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Biomedical subjects

R K Sharma

Publications and source records attributed to R K Sharma.

At least 55 records · Page 3Linked to original sources

Efficacy of chitosan microspheres for controlled intra-articular delivery of celecoxib in inflamed joints.

The use of polymeric carriers in formulations of therapeutic drug delivery systems has gained widespread application, due to their advantage of being biodegradable and biocompatible. In this study, we aimed to prepare celecoxib-loaded chitosan microspheres for intra-articular administration and to compare the retention of the celecoxib solution and chitosan microspheres in the joint cavity. The microspheres were characterized for entrapment efficiency, particle size and surface morphology by scanning electron microscopy. In-vitro drug release studies of microspheres revealed that the microspheres are able to control the release of celecoxib over a period of 96 h. Biodistribution studies of celecoxib and chitosan microspheres were performed by radiolabelling with( 99m)Tc and injecting intraarticularly in rats. The study indicated that following intra-articular administration the distribution of the drug to the organs, like liver and spleen, is very rapid compared with that of the microspheres. Compared with the drug solution, a 10-fold increase in the concentration of the drug in the joint was observed 24 h post intra-articular injection (P < 0.005) when drug was encapsulated in microspheres.

Animals↗

Suicide by a transvestite or sexual asphyxia? A case report.

Autoerotic asphyxial activity may at times result in unexpected death. Although the majority of deaths that occur during autoerotic asphyxial episodes are accidental, the possibility of suicide must always be entertained. In the case presented here, a 22-year-old married male was found hanging by his neck in his bedroom, which was locked from the inside. He was suspended by a 'lungi' (male wrap-around cloth) from the ceiling fan hook in his room, with his feet touching the ground. He was dressed in a brassiere, panties, and silver anklets. There was no evidence of previous perverse behaviour, and investigation disclosed no evidence of previous autoerotic sexual activity, homosexual behaviour, drug abuse or suicidal ideation.

Asphyxia↗

Serum & urinary interleukin-2 levels as predictors in acute renal allograft rejection.

BACKGROUND & OBJECTIVES: In spite of potent immunosuppression, acute rejection continues to be the single largest cause of graft dysfunction after renal transplantation. Renal allograft biopsy, though invasive, continues to be the reference standard, though certain clinical and biochemical parameters are helpful in assessment of these patients. Acute renal allograft rejection is mediated by T lymphocytes, which express increased number of interleukin-2 receptors (IL-2R). The soluble component of IL-2R in serum and urine may be useful in detecting early graft rejection. This study assesses the possibility of using serum and urinary IL-2R estimation in early prediction and diagnosis of acute renal allograft rejection. METHODS: Sequential estimation of serum and urinary IL-2R levels along with serum creatinine values were assessed in 23 live related renal allograft recipients. The age of renal allograft recipients was 35+/-8.3 yr, with male:female ratio of 22:1. Samples were collected pre-transplant (day 0) and post-transplant upto 30 days and the patients were followed for 6 months after transplantation. Eight recipients experienced graft dysfunction and graft biopsies were evaluated. RESULTS: Serum and urinary IL-2R patterns along with serum creatinine levels were correlated with the occurrence of graft rejection on histology. Eight recipients experienced acute graft rejection after transplantation and 15 had stable graft function. Serum IL-2R levels at various periods after transplantation were found to be significantly (P<0.05) elevated in graft recipients experiencing acute rejection as compared to the non-rejection group. The rise in urinary IL-2R levels in some of the rejection group recipients, was not statistically significant. INTERPRETATION & CONCLUSION: Sequential serum and urinary IL-2R assay may serve as a predicter for early graft dysfunction. Study with larger sample size and for longer duration is required to further validate the results.

Adolescent↗

Sperm DNA damage and its clinical relevance in assessing reproductive outcome.

The routine examination of semen, which assesses sperm concentration, percentage motility and morphology, does not identify subtle defects in sperm chromatin architecture. The focus on the genomic integrity of the male gamete has intensified recently due to the growing concern that genetic diseases may be transmitted via assisted reproductive techniques (ART). Accordingly, the intent of this review is to describe the details of the information pertaining to mitochondrial/nuclear sperm DNA damage with an emphasis on its clinical significance and its relationship with male infertility. Assessment of sperm DNA damage appears to be a potential tool for evaluating semen samples prior to their use in ART. Testing DNA integrity may help select spermatozoa with intact DNA or with the least amount of DNA damage for use in assisted conception. In turn, this may alleviate the financial, social and emotional problems associated with failed ART attempts.

Adult↗

Calvarial malignant fibrous histiocytoma.

Primary malignant fibrous histiocytoma (MFH) of the central nervous system (CNS) is uncommon. We report cases of two young patients of MFH arising from the cranial meninges and involving the adjacent skull and scalp. There was infiltration of the brain in one case. Both the lesions were excised and primary scalp repair was performed.

Adult↗

Factors influencing refusal by relatives of brain-dead patients to give consent for organ donation: experience at a transplant centre.

To analyse the reasons for family refusal for donating the organs of their deceased relatives, 33 families were approached and interviewed as a part of the consent process. Thirty of these refused and their reasons for refusal were documented. In 83%, the principle reason for refusal to give consent was the non-acceptance of brain death. Superstitions relating to being reborn with a missing organ (that had been donated) in 40% or that tampering with the body would not free their dead relatives from the cycle of life-death-rebirth in 26% were next most frequently voiced. A delay in funeral (23%), lack of consensus within family members (17%), fear of social criticism (10%), dissatisfaction with the hospital staff (10%) and being unaware of their deceased relatives' wishes (6%) were the other reasons cited.

Attitude to Health↗

Studies on photo-degradation of 2,4-dinitro toluene in aqueous phase.

The efficiency of different photo-degradation processes was evaluated for degrading 2,4-dinitro toluene (DNT) in aqueous phase. The rate and extent of DNT degradation and removal of total organic carbon (TOC) and total nitrogen (TN) contents were compared for direct photolytic and photo-oxidative reactions using various concentrations of H2O2 and Fenton's reagent with a 125 W medium pressure UV lamp. DNT was degraded rapidly under photo-oxidative conditions. Complete destruction was obtained using Fenton's reagent, wherein 100 ppm of DNT was degraded within 60 min of irradiation time. Removal of TOC and TN contents in the photo-Fenton system was 96% and 57%, respectively, after 2 h of UV irradiation. Degradation of DNT followed first order reaction kinetics. Photo-Fenton oxidation is found to be the most suitable technique to degrade DNT in aqueous phase.

Carbon↗

Testicular development and its relationship to semen production in Murrah buffalo bulls.

The objectives of this study were to determine the relationship of age and body weight to testicular development and to establish norms for breeding soundness evaluations of Murrah buffalo bulls. Testicular measurements of 133 Murrah buffalo bulls of various ages were recorded with a caliper and a tape. Semen was collected twice a week for 5 weeks from groups of bulls which were 25-36 (n=17), 37-48 (n=16), 49-60 (n=14), of >60 (n=10) months of age. After examining volume, sperm concentration, and progressive motility semen was diluted in Tris-citric acid-egg yolk-fructose extender and frozen in 0.5 ml French straws. Testicular measurements of buffalo bulls were lower than those recorded for European breeds of cattle bulls. Nevertheless, like cattle bulls, scrotal circumference was highly correlated with other testicular measurements. Also, it had a significant positive relationship with semen volume and sperm concentration per ejaculate. Average sperm output per week in order of increasing age group was 15.3, 18.2, 19.8 and 23.6 x 10(9). Corresponding values for sperm output per week per gram of testis were 59.1, 45.8, 41.1, 36.2 x 10(6) indicating a reduction in spermatogenesis per unit of testis with advancing age. Compared to European breeds, daily sperm output in Murrah bulls was nearly 45% lower, presumably due to their nearly 40% lower scrotal circumference than Holstein bulls of the same age. These results indicate that in buffalo, as in cattle, scrotal circumference is a useful indicator of potential sperm output and may serve as an important criterion for selecting young bulls as AI sires.

Aging↗

Preparation, characterisation and biodistribution of 99mTc-labeled liposome encapsulated cyclosporine.

The present study investigated the effect of charge (neutral, negative and positive) on liposomal membrane on the distribution of cyclosporine encapsulated in it to various organs. Liposomes were prepared by using different phospholipids by thin film hydration followed by sequential extrusion through polycarbonate membranes to achieve a desired particle size, with high entrapment efficiency and then lyophilised using sucrose as cryoprotectant. The possible in vivo distribution of cyclosporine and its liposomes after direct labeling with reduced technetium-99m has been studied in mice. The blood kinetics and biodistribution study of these labeled complexes shows prolonged circulation of positive and neutral charged liposomes in blood compared to free drug and negative charged liposomal formulation. The biodistribution of the tagged liposomes confirms that increased radioactivity was seen in liver and spleen, with minimal involvement of the kidney. At 4 h post injection the biodistribution data in kidney reveals approximately 1-2% of the injected dose was present for cyclosporine loaded liposomes, which elicits the possibility of reducing the nephrotoxicity, generally seen in free cyclosporine. Interestingly, the biodistribution and gamma imaging studies of the charged cyclosporine liposomes indicated that an appreciable amount of these labeled complexes goes to bone marrow when compared to the free cyclosporine. The findings demonstrate the distribution of these liposomes within various organs and proved that the positively charged liposomes experience increased bone uptake and prolonged circulation half-life. Hence this finding implies the possibility of using these formulations for liver and bone marrow transplantation.

Animals↗

Cytotoxic mannich bases of 1-arylidene-2-tetralones.

Various 1-arylidene-2-tetralones 1 had been shown previously to possess moderate cytotoxic properties unaccompanied by murine toxicity. The objective of the present investigation was to undertake different molecular modifications of representative members of series 1 with a view to discerning those structural features leading to increased potencies. All compounds were evaluated using human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. The Mannich bases 2, 4, 5 and 7 possessed increased potencies compared to the corresponding unsaturated ketones 1 and in general were potent cytotoxics having IC50 values in the 0.2-10 microM range. QSAR using the cytotoxicity data for 2a-e suggested that potency was positively correlated with the size of the substituents in the arylidene aryl ring. Compounds 2a-f were evaluated using a panel of approximately 53 human tumour cell lines and, when all cell lines were considered, were more potent than the reference drug melphalan. In particular, marked antileukemic activity was displayed. Molecular modeling was utilized in order to evaluate whether the shapes of the different compounds contributed to the varying potencies observed. Representative compounds demonstrated minimal or no inhibiting properties towards human N-myristoyltransferase (NMT) and did not bind to calf thymus DNA. This study has revealed a number of unique lead molecules as candidate anti-neoplastic agents serving as prototypes for future development.

Acyltransferases↗

3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones: a novel group of cytotoxic agents.

A series of novel 3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones 3 have been synthesized which displayed potent cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. In contrast, the related N-arylmaleamic acids 4 possessed little or no cytotoxicity in these four screens. Molecular modeling revealed certain interplanar and bond angles and interatomic distances which were perceived to contribute to the observed bioactivity as well as providing suggestions for future structural modifications of the piperidones 3. Evaluation of representative compounds in series 3 and 4 on the activity of human N-myristoyltransferase revealed that, at the maximum concentration utilized, namely 250 microM, only weak inhibiting properties were displayed by some of the compounds in series 4. Various members of series 3 and 4 were well tolerated in mice.

Animals↗

Role of vascular access as a risk factor for infections in hemodialysis.

Infections are a major cause of morbidity and mortality in chronic hemodialysis patients. This single center prospective study was carried out to determine the incidence and risk factors for infection in hemodialysis patients and plan appropriate strategies to reduce the risk of infection. A total of 84 consecutive patients who were initiated on hemodialysis over a 2-year period were followed until they either received a kidney transplant or died. In our hospital, as a policy, patients are offered hemodialysis as a bridge therapy to a kidney transplant. The mean duration of follow up was 3 months (range 1-11.8 months). The factors associated with at least one episode of infection were evaluated. Statistical analysis was done by multivariate stepwise logistic regression method. Fifty-one patients had a total of 57 episodes (67.8%) of infection. Of the 44 episodes of acute bacterial infections, vascular access exit site infection was the commonest followed by septicemia (13 patients, 29.5%). Staphylococcus aureus was the commonest bacterial isolate observed in 14 patients. On multivariate analysis, three risk factors for infection were identified: (1) nonarteriovenous fistula (AVF) vascular access for hemodialysis (p = 0.02), (2) increased number of hemodialysis sessions (p = 0.03), and (3) lower serum calcium level (p = 0.02). NonAVF vascular access was found to be the most important risk factor for infection in hemodialysis patients. Creation of an AV fistula, preferably at an early stage, appears beneficial for minimizing the risk of infection even in patients who are on short-term hemodialysis as a bridge therapy towards a kidney transplant.

Adult↗

Technique for secondary tracheo-oesophageal puncture in difficult necks.

A secondary tracheo-oesophageal puncture is required for voice restoration post-laryngectomy either for reasons of closure of the primary fistula or as a planned secondary procedure. A method of doing this safely is described using an endotracheal tube and a flexible nasopharyngoscope in especially difficult cases.

Esophagus↗

Melanotic neuroectodermal tumour in an infant.

Most jaw swellings in infancy are benign odontogenic cysts or tumours. The encounter with an unusual melanotic neuroectodermal tumour of the jaw in a young infant is described in this report. There has been no recurrence, after complete surgical excision, in a follow-up period of six months.

Female↗

Do current recommendations for kidney biopsy in nephrotic syndrome need modifications?

The current recommendations of kidney biopsy in childhood idiopathic nephrotic syndrome (CINS) were put forward to minimize unnecessary kidney biopsies in underlying minimal change disease (MCD). However, there remains a diversity of opinion about the criteria for biopsying children with idiopathic nephrotic syndrome. This study was conducted to prospectively study their usefulness in avoiding biopsies in MCD and to evaluate further modifications for minimizing biopsies in CINS. Of 400 consecutive CINS patients, 222 patients were subjected to kidney biopsy according to the current recommendations. The histopathology spectrum of these selectively biopsied children revealed focal segmental glomerulosclerosis (FSGS) in 39%, MCD in 34.2%, membranoproliferative glomerulonephritis (MPGN) in 16.2%, mesangioproliferative glomerulonephritis (MesPGN) in 7.6%, membranous nephropathy (MN) in 1.8%, and diffuse mesangial sclerosis (DMS) in 0.9%. We observed that despite the current recommendations and efforts to minimize biopsy, 34% of children had MCD on histopathology. Two or more clinical (hematuria and hypertension) or biochemical (renal insufficiency) parameters were present in all children with MPGN. Low C3 was present only in children with MPGN. All the steroid responders were found to have MCD, FSGS, or MesPGN on biopsy. Cyclophosphamide response correlated better with steroid responsiveness ( P=0.02) than with histo- pathology ( P=0.80) in MCD, FSGS, and MesPGN. Based on these observations, we suggest some modifications in current recommendations for kidney biopsy to minimize biopsying children with MCD. These are (1) biopsies in children (age 1-16 years) should be restricted (a) to a subgroup with two or more clinical and biochemical parameters and (b) in steroid non-responders, (2) the decision to administer cyclophosphamide should be based on steroid response pattern without requiring a prior routine biopsy.

Adolescent↗