Formulation and evaluation of sublingual tablets of losartan potassium

ObjectiveSublingual tablets of Losartan Potassium were prepared to improve its bioavailability, to avoid pre-systemic metabolism in the gastrointestinal tract and hepatic first pass elimination.MethodsThe Sublingual tablets were prepared by direct compression procedure using different concentration of Starch 1500 and microcrystalline cellulose. Compatibility studies of drug and polymer were performed by FTIR spectroscopy and DSC. Preformulation property of API was evaluated. Postcompressional parameters such disintegration time, wetting time, water absorption ratio, in vitro drug release and in vivo bioavailability study of optimized formulation were determined.ResultsFTIR spectroscopy and DSC study revealed that there was no possible interaction between drug and polymers. The precompression parameters were in acceptable range of pharmacopoeial specification. The disintegration time of optimized formulation (F3) was upto 48 sec. The in vitro release of Losartan Potassium was upto 15 min. The percentage relative bioavailability of Losartan Potassium from optimized sublingual tablets was found to be 144.7 %.ConclusionsSublingual tablets of Losartan Potassium were successfully prepared with improved bioavailability.     

Cholesteatoma Induced Labyrinthine Fistula: Is Aggressiveness in Removing Disease Justified?

Issues of complete disease clearance and hearing preservation in cholesteatoma induced labyrinthine fistula cases has been discussed and updated in this article. Successful disease clearance and hearing preservation in a case of cholesteatoma induced isolated cochlear promontory fistula encouraged us to retrospectively analyse 13 more cases of cholesteatoma induced labyrinthine fistula who presented in emergency service as complicated chronic suppurtive otitis media. Pre-operatively nine patients experienced vertigo, two had profound sensori neural hearing loss and radiology was suggestive of labyrinthine fistula in 12 patients. Lateral semicircular canal was involved in 13 cases. In all cases cholesteatoma matrix was completely removed from the fistula site irrespective of the fistula size and hearing status. Hearing was preserved in 11 out of 12 patients. Gentle and meticulous removal of the matrix and careful repair of labyrinthine fistula delivers significant hearing preservation rate along with a safe and dry ear which avoids a second look surgery.     

Introduction of new vaccines in state immunization schedule — Delhi’s experience

Immunization is an established, cost-effective, preventive intervention to improve child survival. To provide protection against vaccine preventable diseases, all countries in the world have an immunization program that offers selected vaccines to the eligible beneficiaries. In India, Expanded Program of Immunization was started in 1978, and then Universal Immunization Program was launched in 1985 with six antigens. This article describes the experience with institutionalization of four state-specific vaccines by Delhi in its immunization schedule to enlarge the ambit of immunization services. It attempts to highlight the state’s perspective in terms of the implementation policy, operational strategy adopted and evolution of immunization program in the state over 16 years.     

Penile Gangrene and Urethrocutaneous Fistula Following Transurethral Resection of Prostatic Carcinoma. A Case Report

Channel transurethral resection of prostate (TURP) is an accepted treatment for advanced carcinoma of prostate (CaP) to improve quality of life. We are presenting a case of penile gangrene and urethrocutaneous fistula following TURP in a CaP. This is the first case in literature to our knowledge.     

Lifespan extension of Drosophila melanogaster through hormesis by repeated mild heat stress

We assessed the impact of repeated episodes of a mild heat stress on lifespan, fecundity, heat stress resistance and Hsp70 expression in Drosophila melanogaster. There was a significant increase in lifespan of females repeatedly exposed to a mild heat stress when measured in both a pair and a group situation. There was no effect on fecundity when the flies were first exposed to the mild heat stress at an age later than 3 days old, but when it did occur on day 3, there was a significant effect on cumulative fecundity levels over 18 days. The negative fitness effect appears to be the result of a direct cessation or reduction of oviposition during the first bout of stress exposure, and is influenced by the age at which this first exposure occurs. The mild heat stress had no impacton egg viability. The mild heat stress exposures increased resistance to potentially lethal heat stress and levels of Hsp70 expression in heat-exposed flies were higher than those in controls. This revised version was published online in July 2006 with corrections to the Cover Date.     

Review: peroxisome proliferator-activated receptor-gamma and its role in the development and treatment of diabetes

Since its identification as the receptor for antidiabetic thiazolidinedione drugs, peroxisome proliferator-activated receptor-gamma (PPARgamma) has been the focus of pharmaceutical drug discovery programs directed toward finding better drugs for the treatment of diabetes, as well as the object of basic research aimed at understanding its role in the regulation of metabolism. We now understand a great deal about the crucial role that PPARgamma plays in adipocyte differentiation and development, and are rapidly gaining knowledge about the role of the receptor in the regulation of metabolism. However, many crucial aspects of the molecular mechanism by which modulation of PPARgamma activity affects insulin resistance and glucose homeostasis are still not clearly understood. Here the authors review the current status of PPARgamma research, with an emphasis on its role in the causes and treatment of type 2 diabetes.     

A randomized trial of nicotine enemas for active ulcerative colitis.

BACKGROUND & AIMS: Ulcerative colitis (UC) is largely a disease of nonsmokers in which transdermal nicotine improves the symptoms but often causes adverse events (AEs). Nicotine enemas cause fewer AEs and were used as supplemental treatment for active UC. METHODS: We treated 104 patients with active UC with either 6-mg nicotine enemas or placebo enemas for 6 weeks in a randomized double-blind study. Patients continued their oral therapy, if any, for UC: 68 patients were taking mesalamine, 15 patients were taking prednisolone, and 12 patients were taking thiopurines during the study. Clinical, sigmoidoscopic, and histologic assessments were made at baseline and at the end of the study and symptoms were recorded daily on a diary card. The primary end point was induction of clinical remission and clinical improvement also was measured by the UC disease activity index. After the study, patients then used nicotine enemas daily for 4 weeks and sigmoidoscopy with a biopsy examination was repeated. AEs and salivary cotinine levels were monitored throughout the study. RESULTS: Clinical remission was achieved in 14 of 52 (27%) patients on active treatment and 14 of 43 (33%) patients on placebo (P = .55). The UC disease activity index improved by 1.45 points in the active group and by 1.65 points for those on placebo (P = .88). Only 1 patient discontinued treatment because of an AE (abdominal pain). In the 47 patients taking mesalamine only, active treatment conferred benefit that was not statistically significant; disease remission occurred in 9 of 25 patients on active therapy and 4 of 21 patients on placebo (P = .20). CONCLUSIONS: Six-milligram nicotine enemas were well tolerated but were not found to be efficacious for active UC.     

Hemophilia A: role of FVIIIC/vWF Ag in assisting linkage analysis for carrier detection.

Carrier detection for hemophilia A was carried out in 52 females from 30 families presenting to the Haematology Department AIIMS, using linkage analysis and factor VIIIC (FVIIIC)-von Willebrand factor (vWF) antigen assay. The allelic frequency for the marker Bcl 1 and Xba 1 was 0.58 and 0.54, respectively, for the positive alleles and 0.42 and 0.46, respectively, for the negative alleles. The heterozygosity frequency of Bcl I and Xba 1 was 0.65 and 0.55, respectively. Of the 52 females, 30 were mothers of hemophilic patients and 22 were sisters of hemophilic patients. Of the 30 mothers, positive family history was present in 14. In these patients, the defective X chromosome was tracked in 10, and in four the defective X chromosome could not be tracked because the mothers were homozygous for the marker used. Of the 16 mothers without a family history of disease, three were observed to be carriers based on linkage analysis and reduced factor VIII levels in mother/sister. Possible defective X chromosome was tracked in 11 mothers and five were noninformative because they did not show heterozygosity for the markers used. Using linkage analysis, nine of the 22 sisters were found to be definite carriers, 10 noncarriers, and three were noninformative. It is thus concluded that using Bcl 1 and Xba 1 linkage analysis, carrier status can be definitely ascertained in 50% females and this level of information can be increased to 61.5% by measuring FVIIIC/vWF antigen levels in them.     

Analysis of the functional integrity of cryopreserved human liver cells including xenografting in immunodeficient mice to address suitability for clinical applications.

BACKGROUND: The availability of well-characterized human liver cell populations that can be frozen and thawed will be critical for cell therapy. We addressed whether human hepatocytes can recover after cryopreservation and engraft in immunodeficient mice. METHODS: We isolated cells from discarded human livers and studied the properties of cryopreserved cells. The viability of thawed cells was established with multiple in vitro assays, including analysis of liver gene expression, ureagenesis, cytochrome P450 activity, and growth factor-induced cell proliferation. The fate of transplanted cells was analysed in immunodeficient NOD-SCID mice. RESULTS: After thawing, the viability of human hepatocytes exceeded 60%. Cells attached to culture dishes, proliferated following growth factor stimulation and exhibited liver-specific functions. After transplantation in NOD-SCID mice, cells engrafted in the peritoneal cavity, a heterologous site, as well as the liver itself, retained hepatic function and proliferated in response to liver injury. Transplanted hepatocytes were integrated in the liver parenchyma. Occasionally, transplanted cells were integrated in bile ducts. CONCLUSIONS: Cryopreserved human liver cell showed the ability to retain functional integrity and to reconstitute both hepatic and biliary lineages in mice. These studies offer suitable paradigms aimed at characterizing liver cells prior to transplantation in people.