Tb(III) speciation in human blood plasma by computer simulation

A multi-phase model was developed and Tb(III) speciation in human blood plasma was studied. At a concentration below 3.744x 10(-4) mol/L (or at the concentration), Tb(III) is mostly bound to phosphate to form precipitate of TbPO4. As the concentration of Tb(III) increases, phosphate is exceeded and another kind of precipitate of Tb-2(CO3)(3) appears. Among soluble Tb(III) species, Tb(III) mainly distribute in [Tb (Tf)] at low concentration and in [Tb (HSAA, [Tb-2 (Tf)], [Th (IgG)], [Tb (Lactate)](2+), [Tb (CitArgH)] and free Tb(III) at high concentration.

Influence of blood donation on O-2 uptake on-kinetics, peak O-2 uptake and time to exhaustion during severe-intensity cycle exercise in humans

Thatcher, Rhys, et al., 'Influence of blood donation on O-2 uptake on-kinetics, peak O-2 uptake and time to exhaustion during severe-intensity cycle exercise in humans', Experimental Physiology (2006) 91(3) pp.499-509 RAE2008

Triose phosphate isomerase from the blood fluke Schistosoma mansoni:Biochemical characterisation of a potential drug and vaccine target

The glycolytic enzyme triose phosphate isomerase from Schistosoma mansoni is a potential target for drugs and vaccines. Molecular modelling of the enzyme predicted that a Ser-Ala-Asp motif which is believed to be a helminth-specific epitope is exposed. The enzyme is dimeric (as judged by gel filtration and cross-linking), resistant to proteolysis and highly stable to thermal denaturation (melting temperature of 82.0°C). The steady-state kinetic parameters are high (Km for dihydroxyacetone phosphate is 0.51mM; Km for glyceraldehyde 3-phosphate is 1.1mM; kcat for dihydroxyacetone phosphate is 7800s(-1) and kcat for glyceraldehyde 3-phosphate is 6.9s(-1)).

Is the formula of Traub still up to date in antemortem blood glucose level estimation?

According to the hypothesis of Traub, also known as the 'formula of Traub', postmortem values of glucose and lactate found in the cerebrospinal fluid or vitreous humor are considered indicators of antemortem blood glucose levels. However, because the lactate concentration increases in the vitreous and cerebrospinal fluid after death, some authors postulated that using the sum value to estimate antemortem blood glucose levels could lead to an overestimation of the cases of glucose metabolic disorders with fatal outcomes, such as diabetic ketoacidosis. The aim of our study, performed on 470 consecutive forensic cases, was to ascertain the advantages of the sum value to estimate antemortem blood glucose concentrations and, consequently, to rule out fatal diabetic ketoacidosis as the cause of death. Other biochemical parameters, such as blood 3-beta-hydroxybutyrate, acetoacetate, acetone, glycated haemoglobin and urine glucose levels, were also determined. In addition, postmortem native CT scan, autopsy, histology, neuropathology and toxicology were performed to confirm diabetic ketoacidosis as the cause of death. According to our results, the sum value does not add any further information for the estimation of antemortem blood glucose concentration. The vitreous glucose concentration appears to be the most reliable marker to estimate antemortem hyperglycaemia and, along with the determination of other biochemical markers (such as blood acetone and 3-beta-hydroxybutyrate, urine glucose and glycated haemoglobin), to confirm diabetic ketoacidosis as the cause of death.

A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia.

Lactate has been shown to offer neuroprotection in several pathologic conditions. This beneficial effect has been attributed to its use as an alternative energy substrate. However, recent description of the expression of the HCA1 receptor for lactate in the central nervous system calls for reassessment of the mechanism by which lactate exerts its neuroprotective effects. Here, we show that HCA1 receptor expression is enhanced 24 hours after reperfusion in an middle cerebral artery occlusion stroke model, in the ischemic cortex. Interestingly, intravenous injection of L-lactate at reperfusion led to further enhancement of HCA1 receptor expression in the cortex and striatum. Using an in vitro oxygen-glucose deprivation model, we show that the HCA1 receptor agonist 3,5-dihydroxybenzoic acid reduces cell death. We also observed that D-lactate, a reputedly non-metabolizable substrate but partial HCA1 receptor agonist, also provided neuroprotection in both in vitro and in vivo ischemia models. Quite unexpectedly, we show D-lactate to be partly extracted and oxidized by the rodent brain. Finally, pyruvate offered neuroprotection in vitro whereas acetate was ineffective. Our data suggest that L- and D-lactate offer neuroprotection in ischemia most likely by acting as both an HCA1 receptor agonist for non-astrocytic (most likely neuronal) cells as well as an energy substrate.

Increase brain lactate in hepatic encephalopathy: Cause or consequence?

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome which develops as a result of liver failure or disease. Increased concentrations of brain lactate (microdialysate, cerebrospinal fluid, tissue) are commonly measured in patients with HE induced by either acute or chronic liver failure. Whether an increase in brain lactate is a cause or a consequence of HE remains undetermined. A rise in cerebral lactate may occur due to (1) blood-borne lactate (hyperlactataemia) crossing the blood-brain barrier, (2) increased glycolysis due to energy failure or impairment and (3) increased lactate production/release or decreased lactate utilization/uptake. This review explores the different reasons for lactate accumulation in the brain during liver failure and describes the possible roles of lactate in the pathogenesis of HE.

Mild hypothermia prevents cerebral edema and CSF lactate accumulation in acute liver failure.

Evidence from both clinical and experimental studies demonstrates that mild hypothermia prevents encephalopathy and brain edema in acute liver failure (ALF). As part of a series of studies to elucidate the mechanism(s) involved in this protective effect, groups of rats with ALF resulting from hepatic devascularization were maintained at either 37°C (normothermic) or 35°C (hypothermic), and neurological status was monitored in relation to cerebrospinal fluid (CSF) concentrations of ammonia and lactate. CSF was removed via implanted cisterna magna catheters. Mild hypothermia resulted in a delay in onset of encephalopathy and prevention of brain edema; CSF concentrations of ammonia and lactate were concomitantly decreased. Blood ammonia concentrations, on the other hand, were not affected by hypothermia in ALF rats. These findings suggest that brain edema and encephalopathy in ALF are the consequence of ammonia-induced impairment of brain energy metabolism and open the way for magnetic resonance spectroscopic monitoring of cerebral function in ALF. Mild hypothermia could be beneficial in the prevention of severe encephalopathy and brain edema in patients with ALF awaiting liver transplantation.

Association of reduced extracellular brain ammonia, lactate, and intracranial pressure in pigs with acute liver failure.

We previously demonstrated in pigs with acute liver failure (ALF) that albumin dialysis using the molecular adsorbents recirculating system (MARS) attenuated a rise in intracranial pressure (ICP). This was independent of changes in arterial ammonia, cerebral blood flow and inflammation, allowing alternative hypotheses to be tested. The aims of the present study were to determine whether changes in cerebral extracellular ammonia, lactate, glutamine, glutamate, and energy metabolites were associated with the beneficial effects of MARS on ICP. Three randomized groups [sham, ALF (induced by portacaval anastomosis and hepatic artery ligation), and ALF+MARS] were studied over a 6-hour period with a 4-hour MARS treatment given beginning 2 hours after devascularization. Using cerebral microdialysis, the ALF-induced increase in extracellular brain ammonia, lactate, and glutamate was significantly attenuated in the ALF+MARS group as well as the increases in extracellular lactate/pyruvate and lactate/glucose ratios. The percent change in extracellular brain ammonia correlated with the percent change in ICP (r(2) = 0.511). Increases in brain lactate dehydrogenase activity and mitochondrial complex activity for complex IV were found in ALF compared with those in the sham, which was unaffected by MARS treatment. Brain oxygen consumption did not differ among the study groups. Conclusion: The observation that brain oxygen consumption and mitochondrial complex enzyme activity changed in parallel in both ALF- and MARS-treated animals indicates that the attenuation of increased extracellular brain ammonia (and extracellular brain glutamate) in the MARS-treated animals reduces energy demand and increases supply, resulting in attenuation of increased extracellular brain lactate. The mechanism of how MARS reduces extracellular brain ammonia requires further investigation.

Kinetic Studies of Purified malate Dehydrogenase in Liver of Streptozotocindiabetic Rats and the Effect of Leaf Extract of Aegle Marmelose (L.) Correa ex Roxb

The functional basis of diabetes-mellitus to a certain extent, can be elucidated by studying diabetes-induced changes in metabolic enzymes. Malate dehydrogenase (MDH), is an enzyme directly involved in glucose metabolism. The kinetic parameters of MDH and its purified cytosolic isozyme, S-MDH, have been studied in the liver of streptozotocin- diabetic rats; also the potential of the leaf extract of A. marmelose as an was investigated. The Km of the liver enzyme increased significantly, in both crude and purified preparations in the diabetic state when compared to Lhe respective controls. Insulin as well as leaf- •extract treatment of the diabetic rats brought about a reversal of K. values to near normal. Vmax of purified S-MDH was significantly higher in the diabetic state when compared to the control. Insulin and leaf extract treatment did not reverse this change. Since MDH is an important enzyme in glucose metabolism, the variation in its quantitative and qualitative nature may contribute to the pathological status of diabetes. The fact that leaf extract of A. marmelose was found to be as effective as insulin in restoration of blood glucose and body weight to normal levels, the use of A. marmelose as potential hypoglycemic agent is suggested.

Effects of melatonin on hemolymph glucose and lactate concentrations in the fiddler crab, uca pugilator

Melatonin (N-acetyl-5-methoxytryptamine) is an indolamine hormone produced by the pineal gland that works to regulate sleep/wake cycles and activity rhythms. The effects of melatonin in metabolism are far from understood. Melatonin was injected into the fiddler crab, Uca pugilator, to investigate the effects of melatonin on hemolymph glucose and lactate levels. Following injection at t=O, hemolymph samples were collected at t=O.5, 1.0, 1.5 and 5.0 hours. Melatonin caused a decrease in the stress response to injection and also caused delayed hyperglycemia. Melatonin-injected crabs also retained the glucose and lactate rhythymicity when compared to saline-injected crabs. Glucose and lactate rhythms followed the same pattern indicating that the cycles are coupled. Also, melatonin was synthesized using tbe Fischer Indole synthesis and characterized using H?NMR. The synthetic melatonin demonstrated biological activity when injected into the crabs as when compared to pure melatonin on the effects on glucose and lactate concentrations. Overall, melatonin influences both glucose metabolism and the production of lactate.

Lactate sequestration by osteoderms of the broad-nose caiman, Caiman latirostris, following capture and forced submergence

Lactate accumulation in osteoderms; of the broad-nose caiman, Caiman latirostris, was determined following capture and surgery and after a period of forced submergence and related to concurrent values in blood. Control samples of bone and blood were taken after recovery from surgery and before submergence. In addition, samples of osteoderm were incubated in a lactate solution to determine equilibrium concentration, and additional samples were analyzed for elemental and CO2 concentrations. The composition of the osteoderms closely resembles that of typical vertebrate bone, with a high concentration of calcium and phosphate. Plasma and osteoderm lactate concentrations were both elevated following surgery and decreased significantly after 1 day of recovery. Submergence produced a typical lactate pattern in the plasma, with only a modest increase during the dive and then a sharp increase during recovery to a peak of 31.2 +/- 1.9 mumol ml(-1) after 1 h. When caimans were anesthetized 2 h after submergence, osteoderm lactate in the same animals was significantly increased to 14.8 mumol g(-1) wet mass. The ratio of the osteoderm: plasma lactate concentration after submergence was similar to the ratio observed in the incubated samples, suggesting that osteoderm lactate concentrations in vivo were equilibrated with circulating plasma levels. We conclude that caiman osteoderms sequester lactate during lactic acidosis and that the time course is fast enough to have benefit to these animals following normal anaerobic burst activity.

Blood serum components and serum protein test of Hybro-PG broilers of different ages

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Reduction of enantioselectivity in the kinetic disposition and metabolism of verapamil in rats exposed to toluene

Toluene and verapamil are subject to extensive oxidative metabolism mediated by CYP enzymes, and their interaction can be stereoselective. In the present study we investigated the influence of toluene inhalation on the enantioselective kinetic disposition of verapamil and its metabolite, norverapamil, in rats. Male Wistar rats (n = 6 per group) received a single dose of racemic verapamil (10 mg/kg) orally at the fifth day of nose-only toluene or air (control group) inhalation for 6 h/day (25, 50, and 100 ppm). Serial blood samples were collected from the tail up to 6 h after verapamil administration. The plasma concentrations of verapamil and norverapamil enantiomers were analyzed by LC-MS/MS by using a Chiralpak AD column. Toluene inhalation did not influence the kinetic disposition of verapamil or norverapamil enantiomers (p > 0.05, Kruskal-Wallis test) in rats. The pharmacokinetics of verapamil was enantioselective in the control group, with a higher plasma proportion of the S-verapamil (AUC 250.8 versus 120.4 ng.h.mL(-1); p <= 0.05, Wilcoxon test) and S-norverapamil (AUC 72.3 versus 52.3 ng.h.mL(-1); p <= 0.05, Wilcoxon test). Nose-only exposure to toluene at 25, 50, or 100 ppm resulted in a lack of enantioselectivity for both verapamil and norverapamil. The study demonstrates the importance of the application of enantioselective methods in studies on the interaction between solvents and chiral drugs.

Intraoperative lactate levels and postoperative complications of pediatric cardiac surgery

Objectives: Correlate arterial lactate levels during the intraoperative period of children undergoing cardiac surgery and the occurrence of complications in the postoperative period. Aim: Arterial lactate levels can indicate hypoperfusion states, serving as prognostic markers of morbidity and mortality in this population. Background: Anesthesia for cardiac pediatric surgery is frequently performed on patients with serious abnormal physiological conditions. During the intraoperative period, there are significant variations of blood volume, body temperature, plasma composition, and tissue blood flow, as well as the activation of inflammation, with important pathophysiological consequences. Methods/Materials: Chart data relating to the procedures and perioperative conditions of the patients were collected on a standardized form. Comparisons of arterial lactate values at the end of the intraoperative period of the patients that presented, or not, with postoperative complications and frequencies related to perioperative conditions were established by odds ratio and nonparametric univariate analysis. Results: After surgeries without cardiopulmonary bypass (CPB), higher levels of arterial lactate upon ICU admission were observed in patients who had renal complications (2.96 vs 1.31 mm) and those who died (2.93 vs 1.40 mm). For surgeries with CPB, the same association was observed for cardiovascular (2.90 mm x 2.06 mm), renal (3.34 vs 2.33 mm), respiratory (2.98 vs 2.12 mm) and hematological complications (2.99 vs 1.95 mm), and death (3.38 vs 2.40 mm). Conclusion: Elevated intraoperative arterial lactate levels are associated with a higher morbidity and mortality in low- and medium-risk procedures, with or without CPB, in pediatric cardiac surgery.

Serum cortisol, lactate and creatinine concentrations in Thoroughbred fillies of different ages and states of training

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)