Enterohepatic circulation of tetracycline in rats.

The absorption of tetracycline hydrochloride excreted in the bile of rats was evaluated using the insitu intestinal preparation. For comparative purposes, the absorption of the drug from an aqueous solution having the same pH as that of the bile was also determined. After 4 hr, the amounts of tetracycline absorbed from the bile and aqueous solutions were 72.92 and 77.34%, respectively. There was no significant difference in the amount of drug accumulated in the gut tissue. The disappearance of the drug from the intestinal lumen was biexponential, and the kinetic parameters appeared to be similar. It was concluded that tetracycline excreted in the bile is readily absorbed from the rat intestine. Accordingly, biliary excretion does not seem to account for a significant elimination of this antibiotic from the body.     

Safety and efficacy of pregabalin in patients with central post-stroke pain

Pregabalin has demonstrated efficacy in several forms of neuropathic pain, but its long-term efficacy in central post-stroke pain (CPSP) is unproven. We evaluated the efficacy and safety of pregabalin versus placebo in patients with CPSP. A 13-week, randomized, double-blind, multicenter, placebo-controlled, parallel group study of 150 to 600 mg/day pregabalin was conducted in patients aged ?18 years with CPSP. The primary efficacy endpoint was the mean pain score on the Daily Pain Rating Scale over the last 7 days on study drug up to week 12 or early termination visit. Secondary endpoints included other pain parameters and patient-reported sleep and health-related quality-of-life measures. A total of 219 patients were treated (pregabalin n = 110; placebo n = 109). A mean pain score at baseline of 6.5 in the pregabalin group and 6.3 in the placebo group reduced at endpoint to 4.9 in the pregabalin group and 5.0 in the placebo group (LS mean difference = -0.2; 95% CI = -0.7, 0.4; P = 0.578). Treatment with pregabalin resulted in significant improvements, compared with placebo, on secondary endpoints including MOS-sleep, HADS-A anxiety, and clinician global impression of change (CGIC) P < 0.05. Adverse events were more frequent with pregabalin than with placebo and caused discontinuation in 9 (8.2%) of pregabalin patients versus 4 (3.7%) of placebo patients. Although pain reductions at endpoint did not differ significantly between pregabalin and placebo, improvements in sleep, anxiety, and CGIC suggest some utility of pregabalin in the management of CPSP.     

Behavioral consequences of minimal traumatic brain injury in mice

Victims of minor traumatic brain injury (mTBI), who show no clear morphological brain defects, frequently manifest cognitive, behavioral and emotional difficulties that can be long-lasting. In this paper we present a modified weight drop model used to deliver a closed head minimal traumatic brain injury to mice, which closely mimics real-life injuries and the symptoms observed in mTBI patients. Our choice of impact force does not produce structural damage to the brain and its surrounding tissue (as examined by MRI), any skull fracture, no edema and no evident damage to the blood-brain barrier (BBB). Moreover, our mTBI mice show no abnormal behavior on recovering from the weight drop, or any change in other brain functions such as reflexes, balance, exploration, strength, locomotor activity and swim speed. Since our mTBI model does not produce neurological, motor or sensory damage to the mice, it allows the direct evaluation of mTBI sequelae on the mice behavior and cognitive abilities. Using a variety of cognitive and behavioral tests (Morris water maze, staircase test, passive avoidance test, water T-maze, hot palate, elevated plus maze and forced swimming test) we assessed the short- and long-term sequelae induced by our model. Our results indicate that our closed head mTBI cause profound and long-lasting, irreversible learning and memory impairments, accompanied by a depressive-like behavior in mice that are evident even 90 days post injury. Our results indicate that the closed head mTBI model presented here may be useful in the development of novel therapeutic approaches, such as neuroprotective agents, for mTBI.     

The intriguing effects of ecstasy (MDMA) on cognitive function in mice subjected to a minimal traumatic brain injury (mTBI)

Rationale  

The use of ecstasy (MDMA) among young adults has dramatically increased over the years. Since MDMA may impair the users' driving ability, the risk of being involved in a motor vehicle accident (MVA) is notably increased. Minimal traumatic brain injury (mTBI) a common consequence of MVAs—produces short- and long-term physical, cognitive, and emotional impairments.     

Women With Mental Illness Seeking Assisted Reproduction Considerations in Ethical Candidate Selection

Purpose of Review

This review aims to provide guidance to clinicians facing requests for assisted reproduction from women with mental illness.

Recent Findings

The paper explores the clinical and safety aspects of initiating fertility treatment in this context, including the use of psychotropic medication and the risk of untreated psychiatric mood or psychotic disorders. It also presents the ethical considerations involved in candidate selection, including treating similar cases equitably to avoid biased decisions based solely on “gut-feelings,” respect for women’s reproductive autonomy, and an effort to protect patients and prospective fetuses/children from harm by employing optimal strategies regarding medication and psychosocial support.

Summary

Clinicians ought to be informed regarding recent evidence related to the safety and efficacy of psychopharmacologic treatment of women during pregnancy and the post-partum. They should also carry out a thoughtful ethical analysis to ensure minimal violation of women’s reproductive autonomy.

     

Bariatric Surgery-Associated Myelopathy

Bariatric surgery is gaining acceptance as an efficient treatment modality for adults and adolescents with morbid obesity. The early postbariatric period has the potential to induce an immunomodulatory imbalance due to the development or worsening of nutritional deficiencies, changes in hormonal balance (specifically after sleeve gastrectomy), and a shift in the proinflammatory cytokine profile along with a major change in the gut microbiome and permeability. These changes may induce encephalomyelitic T cell activity, change neural barrier permeability, and induce gut dysbioisis, favoring a proinflammatory metabolic profile. Such changes, in genetically prone individuals or those with additional risk factors, may lead to the development of myelopathy, particularly MS.Key MessagePostbariatric myelopathy is rare but should be considered in bariatric patients with relevant complaints in the postoperative period.     

Pharmacokinetics of bretylium in man after intravenous administration

The pharmacokinetic profile of bretylium was studied in four normal male volunteers using a new sensitive EC-GC procedure for its quantitation in biological fluids. The plasma concentrations and urinary excretion rates following the constant i.v. infusion of a single 4mg/kg dose of bretylium tosylate declined biexponentially and the data were fitted to a two-compartment model with a renal and a nonrenal route of elimination. The drug had a mean half-life (t_1/2)of 7.8 hr and apparent volume of distribution (V_d,)of 8.18 liters/kg. The renal clearance, which was 6 times that of the glomerular filtration rate, accounted for almost 84% of the total body clearance and correlated linearly with the subjects' creatinine clearance. The observed side effects of bretylium were mild and similar to those of other adrenergic blocking agents.This work was supported in part by a grant from Arnar-Stone Laboratories, Inc., McGaw Park, Illinois.