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Neeraj Sharma

Publications and source records attributed to Neeraj Sharma.

6 recordsLinked to original sources
PubMed2006

Kinetic characterization of Zinc transport process and its inhibition by Cadmium in isolated rat renal basolateral membrane vesicles: in vitro and in vivo studies.

We firstly characterized zinc uptake phenomenon across basolateral membrane vesicles (BLMVs) isolated from normal rat kidney. The process was found to be time, temperature, and substrate concentration dependent, and displayed saturability. Zn(2+) uptake was competitively inhibited in the presence of 2 mM Cd with Ki of 3.9 mM. Zinc uptake was also inhibited in the presence of sulfhydryl reacting compound suggesting involvement of [-]SH groups in the transport process. Further, to elucidate the effect of in vivo Cd on zinc transport in BLMVs, Cd nephrotoxicity was induced by subcutaneous administration of CdCl(2) at dose of 0.6 mg/kg/d for 5 days in a week for 12 weeks. An indolent renal failure developed in Cd exposed rats was accompanied with a significantly high urinary excretion of Cd(2+), Zn(2+) and proteins. The histopathology and electron microscopy of kidneys of Cd exposed rats documented changes of proximal tubular degeneration. Notably, Cd content in renal cortex of Cd exposed rats was 215 microg/g tissue that was higher than the critical concentration of Cd in kidneys which was associated with significantly higher Zn and metallothionein (MT) contents. Zinc uptake in BLMVs isolated from kidneys of Cd exposed rats was significantly reduced. Further, kinetic studies revealed that decrease in zinc uptake synchronized with decrease in maximal velocity (V(max)) and increase in affinity constant which is suggestive of decreased number of active zinc transporters. Furthermore, conformational modulation of Zn transporter in BLM was further supported by observed variation in transition temperature for zinc transport in BLMVs isolated from Cd-exposed kidney.

Animals↗
PubMed2006

Erythrocyte metabolism and antioxidant status of patients with Wilson disease with hemolytic anemia.

Wilson disease (WD) is an autosomal recessive disorder due to the defect in ATP7B gene characterized by excessive accumulation of copper in the liver with progressive hepatic damage and subsequent redistribution to various extrahepatic tissues including the brain, kidneys, and cornea. Strikingly, the total serum copper concentration is always low in WD, even though the non-ceruloplasmin copper level is still expected to be high. To assess the role of free radical reactions catalyzed by non-ceruloplasmin copper, we investigated erythrocyte metabolism and oxidative stress as a mechanism for hemolysis in eight WD patients during episodes of acute hemolysis and compared them with eight follow-up cases of WD on d-penicillamine therapy and eight healthy, age-matched children. Elevated levels of non-ceruloplasmin copper were found in all the WD patients during an episode of hemolytic anemia. There was marked inhibition in erythrocyte enzymes, namely, hexokinase, total adenosine triphosphatase (ATPase), and glucose-6-phosphate dehydrogenase (G-6-PD) from WD patients compared with patients on penicillamine and healthy children, indicating altered erythrocyte metabolism during a hemolytic crisis. Antioxidant status was also found to be compromised as is evident from decreased glutathione (GSH) levels, decreased antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), increased lipid peroxidation, and deranged plasma antioxidants. Uric acid showed maximum decrease followed by ascorbic acid. These findings suggest that the free radical production by elevated non-ceruloplasmin copper through transition metal catalyzed reactions leads to oxidative injury resulting in altered erythrocyte metabolism and severely compromised antioxidant status of WD patients during hemolytic anemia.

Adolescent↗
PubMed2004

Susceptibility pattern and molecular type of species-specific Candida in oropharyngeal lesions of Indian human immunodeficiency virus-positive patients.

A study of oropharyngeal candidiasis (OPC) in Indian human immunodeficiency virus (HIV)/AIDS patients was conducted over a period of 15 months. This study revealed that 75% of the HIV/AIDS patients had OPC. MIC testing revealed that 5% of the Candida isolates were fluconazole resistant. A correlation between CD4(+)-T-cell counts and development of OPC in HIV/AIDS patients was also observed. Molecular typing of C. albicans isolates showed that all were genetically unrelated.

AIDS-Related Opportunistic Infections↗
PubMed2003

324 cases of misplaced IUCD--a 5-year study.

Copper-T remains the mainstay of family planning measures in developing countries but is associated with serious complications like bleeding, perforation and migration to adjacent organs or omentum. Patients with misplaced intrauterine contraceptive device (IUCD) may present with pregnancy or lost strings or may remain asymptomatic for years. In our series of 324 cases with misplaced IUCD1; in 258 (79.93%) cases copper-T was found in the uterine cavity and in 47 cases (14.51%) it was removed from cervical canal. In only 18 cases (5.56%), it was translocated and of these 66.67% were inserted at primary health centres. Laparoscopic retrieval was successful in 61.11% cases. Endoscopy thus helps in the localization and retrieval of misplaced IUCDs. A regular follow up of IUCDs for visible threads would help in earlier detection of misplaced IUCDs. Proper training of paramedical staff is mandatory in developing countries to provide safe and better family planning services.

Adult↗
PubMed2003

Phase II study of an alternate carboplatin and gemcitabine dosing schedule in advanced non-small-cell lung cancer.

We conducted a phase II single-institution trial in a homogenous patient population with advanced non-small-cell lung cancer to determine whether changing the carboplatin schedule in the carboplatin/gemcitabine doublet would enhance tolerability and/or results. Thirty patients with stage IIIB (with malignant effusion) or stage IV disease received gemcitabine 1100 mg/m2, days 1 and 8 plus carboplatin at an area under the curve of 5 on day 8. Cycles were repeated every 28 days, up to 6 cycles. A response rate of 10% was demonstrated (none complete), but an additional 45% of patients had stable disease. The median time to progression was 5.8 months and the median survival was 8.3 months. A 1-year survival rate of 27% and a 2-year survival rate of 16% were seen. The main nonhematologic toxicity was non-neutropenic infection. Thrombocytopenia occurred in 8 patients (27%; 7 grade 3, 1 grade 4). Carboplatin/gemcitabine with a day 8 administration of carboplatin is well tolerated with a similar survival to established platinum-based doublets.

Aged↗