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Moderate concentrations of ethanol reduce the velocity of uptake of three representative Na+-symport systems (D-glucose, L-alanine, L-ascorbate), whether electrogenic (the first two) or electroneutral (L-ascorbate). This 'inhibition' is observed only if these transport systems are tested in the presence of an initial Na+ gradient (out greater than in); no inhibition is found in tracer-equilibrium exchange measurements. A representative Na+-independent system (D-fructose) is not inhibited by ethanol. 'Passive diffusion' (measured as uptake of L-glucose) is increased somewhat by alcohol. All these observations can be rationalized [as suggested by Tillotson et al. (1981) Arch. Biochem. Biophys. 207, 360-370] by an effect of ethanol on passive diffusion, which leads to a faster collapse of the Na+ gradient, with the resulting reduction of the uptake velocities of Na+-dependent transport systems when tested with the added driving force of an Na+ out----in gradient.
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PMID:Ethanol selectively affects Na+-gradient dependent intestinal transport systems. 394 Aug 86

Pressure-diameter relationships of segments of human finger arteries, aged 57-85 years, were measured in vitro. The arteries, obtained at autopsy within 48 h after death, were stored in glucose-free Tyrode at 4 degrees C. Experiments began within 40 h after autopsy. The diameter responses to various transmural pressure changes, with and without the addition of noradrenaline to the Tyrode solution in the specimen chamber, were compared with the responses of freshly excised rat tail arteries. In general, pressure-diameter relations of human finger artery segments were similar to those of rat tail artery segments, with a steep slope in the collapse region near zero pressure. Also, spontaneous rhythmic contractions and myogenic activity induced by high transmural pressures were similar to those observed in the fresh rat tail arteries. Human finger arteries, however, could contract to complete closure both spontaneously and after addition of noradrenaline, while rat tail arteries did not. The diameter changes of the arterial segments during forced 1 Hz oscillations of 20-50 mm Hg (2.7-6.7 kPa) amplitude superimposed on a mean transmural pressure were substantially smaller than those during quasi-steady inflation-deflation ramps over the same pressure range, indicating the presence of a strong viscous wall component.
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PMID:Pressure-diameter relationships of segments of human finger arteries. 395 18

Streptococcus faecalis obtains metabolic energy chiefly from the conversion of glucose to lactic acid; the present experiments deal with the mechanism of lactic acid translocation across the cytoplasmic membrane. Efflux of [(14)C]lactate from preloaded cells was accelerated by raising the external pH, and also by the ionophores nigericin and valinomycin. These results suggest that lactate leaves the cell by an electroneutral process, presumably as lactic acid. Further evidence was obtained by studying the entry of [(14)C]lactate into nonmetabolizing cells. It appears that the membrane is essentially impermeable to the lactate anion, but allows passage of lactic acid. The most persuasive evidence is that, upon establishment of a pH gradient such that the cytoplasm was alkaline, l-[(14)C]lactate accumulated in the cells against the concentration gradient. Accumulation was transient, and dissipated in parallel with the collapse of the pH gradient. The concentration gradient attained at the peak was a function of the pH difference. Ionophores which are known to collapse a pH gradient, such as nigericin and valinomycin, abolished accumulation of l-lactate. We infer that lactic acid translocation, whether into the cells or outward, is an electroneutral process and for that reason the distribution of lactic acid across the membrane is a function of the pH of cytoplasm and medium. The specificity of translocation and its kinetic parameters suggest that it is mediated by a carrier of low specificity.
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PMID:Lactic acid translocation: terminal step in glycolysis by Streptococcus faecalis. 420 90

Light and electron microscope studies were conducted on the nature of the degenerative changes in amputated nerve fibers of cultured rat sensory ganglia and on the effects of media with differing calcium concentrations upon these changes. With glucose-enriched Eagle's media (MEM) containing 1.6 mM calcium, the amputated myelinated and unmyelinated axons undergo a progressive granular disintegration of their axoplasm with collapse and fragmentation of myelin sheaths between 6 and 24 h after transection. With MEM containing only 25-50 microM calcium, the granular axoplasmic degeneration does not occur in transected fibers and they retain their longitudinal continuity and segmental myelin ensheathment for at least 48 h. Addition of 6 mM EGTA to MEM (reducing the estimated Ca(++) below 0.3 microM) results in the structural preservation of both microtubules and neurofilaments within transected axons. A transient focal swelling of amputated axons occurs, however, in cultures with normal and reduced calcium. These observations suggest that an alteration in the permeability of the axolemma is a crucial initiating event leading to axonal degenerative changes distal to nerve transection. The loss of microtubules and neurofilaments and the associated granular alterations of the axoplasm in transected fibers appears to result from the influx of calcium into the axoplasm.
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PMID:Effects of calcium ion concentration on the degeneration of amputated axons in tissue culture. 480 10

Allopurinol, a xanthine-oxidase inhibitor and potential cell-stabilizing compound, was studied as a possible therapeutic agent in canine endotoxin shock. Circulatory collapse was produced in anesthetized mongrel dogs by IV administration of an LD75 dose of endotoxin. Treatment, with dextran alone, or with dextran and an IV bolus of allopurinol, was initiated 15 minutes after the onset of shock. The administration of 25, 50, or 100 mg/kg of IV allopurinol, accompanied by adequate volume replenishment, produced a significant reduction in the total peripheral vascular resistance and significant increases in cardiac output, blood glucose concentration, and arterial lactate concentration. Survival was not enhanced by allopurinol therapy, and allopurinol administration in normal dogs did not affect the vascular tone or the arterial lactic acid concentration. There was a transient hyperglycemic response and a decrease in the cardiac index in normal animals. The infusion of a postassium-insulin solution, in association with 100 mg/kg of allopurinol, did not significantly improve survival. In summary, although a number of potentially beneficial hemodynamic and metabolic effects were observed following allopurinol administration, survival in canine endotoxin shock was not enhanced.
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PMID:Experiences with allopurinal in canine endotoxin shock. 617 28

Glucose-insulin-potassium (GIK) has beneficial effects during endotoxin shock, possibly through improvement of myocardial function, but the mechanism is not clear. We have studied the effects of GIK on left ventricular function, coronary flow, and oxygen consumption in controls and dogs treated with endotoxin (1.5 mg/kg-1). The animals were anaesthetized (etomidate 4 mg/kg-1/hr-1) and ventilated (N2O:O2 = 2:1). We have measured left ventricular pressure, left ventricular end-diastolic pressure (LVEDP) and LVdP/dt, systemic blood pressure, cardiac output (CO; thermodilution), coronary blood flow (CBF; radioactive microspheres), and oxygen content and lactate in arterial and coronary sinus blood. Endotoxin caused a rapid fall of CO and blood pressure with a temporary recovery followed by gradual circulatory collapse. GIK infusion (50% glucose, 2 g/kg-1 bw, 8 mmol KCl, and 3 U insulin/kg-1 bw) increased CO (56%), CBF (61%), blood pressure (21%), LVEDP (77%), and LVdP/dt (28%), and systemic vascular resistance decreased (23%). Stroke work (80%) and tension time index (42%) decreased during shock, but GIK temporarily improved these variables. The ratio of stroke work, respectively tension time index to oxygen consumption, suggests that myocardial efficiency decreased during shock and improved after GIK. Endotoxin decreased the ratio of endo- to epicardial flow. GIK did not change this ratio. However, for the same endo to epi ratio, increased CBF implies increased flow to endocardium.
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PMID:Effects of glucose-insulin-potassium (GIK) on myocardial blood flow and metabolism in canine endotoxin shock. 638 52

When exposed to hypoxia, intact mice, with elevated blood ketones, live longer than mice with normal blood ketones. To evaluate a possible mechanism responsible for this phenomenon a rat brain slice preparation was used to determine if brain tissue would utilize glucose or ketones preferentially during exposure to reduced oxygen. Reducing available oxygen in the incubation medium from 95%, in steps, to 5% produced the expected gradual reduction in the carbon dioxide formation from glucose. In contrast, reducing the oxygen level to 40 and 20% resulted in a statistically significant stimulation of the production of carbon dioxide from the ketone beta-hydroxybutyrate. At very low oxygen levels carbon dioxide production from either substrate was reduced. These results are consistent with the hypothesis that ketones can be used in addition to glucose as a substrate for brain energy production even during reduced oxygen availability. If the increase in carbon dioxide production from ketones can be equated with an increase in energy production from this supplemental substrate then ketones may be therapeutically useful in avoiding the collapse of brain function during moderate hypoxia.
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PMID:Hypoxia induced preferential ketone utilization by rat brain slices. 642 88

Patients hospitalized in critical care unit for acute renal failure (ARF) in a multiorgan failure syndrome have often a poor intra-dialysis tolerance. Change from Ac to Bi for dialysate buffering has been advocated to improve this dialytic tolerance. In a retrospective study, 70 patients who received Bi hemodialysis are compared with 106 patients who received Ac hemodialysis. If the mortality is not different between these two groups, intra-dialysis tolerance is significantly better (p less than 0.001) in the Bi group according to the mean intra-dialysis systolic blood pressure decrease, the collapse occurrence and the mean vascular volume infusion. Ultrafiltration rate is higher and reach more often the desired values. On a biochemical point of view, hemodialysis efficacy is the same in the two groups according to urea and creatinin clearance, but end dialysis Bi plasma concentrations are higher and nearer of the normal range in the Bi group even though predialysis Bi plasma concentrations were similar. The only side effect observed with Bi dialysis was a hypoglycemic episode without clinical consequence, due to the lack of glucose in the bicarbonate dialysate. Nevertheless, in patients under controlled ventilation, a end dialysis alkalosis can occur if a hyperventilation is imposed. Change from Ac to Bi in dialysate buffering improves the intra-dialysis tolerance of patients with ARF in a multiorgan failure syndrome. This kind of hemodialysis is now used routinely in our critical care unit.
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PMID:[Acute kidney failure in a resuscitation milieu: improvement of dialysis tolerance using bicarbonates in the dialysate]. 666 39

The efficiency of insulin (decrease of the blood glucose per unit of insulin administered) was assessed in 610 cases of diabetic ketoacidosis (316 females, 274 males, aged 3 to 72 years) in terms of the degree of plasma acidemia. The 610 cases were grouped into 4 ketoacidosis stages, defined according to pH values as incipient, pH > 7.35 (77 cases); moderate, pH 7.31-7.35 (163 cases); advanced, 7.21-7.30 (160 cases); severe, pH < 7.20 (210 cases). The mean [H+]-ion concentration recorded on admission in the 4 stages of ketoacidosis was 41 nEq/1, 46 nEq/1, 53 nEq/1, and 91 nEq/1, respectively. The efficiency of insulin for the first 2 hours of treatment (interval during which acidemia was only partly corrected) was comparable in the four ketoacidosis stages, i.e. 31.1 mg/l, 32.9 mg/l, 29.5 mg/l and, respectively 28.9 mg/l per unit of insulin injected as a bolus. The somewhat lower efficiency of insulin in the advanced and severe cases of ketoacidosis appears to be due to vascular collapse encountered in 38 cases (6 advanced ketoacidosis and 32 severe ketoacidosis), since in these patients the fall in blood glucose per unit insulin was only 15.8 mg/l.
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PMID:Relationship between the concentration of H+-ions and the efficiency of insulin in the treatment of diabetic ketoacidosis. 677 93

1. In the presence of a high concentration of p-nitrophenyl beta-D-glucopyranoside (donor) the rates of production of p-nitrophenol and a transglucosylation product (1-glyceryl beta-D-glucopyranoside) increased, whereas the rate of production of glucose decreased with increasing concentration of glycerol in reactions catalysed by the high-molecular-weight beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) obtained from culture filtrates of Botryodiplodia theobromae Pat. 2. When [donor] greater than Km the rate of production of p-nitrophenol was higher in the presence of glycerol than in its absence, whereas when [donor] less than Km the rate of production of p-nitrophenol was lower in the presence of glycerol than in its absence. 3. Glycerol increased both the Michaelis constant (Km) and maximum velocity (Vmax.), whereas dioxan increased Km but decreased Vmax. 4. Up to 1 mM-AgNO3 had no effect on enzyme activity. 5. A 2H-solvent-isotope-effect [Vmax. (H2O)/V max. (2H2O)] value of 1.40 +/- 0.05 was found at pH (or p2H) 5.8 6. alpha-2H-kinetic isotope-effect (kappa H/kappa 2H) values of 1.03 +/- 0.01 and 1.05 +/- 0.01 were found in the absence and presence of glycerol respectively. 7. Although maltose was a non-competitive inhibitor of beta-glucosidase activity, the ratio of velocity in the presence of glycerol to that in its absence increased, after an initial decline, with increasing concentration of maltose. 8. These results are discussed in terms of a mechanism involving a solvent-separated glucosyl cation-carboxylate ion-pair, which has greater affinity for alcoholic glucosyl acceptors, and an intimate ion-pair, which has greater affinity for water as a glucosyl acceptor and which could collapse reversibly and rapidly into a preponderance of an unreactive covalent glucosyl-enzyme.
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PMID:The beta-glucosidase from Botryodiplodia theobromae. Mechanism of enzyme action. 680 33


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