EFFICACY OF AYURVEDA FORMULATIONS AND BASTI CHIKITSA ON MUTRAGHATA W.S.R. TO BENIGN PROSTATIC HYPERPLASIA: A REVIEW ON RESEARCHES CONDUCTED AT GUJARAT AYURVED UNIVERSITY, JAMNAGAR

Benign Prostatic Hyperplasia (BPH) is major geriatric problem of obstructive uropathic disorders described in Ayurveda classic as one type of Mutraghata (urinary disorders). Twelve types of Mutraghata reflect the symptoms of retention, incomplete voiding, dribbling, hesitancy, incontinence of urine, etc. These are basically presented the features related to the Lower Urinary Tract Symptoms (LUTS) and can be co-related with Benign Prostatic Hyperplasia (BPH) in modern parlance. BPH is a non-malignant enlargement of the prostate gland, caused by the excessive growth of prostatic nodules. The overall incidence rate of BPH is about 15 per 1000 men per year. The conservative treatments have been mentioned to relieve the obstructive uropathy by reducing prostate size and enhancing the tone of urinary bladder musculature in contemporary medical science. Similarly in Ayurveda also, various researches are going on to find out a suitable treatment option to manage Mutraghata. In the Sushruta Samhita the choice of treatment for Mutraghata is Uttara Basti as Shodhan Chikitsa. In this review, in most of the studies Matra Basti was given in one group of patients and showed the encouraging results. This review article is attributed to the researches on Mutraghata carried out at I.P.G.T. & R.A., Gujarat Ayurved University, Jamnagar, Gujarat

Spontaneous Perforation of a Choledochal Cyst, Clues for Diagnosis

Aim: Spontaneous perforation is a rare complication of a choledochal cyst that is difficult to diagnose because of its nonspecific clinical presentation. These patients usually present with an insidious course characterized by progressive abdominal distension, vomiting, and pain. Here, we present a series of three cases for clues for diagnosis.Materials and methods: All patients with spontaneous perforation of a choledochal cyst who were presented to our institute from January 2009 to December 2011 were included in the study and symptoms and signs at the time of presentation were analyzed.Results: All patients had clinical jaundice and acholic stools at the time of presentation; pain and vomiting was not a consistent feature. Abdominal paracentesis helped us diagnose these cases.Conclusion: Abdominal paracentesis is very useful in cases of suspected spontaneous perforation of the bile duct. Simple drainage with a T-tube, if possible, is safe, efficacious, has low morbidity, and aids in the establishment of the diagnosis as well as delineation of the anatomy of the concerned region for definitive surgery.Keywords: Choledochal Cyst, Spontaneous Perforation of Bile Duct, T-tub

Single-Stage Repair versus Traditional Repair of High Anorectal Malformations, Functional Results’ Correlation with Kelly’s Score and Postoperative Magnetic Resonance Imaging Findings

Introduction: Posterior sagittal anorectoplasty (PSARP) is the standard treatment for anorectal malformations. In the present study, the clinical evaluation of anal continence was carried out using Kelly’s scoring system and the results of primary PSARP or abdomino-PSARP were compared with the traditional three-stage procedure and the functional outcome was correlated with the findings of MRI, which was used as an objective method of evaluation.Patients and methods: A total of 40 patients with intermediate and high anorectal malformations were studied and were divided into two groups on the basis of a random number table. The patients in group A were treated with a single-stage operation, whereas the patients in group B were treated with a standard staged operation (either PSARP or abdominoperineal pull-through). After clinical evaluation using the Kelly score, patients were divided into three clinical groups irrespective of whether they were operated in one stage or in three stages. All patients were subjected to MRI at the age of 3 years and the findings were correlated with the clinical scoring system.Result: Patients were categorized according to their Kelly’s scores as follows: group 1: clinically good (score 5–6); group 2: clinically fair (score 3–4); and group 3: clinically poor (score 0–2). The proportions of good development of the muscles (puborectalis, external sphincter muscle, and levator muscle hammock) were 78.9% in group 1, 40% in group 2, and none in group 3. Development of muscles was found to be a significant factor for anal continence. Other significant factors for anal continence are rectal diameter and anorectal angle.Conclusion: Clinical assessment using the Kelly score was similar for the single-stage operation and the staged procedure, and this was supported by MRI findings. Therefore, we recommend the single-stage procedure to achieve a better outcome in intermediate and high anorectal malformation.Keywords: Anorectal Malformations, MRI, Posterior Sagittal Anorectoplast

Determinants of Salivary Cotinine among Smokeless Tobacco Users : A Cross-Sectional Survey in Bangladesh

INTRODUCTION: More than 80% of all smokeless tobacco (ST) products in the world are consumed in South Asia; yet little is known about their consumption behaviour, addictiveness, and toxic properties. This paper, for the first time, describes associations between salivary cotinine concentrations among ST users in Bangladesh and their socio-demographic characteristics and tobacco use behaviours. METHODS: In a survey of ST users in Dhaka, Bangladesh, we purposively recruited 200 adults who were non-smokers but consumed ST on a regular basis. In-person interviews were conducted to obtain information about socio-demographic and ST use behaviours, and saliva samples were collected to measure cotinine concentration. Simple and multiple linear regression analyses were conducted to test associations between the log transformed salivary cotinine concentration and other study variables. RESULTS: The geometric mean of cotinine concentration among ST users was 380ng/ml (GSD:2). Total duration of daily ST use in months had a statistically significant association with cotinine concentration. Other ST use characteristics including type and quantity of ST use, swallowing of tobacco juice, urges and strength of urges and attempts to cut down on tobacco use were not found to be associated with cotinine concentration in a multivariable model. CONCLUSION: This is the first report from Bangladesh studying cotinine concentration among ST users and it points towards high levels of addiction. This warrants effective tobacco control policies to help ST cessation and prevention

Solving Multi-choice Secretary Problem in Parallel: An Optimal Observation-Selection Protocol

The classical secretary problem investigates the question of how to hire the best secretary from $n$ candidates who come in a uniformly random order. In this work we investigate a parallel generalizations of this problem introduced by Feldman and Tennenholtz [14]. We call it shared $Q$-queue $J$-choice $K$-best secretary problem. In this problem, $n$ candidates are evenly distributed into $Q$ queues, and instead of hiring the best one, the employer wants to hire $J$ candidates among the best $K$ persons. The $J$ quotas are shared by all queues. This problem is a generalized version of $J$-choice $K$-best problem which has been extensively studied and it has more practical value as it characterizes the parallel situation. Although a few of works have been done about this generalization, to the best of our knowledge, no optimal deterministic protocol was known with general $Q$ queues. In this paper, we provide an optimal deterministic protocol for this problem. The protocol is in the same style of the $1\over e$-solution for the classical secretary problem, but with multiple phases and adaptive criteria. Our protocol is very simple and efficient, and we show that several generalizations, such as the fractional $J$-choice $K$-best secretary problem and exclusive $Q$-queue $J$-choice $K$-best secretary problem, can be solved optimally by this protocol with slight modification and the latter one solves an open problem of Feldman and Tennenholtz [14]. In addition, we provide theoretical analysis for two typical cases, including the 1-queue 1-choice $K$-best problem and the shared 2-queue 2-choice 2-best problem. For the former, we prove a lower bound $1-O(\frac{\ln^2K}{K^2})$ of the competitive ratio. For the latter, we show the optimal competitive ratio is $\approx0.372$ while previously the best known result is 0.356 [14].Comment: This work is accepted by ISAAC 201

A Compensatory Mutation Provides Resistance to Disparate HIV Fusion Inhibitor Peptides and Enhances Membrane Fusion

Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations. © 2013 Wood et al

Membrane transport of camptothecin: facilitation by human P-glycoprotein (ABCB1) and multidrug resistance protein 2 (ABCC2)

BACKGROUND: The purpose of the present study was to continue the investigation of the membrane transport mechanisms of 20-(S)-camptothecin (CPT) in order to understand the possible role of membrane transporters on its oral bioavailability and disposition. METHODS: The intestinal transport kinetics of CPT were characterized using Caco-2 cells, MDCKII wild-type cells and MDCKII cells transfected with human P-glycoprotein (PGP) (ABCB1) or human multidrug resistance protein 2 (MRP2) (ABCC2). The effects of drug concentration, inhibitors and temperature on CPT directional permeability were determined. RESULTS: The absorptive (apical to basolateral) and secretory (basolateral to apical) permeabilities of CPT were found to be saturable. Reduced secretory CPT permeabilities with decreasing temperatures suggests the involvement of an active, transporter-mediated secretory pathway. In the presence of etoposide, the CPT secretory permeability decreased 25.6%. However, inhibition was greater in the presence of PGP and of the breast cancer resistant protein inhibitor, GF120918 (52.5%). The involvement of additional secretory transporters was suggested since the basolateral to apical permeability of CPT was not further reduced in the presence of increasing concentrations of GF120918. To investigate the involvement of specific apically-located secretory membrane transporters, CPT transport studies were conducted using MDCKII/PGP cells and MDCKII/MRP2 cells. CPT carrier-mediated permeability was approximately twofold greater in MDCKII/PGP cells and MDCKII/MRP2 cells than in MDCKII/wild-type cells, while the apparent K(m )values were comparable in all three cell lines. The efflux ratio of CPT in MDCKII/PGP in the presence of 0.2 μM GF120918 was not completely reversed (3.36 to 1.49). However, the decrease in the efflux ratio of CPT in MDCKII/MRP2 cells (2.31 to 1.03) suggests that CPT efflux was completely inhibited by MK571, a potent inhibitor of the Multidrug Resistance Protein transporter family. CONCLUSIONS: The current results provide evidence that PGP and MRP2 mediate the secretory transport of CPT in vitro. However, the involvement of other transporters cannot be ruled out based on these studies. Since these transporters are expressed in the intestine, liver and kidney variations in their expression levels and/or regulation may be responsible for the erratic oral absorption and biliary excretion of CPT observed in human subjects

Charged-Higgs phenomenology in the Aligned two-Higgs-doublet model

The alignment in flavour space of the Yukawa matrices of a general two-Higgs-doublet model results in the absence of tree-level flavour-changing neutral currents. In addition to the usual fermion masses and mixings, the aligned Yukawa structure only contains three complex parameters, which are potential new sources of CP violation. For particular values of these three parameters all known specific implementations of the model based on discrete Z_2 symmetries are recovered. One of the most distinctive features of the two-Higgs-doublet model is the presence of a charged scalar. In this work, we discuss its main phenomenological consequences in flavour-changing processes at low energies and derive the corresponding constraints on the parameters of the aligned two-Higgs-doublet model.Comment: 46 pages, 19 figures. Version accepted for publication in JHEP. References added. Discussion slightly extended. Conclusions unchange