Sex and estrus cycle differences in the modulatory effects of morphine on seizure susceptibility in mice

PURPOSE: To evaluate the effects of sex and estrus cycle on biphasic anticonvulsant and proconvulsant modulation of seizure threshold by morphine. METHODS: The threshold for the clonic seizures (CST) induced by acute intravenous administration of gamma-aminobutyric acid (GABA)-antagonist pentylenetetrazole (PTZ) was assessed in male and female mice. Estrus cycle was assessed by vaginal smears. The effect of removing circulating sex hormones was assessed by gonadectomy. RESULTS: At baseline, diestrus females had a higher CST compared with males and estrus females. Morphine at lower doses (0.5-3 mg/kg) had a significant anticonvulsant effect in males and estrus females compared with that in vehicle-treated controls, whereas female mice in diestrus phase showed a relative subsensitivity to this effect. Morphine at higher doses (30 and 60 mg/kg) significantly decreased CST in males and diestrus females, with less relative effect in estrus mice. In both phases, morphine exerted stronger effects in males compared with females. Ovariectomy brought the baseline CST to the male level and resulted in significant expression of both phases of morphine effect but did not abolish the sex difference in responsiveness to morphine. CONCLUSIONS: The biphasic modulation of seizure threshold is subject to both constitutive sex differences in sensitivity to morphine and hormonal fluctuations during the estrus cycle.     

Wear Rates With Large Metal and Ceramic Heads on a Second Generation Highly Cross-Linked Polyethylene at Mean 6-Year Follow-Up

Background

Bearing surface wear and osteolysis are major factors limiting the durability of total hip arthroplasty (THA). Second generation annealed highly cross-linked polyethylene (HXLPE) and ceramics were introduced to THA for their excellent wear rates. However, there is little data comparing the wear rates of metal and ceramic heads on second generation HXLPE.

Prognostic Value of Cardiac Magnetic Resonance Imaging in Acute Coronary Syndrome Patients With Troponin Elevation and Nonobstructive Coronary Arteries

ObjectiveTo define the diagnostic yield of cardiac magnetic resonance (CMR) in differentiating the underlying causes of myocardial infarction with nonobstructive coronary arteries (MINOCA) and to determine the long-term prognostic implications of such diagnoses.MethodsCardiac magnetic resonance evaluation was performed in 227 patients (mean age, 56.4±14.9 years; 120 [53%] female) with a “working diagnosis” of MINOCA as defined by presentation with a troponin-positive acute coronary syndrome (troponin I >0.04 μg/L) and nonobstructed coronary arteries between January 1, 2007, and February 28, 2013. Follow-up was performed to assess the primary composite end point of myocardial infarction, heart failure, and all-cause mortality.ResultsCardiac magnetic resonance identified nonstructural cardiomyopathies in 97 (43%) patients, myocardial infarction in 55 (24%) patients, structural cardiomyopathies in 27 (12%) patients, and pulmonary embolism in 1 patient. No CMR abnormalities were identified in the remaining patients. Kaplan-Meier analysis demonstrated the ability of a CMR diagnosis to predict the risk of the primary composite end point (P=.005) at 5-year follow-up. Worse outcomes were seen among patients with “true” MINOCA and a normal CMR image compared with those with CMR-confirmed myocardial infarction (P=.02). Use of antiplatelets (78% [37/45] vs 95% [52/55]; P=.01), beta blockers (56% [25/45] vs 82% [45/55]; P=.004), and statins (64% [29/45] vs 85% [47/55]; P=.01) was significantly lower in patients with true MINOCA with normal CMR imaging compared with those with CMR-confirmed myocardial infarction.ConclusionsCardiac magnetic resonance carries a high diagnostic yield in patients with MINOCA and predicts long-term prognosis. Patients with MINOCA with normal CMR imaging had an increased rate of major adverse cardiac events and lower use of guideline-recommended myocardial infarction therapy compared with those with CMR-confirmed myocardial infarction.     

Methamphetamine‐induced enhancement of hippocampal long‐term potentiation is modulated by NMDA and GABA receptors in the shell–accumbens

Addictive drugs modulate synaptic transmission in the meso‐corticolimbic system by hijacking normal adaptive forms of experience‐dependent synaptic plasticity. Psychostimulants such as METH have been shown to affect hippocampal synaptic plasticity, albeit with a less understood synaptic mechanism. METH is one of the most addictive drugs that elicit long‐term alterations in the synaptic plasticity in brain areas involved in reinforcement learning and reward processing. Dopamine transporter (DAT) is one of the main targets of METH. As a substrate for DAT, METH decreases dopamine uptake and increases dopamine efflux via the transporter in the target brain regions such as nucleus accumbens (NAc) and hippocampus. Due to cross talk between NAc and hippocampus, stimulation of NAc has been shown to alter hippocampal plasticity. In this study, we tested the hypothesis that manipulation of glutamatergic and GABA‐ergic systems in the shell‐NAc modulates METH‐induced enhancement of long term potentiation (LTP) in the hippocampus. Rats treated with METH (four injections of 5 mg/kg) exhibited enhanced LTP as compared to saline‐treated animals. Intra‐NAc infusion of muscimol (GABA receptor agonist) decreased METH‐induced enhancement of dentate gyrus (DG)‐LTP, while infusion of AP5 (NMDA receptor antagonist) prevented METH‐induced enhancement of LTP. These data support the interpretation that reducing NAc activity can ameliorate METH‐induced hippocampal LTP through a hippocampus‐NAc‐VTA circuit loop. Synapse 70:325–335, 2016 . © 2016 Wiley Periodicals, Inc.     

Anticancer Activity and Tolerance of Treatments Received Beyond Progression in Men Treated Upfront with Androgen Deprivation Therapy With or Without Docetaxel for Metastatic Castration-naïve Prostate Cancer in the GETUG-AFU 15 Phase 3 Trial

Background

Androgen deprivation therapy (ADT) plus docetaxel is the standard of care in fit men with metastatic castration-naive prostate cancer (mCNPC) following results from GETUG-AFU 15, CHAARTED, and STAMPEDE. No data are available on the efficacy of treatments used for metastatic castration-resistant prostate cancer (mCRPC) in men treated upfront with ADT plus docetaxel for mCNPC.

Effect of fentanyl and vitamin B12 on abdominal pain in patients addicted to oral opium: A clinical trial

Background: Pain is a common complaint among patients referring to the emergency department. This study aimed at comparing the effect of fentanyl and vitamin B₁₂ to decrease the abdominal pain in patients who are addicted to oral opium.

Methods: This study conducted a double-blind randomized clinical trial on patients addicted to oral opium during a one-year period. The effects of fentanyl and vitamin B12 were compared for the relief of abdominal pain in such patients.

Results: The 136 patients studied had a mean age of 47.77 ± 13.6 years (mean ± SD). There was a significant difference in mean pain severity at 10, 15, 30, 45, 60, and 120 min (P < .05). The mean pain severity in the fentanyl group was significant at 30 min compared to the earlier times and showed a decreasing trend in pain severity (P < .05). This decreasing trend was observed up to 120 min for the fentanyl + vitamin B12 group, which showed a significant difference between each time and the time preceding it (P < .05).

Conclusions: The proper and permanent control of abdominal pain experienced by patients addicted to oral opium is essential. The combined use of fentanyl and vitamin B12 is effective in reaching this goal.     

Detection of VEB-1, OXA-10 and PER-1 genotypes in extended-spectrum β-lactamase-producing Pseudomonas aeruginosa strains isolated from burn patients

Resistance of Pseudomonas aeruginosa strains to the broad-spectrum cephalosporins may be mediated by the extended-spectrum β-lactamases (ESBLs). These enzymes are encoded by different genes located on either chromosomes or plasmids. This study aimed to investigate the prevalence of ESBLs and antimicrobial susceptibilities of P. aeruginosa isolated from burn patients in Tehran, Iran. Antimicrobial susceptibility of 170 isolates to cefpodoxime, aztreonam, ciprofloxacin, ofloxacin, ceftazidime, cefepime, imipenem, meropenem, cefotaxime, levofloxacin, piperacillin–tazobactam and ceftriaxone was determined by disc agar diffusion test. Polymerase chain reaction (PCR) amplification of the genes encoding OXA-10, PER-1 and VEB-1 was also performed. All isolates (100%) were resistant to ceftazidime, cefotaxime, cefepime and aztreonam. Imipenem and meropenem were the most effective anti-pseudomonal agents. The results revealed that 148 (87.05%) of the isolates were multidrug resistant and 67 (39.41%) of the isolates were ESBL positive. Fifty (74.62%), 33 (49.25%) and 21 (31.34%) strains among 67 ESBL-producing strains amplified bla_OXA-10, bla_PER-1 and bla_VEB-1 respectively.