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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the feasibility of monitoring local skeletal muscle blood flow in the rat by including ethanol in the perfusion medium passing through a microdialysis probe placed in muscle tissue. Ethanol at 5, 55, or 1100 mM did not directly influence local muscle metabolism, as measured by dialysate glucose, lactate, and glycerol concentrations. The clearance of ethanol from the perfusion medium can be described by the outflow/inflow ratio ([ethanol]collected dialysate/[ethanol]infused perfusion medium), which was found to be similar (between 0.36 and 0.38) at all ethanol perfusion concentrations studied. With probes inserted in a flow-chamber, this ratio changed in a flow-dependent way in the external flow range of 5-20 microliters min-1. The ethanol outflow/inflow ratio in vivo was significantly (P less than 0.001) increased (to a maximum of 127 +/- 2.8% and 144 +/- 7.4% of the baseline, mean +/- SEM) when blood flow was reduced by either leg constriction or local vasopressin administration, and significantly (P less than 0.001) reduced (to 62 +/- 6.4% and 43 +/- 4.4% of baseline) with increases in blood flow during external heating or local 2-chloroadenosine administration, respectively. Dialysate glucose concentrations correlated negatively with the ethanol outflow/inflow ratio (P less than 0.01) and consequently decreased (to 46 +/- 7.6% and 56 +/- 5.6% of baseline) with constriction and vasopressin administration and increased (to 169 +/- 32.5% and 262 +/- 16.7% of baseline) following heating and 2-chloroadenosine administration. Dialysate lactate concentrations were significantly increased (approximately 2-fold, P less than 0.001) during all perturbations of blood flow. In conclusion, this technique makes it possible to monitor changes in skeletal muscle blood flow; however, methods of quantification remain to be established. The fact that blood flow changes were found to significantly affect interstitial glucose and lactate concentrations as revealed by microdialysis indicates that this information is critical in microdialysis experiments.
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PMID:The ethanol technique of monitoring local blood flow changes in rat skeletal muscle: implications for microdialysis. 144 30

Isolated rat hearts perfused with hyperosmotic Krebs-Henseleit buffer containing 60 mmol/L NaCl lose 10% of their tissue water. Perfusion of the rat hearts with Krebs-Henseleit buffer containing polyethylene glycol 8000 caused a concentration-dependent reduction in tissue water. In a study of the effect of different cryoprotectants on cardiac preservation, isolated rat hearts were flushed with a cardioplegic solution (CP-14), or CP-14 with either 50 mmol/L glycerol (CP-15), or 5% polyethylene glycol (CP-16) and frozen at -1.4 degrees C for 5 hours. Thawed hearts were reperfused in working mode to assess function. There was no recovery in CP-14 hearts. Hearts treated with CP-15 recovered 39.3% +/- 2.9% (mean +/- SEM) of control cardiac output. CP-16 boosted the recovery of cardiac output to 54.4% +/- 5.7% (p less than 0.05 vs CP-15). Glycerol significantly reduced tissue ice content; PEG further decreased the ice content to 31.7% +/- 0.6%, which was distinctively lower than that in CP-14 (44.7% +/- 1.1%) and in CP-15 hearts (34.6% +/- 1.1%). Tissue water content of CP-14 and CP-15 hearts was similar (3.83 and 3.87 gm H2O/gm dry weight). Polyethylene glycol reduced the tissue water content to 3.24 +/- 0.04 gm H2O/gm dry (p less than 0.01 vs CP-14 and CP-15 by ANOVA). Thus both glycerol and polyethylene glycol offered cryoprotection to the heart explant by reducing tissue ice formation. Polyethylene glycol was superior to glycerol by dehydrating myocardial tissue and further minimizing freezing damage.
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PMID:Freezing preservation of the mammalian heart explant. III. Tissue dehydration and cryoprotection by polyethylene glycol. 149 24

We measured circulating levels of C-peptide, pancreatic glucagon, cortisol, growth hormone and metabolites (glucose, non-esterified fatty acids, glycerol and 3-hydroxybutyrate) in fibro-calculous-pancreatic diabetic (FCPD, n = 28), insulin-dependent diabetic (IDDM, n = 28) and non-diabetic control (n = 27) subjects during an oral glucose tolerance test. There was no difference in the two diabetic groups in age (FCPD 24 +/- 2, IDDM 21 +/- 2 years, mean +/- SEM), BMI (FCPD 16.0 +/- 0.6, IDDM 15.7 +/- 0.4 kg/m2), triceps skinfold thickness (FCPD 8 +/- 1, IDDM 7 +/- 1 mm), glycaemic status (fasting plasma glucose, FCPD 12.5 +/- 1.5, IDDM 14.5 +/- 1.2 mmol/l), fasting plasma C-peptide (FCPD 0.13 +/- 0.03, IDDM 0.08 +/- 0.01 nmol/l), peak plasma C-peptide during OGTT (FCPD 0.36 +/- 0.10, IDDM 0.08 +/- 0.03 nmol/l) and fasting plasma glucagon (FCPD 35 +/- 4, IDDM 37 +/- 4 ng/l). FCPD patients, however, showed lower circulating concentrations of non-esterified fatty acids (0.73 +/- 0.11 mmol/l), glycerol (0.11 +/- 0.02 mmol/l) and 3-hydroxybutyrate (0.15 +/- 0.03 mmol/l) compared to IDDM patients (1.13 +/- 0.14, 0.25 +/- 0.05 and 0.29 +/- 0.08 mmol/l, respectively). This could be due to enhanced sensitivity of adipose tissue lipolysis to the suppressive action of circulating insulin and possibly also to insensitivity of hepatic ketogenesis to glucagon. Our results also demonstrate preservation of alpha-cell function in FCPD patients when beta-cell function is severely diminished, suggesting a more selective beta-cell dysfunction or destruction than hitherto believed.
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PMID:The ketosis-resistance in fibro-calculous-pancreatic-diabetes. 1. Clinical observations and endocrine-metabolic measurements during oral glucose tolerance test. 156 31

The contribution of insulin (3.6 pmol.kg body mass-1.min-1) to adrenaline-induced (0.164 nmol.kg fat free mass-1.min-1) thermogenesis was studied in ten postabsorptive healthy volunteers using two sequential protocols. Variables considered were oxygen consumption as well as carbon dioxide production, heart rate, blood pressure, plasma concentrations of glucose, insulin, glycerol, free fatty acids, beta-HO-butyrate and lactate. Adrenaline increased plasma concentrations of glucose, glycerol, free fatty acids, and beta-HO-butyrate, and heart rate and metabolic rate during normo-insulinaemia [61.3 (SEM 6.6) pmol.l-1]. Similar effects were observed during hyperinsulinaemia [167.9 (SEM 18.7) pmol.l-1], but the effect of adrenaline on oxygen consumption was reduced. On average, metabolic rate increased by 12.9% during normo-insulinaemia and by 8.9% during hyperinsulinaemia. We concluded that relative hyperinsulinaemia resulted in decreased adrenaline-induced thermogenesis and therefore increased whole body anabolism.
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PMID:Thermogenic effect of adrenaline: interaction with insulin. 176 54

Tumor-caused weight loss is frequently associated with a high rate of lipolysis and fat oxidation. In order to differentiate the effect of weight-loss from the tumour-dependent regulation of fat metabolism, we studied weight-stable and well nourished patients (ideal body weight 109 +/- 4% (+/- SEM), body mass index 25.1 +/- 0.9 kg/m2). Parameters of lipolysis (glycerol-, fatty acid concentrations) and the calorimetric determined fat oxidation rate of five male tumor patients were examined before and during an euglycaemic insulinclamp (0.2 mU insulin/kg/min). Concomitant with a high rate of lipolysis (glycerol concentration 112 +/- 20 mumol/l, free fatty acid concentration 0.72 +/- 0.13 mmol/l) and fat oxidation (60% of energy expenditure) there was a low normal insulin level (5.9 +/- 0.5 mU/l). Insulin reduced lipolysis and fat oxidation and stimulated glucose oxidation. Weight-stable tumor patients have a high basal rate of lipolysis and fat oxidation; yet the insulin dependent regulation of the fat metabolism is intact, as we have already shown for weight-losing cancer patients.
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PMID:[Lipolysis and lipid oxidation of weight stable patients with malignant tumors of the digestive system]. 185 3

Upon engagement of chemoattractant receptors, neutrophils generate inositol trisphosphate and diacylglycerol (DG) by means of a phosphatidylinositol-specific phospholipase C (PI-PLC) which is regulated by a GTP-binding protein(s). We have previously reported (Reibman, J., H. M. Korchak, L. B. Vosshall, K. A. Haines, A. M. Rich, and G. Weissmann. 1988. J. Biol. Chem. 263:6322-6328) a biphasic rise in DG after exposure of neutrophils to the chemoattractant FMLP: a rapid (less than or equal to 15 s) phase ("triggering") and a slow (greater than or equal to 30 s) phase ("activation"). These derive from distinct intracellular lipid pools. To study the source of rapid and slow DG, we have used a unique probe, protein I, a porin that is the major outer membrane protein of Neisseria gonorrhoeae. Treatment of neutrophils with protein I inhibits exocytosis and homotypic cell adhesion provoked by FMLP without inhibiting assembly of the NADPH oxidase responsible for O2-. generation. DG turnover in PMN labeled with [3H]arachidonate and [14C]glycerol was profoundly altered by protein I. Whereas the rapid peak of DG was only modestly diminished (FMLP vs. FMLP plus protein I = DG labeled with [3H]arachidonic acid (3H-a.a.-DG): 142 +/- 14% SEM vs. 125 +/- 22%; DG labeled with the glycerol backbone with [14C]glycerol (D-14C-G): 125 +/- 10% SEM vs. 107 +/- 8.5% SEM), the slow rise in both 3H-a.a.-DG and D-14C-G was essentially abolished. Moreover, treatment of neutrophils with 4-4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), which, like protein I, inhibits exocytosis without affecting O2-. generation also inhibited slow DG. However, protein phosphorylation and dephosphorylation (47phox, 66phox) were unaffected in the absence of slow DG. To determine the source of the slow DG, we have analyzed radiolabeled phospholipid (PL) turnover after FMLP +/- protein I (P.I.). Treatment of PMN with FMLP (0.1 microM) resulted in breakdown of phosphatidylcholine (PC), beginning at 30 s, and reaching a nadir at 60 s (3H-PC = 59 +/- 10.2% SEM of resting, 14C-PC = 57 +/- 6.4%). Protein I (0.25 microM) significantly inhibited PC turnover after FMLP ([3H]PC = 95 +/- 5.6% and [14C]PC = 86 +/- 8.4% of resting at 60 s), but failed to alter the metabolism of 3H- or 14C-phosphatidylinositol after FMLP (91 +/- 19.6 and 88 +/- 16.5% vs. 92 +/- 9.2 and 91 +/- 16% at 60 s).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of protein I of Neisseria gonorrhoeae on neutrophil activation: generation of diacylglycerol from phosphatidylcholine via a specific phospholipase C is associated with exocytosis. 190 86

In a previous study we have shown a role for reactive oxygen metabolites in glycerol-induced acute renal failure, a well-established model for myoglobinuric acute renal failure. In the present study we examined the role of glutathione in this model of acute renal failure. Administration of 50% (vol/vol) glycerol at a dose of 10 ml/kg of body weight to rats intramuscularly resulted in significant renal failure associated with depletion of total kidney glutathione (GSH) from 2.6 +/- 0.1 mumol/g (mean +/- SEM control level) to 1.7 +/- 0.1 mumol/g after 6 hr (P less than 0.001). If GSH were important in glycerol-induced acute renal failure, one would anticipate that exogenously administered GSH should afford protection, while injury should be potentiated if endogenous GSH is depleted. We examined the effect of i.p. administration of L-buthionine-(S,R)-sulfoximine (BSO) at 2 mmol/kg (which results in depletion of kidney GSH) and the effect of increasing renal GSH by i.v. administration of reduced GSH (2 mmol/kg every 3 hr) on kidney function in glycerol-treated rats. Glycerol-injected rats treated with BSO showed significantly worse renal failure than did rats given glycerol alone, while administration of GSH resulted in significant amelioration of glycerol-induced acute renal failure [glycerol treatment alone, blood urea nitrogen (BUN) = 96 +/- 10 and creatinine = 2.5 +/- 0.4 mg/dl; BSO + glycerol treatment, BUN = 123 +/- 7 and creatinine = 3.5 +/- 0.1 mg/dl (n = 9, P less than 0.05); GSH + glycerol treatment, BUN = 78 +/- 10 and creatinine = 1.25 +/- 0.2 mg/dl (n = 8, P less than 0.05)]. In separate experiments 1,3-bis(chloroethyl)-1-nitrosourea (BCNU) [which interferes with the enzyme GSH reductase and prevents recycling of oxidized GSH (GSSG) into GSH] resulted in worsening of glycerol-induced acute renal failure similar to that produced by BSO. These functional differences between GSH-depleted and GSH-repleted rats were further substantiated by significant histological differences in tubular injury. Taken together, these results provide evidence for an important role of GSH in glycerol-induced acute renal failure.
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PMID:Role of glutathione in an animal model of myoglobinuric acute renal failure. 194 9

The present study adapted the overwintering strategy employed by freeze-tolerant amphibians and reptiles to freeze-preserve the isolated rat heart. The heart was flushed with a cardioplegic solution and supercooled to -1.2 and -3 degrees C. Then freezing was induced by inoculation of ice crystal. The viability of the heart explant was assessed after reanimation by the isolated working heart perfusion. There was no recovery of function in hearts flushed with solution containing 0.28 mM CaCl2. Lowering the concentration of CaCl2 to 0.15 mM, however, rendered good functional return. Furthermore, inclusion of 50 mM glycerol in the flush solution dramatically improved functional preservation. Under the best conditions defined here, the recoveries of aortic flow, coronary flow, cardiac output, systolic pressure, and work in hearts stored at -1.2 degrees C for 3 h were 72.8 +/- 6.8, 87.2 +/- 4.2, 77.6 +/- 5.4, 83.4 +/- 2.8, and 66.6 +/- 5.9% (mean +/- SEM, n = 8) of the unstored control levels, respectively. The myocardial ice content was 18.6 +/- 5.4% (n = 5) of tissue water. Prolonging the storage time to 5 h increased the ice content to 45.3 +/- 8.1% and reduced the recovery of cardiac output to 23 +/- 11% of the control value (mean +/- SEM, n = 5). Hearts frozen at -3 degrees C for 1.5 h showed 29.4 +/- 8.7% (n = 3) of control cardiac output during reperfusion. This novel approach may provide an opportunity to advance our knowledge about freezing preservation of not only the heart but other solid organs as well.
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PMID:Freezing preservation of adult mammalian heart at high subzero temperatures. 207 Jun 19

The authors describe the diurnal profile of plasma metformin concentrations in a group of 6 Type 2 (noninsulin-dependent) diabetic patients studied at two different daily metformin doses (500 mg and 850 mg b.d.) and report data on the relationships between plasma metformin and metabolic effects over a 14 h period. In addition, the effect of circulating metformin on insulin binding to isolated monocytes has been evaluated. At the two different daily doses fasting plasma metformin concentrations were similar (3.23 +/- 0.35 mumol/l and 3.86 +/- 0.72 mumol/l, mean values +/- SEM, at low and high dose respectively). Drug peak values and averaged concentrations (4.66 +/- 0.39 mumol/l vs 6.35 +/- 0.69 mumol/l) were significantly higher when more drug was administered. Mean plasma glucose was lower when 1,700 mg/day instead of 1,000 mg/day of metformin was given (7.3 +/- 0.4 mmol/l vs 9.1 +/- 0.9 mmol/l, p less than 0.05). After dosing, at higher plasma metformin concentrations corresponded lower plasma glucose values. The averaged blood lactate levels resulted 1.46 +/- 0.4 mmol/l (p less than 0.05 vs matched diet treated diabetic patients) at the higher drug dose. A significant positive correlation emerged between mean plasma metformin concentrations and mean blood lactate levels (r: 0.76, p less than 0.02). Alanine, glycerol and B-OH-butyrate levels were similar at the two metformin daily doses, and were not correlated to plasma metformin. The binding of insulin to isolated human monocytes was similar in metformin-treated diabetic patients (4.48 +/- 0.45) as in healthy volunteers (4.62 +/- 0.34); insulin binding was correlated (p less than 0.05) with plasma metformin levels.
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PMID:Diurnal pattern of plasma metformin concentrations and its relation to metabolic effects in type 2 (non-insulin-dependent) diabetic patients. 208 78

1. The effects of increasing glucose intake on nitrogen balance, energy expenditure and fuel utilization were measured in 12 malnourished adult patients receiving parenteral nutrition with constant, very high nitrogen intake (500 mg of N/kg), high (105 kJ/kg) or low (30 kJ/kg) glucose intake and constant fat intake (7 kJ/kg). Each patient received each diet for 8-day periods in random order. 2. Energy balance and nitrogen balance were determined daily. Blood samples, taken at admission, during 5% (w/v) dextrose (D-glucose) infusion and at the end of days 7 and 8 of each diet, were analysed for urea, glucose, lactate, triacylglycerols, fatty acids, glycerol, 3-hydroxybutyrate, insulin and glucagon. 3. The effect of increasing glucose intake was to increase nitrogen balance by 0.60 +/- 0.25 (SEM) mg/kJ. At zero energy balance, nitrogen balance was 48 mg day-1 kg-1. This confirms findings of previous studies: that the effects of glucose on nitrogen balance are greater at high than at low nitrogen intakes, and that, in malnourished patients, unlike in normal adults, markedly positive nitrogen balance can be achieved at zero or negative energy balances. 4. Changes in nitrogen balance were due almost entirely to changes in urea excretion. 5. The high nitrogen intake markedly increased plasma insulin and glucagon concentrations and reduced glycerol, fatty acid and 3-hydroxybutyrate concentrations, independent of any glucose effect. Glucagon concentrations were significantly decreased by added glucose intake, an effect not previously seen at low nitrogen intakes. At this high nitrogen intake, the effects of added glucose appear to be mediated by both insulin and glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of glucose on nitrogen balance during high nitrogen intake in malnourished patients. 215 47


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