Neutrophil-Lymphocyte Ratio as a Predictor of the Risk of Death in Severe Cases of COVID-19.

BACKGROUND: Identifying clinical characteristics and risk factors, comorbid conditions, and complications arising from SARS-CoV-2 infection is important to predict the progression to more severe forms of the disease among hospitalized individuals to enable timely intervention and to prevent fatal outcomes. The aim of the study is to assess the possible role of the neutrophil/lymphocyte ratio (NLR) as a biomarker of the risk of death in patients with comorbidities hospitalized with COVID-19 in a tertiary hospital in southern Brazil. METHODS: This is a prospective cohort study on patients with SARS-CoV-2 infection admitted to a hospital in the metropolitan region of Porto Alegre from September 2020 to March 2022. RESULTS: The sample consisted of 185 patients with associated comorbidities, namely, hypertension, diabetes mellitus, obesity, cardiovascular, pulmonary, and renal diseases, hospitalized with COVID-19. Of these, 78 died and 107 were discharged alive. The mean age was 66.5 years for the group that died and 60.1 years for the group discharged. Statistical analysis revealed that a difference greater than or equal to 1.55 in the NLR, from hospitalization to the 5th day, was associated with a relative risk of death greater than 2. CONCLUSIONS: Measuring a simple inflammatory marker such as NLR may improve the risk stratification of comorbid patients with COVID-19 and can be considered a useful biomarker.

Systematic Review of the Clinical and Experimental Research Assessing the Effects of Craniosynostosis on the Brain.

Although neurocognitive impairment has been considered as the main argument for the surgical treatment of craniosynostosis (CS), recent studies reported subtle deficits in neurological function even in operated patients. However, the cause of these deficits remains poorly understood. This systematic review sought to examine the impact of CS on the brain microstructure, mainly on functional connectivity, and comprehensively summarize the clinical and experimental research available on this topic. A systematic review was performed considering the publications of the last 20 years in PubMed and Web of Science, including relevant human and animal studies of the types of brain-microstructure disturbances in CS. Among the 560 papers identified, 11 were selected for analysis. Seven of those were conducted in humans and 4 in animal models. Resting-state functional magnetic resonance imaging, task-based magnetic resonance imaging, and diffusion tensor imaging were the main instruments used to investigate brain connectivity in humans. The main findings were increased connectivity of the posterior segment of cingulum gyri, reduced interconnectivity of the frontal lobes, and reduced diffusivity on diffusion tensor imaging, which were associated with hyperactivity behaviors and poorer performance on neurocognitive tests. Conversely, despite the lack of evidence of brain dysfunction in animal studies, they reported a tendency toward the development of hyperactive behaviors and impairment of neurocognitive function. Skull restriction caused by CS apparently chronically increases the intracranial pressure and produces white matter injuries. The current evidence supports the contention that an early surgical approach could minimize brain-connectivity impairment in this context.

Anti-inflammatory effect of rosmarinic acid isolated from Blechnum brasiliense in adult zebrafish brain.

Neuroinflammation has been associated to neurodegenerative disease development, with evidence suggesting that high levels of proinflammatory cytokines promote neuronal dysfunction and death. Therefore, it is necessary to study new compounds that may be used as adjuvant treatments of neurodegenerative diseases by attenuating the inflammatory response in the central nervous system (CNS). The aim of this study was to utilize the lipopolysaccharide (LPS) induction model of neuroinflammation to evaluate the modulation of inflammation by rosmarinic acid (RA) isolated from Blechnum brasiliense in adult zebrafish. First, we investigated the toxicity and antioxidant properties of fractionated B. brasiliense extract (ethyl acetate fraction- EAF) and the isolated RA in zebrafish embryos. Next, we developed a model of neuroinflammation induction by intraperitoneal (i.p.) injection of LPS to observe the RA modulation of proinflammatory cytokines. The median lethal concentration (LC50) calculated was 185.2 ± 1.24 µg/mL for the ethyl acetate fraction (EAF) and 296.0 ± 1.27 µM for RA. The EAF showed free radical inhibition ranging from 23.09% to 63.44% at concentrations of 10-250 µg/mL. The RA presented a concentration-dependent response ranging from 18.24% to 47.63% at 10-250 µM. Furthermore, the RA reduced LPS induction of TNF-α and IL-1ß levels, with the greatest effect observed 6 h after LPS administration. Thus, the data suggested an anti-inflammatory effect of RA isolated from B. brasiliense and reinforced the utility of the new model of neuroinflammation to test the possible neuroprotective effects of novel drugs or compounds.

Fructose-1,6-bisphosphate preserves glucose metabolism integrity and reduces reactive oxygen species in the brain during experimental sepsis.

Sepsis is one of the main causes of hospitalization and mortality in Intensive Care Units. One of the first manifestations of sepsis is encephalopathy, reported in up to 70% of patients, being associated with higher mortality and morbidity. The factors that cause sepsis-associated encephalopathy (SAE) are still not well known, and may be multifactorial, as perfusion changes, neuroinflammation, oxidative stress and glycolytic metabolism alterations. Fructose-1,6-bisphosphate (FBP), a metabolite of the glycolytic route, has been reported as neuroprotective agent. The present study used an experimental sepsis model in C57BL/6 mice. We used in vivo brain imaging to evaluate glycolytic metabolism through microPET scans and the radiopharmaceutical 18F-fluoro-2-deoxy-D-glucose (18F-FDG). Brain images were obtained before and 12 h after the induction of sepsis in animals with and without FBP treatment. We also evaluated the treatment effects in the brain oxidative stress by measuring the production of reactive oxygen species (ROS), the activity of catalase (CAT) and glutathione peroxidase (GPx), and the levels of fluorescent marker 2'7'-dichlorofluorescein diacetate (DCF). There was a significant decrease in brain glucose metabolism due to experimental sepsis. A significant protective effect of FBP treatment was observed in the cerebral metabolic outcomes. FBP also modulated the production of ROS, evidenced by reduced CAT activity and lower levels of DCF. Our results suggest that FBP may be a possible candidate in the treatment of SAE.

Therapeutic Hypothermia Reduces Oxidative Damage and Alters Antioxidant Defenses after Cardiac Arrest.

After cardiac arrest, organ damage consequent to ischemia-reperfusion has been attributed to oxidative stress. Mild therapeutic hypothermia has been applied to reduce this damage, and it may reduce oxidative damage as well. This study aimed to compare oxidative damage and antioxidant defenses in patients treated with controlled normothermia versus mild therapeutic hypothermia during postcardiac arrest syndrome. The sample consisted of 31 patients under controlled normothermia (36°C) and 11 patients treated with 24 h mild therapeutic hypothermia (33°C), victims of in- or out-of-hospital cardiac arrest. Parameters were assessed at 6, 12, 36, and 72 h after cardiac arrest in the central venous blood samples. Hypothermic and normothermic patients had similar S100B levels, a biomarker of brain injury. Xanthine oxidase activity is similar between hypothermic and normothermic patients; however, it decreases posthypothermia treatment. Xanthine oxidase activity is positively correlated with lactate and S100B and inversely correlated with pH, calcium, and sodium levels. Hypothermia reduces malondialdehyde and protein carbonyl levels, markers of oxidative damage. Concomitantly, hypothermia increases the activity of erythrocyte antioxidant enzymes superoxide dismutase, glutathione peroxidase, and glutathione S-transferase while decreasing the activity of serum paraoxonase-1. These findings suggest that mild therapeutic hypothermia reduces oxidative damage and alters antioxidant defenses in postcardiac arrest patients.

Reduced insulin secretion and glucose intolerance are involved in the fasting susceptibility of common vampire bats.

Susceptibility during fasting has been reported for the common vampire bat (Desmodus rotundus), to the point of untimely deaths after only 2-3 nights of fasting. To investigate the underlying physiology of this critical metabolic condition, we analyzed serum insulin levels, pancreatic islets morphometry and immunocytochemistry (ICC), static insulin secretion in pancreas fragments, and insulin signaling mechanism in male vampire bats. A glucose tolerance test (ipGTT) was also performed. Serum insulin was found to be lower in fed vampires compared to other mammals, and was significantly reduced after 24h fasting. Morphometrical analyses revealed small irregular pancreatic islets with reduced percentage of ß-cell mass compared to other bats. Static insulin secretion analysis showed that glucose-stimulated insulin secretion was impaired, as insulin levels did not reach significance under high glucose concentrations, whereas the response to the amino acid leucin was preserved. Results from ipGTT showed a failure on glucose clearance, indicating glucose intolerance due to diminished pancreatic insulin secretion and/or decreased ß-cell response to glucose. In conclusion, data presented here indicate lower insulinemia and impaired insulin secretion in D. rotundus, which is consistent with the limited ability to store body energy reserves, previously reported in these animals. Whether these metabolic and hormonal features are associated with their blood diet remains to be determined. The peculiar food sharing through blood regurgitation, reported to this species, might be an adaptive mechanism overcoming this metabolic susceptibility.

Homocysteine induces energy imbalance in rat skeletal muscle: is creatine a protector?

Homocystinuria is a neurometabolic disease caused by a severe deficiency of cystathionine beta-synthase activity, resulting in severe hyperhomocysteinemia. Affected patients present several symptoms including a variable degree of motor dysfunction. In this study, we investigated the effect of chronic hyperhomocysteinemia on the cell viability of the mitochondrion, as well as on some parameters of energy metabolism, such as glucose oxidation and activities of pyruvate kinase, citrate synthase, isocitrate dehydrogenase, malate dehydrogenase, respiratory chain complexes and creatine kinase in gastrocnemius rat skeletal muscle. We also evaluated the effect of creatine on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injections of homocysteine (0.3-0.6 µmol/g body weight) and/or creatine (50 mg/kg body weight) from the 6th to the 28th days of age. The animals were decapitated 12 h after the last injection. Homocysteine decreased the cell viability of the mitochondrion and the activities of pyruvate kinase and creatine kinase. Succinate dehydrogenase was increased other evaluated parameters were not changed by this amino acid. Creatine, when combined with homocysteine, prevented or caused a synergistic effect on some changes provoked by this amino acid. Creatine per se or creatine plus homocysteine altered glucose oxidation. These findings provide insights into the mechanisms by which homocysteine exerts its effects on skeletal muscle function, more studies are needed to elucidate them. Although creatine prevents some alterations caused by homocysteine, it should be used with caution, mainly in healthy individuals because it could change the homeostasis of normal physiological functions.

Effects of the putative antipsychotic alstonine on glutamate uptake in acute hippocampal slices.

A dysfunctional glutamatergic system is thought to be central to the negative symptoms and cognitive deficits recognized as determinant to the poor quality of life of people with schizophrenia. Modulating glutamate uptake has, thus, been suggested as a novel target for antipsychotics. Alstonine is an indole alkaloid sharing with atypical antipsychotics the profile in animal models relevant to schizophrenia, though divergent in its mechanism of action. The aim of this study was to evaluate the effects of alstonine on glutamate uptake. Additionally, the effects on glutathione content and extracellular S100B levels were assessed. Acute hippocampal slices were incubated with haloperidol (10µM), clozapine (10 and 100µM) or alstonine (1-100µM), alone or in combination with apomorphine (100µM), and 5-HT(2) receptor antagonists (0.01µM altanserin and 0.1µM SB 242084). A reduction in glutamate uptake was observed with alstonine and clozapine, but not haloperidol. Apomorphine abolished the effect of clozapine, whereas 5-HT(2A) and 5-HT(2C) antagonists abolished the effects of alstonine. Increased levels of glutathione were observed only with alstonine, also the only compound that failed to decrease the release of S100B. This study shows that alstonine decreases glutamate uptake, which may be beneficial to the glutamatergic deficit observed in schizophrenia. Noteworthily, the decrease in glutamate uptake is compatible with the reversal of MK-801-induced social interaction and working memory deficits. An additional potential benefit of alstonine as an antipsychotic is its ability to increase glutathione, a key cellular antioxidant reported to be decreased in the brain of patients with schizophrenia. Adding to the characterization of the novel mechanism of action of alstonine, the lack of effect of apomorphine in alstonine-induced changes in glutamate uptake reinforces that D(2) receptors are not primarily implicated. Though clearly mediated by 5-HT(2A) and 5-HT(2C) serotonin receptors, the precise mechanisms that result in the effects of alstonine on glutamate uptake warrant elucidation.

Gene polymorphisms against DNA damage induced by hydrogen peroxide in leukocytes of healthy humans through comet assay: a quasi-experimental study.

BACKGROUND: Normal cellular metabolism is well established as the source of endogenous reactive oxygen species which account for the background levels of oxidative DNA damage detected in normal tissue. Hydrogen peroxide imposes an oxidative stress condition on cells that can result in DNA damage, leading to mutagenesis and cell death. Several potentially significant genetic variants related to oxidative stress have already been identified, and angiotensin I-converting enzyme (ACE) inhibitors have been reported as possible antioxidant agents that can reduce vascular oxidative stress in cardiovascular events. METHODS: We investigate the influences of haptoglobin, manganese superoxide dismutase (MnSOD Val9Ala), catalase (CAT -21A/T), glutathione peroxidase 1 (GPx-1 Pro198Leu), ACE (I/D) and gluthatione S-transferases GSTM1 and GSTT1 gene polymorphisms against DNA damage and oxidative stress. These were induced by exposing leukocytes from peripheral blood of healthy humans (N = 135) to hydrogen peroxide (H2O2), and the effects were tested by comet assay. Blood samples were submitted to genotyping and comet assay (before and after treatment with H2O2 at 250 microM and 1 mM). RESULTS: After treatment with H2O2 at 250 microM, the GPx-1 polymorphism significantly influenced results of comet assay and a possible association of the Pro/Leu genotype with higher DNA damage was found. The highest or lowest DNA damage also depended on interaction between GPX-1/ACE and Hp/GSTM1T1 polymorphisms when hydrogen peroxide treatment increased oxidative stress. CONCLUSIONS: The GPx-1 polymorphism and the interactions between GPX-1/ACE and Hp/GSTM1T1 can be determining factors for DNA oxidation provoked by hydrogen peroxide, and thus for higher susceptibility to or protection against oxidative stress suffered by healthy individuals.

Characterization and in vitro hemocompatibility of bi-soft segment, polycaprolactone-based poly(ester urethane urea) membranes.

In this study, surface, bulk, and hemocompatibility characteristics of crosslinked, bi-soft segment poly (ester urethane urea) membranes, prepared by extending a poly(propylene oxide)-based triisocyanate-terminated prepolymer (PU) with a polycaprolactone diol (PCL), were investigated. Variation of the ratio of PU to PCL diol content in the membrane formulation yielded alteration of surface energy, phase morphology both in the bulk and in the region near the surface, and it affected hemocompatibility. Nearly all membranes were nonhemolytic, with hemolysis degrees between 1 and 2.1% and, for short-time contact with blood (15 min), all membranes showed in vitro thrombosis degrees between 27 and 42%. The membranes prepared with 5 and 25% of PCL diol showed almost no adherent platelets. These two membranes had a higher hard segment aggregation in the region near the surface and mixing between the two soft segments in the bulk, but showed contrasting surface energy characteristics. The results obtained in this work give evidence that surface energy and its polar and dispersive components did not correlate with any of the hemocompatibility aspects studied. In contrast, the phase morphology in the region near the surface was a major influence on membrane hemocompatibility.

Pequi fruit (Caryocar brasiliense Camb.) pulp oil reduces exercise-induced inflammatory markers and blood pressure of male and female runners.

The objective of this study was to investigate the anti-inflammatory properties of pequi (Caryocar brasiliense) fruit oil and its effects on the postprandial lipidemia and arterial blood pressure of male and female athletes. These athletes were evaluated after races in the same environment and under the same type, intensity, and length of weekly training conditions, both before and after ingestion of 400 mg pequi oil capsules for 14 days. Pequi fruit contains several antioxidants, and its oil has been associated with anti-inflammatory properties in other pequi species. Because the oil of pequi is mostly composed of oleic and palmitic fatty acids, the oil may alter the ratio of triglyceride to cholesterol in postprandial lipidemia. Epidemiologic studies suggest that an increased intake of monounsaturated fatty acids (such as oleic acid) is inversely related to blood pressure. Thus, we hypothesize that pequi oil could reduce exercise-induced inflammation and blood pressure, and modulate postprandial lipidemia in runners. To test this hypothesis, arterial blood pressures were checked before races; blood samples were taken after the races and submitted for analysis of leukocytes and platelets analysis, high-sensitivity C-reactive protein values, and postprandial lipids. Pequi oil resulted in anti-inflammatory effects and reduced the total cholesterol and low-density lipoprotein in the age group older than 45 years, mainly for men. The results showed a general trend for reduced arterial pressure, suggesting that pequi oil may have a hypotensive effect. However, this finding needs additional investigation. Thus, pequi oil, besides possessing many nutritional properties, may be a good candidate supplement for athletes.

High fat and highly thermolyzed fat diets promote insulin resistance and increase DNA damage in rats.

Many studies have demonstrated that DNA damage may be associated with type 2 diabetes mellitus (T2DM) and its complications. The goal of this study was to evaluate the effects of the potential relationship between fat (thermolyzed) intake, glucose dyshomeostasis and DNA injury in rats. Biochemical parameters related to glucose metabolism (i.e., blood glucose levels, insulin tolerance tests, glucose tolerance tests and fat cell glucose oxidation) and general health parameters (i.e., body weight, retroperitoneal and epididymal adipose tissue) were evaluated in rats after a 12-month treatment with either a high fat or a high thermolyzed fat diet. The high fat diet (HFD) and high fat thermolyzed diet (HFTD) showed increased body weight and impaired insulin sensitivity at the studied time-points in insulin tolerance test (ITT) and glucose tolerance test (GTT). Interestingly, only animals subjected to the HFTD diet showed decreased epididymal fat cell glucose oxidation. We show which high fat diets have the capacity to reduce glycogen synthesis by direct and indirect pathways. HFTD promoted an increase in lipid peroxidation in the liver, demonstrating significant damage in lipids in relation to other groups. Blood and hippocampus DNA damage was significantly higher in animals subjected to HFDs, and the highest damage was observed in animals from the HFTD group. Striatum DNA damage was significantly higher in animals subjected to HFDs, compared with the control group. These results show a positive correlation between high fat diet, glucose dyshomeostasis, oxidative stress and DNA damage.

3-Nitrotyrosine and glutathione antioxidant system in patients in the early and late stages of bipolar disorder.

BACKGROUND: There has been an increasing interest in the role of oxidative stress in the pathophysiology of bipolar disorder. To explore this further, we evaluated the activity of glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST), as well as 3-nitrotyrosine levels and carbonyl content in patients in the early (within 3 years of illness onset) and late (a minimum of 10 years of illness) stages of bipolar disorder. METHODS: We matched 30 patients in the early stage and 30 patients in the late stage of bipolar disorder, diagnosed according to DSM-IV criteria, with 60 healthy controls (30 matched for each group of patients). We measured symptomatic status using the Hamilton Rating Scale for Depression and the Young Mania Rating Scale. RESULTS: We found a significant increase in 3-nitrotyrosine levels among patients in the early (p < 0.010) and late (p < 0.010) stages of bipolar disorder. The activity of GR and GST was increased only among patients in the late stage of illness. Glutathione peroxidase activity and carbonyl content did not differ among the groups. LIMITATIONS: Limitations of our study include its cross-sectional design, which did not allow us to examine direct causative mechanisms or the effects of progression of illness, and the potential environmental bias introduced by comparing patient groups recruited from different regions of the world. CONCLUSION: Our data indicate a possible tyrosine nitration-induced damage in patients with bipolar disorder that is present from the early stage of illness. Our data also indicate that patients in the late stage of illness demonstrate enhanced activity of GR and GST, which could suggest the involvement of a compensatory system in bipolar disorder.

Morphological changes in hippocampal astrocytes induced by environmental enrichment in mice.

Environmental enrichment is known to induce plastic changes in the brain, including morphological changes in hippocampal neurons, with increases in synaptic and spine densities. In recent years, the evidence for a role of astrocytes in regulating synaptic transmission and plasticity has increased, and it is likely that morphological and functional changes in astrocytes play an important role in brain plasticity. Our study was designed to evaluate changes in astrocytes induced by environmental enrichment in the CA1 region of the hippocampus, focusing on astrocytic density and on morphological changes in astrocytic processes. After 8 weeks of environmental enrichment starting at weaning, male CF-1 mice presented no significant changes in astrocyte number or in the density of glial fibrillary acidic protein (GFAP) immunoreactivity in the stratum radiatum. However, they did present changes in astrocytic morphology in the same region, as expressed by a significant increase in the ramification of astrocytic processes measured by the Sholl concentric circles method, as well as by an increase in the number and length of primary processes extending in a parallel orientation to CA1 nerve fibers. This led astrocytes to acquire a more stellate morphology, a fact which could be related to the increase in hippocampal synaptic density observed in previous studies. These findings corroborate the idea that structural changes in astrocytic networks are an integral part of plasticity processes occurring in the brain.

Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: protective effect of folic acid.

We have previously demonstrated that acute hyperhomocysteinemia induces oxidative stress in rat brain. In the present study, we initially investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative damage, namely total radical-trapping antioxidant potential and activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), as well as on DNA damage in parietal cortex and blood of rats. We also evaluated the effect of folic acid on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injection of Hcy (0.3-0.6 micromol/g body weight), and/or folic acid (0.011 micromol/g body weight) from their 6th to their 28th day of life. Twelve hours after the last injection the rats were sacrificed, parietal cortex and total blood was collected. Results showed that chronic homocysteine administration increased DNA damage, evaluated by comet assay, and disrupted antioxidant defenses (enzymatic and non-enzymatic) in parietal cortex and blood/plasma. Folic acid concurrent administration prevented homocysteine effects, possibly by its antioxidant and DNA stability maintenance properties. If confirmed in human beings, our results could propose that the supplementation of folic acid can be used as an adjuvant therapy in disorders that accumulate homocysteine.

Effects of mood stabilizers on DNA damage in an animal model of mania.

OBJECTIVE: Recent studies have suggested that oxidative stress and DNA damage may play a role in the pathophysiology of bipolar disorder (BD). We investigated the effects of the mood stabilizers lithium and valproate on amphetamine-induced DNA damage in an animal model of mania and their correlation with oxidative stress markers. METHODS: In the first experiment (reversal model), we treated adult male Wistar rats with D-amphetamine (AMPH) or saline for 14 days; between the 8th and 14th days, rats also received lithium, valproate or saline. In the second experiment (prevention model), rats received either lithium, valproate or saline for 14 days; between the 8th and 14th days, we added AMPH or saline. We evaluated DNA damage using single-cell gel electrophoresis (comet assay), and we assessed the mutagenic potential using the micronucleus test. We assessed oxidative stress levels by lipid peroxidation levels (TBARS) and antioxidant enzyme activities (superoxide dismutase and catalase). We assessed DNA damage and oxidative stress markers in blood/plasma and hippocampal samples. We evaluated mutagenesis in fresh lymphocytes. RESULTS: In both models, we found that AMPH increased peripheral and hippocampal DNA damage. The index of DNA damage correlated positively with lipid peroxidation, whereas lithium and valproate were able to modulate the oxidative balance and prevent recent damage to the DNA. However, lithium and valproate were not able to prevent micronucleus formation. CONCLUSION: Our results support the notion that lithium and valproate exert central and peripheral antioxidant-like properties. In addition, the protection to the integrity of DNA conferred by lithium seems to be limited to transient DNA damage and does not alter micronuclei formation.

Investigation of serum high-sensitive C-reactive protein levels across all mood states in bipolar disorder.

There has been an increasing interest in the role of the immune and inflammatory systems in mood disorders. Mood episodes are associated with changes in acute phase proteins such as high-sensitivity C-reactive protein (hsCRP). The present study investigated serum hsCRP in manic, depressed, and euthymic BD patients as compared to matched healthy controls. Serum hsCRP was assessed using an ultrasensitive assay of particle-enhanced immunoturbidimetric latex agglutination. Serum hsCRP levels were increased in manic BD patients, as compared to euthymic, depressed patients and healthy controls (P < 0.001). These findings add to the notion that changes in the inflammatory system take place during acute episodes of mania.

Increased S100B serum levels in dilated cardiomyopathy patients.

BACKGROUND: The S100B protein is considered a biochemical marker for brain injuries. However, our group demonstrated that the isolated rat heart releases S100B. In this study, we investigated the serum levels of S100B in dilated cardiomyopathy (DCM) patients to evaluate its levels in heart disease. METHODS AND RESULTS: We selected DCM patients, excluding any condition that could influence S100B serum levels. Control individuals were sex and age matched. Both groups were submitted to clinical evaluation and echocardiography. We measured the S100B and NT-proBNP serum levels (expressed as median [interquartile range]). NT-proBNP levels in patients group (1462 pg/mL [426-3591]) were higher than in controls (35 pg/mL [29-55]), P < .001. S100B serum levels were higher in patients group (0.051 microg/L [0.022-0.144]) than in controls (0.017 microg/L [0.003-0.036]), P = .009. Additionally, we found a positive correlation between S100B and NT-proBNP serum levels only in patients group (Spearman's coefficient r = 0.534; P = .013). CONCLUSIONS: Although we cannot rule out the influence of S100B from brain, the positive correlation between S100B and NT-proBNP levels in DCM patients points to the myocardium as the main source for the rise in S100B serum levels.

S100B levels in the cerebrospinal fluid of rats are sex and anaesthetic dependent.

1. S100B is a calcium-binding protein that acts as a neurotrophic cytokine and is expressed in the central nervous system, predominantly by astrocytes. At nanomolar concentrations, S100B stimulates neurite outgrowth and glial glutamate uptake, as well as protecting neurons against glutamate excitoxicity. 2. Peripheral S100B concentrations, particularly in the serum and cerebrospinal fluid (CSF), have been used as a parameter of glial activation or death in several physiological and pathological conditions. 3. In the present study, we investigated the effect of anaesthetics (thiopental, ketamine and halothane) on CSF concentrations of S100B, as well as a possible sex dependence, because several studies have suggested astrocytes as putative targets for oestrogen. 4. Higher levels of CSF S100B were found when rats were anaesthetized with thiopental; these levels, independently of anaesthetic, were sex dependent. Conversely, no effect of anaesthetic or sex was observed on serum concentrations of S100B. 5. The increase in CSF concentrations of S100B induced by thiopental was confirmed in non-anaesthetized neonatal rats and cortical astrocyte cultures. 6. Assuming CSF S100B as a marker of development, glial activation or even brain damage, investigations regarding the sex dependence of its concentration may be useful in gaining an understanding of sex variations in the behaviour and the pathological course of, as well as susceptibility to, many brain disorders. The findings of the present study reinforce the sex effect on synaptic plasticity and suggest a sex dependence of neural communication mediated by extracellular S100B without restricting the influence of astrocytes on the developmental phase.

Serum neurotrophin-3 is increased during manic and depressive episodes in bipolar disorder.

Accumulating evidence suggest that neural changes and cognitive impairment may accompany the course of bipolar disorder. Such detrimental effects of cumulative mood episodes may be related to changes in neurotrophins that take place during mood episodes but not during euthymic phases. The present study investigated serum neurotrophin-3 (NT-3) levels in patients with bipolar disorder during manic, depressed, and euthymic states, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum NT-3 levels were increased in manic (p<0.001) and depressed (p<0.001) BD patients, as compared with euthymic patients and normal controls. These findings suggest that the NT-3 signaling system may play a role in the pathophysiology of BD.