High Levels Of Taurine Research Articles

Abstract 101: PHLPP Inhibitory Peptide Administered During CPR Improves Survival After Prolonged Cardiac Arrest

Introduction: Active cooling is more effective than targeted temperature management in improving sudden cardiac arrest (SCA) survival, but can be difficult to implement clinically. We are developing drugs that mimic cooling effects without the need for physical cooling. Cooling protection is mediated by Akt activation. PH domain and Leucine rich repeat Protein Phosphatases (PHLPP) is a phosphatase that negatively regulates Akt. We developed a cell-permeable peptide TAT-PHLPP9c that inhibits PHLPP and reaches heart and brain within 5 min of intravenous administration. Hypothesis: We hypothesize that TAT-PHLPP9c improves outcomes following SCA. This protection involves the improved early metabolic recovery. Methods: C57BL6 mice (n=20) were randomized to receive peptide treatment and appropriate blinding was ensured. A 12 min asystolic arrest was induced with KCl. CPR was started along with TAT-PHLPP9c (7.5 mg/kg) via i.v. Survival was evaluated. Cerebral blood flow (CBF) and metabolic chemical exchange saturation transfer (CEST) contrast were measured with endogenous and dynamic arterial spin labeling (ASL) and CEST MRI respectively. Glucose utilization was assessed by pyruvate dehydrogenase (PDH) phosphorylation and ATP generation. Further, blood taurine and glutamate were measured. Results: Compared to control, TAT-PHLPP9c significantly improved ROSC rates. 3 ROSC mice in the control group died within 10 min while 8 out of 10 ROSC mice in the treatment group survived over 1 h and 4 mice survived to 4 h despite a 12-min arrest. Progressively increased CBF and metabolic CEST contrast were observed in the treated mice compared to controls. p-PDH was decreased by TAT-PHLPP9c (increased activity) at 15 min post-ROSC in both heart and brain. ATP generation was replenished with the peptide treatment. Plasma taurine and glutamate concentrations was reduced by TAT-PHLPP9c as early as 5 min post-ROSC. Further, higher levels of taurine and glutamate were detected in the non-survivors than the survivors. Conclusions: This novel treatment strategy may have a high translational potential to reproduce critical outcomes of CPR cooling without physical cooling.

Taurine supplementation to anti-seizure drugs as the promising approach to treat pharmacoresistant epilepsy: A pre-clinical study

BackgroundPharmacoresistance leads to severe, irreversible disabilities and premature death in ∼30% cases of epilepsy despite adequate and appropriate treatment with available anti-seizure drugs (ASDs) without any underlying cause. In light of the large body of evidence which suggests the anti-seizure action of taurine in experimental animals and its wide safety margins in human, supplementation of this inhibitory amino-sulfonic acid to available ASDs seems promising to treat pharmacoresistant epilepsy. MethodsWe examined the anti-seizure effect of lamotrigine (15mg/kg), levetiracetam (40mg/kg), carbamazepine (40mg/kg), phenytoin (35mg/kg) & taurine (50, 100 & 200mg/kg) in lamotrigine pre-treated pentylenetetrazole-kindled mice (LPK) which mimic core features of pharmacoresistant epilepsy, either alone ASDs or in combinations whereby three different doses of taurine were supplemented with tested ASDs. ResultsBoth, the ASDs and the taurine were failed to suppress generalized tonic-clonic seizures in LPK mice. However, taurine supplementation clearly restored the anti-seizure effect of tested ASDs. Further neurochemical studies revealed that higher levels of taurine in the hippocampus and cerebral cortex restored the imbalance between major excitatory neurotransmitters glutamate & its inhibitory counterpart GABA. ConclusionsThese findings emphasize that supplementation of taurine with ASDs may be useful to treat pharmacoresistant epilepsy. Thus, further clinical validation is encouraged.

Prognostic and clinicopathological role of long non-coding RNA taurine upregulated 1 in various human malignancies: A systemic review and meta-analysis.

The aberrant dysregulation of taurine upregulated 1, a novel discovered long non-coding RNA, was ubiquitous in different human solid tumors. Accumulating researches have indicated that taurine upregulated 1 is an independent prognostic indicator in cancer patients. This investigation aimed to further explore the prognostic and clinical significance of taurine upregulated 1 in various types of cancers. Eligible studies were systematically searched in PubMed, Embase, Medline, and Web of Science databases. A total of 12/14 studies with 1303/1228 individuals were included to evaluate the association of taurine upregulated 1 with overall survival and clinicopathological features by pooled hazard ratio and odds ratio in malignancies. The meta-analysis suggested overexpression of taurine upregulated 1 was significantly correlated with unfavorable overall survival in patients with cancer (pooled hazard ratio = 1.63, 95% confidence interval: 1.29-2.06). There was also a significantly positive correlation between high level of taurine upregulated 1 and high pathological grade carcinoma (pooled odds ratio = 4.41, 95% confidence interval: 3.07-6.43) and positive lymphatic metastasis (pooled odds ratio = 2.00, 95% confidence interval: 1.31-3.06). In summary, upregulated taurine upregulated 1 is correlated with more advanced clinicopathological characteristics and poor prognosis, suggesting that taurine upregulated 1 may serve as a novel predictive biomarker of patients with numerous tumors.

Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats.

Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM). Proton Nuclear Magnetic Resonance (1H-NMR) spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese–diabetic (obdb) rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract.

Plasma Taurine, Diabetes Genetic Predisposition, and Changes of Insulin Sensitivity in Response to Weight-Loss Diets.

Taurine metabolism disturbance is closely linked to obesity, insulin resistance, and diabetes. Previous evidence suggested that the preventative effects of taurine on diabetes might be through regulating the expression levels of diabetes-related genes. We estimated whether blood taurine levels modified the overall genetic susceptibility to diabetes on improvement of insulin sensitivity in a randomized dietary trial. We genotyped 31 diabetes-associated variants to calculate a genetic risk score (GRS) and measured plasma taurine levels and glycemic traits among participants from the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial. Seven-hundred eleven overweight or obese participants (age 30-70 y; 60% females) had genetic variants genotyped and blood taurine levels measured. Participants went on 2-year weight-loss diets, which were different in macronutrient composition. Improvements in glycemic traits were measured. We found that baseline taurine levels significantly modified the effects of diabetes GRS on changes in fasting glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) during the 2-year diet intervention (P-interaction = .04, .01, .002, respectively), regardless of weight loss. High baseline taurine levels were associated with a less reduction in both glucose and HOMA-IR among the participants with the lowest tertile of diabetes GRS (both P = .02), and with a greater reduction in both insulin and HOMA-IR among those with the highest tertile of diabetes GRS (both P = .04). Our data suggest that blood taurine levels might differentially modulate the effects of diabetes-related genes on improvement of insulin sensitivity among overweight/obese patients on weight-loss diets.

TonEBP modulates the protective effect of taurine in ischemia-induced cytotoxicity in cardiomyocytes.

Taurine, which is found at high concentration in the heart, exerts several protective actions on myocardium. Physically, the high level of taurine in heart is maintained by a taurine transporter (TauT), the expression of which is suppressed under ischemic insult. Although taurine supplementation upregulates TauT expression, elevates the intracellular taurine content and ameliorates the ischemic injury of cardiomyocytes (CMs), little is known about the regulatory mechanisms of taurine governing TauT expression under ischemia. In this study, we describe the TonE (tonicity-responsive element)/TonEBP (TonE-binding protein) pathway involved in the taurine-regulated TauT expression in ischemic CMs. Taurine inhibited the ubiquitin-dependent proteasomal degradation of TonEBP, promoted the translocation of TonEBP into the nucleus, enhanced TauT promoter activity and finally upregulated TauT expression in CMs. In addition, we observed that TonEBP had an anti-apoptotic and anti-oxidative role in CMs under ischemia. Moreover, the protective effects of taurine on myocardial ischemia were TonEBP dependent. Collectively, our findings suggest that TonEBP is a core molecule in the protective mechanism of taurine in CMs under ischemic insult.

The effects of taurine administration against inflammation in heavily exercised skeletal muscle of rats.

AbstractTaurine protects against tissue damage in a variety of models that share inflammation as a common pathogenic feature. Heavy exercise has been shown to cause inflammation and oxidative stress and to damage muscle tissue. High taurine levels are present in skeletal muscle and may play a role as a cellular defense against free radical-mediated damage. The aim of this study was to determine whether taurine injected in the abdomen alters markers of inflammation and free radical damage after varying degrees of heavy exercise. The effect of intra-abdominal administration of taurine 1 h before heavy exercise was examined. On a daily basis for 10 consecutive days, a speed of 20 m/min for 20 min. Muscle damage was associated with an increase in IL-6 and CD68 of the skeletal muscle. The immunoreactivities for IL-6 and CD68 are shown increase in the 20 min heavy exercise group. The increase in IL-6 and CD68 was suppressed in the 20 min heavy exercise group that received an intra-abdominal injection of taurine. Data from this study show that exercise-induced muscle inflammation is reduced in SOL and EDL of rats treated with taurine prior to exercise.KeywordsSkeletal muscleInflammationExerciseCD68IL-6TNF-alpha

English

The objective of this study was to identify molecular mechanisms underlying the beneficial effects of cod protein feeding on skeletal muscle recovery through detailed analyses of the IGF1-Akt/PKB signaling pathway. Acute mucle injury was induced by injecting bupivacaine in one tibialis anterior of Wistar rats fed isoenergetic diets containing either casein (C), cod protein (CP), or casein supplemented with a mixture of arginine, glycine, taurine and lysine (C+), matching their respective levels as in CP; downstream IGF1-Akt/PKB (protein kinase B) effectors were measured post-injury. Rats fed the CP-diet exhibited a 50% reduction of the muscle ring finger1 (MuRF1) level compared with those fed the C-diet (p=0.01), while the reduction induced by the C+-diet was intermediary to, but did not differ significantly (p=0.07) from the C-diet at day 2 post-injury. These findings indicate a decrease in the ubiquitination of muscle proteins and their degradation in the CP-group partly because of its high levels of arginine, glycine, taurine and lysine. Futhermore, phospho-Akt Ser473, a phosphorylation required for maximum activation of Akt, was increased in the CP-group at day 5 (p<0.0001) and day 28 post-injury (p=0.002) compared with C, and at day 5 compared with C+ (p=0.0005). The phosphorylated form of GSK-3 was also increased with CP feeding at day 28 post-injury compared with C (p=0.05), suggesting enhanced protein synthesis in the CP group. C+ enhanced phospho-Akt Ser473 compared with C (p=0.008) only at day 28 post-injury, with no effect on GSK-3 phosphorylation. Therefore, CP may reduce protein degradation induced by muscle injury through early modulation of the ubiquitination process, while enhancing muscle protein synthesis through Akt phosphorylation at later time points.

Mapping pathological phenotypes in reelin mutant mice.

Autism Spectrum Disorders (ASD) are neurodevelopmental disorders with multifactorial origin characterized by social communication deficits and the presence of repetitive behaviors/interests. Several studies showed an association between the reelin gene mutation and increased risk of ASD and a reduced reelin expression in some brain regions of ASD subjects, suggesting a role for reelin deficiency in ASD etiology. Reelin is a large extracellular matrix glycoprotein playing important roles during development of the central nervous system. To deeply investigate the role of reelin dysfunction as vulnerability factor in ASD, we assessed the behavioral, neurochemical, and brain morphological features of reeler male mice. We recently reported a genotype-dependent deviation in the ultrasonic vocal repertoire and a general delay in motor development of reeler pups. We now report that adult male heterozygous (Het) reeler mice did not show social behavior and communication deficits during male–female social interactions. Wildtype and Het mice showed a typical light/dark locomotor activity profile, with a peak during the central interval of the dark phase. However, when faced with a mild stressful stimulus (a saline injection) only Het mice showed an over response to stress. In addition to the behavioral studies, we conducted high performance liquid chromatography and magnetic resonance imaging and spectroscopy to investigate whether reelin mutation influences brain monoamine and metabolites levels in regions involved in ASD. Low levels of dopamine in cortex and high levels of glutamate and taurine in hippocampus were detected in Het mice, in line with clinical data collected on ASD children. Altogether, our data detected subtle but relevant neurochemical abnormalities in reeler mice supporting this mutant line, particularly male subjects, as a valid experimental model to estimate the contribution played by reelin deficiency in the global ASD neurobehavioral phenotype.

Interactive effects of dietary taurine and glutamine on growth performance, blood parameters and oxidative status of Japanese flounder Paralichthys olivaceus

Abstract Both taurine and glutamine play important roles in growth performance, feed utilization and anti-oxidation status. Therefore, a 60-day feeding trial was conducted to determine the interactive effects of dietary taurine and glutamine on growth performance, feed utilization, blood parameters and oxidative status of juvenile Japanese flounder. No interactive effect is shown in the selected parameters except for glutamic-pyruvate transaminase (GPT) of Japanese flounder in this study. The growth parameters (final body weight, body weight gain and special growth rate) and feed intake were significantly affected by either taurine or glutamine, meanwhile, plasma glucose, glutamyl oxaloacetic transaminase (GOT), glutamic-pyruvate transaminase (GPT) and triglycerides of Japanese flounder were significantly dec,reased when fed with high level of dietary taurine (1.6 g free taurine of 100 g dry diet). The other blood parameters (hematocrit, hemoglobin, glucose, total protein, total cholesterol, total bilirubin and triglycerides) were not significantly altered by various diets. The muscle free taurine concentration of Japanese flounder directly reflected the dietary taurine level, which was not affected by dietary glutamine. Interestingly, fish fed with both high levels of taurine (1.6 g free taurine of 100 g dry diet) and glutamine (1.5 g free glutamine of 100 g dry diet) showed higher oxidation resistance, which indicated the important roles of taurine and glutamine in fish oxidative stress protection.

Beneficial Effects of Cod Protein on Inflammatory Cell Accumulation in Rat Skeletal Muscle after Injury Are Driven by Its High Levels of Arginine, Glycine, Taurine and Lysine

We have shown that feeding cod protein, which is rich in anti-inflammatory arginine, glycine, and taurine, may beneficially modulate the inflammatory response during recovery following skeletal muscle injury; however it is unknown if these amino acids are responsible for this effect. This study was designed to assess whether supplementing casein with an amino acid mixture composed of arginine, glycine, taurine and lysine, matching their respective levels in cod protein, may account for the anti-inflammatory effect of cod protein. Male Wistar rats were fed isoenergetic diets containing either casein, cod protein, or casein supplemented with L-arginine (0.45%), glycine (0.43%), L-taurine (0.17%) and L-lysine (0.44%) (casein+). After 21 days of ad libitum feeding, one tibialis anterior muscle was injured with 200 µl bupivacaine while the saline-injected contra-lateral tibialis anterior was served as sham. Cod protein and casein+ similarly modulated the inflammation as they decreased COX-2 level at day 2 post-injury (cod protein, p=0.014; casein+, p=0.029) and ED1+ macrophage density at days 2 (cod protein, p=0.012; casein+, p<0.0001), 5 (cod protein, p=0.001; casein+, p<0.0001) and 14 (cod protein, p<0.0001; casein+, p<0.0001) post-injury, and increased ED2+ macrophage density at days 5 (cod protein, p<0.0001; casein+, p=0.006), 14 (cod protein, p=0.001; casein+, p<0.002) and 28 (cod protein, p<0.009; casein+, p<0.005) post-injury compared with casein. Furthermore, cod protein up-regulated (p=0.037) whereas casein+ tended to up-regulate (p=0.062) myogenin expression at day 5 post-injury compared with casein. In the cod protein-fed group, these changes resulted in greater muscle mass at days 14 (p=0.002), and 28 (p=0.001) post-injury and larger myofiber cross-sectional area at day 28 post-injury compared with casein (p=0.012). No such effects were observed with casein+. These data indicate that anti-inflammatory actions of cod protein, contrary to its effect on muscle mass recovery, are driven by its high levels of arginine, glycine, taurine and lysine.

Altered Metabolites in the Plasma of Autism Spectrum Disorder: A Capillary Electrophoresis Time-of-Flight Mass Spectroscopy Study

Clinical diagnosis and severity of autism spectrum disorders (ASD) are determined by trained clinicians based on clinical evaluations of observed behaviors. As such, this approach is inevitably dependent on the expertise and subjective assessment of those administering the clinical evaluations. There is a need to identify objective biological markers associated with diagnosis or clinical severity of the disorder. To identify novel candidate metabolites as potential biomarkers for ASD, the current study applied capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) for high-throughput profiling of metabolite levels in the plasma of 25 psychotropic-naïve adult males with high-functioning ASD and 28 age-matched typically-developed control subjects. Ten ASD participants and ten age-matched controls were assigned in the first exploration set, while 15 ASD participants and 18 controls were included in the second replication set. By CE-TOFMS analysis, a total of 143 metabolites were detected in the plasma of the first set. Of these, 17 metabolites showed significantly different relative areas between the ASD participants and the controls (p<0.05). Of the 17 metabolites, we consistently found that the ASD participants had significantly high plasma levels of arginine (p = 0.024) and taurine (p = 0.018), and significantly low levels of 5-oxoproline (p<0.001) and lactic acid (p = 0.031) compared with the controls in the second sample set. Further confirmatory analysis using quantification of absolute metabolite concentrations supported the robustness of high arginine (p = 0.001) and low lactic acid (p = 0.003) in the combined sample (n = 53). The present study identified deviated plasma metabolite levels associated with oxidative stress and mitochondrial dysfunction in individuals with ASD.

Dietary Cod Protein Improves the IGF1‐Akt/PKB Signaling Pathway in Rat Skeletal Muscle during Recovery from Injury

This study was designed to assess the mechanisms by which dietary cod protein may facilitate skeletal muscle recovery from injury through analyses of the IGF1‐Akt/PKB signaling pathway. Male Wistar rats were fed isoenergetic diets containing either casein (C), cod protein (CP), or casein supplemented with a mixture of arginine, glycine, taurine and lysine (C+), matching their respective levels as in CP. Muscle injury was induced by bupivacaine injection and downstream IGF1‐Akt/PKB effectors were measured post‐injury. At day 2 post‐injury, C+ upregulated (p=0.0008) whereas CP tended to upregulate phospho‐Akt Thr308 compared with C (p=0.075), suggesting that the myogenic effect of CP is due in part to its high levels of arginine, glycine, taurine and lysine. At day 2 post‐injury, CP reduced the expression of MuRF‐1 by 38% compared with C (p=0.03), supporting a decrease in the ubiquitylation of muscle proteins and their degradation. At day 5 post‐injury, CP tended to increase the muscle IGF‐1 level compared with C (p=0.098); phospho‐Akt Ser473, a phosphorylation required for maximum activation of Akt in addition to phosphorylation at Thr308, was also increased (p&lt;0.0001). These findings suggest that at early time‐points of recovery, CP can reduce muscle protein degradation through modulation of the ubiquitination process and upregulate protein synthesis through enhanced Akt activation.Supported by NSERC

Prey choice, provisioning behaviour, and effects of early nutrition on nestling phenotype of titmice

It is generally assumed that blue and great tits (Cyanistes caeruleus, Parus major) compete for the same type of food (Lepidoptera larvae) during the breeding season and that the former have some advantage because they are usually earlier and can exploit small caterpillars that are often more abundant and are not consumed by great tits. However, it is not clear whether, when confronted with similar circumstances (e.g., nestling demand), blue and great tits show similar preferences for a particular caterpillar type. In this 2-y study, we compare the diet of both tit species in detail by controlling for hatching date and brood size. We also examine how the contribution of caterpillars and spiders to the diet is related to nestling development. A positive relationship was found between the percentage of spiders in the diet and nestling tarsus length in both species, reinforcing the idea that neonatal nutrition could have a strong influence on nestling phenotype (e.g., offspring size). Such a correlation may arise because spiders contain a high level of taurine, an essential nutrient in the early development of young, and/or this prey type contains more calcium than other food items, which may affect the rate of nestling bone mineralization. Blue tits fed their young double the number of tortricid larvae in comparison with great tits, whereas the latter showed a clear preference for noctuids and exploited, with a low frequency, a type of larvae not consumed by blue tits, hairy caterpillars (Lasiocampidae). Our results point to resource partitioning by these species in this forest ecosystem and contribute to a better understanding of feeding ecology of titmice, which is particularly timely in a global warming context.

Selective breeding for helplessness in rats alters the metabolic profile of the hippocampus and frontal cortex: a 1H-MRS study at 9.4 T

In humans metabolic changes, particularly in frontal areas of the brain, accompany depressive disorders, but few studies were conducted in animal models of depression. We used hydrogen-1 magnetic resonance spectroscopy at 9.4 T to measure the metabolic profiles of the hippocampus and frontal cortex in congenital learned helpless (cLH) and wild-type (WT) rats. The learned helplessness model of depression exposes animals to uncontrollable stress to induce changes in emotion, cognition and behaviour, but cLH rats were selectively bred to show changes in behaviour even without exposure to uncontrollable stress. Experimentally naive male 8- to 10-wk-old cLH (n = 10) and WT rats (n = 22) underwent spectroscopy and were exposed to uncontrollable stress 1 wk after the scan. We found that cLH compared to WT rats had lower levels of glutamate in the hippocampus and lower levels of choline-containing compounds in the hippocampus and frontal cortex, but higher levels of taurine and phosphocreatine in these regions, pointing to compensatory efforts of the brain to reduce excitotoxic potential and to increase neuroprotection and energy, possibly as a result of cellular stress and damage. The reduction in choline-containing phospholipids might represent a source or correlate of such stress. Overall, the results indicate that metabolic abnormalities are present in animals with a predisposition to helplessness even without exposure to explicit stress and may help identify non-invasive biomarkers in individuals who are prone to depression.

Deletion of TRAAK Potassium Channel Affects Brain Metabolism and Protects against Ischemia

Cerebral stroke is a worldwide leading cause of disability. The two-pore domain K+ channels identified as background channels are involved in many functions in brain under physiological and pathological conditions. We addressed the hypothesis that TRAAK, a mechano-gated and lipid-sensitive two-pore domain K+ channel, is involved in the pathophysiology of brain ischemia. We studied the effects of TRAAK deletion on brain morphology and metabolism under physiological conditions, and during temporary focal cerebral ischemia in Traak−/− mice using a combination of in vivo magnetic resonance imaging (MRI) techniques and multinuclear magnetic resonance spectroscopy (MRS) methods. We provide the first in vivo evidence establishing a link between TRAAK and neurometabolism. Under physiological conditions, Traak−/− mice showed a particular metabolic phenotype characterized by higher levels of taurine and myo-inositol than Traak+/+ mice. Upon ischemia, Traak−/− mice had a smaller infarcted volume, with lower contribution of cellular edema than Traak+/+ mice. Moreover, brain microcirculation was less damaged, and brain metabolism and pH were preserved. Our results show that expression of TRAAK strongly influences tissue levels of organic osmolytes. Traak−/− mice resilience to cellular edema under ischemia appears related to their physiologically high levels of myo-inositol and of taurine, an aminoacid involved in the modulation of mitochondrial activity and cell death. The beneficial effects of TRAAK deletion designate this channel as a promising pharmacological target for the treatment against stroke.

Monitoring the brain metabolites of children with acute encephalopathy caused by the H1N1 virus responsible for the 2009 influenza pandemic: a quantitative in vivo 1H MR spectroscopy study

Background and PurposeInfluenza viral infection, which results in central nervous system dysfunction, is a major cause of acute encephalopathy (AE). The purpose of this study was to investigate the changes in the concentrations of brain metabolites in children with AE using single-voxel magnetic resonance spectroscopy (MRS) and to provide diagnostic information about the relationship between the symptoms of AE and metabolite concentrations. Materials and MethodsThe subjects were 10 children (mean age: 6.2 years; range: 1–13) with AE caused by the novel influenza A virus responsible for the 2009 influenza pandemic. The serial MRS data (TE/TR=30/5000 ms, 3 T) acquired from the basal ganglia (BG) and centrum semiovale (CS) of each patient were categorized into three periods: (1) initial neurological symptom presentation and the start of treatment (n=10), (2) short-term follow-up (n=9) and (3) long-term follow-up (n=3). As controls, the magnetic resonance (MR) spectra of eight age-matched children were also investigated. ResultsIn both regions, the concentrations of the major metabolites (N-acetylaspartate, creatine, choline, myo-inositol, glutamate/glutamine complex and glutamate) only showed minor fluctuations between the three periods. On the other hand, higher levels of taurine (Tau) were observed in the BG during the second period (P=.005), and increased levels of glucose were observed in the CS during the first (P=.005) and second (P=.036) periods. ConclusionsSerial monitoring of brain metabolite changes was carried out with a clinical MR system. The concentrations of major metabolites only displayed very minor fluctuations in response to mild H1N1-related AE. However, a higher Tau concentration was found to be associated with neurological symptoms. Further studies are required to improve our understanding of the detailed activity of Tau in AE.

Computational molecular phenotyping of retinal sheet transplants to rats with retinal degeneration

Retinal progenitor sheet transplants have been shown to extend neuronal processes into a degenerating host retina and to restore visual responses in the brain. The aim of this study was to identify cells involved in transplant signals to retinal degenerate hosts using computational molecular phenotyping (CMP). S334ter line 3 rats received fetal retinal sheet transplants at the age of 24-40 days. Donor tissues were incubated with slow-releasing microspheres containing brain-derived neurotrophic factor or glial cell-derived neurotrophic factor. Up to 265 days after surgery, eyes of selected rats were vibratome-sectioned through the transplant area (some slices stained for donor marker human placental alkaline phosphatase), dehydrated and embedded in Eponate, sectioned into serial ultrathin datasets and probed for rhodopsin, cone opsin, CRALBP (cellular retinaldehyde binding protein), l-glutamate, l-glutamine, glutathione, glycine, taurine, γ-aminobutyric acid (GABA) and DAPI (4',6-diamidino-2-phenylindole). In large transplant areas, photoreceptor outer segments in contact with host retinal pigment epithelium revealed rod and cone opsin immunoreactivity whereas no such staining was found in the degenerate host retina. Transplant photoreceptor layers contained high taurine levels. Glutamate levels in the transplants were higher than in the host retina whereas GABA levels were similar. The transplant inner nuclear layer showed some loss of neurons, but amacrine cells and horizontal cells were not reduced. In many areas, glial hypertrophy between the host and transplant was absent and host and transplant neuropil appeared to intermingle. CMP data indicate that horizontal cells and both glycinergic and GABAergic amacrine cells are involved in a novel circuit between transplant and host, generating alternative signal pathways between transplant and degenerating host retina.

Dietary Cod Protein Improves Skeletal Muscle Regeneration Partly Through Its High Levels of Arginine, Lysine, Glycine and Taurine

Feeding cod protein may beneficially influence the time course of inflammation during recovery following skeletal muscle injury. The objective of this study was to identify amino acids in cod protein having a beneficial impact on muscle repair. Male Wistar rats were fed isoenergetic diets containing either casein (C), cod protein (CP), or casein supplemented with arginine (1.9%), glycine (1.9%), taurine (0.7%) and lysine (1.7%) (C+). After 21 d of ad libitum feeding, one tibialis anterior muscle (TA) was injured by injecting 200μl of bupivacaine while the contra‐lateral TA was injected with saline and served as sham. Rats fed CP exhibited higher muscle weight at days 5, 14, and 28 post‐injury and higher myofiber cross‐sectional area at days 5 and 28 post‐injury compared with C. CP and C+ similarly modulated the inflammation as they decreased ED1+ macrophages and COX‐2 level at day 2 post injury compared with casein (p=0.01), and increased ED2+ macrophages compared with C. The C+ diet upregulated (p=0.02) whereas the CP diet tended to upregulate myogenin expression at day 5 post‐injury compared with C (p=0.06). These data support the hypothesis that the beneficial impact of cod protein on skeletal muscle recovery is partly attributed to the anti‐inflammatory and myogenic action of its high arginine, lysine, glycine and taurine levels.Supported by The Natural Sciences and Engineering Research Council of Canada.

Serum taurine and risk of coronary heart disease: a prospective, nested case–control study

Taurine (2-aminoethanesulfonic acid), a molecule obtained from diet, is involved in bile acid conjugation, blood pressure regulation, anti-oxidation and anti-inflammation. We performed the first prospective study of taurine and CHD risk. We conducted a case-control study nested in the New York University Women's Health Study to evaluate the association between circulating taurine levels and risk of coronary heart disease (CHD). Taurine was measured in two yearly pre-diagnostic serum samples of 223 CHD cases and 223 matched controls and averaged for a more reliable measurement of long-term taurine levels. Mean serum taurine was positively related to age and dietary intake of poultry, niacin, vitamin B1, fiber and iron, and negatively related to dietary intake of saturated fat (all p values ≤ 0.05). There was no statistically significant association between serum taurine levels and the risk of CHD in the overall study population. The adjusted ORs for CHD in increasing taurine tertiles were 1.0 (reference), 0.85 (95% CI, 0.51-1.40) and 0.66 (0.39-1.13; p for trend = 0.14). There was a significant inverse association between serum taurine and CHD risk among women with high total serum cholesterol (>250 mg/dL) (adjusted OR = 0.39 (0.19-0.83) for the third versus first tertile; p for trend = 0.02) but not among those with low total serum cholesterol (p for interaction = 0.01). The data suggest a possible inverse association of serum taurine with diabetes and hypertension risk. The findings suggest that high levels of taurine may be protective against CHD among individuals with high serum cholesterol levels.