Effects of Lepidium sativum,Nigella sativa and Trigonella foenum‐graceum on Phenytoin Pharmacokinetics in Beagle Dogs

The present work was designed to evaluate the effect of some commonly used herbs viz. garden cress (Lepidium sativum), black seed (Nigella sativa) and fenugreek (Trigonella foenum‐graceum) on the disposition of phenytoin after oral administration in a dog model. Phenytoin was given orally at a dose of 50 mg, and blood samples were obtained for the determination of drug's pharmacokinetic parameters. After a suitable washout period, animals were commenced on a specific herb treatment for one week. Garden cress treatment caused a modest increase in maximum observed concentration (C_max) and terminal half‐life (T_1/2λ) of phenytoin with a reduction in clearance by 33%. The effect of black seed therapy was more drastic on drug elimination and to a lesser extent on its volume of distribution at steady state (V_ss) with a consequent reduction in systemic exposure measured by area under the curve (AUC_0‐∞) by about 87%. The effect of fenugreek therapy resembled, albeit to a lesser extent, that of black seed with a significant reduction in AUC_0‐∞ by ~72%. In addition, there was a 73% increase in V_ss. Our findings suggest that the phenytoin disposition can be significantly altered by the concurrent consumption of tested herbal products. Copyright © 2013 John Wiley & Sons, Ltd.     

A Prospective,Longitudinal Study of the Effect of Remission on Cortical Thickness and Hippocampal Volume in Patients with Treatment-Resistant Depression

Background:

Magnetic resonance imaging studies have provided evidence of structural modifications in cortical-limbic regions in major depressive disorder. To date, however, few studies have tracked structural changes in patients during treatment. This prospective, longitudinal imaging study investigated associations between brain structure and clinical responsiveness in a sample of patients with treatment-resistant major depressive disorder during an approximate 1-year follow-up period.

Methods:

FreeSurfer software was used to extract volume or cortical thickness values from 6 regions of interest (hippocampus, rostral middle frontal gyrus, orbitofrontal cortex, rostral and caudal anterior cingulate cortices, and inferior temporal gyrus) in patients (n = 26) and matched healthy controls (n = 28). Regions of interest were selected based on previous evidence of potential associations between morphometric characteristics in these regions and treatment response or remission. Analyses were conducted to compare volume and cortical thickness in patients and controls at baseline imaging, determine whether patients’ brain structure at treatment initiation was associated with response over follow-up, and compare longitudinal changes in volume and cortical thickness in patients who achieved sustained 6-month remission (Montgomery-Åsberg Depression Rating Scale Score ≤12) with nonremitters.

Results:

Patients and controls showed no structural differences at baseline. Among patients, thicker right caudal anterior cingulate cortex at baseline was associated with greater symptom improvement over follow-up. Remitters and nonremitters showed subtle changes in volume and thickness over time in opposing directions, with increased hippocampal volume and cortical thickness in the rostral middle frontal gyrus, orbitofrontal cortex, and inferior temporal gyrus in remitters, and decreased volume or thickness in these regions in nonremitters.

Conclusions:

The results suggest that longitudinal structural trajectories may differ in major depressive disorder patients according to their clinical response to treatment.     

Systemic delivery of β-blockers via transdermal route for hypertension

Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later.     

Renal aquaporin-4 associated pathology in TG-26 mice

Human immunodeficiency virus-associated nephropathy (HIVAN) is a leading cause of end-stage renal disease in HIV patients, which is characterized by glomerulosclerosis and renal tubular dysfunction. Aquaporin-4 (AQP-4) is a membrane bound water channel protein that plays a distinct role in water reabsorption from renal tubular fluid. It has been proven that failure of AQP-4 insertion into the renal tubular membrane leads to renal dysfunction. However, the role of AQP-4 in HIVAN is unclear. We hypothesize that impaired water reabsorption leads to renal injury in HIVAN, where AQP-4 plays a crucial role. Renal function is assessed by urinary protein and serum blood urea nitrogen (BUN). Kidneys from HIV Transgenic (TG26) mice (HIVAN animal model) were compared to wild type mice by immunostaining, immunoblotting and quantitative RT-PCR. TG26 mice had increased proteinuria and BUN. We found decreased AQP-4 levels in the renal medulla, increased endothelin-1, endothelin receptor A and reduced Sirtuin1 (SIRT-1) levels in TG26 mice. Also, oxidative and endoplasmic reticulum stress was enhanced in kidneys of TG26 mice. We provide the first evidence that AQP-4 is inhibited due to induction of HIV associated stress in the kidneys of TG26 mice which limits water reabsorption in the kidney which may be one of the cause associated with HIVAN, impairing kidney physiology. AQP-4 dysregulation in TG26 mice suggests that similar changes may occur in HIVAN patients. This work may identify new therapeutic targets to be evaluated in HIVAN.     

Prevalence and Predictors of Gastroesophageal Reflux Disease After Laparoscopic Sleeve Gastrectomy

Background and Aims

Laparoscopic sleeve gastrectomy (LSG) might be associated with a new onset or worsening of gastroesophageal reflux disease (GERD). We aim to evaluate the prevalence of post-LSG GERD symptoms and its predictors.

Methods

We included patients who underwent primary LSG at a university hospital from 2009 to 2015. We used the GERD-Health-Related Quality of Life (GERD-HRQL) questionnaire and included questions regarding regurgitation to evaluate symptoms before and after LSG; each item was scored from 1 to 5 based on the symptom severity.

Results

A total of 213 patients (mean age, 36.08 ± 10.22 years; 48.36% were men) were included. The mean preoperative body mass index (BMI) was 47.84 kg/m², mean percent total weight loss was 37.99% (95% CI, 36.64 to 39.34), mean percent excess weight loss was 84.14% (95% CI, 80.91 to 87.36), and the mean percent excess BMI loss was 84.17% (95% CI, 80.94 to 87.41). The mean heartburn score while standing increased (0.71 vs. 1.09, p < 0.01) as well as the score of heartburn requiring a diet change (0.67 vs. 1.16, p < 0.01) post-LSG. The scores for dysphagia, odynophagia, and regurgitation increased. New-onset heartburn was reported in 47.06% of our cohort. Those with high preoperative BMIs were less likely to develop new-onset or worsening symptoms of GERD (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.95–0.99). More severe heartburn symptoms while standing were associated with higher risks of developing or worsening GERD symptoms (OR, 1.22; 95% CI, 1.01–1.47). None of the other variables could predict the development or worsening of the GERD symptoms.

Conclusion

Symptoms of heartburn and regurgitation are common after LSG; however, none of the variables preoperatively could strongly predict patients who would develop new onset or experience worsening of symptoms postoperatively.

     

Health-Related Anxiety and Hypochondriacal Concerns in Medical Students: A Cross-Sectional Study From Pakistan

Phenomenon: Transient health-related anxiety/hypochondriacal concerns in medical students are well documented. The literature suggests that after studying a particular disease, medical students are likely to consider any symptoms earlier regarded as normal to be signs of the disease they are studying. The aim of this study was to investigate the prevalence of these phenomena and their cognitive and distress aspects among medicals students in Karachi, Pakistan. Approach: This was an analytical, cross-sectional study. Self-administered questionnaires comprising demographic details, the Short Health Anxiety Inventory, Medical Students’ Disease (MSD) Perception Scale, and MSD Distress Scale were distributed to 1st- through 5th-year medical students. Findings: In total, 513 medical students (66% female) participated. Their mean age was 21 ± 1.6 years. Three hundred seventy-five students (73%) reported having visited a doctor at least once in the past 6 months. Fifty students (9.9%) admitted to having addictions. The overall prevalence of significant hypochondriacal concerns was 11.9% (61 students). The presence of addiction was associated with a greater likelihood of developing significant health-related anxiety (odds ratio = 3.82, p = .003), 95% confidence interval [1.51, 7.11]. Age, gender, medical school, year of medical school, and visits to the doctor in the previous 6 months were not associated with greater likelihood of developing significant health-related anxiety. Second-year medical students experienced a significantly greater degree of worry (MSD–Distress scale) than 5th-year students (M score = 12.6 ± 4.6 vs. 10.7 ± 4.4, p = .04). Insights: The prevalence of substantial hypochondriacal concerns in medical students in Pakistan was low in comparison to similar studies published in literature. Student health physicians should be aware of the true prevalence of hypochondriacal concerns and behavior and not dismiss legitimate complaints. Educational sessions to counteract this phenomenon can be incorporated into the curriculum of undergraduate medicine. By defining heightened awareness of symptoms as a normal process, different coping techniques can be discussed to help medical students reduce their level of stress.     

Role of neutrophils in acrylonitrile-induced gastric mucosal damage

Acrylonitrile (ACN) is a widely used intermediate in the manufacture of plastics, acrylic ?bers, synthetic rubbers and resins that are used in a variety of products including food containers and medical devices. ACN is a possible human carcinogen and a documented animal carcinogen, with the stomach being an important target of its toxicity. ACN has been previously reported to require metabolic activation to reactive intermediates and finally to cyanide (CN⁻). The current study aimed at exploring the potential role of neutrophils in ACN-induced gastric damage in rats. Experimental neutropenia was attained by injecting rats with methotrexate. This significantly ameliorated gastric mucosal injury induced by ACN. This is evidenced by protection against the increase in gastric ulcer index, myeloperoxidase (MPO) activity and CN⁻ level. Also, neutropenia guarded against the decrease in prostaglandin E2 (PGE2), induction of oxidative stress and reduction of total nitrites and alleviated histopathological alterations in rat stomachs. These data indicate that neutrophil infiltration is, at least partly, involved in ACN-induced gastric damage in rats.     

WHO guidelines for treatment of tuberculosis: the missing links

Worldwide, the treatment of tuberculosis is based on evidence-based guidelines developed by the World Health Organization (WHO) for national tuberculosis programs. However, the importance of health related quality of life, the adequate management of side effects associated with antituberculosis drugs and the elaboration of tuberculosis treatment outcome categories are a few issues that need to be addressed in forthcoming WHO guidelines for the treatment of tuberculosis.