Changes in extracellular levels of glutamate in the nucleus accumbens after ethanol-induced behavioral sensitization in adolescent and adult mice

Repeated administration of low doses of ethanol gradually increases locomotor responses to ethanol in adult Swiss mice. This phenomenon is known as behavioral sensitization. However, we have shown that adolescent Swiss mice show either behavioral tolerance or no sensitization after repeated ethanol injections. Although the mesolimbic dopamine system has been extensively implicated in behavioral sensitization, several studies have demonstrated an important role of glutamatergic transmission in this phenomenon. In addition, relatively few studies have examined the role of developmental factors in behavioral sensitization to ethanol. To examine the relationship between age differences in behavioral sensitization to ethanol and the neurochemical adaptations related to glutamate within nucleus accumbens (NAc), in vivo microdialysis was conducted in adolescent and adult Swiss mice treated with ethanol (1.8 g/kg) or saline for 15 days and subsequently challenged with an acute dose (1.8 g/kg) of ethanol 6 days later. Consistent with previous findings, only adult mice demonstrated evidence of behavioral sensitization. However, ethanol-treated adolescent mice demonstrated a 196.1 +/- 40.0% peak increase in extracellular levels of glutamate in the NAc after ethanol challenge in comparison with the basal values, whereas ethanol-treated adult mice demonstrated a 52.2 +/- 6.2% reduction in extracellular levels of glutamate in the NAc after ethanol challenge. These observations suggest an age-dependent inverse relationship between behavioral and glutamatergic responses to repeated ethanol exposure. (C) 2011 Elsevier Inc. All rights reserved.

Environmental modulation of ethanol-induced locomotor activity: Correlation with neuronal activity in distinct brain regions of adolescent and adult Swiss mice

Drug abuse is a concerning health problem in adults and has been recognized as a major problem in adolescents. induction of immediate-early genes (IEG), such as c-Fos or Egr-1, is used to identify brain areas that become activated in response to various stimuli, including addictive drugs. It is known that the environment can alter the response to drugs of abuse. Accordingly, environmental cues may trigger drug-seeking behavior when the drug is repeatedly administered in a given environment. The goal of this study was first to examine for age differences in context-dependent sensitization and then evaluate IEG expression in different brain regions. For this, groups of mice received i.p. ethanol (2.0 g/kg) or saline in the test apparatus, while other groups received the solutions in the home cage, for 15 days. One week after this treatment phase, mice were challenged with ethanol injection. Acutely, ethanol increased both locomotor activity and IEG expression in different brain regions, indistinctly, in adolescent and adult mice. However, adults exhibited a typical context-dependent behavioral sensitization following repeated ethanol treatment, while adolescent mice presented gradually smaller locomotion across treatment, when ethanol was administered in a paired regimen with environment. Conversely, ethanol-treated adolescents expressed context-independent behavioral sensitization. Overall, repeated ethanol administration desensitized IEG expression in both adolescent and adult mice, but this effect was greatest in the nucleus accumbens and prefrontal cortex of adolescents treated in the context-dependent paradigm. These results suggest developmental differences in the sensitivity to the conditioned and unconditioned locomotor effects of ethanol. (C) 2008 Elsevier B.V. All rights reserved.

Population-Based Multicentric Survey of Hepatitis B Infection and Risk Factor Differences among Three Regions in Brazil

This multicentric population-based study in Brazil is the first national effort to estimate the prevalence of hepatitis B (HBV) and risk factors in the capital cities of the Northeast. Central-West, and Federal Districts (2004-2005). Random multistage cluster sampling was used to select persons 13-69 years of age. Markers for HBV were tested by enzyme-linked immunosorbent assay. The HBV genotypes were determined by sequencing hepatitis B surface antigen (HBsAg). Multivariate analyses and simple catalytic model were performed. Overall. 7,881 persons were inculded < 70% were not vaccinated. Positivity for HBsAg was less than 1% among non-vaccinated persons and genotypes A, D, and F co-circulated. The incidence of infection increased with age with similar force of infection in all regions. Males and persons having initiated sexual activity were associated with HBV infection in the two settings: healthcare jobs and prior hospitalization were risk factors in the Federal District. Our survey classified these regions as areas with HBV endemicity and highlighted the risk factors differences among the settings.

The renin-angiotensin system is modulated by swimming training depending on the age of spontaneously hypertensive rats

Aim: To investigate the effects of swimming training on the renin-angiotensin system (RAS) during the development of hypertensive disease. Main methods: Male spontaneously hypertensive rats (SHR) were randomized into: sedentary young (SY), trained young (TV), sedentary adult (SA), and trained adult (TA) groups. Swimming was performed 5 times/wk/8wks. Key findings: Trained young and adult rats showed both decreased systolic and mean blood pressure, and bradycardia after the training protocol. The left ventricular hypertrophy (LVH) was observed only in the TA group (12.7%), but there was no increase on the collagen volume fraction. Regarding the components of the RAS, TV showed lower activity and gene expression of angiotensinogen (AGT) compared to SY. The TA group showed lower activity of circulatory RAS components, such as decreased serum ACE activity and plasma renin activity compared to SA. However, depending on the age, although there were marked differences in the modulation of the RAS by training, both trained groups showed a reduction in circulating angiotensin II levels which may explain the lower blood pressure in both groups after swimming training. Significance: Swimming training regulates the RAS differently in adult and young SHR rats. Decreased local cardiac RAS may have prevented the LVH exercise-induced in the TV group. Both groups decreased serum angiotensin II content, which may, at least in part, contribute to the lowering blood pressure effect of exercise training. (C) 2011 Elsevier Inc. All rights reserved.

S100 beta Protein Expression: Gender- and Age-Related Daily Changes

S100 beta is a soluble protein released by glial cells mainly under the activation of the 5-HT1A receptor. It has been reported as a neuro-trophic and -tropic factor that promotes neurite maturation and outgrowth during development. This protein also plays a role in axonal stability and the plasticity underlying long-term potentiation in adult brains. The ability of S100 beta to rapidly regulate neuronal morphology raises the interesting point of whether there are daily rhythm or gender differences in S100 beta level in the brain. To answer this question, the S100 beta expression in adult female and male rats, as well as in adult female CD-21 and S100 beta -/- female mice, were investigated. Scintillation counting and morphometric analysis of the immunoreactivity of S100 beta, showed rhythmic daily expression. The female and male rats showed opposite cycles. Females presented the highest value at the beginning of the rest phase (5:00 h), while in males the maximum value appeared in the beginning of the motor activity period (21:00 h). These results confirm previous S100 beta evaluations in human serum and cerebrospinal fluid reporting the protein`s function as a biomarker for brain damage (Gazzolo et al. in Clin Chem 49:967-970, 2003; Clin Chim Acta 330:131-133, 2003; Pediatr Res 58:1170-1174, 2005), similar behavior was also observed for GFAP in relation to Alzheimer Disease (Fukuyama et al. in Eur Neurol 46:35-38, 2001). The data should be taken into account when considering S100 beta as a biomarker of health condition. In addition, the results raise questions on which structure or condition imposes these rhythms as well as on the physiological meaning of the observed gender differences.

Effect of Age on Outcome of Reduced-Intensity Hematopoietic Cell Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission or With Myelodysplastic Syndrome

Purpose Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) primarily afflict older individuals. Hematopoietic cell transplantation (HCT) is generally not offered because of concerns of excess morbidity and mortality. Reduced-intensity conditioning (RIC) regimens allow increased use of allogeneic HCT for older patients. To define prognostic factors impacting long-term outcomes of RIC regimens in patients older than age 40 years with AML in first complete remission or MDS and to determine the impact of age, we analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR). Patients and Methods We reviewed data reported to the CIBMTR (1995 to 2005) on 1,080 patients undergoing RIC HCT. Outcomes analyzed included neutrophil recovery, incidence of acute or chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, disease-free survival (DFS), and overall survival (OS). Results Univariate analyses demonstrated no age group differences in NRM, grade 2 to 4 acute GVHD, chronic GVHD, or relapse. Patients age 40 to 54, 55 to 59, 60 to 64, and >= 65 years had 2-year survival rates as follows: 44% (95% Cl, 37% to 52%), 50% (95% Cl, 41% to 59%), 34% (95% Cl, 25% to 43%), and 36% (95% Cl, 24% to 49%), respectively, for patients with AML (P = .06); and 42% (95% Cl, 35% to 49%), 35% (95% Cl, 27% to 43%), 45% (95% Cl, 36% to 54%), and 38% (95% Cl, 25% to 51%), respectively, for patients with MDS (P = .37). Multivariate analysis revealed no significant impact of age on NRM, relapse, DFS, or OS (all P>.3). Greater HLA disparity adversely affected 2-year NRM, DFS, and OS. Unfavorable cytogenetics adversely impacted relapse, DFS, and OS. Better pre-HCT performance status predicted improved 2-year OS. Conclusion With these similar outcomes observed in older patients, we conclude that older age alone should not be considered a contraindication to HCT.

Obsessive-compulsive disorder: Influence of age at onset on comorbidity patterns

Purpose. - This study investigates the influence of age at onset of OCS on psychiatric comorbidities, and tries to establish a cut-off point for age at onset. Methods. - Three hundred and thirty OCD patients were consecutively recruited and interviewed using the following structured interviews: Yale-Brown Obsessive Compulsive Scale; Yale Global Tic Severity Scale and the Structured Clinical Interview for DSM-IV. Data were analyzed with regression and cluster analysis. Results. - Lower age at onset was associated with a higher probability of having comorbidity with tic, anxiety, somatoform, eating and impulse-control disorders. Longer illness duration was associated with lower chance of having tics. Female gender was associated with anxiety, eating and impulse-control disorders. Tic disorders were associated with anxiety disorders and attention-deficit/hyperactivity disorder. No cutoff age at onset was found to clearly divide the sample in homogeneous subgroups. However, cluster analyses revealed that differences started to emerge at the age of 10 and were more pronounced at the age of 17, suggesting that these were the best cut-off points on this sample. Conclusions. - Age at onset is associated with specific comorbidity patterns in OCD patients. More prominent differences are obtained when analyzing age at onset as an absolute value. (C) 2008 Elsevier Masson SAS. All rights reserved.