Mukesh Sharma

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that plays a central role in inflammation. Glomerular levels of TNF-alpha are elevated in human and experimental glomerulonephritis. Glomerular cells produce and respond to TNF-alpha. One of the mechanisms by which these cells respond to TNF-alpha is through generation of reactive oxygen species. In this study, the effect of TNF-alpha on albumin permeability (P(albumin)) of isolated rat glomeruli and the possible mechanism of this effect were examined. Isolated rat glomeruli were incubated with TNF-alpha (0.4 ng/ml), TNF-alpha with anti-TNF-alpha antibodies, and TNF-alpha with the reactive oxygen species scavengers superoxide dismutase, catalase, DMSO, or dimethylthiourea for 12 min at 37 degrees C, and P(albumin) was calculated. TNF-alpha increased P(albumin) of isolated glomeruli compared with control (0.70 +/- 0.02, n = 25 versus 0.00 +/- 0.05, n = 26), and this effect was abrogated by anti-TNF-alpha antibodies (-0.18 +/- 0.05, n = 23). Superoxide dismutase abolished the increase in P(albumin) (-0.04 +/- 0.11, n = 23), whereas catalase (0.73 +/- 0.08, n = 30), DMSO (0.64 +/- 0.03, n = 10), or dimethylthiourea (0.51 +/- 0.08, n = 10) did not alter the effect of TNF-alpha. These results indicate that TNF-alpha increased P(albumin+)++ of isolated glomeruli and that the mediator of the increased P(albumin) is superoxide. It is concluded that TNF-alpha derived from glomerular or extraglomerular sources can increase glomerular P(albumin) through generation of superoxide and may lead to proteinuria.

CONTEXT: Breast cancer incidence is increasing rapidly in India. The lifestyle, built, genetic makeup, reproductive and breastfeeding patterns are quite different in Indian females when compared to the Western population. Generalizing the Western data to the population residing in the Himalayan region would breed inaccuracies. AIM: The aim of our study was to identify risk factors in our own population in a Western Himalayan state of Himachal Pradesh, India. SUBJECTS AND METHODS: A case-control study with 377 cases of invasive breast cancer and 346 hospital-based controls was conducted for 1 year. The data were collected by interviewing the individuals during their visit to hospital using a questionnaire. The data were analyzed using standard statistical techniques using SPSS version 17 software. RESULTS: Factors found to have strong association with invasive breast cancer on multivariate analysis are late age at first childbirth >30 years, which is the strongest risk factor associated, late age of menopause > 50 years, high socioeconomic class, and age of female above 50 years. CONCLUSION: In our females, age >50 years, late age of menopause (>50 years), late age at first childbirth (>30 years), and high socioeconomic status were found to be major risk factors associated with breast cancer. Several factors implicated in the Western data were not found to be significant in our study. We need to identify such aspects in reproductive and breastfeeding patterns of women and spread awareness regarding the same.

Nanogels are innovative drug delivery system that can play an integral part in pointing out many issues related to old and modern courses of treatment such as nonspecific effects and poor stability. Biomedical and pharmaceutical applications of Nanogels have been explored for tissue regeneration, wound healing, surgical device, implantation, and peroral, rectal, vaginal, ocular, and transdermal drug delivery. Nanogels are proficiently internalized by the target cells, avoid accumulating in nontarget tissues thereby lower the therapeutic dosage and minimize harmful side effects. Nanogels may be defined as highly cross linked nano-sized hydrogels ranges from 20-200 nm. They can be administered through various routes, including oral, pulmonary, nasal, parenteral, intra-ocular etc. They have a high degree of drug loading capacity and it shows better permeation capabilities due to smaller size. Nanogels are the novel drug delivery systems for both hydrophilic and hydrophobic drugs.

Both sheep and goat pox are contagious viral diseases and affect small ruminants and are caused by sheep pox virus and goat pox virus respectively that belong to genus Capripoxvirus of Poxviridae family. Huge economic losses emanating from the disease outbreaks are the results of the wool and hide damage, subsequent production losses and also the morbidities and mortalities associated with the disease. This communication highlights clinico-epidemiological observations from the two sheep pox and one goat pox outbreaks. Grossly, multisystemic nodular lesions, mucopurulent nasal discharges and respiratory symptoms were observed in the affected animals. The morbidity, mortality and case fatality rates were 5.18%, 2.45% and 32.37%, respectively. Histopathological, haematological, molecular and serological techniques and also isolation of virus in embryonated chicken eggs were used for the diagnosis of the diseases. The spatial distribution of the disease signifies the role of common pasturelands used for grazing the animals while temporally all three outbreaks occurred in winters and were probably associated with cold stress and fodder scarcity. This is the first recorded report of Capripoxvirus infection in recent times and it highlights the disease as one of the emerging diseases in the northern state of Himachal Pradesh in India.

We previously observed encouraging results and acceptable toxicity in phase II trials testing preoperative split-course thoracic radiation and simultaneous cisplatin, etoposide, and 5-fluorouracil in stage III non-small cell lung cancer patients. We decided to delete 5-fluorouracil and to incorporate paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) into our combined-modality treatment. The first group of patients received carboplatin dosed at an area under the concentration-time curve of 4 on day 2, etoposide 50 mg orally days 1 to 5 and 8 to 12, cisplatin 50 mg/m2 on day 21, and paclitaxel 35 mg/m2 escalated to 45 mg/m2 on days 1 and 8. Group 2 patients received carboplatin dosed at an area under the concentration-time curve of 4 on day 1, etoposide 45 mg/m2 intravenously daily on days 2 to 5, and paclitaxel 80 mg/m2 (escalating to 120 mg/m2) on day 1. Patients in group 3 received carboplatin dosed at an area under the concentration-time curve of 4 on day 1 and paclitaxel 120 mg/m2 (escalating to 140 mg/m2) on day 1. Each patient received radiation 2 Gy daily on days 1 to 5 and 8 to 12, and a total of two cycles was given at 28-day intervals. Twenty-one patients received preoperative chemoradiotherapy: group 1, five patients; group 2, 11 patients; and group 3, five patients. Thoracotomy was not done in five patients due to cerebrovascular accident in one and progressive tumor in four. The remaining 16 patients had the following procedures: pneumonectomy, eight; lobectomy, six; chest wall resection, one; and no resection, one. Postoperative complications included bronchopleural fistula in one patient each in groups 1 and 3, hypoxia in one patient in group 1, pulmonary hypertension in one patient in group 2, pneumonia in one patient in group 2, and adult respiratory distress syndrome in one patient in group 3, which proved lethal. Thus, six of 16 patients had serious postoperative complications. The relatively high incidence of postoperative bronchopulmonary complications suggests that the use of preoperative paclitaxel-containing chemotherapy and simultaneous thoracic radiation may not be feasible.