Heterogeneous effect of increasing spinal cord perfusion pressure on sensory evoked potentials recorded from acutely injured human spinal cord.

PURPOSE: To investigate the effect of increasing spinal cord perfusion pressure (SCPP) on sensory evoked potentials (SEPs) and injury site metabolism in patients with severe traumatic spinal cord injury TSCI. MATERIALS AND METHODS: In 12 TSCI patients we placed a pressure probe, a microdialysis catheter and a strip electrode with 8 contacts on the surface of the injured cord. We monitored SCPP, lactate-to-pyruvate ratio (LPR) and SEPs (after median or posterior tibial nerve stimulation). RESULTS: Increase in SCPP by ~20 mmHg produced a heterogeneous response in SEPs and injury site metabolism. In some patients, SEP amplitudes increased and the LPR decreased indicating improved tissue metab olism. In others, SEP amplitudes decreased and the LPR increased indicating more impaired metabolism. Compared with patients who did not improve at follow-up, those who improved had significantly more electrode contacts with SEP amplitude increase in response to increasing SCPP. CONCLUSIONS: Increasing SCPP after acute, severe TSCI may be beneficial (if associated with increase in SEP amplitude) or detrimental (if associated with decrease in SEP amplitude). Our findings support individualized management of patients with acute, severe TSCI guided by monitoring from the injury site rather than applying universal blood pressure targets as is current clinical practice.

Investigating the effects of lycopene and green tea on the metabolome of men at risk of prostate cancer: The ProDiet randomised controlled trial.

Lycopene and green tea consumption have been observationally associated with reduced prostate cancer risk, but the underlying mechanisms have not been fully elucidated. We investigated the effect of factorial randomisation to a 6-month lycopene and green tea dietary advice or supplementation intervention on 159 serum metabolite measures in 128 men with raised PSA levels (but prostate cancer-free), analysed by intention-to-treat. The causal effects of metabolites modified by the intervention on prostate cancer risk were then assessed by Mendelian randomisation, using summary statistics from 44,825 prostate cancer cases and 27,904 controls. The systemic effects of lycopene and green tea supplementation on serum metabolic profile were comparable to the effects of the respective dietary advice interventions (R2 = 0.65 and 0.76 for lycopene and green tea respectively). Metabolites which were altered in response to lycopene supplementation were acetate [ß (standard deviation difference vs. placebo): 0.69; 95% CI = 0.24, 1.15; p = 0.003], valine (ß: -0.62; -1.03, -0.02; p = 0.004), pyruvate (ß: -0.56; -0.95, -0.16; p = 0.006) and docosahexaenoic acid (ß: -0.50; -085, -0.14; p = 0.006). Valine and diacylglycerol were lower in the lycopene dietary advice group (ß: -0.65; -1.04, -0.26; p = 0.001 and ß: -0.59; -1.01, -0.18; p = 0.006). A genetically instrumented SD increase in pyruvate increased the odds of prostate cancer by 1.29 (1.03, 1.62; p = 0.027). An intervention to increase lycopene intake altered the serum metabolome of men at risk of prostate cancer. Lycopene lowered levels of pyruvate, which our Mendelian randomisation analysis suggests may be causally related to reduced prostate cancer risk.

The ginseng's fireness is associated with the lowering activity of liver Na(+)-K(+)-ATPase.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng is an herbal medicine used worldwide that possesses a wide range of pharmacological activities. However, its side effects are rarely discussed. The experience of Chinese medicine has revealed that taking ginseng at a high dose chronically can cause fireness, i.e., the ginseng-abuse syndrome. Here, we explored the mechanism of ginseng's fireness by comparing the energy metabolism of mice affected by red ginseng (RG), ginseng (GS), ginseng leaves (GL) and American ginseng (AG), which exhibit different drug properties according to the theory of TCM. MATERIALS AND METHODS: KM mice were randomly divided into five groups (n≥30 per group) and administered distilled water or drugs, respectively. Mice receiving RG, GS, or GL received 4.5g/(kgday), while the mice receiving AG received 3g/(kgday). Control mice received distilled water. The duration of exposure for all groups was 31 days. The mice's physical characteristics, such as eye condition, rectal temperature, saliva secretion, urine, stool weight, blood coagulation time and swimming time, were measured at different times after administration. Energy metabolism indexes were measured via TSE phenoMaster/LabMaster animal monitoring system, including the mice' 24h oxygen consumption (VO2), carbon dioxide production (VCO2), heat production (H) and energy expenditure (EE). Biochemical indices were measured by ultraviolet spectrophotometer and microplate reader, including pyruvic acid content in serum and succinate dehydrogenase (SDH) activity, lactate dehydrogenase (LDH) activity, the Na(+)-K(+)-ATPase activity and the content of glycogen in the liver tissue. RESULTS: After 31 days of drug administration, mice in the RG and GS groups exhibited obviously more eye secretions, less saliva secretion and less urine. Compared with the control group, the swimming times of mice in the GS, AG and GL groups were significantly prolonged; the clotting time of mice in the GL was extended significantly; VCO2, H and EE of mice in the GS group were obviously increased; Pyruvate content of mice in the RG group showed an initial decrease followed by an increase; SDH activity of mice in the AG and GL groups was significantly inhibited; LDH activity of the mice showed no significant difference among different groups; Na(+)-K(+)-ATP enzyme activity of the RG and GS groups showed up-regulation initially and then down-regulation; the content of hepatic glycogen of mice in the GS and GL groups increased significantly. CONCLUSION: The results demonstrated that RG and GS with their warm drug nature could enhance the body's energy metabolism to produce their dryness to the body. The liver Na(+)-K(+)-ATP enzyme activity may be the primary index for indicating the fireness of ginseng. In addition, our results demonstrated that ginseng, especially red ginseng, is not suitable for long time application with a higher dose.

Riboflavin supplementation improves energy metabolism in mice exposed to acute hypoxia.

This study investigated the effects of riboflavin on energy metabolism in hypoxic mice. Kunming mice were fed diets containing riboflavin at doses of 6, 12, 24 and 48 mg/kg, respectively for 2 weeks before exposure to a simulated altitude of 6000 m for 8 h. Changes of riboflavin status and energy metabolism were assessed biochemically. Simultaneously, a (1)H nuclear magnetic resonance (NMR) based metabolomic technique was used to track the changes of plasma metabolic profiling. It was found that the content of hepatic riboflavin was decreased and erythrocyte glutathione activation coefficient was elevated significantly under hypoxic condition. Meanwhile, increased plasma pyruvate, lactate, beta-hydroxybutyrate and urea, as well as decreased plasma carnitine were observed. Riboflavin supplementation improved riboflavin status remarkably in hypoxic mice and decreased plasma levels of pyruvate, free fatty acids and beta-hydroxybutyrate significantly. Plasma carnitine was increased in response to riboflavin supplementation. Results obtained from (1)H NMR analysis were basically in line with the data from biochemical assays and remarkable changes in plasma taurine, choline and some other metabolites were also indicated. It was concluded that riboflavin requirement was increased under acute hypoxic condition and riboflavin supplementation was effective in improving energy metabolism in hypoxic mice.

Combination of LC-MS- and GC-MS-based metabolomics to study the effect of ozonated autohemotherapy on human blood.

Ozonated autohemotherapy (O3-AHT) is a medical approach during which blood obtained from the patient is ozonated and injected back into the body. Despite an increasing number of evidence that O3-AHT is safe, this type of therapy remains controversial. To extend knowledge about the changes in blood evoked by O3-AHT, LC-MS- and GC-MS-based metabolic fingerprinting was used to compare plasma samples obtained from blood before and after the treatment with potentially therapeutic concentrations of ozone. The procedure was performed in PVC bags utilized for blood storage to study also possible interactions between ozone and plastic. By use of GC-MS, an increase in lactic acid and pyruvic acid was observed, which indicated an increased rate of glycolysis. With LC-MS, changes in plasma antioxidants were observed. Moreover, concentrations of lipid oxidation products (LOP) and lysophospholipids were increased after ozone treatment. This is the first report of increased LOPs metabolites after ozonation of blood. Seven metabolites detected by LC-QTOF-MS only in ozonated samples could be considered as novel biomarkers of oxidative stress. Several plasticizers have been detected by both techniques in blood stored in PVC bags. PVC is known to be an ozone resistant material, but ozonation of blood in PVC bags stimulates leaching of plasticizers into the blood.

[Plasma metabonomics study of ischemic cerebral apoplexy rats treated with Tongsaimai pellets].

OBJECTIVE: To observe abnormal metabolic changes caused by ischemic cerebral apoplexy and the regulating action of Tongsaimai pellets on abnormal metabolism by analyzing the change of small molecules in plasma of ischemic cerebral apoplexy rat. To find the potential biomarkers, and to explore metabolic mechanisms of Tongsaimai pellets. METHOD: Rat models of middle cerebral artery occlusion was established with electric coagulation, and rats were divided into 4 groups, model group, sham-operation group, Tongsaimai pellets group and positive control group. Tongsaimai pellets and positive control group were orally administrated by 13.2 g x kg(-1) x d(-1) of crude drugs and 32 mg x kg(-1) x d(-1) of Nimodipine respectively, m odel and sham-operation group by equal volume of distilled water for a week. Plasma of model and sham-operation group were collected, and plasma of Tongsaimai pellets and positive control group were collected on the 1st, 3rd , 7th day after administration. Endogenous metabolites of four groups were determined with GC-MS. Partial least squares discriminant analysis (PLS-DA) was applied to analyze multivariate data and set up model, and T-test was used in significant statistical analysis. RESULT: Compared with sham-operation group rats, pyruvic acid, taurine and hydroxyproline obviously increased in model group rats, while lactic acid, glyceric acid, aminomalonic acid, fructose, tryptophan and leucine significantly decreased, so these metabolites were potential metabolic biomarkers. These endogenous metabolites except taurine got restoration in Tongsaimai group rats. CONCLUSION: Abnormal metabolite level in plasma can be certainly recovered by Tongsaimai pellets, and the treatment of Tongsaimai pellets can be connected with the regulation of related metabolic pathways.

Beneficial effect of pyruvate therapy on Leigh syndrome due to a novel mutation in PDH E1α gene.

Leigh syndrome (LS) is a progressive untreatable degenerating mitochondrial disorder caused by either mitochondrial or nuclear DNA mutations. A patient was a second child of unconsanguineous parents. On the third day of birth, he was transferred to neonatal intensive care units because of severe lactic acidosis. Since he was showing continuous lactic acidosis, the oral supplementation of dichloroacetate (DCA) was introduced on 31st day of birth at initial dose of 50 mg/kg, followed by maintenance dose of 25 mg/kg/every 12 h. The patient was diagnosed with LS due to a point mutation of an A-C at nucleotide 599 in exon 6 in the pyruvate dehydrogenase E1α gene, resulting in the substitution of aspartate for threonine at position 200 (N200T). Although the concentrations of lactate and pyruvate in blood were slightly decreased, his clinical conditions were deteriorating progressively. In order to overcome the mitochondrial or cytosolic energy crisis indicated by lactic acidosis as well as clinical symptoms, we terminated the DCA and administered 0.5 g/kg/day TID of sodium pyruvate orally. We analyzed the therapeutic effects of DCA or sodium pyruvate in the patient, and found that pyruvate therapy significantly decreased lactate, pyruvate and alanine levels, showed no adverse effects such as severe neuropathy seen in DCA, and had better clinical response on development and epilepsy. Though the efficacy of pyruvate on LS will be evaluated by randomized double-blind placebo-controlled study design in future, pyruvate therapy is a possible candidate for therapeutic choice for currently incurable mitochondrial disorders such as LS.

Substrate oxidation and cardiac performance during exercise in disorders of long chain fatty acid oxidation.

BACKGROUND: The use of long-chain fatty acids (LCFAs) for energy is inhibited in inherited disorders of long-chain fatty acid oxidation (FAO). Increased energy demands during exercise can lead to cardiomyopathy and rhabdomyolysis. Medium-chain triglycerides (MCTs) bypass the block in long-chain FAO and may provide an alternative energy substrate to exercising muscle. OBJECTIVES: To determine the influence of isocaloric MCT versus carbohydrate (CHO) supplementation prior to exercise on substrate oxidation and cardiac workload in participants with carnitine palmitoyltransferase 2 (CPT2), very long-chain acyl-CoA dehydrogenase (VLCAD) and long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiencies. DESIGN: Eleven subjects completed two 45-minute, moderate intensity, treadmill exercise studies in a randomized crossover design. An isocaloric oral dose of CHO or MCT-oil was administered prior to exercise; hemodynamic and metabolic indices were assessed during exertion. RESULTS: When exercise was pretreated with MCT, respiratory exchange ratio (RER), steady state heart rate and generation of glycolytic intermediates significantly decreased while circulating ketone bodies significantly increased. CONCLUSIONS: MCT supplementation prior to exercise increases the oxidation of medium chain fats, decreases the oxidation of glucose and acutely lowers cardiac workload during exercise for the same amount of work performed when compared with CHO pre-supplementation. We propose that MCT may expand the usable energy supply, particularly in the form of ketone bodies, and improve the oxidative capacity of the heart in this population.

Cassava root diet induces low pyruvate levels.

The high cyanogenic-glucoside carbohydrate of the cassava root (Manihot esculenta) has special properties that make it an ideal therapeutic food for lowering nicotinamide adenine dinucleotide reduced form (NADH) and inducing Sirtuin (Sirt) gene overexpression when eaten in an exclusive mono-food diet regime. The author, using himself as the sole test subject, repeatedly induced low pyruvate levels (reflective of NADH levels) after being on the diet for 1-2 weeks at a time. The possible influences of exclusive cassava dieting on redox control and Sirtuin activation will be discussed.

Thiamine supplementation increases serum thiamine and reduces pyruvate and lactate levels in burn patients.

The importance of vitamins for optimal metabolism is well established. However, currently little is known about the optimal vitamin levels required for burn patients. As a consequence, current practice both for macronutrient supplementation and vitamin supplementation varies widely between burn units. A better understanding of the effects of vitamins on metabolism may lead to better nutrition and subsequently improved outcomes for burn patients. Thiamine is an important co-factor required for multiple enzymes involved in carbohydrate metabolism. We have examined the levels of thiamine (B1) in burn patients as well as the effects of thiamine supplementation on the levels of serum thiamine, pyruvate and lactate. Twenty patients had blood samples taken on the day of admission, then on days 1, 3, and 7 post-admission and weekly thereafter until discharge. Of these, nine received enteral feeding. Six patients received thiamine supplementation. Serum thiamine, pyruvate and lactate levels were measured at each time point. Serum thiamine levels increased significantly with thiamine supplementation (p<0.001). Serum thiamine levels also increased with time of supplementation (p<0.001). Serum thiamine level was closely associated with pyruvate and lactate levels, with a decrease in both pyruvate and lactate associated with increased serum thiamine. Lastly, pyruvate and lactate levels appear closely associated in a linear relationship. This study suggests thiamine supplementation increases serum thiamine and that this increase is associated with a decrease in pyruvate and lactate levels. Further study of changes in metabolic flux associated with thiamine supplementation and a randomised control trial of thiamine supplementation are required to establish whether thiamine supplementation is beneficial to burn patients' metabolism and recovery.

Alpha-tocopherol supplementation prevents the exercise-induced reduction of serum paraoxonase 1/arylesterase activities in healthy individuals.

OBJECTIVE: To investigate PON 1/Aryl activities in basketball players with or without alpha-T supplementation pre- and post-training. Vitamin E (alpha-tocopherol, alpha-T) reduces lipid peroxidation. Paraoxonase 1/arylesterase (PON 1/Aryl) activities are closely related to oxidation and atherogenesis. SUBJECT/METHODS: Blood was obtained from 10 players pre- (group A), post-exercise (group B) and after 1 month on alpha-T (200 mg per 24 h orally) supplementation pre- (group C) and post-exercise (group D). Lactate, pyruvate, muscle enzyme activities, creatine kinase, lactate dehydrogenase and total antioxidant status (TAS) were measured with commercial kits. Catecholamines and alpha-T were determined with high-performance liquid chromatography methods and PON 1/Aryl activities spectrophotometrically. RESULTS: Lactate, pyruvate, muscle enzyme activities and catecholamines were increased (P<0.001) in all groups post-training. Alpha-T levels remained unaltered pre- vs post-exercise. TAS was decreased in all the groups post training. PON 1/Aryl activities were significantly decreased post-exercise (group B) (PON1: 65+/-12 U min(-1) ml(-1), Aryl: 58+/-14 KU min(-1) ml(-1)) as compared to those pre-exercise (group A) (PON1: 142+/-16 U min(-1) ml(-1), Aryl: 114+/-12 KU min(-1) ml(-1), P<0.001). In contrast, the studied enzyme activities remained practically unaltered after alpha-T supplementation pre- vs post-training. Both enzyme activities positively correlated to TAS (r=0.60, P<0.001). CONCLUSIONS: Alpha-T supplementation may result in protection of the enzyme PON 1/Aryl activities from free radical production.

The in vivo and in vitro effects of L-carnitine supplementation on the erythrocyte membrane acetylcholinesterase, Na+, K+-ATPase and Mg2+-ATPase activities in basketball players.

BACKGROUND: We investigated whether the activities of erythrocyte membrane acetylcholinesterase (AChE), Na+, K+-ATPase and Mg2+-ATPase are modulated in basketball players pre- vs. post-forced training with or without L-carnitine (L-C) supplementation. METHODS: Blood was obtained from 10 male players pre-game (group A) and post-game (group B) and after 1 month L-C supplementation (2 g/24 h orally) pre-training (group C) and post-training (group D). Lactate, pyruvate and total antioxidant status (TAS) were measured with commercial kits, catecholamines with HPLC and the enzyme activities spectrophotometrically. RESULTS: Lactate, pyruvate, AChE, Na+, K+-ATPase and catecholamines were increased (p<0.001) and TAS was decreased (p<0.001) in group B. In contrast, TAS remained unaltered and the all enzyme activities were reduced (p<0.001) in group D at the same time of study. Mg2+-ATPase activity remained unchanged. In vitro incubation of the modulated AChE and Na+, K+-ATPase with L-C (25 microM) from group B and group D resulted in a non-significant reduction of the enzymes in group B and complete restoration of their activities in group D. CONCLUSIONS: The increase of AChE and Na+, K+-ATPase activities may be due to the elevation of catecholamines in group B. Carnitine utilization by the muscles during training may result in a reduction of the enzyme activities (group D). The latter is supported by the recovery of the enzyme activities after incubation of the membranes from group D with L-C.

Effects of magnesium sulfate on dynamic changes of brain glucose and its metabolites during a short-term forced swimming in gerbils.

This investigation examined the acute effects of magnesium on the dynamic changes of brain glucose, lactate, pyruvate and magnesium levels in conscious gerbils during forced swimming. Gerbils were pretreated with saline (control group) and magnesium sulfate (90 mg kg(-1), intraperitoneal injection) before a 15 min forced swimming period. The basal levels of glucose, pyruvate, lactate, and magnesium in brain dialysates were 338 +/- 18, 21 +/- 2, 450 +/- 39, and 2.1 +/- 0.1 microM, respectively, with no significant difference between groups. Magnesium levels were found slightly higher (but not significant) in the magnesium-treated group. However, brain glucose and pyruvate levels in the control group decreased to about 50 and 60% of the basal level (P = 0.01) after swimming, respectively. Pretreatment with magnesium sulfate immediately increased glucose levels to about 140% of the basal level, and increased pyruvate levels to about 150% of the basal level during forced swimming (P = 0.01). Both glucose and pyruvate levels returned to the basal level after 30 min of the recovery. The lactate levels of the control group increased to about 160% of the basal level (P = 0.01) during swimming, whereas pretreatment with magnesium sulfate attenuated lactate levels to 130% of the basal level (P = 0.01). Magnesium supplementation may be beneficial because it provides an additional glucose source and may also promote the recovery of energy substrates in the brain during and after forced exercise. In order to achieve optimal physical performance, further investigation as to dosage of magnesium supplementation is needed.

Dynamic change in energy metabolism by electroacupuncture stimulation in rats.

The electrical stimulation of meridian points in rats inhibits the withdrawal reflex of the nociceptive tail. Its pain mechanisms are well-documented. Moreover, electroacupuncture (EA) at special abdominal acupoints has been shown to induce a short-term hypoglycemia effect in streptozotocin diabetic rats. The Zusanli and Zhongwan acupoints have been widely used in traditional Chinese medicine to relieve symptoms of diabetes mellitus. It is still unclear whether they can affect extracellular glucose and lactate metabolites at the cellular level. The aim of this study is to evaluate these effects using a rat model for the analysis of extracellular neurochemicals. First, electrical stimulus of 2 ms 2 Hz square pulses (30 minutes) was applied to anesthetized intact rats (n = 7) at the Zusanli points. One and a half hours later, a second electrical stimulus (2 Hz pulses, 30 minutes) was delivered to two of the rats at the same spot. Another two rats received a different stimulation (100 Hz pulses, 30 minutes) at the same location. In the final three rats, a second electrical stimulus of 2 Hz pulses was delivered to non-acupoints. An automated micro-blood sample collector was used to examine the glucose, pyruvate and lactate concentrations. The EA signal has an influence on the biologic process of energy metabolism by mediating dynamic extracellular neurochemical changes. The EA at limb acupoints of the lower limbs induces a decrease in glucose, an increase in lactate metabolites and a decrease in the lactate/glucose ratio. Moreover, the increased lactate/glucose ratio suggests that the cell has an increased anaerobic glucose metabolism.

Effects of calcium pyruvate supplementation during training on body composition, exercise capacity, and metabolic responses to exercise.

OBJECTIVE: We evaluated the effects of calcium pyruvate supplementation during training on body composition and metabolic responses to exercise. METHODS: Twenty-three untrained females were matched and assigned to ingest in a double blind and randomized manner either 5 g of calcium pyruvate (PYR) or a placebo (PL) twice daily for 30 d while participating in a supervised exercise program. Prior to and following supplementation, subjects had body composition determined via hydrodensiometry; performed a maximal cardiopulmonary exercise test; and performed a 45-min walk test at 70% of pre-training VO2 max in which fasting pre- and post exercise blood samples determined. RESULTS: No significant differences were observed between groups in energy intake or training volume. Univariate repeated measures ANOVA revealed that subjects in the PYR group gained less weight (PL 1.2 +/- 0.3, PYR 0.3 +/- 0.3 kg, P = 0.04), lost more fat (PL 1.1 +/- 0.5; PYR -0.4 +/- 0.5 kg, P = 0.03), and tended to lose a greater percentage of body fat (PL 1.0 +/- 0.7; PYR -0.65 +/- 0.6%, P = 0.07), with no differences observed in fat-free mass (PL 0.1 +/- 0.5; PYR 0.7 +/- 0.3 kg, P = 0.29). However, these changes were not significant when body composition data were analyzed by MANOVA (P = 0.16). There was some evidence that PYR may negate some of the beneficial effects of exercise on HDL values. No significant differences were observed between groups in maximal exercise responses or metabolic responses to submaximal walking. CONCLUSIONS: Results indicate that PYR supplementation during training does not significantly affect body composition or exercise performance and may negatively affect some blood lipid levels.

Biochemical changes elicited by isosaline leaf and stem-bark extracts of Harungana madagascariensis in the rat.

Isosaline leaf and stem-bark extracts of Harungana madagascariensis (L) administered intraperitoneally into healthy albino rats of the Sprague-Dawley strain at a dose of 400 mg/kg body weight resulted in a significant elevation of liver, kidney and serum alanine and aspartate aminotransferase activities. Serum urea, total proteins, total triglyceride, cholesterol, pyruvate and lactate were also significantly elevated in the treated rats. While the stem-bark extract significantly increased the blood glucose level, the leaf extract significantly lowered it. However, both extracts significantly reduced supernatant protein concentrations of the liver and kidney. The significant increase in aminotransferase activities and the concomitant reduction in protein concentrations of the liver and kidney suggests increased catabolism of proteins in these organs, while the catabolites produced are probably channelled to other metabolic pathways resulting in the observed hyperpyruvicaemia, hypertriglyceridaemia and lactic acidaemia in the treated animals. The increased serum cholesterol also suggests a probable degenerative change that these extracts may have on membranes. The results obtained clearly indicate that these extracts alter metabolic activities in both the liver and kidney of treated rats and hence, should be employed in herbal preparations with caution.

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.

A randomized, controlled trial of parenteral glutamine in ill, very low birth-weight neonates.

OBJECTIVE: The role of "novel substrates" in neonatal nutrition has generated much interest in recent years. Glutamine has been recognized as a "conditionally essential" amino acid in critically ill adults, particularly for gut and immune function; however, its potential role in the neonate remains unclear. The authors examined the safety and benefits of parenteral glutamine in ill, preterm neonates. DESIGN: Randomized controlled trial. METHODS: Thirty-five ill preterm neonates of <1000 g birth-weight were randomized to receive either glutamine-supplemented parenteral nutrition (PN) (n = 17) or standard PN (n = 18). RESULTS: There were no significant differences in birth-weight, gestational age, male-to-female ratio, or Clinical Risk Index for Babies (CRIB) score between the two groups. During PN there were no significant differences between the groups in white cell count, differential white cell count, blood urea nitrogen, plasma ammonia, lactate, pyruvate, plasma glutamine, or glutamate. The median time to achieving full enteral nutrition (FEN) was shorter in the study group (13 days vs. 21 days, P < 0.05). The number of episodes of culture-positive sepsis or age at discharge did not differ between groups. CONCLUSIONS: Parenteral glutamine appears to be well tolerated and safe in the ill, preterm neonate. It may reduce the time to achieving FEN.

Does tissue oxygen-tension reliably reflect cerebral oxygen delivery and consumption?

We investigated the value of brain oxygen partial pressure (P(br)O(2)) with respect to predicting cerebral energetic failure in a rabbit model of global cerebral ischemia and hypoxia. Local cortical blood flow (l(co)CBF), P(br)O(2), extracellular lactate, pyruvate, and glutamate concentrations, as well as microvascular hemoglobin saturation (S(mv)O(2)), cytochrome oxidase redox level (Cyt a+a(3) oxidation), and brain electrical activity, were assessed during variable degrees of cerebral ischemia and hypoxia, induced by cisternal infusion of artificial cerebrospinal fluid or an admixture of nitrous oxide to inspiratory gas in 10 animals each. Arteriovenous difference in oxygen content, cerebral metabolic rate for oxygen, and oxygen extraction were derived from multimodal data. P(br)O(2), S(mv)O(2), and Cyt a+a(3) oxidation were closely related to cerebral blood flow and indices of oxidative metabolism. P(br)O(2) /=2.8 mL. 100 g(-1). min(-1), arteriovenous difference in oxygen content

Hepatic oxygen exchange and energy metabolism in hyperdynamic porcine endotoxemia: effects of the combined thromboxane receptor antagonist and synthase inhibitor DTTX30.

OBJECTIVE: We compared the effects of thromboxane receptor antagonist and synthase inhibitor DTTX30 on systemic and liver blood flow, oxygen (O2) exchange and energy metabolism during 24 h of hyperdynamic endotoxemia with untreated endotoxemia. DESIGN: Prospective, randomized, experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Twenty-seven domestic pigs: 16 during endotoxemia with volume resuscitation alone; 11 with endotoxemia, volume resuscitation and treatment with DTTX30. INTERVENTIONS: Continuous infusion of Escherichia coli lipopolysaccharide (LPS) for 24 h together with volume resuscitation. After 12 h of endotoxemia, DTTX30 was administered as a bolus of 0.12 mg kg-1 followed by 12 h continuous infusion of 0.29 mg kg-1 per h. MEASUREMENTS AND RESULTS: DTTX30 effectively counteracted the endotoxin-associated increase in TXB2 levels and increased 6-keto-PGF1 alpha with a significant shift of the thromboxane/prostacyclin ratio towards predominance of prostacyclin. DTTX30 prevented the significant progressive endotoxin-induced decrease of mean arterial pressure (MAP) below baseline while maintaining cardiac output (CO), and increased the fractional contribution of liver blood flow to CO without an effect on either hepatic O2 delivery or O2 uptake. The mean capillary hemoglobin O2 saturation (HbO2) on the liver surface and HbO2 frequency distributions remained unchanged as well. CONCLUSIONS: DTTX30 significantly attenuated the endotoxin-induced derangements of cellular energy metabolism as reflected by the diminished progressive decrease in hepatic lactate uptake rate and a blunted increase in hepatic venous lactate/pyruvate ratios. While endotoxin significantly increased the endogenous glucose production (EGP) rate, EGP returned towards baseline levels in the DTTX30-treated group. Thus, in our model DTTX30 resulted in hemodynamic stabilization concomitant with improved hepatic metabolic performance.