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Biomedical subjects

R K Sharma

Publications and source records attributed to R K Sharma.

At least 19 recordsLinked to original sources
PubMed2006

High prevalence of ACE DD genotype among north Indian end stage renal disease patients.

BACKGROUND: The Renin-Angiotensin system (RAS) is a key regulator of both blood pressure and kidney functions and their interaction. In such a situation, genetic variability in the genes of different components of RAS is likely to contribute for its heterogeneous association in the renal disease patients. Angiotensin converting enzyme-1 (ACE-1) is an important component of RAS which determines the vasoactive peptide Angiotensin-II. METHODS: In the present study, we have investigated 127 ESRD patients and 150 normal healthy controls from north India to deduce the association between ACE gene polymorphism and ESRD. The inclusion criteria for patients included a constantly elevated serum creatinine level above normal range (ranging from 3.4 to 15.8) and further the patients were recommended for renal transplantation. A total of 150 normal healthy controls were also genotyped for ACE I/D polymorphism. The criterion of defining control sample as normal was totally based on the absence of any kidney disease determined from the serum creatinin level. Genotyping of ACE I/D were assayed by polymerase chain reaction (PCR) based DNA amplification using specific flanking primers Based on the method described elsewhere. RESULTS: The difference of DD and II genotypes was found highly significant among the two groups (p = 0.025; OR = 3.524; 95% CI = 1.54-8.07). The combined genotype DD v/s ID+II comparison validated that DD genotype is a high risk genotype for ESRD (p = 0.001; OR = 5.74; 95% CI limit = 3.4-8.5). However, no correlation was obtained for different biochemical parameters of lipid profile and renal function among DD and non DD genotype. Interestingly, approximately 87% of the DD ESRD patients were found hypertensive in comparison to the 65% patients of non DD genotype CONCLUSION: Based on these observations we conclude that ACE DD genotype implicate a strong possible role in the hypertensive state and in renal damage among north Indians. The study will help in predetermining the timing, type and doses of anti-hypertensive therapy for ESRD patients.

Adult↗
PubMed2006

Synthesis and pharmacological study of novel pyrido-quinazolone analogues as anti-fungal, antibacterial, and anticancer agents.

A versatile method for novel pyrido-quinazolones was described here and tested for anti-fungal, antibacterial, and anticancerous activities. These synthesized compounds were characterized on the basis of spectroscopic techniques and evaluated for specific radiopharmaceuticals. Preliminary radiolabeling results with (99m)Tc and biological evaluation studies showed promising results for further evaluation in vivo. The efficiency of labeling was more than 98% and complexes were stable for about 18 h at 25 degrees C in the presence of serum.

Adenocarcinoma↗
PubMed2006

Zingiber officinale exhibits behavioral radioprotection against radiation-induced CTA in a gender-specific manner.

At the organismic level, exposure to radiation can produce taste aversion (CTA) learning and emesis, which have been proposed as behavioral endpoints that are mediated by harmful effects of radiations on peripheral systems, primarily the gastrointestinal system. Thus, the aim of the present investigation was to study the gastroprotective action of hydroalcoholic extract of zingiber rhizome (Zingiber officinale Rosc.) against radiation-induced conditioned taste aversion (CTA) in both male and female species of animals, for testing its potential as a behavioral radioprotector. Administration of zingiber extract 1 h before 2-Gy gamma-radiation was significantly effective in blocking the saccharin avoidance response, with 200 and 250 mg/kg b.wt. i.p., being the most effective doses for male and female rats, respectively. A comparison of the efficacy of zingiber extract with two antiemetic drugs, ondansteron and dexamethasone, revealed that the extract rendered comparable protection against radiation-induced CTA. Our experiments also confirmed the existence of sex dichotomy (i.e., the sex of animal greatly influenced response towards radiation exposure) in relation to behavioral responses (CTA) or differential metabolism. The observed gender variations were hypothesized to be a result of hormonal fluctuations and differences in pharmacological parameters in male and female rats. To correlate the mechanism of action, the free-radical-scavenging potential of zingiber extract to scavenge hydroxyl ion and nitric oxide was also tested, in cell-free system and a concentration of 1000 microg/ml, was found to be the most potent, which has been proposed as one the many activities assisting in its overall ability to modulate radiation-induced taste aversion. The results demonstrate that Z. officinale possesses antioxidant, radioprotective and neuromodulatory properties that can be effectively utilized for behavioral radioprotection and for efficiently mitigating radiation-induced CTA in both males and females species.

Animals↗
PubMed2006

Grommet insertion: a novel technique.

We describe a new technique for inserting grommets which is both easy to master and provides better visualization of the tympanic membrane. This is particularly helpful in patients with narrow ear canals.

Humans↗
PubMed2006

Preliminary brain-targeting studies on intranasal mucoadhesive microemulsions of sumatriptan.

The aim of this investigation was to prepare microemulsions containing sumatriptan (ST) and sumatriptan succinate (SS) to accomplish rapid delivery of drug to the brain in acute attacks of migraine and perform comparative in vivo evaluation in rats. Sumatriptan microemulsions (SME)/sumatriptan succinate microemulsions (SSME) were prepared using titration method and characterized for drug content, globule size and size distribution, and zeta potential. Biodistribution of SME, SSME, sumatriptan solution (SSS), and marketed product (SMP) in the brain and blood of Swiss albino rats following intranasal and intravenous (IV) administrations were examined using optimized technetium-labeled ((99m)Tc-labeled) ST formulations. The pharmacokinetic parameters, drug targeting efficiency (DTE), and direct drug transport (DTP) were derived. Gamma scintigraphy imaging of rat brain following IV and intranasal administrations were performed to ascertain the localization of drug. SME and SSME were transparent and stable with mean globule size 38 +/- 20 nm and zeta potential between -35 to -55 mV. Brain/blood uptake ratios at 0.5 hour following IV administration of SME and intranasal administrations of SME, SMME, and SSS were found to be 0.20, 0.50, 0.60, and 0.26, respectively, suggesting effective transport of drug following intranasal administration of microemulsions. Higher DTE and DTP for mucoadhesive microemulsions indicated more effective targeting following intranasal administration and best brain targeting of ST from mucoadhesive microemulsions. Rat brain scintigraphy endorsed higher uptake of ST into the brain. Studies conclusively demonstrated rapid and larger extent of transport of microemulsion of ST compared with microemulsion of SS, SMP, and SSS into the rat brain. Hence, intranasal delivery of ST microemulsion developed in this investigation can play a promising role in the treatment of acute attacks of migraine.

Administration, Intranasal↗
PubMed2006

Intranasal mucoadhesive microemulsions of clonazepam: preliminary studies on brain targeting.

The aim of this investigation was to prepare clonazepam microemulsions (CME) for rapid drug delivery to the brain to treat acute status epileptic patients and to characterize and evaluate the performance of CME in vitro and in vivo in rats. The CME were prepared by the titration method and were characterized for globule size and size distribution, zeta potential, and drug content. CME was radiolabeled with (99m)Tc (technetium) and biodistribution of drug in the brain was studied in Swiss albino rats after intranasal and intravenous administrations. Brain scintigraphy imaging in rabbits was also performed to ascertain the uptake of the drug into the brain. Pre and postCME formulation treated human nasal mucosa was subjected to transmission electron microscopy to investigate the mechanism of drug uptake across the nasal mucosa. CME were transparent and stable with mean globule size of 15 +/- 10 nm and zeta potential of -30 mV to -40 mV. (99m)Tc-labeled clonazepam solution ((99m)Tc CS)/ clonazepam microemulsion (CME)/clonazepam mucoadhesive microemulsion (CMME) were found to be stable and suitable for in vivo studies. Brain/blood uptake ratios at 0.50 hour (h) following intranasal CMME, CME, clonazepam solution (CS), and intravenous CME administrations were found to be 0.67, 0.50, 0.48, and 0.13, respectively indicating more effective targeting with intranasal administration and best targeting of the brain with intranasal CMME. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of CMME compared to intravenous was found to be twofold higher indicating larger extent of distribution of the drug in brain. Rabbit brain scintigraphy also showed higher intranasal uptake of the drug into the brain. Transmission electron microscopy revealed significant accretion of CMME within interstitial spaces and paracellular mode of transport due to stretching of the tight junctions present in the nasal mucosa. This investigation demonstrates a more rapid and larger extent of transport of clonazepam into the rat brain with intranasal CMME, which may prove useful in treating acute status epileptics.

Administration, Intranasal↗
PubMed2006

Cell death regulation by B-cell lymphoma protein.

Bcl-2 (B Cell Lymphoma) protein is an anti-apoptotic member of Bcl-2 family, which is comprised of pro- and anti-apoptotic members. It regulates cellular proliferation and death by inter- and intra-family interactions. It has a potential to suppress apoptotic cell death under variety of stress conditions by modulating mitochondrial transmembrane potential. However, prevalence of constitutively activated Bcl-2 cellular activity is not always required in cells; a mechanism likely exists in cells, which controls its activity. When expression of Bcl-2 is unregulated, it generates lymphoma like, follicular B-cell lymphoma. This article reviews the structural and functional regulation of Bcl-2 activity at transcriptional, translational, domain, structural and post-translational level, which also accounts for the effects of its deletion and site-directed mutants in the regulation of cellular proliferation and differentiation in vitro and in vivo. This concisely reviewed information on Bcl-2 helps us to update our understanding of cell death and its modulation by Bcl-2 and its mutant's interaction, which has gained therapeutic benefits in cell growth and proliferation, particularly for sensitive human hematopoietic stem cells.

Animals↗
PubMed2006

PU.1: An ETS family transcription factor that regulates leukemogenesis besides normal hematopoiesis.

The hematopoietic transcription factor PU.1, which is required for lymphomyeloid differentiation of stem cells, was originally identified as an oncogene. In erythroid progenitors, the integration of spleen focus-forming virus (SFFV) into the PU.1 locus causes its overexpression, which blocks their terminal differentiation into erythrocytes and ultimately leads to the development of erythroleukemia. However, in myeloid lineages, PU.1 promotes granulocytic and monocytic differentiation, and graded reduction in its expression blocks their differentiation or maturation and thereby causes myelogenous leukemia. Thus, in addition to normal hematopoietic regulation, PU.1 plays a significant role in leukemogenesis. In the following review, we have consolidated our understanding of the role of transcription factor PU.1 in the development of erythroid as well myeloid leukemia.

Animals↗
PubMed2006

Toll like receptor-4 expression in lipopolysaccharide induced lung inflammation.

Bacterial lipopolysaccharides (LPS) initiate immune response through Toll-like receptor 4 (TLR4). Because many a times host is confronted with secondary bacterial challenges, it is critical to understand TLR4 expression following initial provocation. We studied TLR4 expression in rats at various times after intra-tracheal instillation of LPS. Although TLR4 mRNA was undetectable in normal lungs, it increased at 6h and 12h and declined at 36h post-LPS treatment. Western blots showed TLR4 protein at all time points. Immunohistochemistry localized TLR4 in alveolar septal cells, bronchial epithelium, macrophages and endothelium of large and peribronchial blood vessels. Dual label immunoelectron microscopy showed co-localization of TLR4 and LPS in the cytoplasm and nucleus of various lung and inflammatory cells. Nuclear localization of TLR4 was confirmed with Western blots on lung nuclear extracts. We conclude that TLR4 expression in lung is sustained up to 36 hours and that TLR4 and LPS are localized in the cytoplasm and nuclei of lung cells.

Animals↗
PubMed2006

Histopathological changes in liver, kidney and muscles of pesticides exposed malnourished and diabetic rats.

Histopathological changes were observed in liver, kidney and muscles of normal, protein-malnourished, diabetic as well as both protein-malnourished and diabetic albino rats when exposed to a mixture of monocrotophos, hexachlorocyclohexane and endosulfan at varying intervals. The examination revealed hepatotoxic, nephrotoxic and muscular necrotic effects in pesticides exposed rats. Toxicity was aggravated in protein-malnourished and diabetic animals and more so, if the animals were both diabetic and protein-malnourished.

Animals↗
PubMed2006

Omental cyst--a rare entity.

A case of omental cyst in a young girl who presented with distension and a lump in abdomen and having difficulty in micturition is reported. Pre-operative diagnosis was achieved by ultrasonography. An exploratory laparotomy with excision of cyst was done and histopathologic examination of the specimen confirmed the diagnosis. The postoperative course was uneventful. The aetiopathogenesis, special features of the disease and review of literature is discussed.

Child↗
PubMed2005

Stenting for bilateral congenital choanal atresia--a new technique.

We describe a new nasal stent for the treatment of bilateral congenital choanal atresia. The stent is made up of reinforced endotracheal tube mounted on a portex carrier tube. It potentially causes less internal crusting and stent blockage and is secured without sutures. It remains patent for at least 4 weeks. We have used the stent successfully in six patients between 1998 and 2004 at Leeds General Infirmary and present the data collected retrospectively. The current practice in the UK for treatment and stenting for congenital choanal atresia was investigated by a prospective internet based questionnaire sent to 18 consultant paediatric otolaryngologists of whom 12 (67%) responded. Their experience and results are reported. The literature has been reviewed.

Choanal Atresia↗
PubMed2005

Amoebic renal cyst: a case report.

Entamoeba histolytica can infect any organ of the body, but only one case of renal involvement has been reported till now in the literature. We report a rare case of amoebic renal cyst in a 78-year showing favorable outcome with metronidazole treatment and therapeutic drainage.

Aged↗
PubMed2005

Influence of administration route on tumor uptake and biodistribution of etoposide loaded solid lipid nanoparticles in Dalton's lymphoma tumor bearing mice.

The study evaluates the capability of tripalmitin nanoparticles in enhancing the tumor uptake of etoposide, and the influence of administration route on the biodistribution and tumor uptake of etoposide loaded tripalmitin (ETPL) nanoparticles in Dalton's lymphoma tumor bearing mice. ETPL nanoparticles were prepared by melt-emulsification and high pressure homogenization followed by the spray drying of nanodispersion. Characterization of the nanoparticles was done by particle size analysis, zeta potential measurement and scanning electron microscopy. The size of ETPL nanoparticles was 387 nm and possessed negative charge. Etoposide and ETPL nanoparticles were radiolabeled with 99mTc with high labeling efficiency. The labeled complexes showed good in vitro stability in the presence of DTPA/cysteine and serum stability. Etoposide and ETPL nanoparticles were injected by subcutaneous, intravenous or intraperitoneal routes and their biodistribution and tumor uptake were determined. Subcutaneous injection reduced the distribution of ETPL nanoparticles to all the tissues studied whereas after intraperitoneal injection, the distribution of ETPL nanoparticles to tissues was higher than free etoposide. The intravenous injection resulted in lower concentrations of ETPL nanoparticles in the organs of RES compared to free etoposide. ETPL nanoparticles experienced significantly high brain distribution after intraperitoneal injection indicating its potential use in targeting etoposide to brain tumors. After subcutaneous injection, the tissue distribution of ETPL nanoparticles increased with time indicating their accumulation at the injection site for a longer time. The tumor uptake of both etoposide and ETPL nanoparticles was significantly high after subcutaneous injection (P<0.001) compared to the other routes of administration. The tumor concentration of ETPL nanoparticles after subcutaneous injection was 59 folds higher than that obtained after intravenous and 8 folds higher than after intraperitoneal route at 24 h post-injection. The tumor concentration of ETPL nanoparticles increased with time after subcutaneous injection indicating the slower and progressive penetration from the injection site into the tumor. The study signifies the advantage of incorporating etoposide into tripalmitin nanoparticles in controlling its biodistribution and enhancing the tumor uptake by several folds. The study also reveals that, of the three routes investigated, subcutaneous injection is the route of preference for facilitating high tumor uptake and retention and is likely to have greater antitumor effect resulting in tumor regression.

Animals↗