Lateral parabrachial lesions disrupt paraoxon-induced conditioned flavor avoidance.

Preliminary clinical evidence obtained in Gulf War veterans and patients suffering multiple chemical sensitivity points to the existence of a potential link between environmental exposure to organosphosphates (OPs) and the emergence of unspecific sickness syndromes in which associative Pavlovian conditioning might be partly involved. A laboratory animal model might be a useful tool for analyzing the involvement of conditioning in sickness syndromes potentially linked to OP poisoning. The first objective in the present study was to determine if paraoxon (PX), the neuroactive metabolite of the OP parathion, elicits a conditioned avoidance response to a novel stimulus (a taste-odor compound) in a conditioned flavor aversion procedure. Data obtained in Experiment 1 show conditioned flavor avoidance, demonstrative of the associative nature of the sickness properties of PX. The second objective was to characterize the nature of the specific physiological cue serving as the unconditioned stimulus in PX-induced conditioned avoidance. Despite PX administration did induce cholinergic hyperactivity, as measured by body hypothermia and increased jaw movements, lesions of the lateral parabrachial area (lPB) disrupted PX-elicited flavor avoidance responses, indicating that cholinergic signs were not sufficient as unconditioned stimuli supporting avoidance responses. Given that lPB neural integrity is necessary to process aversive interoceptive information, disruption of conditioned flavor avoidance as a result of lPB lesions is consistent with a central interruption of interoceptive processing in PX-poisoned animals. Data are discussed under the light of the hypothesis claiming the importance of associative processes and noncholinesterase targets in sickness syndromes potentially induced by OP exposure.     

Identification of novel candidate target genes in amplicons of Glioblastoma multiforme tumors detected by expression and CGH microarray profiling

Background  

Conventional cytogenetic and comparative genomic hybridization (CGH) studies in brain malignancies have shown that glioblastoma multiforme (GBM) is characterized by complex structural and numerical alterations. However, the limited resolution of these techniques has precluded the precise identification of detailed specific gene copy number alterations.     

General Treatment of the Enterohepatic Recirculation of Drugs and Its Influence on the Area Under the Plasma Level Curves,Bioavailability, and Clearance

A general treatment of enterohepatic recirculation of drugs has been developed based on the fraction of drug in systemic circulation that is excreted in the bile and the fraction of drug reabsorbed from the gut that reaches systemic circulation in each enterohepatic cycle. The deduced equations make it possible to establish mathematical relationships between the areas under the blood level curves (AUC) of a drug when administered to normal and bile duct-cannulated animals and to predict the effect of enterohepatic recycling on bio-availability and clearance. The results were compared with those obtained by other authors using different approaches to enterohepatic recirculation, and some discrepancies were found in the equations describing the effect of enterohepatic recycling on AUC and bioavailability of drugs. The cause of such discrepancies and the problems associated with the prediction of hepatic extraction ratio from in vitro studies are discussed.     

Chronic mild stress induces behavioral and physiological changes,and may alter serotonin 1A receptor function,in male and cycling female rats

Rationale Interactions among stress, serotonin 1A (5-HT_1A) receptors, and the hypothalamic–pituitary–adrenocortical (HPA) system have been proposed to influence the development of depression in humans. The investigation of depression-relevant behaviors and physiological responses to environmental stressors in animal models of depression may provide valuable insight regarding these mechanisms.Objectives The purpose of these experiments was to investigate the interactions among central 5-HT_1A receptors, endocrine function, and behavior in an animal model of depression, chronic mild stress (CMS).Methods The current study examined behavioral responses to a pleasurable stimulus (sucrose), estrous cycle length (in female rats), and plasma hormone levels following systemic administration of a selective 5-HT_1A receptor agonist [(+)8-hydroxy-N,N-dipropyl-2-aminotetralin hydrobromide (8-OH-DPAT); 40 g/kg, s.c.; administered 15 min prior to sacrifice], in male and female rats exposed to 4 weeks of CMS.Results Four weeks of CMS produced a reduction in the intake of 1% sucrose (anhedonia), as well as attenuated adrenocorticotropic hormone (ACTH) responses to 8-OH-DPAT in both male and female rats (22 and 18% lower than the control groups, respectively). Corticosterone and oxytocin responses to 8-OH-DPAT were not altered by exposure to CMS. In female rats, CMS induced a lengthening of the estrous cycle by 40%.Conclusions CMS produces minor HPA disruptions along with behavioral disruptions. Alterations in 5-HT_1A receptor function in specific populations of neurons in the central nervous system may be associated with the CMS model. The current findings contribute to our understanding of the relations that stress and neuroendocrine function have to depressive disorders.     

Antioxidant effect of nimodipine in young rats after pilocarpine-induced seizures

Nimodipine (ND) is a centrally active calcium antagonist that blocks the voltage-dependent L-type channels. Its antiepileptic properties have been proved in various animal models, including pilocarpine-induced seizures in adult rats. In order to investigate protective effects of the ND (10 (ND10) and 30 mg/kg (ND30), i.p.), young male rats (21-day-old) received ND injections before pilocarpine administration (400 mg/kg, s.c., pilocarpine group (P400)). The pretreatment with ND10 and ND30 prolonged the latencies of seizures and death on this seizure model. ND pretreatment in two doses decreased the levels of lipid peroxidation when compared to pilocarpine group. The P400 administration increased the striatal catalase activity. However, the administration of ND, in dose of 30 mg/kg, 30 min before pilocarpine, preserved catalase activity in normal levels. On the other hand, no change was detected in the animals treated with the dose of 10 mg/kg. Our results confirm the neuroprotective effect of ND on the seizures in young rats, suggesting that this drug acts positively on lipid peroxidation. Our observations shows that nimodipine cannot induces these effects via blockade of Ca(2+)-channel.     

The services for women victims of sexual violence: a qualitative study

OBJECTIVE: To assess public services attending female victims of sexual violence in the city of Sao Paulo. METHODS: This is a qualitative study conducted in two public services attending female victims of sexual violence. Interviews with 42 women were conducted, 13 of whom had sought these services for assistance and 29 were professionals working in these services. Evaluation of the services was based on the categories: reception, access, resolvability and sanitary responsibility. RESULTS: The analysis of the interviews per category has shown that there was reception in both services, problems with respect to access due to the lack of information concerning these services, and quality resolvability with a multi-professional team. As to the sanitary responsibility, it is present in these specialized services but is deficient in the emergency services and basic health care units. Many women are unaware of the rights they are entitled to with respect to specialized services. Frequently their late arrival compromises the efficacy of care. There are deficiencies both in terms of reference and counter reference. CONCLUSIONS: The results ratify the importance of these services and the need for their decentralized expansion. Health courses should introduce the theme of sexual violence at the undergraduate level.     

Clinical evaluation of multisurface ART restorations

The aim of this study was to evaluate the performance of two different glass-ionomer cements: a high-density (Ketac Molar - ESPE) and a resin-modified cement (Fuji VIII - GC) using the Atraumatic Restorative Treatment technique to restore multisurface cavities in permanent teeth. A total of 60 ART restorations (30 with each material) were placed in schoolchildren (9-16 years of age) by two operators. After a period of 6 months, two independent examiners evaluated 59 restorations according to the criteria used in previous ART studies. Data were submitted to McNemar and Fischer tests. The success rate of the treatment was 98.3%. One restoration (Ketac Molar) was replaced by another material and was recorded as failure. The success rates of the restorations were 100% and 96.6% for Fuji VIII and Ketac Molar, respectively. There was no statistically significant difference in the restorations success between baseline and 6 months (p>0.05). In the same way, no significant differences were found between materials, cavity types or operators (p>0.05). The ART approach was highly appropriate and effective in restorations involving two or more tooth surfaces, after 6 months. The results showed a promising performance of the ART technique with both materials.     

Ciprofloxacin, but not levofloxacin, affects cyclosporine blood levels in a patient with pure red blood cell aplasia

A 38-year-old man diagnosed with pure red blood cell aplasia was undergoing treatment with cyclosporine 200 mg/day. On day 41, the cyclosporine dose was increased to 250 mg/day. On day 45, the patient was hospitalized with fever, and ciprofloxacin 200 mg IV tid was begun. The level of cyclosporine was 297 ng/mL, which obliged us to reduce cyclosporine to 200 mg/day. On day 59, ciprofloxacin was discontinued. On day 80, the patient was hospitalized with fever, and levofloxacin 500 mg/d IV was begun. The patient was continued on cyclosporine 250 mg/day. On day 90, levofloxacin was discontinued. The cyclosporine dose-to-blood level ratio was maintained constant in subsequent controls. In this patient, the substantial and sustained increase in cyclosporine blood levels after ciprofloxacin was added to the patient's therapy and the decrease in cyclosporine blood levels after the withdrawal of ciprofloxacin suggest a potential interaction. Levofloxacin therapy could be a therapeutic alternative, although pharmacokinetic/pharmacodynamic studies should be conducted.     

Decreased gonadotropin-releasing hormone neuronal activity is associated with decreased fertility and dysregulation of food intake in the female GPR-4 transgenic rat

Expression of a cAMP-specific phosphodiesterase in GnRH neurons in the GPR-4 transgenic rat resulted in decreased LH levels and pulse frequency and diminished fertility. We have characterized changes in fertility, adiposity, and reproductive and metabolic hormones with age. Although LH levels were decreased in 3-, 6-, and 9-month-old GPR-4 females relative to wild-type (WT) controls, GPR-4 females did not become anovulatory until 6 months of age. No differences were observed in FSH, estradiol, or androstenedione levels in 3-, 6-, or 9-month-old GPR-4 and WT females. At 9 months of age, GPR-4 females had significantly increased abdominal and sc fat depot weights that were associated with increased leptin and insulin levels not observed in WT females. We tested the hypothesis that metabolic changes observed at 9 months of age were the result of dysregulation of the mechanisms controlling energy balance. Two-month-old female GPR-4 rats placed on a high-energy diet gained weight at a rate significantly greater than WT females and, after 24 d, developed the same metabolic phenotype observed in 9-month-old GRP-4 females (increased abdominal and sc fat associated with elevated leptin and insulin concentrations). Overeating did not correlate with changes in estradiol or androstenedione levels. We conclude that decreased GnRH neuronal activity is closely associated with decreased reproductive function and dysregulation of food intake.     

Amantadine reduces the duration of levodopa-induced dyskinesia: a randomized, double-blind, placebo-controlled study

We evaluated the effects of amantadine on levodopa-induced dyskinesia (LID) in eighteen consecutive Parkinson's disease (PD) patients in a randomized, double-blind, placebo-controlled study. The primary outcomes were the Clinical Dyskinesia Rating Scale (CDRS) and the Unified Parkinson's Disease Rating Scale (UPDRS) part IVa score changes. The secondary outcomes were the UPDRS II and III score changes. Amantadine did not change the CDRS score for hyperkinesia or dystonia, but decreased the duration of LID and its influence on daily activities (p=0.04) and the UPDRS II score (p=0.01) more than placebo. These findings show that amantadine reduces the duration of LID and improves motor disability in PD.