Corticosterone Potentiation of Cocaine-Induced Reinstatement of Conditioned Place Preference in Mice is Mediated by Blockade of the Organic Cation Transporter 3

The mechanisms by which stressful life events increase the risk of relapse in recovering cocaine addicts are not well understood. We previously reported that stress, via elevated corticosterone, potentiates cocaine-primed reinstatement of cocaine seeking following self-administration in rats and that this potentiation appears to involve corticosterone-induced blockade of dopamine clearance via the organic cation transporter 3 (OCT3). In the present study, we use a conditioned place preference/reinstatement paradigm in mice to directly test the hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3. Consistent with our findings following self-administration in rats, pretreatment of male C57/BL6 mice with corticosterone (using a dose that reproduced stress-level plasma concentrations) potentiated cocaine-primed reinstatement of extinguished cocaine-induced conditioned place preference. Corticosterone failed to re-establish extinguished preference alone but produced a leftward shift in the dose–response curve for cocaine-primed reinstatement. A similar potentiating effect was observed upon pretreatment of mice with the non-glucocorticoid OCT3 blocker, normetanephrine. To determine the role of OCT3 blockade in these effects, we examined the abilities of corticosterone and normetanephrine to potentiate cocaine-primed reinstatement in OCT3-deficient and wild-type mice. Conditioned place preference, extinction and reinstatement of extinguished preference in response to low-dose cocaine administration did not differ between genotypes. However, corticosterone and normetanephrine failed to potentiate cocaine-primed reinstatement in OCT3-deficient mice. Together, these data provide the first direct evidence that the interaction of corticosterone with OCT3 mediates corticosterone effects on drug-seeking behavior and establish OCT3 function as an important determinant of susceptibility to cocaine use

International Veterinary Epilepsy Task Force Consensus Proposal: Diagnostic approach to epilepsy in dogs

This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause. Differentiation of epileptic seizures from other non-epileptic episodic paroxysmal events can be challenging. Criteria that can be used to make this differentiation are presented in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset 6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose

Cut Throat Injuries at a University Teaching Hospital in Northwestern Tanzania: A Review of 98 cases.

Cut throat injuries though rarely reported in literature pose a great therapeutic challenge because multiple vital structures are vulnerable to injuries in the small, confined unprotected area. A sudden increase in the number of cut throat patients in our centre in recent years prompted the authors to analyze this problem. This study was conducted in our local setting to describe the etiology, patterns and treatment outcome of these injuries. This was a combined retrospective and prospective study of cut throat injury patients who were managed at Bugando Medical Centre between February 2009 and January 2013. Statistical data analysis was done using SPSS software version 17.0. A total of 98 patients with cut throat injuries were studied. Males outnumbered females by a ratio of 2.4: 1. The median age of patients was 26 years (range 8 to 78 years). Majority of patients (79.6%) had no employment and most of them (65.3%) came from rural community. Homicide was the commonest (55.1%) cause, followed by suicidal attempts (34.7%) and accidental (10.2%) injuries. Interpersonal conflict (24.4%) was the most common motivating factor for homicidal injury whereas psychiatric illness (16.2%) and road traffic accidents (9.2%) were the most frequent motivating factors of suicidal attempt and accidental injuries respectively. The majority of injuries were in Zone II accounting for 65.3% of cases and most of them had laryngeal (57.1%) injury. Surgical debridement, laryngeal/hypopharynx repair and tracheostomy were the most common surgical procedures performed in 93.9%, 73.5% and 70.4% of patients respectively. Postoperative complication rate was 57.1%, the commonest being surgical site infections in 28.1% of patients and it was significantly associated with late presentation and anatomical zones (P < 0.001). The overall median duration of hospitalization was 12 days. Patients who had postoperative complications stayed longer in the hospital and this was statistically significant (p = 0.011). Mortality rate was 11.2% and was significantly associated with co-morbidities, delayed presentation and presence of complications (p < 0.001). The follow up of patients was poor. Cut throat injuries are a major cause of morbidity and mortality among young adult males in our setting. Addressing the root causes of violence such as poverty, unemployment, and substance abuse will reduce the incidence of these injuries in our environment

Fitness Ranking of Individual Mutants Drives Patterns of Epistatic Interactions in HIV-1

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited