Tacrolimus (Pan Graf) in live related renal transplantation: an initial experience of 101 recipients in India

BACKGROUND: Success of modern transplantation is in large part due to the successful development of effective immunosuppressive agents. The safety and efficacy of tacrolimus in transplantation is well established. However, tacrolimus (Pan Graf, Panacea Biotec Ltd, India) has only been available in India for the last 2 years. This study was conducted to assess the safety and efficacy of tacrolimus in live related kidney transplantation. We report an initial experience of tacrolimus as de novo therapy in a live related renal transplantation program. MATERIALS AND METHODS: One hundred one consecutive recipients of a live renal allograft were commenced on triple immunosuppression consisting of tacrolimus, mycophenolate mofetil or azathioprine, and steroids. The dose of tacrolimus was adjusted to keep trough levels at 10-12 ng/mL in the first 3 months, 8-10 ng/mL in the next 3 months, and 5-8 ng/mL thereafter. All patients were followed up for a period ranging from 4 weeks to 24 months. The effect of this regimen on the incidence of graft rejection, graft survival, patient survival, and new-onset diabetes mellitus was evaluated. Any evidence of graft dysfunction was evaluated using a graft biopsy. RESULTS: There were 89 male and 12 female patients with mean age of 32.08 years. The incidence of acute rejection was 3.96%; 21.05% developed new-onset diabetes mellitus. Six patients were diabetic prior to transplantation and 9 patients were hepatitis C virus (HCV)-positive; 77.7% of HCV-positive patients and 15.1% of HCV-negative patients developed posttransplantation diabetes mellitus. The patient survival rate at the current follow-up was 92.07%. No graft was lost due to rejection. CONCLUSION: Tacrolimus is a safe and effective immunosuppressant in live related renal transplantation.     

Cercarial dermatitis in central India: an emerging health problem among tribal communities

Although cercarial dermatitis is an emerging disease world-wide, cases of such dermatitis may often go undiagnosed, especially in communities that are affected by various skin infections. Between August 2001 and July 2002, 1336 individuals from tribal villages in central India were examined for dermatitis. Skin scrapings were collected and examined for Sarcoptes scabiei and each subject's response to antiscabies treatment was recorded. Freshwater snails were collected from the local ponds used for bathing, and examined for cercariae. The recorded prevalence of dermatitis ranged between 2.1% and 12.5% during the study year, peaking at the end of winter (February-March) and during the rainy season (August-October). Snail positivity for cercariae peaked in the rainy season. The prevalence and the severity of dermatitis were both higher in children than in adults. As most recorded cases of dermatitis were associated with a rash that developed soon after bathing in the local pond, all the skin scrapings were negative for itch mites, and the response to antiscabies treatment was poor, most if not all of the dermatitis observed was probably cercarial. Cercarial dermatitis therefore appears to be a significant health problem among the tribal populations of central India.     

Detection of in-vivo chloroquine resistance in Plasmodium falciparum from Rameswaram Island, a pilgrim centre in southern India

Resistance to chloroquine (CQ) in Plasmodium falciparum is one of the main causes of the wide-spread resurgence of malaria in India and a challenge to the effective control of the disease. In the pilgrim centre of Rameswaram Island, malaria has persisted despite the various control measures undertaken over the years. When CQ resistance in Rameswaram was investigated in vivo, recrudescent parasitaemias were observed in 25 (58%) of the 43 study subjects who were given CQ and completed follow-up, all occurring between days 10 and 28 (late treatment failures). The results of the msp(1), msp(2) and glurp genotyping of paired samples of P. falciparum, collected on day 0 and the day of recrudescence from 23 of the apparent treatment failures, indicated that 21 (91%) of the 23 were probably true treatment failures. All of the paired samples harboured parasites with the K76T mutation in their pfcrt genes, and subsequent sequencing of nine day-0 samples revealed the SVMNT haplotype in all nine. This is the first report of in-vivo drug resistance in P. falciparum from Rameswaram Island. Such resistance, which is probably the result of the indiscriminate use of CQ and/or the import of malaria from mainland India, warrants a change in the drug regimen used locally for the first-line treatment of uncomplicated, P. falciparum malaria, to make treatment more effective and slow the development and spread of more foci of CQ resistance.     

Relating pulmonary oxygen uptake to muscle oxygen consumption at exercise onset: in vivo and in silico studies

Assessment of the rate of muscle oxygen consumption, UO_2m, in vivo during exercise involving a large muscle mass is critical for investigating mechanisms regulating energy metabolism at exercise onset. While UO_2m is technically difficult to obtain under these circumstances, pulmonary oxygen uptake, VO_2p, can be readily measured and used as a proxy to UO_2m. However, the quantitative relationship between VO_2p and UO_2m during the nonsteady phase of exercise in humans, needs to be established. A computational model of oxygen transport and utilization—based on dynamic mass balances in blood and tissue cells—was applied to quantify the dynamic relationship between model-simulated UO_2m and measured VO_2p during moderate (M), heavy (H), and very heavy (V) intensity exercise. In seven human subjects, VO_2p and muscle oxygen saturation, StO_2m, were measured with indirect calorimetry and near infrared spectroscopy (NIRS), respectively. The dynamic responses of VO_2p and StO_2m at each intensity were in agreement with previously published data. The response time of muscle oxygen consumption, estimated by direct comparison between model results and measurements of StO_2m was significantly faster (P < 0.001) than that of pulmonary oxygen uptake, (M: 13 ± 4 vs. 65 ± 7 s; H: 13 ± 4 vs. 100 ± 24 s; V: 15 ± 5 vs. 82 ± 31 s). Thus, by taking into account the dynamics of oxygen stores in blood and tissue and determining muscle oxygen consumption from muscle oxygenation measurements, this study demonstrates a significant temporal dissociation between UO_2m and VO_2p at exercise onset.     

Sulforaphane reduces infarct volume following focal cerebral ischemia in rodents

Stroke is the third leading cause of death and disability in the United States. As several biochemical mechanisms have been proposed to contribute to stroke pathophysiology, treatments acting on multiple targets may be desirable. Sulforaphane (SUL), a naturally occurring isothiocyanate present in cruciferous vegetables, has been shown to induce the expression of multiple NF-E2-related factor-2 (Nrf2) responsive genes. In the present study, we demonstrate that systemically administered SUL can enter the brain as determined by increased mRNA and protein levels of the Nrf2-responsive gene heme oxygenase 1 (HO-1). Delayed administration (15 min) of a single dose of SUL significantly decreased cerebral infarct volume following focal ischemia, suggesting a potential therapeutic value for this compound.     

Wash resistance and bioefficacy of Olyset net--a long-lasting insecticide-treated mosquito net against malaria vectors and nontarget household pests

During recent years, long-lasting insecticide-treated nets (LLINs) have been developed to overcome the problems of low retreatment rates, washing, and erratic dose of the insecticide resulting in the dilution of efficacy of the conventional insecticide-treated mosquito nets. These nets are treated at factory level with insecticide either incorporated into or coated around fibers. Olyset net, a polyethylene net with 2% permethrin incorporated within fibers, is one type of LLIN. Therefore, these nets were evaluated for their wash resistance and bioefficacy against malaria vectors Anopheles culicifacies Giles and Anopheles fluviatilis James (Diptera: Culicidae) and other nontarget species. Cone bioassay tests produced 100% mortality in these two vector species with 3-min exposure. Results of the bioassays on washed nets showed 100% mortality in An. fluviatilis even after 20 washings, whereas in An. culicifacies 100% mortality up to 11 washings and 80% mortality up to 20 washings were observed. Cone bioassay tests also were performed on nontarget mosquito species Culex quinquefasciatus Say; house fly, Musca domestica L.; American cockroach, Periplaneta americana (L.); head louse, Pediculus humanus capitis De Geer; and bed bug, Cimex lectularius L. with 30-min exposure. Except for bed bugs, 100% mortality was observed in these nontarget species after 24-h recovery period. In bed bugs, only 25% mortality was observed. The density of An. culicifacies and An. fluviatilis was significantly reduced in houses with Olyset nets compared with those with untreated nets or no nets. Thus, it may be concluded that Olyset nets are highly effective against malaria vectors and moderately against other nontarget household insects.