Effect of ruminal glucose infusion on dry matter intake, urinary nitrogen composition, and serum metabolite and hormone profiles in Ewes. (9/290)

Twelve 18-mo-old Debouillet ewes were used to determine the effect of ruminal glucose infusion on DMI, on urinary ammonium (NH4+) and urea N (UUN) concentrations, and on serum metabolite and hormone profiles. Ewes were limit-fed a 90% concentrate diet for 30 d, stratified by BW into three groups (average BW = 82.6+/-1.1 kg), and assigned randomly to receive 0, 5, or 10 g of glucose/kg of BW via esophageal intubation. Urine was collected hourly for 12 h and blood (jugular venipuncture) at 30-min intervals for 12 h. After 12 h, ewes were housed individually, allowed free access to the diet, and DMI was recorded for 5 d. Venous blood pH averaged 7.49, 7.48, and 7.48 at 0 h and decreased (linear [L], P < .01) at 12 h (7.41, 7.36, and 7.26) with increasing glucose. Serum glucose increased (L, P = .06) at 3 and 6 h. Serum L(+)-lactate increased (L, P = .08) at 3, 6, and 9 h, whereas serum D(-)-lactate increased linearly (P = .09) at 6 and 9 h and quadratically (P < .10) at 12 h. After the glucose challenge, DMI decreased (L, P < .05). Urinary pH and NH4+ were not influenced by glucose infusion; however, UUN increased at 3 (quadratic [Q], P < .05), 4, 5, 6 (L, P = .03), and 7 h (Q, P < .05) and decreased at 11 and 12 h (L, P = .09). As glucose infusion increased, serum creatinine increased at 9 (L, P < .01) and 12 h (Q, P = .02). Generally, serum Na and P increased (P = .09), whereas K decreased (P < .05), with glucose infusion. Lactate dehydrogenase activity increased with glucose infusion (Q, P < .10) at 3, 6, 9, and 12 h. Increasing glucose infusion increased serum globulin (Q, P = .06), albumin, and total protein (L, P = .08). Serum prolactin and vasopressin were not influenced (P = .22) by glucose infusion. Serum insulin and aldosterone increased quadratically (P = .08), whereas serum growth hormone decreased linearly (P = .08) as a result of increasing glucose infusion. Results suggest that UUN, serum insulin, aldosterone, and several serum constituents may serve as markers of organic acid load in ruminants fed high-concentrate diets.  (+info)

Lactic acidosis associated with stavudine administration: a report of five cases. (10/290)

Type "B" lactic acidosis has been described in patients receiving the nucleoside analogs zidovudine, didanosine, and fialuridine. Lactic acidosis has also been described in 4 patients receiving combination therapy with stavudine and lamivudine. We describe the development of chronic type "B" lactic acidosis in 3 patients receiving stavudine as a single agent and in 2 patients receiving combination therapy with stavudine and either lamivudine or delavirdine, a nonnucleoside analog. All patients presented with abdominal pain, vomiting, and hepatic steatosis. Other signs of mitochondrial toxicity included pancreatitis and myopathy (2 cases). The mean duration of stavudine therapy was 9.4 months, and the mean observed peak lactate level+/-SD was 10.3+/-5 mmol/L. After discontinuation of stavudine treatment, lactic acidosis improved in 4 patients after 4-60 weeks, and 1 patient died. Evaluations for other causes of lactic acidosis, including hypoxemia, malignancy, sepsis, and cardiogenic shock, were negative.  (+info)

Cocaine and exercise: alpha-1 receptor blockade does not alter muscle glycogenolysis or blood lactacidosis. (11/290)

In our previous work, we routinely observed that a combined cocaine-exercise challenge results in an abnormally rapid muscle glycogen depletion and excessive blood lactacidosis. These phenomena occur simultaneously with a rapid rise in norepinephrine and in the absence of any rise in epinephrine. We postulated that norepinephrine may cause vasoconstriction of the muscle vasculature through activation of alpha-1 receptors during cocaine-exercise, thus inducing hypoxia and a concomitant rise in glycogenolysis and lactate accumulation. To test this hypothesis, rats were pretreated with the selective alpha-1-receptor antagonist prazosin (P) (0.1 mg/kg iv) or saline (S). Ten minutes later, the animals were treated with cocaine (-C) (5 mg/kg iv) or saline (-S) and run for 4 or 15 min at 22 m/min at 10% grade. In the S-S group, glycogen content of the white vastus lateralis muscle was unaffected by exercise at both time intervals, whereas in S-C rats glycogen was reduced by 47%. This effect of cocaine-exercise challenge was not attenuated by P. Similarly, blood lactate concentration in S-C rats was threefold higher than that of S-S after exercise, a response also not altered by pretreatment with P. On the basis of these observations, we conclude that the excessive glycogenolysis and lactacidosis observed during cocaine-exercise challenge is not the result of vasoconstriction secondary to norepinephrine activation of alpha-1 receptors.  (+info)

Hyperlactatemia and hepatic abnormalities in 10 human immunodeficiency virus-infected patients receiving nucleoside analogue combination regimens. (12/290)

During a 6-and-a-half month period, we identified 10 human immunodeficiency virus (HIV)-infected men who were receiving antiretroviral regimens, including nucleoside analogues, and who developed unexplained reproducible hyperlactatemia in association with either abdominal symptoms or an unaccounted-for elevated alanine aminotransferase level, or both. After careful consideration of the possible etiologies, antiretrovirals were discontinued; lactate levels normalized in all patients. The estimated incidence of this phenomenon in our clinic was 20.9 cases per 1000 person-years of nucleoside analogue treatment. These observations extend the spectrum of the nucleoside analogue-induced lactic acidosis/hepatic steatosis syndrome by the identification of a subtle and perhaps earlier form, which has characteristic symptoms and laboratory abnormalities, and a favorable prognosis on discontinuation of antiretroviral therapy.  (+info)

Mechanisms of endothelial cell swelling from lactacidosis studied in vitro. (13/290)

One of the early sequelae of ischemia is an increase of circulating lactic acid that occurs in response to anaerobic metabolism. The purpose of the present study was to investigate whether lactic acidosis can induce endothelial swelling in vitro under closely controlled extracellular conditions. Cell volume of suspended cultured bovine aortic endothelial cells was measured by use of an advanced Coulter technique employing the "pulse area analysis" signal-processing technique (CASY1). The isosmotic reduction of pH from 7.4 to 6.8 had no effect on cell volume. Lowering of pH to 6.6, 6.4, or 6.0, however, led to significant, pH-dependent increases of cell volume. Swelling was more pronounced in bicarbonate-buffered media than in HEPES buffer. Specific inhibition of Na(+)/H(+) exchange by ethylisopropylamiloride completely prevented swelling in HEPES-buffered media. Pretreatment with ouabain to partially depolarize the cells did not affect the degree of acidosis-induced swelling. In bicarbonate-buffered media, the inhibition of transmembrane HCO(3)(-) transport by DIDS reduced swelling to a level comparable with that seen in the absence of bicarbonate ions. Lactacidosis-induced endothelial swelling, therefore, is a result of intracellular pH regulatory mechanisms, namely, Na(+)/H(+) exchange and bicarbonate-transporting carriers.  (+info)

Effect of dichloracetate on infarct size in a primate model of focal cerebral ischaemia. (14/290)

Acidosis is a major contributing factor towards spread of the ischaemic focus in the brain. Drugs that increase pyruvate dehydrogenase activity could decrease the formation of lactic acidosis. The sodium salt of dichloracetic acid (DCA) has been found to be effective in reducing lactate. This study was undertaken to study the efficacy of DCA in reducing infarct size in experimental focal ischaemia in monkeys. Macaca radiata monkeys in the treatment group were given 35 mg per kilogram of dichloracetate intravenously immediately before occluding and interrupting the middle cerebral artery, and the control group was given saline as placebo under similar conditions. Mean infarct size expressed as a percentage of the size of the hemisphere in all the three brain slices was 35.38 in the control group as against l2.06 in the treated group (p=0. 0008).  (+info)

Heat stress is associated with decreased lactic acidemia in rat sepsis. (15/290)

BACKGROUND: Elevated plasma lactate has been shown to correlate with mortality in patients with septic shock. Heat stress prior to sepsis has resulted in reduction in acute lung injury and mortality. We investigated whether heat stress resulted in decreased plasma lactate concentration and protected the lung by decreasing the inflammatory response to sepsis. RESULTS: Plasma lactate concentration was elevated in septic rats without prior heat stress. Lactic acid levels were significantly lower in heat-treated septic rats (P < 0.05) and were not significantly different when compared with control rats. Septic rats with or without heat pretreatment had significantly higher myeloperoxidase activity in the lung than did control groups. Heat pretreatment did not prevent neutrophil infiltration or inflammatory mediator production in the lung. CONCLUSION: Prior heat stress ameliorates lactic acidemia in rat sepsis. Heat stress did not attenuate the pulmonary inflammatory process. The mechanism of heat-induced protection from lactic acidemia in sepsis needs to be further explored.  (+info)

The age-related accumulation of a mitochondrial DNA control region mutation in muscle, but not brain, detected by a sensitive PNA-directed PCR clamping based method. (16/290)

The peptide nucleic acid (PNA)-directed PCR clamping technique was modified and applied to the detection of mitochondrial DNA mutations with low heteroplasmy. This method is extremely specific, eliminating false positives in the absence of mutant molecules, and highly sensitive, being capable of detecting mutations at the level of 0.1% of total molecules. Moreover, the reaction can be multiplexed to identify more than one mutation per reaction. Using this technique, the levels of three point mutations, the tRNA(Leu(UUA)) 3243 mutation causing mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS); the tRNA(Lys) 8344 mutation causing myoclonic epilepsy and ragged red fibers (MERRF); and the nucleotide position 414 mutation adjacent to the control region promoters, were evaluated in human brain and muscle from individuals of various ages. While none of the mutations were detected in brain samples from individuals ranging in age from 23 to 93, the 414 mutation could be detected in muscle from individuals 30 years and older. These data demonstrate that the 3243 and 8344 mutations do not accumulate with age to levels greater than 0.1% in brain and muscle. By contrast, the 414 mutation accumulates with age in normal human muscle, though not in brain. The reason for the striking absence of the 414 mutation in aging brain is unknown.  (+info)