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PUBMED | The Australian & New Zealand journal of obstetrics & gynaecology | 9653860 | Blood pressure measurement in pregnancy--a survey of methods used in teaching hospitals in South Australia. | A voluntary, anonymous 10-point multiple choice questionnaire was used to assess variability in methods used to measure blood pressure in pregnancy in 5 South Australian teaching hospitals. Medical and midwifery staff working in maternity units attached to teaching hospitals in South Australia were asked to complete a survey of their current practice related to the measurement of blood pressure in pregnant women; 213 replies were received from 440 surveyed (48% response rate). There was a lack of standardization of practice for: positioning of the patient, use of the 4th or 5th Korotkoff sound for diastolic blood pressure, cuff selection, rounding of the measurement, selection of the left or right arm, and period of premeasurement resting. Systematic errors averaging 10-15 mmHg can be expected in measurement of blood pressure in pregnancy due to failure of standardization of method. There is a need for standardization of method which is not being met by present methods of staff training in teaching hospitals. | Duggan P M PM; Miller J J | 1998-05-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | The Australian & New Zealand journal of obstetrics & gynaecology | 9653868 | A case report of Sheehan syndrome presenting with diabetes insipidus. | Hypopituitarism caused by necrosis of the physiologically enlarged pituitary gland of pregnancy following postpartum haemorrhage was first described by Sheehan (1). Although manifestations of the clinical syndrome are most often caused by deficiencies of hormones of the anterior pituitary gland, involvement of the posterior lobe of the pituitary gland although rare has been described (2,3). This is a report of a case of diabetes insipidus developing within 24 hours postpartum in a grand multipara who had an elective lower segment Caesarean section for twins. | Kan A K AK; Calligerous D D | 1998-05-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of pharmacology | 9653875 | Differential effects of selective adenosine A1 and A2A receptor agonists on dopamine receptor agonist-induced behavioural responses in rats. | The effects of the systemic on different dopamine receptor agonist-induced behaviours were studied in the male rat. CGS 21680 and high doses of CPA, while CGS 21680 was ineffective. These results are consistent with the proposed existence of a selective antagonistic modulation of dopamine D1 and D2 receptors by adenosine A1 and A2A receptors, respectively. The ability of CGS 21680 to counteract apomorphine-induced stereotypies is weaker compared to its previously reported antagonistic effect of amphetamine-induced motor activity. This supports the hypothesis that adenosine A2A receptor agonists may be potential antipsychotic drugs with a low potential for extrapyramidal side effects. | Rimondini R R; Ferré S S; Giménez-Llort L L; Ogren S O SO; Fuxe K K | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of pharmacology | 9653878 | Adenosine A2 receptor mediation of pre- and postsynaptic excitatory effects of adenosine in rat hippocampus in vitro. | Excitatory effects of adenosine in the rat hippocampus were studied by intracellular recording from CA1 pyramidal cells in vitro. Application of 100 microM adenosine induced a rapid hyperpolarization and a decrease in input resistance, and depressed the excitatory postsynaptic potentials, a selective adenosine A2 receptor agonist, induced a slow depolarization associated with an increase in input resistance and, in 11 of 36 neurons, enhanced the amplitude of evoked EPSPs. These excitatory effects of CGS 21680 were blocked by the selective adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine depressed the amplitude of EPSPs evoked by stimulation of Schaffer collateral afferents, yet there was little effect on the resting membrane potential or input resistance despite the fact that 20 microM chloroadenosine caused a pronounced hyperpolarization associated with a decrease in input resistance in the same cell. These results indicate that the excitatory effects of adenosine may be mediated via activation of adenosine A2 receptors at both presynaptic and postsynaptic sites in the hippocampal CA1 region. | Li H H; Henry J L JL | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of pharmacology | 9653883 | Vasopressin mediates the inhibitory effect of central angiotensin II on cerebrospinal fluid formation. | Angiotensin II infused at low doses into the cerebral ventricles decreases cerebrospinal fluid (CSF) production. Since central angiotensin II also activates the sympathetic nervous system and promotes vasopressin release, the roles of these two factors in mediating the inhibitory effect of angiotensin II on CSF formation were studied. CSF production was measured in rats by the ventriculocisternal perfusion method. During central angiotensin II infusion (5 pg min(-1)), the following adrenoceptor antagonists were administered intravenously (i.v.): phentolamine (alpha1/alpha2, 2 mg/kg per h), prazosin (alpha1, 1 mg/kg per h), and propranolol (beta, 1 mg/kg per h). None of these agents affected the inhibitory effect of angiotensin II on CSF formation. In comparison, in animals administered i.v., the vasopressin V1 receptor antagonist, d(CH2)5Tyr(Me)Arg-vasopressin (10 microg/kg per h), the angiotensin II-induced decrease in CSF production was abolished. Our observations indicate, therefore, that vasopressin mediates the inhibitory effect of central angiotensin II on CSF formation. | Chodobski A A; Szmydynger-Chodobska J J; Johanson C E CE | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of pharmacology | 9653885 | Involvement of nitrosothiols, nitric oxide and voltage-gated K+ channels in photorelaxation of vascular smooth muscle. | The effects of nitrosothiol depleting compounds (p-hydroxymercuribenzoate, iodacetamide and ethacrynic acid), a guanylyl cyclase inhibitor (1Hoxadiazoloquinoxalin-1-one, ODQ) and nitric oxide (NO) scavenger agents (xanthine/xanthine oxidase and 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide; carboxy-PTIO) on light-induced photorelaxation in rat thoracic aorta were investigated. Photorelaxation responses were decreased in the presence of nitrosothiol depleting compounds suggesting S-nitrosothiols as the tissue source of the NO, whereas reduction in photorelaxation by the guanylyl cyclase inhibitor and NO scavenger agents indicates involvement of both NO and cGMP in photorelaxation. In addition the sensitivity of photorelaxation to the voltage-gated potassium channel (KV) inhibitor, 4-aminopyridine, indicates that photorelaxation is mediated via a NO/cGMP-dependent, and, perhaps, direct light, activation of KV channels. | Lovren F F; Triggle C R CR | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of pharmacology | 9653886 | Role of nitric oxide in post-ischemic cerebral hyperemia in anesthetized rats. | This study was undertaken to determine the extent to which nitric oxide (NO) mechanisms are involved in cerebral hyperemia following global brain ischemia. The vertebral arteries were cauterized through the first alar foramina in anesthetized male Sprague-Dawley rats and followed by 20-min occlusion of the common carotid arteries. Blood flow from the parietal cerebral cortex was measured using laser-Doppler flowmetry. In saline-treated animals, carotid occlusion reduced cerebral blood flow by approximately 95% with a maximal hyperemia of about 400% observed after 15 min of reperfusion. Pre-treatment with the nonspecific NO synthase inhibitor, L-NAME (NG-nitro-L-arginine methyl ester; 2, 10 and 50 mg kg(-1)), produced dose-related depression of post-ischemic hyperemia, whereas D-NAME (10 mg kg(-1)) was inactive. Pre-treatment with L-arginine (300 mg kg(-1), i.v.) prevented L-NAME attenuation of cerebral hyperemia. The selective neuronal NO synthase inhibitor, 7-nitroindazole (30 mg kg(-1)), was without significant depressant effect. These results suggest that NO (largely from vascular endothelium) is instrumental in development of post-ischemic cerebral hyperemia. | Humphreys S A SA; Koss M C MC | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of pharmacology | 9653889 | Acute and chronic neutral endopeptidase inhibition and the natriuretic response to acute volume expansion. | Neutral endopeptidase inhibition by chronic treatment with SCH 34826 compared to chronic vehicle treatment (4.2 +/- 0.7) indicating an activated renal ANP receptor system. Baseline diuresis and natriuresis were enhanced with acute but not with chronic treatment. After acute volume expansion, ANP increased five-fold with acute NEPI, whereas it only increased about 70% in chronically inhibited rats. The natriuretic (497 +/- 62 versus 329 +/- 42 micromol/60 min with vehicle, P < 0.05) and diuretic responses were significantly enhanced with chronic treatment. Together with an increased cGMP/ANP ratio, these data suggest that chronic activation of the renal ANP system after long-term NEPI facilitated the excretion of an acute volume load. These findings may have therapeutic implications in patients with chronic sodium retention. | Scheuermann M M; Dietz R R; Willenbrock R R | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of pharmacology | 9653893 | Effects of ZD7114, a selective beta3-adrenoceptor agonist, on neuroendocrine mechanisms controlling energy balance. | Selective beta3-adrenoceptor agonists increase energy expenditure by increasing non-shivering thermogenesis in brown adipose tissue. The aim of this study was to investigate how changes in energy balance affect energy intake and interaction of peripheral metabolic feedback signals with central neuroendocrine mechanisms participating in the control of body energy balance. Expression of preproneuropeptide Y-4-[2-[ and CRF gene expression per se. However, the correlation analyses suggest that ZD7114 may modulate feedback connections of brown adipose tissue thermogenesis and plasma insulin with the hypothalamic neuroendocrine mechanisms integrating body energy balance. | Savontaus E E; Pesonen U U; Rouru J J; Huupponen R R; Koulu M M | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of pharmacology | 9653895 | Effect of hypolipidemic drugs on key enzyme activities related to lipid metabolism in normolipidemic rabbits. | The effect of atorvastatin (3 mg kg(-1) day(-1)), simvastatin (3 mg kg(-1) day(-1)) and bezafibrate (100 mg kg(-1) day(-1)) administered for 4 weeks to male New Zealand white rabbits on enzyme activities related to lipid metabolism has been studied. Only the statins reduced plasma cholesterol values, while none of the drugs modified plasma triglyceride or high density lipoprotein (HDL)-cholesterol concentrations, nor the activity of enzymes such as hepatic diacylglycerol acyltransferase, lipoprotein lipase or hepatic lipase, directly involved in triglyceride metabolism. Both statins elicited similar increases in the hepatic microsomal 3-hydroxy-3-methyl-glutaryl Coenzyme A (CoA) reductase activity (147 and 109% induction for simvastatin and atorvastatin, respectively), and none of the drugs assayed modified hepatic acyl-coenzyme A:cholesterol acyltransferase activity significantly. Only bezafibrate induced a significant 57% reduction in the activity of hepatic microsomal cholesterol 7alpha-hydroxylase. Regarding the rate limiting enzyme of phosphatidylcholine biosynthesis, CTP:phosphocholine cytidylyl transferase, atorvastatin and bezafibrate behaved similarly, decreasing the enzyme activity in the liver by 45% and 54%, respectively; simvastatin induced no modification of this activity. The reduction of CTP:phosphocholine cytidylyl transferase activity is not caused by a direct inhibition of the enzyme by bezafibrate and atorvastatin. Further, the inhibitory effect of atorvastatin appears to be unrelated to the inhibition of 3-hydroxy-3-methyl-glutaryl CoA reductase elicited in vivo. | Alegret M M; Verd J C JC; Díaz C C; Hernández G G; Adzet T T; Sánchez R M RM; Laguna J C JC | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of pharmacology | 9653897 | Characterization of alpha1-adrenoceptor subtypes in the pig. | The identities of the alpha1-adrenoceptor subtypes present in various tissues of the pig were studied usingprazosin radioligand binding. The subtypes were characterized by performing competition experiments for various subtype selective drugs. In the cerebral cortex, spleen and heart, both alpha1A- and alpha1B-adrenoceptors were detected. In the liver was found only the alpha1A-subtype, while in the aorta was found only the alpha1B-subtype. An alpha1-adrenoceptor subtype was present in the adrenal gland with a high affinity for prazosin, the pKd value being 9.6, but with relatively low affinities for other alpha1-adrenoceptor binding drugs. The adrenal gland alpha1-adrenoceptor did not seem to represent the classical alpha1D-subtype, since drugs selective for the alpha1D-subtype in other species, including BMY7378 and SKF104856, showed low affinities for the pig adrenal gland alpha1-adrenoceptor. | Wikberg-Matsson A A; Wikberg J E JE; Uhlén S S | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of pharmacology | 9653900 | Pericardial mesothelial cells produce endothelin-1 and possess functional endothelin ETB receptors. | We investigated the endothelin production and endothelin receptor activity of pericardial mesothelial cells obtained from spontaneously hypertensive rats), significantly inhibited the endothelin-1- and endothelin-3-induced changes ini. The endothelin ETA receptor antagonist, FR 1393171 ((R)2-carbonyl]ammino -4-methylpentanoyl]amino-3-propio nyl]amino-3-(2-pyridyl)propionic acid), did not affect these changes. From these results, pericardial mesothelial cells from both SHR and WKY rats shared the ability to produce endothelin-1 spontaneously in culture, although consistently greater production was detected in cultures of SHR origin. Moreover, pericardial mesothelial cells of SHR origin may have increased numbers of endothelin ETB receptors and/or a more active signal transduction system compared with those of WKY rats. These results suggest that endothelin-1 may play an important role in the pericardium in an autocrine and/or paracrine fashion. | Kuwahara M M; Kuwahara M M | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of pharmacology | 9653901 | Evidence that angiotensin II, endothelins and nitric oxide regulate mitogen-activated protein kinase activity in rat aorta. | We measured the activity of mitogen-activated protein (MAP) kinases, enzymes believed to be involved in the pathway for cell proliferation, in rat aortic strips with or without endothelium, and examined effects of angiotensin receptor antagonists, endothelin receptor antagonists and nitric oxide (NO)-related agents. Endothelium removal produced an activation of MAP kinase activity in the strips, whereas the enzyme activity was not affected in the adventitia. The MAP kinase activation was inhibited by either the angiotensin AT1 receptor antagonist losartan or the endothelin ETA receptor antagonist BQ 123. The combination of both antagonists caused an additive inhibition. The angiotensin AT2 receptor antagonist PD 123,319 and the endothelin ETB receptor antagonist BQ 788 did not affect the MAP kinase activation. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) caused an activation of MAP kinase in the endothelium-intact aorta and the MAP kinase activation was inhibited by losartan or BQ123. The NO releaser nitroprusside inhibited the MAP kinase activation induced by endothelium removal or angiotensin II. These results suggest that even in isolated arteries, NO of endothelial origin tonically exert MAP kinase-inhibiting effects and endogenous angiotensin II and endothelins in the media are tonically released to cause MAP kinase-stimulating effects in medial smooth muscle. | Kubo T T; Saito E E; Hanada M M; Kambe T T; Hagiwara Y Y | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of pharmacology | 9653903 | Cyclic GMP inhibits cytoplasmic Ca2+ oscillation by increasing Ca2+-ATPase activity in rat megakaryocytes. | The regulatory effects of cyclic GMP on purinoceptor-operated cytoplasmic Ca2+ oscillation of rat megakaryocytes were investigated by using whole-cell patch-clamp technique. ATP-induced oscillatory K+ currents though Ca2+-activated K+ channels (I(KCa)S) were depressed by pretreatment with the guanylate cyclase activator, sodium nitroprusside, and a stable membrane-permeable cGMP analogue, 8-bromo-cGMP. The inhibition by sodium nitroprusside was blocked by treatment with a cyclic nucleotide-dependent protein kinase inhibitor, N--5-isoquinolinesulfonamide x HCl (H-8) (10 microM), but not by a selective cAMP-dependent-protein kinase inhibitor, Rp-cAMPS (100 microM). The oscillatory I(KCa) directly evoked by intracellular D-myo-inositol-trisphosphate (IP3) perfusion was also inhibited by the application of sodium nitroprusside. The inhibitory effect of sodium nitroprusside disappeared when the ATP-induced oscillatory I(KCa) was changed to a monophasic sustained I(KCa) current by inhibition of Ca2+-ATPase. These results suggested that cGMP depressed Ca2+ mobilization by improving Ca2+-ATPase activity by phosphorylation. | Uneyama C C; Uneyama H H; Akaike N N; Takahashi M M | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of pharmacology | 9653904 | Foetal erythrocytes exhibit an increased ability to scavenge for nitric oxide. | The presence of adult human whole blood inhibited in vitro relaxations of rat aortic rings by the nitric oxide (NO) donor S-nitroso-N-acetyl-DL-penicillamine (SNAP). Incubation with foetal blood containing the same concentration of haemoglobin produced a shift to the right of the relaxation curve. SNAP-induced vasorelaxations were more inhibited by dialysed solutions of haemoglobin than by the presence of erythrocytes in the organ bath, but there were no differences between the effect of adult or foetal haemoglobins. The presence of plasma from adult or foetal blood did not modify the effects of SNAP. Relaxations induced by endogenous, endothelium-derived, NO were more inhibited by foetal than by adult erythrocytes. These results suggest that foetal erythrocytes have a higher NO scavenging effect than those present in adult blood. | Calatayud S S; Beltrán B B; Brines J J; Moncada S S; Esplugues J V JV | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Journal of chromatography. B, Biomedical sciences and applications | 9653946 | Analysis of cysteine and N-acetylcysteine in human plasma by high-performance liquid chromatography at the basal state and after oral administration of N-acetylcysteine. | A high-performance liquid chromatographic method for the determination of free reduced cysteine and N-acetylcysteine in human plasma at the basal state and after oral administration of N-acetylcysteine is described. The method is based on acid-catalysed conversion of plasma thiols to the corresponding S-nitroso derivatives by excess of nitrite and their subsequent cation-pairing RP-HPLC with detection at 333 nm. Recovery rates of cysteine and N-acetylcysteine added to human plasma were 94.6 and 99.6%, respectively. Inter- and intra-day precision were below 6%. In healthy humans (n = 5), free reduced cysteine was determined to be (mean+/-S.E.) 10.0+/-0.96 microM. No N-acetylcysteine was detected in plasma of these subjects above the limit of detection (for example 170 nM). The method was successfully applied to a pharmacokinetic study on orally administered N-acetylcysteine to healthy volunteers. | Tsikas D D; Sandmann J J; Ikic M M; Fauler J J; Stichtenoth D O DO; Frölich J C JC | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Journal of chromatography. B, Biomedical sciences and applications | 9653958 | Simultaneous high-performance liquid chromatographic determination of quinupristin, dalfopristin and their main metabolites in human plasma. | Quinupristin-dalfopristin and dalfopristin and their main metabolites in human plasma. The metabolites measured by this method were RP 69012 from quinupristin and RP 12536 for RP 57669, RP 54476 and RP 12536, and of 0.010 mg l. The validated range of concentrations of the method was: 0.025-5000 mg l for RP 69012 and RPR 100391. | Le Liboux A A; Pasquier O O; Montay G G | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Journal of chromatography. B, Biomedical sciences and applications | 9653964 | High-performance liquid chromatographic method for the determination of the major quinine metabolite, 3-hydroxyquinine, in plasma and urine. | The determination of 3-hydroxyquinine in urine and plasma samples is described. Extraction was performed using a mixture of toluene-butanol (75:25, v/v), followed by back-extraction into the mobile phase, which consisted of 0.1 M phosphate buffer, acetonitrile, tetrahydrofuran and triethylamine. A reversed-phase liquid chromatography system with fluorescence detection and a CT-sil C18 column were used. The within-assay coefficient of variation of the method was 2% at the higher concentration values in plasma, 2.95 microM, 4% at 227 nM and 9% at the lower limit of quantitation, 4.5 nM. In urine, the coefficient of variation was 11% at the lower concentration, 227 nM and was 3% at 56.8 microM. The between-assay coefficient of variation was 4% at the low concentration (5.1 nM) in plasma, 2% at 276.8 nM and 3% at 1.97 microM. In urine, the between assay coefficient of variation was 4% at 204.6 nM, 3% at 5.12 microM and 2% at 56.8 microM. | Mirghani R A RA; Ericsson O O; Gustafsson L L LL | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Journal of chromatography. B, Biomedical sciences and applications | 9653968 | Determination of pravastatin in human plasma by high-performance liquid chromatography with ultraviolet detection. | A sensitive high-performance liquid chromatographic (HPLC) method for the quantitation of the HMG-CoA reductase inhibitor pravastatin in human plasma is described. Sample preparation based on reversed-phase solid-phase extraction using triamcinolone acetonide as internal standard (I.S.). The compounds were separated on C18 reversed-phase analytical column and then determined by ultraviolet detection. The recovery of pravastatin from plasma was 69.2+/-6.7% (mean+/-S.D.). The limit of detection for pravastatin in aqueous solution was 0.4 ng, the limit of quantitation in plasma was 2 ng/ml. In a preliminary pharmacokinetic study with two healthy volunteers the t1/2 of pravastatin in plasma was found to be 0.8 and 2.3 h. | Otter K K; Mignat C C | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Journal of chromatography. B, Biomedical sciences and applications | 9653973 | Determination of metformin in plasma by capillary electrophoresis using field-amplified sample stacking technique. | A capillary electrophoresis method was described for the determination of metformin in human plasma based on the extraction of the ion-pair with bromothymol blue into chloroform. Phenformin was used as internal standard. Field-amplified sample stacking injection was employed with an electrokinetic injection voltage of 10 kV for 10 s. The running buffer was 0.1 M phosphate buffer (pH 2.5), running voltage was 20 kV and the UV absorbance detection was set at 195 nm. The limit of quantitation was 0.25 microg/ml. Linearity range of calibration curve was 0.25 to 3.5 microg/ml. Recoveries for three levels (0.25, 1 and 2 microg/ml) were 80.24%, 67.44% and 58.97% (n = 5 for each level), respectively. The intra-day precisions for the three levels were 11.9%, 3.09% and 4.33% and the inter-day precisions were 12.4%, 4.57% and 4.94%, respectively. The concentrations of metformin hydrochloride in human plasma of eight volunteers were measured after orally administrating metformin enteric-capsule and tablet. | Song J Z JZ; Chen H F HF; Tian S J SJ; Sun Z P ZP | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Journal of chromatography. B, Biomedical sciences and applications | 9653982 | High-performance liquid chromatographic determination of propiverine and its N-oxide in human serum. | A high-performance liquid chromatographic method has been developed for the determination of propiverine hydrochloride (P4) and its main metabolite, propiverine N-oxide (P4NO) in human serum. P4 has been shown to be efficacious in those patients who have either idiopathic bladder instability, or neurogenic bladder (detrusor hyperflexia) resulting from spinal cord injuries. In the present method, the analytes were extracted from serum (1 ml, pH 8) into methyl tert.-butyl ether. The separation was performed on a reversed-phase C8 (RP-select B) column using phosphate buffer-acetonitrile (30:70, v/v). UV absorption was used for measuring the analytes, with a limit of quantitation of about 10 ng/ml, which is appropriate for pharmacokinetic studies. | Richter K K; Scheithauer S S; Thümmler D D | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Journal of chromatography. B, Biomedical sciences and applications | 9653983 | Direct enantioseparation of some beta-adrenergic blocking agents using impregnated thin-layer chromatography. | The resolution of (+/-)-atenolol, (+/-)-propranolol and (+/-)-metoprolol into their enantiomers was achieved by TLC on silica-gel plates impregnated with optically pure L-lysine (0.5%) and L-arginine (0.5%) as the chiral selectors. In all cases, different combinations of acetonitrile-methanol solvent systems were found to be successful in resolving these compounds. Spots were detected using iodine vapour. The detection limit for both (+/-)-atenolol and (+/-)-propranolol was 2.6 microg and for (+/-)-metoprolol, it was 0.26 microg. | Bhushan R R; Thiongo G T GT | 1998-04-24 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of biochemistry | 9654058 | Glucocorticoids induce the expression of the leptin gene through a non-classical mechanism of transcriptional activation. | Leptin is a hormone which is produced in adipose tissue and which plays a role in the regulation of energy homeostasis. The expression of the ob gene, encoding leptin, is under multi-hormonal control. We have shown previously that high doses of glucocorticoids are positive regulators of leptin expression in rats and that they concomitantly reduce food intake and body mass gain in these animals. In the present report we analyse the molecular mechanism of this glucocorticoid regulation of leptin expression. In cultured rat adipocytes dexamethasone induces leptin mRNA levels, an effect not inhibited by the protein synthesis inhibitor cycloheximide. In addition, our data indicate that the induction of the expression of the leptin gene by dexamethasone is at least in part due to a transcriptional activation that is mediated by the glucocorticoid receptor. Deletion mapping of the human leptin promoter shows that cis-elements involved in the glucocorticoid effect are located between -55 and +31 relative to the transcription initiation site. Since this region does not contain a binding site for the glucocorticoid receptor, the effect does not rely on the classical molecular mechanism of glucocorticoid receptor action. A role of C/EBP and Sp-1 in mediating this glucocorticoid effect was furthermore excluded. Multiple nuclear factors from 3T3-L1 preadipocytes interact with this promoter region of the human leptin gene and may be potential mediators of the induction by glucocorticoids. | De Vos P P; Lefebvre A M AM; Shrivo I I; Fruchart J C JC; Auwerx J J | 1998-05-01 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of biochemistry | 9654059 | Dicyclohexylcarbodiimide interaction with the voltage-dependent anion channel from sarcoplasmic reticulum. | In a recent study we have demonstrated the presence of the voltage-dependent anion channel (VDAC) in skeletal muscle sarcoplasmic reticulum (SR) as supported here by co-localization of VDAC and (Ca2+ + Mg2+)ATPase in the SR using double-immunogold labeling. The interaction of the carboxyl-modifying reagent dicyclohexylcarbodiimide with the SR-VDAC is characterized by labeling withdicyclohexylcarbodiimide and by dicyclohexylcarbodiimide modification of the reconstituted-purified VDAC channel activity. In both SR and mitochondrial membranes,dicyclohexylcarbodiimide most specifically labeled a 35-kDa protein, identified as VDAC by specific anti-VDAC Ig. Labeling of the SR-VDAC was about twofold higher than that of the mitochondrial VDAC, which could result either form higher labeling of the SR protein or from relatively higher amounts of VDAC/mg total protein in the SR membranes.Dicyclohexylcarbodiimide labeling of the SR, but not the mitochondrial VDAC, was biphasic with respect to time and concentration ofdicyclohexylcarbodiimide. Partial digestion ofdicyclohexylcarbodiimide-labeled SR-VDAC with chymotrypsin yielded five proteolytic fragments which were recognized by the anti-VDAC Ig, and the dicyclohexylcarbodiimide-binding site was localized in the 19-kDa fragment. VDAC was purified from SR and mitochondrial membranes by spermine-agarose column. The interaction of dicyclohexylcarbodiimide with functional carboxyl residue(s) in the purified VDAC is demonstrated by recording its channel activity, following its reconstitution into planar lipid bilayer (PLB). Dicyclohexylcarbodiimide inhibited the channel activity in a voltage-dependent manner, requiring incubation with dicyclohexylcarbodiimide at high (negative or positive) potentials. Dicyclohexylcarbodiimide slowed down the transition from the high-conducting to a long-lived low-conducting states of the channel (approximately 20% of its maximal conductance), by stabilizing the intermediate states. Similar results were also obtained with purified-reconstituted mitochondrial VDAC. Hydrophilic carboxyl reagents carbodiimide, N-ethyl-phenylisoxazolium-3'-sulfonate] neither modified the channel activity nor preventeddicyclohexylcarbodiimide labeling. These results indicate that dicyclohexylcarbodiimide interacts with a carboxyl group located in a hydrophobic region of the protein which is involved in the channel gating. | Shafir I I; Feng W W; Shoshan-Barmatz V V | 1998-05-01 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of biochemistry | 9654060 | Inhibition of growth and aggregation of calcium oxalate crystals in vitro--a comparison of four human proteins. | The aim of this study was to compare directly, in the absence of interfering contaminants, the inhibitory effects of Tamm-Horsfall glycoprotein (THG), human serum albumin (HSA), alpha1-microglobulin and prothrombin fragment 1 (PTF1) on calcium oxalate crystallization. These proteins have been detected in urinary calculi, and with the exception of THG in calcium oxalate crystals generated from undiluted human urine. THG was isolated from the urine of healthy men, while PTF1 was purified from Prothrombinex-HT, a human blood concentrate; HSA and alpha1-microglobulin were obtained from commercial sources. The effects of these proteins were determined, separately, at the same final concentration (32 nM) on calcium oxalate crystallization in a seeded, inorganic reaction system, using Coulter Counter andoxalate analysis. Analysis ofoxalate data showed that THG, HSA and alpha1-microglobulin had no measurable effect on deposition of calcium oxalate. However, PTF1 significantly inhibited mineral deposition by 19.6%. The average size of the particles precipitated was reduced from the control value of 8.6 microm to 7.3, 5.9, 5.6 and 4.0 microm in the presence of alpha1-microglobulin, HSA, THG and PTF1 respectively. These findings were confirmed by scanning electron microscopy, which also revealed that the smaller particles deposited in the presence of the proteins resulted from reduced crystal aggregation rather than a decrease in the size of the individual crystals. It was concluded that, on a molar basis, PTF1 is a more potent inhibitor of calcium oxalate crystal aggregation than THG, HSA and alpha1-microglobulin. Moreover, unlike those proteins it significantly inhibits the deposition of calcium oxalate. These findings have implications for the putative role of urinary proteins in the formation of calcium oxalate stones. | Grover P K PK; Moritz R L RL; Simpson R J RJ; Ryall R L RL | 1998-05-01 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | European journal of biochemistry | 9654093 | Expression of fatty-acid-binding proteins in cells involved in lung-specific lipid metabolism. | Members of the fatty-acid-binding protein (FABP) family are thought to play an important role in fatty acid transport within the cytosol and thus to be involved in lipid metabolism. As previous data on the occurrence of distinct FABP types in total lung are contradictory, we determined the expression of FABP types in three isolated cell types of rat lung, which are characterised by active lipid metabolism. Alveolar type-II cells synthesise, store and secrete pulmonary surfactant, a phospholipid-rich surface-tension-lowering agent, whereas lung fibroblasts, localised adjacent to the alveolar type-II cells, are assumed to provide neutral lipid substrate to alveolar type-II cells around birth, and alveolar macrophages are known to degrade complex lipids. Initial screening by reverse transcriptase PCR revealed the occurrence of heart (H-), epidermal (E-) and liver FABP in rat lung, the latter being not detectable in the three cell types studied. Cells were analysed by northern and western blotting, then quantitatively by sandwich ELISA, for which recombinant rat E-FABP was prepared. E-FABP mRNA was found in all three cell types, and E-FABP was detected in the following amounts: 240.9 +/- 19.0 ng/mg cytosolic protein in alveolar type-II cells; 172.3 +/- 0.7 ng/mg protein for lung fibroblasts; and 36.9 +/- 3.5 ng/mg protein for alveolar macrophages. This indicates a basic function of E-FABP in cellular lipid metabolism. In contrast, H-FABP probably is involved in the metabolism of neutral lipids because H-FABP mRNA was found only in lung fibroblasts with a corresponding protein level of 315.5 +/- 6.9 ng/mg. Small amounts of H-FABP protein were present in alveolar type-II cells and alveolar macrophages. | Guthmann F F; Hohoff C C; Fechner H H; Humbert P P; Börchers T T; Spener F F; Rüstow B B | 1998-04-15 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Cancer chemotherapy and pharmacology | 9654110 | Phase I and pharmacokinetic study of D-limonene in patients with advanced cancer. Cancer Research Campaign Phase I/II Clinical Trials Committee. | PURPOSE: D-Limonene is a natural monoterpene with pronounced chemotherapeutic activity and minimal toxicity in preclinical studies. A phase I clinical trial to assess toxicity, the maximum tolerated dose (MTD) and pharmacokinetics in patients with advanced cancer was followed by a limited phase II evaluation in breast cancer. METHODS: A group of 32 patients with refractory solid tumors completed 99 courses of D-limonene 0.5 to 12 g/m2 per day administered orally in 21-day cycles. Pharmacokinetics were analyzed by liquid chromatography-mass spectrometry. Ten additional breast cancer patients received 15 cycles of D-limonene at 8 g/m2 per day. Intratumoral monoterpene levels were measured in two patients. RESULTS: The MTD was 8 g/m2 per day; nausea, vomiting and diarrhea were dose limiting. One partial response in a breast cancer patient on 8 g/m2 per day was maintained for 11 months; three patients with colorectal carcinoma had prolonged stable disease. There were no responses in the phase II study. Peak plasma concentration (Cmax) for D-limonene ranged from 10.8+/-6.7 to 20.5+/-11.2 microM. Predominant circulating metabolites were perillic acid (Cmax 20.7+/-13.2 to 71+/-29.3 microM), dihydroperillic acid (Cmax 16.6+/-7.9 to 28.1+/-3.1 microM), limonene-1,2-diol (Cmax 10.1+/-8 to 20.7+/-8.6 microM), uroterpenol (Cmax 14.3+/-1.5 to 45.1+/-1.8 microM), and an isomer of perillic acid. Both isomers of perillic acid, and cis and trans isomers of dihydroperillic acid were in urine hydrolysates. Intratumoral levels of D-limonene and uroterpenol exceeded the corresponding plasma levels. Other metabolites were trace constituents in tissue. CONCLUSIONS: D-Limonene is well tolerated in cancer patients at doses which may have clinical activity. The favorable toxicity profile supports further clinical evaluation. | Vigushin D M DM; Poon G K GK; Boddy A A; English J J; Halbert G W GW; Pagonis C C; Jarman M M; Coombes R C RC | 1998-10-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Cancer chemotherapy and pharmacology | 9654117 | Renal toxicity of the anticancer drug fostriecin. | PURPOSE: Fostriecin is an inhibitor of topoisomerase II catalytic activity. In a phase I trial we observed renal toxicity, documented as a rise in serum creatinine, which was reversible and non-dose-limiting. The purpose of this study was a detailed analysis of this toxicity. METHODS: A total of 20 patients received fostriecin as a 1-h i.v. infusion daily x 5 at doses ranging from 2 to 20 mg/m2 per day. Serum creatinine determination and urinalysis were performed daily during drug administration. Renal hemodynamics were measured by means of clearance studies using 125I-iothalamate and (131)I-hippuran in eight patients at doses of > or =4 mg/m2 per day at baseline, on day 3 or 4 during the first course, and 3 weeks after the second course. RESULTS: The rise in serum creatinine was maximal after one to two doses despite continued administration. This increase showed no correlation with the dose level at fostriecin doses of > or =4 mg/m2 per day. Urinary beta2-microglobulin concentrations increased 150-fold (median), which is compatible with impaired tubular reabsorption. The median change in the glomerular filtration rate (GFR) was -36% (range -28% to -44%), that in effective renal plasma flow (ERPF) was -23% (range -11% to -36%), and the filtration fraction (FF) decreased in all patients during the first course of treatment. The values measured 3 weeks after the second course, however, did not differ from baseline. CONCLUSIONS: Fostriecin induces reversible renal hemodynamic changes compatible with renal tubular damage. | de Jong R S RS; de Vries E G EG; Meijer S S; de Jong P E PE; Mulder N H NH | 1998-10-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | FEBS letters | 9654124 | Requirement of membrane-proximal amino acids in the carboxyl-terminal tail for expression of the rat AT1a angiotensin receptor. | A series of deletion mutants was created to analyze the function of the membrane-proximal region of the cytoplasmic tail of the rat type 1a (AT1a) angiotensin receptor. In transiently transfected COS-7 cells, the truncated mutant receptors showed a progressive decrease in surface expression, with no major change in binding affinity for the peptide antagonist,angiotensin II. In parallel with the decrease in receptor expression, a progressive decrease in angiotensin II-induced inositol phosphate responses was observed. Alanine substitutions in the region 307-311 identified the highly conserved phenylalanine309 and adjacent lysine residues as significant determinants of AT1a receptor expression. | Gáborik Z Z; Mihalik B B; Jayadev S S; Jagadeesh G G; Catt K J KJ; Hunyady L L | 1998-05-29 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | FEBS letters | 9654154 | Purification of a novel endothelin-converting enzyme specific for big endothelin-3. | Endothelin-3 (ET-3), a potent vasoactive peptide, is considered to be produced from big ET-3 by endothelin-converting enzyme (ECE) like the other members of the endothelin family (ET-1 and ET-2). We purified a novel ECE from bovine iris microsomes. The purified enzyme, a 140 kDa protein by SDS-PAGE analysis, converted big ET-3 to ET-3 but not big ET-1, with a Km value of 0.14 microM for big ET-3. The conversion to ET-3 was confirmed with sandwich EIA by monoclonal antibodies, the elution profile of HPLC, and intracellular calcium mobilization in CHO-K1 cells expressing recombinant human ET(B) receptors. The conversion activity was inhibited by an inhibitor of neutral endopeptidase 24.11 (NEP) phosphoramidon. These results show that ECE-3 purified from bovine iris is a novel metalloprotease totally different from ECE-1 or ECE-2, in that the enzyme is highly specific for big ET-3. | Hasegawa H H; Hiki K K; Sawamura T T; Aoyama T T; Okamoto Y Y; Miwa S S; Shimohama S S; Kimura J J; Masaki T T | 1998-05-29 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Acta obstetricia et gynecologica Scandinavica | 9654170 | Consumption of anti-D in the erythroblastotic fetus. | BACKGROUND: Maternal serum anti-D is actively transported across the placenta into the fetal blood where it adheres to D-positive erythrocytes. The anti-D coated red cells attach to Fc-receptors on fetal reticuloendothelial cells and are subsequently phagocytosed and hemolysed. It is not known if anti-D is consumed or recirculated in this process. MAIN QUESTION: Is anti-D in the fetus consumed in the hemolytic process in the erythroblastotic fetus and can the consumption be modulated by high-dose immunoglobulins (i.v.IG) given to the mother? METHODS: Fetal/maternal serum anti-D concentration ratios were calculated for simultaneously taken blood samples from three groups of Rh(D) immunized pregnant women; six women with fetuses who were of Rh(D) negative phenotype, 19 women with fetuses who were Rh(D) positive and received no treatment and, seven women who were treated with i.v.IG because they bore anemic, Rh(D) positive fetuses. RESULTS: Fetuses with a Rh(D) negative phenotype expressed an increase in fetal/maternal anti-D concentration ratios from 10 to 55% between 25 and 31 gestational weeks, while Rh(D) positive fetuses without i.v.IG treatment had stable values at the 10% level between 24 and 35 gestational weeks. During i.v.IG-treatment of the mothers, Rh(D) positive fetuses showed an increase in ratio from 10 to 30% between 26 and 34 gestational weeks. There was a statistically significant (p<0.001) difference between regression results of the three groups. CONCLUSIONS: Fetal anti-D is consumed in the hemolytic process and the consumption can be modulated by i.v.IG given to the mother. | Gottvall T T; Selbing A A | 1998-05-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Acta obstetricia et gynecologica Scandinavica | 9654171 | Placental isoferritin in gestational diabetes mellitus. | BACKGROUND: Serum placental isoferritin, an immunosuppressive cytokine like protein, was found to be elevated in type I diabetes at diagnosis and low in high risk pregnant women. Further to this observation, the possible role of this placental product was assessed in pregnant women with gestational diabetes mellitus. METHODS: A comparative study. One hundred and seventy-four pregnant women were included in the study: 28 were diagnosed as gestational diabetes mellitus and 146 were normal controls. MAIN OUTCOME MEASURES: Samples for serum placental ferritin were measured in the second and third trimesters of pregnancy. RESULTS: Serum placental isoferritin values were significantly lower in the second trimester of pregnancy in the gestational diabetes mellitus group, and were also significantly lower in the third trimester. CONCLUSIONS: Low serum PLF values detected in gestational diabetes mellitus may reflect placental function and be related to insulin treatment. | Bar J J; Hod M M; Maymon R R; Moroz C C | 1998-05-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Human genetics | 9654205 | LDL-R and Apo-B-100 gene mutations in Polish familial hypercholesterolemias. | A group of 30 Polish families with clinical signs of familial hypercholesterolemia was studied for the presence of germ-line mutations in the LDL-R and ApoB-100 genes. Screening of the LDL-R gene was performed at the genomic DNA level by single-strand conformation polymorphism analysis of all 18 exons and extended by sequencing of polymerase chain reaction. Of the mutations not previously recognized and identified in Polish families, there were three small deletions (2-bp deletion AG at codon 291; 4-bp deletion CCCT at codons 661-662; 1-bp deletion A at codon 830), and four point mutations (Arg239Stop, Cys331Stop, Asn543Ser, Gln665Stop). Additionally, one large (approximately 1-kb) LDL-R gene deletion between exons 6 and 9 was identified. In five families, the B-3500 mutation within the ApoB-100 gene was revealed. | Górski B B; Kubalska J J; Naruszewicz M M; Lubiński J J | 1998-05-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Human genetics | 9654208 | Structural organisation of the gene encoding the alpha-subunit of the human amiloride-sensitive epithelial sodium channel. | The human amiloride-sensitive epithelial sodium channel (ENaC) is a member of the degenerin/ENaC family of ion channels and regulates fluid and electrolyte absorption across a number of epithelia, including kidney, colon and lung. Native ENaC has been shown to be a multimer made up of at least three homologous subunits (alpha, beta, gamma) and mutations affecting the channel complex have been identified in various human diseases. "Gain of function" mutations in one of the three ENaC subunits have been found to cause pseudoaldosteronism (Liddle's syndrome) and ENaC "reduction of function" mutations are found in patients affected with the recessive form of pseudohypoaldosteronism (PHA) type 1. In this report, we describe the genomic organisation of the human alphaENaC gene. Human alphaENaC consists of 13 exons spanning 17 kb on chromosome 12p13 and contains at least eight Alu sequences. In addition to the intron/exon boundaries, we have deciphered almost all the intron sequences and 475 bp of the CCAAT-less and TATA-less 5' flanking region. | Ludwig M M; Bolkenius U U; Wickert L L; Marynen P P; Bidlingmaier F F | 1998-05-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Pharmacology | 9654216 | Pharmacokinetics and pharmacodynamics of mibefradil in hypertensive patients with varying degrees of renal insufficiency. | Mibefradil, the first member of the tetralol derivatives, a new class of calcium antagonists, is used for the treatment of hypertension and angina pectoris. This study was designed to investigate the effect of varying degrees of chronic renal impairment on mibefradil pharmacokinetics and pharmacodynamics. Neither pharmacokinetic nor pharmacodynamic parameters varied as a function of renal status. Additionally, hemodialysis removed only a relatively small fraction of drug from the body. It was concluded that the majority of renal-failure patients will not require a change in mibefradil dosage relative to patients with normal renal function. Following hemodialysis, supplemental mibefradil treatment should not be necessary. | Welker H A HA; Weidekamm E E; Houwing N N; de Chatel R R | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Pharmacology | 9654215 | Acute natriuretic effect of fasidotrilat, a mixed inhibitor of neutral endopeptidase and angiotensin I-converting enzyme, in rats with heart failure. | The acute diuretic and natriuretic effects of fasidotrilat, a mixed inhibitor of neutral endopeptidase (NEP) and angiotensin I-converting enzyme (ACE) were evaluated in control and myocardial-infarcted rats. Fasidotrilat injection (10 mg/kg i.v.) had no significant effect on arterial blood pressure and led to significant elevations in urine volume (+57% in control rats and +114% in infarcted rats) and of urinary sodium excretion (+81% in control rats and +225% in infarcted rats). Comparison between control and infarcted rats showed that fasidotrilat-induced changes in diuresis and natriuresis were higher in infarcted rats (2.4-fold for diuresis and 4.7-fold for natriuresis, p < 0.05), despite a lower perfusion pressure (-10 mm Hg) in infarcted rats. These data show the potential therapeutic interest of mixed NEP/ACE inhibitors in congestive heart failure. | Marie C C; Mossiat C C; Lecomte J M JM; Bralet J J | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Journal of cardiovascular electrophysiology | 9654226 | Antibodies against myosin in sera of patients with idiopathic paroxysmal atrial fibrillation. | INTRODUCTION: Circulating autoantibodies against myosin heavy chain have been detected in patients with ventricular myocarditis and in patients with dilated cardiomyopathy. This study investigated the presence of antibodies against myosin in sera of healthy control persons as compared with patients with idiopathic paroxysmal atrial fibrillation refractory to antiarrhythmic therapy. METHODS AND RESULTS: An SDS-PAGE (sodium dodecylsulfate polyacrylamide gel electrophoresis) procedure, followed by Western blotting with homogenates and membrane fractions of human left ventricular and atrial specimen as antigens, was used to analyze sera of 10 patients with idiopathic paroxysmal atrial fibrillation and 10 age-matched healthy control subjects. Circulating immunoglobulin G reactivity against cardiac myosin heavy chain was detected in 6 patients (60%) as compared with 1 control subject (10%). This difference was statistically significant (P < 0.05). All patients with idiopathic paroxysmal atrial fibrillation who showed reactivity against myosin heavy chain also had specific reactivity in their sera that exhibited reactivities to both ventricular and atrial cardiac myosin heavy chain isoforms. CONCLUSION: This study demonstrates the presence of circulating autoantibodies against myosin heavy chain in a significant percentage of patients with idiopathic paroxysmal atrial fibrillation and raises the possibility of an autoimmune process in some patients with paroxysmal atrial fibrillation. | Maixent J M JM; Paganelli F F; Scaglione J J; Lévy S S | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Journal of cardiovascular electrophysiology | 9654233 | Becker muscular dystrophy with bundle branch reentry ventricular tachycardia. | This report describes a case of Becker muscular dystrophy presenting with recurrent symptomatic wide complex tachycardia. Electrophysiologic testing demonstrated the mechanism to be bundle branch reentry ventricular tachycardia. It is important to consider this potential mechanism in patients with ventricular arrhythmias who have this particular clinical entity, since radiofrequency catheter ablation can represent a curative treatment. | Negri S M SM; Cowan M D MD | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Lancet (London, England) | 9654259 | Beta-glucocerebrosidase gene locus as a link for Gaucher's disease and familial hypo-alpha-lipoproteinaemia. | BACKGROUND: Gaucher's disease is the most common lysosomal storage disorder, caused by deficiency of glucocerebrosidase resulting from homozygosity for any of several mutations of the glucocerebrosidase gene locus. Affected people have decreased concentrations of LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C). We assessed the association between mutations in the glucocerebrosidase locus and hypo-alpha-lipoproteinaemia. METHODS: We studied 258 people from 43 unrelated Spanish families. 57 participants were affected, 137 were non-affected carriers, and 64 were non-carriers. We determined glucocerebrosidase genotypes and measured plasmid lipids, apolipoproteins A-I, B, and E, and leucocyte glucocerebrosidase activity. FINDINGS: The most common glucocerebrosidase mutations were N370S (45%), L444P (23%), and G377S (5%). Deletions and recombinants accounted for another 5%, and point mutations in exons 5, 6, 9, and 10 were present in 12%. Affected participants had lower LDL-C and HDL-C concentrations than non-affected carriers (p<0.001) and non-carriers (p<0.001). HDL-C values were also significantly different between the non-affected carriers and non-carriers. Mutations at this locus may account for as much as 19.5% of the genetic variability in HDL-C in the population studied. INTERPRETATION: Heterozygosity for these mutations at the glucocerebrosidase locus does not result in clinical expression of Gaucher's disease but can decrease HDL-C concentrations. Given the high frequency of these mutations, the glucocerebrosidase locus might lead to familial low alpha-lipoproteinaemia in up to 2% of the general population and be one of the most common known genetic causes of HDL-C. | Pocovi M M; Cenarro A A; Civeira F F; Torralba M A MA; Perez-Calvo J I JI; Mozas P P; Giraldo P P; Giralt M M; Myers R H RH; Cupples L A LA; Ordovas J M JM | 1998-06-27 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | New horizons (Baltimore, Md.) | 9654319 | Hypovolemic shock in pediatric patients. | Hypovolemic shock is a common disease treated in pediatric ICUs and emergency departments worldwide. A wide variety of etiologic factors may cause this disease, with the common net result of decreased intravascular volume leading to decreased venous return to the heart and decreased stroke volume. Inadequate perfusion results in impairment of delivery of nutrients and oxygen to vital end organs. With the advent of pediatric critical care and pediatric emergency medicine as specialties, deaths from hypovolemic shock have become increasingly rare in the United States. The physical signs of hypovolemic shock in children must be quickly recognized, and aggressive volume resuscitation must be administered before irreversible end-organ dysfunction occurs. This is best accomplished by large peripheral or central intravenous access, with intraosseous access an alternative option in the pediatric patient. The amount as well as the type of volume administered must be tailored for each individual patient, taking into account the amount of intravascular depletion and the disease state in which the shock has occurred. It is not uncommon for children to require large amounts of fluid for resuscitation, and close attention must be paid to children with fluid-refractory shock, who may require catecholamine and/or exogenous steroid support in combination with aggressive fluid resuscitation. | Thomas N J NJ; Carcillo J A JA | 1998-05-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Neuroscience letters | 9654340 | Adenosine induces apoptosis by inhibiting mRNA and protein synthesis in chick embryonic sympathetic neurons. | Our previous work has established that adenosine is toxic to chick embryonic sympathetic neurons and kills freshly plated neurons by a process of apoptosis. Although the exact mechanism remains unknown, we found that phosphorylation of adenosine was essential to the toxicity. Using markers for RNA (uridine) and protein (methionine) synthesis we demonstrate here that in freshly plated sympathetic neurons adenosine inhibits RNA and protein synthesis by about 50%. The inhibitory effects of adenosine on RNA and protein synthesis, and increased ATP synthesis were blocked by adenosine kinase inhibitor, suggesting that phosphorylated products are responsible for inhibition of RNA and protein synthesis and cell death. Adenosine-induced inhibition of RNA and protein synthesis in neuronal cells provides a new role for adenosine in the regulation of cell function. | Kulkarni J S JS; Przywara D A DA; Wakade T D TD; Wakade A R AR | 1998-06-05 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Neuroscience letters | 9654342 | Intracellular Ca2+ store-operated influx of Ca2+ through TRP-R, a rat homolog of TRP, expressed in Xenopus oocytes. | To elucidate whether rat transient receptor potential (TRP-R), a rat TRP4 homolog, functions as a store-operated Ca2+ channel (SOC), we have measured the Ca2+ entry after thapsigargin treatment in Xenopus oocytes injected with mRNA for TRP-R. While non-injected oocytes elicited an SOC response, significantly larger responses were observed in the oocytes expressing TRP-R. The oocyte-native SOC response was inhibited by injection of antisense oligodeoxyribonucleotide for mammalian TRP1. When Ca2+ concentration-SOC response curve was examined, the EC50 value was much smaller in oocytes expressing TRP-R than that of non-injected oocytes. These results suggest that TRP-R functions as SOC having higher sensitivity to external Ca2+ than amphibian TRP1 channel. | Tomita Y Y; Kaneko S S; Funayama M M; Kondo H H; Satoh M M; Akaike A A | 1998-06-05 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Neuroscience letters | 9654354 | m-Calpain (calcium-activated neutral proteinase) in Alzheimer's disease brains. | An antibody specific for the calpain isoform m-calpain was used to resolve conflicting results from several studies on the possible role of m-calpain in the pathogenesis of Alzheimer's disease (AD). Levels of the enzyme in both cytosolic and membranous fractions of brain tissue were determined by Western blot analysis. We also demonstrated changes in m-calpain molecules in AD brains using high-resolution 2D gel electrophoresis (2DE). The levels of the m-calpain isoform detected in the cytosolic fraction were significantly increased in AD brains when compared with the levels in controls. On 2DE, m-calpain molecules resolved into eight main spots. These spots were detected in AD brains as well as in control brains, suggesting that the calpain molecule was not qualitatively changed in AD. Quantitative analysis of the m-calpain spots on 2DE, on the other hand, indicated that the ratio of the intensity of four protein spots in the acidic region to that of the total spots was increased in AD brains. | Tsuji T T; Shimohama S S; Kimura J J; Shimizu K K | 1998-05-29 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Neuroscience letters | 9654355 | Dependence of sympathetic vasomotor tone on bilateral inputs from the rostral ventrolateral medulla in the rabbit: role of baroreceptor reflexes. | A unilateral microinjection of muscimol into the pressor region in the rostral ventrolateral medulla (RVLM) of anaesthetised baroreceptor-denervated rabbits resulted in large and sustained decreases in mean arterial pressure, renal sympathetic nerve activity and heart rate (maximal decreases of 41 +/- 4 mmHg, 64 +/- 3%, and 59 +/- 8 beats/min, respectively). Subsequently, muscimol microinjection into the contralateral RVLM pressor region resulted in further but much smaller decreases in these variables. In contrast, it is well established that in baro-intact animals unilateral inactivation of the RVLM pressor region has little effect on resting sympathetic activity or arterial pressure - bilateral inactivation is required to produce large and sustained decreases. The results of the present study indicate that the baroreceptor reflex plays a crucial role in maintaining resting sympathetic vasomotor activity under circumstances in which the activity of RVLM presympathetic neurons is partially impaired. | Horiuchi J J; Dampney R A RA | 1998-05-29 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Neuroscience letters | 9654359 | Nitric oxide activates Ca2+-activated K+ channels in cultured bovine adrenal chromaffin cells. | The effects of sodium nitroprusside (SNP) on Ca2+-dependent K+ (KCa) channels in cultured bovine adrenal chromaffin cells were investigated using single channel recording patch-clamp techniques. KCa channels were activated by application of 100 microM SNP to the extracellular side of cell-attached patches. Methylene blue (300 microM), an inhibitor of soluble guanylate cyclase, or H-8 (1 microM), a protein kinase inhibitor with relative specificity for cGMP-dependent protein kinase, diminished but did not completely abolish the SNP-induced KCa channel activation. Diethylamine/NO complex (DEA/NO), an NO donor, also activated KCa channels in cell-attached patches. Furthermore, application of 100 microM SNP or 100 nM DEA/NO to the intracellular surface of excised inside-out patches also activated KCa channels in the bath solution which contained 1 microM Ca2+. These results indicate that SNP is capable of activating the KCa channel via cGMP-dependent and -independent mechanisms. These studies demonstrate that NO may serve as an important regulatory mechanism for catecholamine secretion in chromaffin cells via the activation of KCa channels. | Chen C H CH; Houchi H H; Ohnaka M M; Sakamoto S S; Niwa Y Y; Nakaya Y Y | 1998-05-29 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Neuroscience letters | 9654364 | Central administration of urocortin inhibits vasopressin release in conscious rats. | Urocortin (UCN) is a new mammalian member of the corticotropin releasing factor (CRF) family and supposed to be an endogenous ligand for type 2 CRF receptors. Previous studies have revealed that UCN mRNA exists in the supraoptic nucleus (SON), and that water deprivation increases UCN immunoreactivity in SON. In this study, we examined the effect of centrally-administered UCN on arginine vasopressin (AVP) release in conscious rats. Intracerebroventricular (i.c.v.) injection of UCN (5.0 microg/rat) significantly attenuated AVP release induced by hyperosmolality at 30 min after the injection. In contrast, CRF (5.0 microg/rat) injected i.c.v. had no significant effect on AVP release. These results suggest that central UCN play an inhibitory role in osmoregulation of AVP release. | Kakiya S S; Yokoi H H; Arima H H; Iwasaki Y Y; Oki Y Y; Oiso Y Y | 1998-05-29 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Prostaglandins, leukotrienes, and essential fatty acids | 9654400 | Inhibition of EGF-dependent mitogenesis by prostaglandin E2 in Syrian hamster embryo fibroblasts. | Lipid metabolism can play an important role in the development and progression of human cancers. We have used Syrian hamster embryo (SHE) fibroblasts as a model system to study how lipid metabolites can alter cell proliferation and apoptosis. For example, the linoleic acid metabolite 13(S)-HpODE enhances EGF-dependent growth by inhibiting de-phosphorylation of the EGFR which leads to activation of the MAP kinase pathway. In contrast, the arachidonic acid metabolite, PGE2, inhibits EGF-dependent mitogenesis and the expression of the proto-oncogenes c-myc, c-jun, and jun-B. In this study, we have investigated the mechanism by which PGE2 attenuates these responses by studying the EGF signaling cascade in SHE cells. PGE2 pretreatment caused a concentration-dependent decrease in EGF-dependent phosphorylation of MAP kinase and a corresponding inhibition of EGF-stimulated MAP kinase activity. Pretreatment of the SHE cells with PGE2 had little effect on the magnitude of EGF-dependent receptor auto-phosphorylation and the phosphorylation of GAP suggesting a down-stream target. Treatment of cells with forskolin and EGF causes similar inhibition of MAP kinase phosphorylation as observed with PGE2 and EGF. Since PGE2 elevates cAMP in these cells, it may act by altering cAMP accumulation. Raf-1 activity can be inhibited by a cAMP-dependent process. Raf-1 activity, measured by phosphorylation of Mek-1, was attenuated by the addition of PGE2. To determine if inhibition of Raf-1 activity causes inhibition of the MAP kinase pathway, cells were concomitantly incubated with PGE2 and EGF. Inhibition of MAP kinase phosphorylation was observed. From these data, we propose that in SHE cells PGE2 increases cAMP levels, which in turn causes inhibition of Raf-1 activity. The MAP kinase pathway is thus downregulated which decreases mitogenesis and proto-oncogene expression. This study demonstrates that an arachidonic acid metabolite can modulate phosphorylation and activity of key signal transduction proteins in a growth factor mitogenic pathway. | Hsi L C LC; Eling T E TE | 1998-04-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Prostaglandins, leukotrienes, and essential fatty acids | 9654399 | Inhibition of leukotriene synthesis by terfenadine in vitro. | To determine the inhibitory mechanisms of terfenadine on the synthesis of leukotriene C4 (LTC4), an important mediator in allergic diseases, we evaluated the action of terfenadine on the IgE-dependent production of LTC4 in rat basophilic leukaemia 2H3 cells. Rat IgE-loaded cells were stimulated with anti-IgE in the presence or absence of various concentrations of terfenadine and the level of LTC4 released into the medium was measured by performing a specific radio immunoassay. Terfenadine inhibited the synthesis of LTC4 to 67.2% at a concentration of 5 microg/ml. LT synthesis was directly suppressed by inhibition of 5-lipoxygenase (5-LO) through calcium ion-independent mechanisms, and was also possibly suppressed by inhibition of cytosolic phospholipase A2 and 5-LO by blocking the influx of intracellular calcium ion that was initiated by IgE-related stimulation. | Hamasaki Y Y; Kita M M; Hayasaki R R; Zaitu M M; Muro E E; Yamamoto S S; Kobayashi I I; Matsuo M M; Ichimaru T T; Miyazaki S S | 1998-04-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Prostaglandins, leukotrienes, and essential fatty acids | 9654402 | Effect of dietary n-3 fatty acids on interleukin-2 and interleukin-2 receptor alpha expression in activated murine lymphocytes. | Dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) suppress interleukin-2 (IL-2) secretion and impair T-lymphocyte proliferation. To determine the mechanism of action, mice were fed diets containing either safflower oil (control diet enriched in linoleic acid, 18:2n-6), EPA, DHA or arachidonic acid (20:4n-6). Splenic lymphocytes were isolated and concanavalin A-induced kinetics of IL-2 and IL-2 receptor alpha mRNA expression were determined by relative competitive-PCR. EPA and DHA did not affect IL-2 mRNA expression but suppressed IL-2 receptor alpha mRNA levels. These data show, for the first time, the selective effects of dietary EPA and DHA on T-lymphocyte gene expression. | Jolly C A CA; McMurray D N DN; Chapkin R S RS | 1998-04-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Prostaglandins, leukotrienes, and essential fatty acids | 9654403 | Induction of apoptosis, p53 and heme oxygenase-1 by cytotoxic prostaglandin delta12-PGJ2 in transformed endothelial cells. | Delta12-prostaglandin (PG)J2, which has been reported to have potent growth inhibitory activity in various tumor cells, induced apoptosis at 5 microg/ml culture medium in transformed mouse endothelial (F2) cells. Immunoblot analysis using anti-p53 or anti-WAF1 antibodies demonstrated that these two proteins had increased following delta12-PGJ2 treatment in F2 cells. Western blotting analysis using anti-heme oxygenase-1 (heat shock protein (HSP)32) antibody also revealed that delta12-PGJ2 induced HSP32 formation in F2 cells. HSP32 was also induced by heat shock treatment at 43 degrees C for 90 min. In contrast, HSP72 was not induced by heat shock or by delta12-PGJ2 treatment. In agreement with these findings, HSP32 immunofluorescence in the cytoplasm of F2 cells was intensified by delta12-PGJ2 treatment. More intense HSP32 immunoreactivity was similarly observed after heat shock treatment. These results suggest that delta12-PGJ2 caused the apoptotic cell death of F2 cells, which involved a certain process required for p53 or HSP32 induction. | Ikai K K; Kudo H H; Toda K K; Fukushima M M | 1998-04-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Prostaglandins, leukotrienes, and essential fatty acids | 9654404 | Dietary n-3 fatty acids alter angiotensin-induced contraction and 1,2-diacylglycerol fatty acid composition in thoracic aortas from diabetic rats. | The effect of diabetes on the incorporation of long-chain n-3 fatty acids into thoracic aorta smooth muscle phospholipids and 1,2-diacylglycerol, and on the contractile response of aortic rings to angiotensin II, was examined in streptozotocin-induced diabetic rats. In diabetic animals fed a diet containing 1% of fatty acids as n-3 fatty acids, smooth muscle membrane levels of 18:2n-6 were elevated in phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, whereas 20:4n-6 was depleted. The resultant decreased ratios of 20:3/18:2 and 20:4/20:3 indicate inhibition of delta6- and delta5-desaturase activity in the diabetic state. A diet containing 5% of fatty acids as n-3 fatty acids increased phospholipid levels of eicospentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) several-fold, but with a further reduction in 20:4n-6. Similarly, 1,2-diacylglycerol from rats fed the high n-3 diet was enriched in EPA, DPA and DHA. When incubated with 10(-8) M angiotensin II, the contractile response of intact aortic rings from diabetic animals fed the high n-3 diet was only 60.8+/-9.3% that of controls fed the same diet. However, contractile response was not significantly different from control animals fed the low n-3 diet (55.6+/-7.9%). The results indicate that vascular smooth muscle phospholipid n-6 and n-3 fatty acid metabolism is altered in diabetes, resulting in changes to the fatty acid profile of 1,2-diacylglycerol. Moreover, elevating membrane phospholipid and 1,2-diacylglycerol content of EPA, DPA and DHA partially ameliorates the depressed response to angiotensin II seen in the diabetic state. | Pehowich D J DJ | 1998-04-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | The New England journal of medicine | 9654536 | Reversal of lesions of diabetic nephropathy after pancreas transplantation. | BACKGROUND: In patients with type I diabetes mellitus who do not have uremia and have not received a kidney transplant, pancreas transplantation does not ameliorate established lesions of diabetic nephropathy within five years after transplantation, but the effects of longer periods of normoglycemia are unknown. METHODS: We studied kidney function and performed renal biopsies before pancreas transplantation and 5 and 10 years thereafter in eight patients with type I diabetes but without uremia who had mild to advanced lesions of diabetic nephropathy at the time of transplantation. The biopsy samples were analyzed morphometrically. RESULTS: All patients had persistently normal glycosylated hemoglobin values after transplantation. The median urinary albumin excretion rate was 103 mg per day before transplantation, 30 mg per day 5 years after transplantation, and 20 mg per day 10 years after transplantation (P=0.07 for the comparison of values at base line and at 5 years; P=0.11 for the comparison between base line and 10 years). The mean (+/-SD) creatinine clearance rate declined from 108+/-20 ml per minute per 1.73 m2 of body-surface area at base line to 74+/-16 ml per minute per 1.73 m2 at 5 years (P<0.001) and 74+/-14 ml per minute per 1.73 m2 at 10 years (P<0.001). The thickness of the glomerular and tubular basement membranes was similar at 5 years (570+/-64 and 928+/-173 nm, respectively) and at base line (594+/-81 and 911+/-133 nm, respectively) but had decreased by 10 years (to 404+/-38 and 690+/-111 nm, respectively; P<0.001 and P=0.004 for the comparisons with the base-line values). The mesangial fractional volume (the proportion of the glomerulus occupied by the mesangium) increased from base line (0.33+/-0.07) to 5 years (0.39+/-0.10, P=0.02) but had decreased at 10 years (0.27+/-0.02, P=0.05 for the comparison with the baseline value and P=0.006 for the comparison with the value at 5 years), mostly because of a reduction in mesangial matrix. CONCLUSIONS: Pancreas transplantation can reverse the lesions of diabetic nephropathy, but reversal requires more than five years of normoglycemia. | Fioretto P P; Steffes M W MW; Sutherland D E DE; Goetz F C FC; Mauer M M | 1998-07-09 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Gastrointestinal endoscopy clinics of North America | 9654571 | Enteral feeding solutions. | There has been a widespread proliferation of enteral feeding solutions for general and specific therapeutic use. This article reviews the nutrient substrates and physical characteristics of these solutions with consideration to both psychological and clinically-proven principles pertinent to their application. The rationale for the composition and efficacy studies of disease-specific solutions also is presented. | Matarese L E LE | 1998-07-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Gastrointestinal endoscopy clinics of North America | 9654572 | Design and production of enteral feeding tubes. | The evolution of enteral feeding via tubes, syringes, and other mechanical devices probably began in Egypt before the birth of Christ. Today's feeding tubes are a safe and effective means for providing long-term feeding to patients unable to maintain sufficient nutrition by oral intake. The needs of enterally-fed patients are presently being met with feeding tubes that are biocompatible, easy to use, and relatively inexpensive to manufacture. | Hirsch W H WH; Piontek C J CJ | 1998-07-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Gastrointestinal endoscopy clinics of North America | 9654573 | Enteral feeding in critical care, gastrointestinal diseases, and cancer. | This article discusses the many advantages and changes that have occurred in the nutritional management of critically-ill patients, patients with gastrointestinal diseases, and patients with selected cancers. Mechanical obstruction is the only absolute contraindication to enteral nutrition. This article reviews the present aggressive approach to the use of enteral nutrition. | Kirby D F DF; Teran J C JC | 1998-07-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Gastrointestinal endoscopy clinics of North America | 9654575 | Enteral nutrition in the pediatric population. | Enteral feeding, the provision of liquid nutrients into the gastrointestinal tract, is an important component of pediatric care. For the infant or child with a functioning or even a partially-functioning GI tract, the use of the enteral route provides a safe and efficient means of delivering nutrition at a time of life when requirements are extremely high. In addition to high nutrient requirements in the early years of life, there are a number of specific pediatric conditions, such as failure to thrive, short bowel syndrome, and congenital heart disease, which place further demands on the growing child. These demands can be met through the careful use of enteral feeds. This article reviews the physiology and practical application of enteral feeding to the pediatric age group. | Marchand V V; Baker S S SS; Baker R D RD | 1998-07-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Gastrointestinal endoscopy clinics of North America | 9654578 | Cost and cost-benefit of enteral nutrition. | Enteral nutrition is a therapy provided routinely in the hospital, extended care, and home care settings for patients who are unable to maintain adequate oral nutrition yet have a functioning gastrointestinal tract. Information about the cost and effectiveness or benefits of enteral nutrition in the hospital and home care settings is important to know when making decisions about providing this therapy. This article discusses the methods used in cost analysis, explains the difference between cost and charges, and reviews the current information known about the cost-effectiveness and cost-benefits of enteral nutrition in the acute-care setting and at home. | Goff K L KL | 1998-07-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Gastrointestinal endoscopy clinics of North America | 9654576 | Outcome of long-term enteral feeding. | In the past two decades, many technical advances have made tube enteral feeding much more comfortable and acceptable to patients and their families. This has greatly expanded the use of this therapy, both in clinical conditions where it was traditionally prescribed and in many other diagnoses. This expanded use raises important questions about how much enteral nutrition is being used, the medical outcome in different clinical conditions, and the quality of life experienced by long-term therapy users. This article addresses these outcome issues for patients in the nonhospital setting. | Howard L L; Patton L L; Dahl R S RS | 1998-07-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Pathology oncology research : POR | 9654602 | Recent advances in molecular genetics of cardiovascular disorders. Implications for atherosclerosis and diseases of cellular lipid metabolism. | Two developments in molecular genetics will profoundly influence our understanding and the diagnosis of cardiovascular disorders. First, the identification of genes responsible for monogenic and polygenic traits by analysis of for example large pedigrees and affected sib pairs provides invaluable data regarding the role of specific genes in common diseases like arteriosclerosis, hypertension, diabetes, thrombosis/hemostasis and obesity. Besides the insights into the underlying pathophysiology, this knowledge will permit to identify persons at high risk for disease development. These patients can then obtain a targeted intervention. The second development is related to the availability of new analytical tools for molecular biology. New methods such as sequencing by hybridisation (SBH), DNA-array technology or matrix assisted laser desorption/ionisation-time of flight mass spectroscopy (MALDI-TOF) permit sequence analysis of complete genes within hours. Automated PCR-technologies with homogenous amplicon detection formats simplify PCR and permit its use in the routine laboratory setting. Considering cardiovascular diseases there is a number of genes involved in lipid metabolism (apolipoproteins, lipoprotein receptors, lipolytic enzymes), thrombosis/hemostasis (platelet receptors, pro- and anticoagulant proteins, fibrinogen, PAI's), hypertension (angiotensin converting enzyme, angiotensinogen) glucose metabolism (glucose transporters, enzymes) and obesity (hormones, receptors), that are interesting candidates for sophisticated genetic risk assessment. Furthermore, there are also gene candidates involved in processes of early atherogenesis and chronic inflammation such as complement proteins, cell adhesion molecules, and cellular receptors and enzymes. Most of these gene candidates were derived from pathophysiologic knowledge and subsequent epidemiological studies. However, it is foreseeable that in the coming years genes will be identified which were not known so far to be involved in cardiovascular diseases. Genetic studies will be of prime importance in this area, as is exemplified by animal models. In the long term, analysis of these candidate genes before the implementation of therapy will permit a targeted intervention approach towards high risk patients. This will reduce the overall costs of health care without reducing the quality. | Schmitz G G; Aslanidis C C; Lackner K J KJ | 1998-10-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Spine | 9654632 | Nutritional depletion in staged spinal reconstructive surgery. The effect of total parenteral nutrition. | STUDY DESIGN: A prospective randomized study evaluating nutritional depletion in spine surgery patients. OBJECTIVE: To determine whether use of total parenteral nutrition (TPN) in patients undergoing staged spinal reconstructive procedures could affect their nutritional parameters or decrease their complication rates. SUMMARY OF BACKGROUND DATA: Several studies have shown that nutritional depletion occurs after major spinal surgery and that patients undergoing staged spinal surgery may be at particular risk of nutritional loss and its complications. METHODS: Forty adult patients undergoing staged spinal reconstructive surgery were randomized as to whether they received TPN postoperatively. Nutritional parameters, including skin fold measurement and albumin, pre-albumin, transferrin, and total lymphocyte counts, were obtained pre-operatively and at regular intervals. RESULTS: Five patients did not complete the study, leaving 35 patients for analysis. There was a significant decrease in incidence of albumin and pre-albumin depletion for the patients who did not receive TPN compared with those who did receive TPN (P < 0.025, P < 0.006, respectively). Patients with depleted albumin or pre-albumin counts were more likely to develop other postoperative infectious complications such as pneumonia or urinary tract infections (P < 0.035). There were no statistically significant differences in wound complications in this small patient study. There were no complications secondary to use of the TPN. CONCLUSIONS: For complex patients requiring staged anterior/posterior surgery, TPN appears to significantly lessen the decrease in nutritional parameters. Because depletion of nutritional parameters appears to correlate with an increased likelihood of perioperative infectious complications, use of TPN may result in a decrease of such complications in these patients. | Hu S S SS; Fontaine F F; Kelly B B; Bradford D S DS | 1998-06-15 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Steroids | 9654646 | Effect of sodium restriction on urinary excretion of cortisol and its metabolites in humans. | The adrenal gland is involved in the control of urinary sodium excretion mainly via the secretion of the mineralocorticoid aldosterone. Although under certain conditions glucocorticoid seem to be also involved in the regulation of sodium homeostasis, there are contradictory reports on the relationship between cortisol secretion and sodium intake. Given recent findings linking regulation of physiological activity of steroids to the activity of specific enzymatic pathways, we have examined changes in urinary excretion of cortisol and its metabolites in eight healthy volunteers on a low sodium diet. Urinary steroids were measured with specific radioimmunoassays after extraction and chromatography (F and E) or after dilution (THF and THE). Excretion of cortisol (124 +/-41 nmol/day) was significantly lower on Day 2 (86 +/- 27 nmol/day, p < 0.01) and Day 7 (85 +/- 25 nmol/day, p < 0.01) of sodium restriction. On the same samples calculated ratios of THF/F (55 +/- 15; 61 +/- 22; 68 +/- 21) and E/F (2.5 +/- 0.6; 2.8 +/- 1.4; 3.0 +/- 1.3) reflecting the activity of 5 beta-reductase and 11 beta-hydroxysteroid dehydrogenase, respectively, showed significant increases in the former on both Days 2 and 7 and for the latter only on Day 7. This study supports the notion that sodium restriction decreases urinary cortisol excretion and provides evidence that increased activity of 5 beta-reductase and lowered metabolism by 11 beta-HSD are presumably the mechanisms of this decrease. | Lewicka S S; Nowicki M M; Vecsei P P | 1998-07-09 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Steroids | 9654649 | Ginsenoside Rg1 down-regulates glucocorticoid receptor and displays synergistic effects with cAMP. | Ginsenoside-Rg1 (G-Rg1) from the roots of Panax ginseng C. A. Meyer has been shown to bind to the glucocorticoid receptor (GR). To further explore the effect of G-Rg1 binding to GR, a luciferase reporter gene containing two copies of a glucocorticoid response element was constructed and transiently transfected into FTO2B rat hepatoma cells. A dose-dependent induction of the reporter gene was observed in response to G-Rg1, and the inductive effect was blocked by treatment with the antiglucocorticoid RU486. In addition, both G-Rg1- and dexamethasone (Dex)-induced transcription was synergistically enhanced by the treatment of dibutyryl cAMP (Bt2-cAMP). G-Rg1 treatment also led to the down-regulation of intracellular GR content, which was similar to the effect of Dex. By showing that G-Rg1 down-regulates GR and induces GR-mediated transcription synergistically with cAMP, we conclude that G-Rg1 is a functional GR ligand in FTO2B cells. | Chung E E; Lee K Y KY; Lee Y J YJ; Lee Y H YH; Lee S K SK | 1998-07-09 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Texas Heart Institute journal | 9654660 | Is nitroglycerin detrimental in patients with coronary artery ectasia? A case report. | During the management of acute myocardial infarction, we observed that clinical and electrocardiographic indications of myocardial ischemia worsened upon nitroglycerin infusion and were promptly relieved upon streptokinase infusion. Subsequent coronary angiography revealed diffuse ectasia with no significant stenosis. We discuss the possible pathophysiologic mechanisms by which nitroglycerin might exacerbate ischemia in patients with non-stenotic ectasia, and we present supporting data from other sources. We also attempt to identify the characteristics of patients whose acute myocardial ischemia might be worsened by the administration of nitroglycerin. | Sanyal S S; Caccavo N N | 1998-10-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Wiener klinische Wochenschrift | 9654689 | The role of (auto-) immunity in atherogenesis. | Recent data from different laboratories have provided evidence that the first stages of atherosclerosis are inflammatory in nature. Research in the last decades on this multifactorial disease has primarily focussed on the role of lipids, with only a few anecdotal findings suggesting the involvement of the immune system in atherogenesis. Within the group of antigens that may be responsible for this immunoactivation during atherogenesis, heat shock protein (hsp) 65/60 became a serious candidate based on the fact that immunization] of normocholesterolemic rabbits with hsp65 leads to the development of arteriosclerotic lesions in the aortic intima and these primary inflammatory lesions are aggravated by a cholesterol-rich diet, thus completely resembling human fatty streaks and atherosclerotic plaques. Furthermore, T cells in atherosclerotic lesions of rabbits have been shown to react specially with mycobacterial hsp65, suggesting that cell-mediated immune responses to hsp60 are also involved in the pathogenesis of this disease In a large epidemiological study we demonstrated that serum antibodies to mycobacterial hsp65 were significantly increased in clinically healthy subjects with sonographically demonstrable carotid atherosclerosis. These antibodies crossreact with human hsp60. Thus further elucidation of the role of the role of the immune system in atherogenesis could enhance our understanding of the mechanism of this vascular disorder, and may lead to new therapeutic strategies for atherosclerosis. | Metzler B B; Xu Q Q; Wick G G | 1998-05-22 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Wiener klinische Wochenschrift | 9654694 | Aldosterone-producing adenoma associated with foci of myelolipoma. | The simultaneous occurrence of adrenal myelolipoma and endocrine disorders is rare. Myelolipomas have occasionally been found in patients with Cushing's syndrome, pheochromocytoma and hyperthyroidism. A recently published study described one well-documented case of adrenal adenoma and myelolipoma in a patient with Conn's syndrome. In this report the patient had a one-year history of treated hyperthyroidism and diagnosed aldosterone-producing adenoma. A disseminated adrenal myelolipoma was found within the adrenocortical adenoma. To our knowledge this histological finding has not been previously reported in association with both Conn's syndrome and hyperthyroidism. | Lazurova I I; Sokol L L; Trejbal D D; Bober J J; Zachar M M; Pajtasova D D | 1998-05-22 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Cryobiology | 9654731 | Cytosolic pH variations in perfused rat liver at 4 degrees C: role of intracellular buffering power. | The effect of low temperature on cytosolic pH regulation and buffering capacity was evaluated in the isolated rat liver. The pH changes were followed by phosphorus-31 nuclear magnetic resonance. Cooling from 37 to 4 degrees C, with Krebs-Heinseleit perfusion at an external pH of 7.35, induced an alkaline shift in cytosolic pH (pHcyt) of 0.13 or 0.75 pH units in the presence of bicarbonate, respectively (dpH cys/dT values were 0.004 and 0.022 unit/degrees C. With 4 degrees C perfusion, in the presence or absence of bicarbonate, acute changes of external pH (from 7.40 to 5.90) did not affect pHcyt. In contrast, intracellular loading with isobutyric acid or NH4Cl induced rapid pHcyt variations. The intrinsic buffering power value (10 to 50 slykes) measured in the absence of bicarbonate depended on pHcyt. The larger value was observed for pHcyt 7.30, a value near the pK value of the imidazole group of intracellular proteins at 4 degrees C. The presence of bicarbonate modified the amplitude of the pHcyt change by increasing the total buffering power. It was demonstrated that during hypothermia, ionic carriers are inactivated and the charged forms of molecules are unable to cross the cell membrane; thus, the pHcyt homeostasis depends essentially on intracellular buffering power. | Durand T T; Vidal G G; Canioni P P; Gallis J L JL | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Cryobiology | 9654735 | Temperature threshold and preservation of signaling for mitochondrial membrane proteins during ischemia in rabbit heart. | Temperature modulates both myocardial energy requirements and production. We have previously demonstrated that myocardial protection induced by hypothermic adaptation preserves expression of genes regulating heat shock protein and the nuclear-encoded mitochondrial proteins, the adenine nucleotide translocator isoform 1 (ANT1), and the beta subunit of F1-ATPase (beta F1-ATPase). This preservation is associated with a reduction in ATP depletion similar to that noted in cardioplegic arrested hearts preserved at a critical temperature (30 degrees C) or below. We tested the hypothesis that expression of these genes may also be subject to this temperature threshold phenomenon. Isolated perfused rabbit hearts were subjected to ischemic cardioplegic arrest at 4, 30, or 34 degrees C for 120 min. Cardiac function indices and steady-state mRNA levels for ANT1, beta F1-ATPase, and HSP70-1 were measured prior to ischemia (B) and after 45 min of reperfusion. Cardiac function was significantly depressed in the 34 degrees C group. Ischemia at 34 degrees C reduced steady-state mRNA levels for ANT1 and beta F1-ATPase from B, but these levels were similarly preserved at 4 and 30 degrees C. HSP70-1 levels were mildly elevated (fourfold) above B to similar levels at all three temperatures. These results indicate that mRNA expression for ANT1 and beta F1-ATPase is specifically preserved in a pattern consistent with the temperature threshold phenomenon. HSP70-1 expression is not influenced by ischemic temperature. Preservation of gene expression for these mitochondrial proteins implies that signaling for mitochondrial biogenesis or resynthesis is maintained after ischemic insult. | Ning X H XH; Xu C S CS; Song Y C YC; Xiao Y Y; Hu Y J YJ; Lupinetti F M FM; Portman M A MA | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Physiological chemistry and physics and medical NMR | 9654774 | Electrolyte concentration in skeletal muscles and plasma of rats during and after exposure to hypokinesia and hyperhydration. | The objective of this investigation was to determine electrolyte concentration in skeletal muscles and plasma of rats during 90 days of hypokinesia (decreased motor activity) and 15 days of posthypokinesia. The animals were divided into three groups: 1) supplemented hypokinetic rats (SHR), that is, rats subjected to hypokinesia and taking daily an additional 9 ml water per 100 g body weight plus 6 ml isotonic sodium chloride per 100 g body weight; 2) unsupplemented hypokinetic rats (UHR), that is, rats subjected to hypokinesia; 3) vivarium control rats (VCR), that is, rats placed under ordinary vivarium conditions. Hypokinesia was effected by keeping SHR and UHR animals in small individual cages that restricted their movements in all directions without hindering food and water intake. Determinations were made of water and electrolyte (sodium potassium, calcium, magnesium) concentrations in muscle tissue; concentration of electrolytes (sodium, potassium, calcium, magnesium, phosphorus, chloride) in plasma; body weight; fluid consumed and eliminated in urine; whole blood, red blood cell and plasma volumes; hematocrit content and plasma protein concentration. During the hypokinetic period, electrolytes and water concentration in muscle tissue and plasma electrolyte concentration changes significantly in the UHR when compared with SHR and VCR while in comparing the SHR with the VCR these same variables had no significant changes. Body weight, water balance, volume of blood, red blood cell and plasma, hematocrit and plasma protein concentration in the UHR were also significantly different when compared with the VCR. No significant difference was seen in these parameters when the SHR and VCR were compared. During the initial seven days of the posthypokinetic period the changes in these same parameters remained significantly different in the UHR when compared with the SHR and VCR while changes were insignificant when the SHR and the VCR were compared. It was concluded that daily hyperhydration may be used to attenuate or normalize water and electrolyte concentrations in muscles and plasma of rats subjected to prolonged restriction of motor activity. | Zorbas Y G YG; Yaroshenko Y Y YY; Kuznetsov N K NK; Madvedev S N SN; Federenko Y F YF | 1997-10-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Phytochemistry | 9654777 | Alphitol, a phenolic substance from Alphitonia zizyphoides which inhibits prostaglandin biosynthesis in vitro. | The new phenolic compound, 3,5-dihydroxy-4-methoxy phenethyl alcohol, named alphitol, and betulinic acid were from the bark of Alphitonia zizyphoides. The chemical structure of alphitol was determined by mass spectrometry in combination with one and two dimensional NMR, including HMBC. Both compounds inhibited prostaglandin biosynthesis in vitro, alphitol with an IC50 value of 0.66mM, which is of the same magnitude as acetyl salicylic acid. | Dunstan C C; Liu B B; Welch C J CJ; Perera P P; Bohlin L L | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Journal of the American Pharmaceutical Association (Washington, D.C. : 1996) | 9654849 | Important features of blood glucose meters. | OBJECTIVE: To provide an overview of several blood glucose meters that will enhance practicing pharmacists' knowledge and understanding of these devices to allow education of the patient with diabetes. DATA SOURCES: Original and review articles, blood glucose meter package inserts and manuals. DATA SYNTHESIS: Careful blood glucose control is essential to prevent long-term complications of diabetes. Newer blood glucose meters have a broad variety of features, including small size, extended memory capacity, blood glucose manipulation techniques, and computer downloading capabilities. The decision to choose a blood glucose meter should be based on a number of criteria, including the patient's needs, ease of use, and affordability. CONCLUSION: Pharmacists must position themselves to differentiate among the numerous blood glucose meters available on the market and make appropriate recommendations based on patient-specific needs. | Kirk J K JK; Rheney C C CC | 1998-07-09 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Journal of the American Pharmaceutical Association (Washington, D.C. : 1996) | 9654867 | Gestational diabetes. | OBJECTIVE: To review the detection, diagnosis, and clinical management of gestational diabetes. DATA SOURCES: MEDLINE, Gestational Diabetes Guideline Review, 1968-1998. STUDY SELECTION: By the author. DATA EXTRACTION: By the author. DATA SYNTHESIS: Gestational diabetes is a common complication of pregnancy, occurring in 2% to 6% of pregnancies. Uncontrolled gestational diabetes is associated with increased infant morbidity and mortality, macrosomia, and cesarean deliveries, and is a strong marker for the future development of maternal diabetes mellitus. Women with risk factors for gestational diabetes should be screened for glucose intolerance at 24 to 28 weeks' gestation. If a screening plasma glucose concentration is 140 mg/dL or greater one hour after a 50 gram oral glucose load, then a diagnostic 100 gram, three-hour oral glucose tolerance test should be performed. Medical nutrition therapy is the cornerstone of management and must be designed to meet individual needs. Self-monitoring of blood glucose should be taught to and performed by all women with gestational diabetes. Insulin, which does not readily cross the placental barrier, is the drug therapy of choice in women failing medical nutrition therapy. CONCLUSION: Pharmacists can optimize overall care by educating, monitoring, and intervening or assisting the patient in the management of gestational diabetes. | Sullivan B A BA; Henderson S T ST; Davis J M JM | 1998-07-09 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | The Journal of surgical research | 9655083 | Ischemia/reperfusion injury of the pancreas: a new animal model. | BACKGROUND: Ischemia/reperfusion is thought to play an important role in the development of postimplantation pancreatitis after pancreas transplantation and also in the transition of edematous pancreatitis into necrotizing pancreatitis. Previous studies have suggested that impairment of microcirculation and hence tissue oxygenation and energy metabolism may be critical steps in this process. MATERIALS AND METHODS: In landrace pigs vascular isolation of the pancreatic tail was performed. Morphological alterations, tissue oxygenation, and energy metabolism were assessed in response to 3 h of global warm ischemia and the following reperfusion. RESULTS: A rapid onset of morphological alterations immediately after reperfusion was noted. Oxygen consumption and ATP levels were markedly decreased, and tissue oxygenation was severely impaired especially during the first hour after reperfusion. ATP tissue levels and oxygen consumption 10 min after reperfusion correlated significantly with the morphological changes at the end of the experiment. CONCLUSION: These findings can be explained by a failure of nutritive capillary perfusion and concomitant shunt perfusion. Therefore an impaired microcirculation rather than an impaired oxygen utilization shortly after reperfusion is of major relevance in the development of the ischemia/reperfusion injury of the pancreas. | Benz S S; Schnabel R R; Morgenroth K K; Weber H H; Pfeffer F F; Hopt U T UT | 1998-03-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | The Journal of surgical research | 9655085 | Nitric oxide inhibits peroxide-mediated endothelial toxicity. | BACKGROUND: Oxidant molecules and nitric oxide (NO) have each been implicated as mediators of endothelial cell damage, but the biologic effect of these molecules acting in concert is incompletely understood. MATERIALS AND METHODS: We studied the effects of an NO donor, S-nitroso-acetyl-D,L-penicillamine (SNAP), in combination with the peroxidants tert-butyl hydroperoxide (TBH) and hydrogen peroxide (H2O2) on rabbit aortic endothelial cells in culture. Cell viability was assessed using Alamar blue, a nontoxic dye indicator of cell metabolism. Lipid peroxidation was assessed using a chemiluminescent single-photon counting technique. RESULTS: After 90 min exposure to test reagents, there was concentration-dependent cytotoxicity for both TBH and H2O2. Peroxidant-induced cytotoxicity was significantly ameliorated by SNAP (10(-4)-10(-3)M). N-Acetylpenicillamine and NO-depleted SNAP failed to demonstrate a cytoprotective effect against peroxidant cellular injury, thus implicating NO as the agent responsible for the protective effect. SNAP reduced lipid peroxidation caused by 10(-3) M TBH in a dose-dependent manner. Preincubation of cells with SNAP before exposure to peroxidants alone had no effect on toxicity. CONCLUSIONS: NO is cytoprotective to the endothelium in the presence of peroxidants through a reduction of lipid peroxidation. | Degnim A C AC; Morrow S E SE; Ku J J; Zar H A HA; Nakayama D K DK | 1998-03-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Muscle & nerve | 9655116 | Alternative dystrophin gene transcripts in golden retriever muscular dystrophy. | Golden retriever muscular dystrophy (GRMD), the canine model of Duchenne muscular dystrophy (DMD), is caused by a splice site mutation in the dystrophin gene. This mutation predicts a premature termination codon in exon 8 and a peptide that is 5% the size of normal dystrophin. Western blot analysis of skeletal muscle from GRMD dogs reveals a slightly truncated 390-kD protein that is approximately 91% the size of normal dystrophin. This 390-kD dystrophin suggests that GRMD dogs, like some DMD patients, employ a mechanism to overcome their predicted frameshift. Reverse-transcriptase polymerase chain reaction on GRMD muscle has revealed two in-frame dystrophin transcripts which lack either exons 3-9 or exons 5-12. Both transcripts could be translated into a dystrophin protein of approximately 390 kD. An understanding of how truncated dystrophin is produced in GRMD may allow this mechanism to be manipulated toward a potential therapy for DMD. | Schatzberg S J SJ; Anderson L V LV; Wilton S D SD; Kornegay J N JN; Mann C J CJ; Solomon G G GG; Sharp N J NJ | 1998-08-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Muscle & nerve | 9655120 | Disruption and reorganization of sodium channels in experimental allergic neuritis. | The axonal distribution of voltage-dependent Na+ channels was determined during inflammatory demyelinating disease of the peripheral nervous system. Experimental allergic neuritis was induced in Lewis rats by active immunization. In diseased spinal roots Na+ channel immunofluorescence at many nodes of Ranvier changed from a highly focal ring to a more diffuse pattern and, as the disease progressed, eventually became undetectable. The loss of nodal channels corresponded closely with the development of clinical signs. Electrophysiological measurements and computations showed that a lateral spread of nodal Na+ channels could contribute significantly to temperature sensitivity and conduction block. During recovery new clusters of Na+ channels were seen. In fibers with large-scale demyelination, the new aggregates formed at the edges of adhering Schwann cells and appeared to fuse to form new nodes. At nodes with demyelination limited to paranodal retraction, Na+ channels were often found divided into two symmetric highly focal clusters. These results suggest that reorganization of Na+ channels plays an important role in the pathogenesis of demyelinating neuropathies. | Novakovic S D SD; Levinson S R SR; Schachner M M; Shrager P P | 1998-08-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Muscle & nerve | 9655125 | Myoglobin as a polymerase chain reaction (PCR) inhibitor: a limitation for PCR from skeletal muscle tissue avoided by the use of Thermus thermophilus polymerase. | Skeletal muscle tissue contains polymerase chain reaction (PCR) inhibitors that are coextracted by conventional nucleic acid extraction procedures. Myoglobin, a heme-containing molecule, was shown to act as a potent Thermus aquaticus DNA polymerase inhibitor and is likely to be involved in muscle tissue-associated PCR inhibition. The use of Thermus thermophilus DNA polymerase avoids muscle tissue-associated PCR inhibition, and should be used in case of small amounts or instability of the targeted nucleic acid. | Bélec L L; Authier J J; Eliezer-Vanerot M C MC; Piédouillet C C; Mohamed A S AS; Gherardi R K RK | 1998-08-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Muscle & nerve | 9655129 | Pseudometabolic expression and phenotypic variability of calpain deficiency in two siblings. | Two siblings originating from Reunion Island were affected by a limb-girdle muscular dystrophy (LGMD) type 2A and carried the same two mutations in the calpain gene: 946-1 AG-->AA, affecting a splice site, and S744G. They demonstrated the clinical variability possible with calpain-3 mutations. Onset was around 20 years of age in each of them. The girl's symptoms mimicked a metabolic myopathy, while her brother, at the same age, presented a classical phenotype of LGMD in an advanced functional stage. | Pénisson-Besnier I I; Richard I I; Dubas F F; Beckmann J S JS; Fardeau M M | 1998-08-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Pediatric neurosurgery | 9655142 | Identification of the volume-sensitive organic osmolyte/anion channel in human glial cells. | Cellular use of small organic solutes known as organic osmolytes for regulation of the volume of the cell is a universal biological phenomenon. During swelling, cells open an anion channel which allows for efflux of these solutes. This channel is known as the volume-sensitive organic osmolyte/anion channel (VSOAC). Anion channels with properties identical to VSOAC were found in human brain cells obtained following pediatric neurosurgical procedures. The tissues examined included tumors as well as putatively normal gray and white matter astrocytes. The cells activated an anion conductance when swollen by hypotonic shock. Baseline currents in these cells were generally small and increased up to 30-fold within 10 min following the onset of swelling. The anion channel activated by swelling was outwardly rectified and inactivated by depolarization, both characteristic of the VSOAC. These observations indicate that human glial cells and tumor cells activate VSOAC following cellular swelling. This suggests that organic osmolyte efflux can be modulated during brain swelling by pharmaceuticals which modulate VSOAC. | Jackson P S PS; Madsen J R JR | 1997-12-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis | 9655151 | The role of Na,K-ATPase inhibitors in hypertension and end-stage renal disease. | OBJECTIVE: To review the role of Na,K-ATPase inhibitors in the pathogenesis of essential hypertension and hypertension associated with end-stage renal disease. DATA SOURCES: MEDLINE search, 1966 to 1997. RESULTS: There is a suggestive physiologic and epidemiologic relationship between Na,K-ATPase inhibition and hypertension. However, clearance data cannot support the hypothesis that differential metabolism of this family of compounds explains the improved hypertensive control seen in patients on peritoneal dialysis compared to those on hemodialysis. CONCLUSIONS: As a result of the complex methodologies involved, it is unclear whether Na,K-ATPase inhibitors play a significant role in the hypertension of end-stage renal disease in general and peritoneal dialysis in particular. | Bargman J M JM | 1998-07-09 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis | 9655152 | Beta-blockers may cause ultrafiltration failure in peritoneal dialysis patients. | OBJECTIVE: To elucidate mechanisms of ultrafiltration failure. There was no intergroup difference in number of women, patient age or weight, incidence of diabetes or previous peritonitis, duration of PD, serum levels of albumin, creatinine, iron, or ferritin, or dosage of erythropoietin. Correlation was found between the daily amount of glucose instilled into the abdomen and serum triglycerides (r = +0.72, p < 0.001), total cholesterol (r = +0.56, p = 0.008), and HbA1C (r =-0.41, p = 0.039). Many patients were high absorbers of dialysis glucose. CONCLUSION: The study indicates that beta-blockers may cause UFF, and that glucose and lipid metabolism differed between these patients and controls without UFF. | Stegmayr B G BG | 1998-07-09 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis | 9655154 | Calcium concentration in the CAPD dialysate: what is optimal and is there a need to individualize? | OBJECTIVE: To evaluate risk/benefit of various continuous ambulatory peritoneal dialysis (CAPD) dialysate calcium concentrations. DATA SOURCES: A review of the literature on the effects of various CAPD dialysate Ca concentrations on plasma Ca, plasma phosphate, plasma parathyroid hormone (PTH), doses of calcium carbonate, doses of vitamin D analogs, and requirements of aluminum-containing phosphate binders. STUDY SELECTION: Eleven studies of nonselected CAPD patients, and 13 studies of CAPD patients with hypercalcemia were reviewed. RESULTS: In nonselected CAPD patients, treatment with a reduced dialysate Ca concentration (1.00, 1.25, or 1.35 mmol/L) improved the tolerance to calcium carbonate and/or vitamin D metabolites and reduced the need for Al-containing phosphate binders. When using dialysate Ca 1.25 or 1.35 mmol/L, the initial decrease of plasma Ca and increase of PTH could easily be reversed with an immediate adjustment of the treatment. After 3 months, stable plasma Ca and PTH levels could be maintained using only monthly investigations. In patients with hypercalcemia and elevated PTH levels, treatment with dialysate Ca concentrations below 1.25 mmol/L implied a considerable risk for the progression of secondary hyperparathyroidism. When hypercalcemia was present in combination with suppressed PTH levels, a controlled increase of PTH could be obtained with a temporary discontinuation of vitamin D and/or a reduction of calcium carbonate treatment in combination with a dialysate Ca concentration of 1.25 or 1.35 mmol/L. CONCLUSION: Most CAPD patients can be treated effectively and safely with a reduced dialysate Ca concentration of 1.35 or 1.25 mmol/L. Treatment with dialysate Ca concentrations below 1.25 mmol/L should not be used. A small fraction of patients with persistent hypocalcemia need treatment with high dialysate Ca, such as 1.75 mmol/L. | Bro S S; Brandi L L; Daugaard H H; Olgaard K K | 1998-07-09 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis | 9655160 | Increased endothelin-1 mRNA expression in peripheral blood monocytes of dialysis patients. | OBJECTIVE: To compare plasma endothelin (ET)-1 level and ET-1 mRNA level in peripheral blood monocytes of patients undergoing hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Endothelin-1 mRNA level in peripheral blood monocytes and plasma ET-1 level were studied in 30 HD patients, 15 CAPD patients, 20 chronic renal failure patients not being dialyzed, and 20 normal healthy controls. Hemodialysis patients were dialyzed three times per week with a bicarbonate dialysate. Different types of dialyzer membrane, viz., cellulose triacetate, cuprophane, polysulfone, polyacrylonitrile, and ethylenevinylalcohol were used in 8, 6, 6, 5, and 5 patients, respectively. Continuous ambulatory peritoneal dialysis patients were dialyzed with four daily exchanges of a 2-L dialysate containing glucose at a concentration of 1.5% to 2.5%. RESULTS: Higher levels of ET-1 mRNA in monocytes were observed in HD patients than in CAPD patients (p < 0.01), chronic renal failure patients (p < 0.01), or normal healthy controls (p < 0.001). The level of ET-1 mRNA in monocytes at the end of HD was not significantly higher than that at the start of HD. In addition, these mRNA levels in HD patients showed little difference with different types of dialysis membrane. Plasma ET-1 level in HD patients (10.2 +/- 2.4 pg/mL) was also higher than that in CAPD patients (7.8 +/- 1.6 pg/mL, p < 0.01), in chronic renal failure patients (4.8 +/- 1.2 pg/mL, p < 0.01), or in normal controls (2.6 +/- 0.8 pg/mL, p < 0.001). CONCLUSION: Dialysis itself did not significantly affect ET-1 mRNA levels in monocytes. Chronic stimulation of peripheral blood monocytes may be associated with higher levels of ET-1 mRNA and plasma ET-1 in HD patients than in CAPD patients. | Ebihara I I; Nakamura T T; Takahashi T T; Tomino Y Y; Shimada N N; Koide H H | 1998-07-09 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis | 9655161 | Serum disaccharides and osmolality in CCPD patients using icodextrin or glucose as daytime dwell. | OBJECTIVE: To evaluate the safety, efficacy, and biocompatibility of icodextrin- and glucose-containing dialysis fluid during continuous cycling peritoneal dialysis, a high molecular weight fraction (G > 10), and total carbohydrate level, as well as a biochemical profile were determined every 3 months in combination with all other study variables. RESULTS: In icodextrin-treated patients, serum disaccharide (maltose) concentrations increased from 0.05 +/- 0.01 (mean +/- SEM) at baseline, to an average concentration in the follow-up visits of 1.14 +/- 0.13 mg/mL (p < 0.001). All icodextrin metabolites increased significantly from baseline, as illustrated by the serum total carbohydrate minus glucose levels: from 0.42 +/- 0.05 mg/mL to an average concentration in the follow-up visits of 5.04 +/- 0.49 mg/mL (p < 0.001). At the same time, serum sodium levels decreased from 138.1 +/- 0.7 mmol/L to an average concentration in the follow-up visits of 135.4 +/- 0.8 mmol/L (p < 0.05). However, after 12 months the serum sodium concentration increased nonsignificantly (NS) from baseline to 136.6 +/- 0.9 mmol/L, after an initial decrease. Serum osmolality increased significantly from baseline in icodextrin users at 9 and 12 months, but did not differ significantly from glucose users in any visit. In icodextrin-treated patients, the calculated serum osmolal gap increased significantly from 4.1 +/- 1.4 mOsm/kg to an average of 11.8 +/- 1.7 mOsm/kg (p < 0.01). The sum of the serum icodextrin metabolites in millimoles/liter equaled the increase in osmolal gap. Body weight increased in icodextrin users (71.9 +/- 2.8 kg to 77.8 +/- 3.0 kg; NS). Clinical adverse effects did not accompany these findings. Residual renal function remained stable during follow-up. CONCLUSIONS: The serum icodextrin metabolite levels in the present study increased markedly and were the same as those found previously in continuous ambulatory peritoneal dialysis patients treated with icodextrin, despite the longer dwell time for CCPD patients (14-16 hr versus 8-12 hr). The initial decrease in serum sodium concentration was followed by an increase to a concentration not different from baseline at 12 months. The pathophysiology of this finding is speculated. Calculated osmolal gap in icodextrin patients increased significantly (p < 0.01) at every follow-up visit, and could be explained by the serum icodextrin metabolite increase. We encountered no clinical side effects of the observed levels of icodextrin metabolites. | Posthuma N N; ter Wee P M PM; Donker A J AJ; Oe P L PL; van Dorp W W; Peers E M EM; Verbrugh H A HA | 1998-07-09 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Molecular and cellular biochemistry | 9655175 | Inhibition of neuronal nitric oxide synthase (n-cNOS) reverses the corticotrophin-induced behavioral effects in rats. | The nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine (N-NMMA) and the competitive substrate for NO synthase L-arginine were used to determine the role of endogenous NO on the behavioral and neuroendocrine responsiveness following systemic corticotrophin in dexamethasone-suppressed rats. Corticotrophin (50-200 mU/kg, s.c.) dose-dependently decreased behavioral activity in the actimeter and produced significant anxiolytic and anti-risk activity in the plus-maze behavior test, without affecting systolic blood pressure. Rats given corticotrophin showed significant increased plasma corticosterone and reduced adrenal ascorbic acid level. These behavioral and adrenal responses of corticotrophin were dose dependently blocked by metyrapone (20 and 50 mg/kg, i.p.), an inhibitor of steroid 11beta-hydroxylase in adrenal and neural tissues that block steroidogenesis. Intracerebroventricular administration of L-NMMA (20 microg/rat in 10 microl) significantly prevented the behavioral hypoactivity and anxiolytic-like responses of corticotrophin without influencing the adrenal responsiveness. The effect of L-NMMA was completely reversed by preadministration of L-arginine (300 mg/kg, i.p.). These results suggest that neuronal nitric oxide pathway plays an important modulating role in the behavioral effects of corticotrophin by mechanisms other than those involving cardiovascular effects. | Reddy D S DS; Kulkarni S K SK | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Molecular and cellular biochemistry | 9655176 | Endothelin-1 and insulin activate the steady-state voltage dependent R-type Ca2+ channel in aortic smooth muscle cells via a pertussis toxin and cholera toxin sensitive G-protein. | In single rabbit aortic smooth muscle cells, and at a concentration known to induce a maximum sustained increase of intracellular Ca2+ via activation of the steady-state voltage dependent R-type Ca2+ channels, endothelin-1 (10(-7) M) and insulin (80 microU/ml) were found to induce a sustained increase in cytosolic free Ca2+ (i elevation via activation of the R-type Ca2+ channels. Moreover, ET-1 and insulin-evoked sustained increases in Ca2+ influx were not attenuated by the selective PKC inhibitor, bisindolylmaleimide (BIS), or the specific L-type Ca2+ channel blocker, nifedipine, but were completely reversed by the R-type Ca2+ channel blocker, (-) PN 200-110 (isradipine). These data suggest that both insulin and ET-1 activate the nifedipine-insensitive but isradipine-sensitive steady state voltage dependent R-type Ca2+ channels present on rabbit VSMCs and these channels are directly coupled to PTX and CTX sensitive G protein(s). | Bkaily G G; Naik R R; Jaalouk D D; Jacques D D; Economos D D; D'Orléans-Juste P P; Pothier P P | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Molecular and cellular biochemistry | 9655179 | Possible mechanism of captopril induced endothelium-dependent relaxation in isolated rabbit aorta. | The mechanism of captopril, an angiotensin converting enzyme (ACE) inhibitor with sulfhydryl group (SH) in its structure, to produce an endothelium-dependent vasorelaxation was studied. In rabbit aorta with intact endothelium and precontracted with phenylephrine, captopril and superoxide dismutase (SOD) produced dose-dependent relaxation. Lisinopril, an ACE inhibitor without a -SH group in its structure, did not produce endothelium-dependent relaxation. It was observed that captopril, like SOD, produced the relaxation by protecting the EDRF from getting inactivated by superoxide anions as pyrogallol and methylene blue inhibited both the captopril and SOD-mediated relaxation. The free radical scavenging action of captopril is further substantiated by the observation that captopril, but not lisinopril, inhibited FeCl3/ascorbic acid-induced lipid peroxidation in whole tissue homogenates of rabbit aorta to a level comparable to that of SOD. These results suggest that endothelium-dependent vasodilation produced by captopril may be due to its ability to scavenge superoxide anion and this property may be ascribed to the -SH group present in its structure. | Mittra S S; Singh M M | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Molecular and cellular biochemistry | 9655182 | Impaired mitochondrial oxidative phosphorylation in skeletal muscle of the dystrophin-deficient mdx mouse. | The mdx mouse, an animal model of the Duchenne muscular dystrophy, was used for the investigation of changes in mitochondrial function associated with dystrophin deficiency. Enzymatic analysis of skeletal muscle showed an approximately 50% decrease in the activity of all respiratory chain-linked enzymes in musculus quadriceps of adult mdx mice as compared with controls, while in cardiac muscle no difference was observed. The activities of cytosolic and mitochondrial matrix enzymes were not significantly different from the control values in both cardiac and skeletal muscles. In saponin-permeabilized skeletal muscle fibers of mdx mice the maximal rates of mitochondrial respiration were about two times lower than those of controls. These changes were also demonstrated on the level of isolated mitochondria. Mdx muscle mitochondria had only 60% of maximal respiration activities of control mice skeletal muscle mitochondria and contained only about 60% of hemoproteins of mitochondrial inner membrane. Similar findings were observed in a skeletal muscle biopsy of a Duchenne muscular dystrophy patient. These data strongly suggest that a specific decrease in the amount of all mitochondrial inner membrane enzymes, most probably as result of Ca2+ overload of muscle fibers, is the reason for the bioenergetic deficits in dystrophin-deficient skeletal muscle. | Kuznetsov A V AV; Winkler K K; Wiedemann F R FR; von Bossanyi P P; Dietzmann K K; Kunz W S WS | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Molecular and cellular biochemistry | 9655181 | Hyperosmolality-induced abnormal patterns of calcium mobilization in smooth muscle cells from non-diabetic and diabetic rats. | Hyperglycemia and/or hyperosmolality may disturb calcium homeostasis in vascular smooth muscle cells (SMCs), leading to altered vascular contractility in diabetes. To test this hypothesis, the KCl-induced increases ini in primarily cultured vascular SMCs exposed to different concentrations of glucose were examined. With glucose concentration in solutions kept at 5.5 mM, KCl induced a fast increase ini which then slowly declined (type 1 response) in 83% of SMCs from non-diabetic rats. In 9% of non-diabetic SMCs KCl induced a slow increase ini (type 2 response). Interestingly, under the same culture conditions KCl induced type 1 and type 2 responses in 47 and 35% of SMCs from diabetic rats. When SMCs from non-diabetic or diabetic rats were cultured in 36 mM glucose, KCl induced a fast increase ini which, however, maintained at a high level (type 3 response). The sustained level ofi in the presence of KCl was significantly higher in cells cultured with 36 mM glucose than that in non-diabetic cells cultured with 5.5 mM glucose. Furthermore, the hyperglycemia-induced alterations in calcium mobilization were similarly observed in cells cultured in high concentration of mannitol (30.5 mM) or L-glucose, indicating that hyperosmolality was mainly responsible for the abnormal calcium mobilization in diabetic SMCs. | Wang R R; Liu Y Y; Sauvé R R; Anand-Srivastava M B MB | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Molecular and cellular biochemistry | 9655183 | The mitogen-activated protein kinase pathway contributes to vanadate toxicity in vascular smooth muscle cells. | Vanadate has been considered in the treatment of diabetes because of its insulin-like effects. However, it has severe toxic effects in both animal and man. In cultured cells, vanadate can either cause death or be growth stimulatory, depending on the cell type and growth conditions. Here, we report that in baboon aortic smooth muscle cells-BB in a dose dependent fashion (IC50: 30 microM). Prolonged exposure to vanadate exerted cytotoxic effects. Cells retracted, rounded up and detached from the substratum. These vanadate-induced morphological changes were blocked in the presence of PD098059. The addition of PDGF-BB further activated p42/p44MAPK/MAPKK in the presence of vanadate and substantially increased vanadate toxicity. We conclude from these observations that activation of the p42/p44MAPK/MAPKK signalling module contributes to the cytotoxic effects induced by vanadate. | Daum G G; Levkau B B; Chamberlain N L NL; Wang Y Y; Clowes A W AW | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Molecular and cellular biochemistry | 9655188 | In vivo oxidized low density lipoprotein: degree of lipoprotein oxidation does not correlate with its atherogenic properties. | We have recently demonstrated that lipids, particularly cholesterol, covalently bound to apolipoprotein B. The present study is an attempt to assess the relationship between the degree of LDL oxidation, evaluated by the content of apoB-bound cholesterol and the ability of LDL to induce cholesterol accumulation in cultured human aortic intimal smooth muscle cells, that is LDL atherogenicity. Native LDL was oxidized in vitro by copper ions, 2,2-azobis-(2-aminopropane hydrochloride), or sodium hypochlorite. Minimum degree of LDL in vitro oxidation necessary to convert LDL into atherogenic one was accompanied by an increase of apoB-bound cholesterol to the level much higher than that usually observed in freshly isolated atherogenic LDL from human blood. Moreover, elimination of LDL aggregates from in vitro oxidized LDL preparations by gel filtration led to loss of its atherogenic properties. Thus, the ability to induce cholesterol accumulation in cells, that is the atherogenicity of in vitro oxidized LDL is a result of LDL aggregation but not oxidation. We also studied the relationship between LDL atherogenicity and apoB-bound cholesterol content in LDL freshly isolated from healthy subjects and normo- and hypercholesterolemic patients with coronary atherosclerosis. The ability of human LDL to induce cholesterol accumulation in aortic smooth muscle cells did not correlate with the degree of in vivo LDL oxidation (r = 0.12, n = 90). It is concluded that LDL atherogenicity does not depend on the degree of lipid peroxidation in LDL particle. | Tertov V V VV; Kaplun V V VV; Orekhov A N AN | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Molecular and cellular biochemistry | 9655190 | Biophysical characterization of rat cardiac Ca2+/Mg2+ ecto-ATPase (myoglein). | Sarcolemmal Ca2+/Mg2+ ecto-ATPase (Myoglein; MW 180 kD) is a membrane bound enzyme which requires a millimolar concentration of either Ca2+ or Mg2+ for maximal hydrolysis of ATP. The isoelectric point (pI) of the cardiac ecto-ATPase was 5.7. The purified Ca2+/Mg2+ ecto-ATPase from the rat heart sarcolemmal appeared as a single band with MW approximately 90 kD in the SDS-PAGE. In order to understand the nature of this enzyme, the 90 kD band in the SDS-PAGE was electroeluted; the analysis of the eluate showed 2 prominent bands with MW approximately 90 and 85 kD. The presence of 2 bands was further confirmed by gradient gel (10-20%) electrophoresis in 0.375 M Tris-HCl buffer, pH 8.8. Analysis of the purified Ca2+/Mg2+ ecto-ATPase as well as the electroeluted protein in a non-equilibrium linear two dimensional electrophoresis (Ampholyte pI 3.0-10.0) also showed two distinct bands. Mass spectroscopic analysis of the enzyme using different matrix combinations revealed the presence of multi-components indicating microheterogeneity in the protein structure. Treatment of the ecto-ATPase with DL-dithiothreitol did not alter the pattern of mass spectroscopic analysis and this indicated that the microheterogeneity may be due to some posttranslational modifications. It is concluded that rat cardiac Ca2+/Mg2+ ecto-ATPase is an acidic protein having two subunits. Furthermore, the enzyme shows microheterogeneity in its molecular structure. | Kannan S S; Elimban V V; Dakshinamurti K K; Dhalla N S NS | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Molecular and cellular biochemistry | 9655189 | Effects of peroxide on endothelial nitric oxide synthase in coronary arteries. | Reactive oxygen species (ROS) are produced in ischemia and reperfusion. Since endothelial nitric oxide synthase (eNOS) is key to the endothelium-dependent vasodilation, we examined the effects of peroxide on this enzyme. We treated cells cultured from pig coronary artery endothelium with different concentrations of hydrogen peroxide, washed them, solubilized them and measured NOS activity by arginine to citrulline conversion. Hydrogen peroxide inhibited the eNOS activity with an IC50 value of 0.85 +/- 0.39 mM. In another experiment, we perfused arteries with solutions containing 0 or 1 mM hydrogen peroxide, washed them, removed the endothelium using a cotton swab, centrifuged and solubilized the endothelium and monitored its NOS activity. Hydrogen peroxide (1 mM) did not affect the NOS activity significantly (p > 0.05) in this assay. We conclude that the inactivation of eNOS by hydrogen peroxide does not play a major role in the ischemia-reperfusion damage because the peroxide concentrations attained during ischemia-perfusion are much lower than those affecting the eNOS activity. | Shah K A KA; Samson S E SE; Grover A K AK | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Molecular and cellular biochemistry | 9655196 | Insulin-induced Glut4 recruitment in the fatty Zucker rat heart is not associated with changes in Glut4 content in the intracellular membrane. | Impaired cardiac glucose metabolism and glucose transport have been shown in the insulin resistant fatty Zucker rat. The aim of the present study was to examine the translocation of the insulin-sensitive glucose transporter (Glut4) in the heart of the fatty Zucker rat under in vivo conditions. Insulin was injected into both lean (FA/?) and fatty (fa/fa) Zucker rats via the tail vein. The time course of cardiac Glut4 translocation was studied by determining the subcellular distribution of Glut4 using a newly developed ELISA quantitation method. Insulin (10 U/kg) caused a 30% and 37% increase in plasma membrane Glut4 content at 20 min after injection in lean and fatty rats respectively. The plasma membrane Glut4 contents in the basal and insulin-stimulated states were significantly lower in the fatty rat when compared to the lean control. The dose effect of insulin (2.5-10 U/kg) on Glut4 mobilization to the plasma membrane was similar in both phenotypes. The time course of Glut4 mobilization to the plasma membrane (5-30 min), which was similar in both lean and fatty Zucker rats, showed that maximal translocation was reached at 5 min post insulin injection and persisted throughout the remaining 25 min. However, in fatty Zucker rats, Glut4 content in the intracellular membrane remained unchanged at all insulin doses and all time points studied. Collectively, these results show that Glut4 recruitment to the plasma membrane is responsive to insulin in the fatty Zucker rat heart and that the maximal response was similar to that in lean Zucker rats. However, the recruitment of Glut4 to the plasma membrane was not associated with changes in the intracellular membrane Glut4 content. | Li W M WM; Cam M C MC; Poucheret P P; McNeill J H JH | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Molecular and cellular biochemistry | 9655199 | Depletion of endogenous dopamine stores and shift in beta-adrenoceptor subtypes in cardiac tissue following five weeks of chronic denervation. | Surgical ablation of extrinsic cardiac nerve fibers results in a chronically denervated state of the left ventricle of the heart. The present study was performed to elucidate the effect of a period of 5 weeks of chronic denervation on cardiac catecholamine levels in general and dopamine in particular. Moreover, the possible effect on cardiac beta-adrenoceptor subtypes was investigated. Experiments were performed on adult dogs. In addition to adrenaline and noradrenaline the tissue levels of dopamine were found to be severely depressed. A significant shift from beta1- to beta2-adrenoceptor subtype was observed, while the total beta-adrenoceptor density remained unaffected. The present findings indicate that catecholamine synthesis in chronically denervated hearts is impaired upstream of dopamine and that a shift in beta-adrenoceptor subtype occurs already within a relatively short period of five weeks of denervation, and suggest that the lack of endogenous catecholamines influence the relative expression levels of the two subtypes of beta-adrenoceptors present in cardiac tissue. | Van der Vusse G J GJ; Dubelaar M L ML; Coumans W A WA; Steinfath M M; Smith C C CC; Drake-Holland A J AJ; Noble M I MI | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Experimental brain research | 9655231 | Influence of hypoglycemic coma on brain water and osmolality. | To study the effects of pronounced hypoglycemia on brain osmolality and brain edema formation, fasted rats were rendered hypoglycemic by injection of insulin, and subjected to 30 min of hypoglycemic coma. Recovery was accomplished by glucose administration. The change in water content in different brain regions was measured as a change in specific gravity after 30 min of hypoglycemic coma, or 30, 60, and 180 min after glucose administration. Plasma and brain tissue osmolality were measured in separate animals. The results show a significant decrease in specific gravity (increase in water content) in all structures measured (caudoputamen, neocortex, hippocampus, and cerebellum) at the end of the period of coma, as well as after 30 min and 60 min of recovery. At 180 min of recovery, brain water was normalized. The edema affected all structures to the same degree regardless of their vulnerability to hypoglycemic damage. Brain tissue osmolality showed a tendency to decrease with decreasing tissue glucose content. The decrease was significant (P<0.01) at 30 min of isoelectric coma. In the recovery phase, normal brain osmolality was restored within 30 min. Measurements of blood-brain barrier (BBB) permeability after 30 min of hypoglycemic coma showed no extravasation of Evan's blue, though a small but significant increase in the permeability for aminoisobutyric acid (AIB) in caudoputamen and in cerebellum was found. To analyze the importance of tissue acidosis for formation of edema, hypoglycemic animals were made acidotic by increasing the CO2 concentration in inspired air to produce an arterial plasma pH of 6.8-6.9. In these animals the edema was of a similar degree to the normocapnic animals, and the permeability for AIB was normal. We conclude that osmolytic mechanisms are not the primary cause of the selective neuronal vulnerability in hypoglycemic coma. Furthermore, the BBB is largely intact during a hypoglycemic insult. | Gisselsson L L; Smith M L ML; Siesjö B K BK | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Experimental brain research | 9655236 | Calcium metabolism of focal and penumbral tissues in rats subjected to transient middle cerebral artery occlusion. | The present experiments were undertaken to define changes in tissue calcium metabolism in focal and perifocal ("penumbral") tissues following 2 h of transient middle cerebral artery occlusion (MCAO) in rats, induced with an intraluminal filament occlusion technique. The extracellular calcium concentration (e) was measured with ion-selective microelectrodes in neocortical focus and penumbra. For measurement of total tissue calcium content, tissue samples from these areas were collected and analyzed with atomic absorption spectrometry. During MCAO,e in a neocortical focal area fell from a normal value of about 1.2 mM to values around 0.1 mM, suggesting translocation of virtually all extracellular calcium to intracellular fluids. Recirculation was accompanied by re-extrusion of calcium within 5-7 min; however,e never returned to normal but stabilized at about 50% of the control value for the first 6 h, and decreased further after 24 h. In penumbral areas,e showed the expected transient decreases associated with spreading depression-like (or ischemic) depolarization waves. Recirculation was followed by return ofe towards normal values. In the focus, water content increased from about 79% to about 80.4% at the end of the 2-h period of ischemia. After 2 h and 4 h of recirculation, the edema was aggravated (mean values 81.9% and 81.2%, respectively). After 6 h and 24 h, the edema was more pronounced (83.6% and 83.8%, respectively). In the penumbra, no significant edema was observed until 6 h and 24 h of recirculation. The total tissue calcium content in the focus (expressed by unit dry weight) increased at the end of the ischemia period demonstrating calcium translocation from blood to tissue. After 6 h and 24 h, the content increased two- to threefold, compared with control. Changes in the penumbra were qualitatively similar but less pronounced, and a significant increase was not observed until after 6 h of recirculation. The results suggest that 2 h of MCAO leads to a profound perturbation of cell calcium metabolism. In focal areas, cells fail to extrude the calcium that is gradually accumulated during reperfusion and show massive calcium overload after the first 4-6 h of recirculation. Penumbral tissues show a similar increase in calcium concentration after 6 h of recirculation. | Kristián T T; Gidö G G; Kuroda S S; Schütz A A; Siesjö B K BK | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Protein science : a publication of the Protein Society | 9655337 | The three-dimensional structure of a helix-less variant of intestinal fatty acid-binding protein. | Intestinal fatty acid-binding protein. This variant, termed delta17-SG, was remarkably stable, exhibited a high beta-sheet content and was able to bind fatty acids with some features characteristic of the wild-type protein. In the present study, we determined the structure of the delta17-SG/palmitate complex at atomic resolution using triple-resonance 3D NMR methods. Sequence-specific 1H, 13C, and 15N resonance assignments were established at pH 7.2 and 25 degrees C and used to define the consensus 1H/13C chemical shift-derived secondary structure. Subsequently, an iterative protocol was used to identify 2,544 NOE-derived interproton distance restraints and to calculate its tertiary structure using a unique distance geometry/simulated annealing algorithm. In spite of the sizable deletion, the delta17-SG structure exhibits a backbone conformation that is nearly superimposable with the beta-sheet domain of the wild-type protein. The selective deletion of the alpha-helical domain creates a very large opening that connects the interior ligand-binding cavity with exterior solvent. Unlike wild-type I-FABP, fatty acid dissociation from delta17-SG is structurally and kinetically unimpeded, and a protein conformational transition is not required. The delta17-SG variant of I-FABP is the only wild-type or engineered member of the intracellular lipid-binding protein family whose structure lacks alpha-helices. Thus, delta17-SG I-FABP constitutes a unique model system for investigating the role of the helical domain in ligand-protein recognition, protein stability and folding, lipid transfer mechanisms, and cellular function. | Steele R A RA; Emmert D A DA; Kao J J; Hodsdon M E ME; Frieden C C; Cistola D P DP | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Pediatric nephrology (Berlin, Germany) | 9655363 | Recombinant human growth hormone treatment of children on hemodialysis. French Society of Pediatric Nephrology. | Forty-two children, aged 2-21.5 years on hemodialysis with a height below -2.0 standard deviation score and was always over 2.5 cm/year. This velocity allowed a catch-up growth of +0.5 height SDS. Neither weight nor the body mass index varied compared with the pretreatment year. No change was observed in urea, creatinine, or glucose tolerance. The mean increment in bone age was 0.9 years. The mean growth velocity decreased over subsequent years, but remained higher than the prestudy velocity. A significant negative correlation was observed during the 1st year between the increase in growth velocity and the prestudy velocity, with the least gain in patients who had the best spontaneous velocity. Pubertal status had no influence on response to rhGH. No significant side effects were observed during the 103 treatment-years. Five patients developed secondary hyperparathyroidism and 1 suffered from acute pancreatitis, but the relationship with rhGH therapy remains uncertain. rhGH therapy appears indicated for children on hemodialysis, even though the potential benefits appear somewhat lower for those with a spontaneous growth velocity over 6 cm/year. | Bérard E E; Crosnier H H; Six-Beneton A A; Chevallier T T; Cochat P P; Broyer M M | 1998-05-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Pediatric nephrology (Berlin, Germany) | 9655365 | Bartter and related syndromes: the puzzle is almost solved. | It is now evident that the term Bartter syndrome does not represent a unique entity but encompasses a variety of disorders of renal electrolyte transport. Application of molecular biology techniques has permitted a better understanding of these "Bartter-like syndromes," which at present can be divided into three different genetic and clinical entities. Neonatal Bartter syndrome is observed in newborn infants and characterized by polyhydramnios, premature delivery, life-threatening episodes of fever and dehydration during the early weeks of life, growth retardation, hypercalciuria, and early-onset nephrocalcinosis. Two molecular defects have been identified: either at the gene encoding the renal bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) or the gene encoding an ATP-sensitive inwardly rectifying K channel (ROMK). "Classic" Bartter syndrome is mostly observed during infancy and childhood and is characterized clinically by polyuria and growth retardation. Nephrocalcinosis is not present. Very recently, either deletions or mutations at the gene encoding a renal chloride channel (ClC-Kb) have been identified. Gitelman syndrome is observed in older children and adults presenting with intermittent episodes of muscle weakness and tetany, hypokalemia, and hypomagnesemia. Mutations at the gene encoding the thiazide-sensitive Na-Cl cotransporter have been identified in the majority of patients studied. Obviously the validity of this classification must be confirmed in the near future when all mutations have been described and genotypic-phenotypic correlations are better defined. | Rodríguez-Soriano J J | 1998-05-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |
PUBMED | Lipids | 9655371 | The metabolism and n-6/n-3 ratio of essential fatty acids in rats: effect of dietary arachidonic acid and a mixture of sesame lignans (sesamin and episesamin). | In this study, we examined the effect of dietary arachidonic acid (AA) and sesame lignans on the content and n-6/n-3 ratio of polyunsaturated fatty acid (PUFA) in rat liver and the concentrations of triglyceride (TG) and ketone bodies in serum. For 4 wk, rats were fed two types of dietary oils: (i) the control oil diet groups (CO and COS): soybean oil/perilla oil = 5:1, and (ii) the AA-rich oil group (AO and AOS): AA ethyl esters/palm oil/perilla oil = 2:2:1, with (COS and AOS) or without (CO and AO) 0.5% (w/w) of sesame lignans. Dietary AA and sesame lignans significantly affected hepatic PUFA metabolism. AA content and n-6/n-3 ratio in the liver were significantly increased in the AO group, despite the dietary total of n-6 PUFA being the same in all groups, while AOS diet reduced AA content and n-6/n-3 ratio to a level similar to the CO and COS groups. These results suggest that (i) dietary AA considerably affects the hepatic profile and n-6/n-3 ratio of PUFA, and (ii) dietary sesame lignans reduce AA content and n-6/n-3 ratio in the liver. In the AO group, the concentration of acetoacetate was significantly increased, but the ratio of beta-hydroxybutyrate/acetoacetate was decreased. On the other hand, the AO diet increased the concentration of TG in serum by almost twofold as compared to other groups. However, the AOS diet significantly reduced serum TG level as compared to the AO group. In addition, the AOS diet significantly increased the acetoacetate level, but reduced the beta-hydroxybutyrate/acetoacetate ratio. These results suggest that dietary sesame lignans promote ketogenesis and reduce PUFA esterification into TG. This study resulted in two findings: (i) sesame lignans inhibited extreme changes of the n-6/n-3 ratio by reducing hepatic PUFA content, and (ii) the reduction of hepatic PUFA content may have occurred because of the effects of sesame lignans on PUFA degradation (oxidation) and esterification. | Umeda-Sawada R R; Ogawa M M; Igarashi O O | 1998-06-02 | pubmed24n0320.xml | 9 | Metabolism & Diabetes | 1995-1999 |