Development and biopharmaceutical evaluation of osmotic pump tablets for controlled delivery of diclofenac sodium

Based on the principles of an elementary osmotic pump (OP), OP tablets were designed and evaluated with the aim to deliver diclofenac sodium (DS) in a controlled manner. In vitro evaluation was done in various release media and kinetics was evaluated using the regression coefficient analysis. Effects of orifice size, coating membrane type, coating thickness, static and stirred conditions and pH variation were studied. In vivo evaluation was performed on six healthy human volunteers and various pharmacokinetic parameters (c(max), t(max), AUC(0-24), MRT) and relative bioavailability were calculated. The results were compared with the performance of two commercial tablets of DS. The drug release from OP tablets was dependent on the type and thickness of the coating membrane, but was independent of the orifice size and static and stirred conditions of the release medium. The OP tablets provided a prolonged and controlled DS release compared to commercial sustained-release and conventional tablets of DS.     

Transdermal iontophoresis of insulin. Part 1: A study on the issues associated with the use of platinum electrodes on rat skin

We have studied the issues associated with the use of platinum electrodes for transdermal iontophoretic delivery of peptides, using insulin as a model peptide. Insulin permeation was studied using full-thickness rat skin by varying the donor solution pH as a function of electrode polarity. The stability of insulin under the iontophoretic conditions was studied using TLC, SDS-polyacrylamide gel electrophoresis and HPLC. Large pH shifts were observed during anodal iontophoresis (AI), when the donor solution pH was above the isoelectric point of insulin and in cathodal iontophoresis (CI), when the donor solution pH was below the isoelectric point of insulin. The direction and magnitude of electroosmotic flow was influenced by pH of the donor solution and the electrode polarity. On the other hand, the buffer used to maintain the pH governed the contribution of electrorepulsion to the overall transport of insulin. Electrochemical degradation of insulin was significant during AI at pH 7.4. Among the pH investigated, AI of insulin at pH 3.6 and CI at pH 8.35 were better, as the pH shift was relatively less and electrochemically more stable during iontophoresis as compared with other pH. In summary, the pH shift caused by platinum electrodes had a significant influence on the permeation and stability of insulin.     

Tobacco consumption in India: a new look using data from the National Sample Survey

This paper examines the various issues surrounding tobacco use in India, using National Sample Survey and other data. The study demonstrates that 150 million Indians used tobacco in 1998 and that during the 1990's, the prevalence increased for both rural and urban areas, as well as in both sexes and in all age groups. Such large numbers have staggering implications for the country's economy, health outcomes and resources, and the magnitude of tobacco control challenges. Bidis hand-rolled cigarettes remain the most commonly used form of tobacco. However, major differences in rates and types of tobacco used were seen among various sex, age, economic and social class groups, suggesting that public health efforts to reduce consumption will require focused initiatives to target various populations and products.     

Coarctation of the Aorta,Aortic Valvar Stenosis,and Supravalvar Aortic Stenosis with Left Coronary Artery Ostial Stenosis: Management Using a Staged Hybrid Approach

In this report, we describe a case of coarctation of the aorta, congenital aortic stenosis with bicuspid valve, and supravalvar aortic stenosis with left coronary artery ostial stenosis. The child underwent staged treatment using a hybrid approach employing both surgical and interventional cardiology methods. A single pericardial patch repair technique for supravalvar aortic stenosis associated with left coronary ostial stenosis is also described.     

Fate of Human Thyroid Tissue Autotransplants

Purpose. We conducted this study to establish whether human thyroid tissue autografts can survive and function in the absence of their native blood supply in muscle. The benefits of this potential could be incorporated in routine surgery to reduce the incidence of post-operative hypothyroidism.Methods. Fifteen patients with benign thyroid disorders, seven of whom had Graves' disease and eight, multinodular goiter (MNG), underwent modified subtotal thyroidectomy and the autotransplantation of thyroid tissue in the sternocleidomastoid muscle. About 3–5g of thyroid tissue was cut and implanted into the sternocleidomastoid muscle. Postoperative clinical assessment, thyroid function tests, and technetium scans of the neck were done to assess the function of remnant and transplanted thyroid tissue.Results. The transplanted tissue was functional in six of the eight patients with MNG and four of the seven with Graves' disease. All the patients with MNG and a functional transplant became euthyroid within 6 months postoperatively. Although the transplanted tissue was functional in four patients with Graves' disease, only one became euthyroid, while the other three required supplemental hormone therapy for postoperative hypothyroidism.Conclusions. These findings demonstrate the ability of autotransplanted thyroid tissue to survive, function, and grow in muscle.     

Expression of glutamate transporter,GABRA6, serine proteinase inhibitor 2 and low levels of glutamate and GABA in the brain of knock-out mouse for Canavan disease

Canavan disease (CD) is an autosomal recessive leukodystrophy characterized by spongy degeneration of the brain. The clinical features of CD are hypotonia, megalencephaly, and mental retardation leading to early death. While aspartoacylase (ASPA) activity increases with age in the wild type mouse brain, there is no ASPA activity in the CD mouse brain. So far ASPA deficiency and elevated NAA have been ascribed with the CD. Other factors affecting the brain that result from ASPA deficiency may lead pathophysiology of CD. The NMR spectra and amino acid analysis showed lower levels of glutamate and gamma-aminobutyric acid in the CD mouse brain compared to the wild type. Microarray gene expression on CD mouse brain showed glutamate transporter-EAAT4 and gamma-aminobutyric acid-A receptor, subunit alpha6 (GABRA6) were lower 9.7- and 119.1-fold, respectively. Serine proteinase inhibitor 2 (Spi2) was 29.9-fold higher in the CD mouse brain compared to the wild type. The decrease of GABRA6 and high expression of Spi2 in CD mouse brain were also confirmed by real-time RT-PCR. This first report showing abnormal expression of EAAT4, GABRA6, Spi2 combined with lower levels of glutamate and GABA are likely to be associated with the pathophysiology of CD.     

Oxytocin: at birth and beyond. A systematic review of the long-term effects of peripartum oxytocin

Oxytocin is one of the most commonly used medications during labour and delivery. Recent insights from basic neuroscience research suggest that the uterotonic effects of oxytocin may arguably be trivial when compared with its profound effects on higher-order human behaviour. The purpose of this review is to highlight the potential consequences of manipulating oxytocinergic signalling during the peripartum period and its long-term impact on the maternal-infant dyad. We identified four domains where modulation of oxytocinergic signalling might be consequential: postpartum depression; breastfeeding; neurodevelopment; and chronic pain, and performed a literature search to address the impact of peripartum oxytocin administration. We have shown modest, but inconsistent, evidence linking peripartum oxytocin administration with postpartum depression. Breastfeeding success appeared to be negatively correlated with peripartum oxytocin exposure, perhaps secondary to impaired primitive neonatal reflexes and maternal-infant bonding. The association between perinatal oxytocin exposure and subsequent development of neurodevelopmental disorders such as autism in the offspring was weak, but these studies were limited by the lack of information on the cumulative dose. Finally, we identified substantial evidence for analgesic and anti-hypersensitivity effects of oxytocin which might partly explain the low incidence of chronic pain after caesarean birth. Although most data presented here are observational, our review points to a compelling need for robust clinical studies to better dissect the impact of peripartum oxytocin administration, and as stewards of its use, increase the precision with which we administer oxytocin to prevent overuse of the drug.     

How do social-psychological concerns impede the delivery of care to people with HIV? Issues for dental education

Oral health is an essential aspect of the overall medical care for patients with HIV. However, fear of status disclosure is a significant barrier to access to care. Preparing future oral health care providers to maintain all aspects of confidentiality and to understand the role stigma plays in the lives of HIV-positive individuals are critical issues that must be addressed by dental education. To provide important perspectives regarding HIV-related stigma and confidentiality, data from the HAART (Highly Active Antiretroviral Therapy) Project is presented. This study is a five-year National Institute of Allergy and Infectious Disease (NIAID)-funded longitudinal qualitative study of sero-positive African Americans' adherence to antiretroviral therapy (N=137). The current literature regarding HIV patient confidentiality and student attitudes regarding HIV/AIDS is also reviewed. Findings suggest that dental student attitudes may be improved by providing more comprehensive experiences and information and that procedures in place in dental clinics should be continuously monitored to ensure that patient confidentiality is maintained. Strategies for addressing these important issues in dental education are presented. Ensuring that dental school graduates are well prepared to maintain confidentiality with sensitivity to the role stigma plays in HIV disease has the potential to enhance access to health care.     

Achilles tendon rupture with open distal tibia and fibula fracture

The authors present a previously unreported case of an open fracture of the distal tibia and fibula with associated Achilles tendon rupture in a 27-year-old motorcyclist. Management followed established trauma principles of wound exploration, debridement, and stabilization of the fracture with reamed locked intramedullary nailing of the tibia. The injury to the Achilles tendon was not identified until surgical exploration for fixation of the fracture. This required a 2-stage operative approach, involving initial debridement and fracture fixation followed by Achilles tendon repair during the second-look wound review procedure. The authors believe this to be the first reported case of Achilles tendon rupture in association with an open transverse distal tibia fracture. Prior to surgical exploration of the wound, Achilles tendon rupture was not suspected, emphasizing the need for clinical suspicion, thorough examination, and adequate wound exploration at operation for fracture fixation.