Nandrolone Supplementation Promotes AMPK Activation and Divergent 18[FDG] PET Brain Connectivity in Adult and Aged Mice.

Decreased anabolic androgen levels are followed by impaired brain energy support and sensing with loss of neural connectivity during physiological aging, providing a neurobiological basis for hormone supplementation. Here, we investigated whether nandrolone decanoate (ND) administration mediates hypothalamic AMPK activation and glucose metabolism, thus affecting metabolic connectivity in brain areas of adult and aged mice. Metabolic interconnected brain areas of rodents can be detected by positron emission tomography using 18FDG-mPET. Albino CF1 mice at 3 and 18 months of age were separated into 4 groups that received daily subcutaneous injections of either ND (15 mg/kg) or vehicle for 15 days. At the in vivo baseline and on the 14th day, brain 18FDG-microPET scans were performed. Hypothalamic pAMPKT172/AMPK protein levels were assessed, and basal mitochondrial respiratory states were evaluated in synaptosomes. A metabolic connectivity network between brain areas was estimated based on 18FDG uptake. We found that ND increased the pAMPKT172/AMPK ratio in both adult and aged mice but increased 18FDG uptake and mitochondrial basal respiration only in adult mice. Furthermore, ND triggered rearrangement in the metabolic connectivity of adult mice and aged mice compared to age-matched controls. Altogether, our findings suggest that ND promotes hypothalamic AMPK activation, and distinct glucose metabolism and metabolic connectivity rearrangements in the brains of adult and aged mice.

Serum S100B in pregnancy complicated by preeclampsia: A case-control study.

BACKGROUND: Serum S100B is a protein produced and released primarily by astrocytes of the Central Nervous System (CNS). Elevated levels of serum S100B are associated with several types of pathological conditions of the brain, including the eclampsia in pregnant women. The aim of this study was to compare serum S100B concentrations in pregnant women with severe and mild preeclampsia (PE) with S100B serum levels in normotensive pregnant women. MATERIAL AND METHODS: Serum S100B protein was measured in normotensive pregnant women (n=15) and in women with mild PE (n=12) or severe PE (n=34). The serum S100B level (µg/L) was determined by an luminometric assay. RESULTS: Sixty-one expectant mothers were studied, aged 26.6±8.7 (mean±SD) years and with a gestational age of 33.3±4.2 weeks. The severe PE group demonstrated higher S100B levels (0.20±0.19), as compared with mild PE (0.07±0.05) or normotensive groups (0.04±0.05). CONCLUSION: Elevated serum S100B levels in pregnant women with severe PE suggest that some kind of neural damage and subsequent astrocytic release of S100B is not dependent on the progression from severe preeclampsia to eclampsia.

Non-alcoholic Wernicke's encephalopathy: broadening the clinicoradiological spectrum.

Wernicke's encephalopathy (WE) is a serious neurological disorder secondary to thiamine deficiency. Improved recognition by radiologists and allied health providers of the different clinical settings and imaging findings associated with this emergency can optimise the management of this condition and help prevent its severe consequences. The aim of this study is to illustrate the broad clinicoradiological spectrum of non-alcoholic WE, while emphasising atypical MRI findings.

Differential regulation of IgG-NMO autoantibodies on S100Beta protein and disability in relapsing neuromyelitis optica.

Neuromyelitis optica (NMO), an uncommon central nervous system (CNS) demyelinating disease, produces transverse myelitis and severe optic neuritis. IgG-NMO autoantibody, a specific immunoglobulin binding aquaporin-4 water channel protein, confirms that NMO is a different entity to multiple sclerosis. Parallel to cytokine down-regulations found in serum of relapsing-NMO (rNMO) patients, it has been reported that IgG-NMO may also confer a worse course of the disease in r-NMO Caribbean patients. In this study, we were interested in exploring the influence of IgG-NMO autoantibody on S100beta levels and clinical parameters from serum of r-NMO patients. Serum samples from 24 rNMO patients and 10 controls were evaluated. The reduction of S100beta observed in r-NMO patients was not significant compared to controls; and no differences were present regarding IgG-NMO immunoreactivity. At the same time, a significant correlation was also observed between IgG-NMO autoantibody serum detection and EDSS (Expanded Disability Status Scale) in rNMO. These results corroborate a differential regulation of IgG-NMO autoantibodies on the S100beta glial marker and on the disability present in rNMO patients.

The Declaration of Sydney on human death.

On 5 August 1968, publication of the Harvard Committee's report on the subject of "irreversible coma" established a standard for diagnosing death on neurological grounds. On the same day, the 22nd World Medical Assembly met in Sydney, Australia, and announced the Declaration of Sydney, a pronouncement on death, which is less often quoted because it was overshadowed by the impact of the Harvard Report. To put those events into present-day perspective, the authors reviewed all papers published on this subject and the World Medical Association web page and documents, and corresponded with Dr A G Romualdez, the son of Dr A Z Romualdez. There was vast neurological expertise among some of the Harvard Committee members, leading to a comprehensible and practical clinical description of the brain death syndrome and the way to diagnose it. This landmark account had a global medical and social impact on the issue of human death, which simultaneously lessened reception of the Declaration of Sydney. Nonetheless, the Declaration of Sydney faced the main conceptual and philosophical issues on human death in a bold and forthright manner. This statement differentiated the meaning of death at the cellular and tissue levels from the death of the person. This was a pioneering view on the discussion of human death, published as early as in 1968, that should be recognised by current and future generations.

Recognizing a mother's voice in the persistent vegetative state.

We studied an 8-year-old boy after a near-drowning left him in a vegetative state (VS) for 4 years before the study. Findings fulfilled all clinical criteria for the diagnosis of VS. The purpose of this study was to investigate whether there was significant differential activation of the brain in response to hearing his mother's voice compared with the voices of unknown women. The data were assessed using quantitative electric tomography (QEEGt), a technique that combines anatomical information of the brain by MRI with EEG patterns to estimate the sources of the EEG within the brain. We found significant differences for EEG frequencies from 14-58 Hz, with a peak at 33.2 Hz (gamma band). The 3D reconstruction showed that these statistical differences were localized in the lateral and posterior regions of the left hemisphere. No significant differences were found between unknown women vs. basal conditions. These results demonstrate recognition of the mother's voice and indicate high-level residual linguistic processing in a patient meeting clinical criteria for VS. These findings launch new ethical and practical implications for the management of VS patients.

QEEG prognostic value in acute stroke.

The objective of our study is to determine the predictive value of QEEG in patients suffering from an acute ischemic cerebral stroke. Twenty-eight patients were studied within the first 72 hours of clinical evolution of middle cerebral artery territory ischemic stroke. Thirty-seven QEEG recordings were obtained: 13 in the first 24 hours after cerebral stroke onset, 9 between 24-48 hours and 15 between 48-72 hours. Absolute Energies (AE) were the QEEG selected variables for statistical analysis: first, AE Z values were calculated using the Cuban QEEG norms, then the maximum and minimum AE Z values were selected within each frequency band and total power. The medians of the five neighboring Z values were also chosen. Regression models were estimated using the RANKIN scores as dependent variables and the selected QEEG variables as independent, then outcome predictions at hospital discharge and 3 months later were calculated. Percentages of concordance and errors between the estimated and real outcome scores were obtained. Alpha and theta AE were the best predictor for short-term outcome and delta AE for long-term outcome. We conclude that QEEG performed within the first 72 hours of ischemic stroke might be a powerful tool predicting short- and long-term outcome.

Highly palatable diet consumption increases protein oxidation in rat frontal cortex and anxiety-like behavior.

Obesity is frequently associated with consumption of high amounts of sugar and/or fat. Studies have demonstrated a high prevalence of overweight and obesity associated or not with increase rates of psychiatry disorders, in particular mood and anxiety disorders. Recent works have demonstrated an association between specific genes involved in oxidative stress metabolism and anxiety-like behavior. The aim of this study was to investigate the effect of a highly palatable diet enriched with sucrose in body fat mass composition, anxiety behavior and brain oxidative status. Twenty male Wistar rats received two different diets during four months: standard chow (SC) and highly palatable (HP). Metabolic parameters, behavioral tests and oxidative stress status were evaluated. Body fat mass, insulin sensitivity and glucose tolerance were altered in the HP group (p<0.01). The same group spends less time in light compartment and had a lower risk assessment behavior (p<0.05) but no differences were observed in the open field test habituation (p>0.05). Protein degradation, DCF and TBARS levels were not different in the hippocampus between groups; however, there were higher levels of protein degration in frontal cortex of HP groups (p<0.05), although DCF and TBARS levels don't differ from the SC group (p>0.05). In conclusion, our data suggest that the consumption of HP diet leads to an obese phenotype, increases protein oxidation in frontal cortex and appears to induce anxiety-like behavior in rats.

Methotrexate induces seizure and decreases glutamate uptake in brain slices: prevention by ionotropic glutamate receptors antagonists and adenosine.

Methotrexate (MTX)-induced neurotoxicity may occur after intrathecal or systemic administration at low, intermediate and high doses for the treatment of malignant or inflammatory diseases. The mechanisms of MTX neurotoxicity are not totally understood, and appear to be multifactorial. In this study we characterized a model of MTX-induced seizures in mice to evaluate the convulsive and toxic MTX properties. Additionally, the effect of MTX-induced seizures on the activity of glutamate transporters, as well as the anticonvulsant role of MK-801, DNQX and adenosine on glutamate uptake in brain slices was investigated . MTX induced tonic-clonic seizures in approximately 95% of animals and pre-treatment with MK-801, DNQX and adenosine prevented seizure in 80%, 62% and 50% of animals, respectively. Moreover, MTX leads 59% of mice to death, which was prevented in 100% and 94% when animals received MK-801 and DNQX, respectively. Glutamate uptake decreased by 20% to 30% in cortical slices after MTX-induced seizures. Interestingly, when seizures were prevented by MK-801, DNQX or adenosine, glutamate uptake activity remained at the same level as the control group. Thus, our results demonstrate the involvement of the glutamatergic system in MTX-induced seizures.

Raised serum S100B protein levels in neuropsychiatric lupus.

OBJECTIVE: To test serum S100B protein levels in patients with and without neuropsychiatric systemic lupus erythematosus (NPSLE) and controls. METHODS: 87 patients with SLE, 23 with and 64 without neuropsychiatric involvement, and 25 control subjects were prospectively evaluated. NPSLE diagnosis was made according to the American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Serum S100B protein levels were determined with a luminescence immunoassay. Statistical analysis was performed using Mann-Whitney and Kruskal-Wallis tests. RESULTS: Among the patients with NPSLE, 9 presented psychosis; 4, cranial neuropathy; 3, cerebrovascular disease; 1, seizures; 1, chorea; 1, peripheral polyneuropathy; 1, multiplex mononeuropathy; 3, dementia. Serum concentrations of S100B protein were significantly higher in patients with NPSLE (median 0.164 ng/ml, interquartile range 0.113-0.332) than in non-NPSLE patients (0.062 ng/ml, 0.026-0.109) and controls (0.088 ng/ml, 0.013-0.124) (p<0.001). Patients with anti-dsDNA antibodies had higher S100B protein levels (p = 0.001). No significant associations were found of lupus activity (among non-NPSLE cases), antiphospholipid antibodies, and reduced complement levels with S100B concentration. CONCLUSIONS: Serum S100B protein level is raised in NPSLE, reflecting continuing neurological damage. The association of anti-dsDNA antibodies with higher S100B protein concentration deserves further study.

Serum and cerebrospinal fluid S100B concentrations in patients with neurocysticercosis.

The clinical manifestations of neurocysticercosis (NC) are varied and depend on the number and location of cysts, as well as on the host immune response. Symptoms usually occur in NC when cysticerci enter a degenerative course associated with an inflammatory response. The expression of brain damage markers may be expected to increase during this phase. S100B is a calcium-binding protein produced and released predominantly by astrocytes that has been used as a marker of reactive gliosis and astrocytic death in many pathological conditions. The aim of the present study was to investigate the levels of S100B in patients in different phases of NC evolution. Cerebrospinal fluid and serum S100B concentrations were measured in 25 patients with NC: 14 patients with degenerative cysts (D), 8 patients with viable cysts (V) and 3 patients with inactive cysts. All NC patients, except 1, had five or less cysts. In most of them, symptoms had been present for at least 1 month before sample collection. Samples from 8 normal controls (C) were also assayed. The albumin quotient was used to estimate the blood-brain barrier permeability. There were no significant differences in serum (P = 0.5) or cerebrospinal fluid (P = 0.91) S100B levels among the V, D, and C groups. These findings suggest that parenchymal changes associated with a relatively small number of degenerating cysts probably have a negligible impact on glial tissue.

Serum and cerebrospinal fluid S100B concentrations in patients with neurocysticercosis

The clinical manifestations of neurocysticercosis (NC) are varied and depend on the number and location of cysts, as well as on the host immune response. Symptoms usually occur in NC when cysticerci enter a degenerative course associated with an inflammatory response. The expression of brain damage markers may be expected to increase during this phase. S100B is a calcium-binding protein produced and released predominantly by astrocytes that has been used as a marker of reactive gliosis and astrocytic death in many pathological conditions. The aim of the present study was to investigate the levels of S100B in patients in different phases of NC evolution. Cerebrospinal fluid and serum S100B concentrations were measured in 25 patients with NC: 14 patients with degenerative cysts (D), 8 patients with viable cysts (V) and 3 patients with inactive cysts. All NC patients, except 1, had five or less cysts. In most of them, symptoms had been present for at least 1 month before sample collection. Samples from 8 normal controls (C) were also assayed. The albumin quotient was used to estimate the blood-brain barrier permeability. There were no significant differences in serum (P = 0.5) or cerebrospinal fluid (P = 0.91) S100B levels among the V, D, and C groups. These findings suggest that parenchymal changes associated with a relatively small number of degenerating cysts probably have a negligible impact on glial tissue.

Methylmercury increases S100B content in rat cerebrospinal fluid.

S100B, a calcium binding protein physiologically produced and released by astrocytes, has been used as a peripheral marker of brain damage. Here, we investigated the effects of subcutaneous injections of methylmercury chloride (MeHg-5mg/kg), an environmental neurotoxicant, on S100B protein content in cerebrospinal fluid (CSF) of adult rats. In addition, the performance of animals in an open field (number of squares crossing and rearings) was also analyzed in order to obtain a possible link between alteration in S100B protein content in CSF and parameters related to neurological injury. MeHg treatment increased serum mercury and S100B protein levels in the CSF. A decrease in the numbers of crossings and rearings was observed in MeHg-treated animals when compared to control group, which suggests a possible neurological injury. The present data show, for the first time, increased S100B levels in CSF after exposure to a neurotoxic metal. Authors discuss the possibility of astrocytic involvement in MeHg-induced neurotoxicity.

Apert syndrome: analysis of associated brain malformations and conformational changes determined by surgical treatment.

Apert Syndrome, also called acrocephalosyndactylia type 1, is characterized by craniostenosis with early fusion of sutures of the vault and/or cranial base, associated to mid-face hypoplasia, symmetric syndactylia of the hands and feet and other systemic malformations. CNS malformations and intracranial hypertension are frequently observed in these patients. Early surgical treatment aims to minimize the deleterious effects of intracranial hypertension. Fronto-orbital advancement, the usual surgical technique, increases the intracranial Volume and improves the disposition of encephalic structures previously deformed by a short skull. This study analyzes CNS alterations revealed by magnetic resonance in 18 patients presenting Apert Syndrome, and the conformational alterations in the encephalic structures after surgical treatment. The patients' age in February 2001 ranged from 14 to 322 Months (m=107). Image study included brain magnetic resonance showing ventricular enlargement in five cases (27.8%), corpus callosum hypoplasia in five cases (27.8%), septum pellucidum hypoplasia in five cases (27.8%), cavum vergae in two cases (11.1%) and, arachnoid cyst in the posterior fossa in two cases (11.1%). Absence of CNS alterations was noted in 44.4% of cases. A corpus callosum morphologic index was established by dividing its height by its length, which revealed values that ranged from 0.4409 to 1.0237. The values of this index were correlated to the occurrence or absence of surgical treatment (p=0.012; t=2.83). Data analysis allowed the conclusion that the corpus callosum morphologic measure quantified the conformational alterations of the cerebral structures determined by the surgical treatment.

Interictal serum S100B levels in chronic neurocysticercosis and idiopathic epilepsy.

OBJECTIVE: To assess whether serum S100B levels could reflect a glial response in patients with epilepsy secondary to neurocysticercosis (NCC) and with idiopathic epilepsy. SUBJECTS AND METHODS: Serum S100B levels were measured using an immunoluminometric assay in 20 patients with focal epilepsy related to chronic NCC (NCC group), and 19 patients with focal epilepsy (EPI group), matched by epidemiological and clinical data. Epileptic patients were compared with 20 healthy controls (CON group) matched by age and sex. RESULTS: No difference was observed in S100B levels among NCC, EPI and CON groups (P>0.39). Serum S100B levels were not affected by antiepileptic drugs, frequency and type of seizures. Preliminarily, significantly higher levels of S100B were observed in patients with bilateral electroencephalographic (EEG) findings than in patients with unilateral and normal EEG findings (P<0.05). CONCLUSION: Serum S100B is normal in patients with focal epilepsy related or not to chronic NCC.

Elevated serum S100B protein in drug-free bipolar patients during first manic episode: a pilot study.

S100B protein is a calcium-binding protein mostly derived from glial cells, which exerts trophic or toxic effects on neural cells depending on its concentration. Since serum S100B levels has been tested as a potential marker in neuropsychiatric disorders, and structural abnormalities on glial cells have been recently associated with bipolar disorder patients, we conducted this preliminary study to examine if S100B serum levels are altered during first manic episode. We quantitated S100B in serum of 40 subjects (20 unmedicated patients during manic episode and 20 healthy matched controls). The mean+/-S.D. values for S100B for bipolar subjects were 0.065+/-0.068 microg/l and 0.018+/-0.029 microg/l for healthy controls. Increased levels of S100B in bipolar mania was statistically significant (Wilcoxon signed ranks test, Z=-2.45, P=0.01). These preliminary findings suggest that mania may increase the levels of S100B in serum of bipolar disorder patients, which could be related to adaptative neural mechanisms in bipolar mania.

[Gender and night work: sleep, daily life and the experiences of night shift workers]. / Gênero e trabalho noturno: sono, cotidiano e vivências de quem troca a noite pelo dia.

This paper deals with the impact of night work from a gender perspective, through a field study at a factory employing men and women on the night shift. It is based on data for hours of sleep over the course of several weeks, socio-demographic data, and job information, using a semi-structured interview. The methodology includes chronobiological aspects of sleep (mainly quantitative data) and workers' discourse concerning gender-related experiences in the day-to-night switch. Despite gender issues and differences in daily life, the switch is perceived quite vividly by both men and women, permeating several aspects of life, like health, leisure, studies, and intimate personal relations. Quantitative sleep analysis showed more severe effects of night work on women, especially those with children. Such sleep patterns were associated with different expectations among men and women, revealing gender issues that are essential for understanding the reality of individuals who work odd hours.

Increased serum S100B protein in schizophrenia: a study in medication-free patients.

S100B protein, a calcium binding protein produced and released by glial cells, has been used as a sensitive marker of brain damage. Previous studies have found alterations in peripheral S100B levels in schizophrenic patients on medication. We compared serum S100B levels of 20 medication-free DSM-IV schizophrenic patients and 20 age-gender matched healthy controls. Schizophrenic patients presented higher serum S100B levels (mean 0.120 ng/ml+/-S.D. 0.140) compared to controls (mean 0.066 ng/ml+/-S.D. 0.067; P=0.014) and there was a negative correlation with illness duration (r=-0.496, P=0.031). The results of this study indicate that serum S100B levels may be a state marker of a limited neurodegenerative process, particularly in the early course of schizophrenia or, at least, in a subgroup of schizophrenic patients.

Gender and sleep in nightworkers: a quantitative analysis of sleep in days off.

Differences in sleep patterns between workdays and days off contribute to shiftwork effects on workers' health and well-being. But regardless of shift schedules, female workers face more difficulties in fulfilling their sleep need because of housework. This study analyzes gender differences concerning sleep in days off by comparing sleep patterns in male and female nightworkers, analyzing sleep as related to the presence of children and testing the association of sleep features between workdays and days off. Male (n = 16) and female (n = 30) workers at a plastic plant, working from 10 p.m. to 6 a.m., on weekdays, filled sleep logs for seven consecutive weeks. Male and female samples did not differ in length of night sleep or in total length of sleep. For both samples, sleep length/day in days off increased, but the difference was lager among females. Also important were the relations between sleep in workdays and days off, specially among women. Among female workers, the results indicated that workers with children tended to sleep less in Saturday mornings, suggesting a negative effect of motherhood on sleep not restricted to workdays. The general results indicate that sleep need on the one hand, and social factors on the other determine the actual amount of sleep.

Digitonin-permeabilization of astrocytes in culture monitored by trypan blue exclusion and loss of S100B by ELISA.

The present protocol details a procedure to permeabilize astrocytes in cultures with digitonin as well as to discuss some data about factors that interfere in permeabilization, particularly divalent cations and nucleotides. Two methods to assess astrocyte permeabilization are described: trypan blue exclusion and ELISA for S100B, a specific protein expressed by these cells. Digitonin-permeabilization of astrocytes has been used to investigate intracellular pools of Ca(2+), internal stores of metabolites, phosphoinositide hydrolysis, and recently we standardized a procedure to study protein phosphorylation (Brain Res. 853 (2000) 32-40). A short incubation time (10 min) with 30 microM digitonin permeabilized at least 75% of cells. A range of media with different ionic nature can be used in cell permeabilization without affecting significantly the extent of permeabilization, but calcium and ATP of the order of 10(-5) M induced a partial resealing which deserves to be considered in assays of permeabilized preparations of astrocytes.