Decrease In Lactate Concentration Research Articles

Effects of administration of caffeine on metabolic variables in neonatal pigs with peripartum asphyxia

To determine effects of 2 doses of caffeine on metabolic variables in neonatal pigs with peripartum asphyxia. 180 neonatal pigs. Neonatal pigs were assigned to 2 groups (groups P and F) on the basis of results for a vitality scale (passed or failed, respectively). Within each group, there were 3 subgroups of 30 pigs each. Within each group, the 3 subgroups received a placebo that consisted of an empty gelatin capsule, a gelatin capsule that contained 20 mg of caffeine, and a gelatin capsule that contained 35 mg of caffeine, respectively; all capsules were administered orally (0 hours). Blood samples were collected immediately before and 24 hours after capsule administration. Pigs in groups P and F that received 20 or 35 mg of caffeine had significant increases in triglyceride concentrations. All pigs in groups P and F had a significant decrease in lactate concentrations, although the placebo-treated pigs in group F had larger decreases than did the group F pigs treated with 20 or 35 mg of caffeine. Glucose concentrations increased significantly in group F pigs treated with 20 or 35 mg of caffeine (30% and 50%, respectively), whereas glucose concentrations remained unchanged in group P pigs. In pigs treated with 35 mg of caffeine, the final weight obtained for group F was approximately 8% lower than that obtained for group P. Administering caffeine immediately after birth to neonatal pigs with severe oxygen restriction resulted in significant improvements in metabolic variables.

Gonadal development in male and female domesticated whiteleg shrimp, Litopenaeus vannamei, in relation to age and weight

Cultivation of whiteleg shrimp ( Litopenaeus vannamei) is now entirely based on closed life-cycle populations, yet few studies have analyzed gonadal development in domesticated shrimp during grow-out in ponds. To determine the effect of age and weight on morphometric, histological, and biochemical variables associated with male and female gonadal development, shrimp from the same cohort, at ages of 6, 8, 10, and 12 months were examined using body weight as a covariable in an ANCOVA design. An additional comparison between two grow-out conditions in 1-year-old shrimp was done to separate the effect of size as a result of initial stocking densities. Age-related growth of gonads was clearly dependent on somatic growth for females but not for males, although differential somatic growth produced by stocking densities explained differences in growth of gonads for both sexes. Increase in oocyte diameter and differentiation associated with age and grow-out condition were independent of body weight. Age-related female gonadal development was accompanied by increases in lipid and protein concentrations, independent of body weight. Maturation of male reproductive organs (testicle, vas deferens, terminal ampoule, and spermatophore) was sequential and depended mainly on age, although body weight could explain differences caused by different grow-out conditions. An age-related decrease in concentration of lactate occurred in all male reproductive organs and could indicate a metabolic adjustment of sperm anaerobic metabolism and lactate clearance associated with gonadal development. We highly recommend waiting for optimal reproductive potential of females at 12 months to enhance spawning frequency and larval quality. At this age, body weight seems to be of secondary importance, although optimal conditions of cultivation are necessary to have adequate growth and balanced nutrition.

Silage supports sulfate reduction in the treatment of metals- and sulfate-containing waste waters

Silage was used as source of carbon and electrons for enrichment of silage-degrading and sulfate reducing bacteria (SRB) from boreal, acidic, metals-containing peat-bog samples and to support their use in batch and semi-batch systems in treatment of synthetic waste water. Sulfidogenic silage utilization resulted in a rapid decrease in lactate concentrations; concentrations of acetate, butyrate and propionate increased concomitantly. Synthetic waste water consisting of Mn, Mg and Fe (II) ions inhibited sulfate reduction at concentrations of 6 g/l, 8 g/l and 1 g/l respectively. During treatment, Mn and Mg ions remained in solution while Fe ions partially precipitated. Up to 87 mg sulfate was reduced per gram of silage. Sulfate reduction rates of 34, 22 and 6 mg/l/day were obtained at temperatures of 30, 20 and 9 °C respectively. In semi-batch reactors operated at low pH, the iron precipitation capacity was controlled by sulfate reduction rates and by partial loss of hydrogen sulfide to the gas phase. Passive reactor systems should, therefore, be operated at neutral pH. Metals tolerant, silage-fermenting (predominantly species belonging to genus Clostridium) and sulfate reducing bacteria (including a species similar to the psychrotolerant Desulfovibrio arcticus) were obtained from the peat bog samples. This work demonstrates that silage supports sulfate reduction and can be used as a low cost carbon and electron source for SRB in treatment of metals-containing waste water.

Insulin differentially influences brain glucose and lactate in traumatic brain injured patients

Hypo- and hyperglycemia must be avoided to prevent additional brain damage following traumatic brain injury (TBI). However, the optimal blood glucose range requiring insulin remains unknown. Cerebral microdialysis is helpful in unmasking signs of metabolic impairment, thereby identifying deleterious blood glucose levels. A retrospective analysis of prospectively collected cerebral microdialysis samples obtained from 20 non-diabetic patients with severe TBI treated at the trauma surgical intensive care unit at the University Hospital Zürich, Switzerland. The impact of different arterial blood glucose values and concomitant insulin administration on cerebral interstitial glucose and lactate levels was investigated. In addition, energetic impairment was determined by calculating lactate-to-glucose ratios. Insulin administration was associated with significantly reduced cerebral glucose concentrations and significantly increased lactate-to-glucose ratios with arterial blood glucose levels <5 mM. At arterial blood glucose levels >7 mM, insulin administration was associated with significantly increased interstitial glucose values, significantly decreased lactate concentrations, and markedly diminished lactate-to-glucose ratios. Insulin exerts differential effects that depend strongly on the underlying arterial blood glucose concentrations. To avoid energetic impairment, insulin should not be administered at arterial blood glucose levels <5 mM. However, at arterial blood glucose levels >7-8 mM, insulin administration appears to be encouraged to increase extracellular glucose concentrations and decrease energetic impairment reflected by reduced interstitial brain lactate and decreased lactate-to-glucose ratios. Nevertheless, frequent analysis is required to minimize the risk of inducing impaired brain metabolism.

Effects of Graduated Compression Stockings on Cardiovascular and Metabolic Responses to Exercise and Exercise Recovery in Persons With Spinal Cord Injury

Rimaud D, Calmels P, Roche F, Mongold J-J, Trudeau F, Devillard X. Effects of graduated compression stockings on cardiovascular and metabolic responses to exercise and exercise recovery in persons with spinal cord injury. Objective To investigate whether reporting blood redistribution by means of graduated elastic stockings affects exercise and postexercise responses in people with spinal cord injury (SCI). Design Crossover trial. Setting Physical medicine and rehabilitation department in France. Participants Fourteen men with traumatic SCI, grouped according to their level of injury. Interventions Subjects performed 2 maximal wheelchair exercise tests 1 week apart, in random order and under a counter-balanced design. One test was done with and the other without graduated elastic stockings (21mmHg). Main Outcome Measures Blood lactate, blood pressure, heart rate, maximal power output, and oxygen consumption (V̇o 2). Results Postexercise venous lactate concentration was reduced in SCI subjects with lesion levels below T6 while wearing graduated elastic stockings during both exercise and recovery (10.9±3.9mmol/L vs 12.5±4.6mmol/L, P<.05). There were no significant differences in submaximal and maximal values (heart rate, V̇ o 2, power output) between subjects tested with and without graduated elastic stockings. Conclusions Wearing elastic stockings affects postexercise responses by decreasing lactate concentration in well-trained, low-level paraplegic patients after a maximal exercise. The relatively low pressure generated by the stockings may not, however, influence the venous system enough to produce improved performance and cardiovascular responses.

Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression

Calcium desensitization plays an important part in the pathophysiology of septic myocardial depression. We postulated that levosimendan, a new calcium sensitizer, would be beneficial in sepsis-induced cardiac dysfunction. Prospective, randomized, controlled study in two university hospital intensive care units. Twenty-eight patients with persisting left ventricular dysfunction related to septic shock after 48 h of conventional treatment including dobutamine (5 microg/kg per minute). After 48 h of conventional treatment patients were randomized to receive a 24-h infusion of either levosimendan (0.2 microg/kg per minute, n=15) or dobutamine (5 microg/kg per minute, n=13). Data from right heart catheterization, echocardiography, gastric tonometry, laser-Doppler flowmetry, and lactate concentrations and creatinine clearance were obtained before and after the 24-h drug infusion. Dobutamine did not change systemic or regional hemodynamic variables. By contrast, at the same mean arterial pressure levosimendan decreased pulmonary artery occlusion pressure and increased cardiac index. Levosimendan decreased left ventricular end-diastolic volume and increased left ventricular ejection fraction. Levosimendan increased gastric mucosal flow, creatinine clearance, and urinary output while it decreased lactate concentrations. These findings show that levosimendan improves systemic hemodynamics and regional perfusion in patients with septic cardiac dysfunction under conditions where administration of 5 microg/kg dobutamine per minute is no longer efficacious. Accordingly, our results suggest that levosimendan can be an alternative to the strategy of increasing the dose of dobutamine under such conditions.

Mechanism of dichloroacetate-induced hypolactatemia in humans with or without cirrhosis

Dichloroacetate (DCA) has been used as an experimental treatment for lactic acidosis because it lowers plasma lactic acid concentration. Three potential mechanisms could underlie the hypolactatemic action of DCA, but the dominant mechanism in vivo remains unclear. This study tested whether DCA-induced hypolactatemia occurs via decreased lactate production, increased lactate clearance, or decreased rate of glycolysis in healthy humans and in patients with end-stage cirrhosis. Cirrhosis is associated with decreased hepatic pyruvate dehydrogenase (PDH) content. Six healthy volunteers and 7 cirrhotic patients received a primed, constant infusion of 1- 13C-pyruvate and 15N-alanine for 5 hours. DCA (35 mg/kg intravenously) was administered at 2 hours. Plasma isotopic enrichment was measured by gas chromatography/mass spectrometry (GC/MS), and exhaled CO 2 enrichment by isotope ratio mass spectrometry. Pyruvate and alanine production rates (Ra) were determined by isotope dilution, and pyruvate oxidation calculated as 13CO 2 production from 13C-pyruvate. Ra lactate was calculated as the difference between Ra pyruvate and its disposal by oxidation to CO 2 and conversion to alanine. Baseline plasma lactate kinetics in cirrhotic patients did not differ from controls. DCA decreased lactate concentration in both groups by approximately 53%. DCA decreased glycolysis (Ra pyruvate) by 24%, increased the fraction of pyruvate oxidized to CO 2 by 26%, and decreased pyruvate transamination to alanine by 25%. DCA also inhibited lactate production by 85%, but decreased plasma lactate clearance by 60% in both groups. DCA reduces plasma lactic acid concentration by inhibiting production, via stimulating pyruvate oxidation and inhibiting glycolysis, rather than increasing clearance. In addition, end-stage cirrhosis does not alter either the mechanism or the magnitude of the metabolic response to DCA.

Repercussões da L-alanil-glutamina sobre as concentrações de lactato e lactato desidrogenase (LDH) em pacientes com isquemia crítica dos membros inferiores submetidos a revascularização distal

OBJETIVO: Investigar efeitos da L-alanil-glutamina nas concentrações musculares de lactato, e nas concentrações sanguíneas de LDH, em pacientes com isquemia crítica dos membros inferiores submetidos à revascularização distal. MÉTODOS: Dezesseis adultos (12-homens/4-mulheres) foram distribuídos em 2 grupos (1-controle/2-estudo). Três horas após injeção endovenosa de 250 ml de L-alanil-glutamina a 20% adicionados a 750 ml de soro fisiológico (Grupo 2), ou 1000 ml de solução salina (Grupo 1), iniciava-se a revascularização, sob raquianestesia. Amostras musculares e de sangue (arterial/venoso) foram coletadas no início do procedimento (TI), no final (TF), e 10 e 20 minutos após isquemia (T1/T2). RESULTADOS: Observou-se redução significante (p&lt;0,05) da concentração de lactato no tecido muscular sadio dos pacientes tratados com L-alanil-glutamina, em comparação ao grupo controle, em todos os tempos estudados. Houve redução significante nas concentrações de LDH no sangue venoso dos pacientes tratados, em todos os tempos (TIV/TFV/T1V/T2V), e no sangue arterial durante a reperfusão (T1A/T2A). CONCLUSÕES: Queda na concentração de lactato no músculo, e redução nas concentrações arteriais e venosas de LDH, em pacientes recipientes de L-alanil-glutamina, sugere maior utilização de piruvato para produção de energia no ciclo de Krebs do que sua conversão para lactato, com prevalência da glicólise aeróbica.

Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo.

Neuronal cultures in vitro readily oxidized both D-[(14)C]glucose and l-[(14)C]lactate to (14)CO(2), whereas astroglial cultures oxidized both substrates sparingly and metabolized glucose predominantly to lactate and released it into the medium. [(14)C]Glucose oxidation to (14)CO(2) varied inversely with unlabeled lactate concentration in the medium, particularly in neurons, and increased progressively with decreasing lactate concentration. Adding unlabeled glucose to the medium inhibited [(14)C]lactate oxidation to (14)CO(2) only in astroglia but not in neurons, indicating a kinetic preference in neurons for oxidation of extracellular lactate over intracellular pyruvatelactate produced by glycolysis. Protein kinase-catalyzed phosphorylation inactivates pyruvate dehydrogenase (PDH), which regulates pyruvate entry into the tricarboxylic acid cycle. Dichloroacetate inhibits this kinase, thus enhancing PDH activity. In vitro dichloroacetate stimulated glucose and lactate oxidation to CO(2) and reduced lactate release mainly in astroglia, indicating that limitations in glucose and lactate oxidation by astroglia may be due to a greater balance of PDH toward the inactive form. To assess the significance of astroglial export of lactate to neurons in vivo, we attempted to diminish this traffic in rats by administering dichloroacetate (50 mgkg) intravenously to stimulate astroglial lactate oxidation and then examined the effects on baseline and functionally activated local cerebral glucose utilization (lCMR(glc)). Dichloroacetate raised baseline lCMR(glc) throughout the brain and decreased the percent increases in lCMR(glc) evoked by functional activation. These studies provide evidence in support of the compartmentalization of glucose metabolism between astroglia and neurons but indicate that the compartmentalization may be neither complete nor entirely obligatory.

The aerobic brain: lactate decrease at the onset of neural activity

The metabolic events of neuronal energetics during functional activity are still partially unexplained. In particular, lactate (and not glucose) was recently proposed as the main substrate for neurons during activity [Proc Natl Acad Sci USA 91 (1994) 10625]. By means of proton magnetic resonance spectroscopy, lactate was reported to increase during the first minutes of prolonged stimulation [Proc Natl Acad Sci USA 88 (1991) 5829; J Cereb Blood Flow Metab 12 (1992) 584; Magn Reson Med 35 (1996) 143], but the studies reported thus far suffered from low temporal resolution. In the present study we used a time-resolved proton magnetic resonance spectroscopy strategy in order to analyse the evolution of lactate during the early seconds following a brief visual stimulation (event-related design). A significant decrease in lactate concentration was observed 5 s after the stimulation, while a recovering of the baseline was observed at 12 s.

Circadian heart rate patterns and schizophrenia

Cold water immersion (CWI) and ice massage (IM) are commonly used treatments to prevent the delay onset of muscle soreness (DOMS); however, little is known on their relative benefits and effectiveness to lower tissue temperature. This study was designed to evaluate the effectiveness of IM and CMI on tissue temperature and potential benefit to preventing DOMS. The research encompassed 36 subjects divided into three groups of twelve depending on the form of recovery: ice massage (IM), cold-water immersion (CWI), or passive recovery (PAS). All the participants were asked to jump as high as possible from a full squat for one minute. Thermal imaging was conducted at rest, immediately following the exercise, immediately after the trial, following the recovery treatment, and after 30 min of rest. Their pain levels were assessed using the Visual Analogue Scale (VAS). After applying the selected method for supporting recovery, the LA level decreased by 4.25 mmol/L in the IM group, and by 4.96 mmol/L in the CWI group (IM vs. CWI p>0.05). The 2.75 mmol/L decrease in lactate concentration in the PAS group was significantly lower than in the other groups (IM vs. PAS p<0.05/ CWI vs. PAS p<0.01). In both groups, Tsk after 30 min was significantly lower (ΔTsk~0.5 °C) than at rest (p<0.05). In turn, Tsk in the PAS group returned to the resting values (p>0.05). Seventy-two hours after the exercise, a clear decrease in discomfort was observed in the IM and CWI groups compared to the PAS group. The two applied treatments have proven to be effective both in utilizing lactate and preventing DOMS. Depending on training requirements, we recommend the use of IM when athletes experience localized muscle fatigue. One the other hand, CWI is recommended in situations of global or generalized muscle injury or fatigue.

Changes in plasma lactate and pyruvate concentrations after taking a bath in hot deep seawater.

The use of deep seawater (DSW) in thalassotherapy has begun in Japan. To clarify the health effects of DSW on the human body, we investigated the changes in plasma lactate and pyruvate concentrations, or subjective judgment scores, after bathing at rest in 9 healthy young men. Subjects were immersed for 10 minutes in DSW, surface seawater (SSW), and tap water (TW) heated to 42 degrees C. Plasma samples were collected before bathing, immediately after bathing, and 60 minutes after bathing. The scores were obtained by an oral comprehension test. In the DSW bathing, plasma lactate and pyruvate concentrations showed no significant changes immediately after bathing or 60 minutes after bathing. In contrast, subjects who bathed in SSW showed a significant decrease in lactate concentrations 60 minutes after bathing compared with immediately after bathing. Subjects who bathed in TW showed a significant increase in lactate concentrations immediately after bathing compared with before bathing, and they showed a significant decrease in lactate and pyruvate concentrations 60 minutes after bathing. We found no significant change in the thermal sensation score in the DSW bathing, though significant differences were found between before and immediately after bathing in the SSW and TW groups. Moreover, the score decreased significantly 60 minutes after bathing compared to immediately after bathing in the TW bathing. Higher concentrations of salts contained DSW such as sodium, nitrate-nitrogen, phosphate-phosphorus, and silicate-silicon may have a good influence on human health. Although additional studies are needed to support our findings, DSW is the mildest water to the human body among the three kinds of water, since no significant changes in the items measured were found only in DSW.

Efeitos metabólicos da L-alanil-glutamina em ratos submetidos à isquemia da pata traseira esquerda seguida de reperfusão

OBJETIVO: Objetivou-se investigar os efeitos metabólicos da L-alanil glutamina no tecido muscular e sangue arterial de ratos Wistar submetidos à isquemia aguda da pata traseira. MÉTODOS: Utilizaram-se 48 ratos machos distribuídos em 4 grupos (1- controle / 2 - experimento), redistribuídos em 2 subgrupos (n=06). Trinta minutos após a injeção de uma solução a 20% de L-alanil-glutamina (0,75mg/ grupo 2) ou solução salina (grupo 1) na veia jugular direita ocluiu-se a artéria ilíaca comum esquerda por 30 minutos, por pinçamento. Amostras musculares e de sangue arterial foram obtidas logo após a remoção da pinça (tempo 0) e 5, 15 e 30 mais tarde. RESULTADOS: Observou-se redução significativa (p &lt; 0,05) da concentração de glicose tissular no animal tratado 15 minutos após o início da reperfusão. Houve aumento significativo das concentrações de glicose (grupo 2) nos tempos 15 min e 30 min em relação ao tempo 0 min. Não houve diferença na glicemia entre os dois grupos. Estes achados sugerem uma maior utilização da glicose pelo músculo isquêmico, através do ciclo malato-aspartato. A ausência de diferenças entre as concentrações de piruvato tissular, comparando-se os 2 grupos poderia ser explicada pelo reduzido tempo de isquemia. CONCLUSÃO: A L-alanil-glutamina estimula a. maior utilização da glicose, via glicólise, pela ativação do ciclo lactato-malato.

Effects of Saccharomyces cerevisiae Culture and Saccharomyces cerevisiae Live Cells on In Vitro Mixed Ruminal Microorganism Fermentation

The objective of this study was to examine the effects of a Saccharomyces cerevisiae live cell product and a S. cerevisiae culture product on the in vitro mixed ruminal microorganism fermentation of ground corn, soluble starch, alfalfa hay, and Coastal bermudagrass hay. In the presence of ground corn, neither concentration (0.35 or 0.73g/L) of S. cerevisiae culture nor live cells had any effect on final pH, H2, CH4, propionate, or butyrate. The S. cerevisiae culture had no effect on acetate, but both concentrations of S. cerevisiae live cells decreased acetate and the acetate:propionate ratio. When soluble starch was the substrate, both concentrations of S. cerevisiae live cells and 0.73g/L of S. cerevisiae culture decreased the acetate:propionate ratio. Although the treatment effects were not statistically significant, both concentrations of live cells and 0.73g/L of the culture decreased lactate concentrations compared with the control incubations. When alfalfa hay served as the substrate, neither the S. cerevisiae culture nor the live cells had an effect on propionate, butyrate, or the acetate:propionate ratio. Both concentrations of S. cerevisiae culture decreased the final pH and in vitro dry matter disappearance, and the 0.73g/L treatment decreased the amount of acetate. However, both treatments of S. cerevisiae live cells increased final pH and decreased acetate and in vitro dry matter disappearance. Neither yeast treatment had much effect on the Coastal bermudagrass hay fermentations. In general, both S. cerevisiae supplements seemed to have similar effects on the mixed ruminal microorganism fermentation.

Changes in Lactate and Other Ions in Plaque and Saliva after a Fluoride Rinse and Subsequent Sucrose Administration

The purpose of this study was to examine plaque and saliva composition after a fluoride rinse and subsequent sucrose application. Fifteen subjects accumulated plaque for 48 h, and then rinsed with a fluoride rinse based on 228 µg/g (ppm) Na₂SiF₆ and some received no rinse. After 60 min, upper and lower buccal molar plaque samples and 1-min saliva samples were collected. The subjects then rinsed with 10% g/g sucrose solution, and 7 and 15 min later, a second and a third set of samples were collected. Plaque fluid and clarified saliva were then recovered from these samples by centrifugation, and the remaining plaque acid extracted. The plaque fluid, centrifuged saliva, and plaque extract samples were then analyzed using micro techniques for pH, free calcium, phosphate, organic acids (plaque fluid and saliva only) and fluoride. Considering both the fluoride rinse and no-rinse groups, the most notable compositional changes in saliva 7 min after the sucrose rinse were pH –0.40 unit, free calcium 0.42 mM, lactate 5.2 mM, phosphate –1.3 mM, and fluoride 2.8 µM; while in plaque fluid, the corresponding changes were pH –1.59 unit, free calcium 1.5 mM, lactate 35 mM, phosphate –1.6 mM and fluoride –26 µM. After sucrose rinsing, undersaturation was found with respect to dicalcium phosphate dihydrate in saliva and plaque fluid and with respect to tooth enamel in some plaque fluid samples. Plaque fluid composition appeared to be strongly influenced by salivary clearance, diffusive loss of ions into the water phase of the rinse, and lower jaw pooling of the sucrose and fluoride components of the rinses. After the experimental rinse, the fluoride concentration in plaque fluid [86 ± 22 mM (upper molar site), 162 ± 150 mM (lower molar site)], saliva (26 ± 18 mM), and whole plaque [99 ± 97 µg/g (upper molar site), 197 ± 412 µg/g (lower molar site)] was comparable to the values in previous studies using this rinse. These very high plaque fluid fluoride concentrations, compared with the ‘no-rinse’ samples, induced an approximately 0.3-unit increase in the plaque fluid pH 7 min after the sucrose rinse, a small decrease (approximately 20%) in lactate production and a modest increase in enamel saturation. Although these changes were all statistically significant, no correlation was found between the decrease in lactate concentration and plaque fluid fluoride, pH or whole plaque fluoride.

Relationship between partial inhibition of glycolysis and hemolysis after induction of gametocytogenesis in synchronous cultures of Plasmodium falciparum

In the present study, the low molecular-weight fraction of the culture supernatant of anti- Plasmodium falciparum antibody-producing hybridoma cells (HybSL) was used in synchronous culture with P. falciparum FVO strain. When synchronous cultures were treated with HybSL solution on day 5, gametocytogenesis was also induced. Gametocytes were consistently found from the third day after treatment and reached a peak on the fourth day. An increase in pH and hemoglobin concentrations and decrease in lactate concentrations were observed on the first day after treatment. These phenomena suggested that HybSL solution partially inhibited glycolysis of erythrocytes parasitized with schizonts and resulted in hemolysis of infected erythrocytes. On the other hand, the production of gametocytes did not increase in cultures treated with HybSL solution on day 4 of synchronous cultures in which ring forms were plentiful. Most ring forms were not killed by HybSL solution and quickly developed to trophozoites and schizonts rather than gametocytes. Consequently, it is assumed that ring forms on day 4 of synchronous cultures have finished differentiation into the asexual stage. The conversion of asexual parasites to gametocytes may be triggered only when late-stage trophozoites or early-stage schizonts are treated with HybSL solution.

MECHANISM OF DICHLOROACETATE-INDUCED HYPOLACTATEMIA IN HUMANS WITH OR WITHOUT CIRRHOSIS

Dichloroacetate (DCA) has been used as an experimental treatment for lactic acidosis because it lowers plasma lactic acid concentration. Three potential mechanisms could underlie the hypolactatemic action of DCA, but the dominant mechanism in vivo remains unclear. This study tested whether DCA-induced hypolactatemia occurs via decreased lactate production, increased lactate clearance, or decreased rate of glycolysis in healthy humans and in patients with end-stage cirrhosis. Cirrhosis is associated with decreased hepatic pyruvate dehydrogenase (PDH) content. Six healthy volunteers and 7 cirrhotic patients received a primed, constant infusion of 1-13C-pyruvate and 15N-alanine for 5 hours. DCA (35 mg/kg intravenously) was administered at 2 hours. Plasma isotopic enrichment was measured by gas chromatography/mass spectrometry (GC/MS), and exhaled CO2 enrichment by isotope ratio mass spectrometry. Pyruvate and alanine production rates (Ra) were determined by isotope dilution, and pyruvate oxidation calculated as 13CO2 production from 13C-pyruvate. Ra lactate was calculated as the difference between Ra pyruvate and its disposal by oxidation to CO2 and conversion to alanine. Baseline plasma lactate kinetics in cirrhotic patients did not differ from controls. DCA decreased lactate concentration in both groups by approximately 53%. DCA decreased glycolysis (Ra pyruvate) by 24%, increased the fraction of pyruvate oxidized to CO2 by 26%, and decreased pyruvate transamination to alanine by 25%. DCA also inhibited lactate production by 85%, but decreased plasma lactate clearance by 60% in both groups. DCA reduces plasma lactic acid concentration by inhibiting production, via stimulating pyruvate oxidation and inhibiting glycolysis, rather than increasing clearance. In addition, end-stage cirrhosis does not alter either the mechanism or the magnitude of the metabolic response to DCA.

A review of in vivo 1H magnetic resonance spectroscopy of cerebral ischemia in rats.

A number of metabolic alterations are initiated by cerebral ischemia including dramatic increases in lactate concentration, decreases in N-acetylaspartate, choline, and creatine concentrations, as well as changes in amino acid levels. A review of proton nuclear magnetic resonance spectroscopy studies of focal and global cerebral ischemia in rats is presented here. In particular, studies in neonatal rats have shown that a continued elevation of lactate levels without recovery after hypoxia-ischemia or a decrease in N-acetylaspartate concentration at any time are indicative of deleterious outcome. Studies of the effect of temperature on ischemic damage in a model of focal ischemia showed that outcome improved with mild hypothermia. Again, lack of recovery of lactate upon reperfusion was shown to be indicative of poor outcome. Dichloroacetic acid was used to treat rats with focal ischemic damage. Animals subjected to transient ischemia that were treated with dichloroacetic acid showed significant decreases in lactate concentration.

Polymyxin-dextran antiendotoxin pretreatment in an ovine model of normotensive sepsis.

To test the hypothesis that adult sheep pretreated with polymyxin-dextran and then made septic by cecal ligation and perforation would have fewer changes in microvascular integrity and cellular architecture in extrapulmonary organs. Prospective, randomized, double-blind, placebo-controlled animal study. An animal research facility in a university-affiliated hospital. Mature, male Suffolk sheep (32 to 67 kg). Animals with chronic indwelling catheters were pretreated with polymyxin B-dextran (6 mg/kg) or placebo (dextran) and an intra-abdominal focus of infection was then produced by cecal ligation and perforation. Treatment (polymyxin B or placebo) was continued every 8 hrs for 48 hrs. Forty-eight hours after randomization, the polymyxin B-dextran group manifested significantly less pyrexia (p = .04), higher mean arterial pressures (p = .02), less variable serum albumin concentrations (p = .05), and a trend toward decreased lactate concentrations (p = .10). Qualitative morphometry and semiquantitative scoring of tissue from gastrocnemius muscle demonstrated that polymyxin B-dextran-treated sheep had significantly increased total capillary (p = .04) and capillary luminal areas (p = .038) and less mitochondrial swelling and damage (p = .03) compared with the placebo sheep. Pretreatment of sheep in a polymicrobial, peritonitis model of sepsis with polymyxin B-dextran resulted in a significant amelioration of sepsis-induced ultrastructural damage. In placebo-treated control animals, these ultrastructural lesions were associated with a greater severity of sepsis, as measured by the presence of pyrexia, increased lactate concentrations, and less stable blood pressures. These findings justify the investigation of the effects of polymyxin B-dextran in a post onset model of sepsis.

Influence of non-essential amino acids on apoptotic and necrotic death of mouse hybridoma cells in batch cultures

Supplementing a medium with non-essential amino acids results in an increased membrane stability during the death phase of a batch hybridoma culture (determined by Trypan Blue). The effect can only be seen when the amino acids are added at the beginning of the culture. This then leads to a different metabolism resulting in a decreased lactate concentration and an increased antibody secretion during the death phase. Surprisingly the addition of the amino acids has no effect on the determined viability (acridine orange and propidium iodine staining).