diabetes were baseline BMI, baseline hyperuricemia, baseline FPG, and 2-h plasma glucose concentration.

Chou P P; Li C L CL; Wu G S GS; Tsai S T ST

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Diabetes care

9653619

Glucokinase gene islet promoter region variant (G-->A) at nucleotide -30 is not associated with reduced insulin secretion in Finns.

OBJECTIVE: To investigate the effect of the islet promoter region variant (G-->A) at nucleotide -30 of the glucokinase (GCK) gene on insulin levels in subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and NIDDM. RESEARCH DESIGN AND METHODS: The study population included 294 subjects with NGT, 83 subjects with IGT, and 36 subjects with NIDDM. Oral glucose tolerance tests (OGTTs) were performed in all subjects, and intravenous glucose tolerance tests (IVGTTs) were performed in subjects with NGT. The islet promoter region of the GCK gene was amplified with polymerase chain reaction and screened for the variant (-30) using single-strand conformation polymorphism analysis. RESULTS: The islet promoter variant (-30) of the GCK gene was found in 17% of subjects with NGT, 23% of subjects with IGT, and 14% of patients with NIDDM (NS between the groups). Fasting, 1-h, and 2-h insulin levels, measured by OGTT, did not differ between subjects with and without this variant in any of the three groups. Furthermore, first-phase insulin secretion, determined by an IVGTT in subjects with NGT, did not associate with presence of the islet promoter region variant (-30) of the GCK gene. CONCLUSIONS: These results indicate that the variant (-30) of the islet promoter region of the GCK gene does not have a significant effect on insulin secretion in Finnish subjects with NGT, IGT, or NIDDM.

Rissanen J J; Saarinen L L; Heikkinen S S; Kekäläinen P P; Mykkänen L L; Kuusisto J J; Deeb S S SS; Laakso M M

1998-07-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Prostaglandins & other lipid mediators

9653772

Differing profiles of prostaglandin formation inhibition between selective prostaglandin H synthase-2 inhibitors and conventional NSAIDs in inflammatory and non-inflammatory sites of the rat.

The present study examined the inhibitory profiles of NS-398 and nimesulide against prostaglandin (PG) formation in inflammatory and non-inflammatory sites, and compared them with those of aspirin and indomethacin. In vitro, indomethacin inhibited PGH synthase (PGHS)-1 and PGHS-2 almost equally, while NS-398 and nimesulide inhibited only PGHS-2. NS-398 (1, 10 mg/kg) and nimesulide (3 mg/kg) slowed the rate of plasma exudation and thus the exudate accumulation in rat carrageenin-induced pleurisy. Aspirin (30, 100 mg/kg) and indomethacin (10 mg/kg) also reduced this rate. NS-398 and nimesulide reduced the PGE2 more potently than TXB2 and 6-keto-PGF1 alpha in the exudate. However, aspirin and indomethacin did not exhibit this selectivity. The levels of PGE2 correlated significantly with the plasma exudation rate. Moreover, nimesulide (3 mg/kg) did not affect PGE2 formation in rat stomachs injected with 1 M NaCl solution, while indomethacin (10 mg/kg) reduced it. Thus, NS-398 and nimesulide exhibit different inhibitory profiles from aspirin and indomethacin against PG formation. These results suggest that PGE2 may be produced by PGHS-2 in the inflammatory site, and may play a more prominent role than PGI2 in plasma exudation.

Harada Y Y; Kawamura M M; Hatanaka K K; Saito M M; Ogino M M; Ohno T T; Ogino K K; Yang Q Q

1998-04-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Prostaglandins & other lipid mediators

9653774

Inhibition of Na+,K(+)-ATPase by platelet-activating factor in dog submandibular glands.

Physiological stimulation of dog submandibular gland has been shown to generate platelet-activating factor (PAF). However, PAF is not released from cells in the tissue. To assess its intracellular activity, the effect of PAF on Na+,K(+)-ATPase was examined in dog submandibular gland cells. PAF inhibited Na+,K(+)-ATPase in membrane preparations, and the inhibitory effect was dependent on the protein concentration in the enzyme preparation. The inhibitory effect of a low concentration of PAF was antagonized by a PAF-receptor antagonist, BN 50,739, but at high concentrations, PAF was not antagonized. Kinetic analysis of PAF inhibition of Na+,K(+)-ATPase suggests that the inhibition of Na+,K(+)-ATPase by PAF is not due to competition by PAF at K(+)- or Na(+)-binding sites on the enzyme, but by complex inhibitory mechanisms. These results suggest that PAF may interact with specific and nonspecific site of action resulting in the inhibition of Na+,K(+)-ATPase. Ouabain increased mucin release from dog submandibular gland cells. Because Na+,K(+)-ATPase and ion exchange pathways are important in the secretory responses of acinar cells, PAF may regulate intracellularly the secretory function of acinar cells by modulating Na+,K(+)-ATPase and ionic homeostasis.

Itadani K K; Morita K K; Kitayama S S; Imai Y Y; Yamaki H H; Akagawa Y Y; Dohi T T

1998-04-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Romanian journal of physiology : physiological sciences

9653807

The renin-angiotensin system and the effect of propranolol upon the cerebral cortical and hypothalamic circulation in hypoxia.

The regulatory mechanisms of the cerebral blood flow have preoccupied the physiology department of Cluj since the end of the 4th decade. These studies continued over the last years. The researches progressed from the studies of regulation by blood pressure changes to the nervous regulation and to the metabolic one. This paper's subject is the renin-angiotensin and adrenalin system influence on the changes of cerebral blood flow during the general hypoxic hypoxia and cephalic ischemia. Experiments were performed in 10 dogs anaesthetised with a mixture of chloralose, urethan and morphine. Hypoxic hypoxia was obtained by breathing a mixture of 11% oxygen in nitrogen, in a closed system and cerebral ischemic hypoxia by partial compression of the carotid arteries, after the ligation of the vertebral and thyroid arteries. The arterial blood pressure and the cerebral and hypothalamic blood flow, measured with the heated thermoelement, were registered. The plasma renin activity was tested radioimmunologically before, at 1.5 min, 5, 10 and 15 min, after the beginning of hypoxia. In ischemic hypoxia the experiment was repeated after venous perfusion with propranolol (0.6 mg/kg/h). The systemic blood pressure increased in both forms of hypoxia. The cortical and hypothalamic blood flow increased with the systemic arterial blood pressure. The hypothalamic blood flow remained stable or diminished a little. Propranolol increased the cerebral blood flow during ischemic hypoxia up to 300%. The i.v. administration of angiotensin (1-5 mg/kg) increased the cortical flow, while the hypothalamic flow remained self-regulated. Plasma renin activity increased more in general hypoxic hypoxia, than in cephalic ischemic hypoxia. After propranolol the increase was higher in this hypoxia. Propranolol produced a major activation of the renin-angiotensin system and of the cortical blood flow in ischemic cephalic hypoxia, the renin-angiotensin system being located in the cerebral structure. As well high doses of angiotensin produced cerebral vasodilatation in small cerebral vessels. This effect was found in our experiments in the cortical blood flow too. Our results indicate a beneficial propranolol effect on cortical circulation in ischemic hypoxia.

Olteanu A A; Grosu L L; Vlasie N N; Pavel T T; Barabas E E; Baciu I I

1997-01-01

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Romanian journal of physiology : physiological sciences

9653814

Investigation of immune reactivity in alcoholism with hepatic disease of various degrees.

The clinical and experimental investigations of alcoholic liver disease, have proved that hepatocytes injury is associated with immunologic abnormalities, which can be one of the sources of these injuries. The acetaldehyde, the main ethanol metabolite modify liver cytosolic proteins and form new antigens. Thus acetaldehyde induces the synthesis of auto-antibodies. Some hypotheses maintain the autoimmune pathogenesis of these diseases. Research was carried out on some patient groups admitted in the alcohol addiction department of the Neurology and Psychiatry hospital "Professor Gh. Marinescu". We have investigated the alcohol depending individuals with various degrees of hepatic injuries. Four groups have been studied: the control group, the alcohol depending patients without liver disease, the patients with alcoholic hepatitis, the group with alcoholic cirrhosis. In order to investigate the immunologic response the research has been carried on, along the following lines: serum immunoglobulins level, serum C3 level, serum protein C reactive level by using IDR, serum circulating immune complexes by Hakova method, auto-antibodies (antinuclear AAN, antimitochondria AM and antismoothmuscle ASM) by using indirect immunofluorescence, T lymphocytes by E rosetting and lymphocytes by direct immuno-fluorescence. Clinical and experimental study of the alcoholic liver has shown that destruction of hepatocytes is accompanied by several immunological events.

Negru T T; Ghiea V V; Păsărica D D

1997-01-01

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Romanian journal of physiology : physiological sciences

9653817

A spectrophotometric assay of folic acid concentrations in rats: correlations with age and organ.

Spectrophotometric assays have been used to determine FA concentration in tissue homogenates from various organs (liver, kidneys, brain, spleen) in white rats; these studies were undertaken to test the age--and organ--dependent variations of FA concentrations in tissue homogenates. The results showed a marked decrease of FA concentration in the adult group of rats when related to the young group, and in the aged group when compared to the adults respectively. Analysing the determined values of folates in tissue homogenates of various organs (in rats belonging to the same group of age), the highest concentration has been found in the liver homogenate, followed in decreasing order by kidneys and to a much greater distance, by the brain and spleen.

Atanasiu V V; Niculescu I I; Niculescu O O; Iacoban S S; Trutia E E

1997-01-01

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

American journal of nephrology

9653831

Can total urinary protein measurements predict microalbuminuria?

We re-addressed the question of whether routine total urinary protein determinations can be used to predict the presence of microalbuminuria by studying 61 patients who attended a diabetic clinic and tested negative or had one positive protein by dipstick. Total urinary protein was measured by the Biorad dye-binding method in undialyzed urine (UND), in dialyzed urine (DIAL), and in dialyzed urine in which albumin and globulins were separated, measured separately with albumin and globulin standards and the results added together to obtain total urinary protein (A + G). The results were compared with albumin measurements obtained by radioimmunoassay (RIA). Compared to DIAL, urinary protein measurements were 43% higher with A + G and 22% higher with UND. Microalbuminuria correlated moderately with UND (r =0.81) and better with the other methods (r=0.87 for DIAL, r=0.91 for A + G). None of the methods predicted microalbuminuria reliably. Taking a protein-to-creatinine ratio of 0.15 and an albumin-to-creatinine ratio of 0.03 as upper limits of normal, we found that UND had a 72% positive predictive value (28% false positives) and 85 % negative predictive value (15% false negatives). DIAL had 90% positive predictive value (10% false positives) and 78% negative predictive value (22% false negatives). A + G had 65% positive predictive value (35% false positives) but 91% negative predictive value (9% false negatives). A + G, which uses the correct standards, would be the most suitable method for screening, having the least number of false negatives, but has more false positives because it is more sensitive. In practice, most routine chemical laboratories find it expedient to use only UND, but physicians interpreting the results of this method should be aware of its limitations.

Stankeviciute N N; Sabah S S; Singh A A; Shaykh M M; Bakir A A AA; Arruda J A JA; Dunea G G

1998-10-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

American journal of nephrology

9653834

Metalloproteinase-9 mRNA expression in monocytes from patients with chronic renal failure.

Long-term dialysis patients suffer from various complications including atherosclerosis. It has been suggested that metalloproteinases (MMPs) contribute to vascular remodeling during the development and progression of human atherosclerosis. Activated human monocytes have been demonstrated to secrete MMPs. In the present study, we measured levels of MMP mRNA in peripheral blood monocytes obtained from patients on continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD) and chronic-renal-failure patients not undergoing dialysis. Twenty patients with chronic renal failure were not undergoing dialysis, 20 patients were on CAPD, 40 patients were on chronic HD and 20 healthy volunteers served as controls. We used cDNA probes encoding for MMP-1, MMP-2, MMP-3 and MMP-9 and glyceraldehyde phosphate dehydrogenase. Higher levels of MMP-9 mRNA in the peripheral blood monocytes were observed in HD patients than in CAPD patients, undialyzed chronic renal failure patients or healthy controls. MMP-9 mRNA levels at the end of HD were not significantly higher than those at the start of HD. MMP-9 mRNA levels from HD patients did not differ among the types of membranes. We could detect minimal MMP-1, MMP-2 and MMP-3 mRNA expression in monocytes from all groups. Serum gelatinase activity was detectable in all samples; however, no significant differences existed among the groups. In summary, MMP-9 mRNA expression is enhanced in monocytes from HD and CAPD patients, and the enhancement may be, in part, associated with cardiovascular complications, including atherosclerosis, in dialysis patients. This increase in monocyte MMP-9 mRNA levels is lower in CAPD patients that it is in HD patients.

Ebihara I I; Nakamura T T; Tomino Y Y; Shimada N N; Koide H H

1998-10-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

Romanian journal of physiology : physiological sciences

9653815

Effect of nifedipine on electrical activity of the brain in rat.

Effect of calcium channel blocker nifedipine on the electrical activity of the brain in anaesthetized rats was studied. The electoencephalographic signals were registered on a computer as series of data and thereafter they were decomposed by Fourier analysis in very narrow fields of frequency. The electrical activity of the brain of the control rats was asymmetrical, with a more important activity in the left brain hemisphere, particularly between 20-30 Hz when the electrical activity of the brain was globally more important. The nifedipine increased the electrical activity of the brain between 0.5-4 Hz and 20-30 Hz in a dose-dependent manner. The drug also increased the interhemispheric asymmetry. Some possible explanations of these effects are analyzed.

Fulga I G IG; Stroescu V V

1997-01-01

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

American journal of nephrology

9653842

Oxidative modification of low-density lipoprotein enhances mesangial cell protein synthesis and gene expression of extracellular matrix proteins.

The proliferation of intrinsic glomerular cells and the accumulation of extracellular matrix proteins are principal histopathological features seen in glomerular injury. Because of the marked similarity between the cellular and molecular events that occur in both atherosclerosis and glomerulosclerosis and the commonly accepted hypothesis that lipoproteins are implicated in the pathogenesis of glomerulosclerosis, we examined the effect of three atherogenic lipoproteins, low-density lipoprotein (LDL), oxidized (ox)-LDL, and minimally modified (mm)-LDL on the synthesis and secretion of extracellular matrix (ECM) proteins by mesangial cells. The incubation of SV-40 transformed murine mesangial cells with LDL (25-100 microg/ml) increased the synthesis and secretion of both fibronectin and laminin in a dose-dependent manner. Similarly, oxidized forms of LDL (25-100 micro/ml) increased fibronectin and laminin synthesis and secretion dose dependently. However, both oxidatively modified forms of LDL had a greater effect on increasing ECM protein synthesis than their native counterpart. Northern blot analysis showed a dose-dependent increase in mRNA transcripts for fibronectin and laminin in response to the incubation of mesangial cells with LDL, ox-LDL, and mm-LDL. Similar to the ECM protein expression data, the oxidatively modified forms of LDL had more pronounced effects on the gene expression of both fibronectin and laminin. These data show that both LDL and, perhaps more importantly, its oxidatively modified forms stimulate mesangial cells to upregulate both the gene expression and synthesis and secretion of ECM proteins, supporting a role for atherogenic lipoproteins in the pathobiology of glomerular injury.

Roh D D DD; Kamanna V S VS; Kirschenbaum M A MA

1998-10-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999

PUBMED

The Australian & New Zealand journal of obstetrics & gynaecology

9653859

Which Korotkoff sound should be used for the diastolic blood pressure in pregnancy?

There is a gathering momentum favouring the adoption of the 5th Korotkoff sound to identify diastolic blood pressure in pregnancy. Our objective was to measure interobserver reliability for indirect blood pressure measurement in pregnancy for systolic and diastolic measurements and to calculate the difference in diastolic pressure measured by the 4th and 5th Korotkoff sounds. To minimize bias we used trained but previously inexperienced observers with proven, normal auditory acuity. The observers were paired in 4 teams and performed a series of 334 blinded, simultaneous observations of systolic and diastolic blood pressure measurements taken from pregnant women between 12-41 weeks' gestation. Reliability was measured by intraclass correlation coefficient for paired measures and kappa for the detection or nondetection of 4th (K4) and 5th (K5) Korotkoff sounds. K4 was undetected in 36% of observations and K5 was undetected in 2% of observations. Reliability for detection or nondetection of Korotkoff sounds was fair for K4 (kappa 0.36) and moderate for K5 (kappa 0.58). Reliability was good between observers for systolic, K4 and K5 diastolic measurements (intraclass correlation > or = 0.80). The mean difference between the diastolic pressure measured by K4 and K5 was 15 mmHg for all measurements and 8 mmHg for the top quartile of measurements (p <0.001). We found K5 to be more often and more reliably detected than K4. If units adopt K5 in preference to K4, consideration will need to be given to lowering treatment thresholds for women with borderline or mild hypertension.

Duggan P M PM

1998-05-02

pubmed24n0320.xml

Metabolism & Diabetes

1995-1999