Microemulsions: a potential drug delivery system

Microemulsions are clear, transparent, thermodynamically stable dispersions of oil and water, stabilised by an interfacial film of surfactant frequently in combination with a co-surfactant. Recently, there has been a considerable interest for the microemulsion formulation, for the delivery of hydrophilic as well as lipophilic drug as drug carriers because of its improved drug solubilisation capacity, long shelf life, easy of preparation and improvement of bioavailability. In this present review, we discuss about the various advantages of microemulsion in pharmaceuticals, along with its composition variables, physicochemical characterisation etc. The potential use of microemulsion for therapeutic application is also discussed.     

Highly selective cyclic peptide ligands for NeutrAvidin and avidin identified by phage display

Screening combinatorial libraries of conformationally constrained peptides against macromolecular targets is utilized in identifying novel drug leads and in developing new reagents for chemical biology. In methods such as phage-display selections, biotinylated macromolecular targets are often immobilized on avidin- and streptavidin-functionalized supports. Thus, the characterization of peptides that bind avidin and streptavidin is necessary for accurate interpretation of screening and selection results. Toward this goal, we panned a phage-displayed cyclic peptide library against NeutrAvidin, a chemically deglycosylated version of avidin. The selection produced a highly homologous consensus motif (Asp-Arg/Leu-Ala-Ser/Thr-Pro-Tyr/Trp). Two of these cyclic peptides, CDRATPYC and CDRASPYC, bound both NeutrAvidin and avidin with low-micromolar dissociation constants, whereas their acyclic counterparts had negligible affinity (< 80-fold). Moreover, these cyclic peptides were very specific for their targets and did not bind the structurally and functionally similar protein, streptavidin. Thus, we have identified a new class of cyclic peptides, distinct from the much-studied streptavidin-binding His-Pro-Gln peptide motif. These results will not only allow for discriminating between desired and background cyclic peptide motifs in selections and screens but also provide a new protein/peptide model system and a useful reagent in chemical biology that can have utility in protein immobilization, purification, and chemical tagging.     

Tumor-suppressive effects of MBP-1 in non-small cell lung cancer cells

Lung cancer is the leading cause of cancer death among both men and women. Only approximately 15% of people diagnosed with non-small cell lung cancer (NSCLC) survive this disease beyond 5 years. Thus, novel therapeutic strategies are urgently needed to improve the clinical management of this devastating disease. We have previously shown the antiproliferative effect of MBP-1 on several human cancer cells. In this study, we have examined the potential of MBP-1 as a gene therapeutic candidate in regression of non-small cell lung tumor growth. We have observed that exogenous expression of MBP-1 in NSCLC cells (H1299) induces massive cell death. To determine the gene therapeutic potential of MBP-1, replication-deficient recombinant adenovirus expressing MBP-1 was given intratumorally in human lung cancer xenografts in nude mice. Our results showed a significant regression of lung tumor growth and prolonged survival on treatment with MBP-1 compared with the control groups (saline or dl312). Subsequently, the mechanism of MBP-1-mediated H1299 cell death was investigated. Our results suggested that MBP-1 induced poly(ADP-ribose) polymerase cleavage in H1299 cells; however, treatment with pan-caspase inhibitor did not protect against MBP-1-induced cell death. Cells transduced with MBP-1 displayed early plasma membrane permeability, mitochondrial damage without cytochrome c release, and extensive cytoplasmic vacuolation, yielding a morphotype that is typical of necrosis. Taken together, this study suggests that MBP-1 expression induces a novel form of necrosis-like cell death and MBP-1 could be a potential gene therapeutic candidate against non-small cell lung tumor growth.     

Meta-analysis of vitamin D receptor polymorphisms and type 1 diabetes: a HuGE review of genetic association studies

Several polymorphisms in the vitamin D receptor (VDR) gene have been reported to be associated with the risk of developing type 1 diabetes, yet published findings have been conflicting. In this study, the authors attempted to evaluate the evidence regarding the association. They searched all relevant reports from original papers published from 1997 to December 2005. Predefined criteria were used to identify 1) case-control association studies examining the FokI (11 studies), BsmI (13 studies), ApaI (9 studies), and TaqI (7 studies) polymorphisms and 2) a few family-transmission studies with analysis of these four polymorphisms. In random-effects modeling, the 95% confidence intervals of the summary odds ratios for all four polymorphisms included 1, indicating no effect. Except for FokI, no heterogeneity was found. The 95% confidence intervals of the transmission proportions all included 0.5, indicating no effect. Thus, the authors found no evidence for an association between VDR gene polymorphisms and type 1 diabetes risk in either case-control studies or family-transmission studies. In fact, a reanalysis of previously published data (McDermott et al., Diabetologia 1997;40:971-5) indicated no evidence of an association as reported.     

Medical abortion in late second trimester--a comparative study with misoprostol through vaginal versus oral followed by vaginal route

A randomised controlled trial was conducted to compare the relative efficacies of two regimens: Misoprostol given only vaginally or orally followed by vaginal administration of the same drug, for second trimester abortion. Multiparous women with a pregnancy of 16 to 20 weeks with no contra-indications to the drug were selected. They were randomly allocated into two groups. Patients in the first group, the 'only vaginal misoprostol' group (n = 30), were given misoprostol 400 microg 6 hourly only through vaginal route up to a maximum of 4 such doses. Women in the other group, the 'oral plus vaginal misoprostol' group (n = 24), received 400 microg of the drug at intervals of 12 hours for 2 doses, followed by 400 microg 6 hourly per vaginum up to a maximum of 4 such. Ten units of oxytocin was started in all cases when os was 4 cm dilated. Complete expulsion was 83.33% with an average time of 13.28 hours in the only vaginal misoprostol group. Complete expulsion occurred in 87.5% of women receiving oral followed by vaginal misoprostol with an average time of 8.93 +/- 0.01 hours from the first vaginal dose (p<0.05). More importantly, 66.67% women in second group delivered within 10 hours of the vaginal dose. Complete expulsion was defined in those cases where no check curettage was needed. Side-effects were not significant. This implies that misoprostol given by the vaginal route following oral priming doses had a higher success rate and a potential for a reduced hospital stay and higher bed turn-over rate.     

Knowledge, attitude and practices of emergency contraception among beneficiaries and providers

In the new millennium emergency contraceptives have become one of the effective methods for control of global population. It can avert many unwanted pregnancies. In the present study the authors have tried to evaluate the knowledge, attitude and practice of different methods of contraceptive techniques available at present and also about the emergency contraceptive which is recently available amongst 140 healthcare providers and 480 beneficiaries. In one of the teaching institution of Kolkata, RG Kar Medical College and in the district of 24 Parganas (N), the participants in the study were evaluated by preset questionnaires which were separate for providers and for beneficiaries. The results were analysed subsequently.     

Unexplained somatic symptoms--diagnostic window for mental disorders

Prevalence of common mental diseases eg, anxiety disorders and depression in primary care, general practice and specialists clinics is high but theirdiagnosis in these settings are poor, main reason being the absence of psychological complaints by patients. Such patients commonly present with physical symptoms suggestive of systemic diseases but examination and investigations often fail to substantiate organic basis of these so-called unexplained somatic symptoms (USSs). Several studies have shown that patients with USSs suffer from anxiety and depression. But these USSs are mostly misinterpreted or ignored by clinicians resulting in poor rates of diagnosis. The study objective was to devise algorithm for better and early diagnosis of. mental diseases in a specialist clinic practice setting. Common USSs were interpreted as regards their symptom-correlates both physical and mental and documented while taking detailed history, physical examination and needed investigations to diagnose systemic diseases. The study was in phases during three years and included 1297 patients in four cohorts which included one group of 154 patients with common USSs, treated with long term antidepressants. Data of all patients were recorded in microsoft excel spread-sheets for analysis. Commonest presenting USSs were so-called "gas", "acidity" and "dysentery" expressed in vernacular terms. On elucidation these were found to mean wide varieties of physical symptoms-complexes that were not typical of specific systemic diseases; 85% in one group and 73% in another with these USSs and their symptom-correlates when positively screened for symptoms of neurotic diseases (ICD-10) after detailed history taking were found to have anxiety and depression. Psychiatric comorbidity with systemic diseases was found in various percentages in three different cohorts when these USSs were properly evaluated. By patients' own assessments, 84.4%, 88% and 90% of those presenting with USSs of so-called "gas", "acidity" and "dysentery" (with their symptom-correlates) and who were put on three different low dose antidepressant treatment groups had satisfactory to good results so long as they were being taken regularly. These common USSs and the underlying physical symptoms-correlates were eponyms of anxiety disorders and non-major depression. General practitioners and specialists eg, gastroenterologists, cardiologists, neurologists, etc, should heed the USSs as the starting point for early diagnosis and treatment of comorbid mental disorders along with the systemic diseases for better treatment compliance and outcome and quality of life. Training of physicians and medical students in the diagnosis and management of patients with USSs should be emphasised in clinical teaching programmes. An algorithm for early diagnosis and management of common mental disorders in general and clinic practice is suggested.     

Hydrocele of the canal of Nuck

Hydrocele of the canal of Nuck is an uncomon and infrequently reported finding in women. A 24-year-old female presented with a painless left groin swelling which was soft, cystic, non-tender with 7.5 cm x 5 cm in measurement. It was more prominent in standing. Ultrasonography revealed an encysted echofree lesion in the left inguinal canal. On surgery, a cyst was found containing clear fluid in the inguinal canal which was dissected out and wound was closed in layers. The patient is doing well till date. Here one such case with diagnosis of hydrocele of the canal of Nuck is reported.