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Biomedical subjects

R Rajendran

Publications and source records attributed to R Rajendran.

At least 37 records · Page 2Linked to original sources

Longitudinal studies in South Indian villages on Japanese encephalitis virus infection in mosquitoes and seroconversion in goats.

Japanese encephalitis (JE) is endemic in Cuddalore district, Tamil Nadu, where Culex tritaeniorhynchus Giles was the major vector. We screened 45 100 adult female Cx. tritaeniorhynchus (902 pools) by enzyme-linked immunosorbent assay and isolated and confirmed JE virus (JEV) by using an insect bioassay system. We had 69 isolates of which 62 (90%) were identified as JEV. The average vector abundance per man hour for Cx. tritaeniorhynchus was 324.5 per month for the period June 1998-May 2000. The average minimum infection rate (MIR) per month in Cx. tritaeniorhynchus was 1.4 (range 0.0-5.6). Every year, a new batch of goats, 20 in the first year and 31 in the second year, born during the non-JE transmission period (January-June), aged <6 months and negative for haemagglutination inhibition (HI) antibodies were procured and placed in the villages as sentinels. Fortnightly, blood specimens were collected from these goats and tested for JE antibodies by HI test. Seroconversions (SCs) were recorded in 14 goats (70%) in the first year and 23 goats (74%) in the second year. JE HI antibody titres in goats were low (1:10-1:80) and these levels declined to undetectable levels in about 4 weeks following SCs. The time sequence of events indicated that four of five peaks of MIR in mosquitoes were followed 1-3 months later by peaks in the proportion of seroconverted goats. We suggest the screening of goats and cattle as a more feasible tool to stratify areas according to JE infection risk to the human population through the regular health system rather than screening mosquitoes using monoclonal antibodies, which is possible only in specialized laboratories.

Animals↗

Long-term population migration: an important aspect to be considered during mass drug administration for elimination of lymphatic filariasis.

Annual 2-drug, single-dose mass drug administration (MDA) to 80-90% of the eligible population for 4-6 years are pre-requisites for the successful elimination of lymphatic filariasis (LF) from endemic communities by interruption of transmission and eventual elimination of new infections. In an experimental intervention project on the control of LF in Villupuram district of Tamil Nadu state, India, migration patterns of the villagers were investigated to determine the appropriate timing to implement MDA in order to attain high coverage in a village-level study. Between January and December 1997, 16 observations took place at 3-week intervals, following MDA with two drugs viz., diethylcarbamazine and ivermectin, in July-August 1996. The migrants from the village constituted 17-27% at different points of time and both short-term and long-term migrating patterns were observed. More villagers were available during the agricultural season (September-January), peaking around mid-January [83%; significantly higher (P < 0.05)] than during most of the remaining months, including a substantial portion of the migrant population. There is an urgent need to reschedule the yearly MDA in this area to take place in January and to plan mopping up operations by involving local self-help groups to include migrants (both short-term and long-term) in the LF elimination efforts.

Adolescent↗

Transmission intensity index to monitor filariasis infection pressure in vectors for the evaluation of filariasis elimination programmes.

We conducted longitudinal studies on filariasis control in Villupuram district of Tamil Nadu, south India, between 1995 and 2000. Overall, 23 entomological (yearly) data sets were available from seven villages, on indoor resting collections [per man hour (PMH) density and transmission intensity index (TII)] and landing collections on human volunteers [PMH and annual transmission potential (ATP)]. All four indices decreased or increased hand-in-hand with interventions or withdrawal of inputs and remained at high levels without interventions under varied circumstances of experimental design. The correlation coefficients between parameters [PMH: resting vs. landing (r = 0.77); and TII vs. ATP (r = 0.81)] were highly significant (P < 0.001). The former indices from resting collections stand a chance of replacing the latter from landing collections in the evaluation of global filariasis elimination efforts. The TII would appear to serve the purpose of a parameter that can measure infection pressure per unit time in the immediate household surroundings of human beings and can reflect the success or otherwise of control/elimination efforts along with human infection parameters. Moreover, it will not pose any additional risk of new infection(s) and avoids infringement of human rights concerns by the experimental procedures of investigators, unlike ATP that poses such a risk to volunteers.

Animals↗

Resurgence in filarial transmission after withdrawal of mass drug administration and the relationship between antigenaemia and microfilaraemia--a longitudinal study.

Seven village units endemic for filariasis were assigned randomly into three arms with different intervention strategies in the years 1995 and 1996. Villages in Group A received two annual mass drug administrations (MDAs) of diethylcarbamazine (DEC) plus ivermectin (IVR). Group B received the same MDAs in combination with vector control; in Group C only placebo was administered. Post-treatment evaluation in 1997 revealed marked reductions in microfilaraemia prevalences (MFP) and geometric mean intensities (GMI). Subsequently, vector control in Group B was continued by the community. Groups A and B received no MDAs between 1997 and 1999 and were re-evaluated in 1999. During this evaluation, antigenaemia prevalence (AGP) was estimated along with MFP, using immunochromatographic test (ICT) kits. The gains of the MDAs were sustained in Group B, while resurgences occurred in Group A, where annual transmission potential (ATP) rose from 21 to 631.6 and MFP doubled. Group C continued to have high ATPs (1057-1617), while Group B had very low ATPs (0-63). After Mulla's corrections, the reductions in MFP were 62.7 and 83.5% and for GMI 72.1 and 91.4% in Group A and B, respectively, compared with Group C. Vector control preserved the gains of MDAs and accounted for 55.8% and 67.1% reductions in MFP and GMI in Group B compared with Group A. The reductions in AGP were 29.4% in Group A and 39.2% in Group B against Group C. The differences between MFP and AGP were nearly uniform across all villages and there was a significant correlation (r=0.98) between the two variables. A similar significant relationship was observed between MFP and AGP values across age groups (r=0.95). Prediction of AGP values from MFP values was proposed with regression equations. We conclude that vector control would be useful as an adjuvant to chemotherapy to prevent resurgences.

Adolescent↗

Efficacy of co-administration of albendazole and diethylcarbamazine against geohelminthiases: a study from South India.

The efficacy of single-dose combination drug therapy with diethylcarbamazine (DEC) plus albendazole (ALB), and single-drug therapy with DEC alone against geohelminths was compared as part of a mass drug administration (MDA) for elimination of filariasis. This study was conducted in two blocks of Villupuram District of Tamil Nadu State, India, covering a population of 321 000 including about 100 000 children 1-15 years of age. Prevalence and intensity of geohelminth infection were determined by the Kato-Katz technique immediately before and 3 weeks after the MDA. A pre-treatment cross-sectional survey was undertaken in 18 statistically selected villages out of 204 villages, including 646 school children. About 60% were infected with one or more geohelminths. The overall prevalence rates were 53.9%, 12.4% and 5.7% for Ascaris lumbricoides, hookworms and Trichuris trichiura, respectively. Combination therapy (DEC + ALB) produced a cure rate of 74.3% and an egg reduction rate of 97.3% for geohelminths, which were higher than the corresponding rates (30.4% and 79.0%) observed in the single drug therapy arm with DEC alone. The odds of cure with combination therapy were significantly higher for roundworm (5.3 times) and hookworms (3.5 times), then odds of cure with DEC alone. Both therapies were equally effective against trichuriasis, recording cure rates >77% and egg reduction rates >83%. In combination therapy, 53.5% of the children noticed expulsion of worms after MDA, while in single drug therapy only 20.9% did. Our study indicated that MDA of combination therapy was operationally feasible at the community level, and it may secure higher community compliance because of its perceived benefits and enhanced efficacy against geohelminths than single-drug therapy.

Adolescent↗

The influence of the mass administration of diethylcarbamazine, alone or with albendazole, on the prevalence of filarial antigenaemia.

The current Indian campaign for the elimination of lymphatic filariasis is largely based on mass drug administration (MDA). As part of this campaign, villagers in the Tirukoilur and Mugaiyur 'blocks' (i.e. revenue units) of Villupuram district, in Tamil Nadu, India, were treated with diethylcarbamazine (DEC), either alone (Mugaiyur) or with albendazole (Tirukoilur), in March 2001. The efficacy of treatment, in each of the two treatment arms, was evaluated by determining the percentages of the subjects who were carrying antigen from adult Wuchereria bancrofti before, 6 months and 12 months after the MDA. In a cross-sectional survey at each time-point, commercial, immunochromatographic tests were used to check 1000-1200, randomly selected, young residents (aged 2-25 years) of 18 index villages for the antigen; at least 300 villagers aged 2-9 years and at least 170 aged 10-25 years from each treatment arm were screened in each survey. Before the MDA, 12.7% of the subjects aged 2-9 years and 23.6% of those aged 10-25 years were found to be positive for the filarial antigen. Although only about 50% of villagers aged 2-9 years were successfully treated, MDA (with DEC alone or DEC plus albendazole) led to a significant (28.7%) reduction in the prevalence of antigenaemia in this age-group 6 months later (P<0.05). Although, the prevalences of antigenaemia among those aged 2-9 years were higher 12 months post-treatment than 6 months post-treatment, they were still lower (by 16%-23%) than those observed pre-treatment. The addition of albendazole to the DEC treatment appeared to offer no additional benefit in terms of the prevalence of antigenaemia in children aged <10 years; in fact, the use of DEC alone produced a slightly greater reduction in the prevalence of antigenaemia than the use of both DEC and albendazole. In the block given MDA based on both DEC and albendazole, the prevalences of antigenaemia among the villagers aged 10-25 years were 19.4% and 16.6% lower 6 and 12 months post-treatment, respectively, than observed pre-treatment. Curiously, in the block given DEC alone, the prevalences in this age-group were higher at both post-treatment follow-ups (by 17.4% at 6 months and 35.1% at 12 months) than observed pre-treatment. In concurrent experimental studies, high drug compliance (90%) among young children (aged 2-5 years) led to a pronounced (62.6%) reduction in the prevalence of antigenaemia after one MDA. In follow-up studies of those found antigen-positive, 40% of those aged 2-9 years but only 23% of those aged 10-25 years cleared their antigenaemias after three (annual) MDA. To maximize the benefits of MDA, greater efforts should be made to increase treatment coverage among young children.

Adolescent↗

Cost-effectiveness of the use of vector control and mass drug administration, separately or in combination, against lymphatic filariasis.

The costs and effects of two intervention strategies for the control of bancroftian filariasis-annual mass drug administrations (MDA) with a combination of diethylcarbamazine and ivermectin, with or without integrated vector control (VC)-were estimated in rural villages in South India. The aim was to compare the cost-effectiveness of MDA alone with that of MDA plus VC. Control of the local vector, Culex quinquefasciatus, was based on the application of polystyrene beads to cesspits, the treatment of drains with larvicidal Bacillus sphaericus and the stocking of wells with larvivorous fish. An itemized cost menu was used to cost MDA and MDA + VC, retrospectively. The annual transmission potential was used to assess the direct outcome of the disease-control methods, whereas the prevalence and intensity of microfilaraemia were used as indicators of the impact of each method. The per-capita costs were 1.49 U.S. dollars for two rounds of MDA, 1.70 U.S. dollars for 2 years of VC and, therefore, 3.19 U.S. dollars for 2 years of MDA + VC. Integration of VC with MDA did not appear to be cost-effective: it cost an estimated 1.80 U.S. dollars to stop an infective mosquito biting a villager using MDA alone but 3.32 U.S. dollars to achieve the same result using MDA + VC. Similarly, the cost to reduce the prevalence of microfilaraemia in a three-village group by 1% was only 96.62 U.S. dollars for MDA alone but 201.16 U.S. dollars when vector control was integrated. The implications of these results for the control and elimination of filariasis in Indian village communities, and the options for sharing and minimizing costs, are discussed.

Animals↗

Age of treatment of undescended testis--a study.

A retrospective study was conducted for a period of 4 years during 1992-1995 at Medical College Hospital, Alappuzha, Kerala to find out whether boys with undescended testis got treated at ideal age. Discharge summaries of boys who were treated for undescended testis in this hospital were studied. There were 139 patients with 162 undescended testes. Mean age of operation was 5 years (range--11 months to 12 years). There were 19.4% patients who were less than 2 years of age. It was found out that 11.1% of total testes were atrophic/vanished. Orchiopexy was done in almost all remaining cases. Majority of boys with undescended testis attended for treatment at a higher age than that recommended. The ideal age of treatment at present and its scientific basis are highlighted.

Age Factors↗

Annual single-dose diethylcarbamazine plus ivermectin for control of bancroftian filariasis: comparative efficacy with and without vector control.

Two intervention strategies for the control of bancroftian filariasis were compared in rural villages of southern India: annual mass treatment with single-dose diethylcarbamazine plus ivermectin, either on its own or combined with vector control. Vector control, based on the use of polystyrene beads and larvivorous fishes in the major breeding sites of Culex quinquefasciatus, brought about a drastic and sustained reduction in vector density and man-biting rates. After the first round of treatment, chemotherapy alone brought about a 60% drop in the annual transmission potential (ATP) whereas the integrated strategy reduced ATP by 96% (P < 0.05). After two annual rounds of treatment, the reduction in ATP was similar for both strategies (91%-96%), with the prevalences of microfilaraemia reduced by 88%-92%. However, when drug pressure was removed in the third and final year of the study, transmission was resumed in the absence of vector control whereas no infective female mosquitoes were detected in the villages with vector control. Vector control, though obviously not cost-effective in the short term, could play an important role in an integrated programme, by preventing re-establishment of transmission after chemotherapy is completed.

Adolescent↗

Binding activity of natto (a fermented food) and Bacillus natto isolates to mutagenic-carcinogenic heterocyclic amines.

The fermented food, whole meal Natto, viscous polymeric material from Natto, Natto bean, cooked soya bean, and 28 bacterial isolates from Natto were studied for their binding capacity to foodborne mutagenic-carcinogenic heterocyclic amines. The mutagenic heterocyclic amines used were Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole); Trp-P-2 (3-amino-1-methyl-5H-pyrido(4,3-b)indole); Glu-P-1 (2-amino-6-methyldipyrido(1,2-a:3'2'-d)imidazole); PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine); IQ (2-amino-3-methylimidazo(4,5-f)quinoline); MeIQ (2-amino-3,4-dimethylimidazo(4,5-f)quinoxaline); MeIQx (2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline); and MeAalphaC (2-amino-3-methyl-9H-pyrido(2,3)indole). The lyophilized Natto and other fractions of Natto exhibited high binding activity towards Trp-P-1, Trp-P-2, PhIP, and MeAalphaC, while Glu-P-1, IQ, and MeIQ were not effectively bound. The binding capacity of bacterial isolates (Bacillus natto) were isolate-mutagen dependent. Heat treated lyophilized cells, cell wall, and cytoplasmic contents of the bacterial isolate with the highest binding capacity were analyzed for their ability to bind different heterocyclic amines. The results indicate the importance of the cell wall in binding to heterocyclic amines, whereas the cytoplasmic contents were less effective. Heat-treated cells were not much different from that of viable cells in their binding. The impact of different factors, such as pH, incubation time, metal ions, different concentrations of sodium chloride and alcohol, various enzymes, and acetylation of mutagens on binding of Trp-P-1 and IQ, were discussed. The significance of the present results is also discussed from the viewpoint that Natto, a fermented food, is able to scavenge dietary mutagenic heterocyclic amines through binding.

Amines↗

Novel ligands that function as selective estrogens or antiestrogens for estrogen receptor-alpha or estrogen receptor-beta.

We report on the identification of novel, nonsteroidal ligands that show pronounced subtype-selective differences in ligand binding and transcriptional potency or efficacy for the two estrogen receptor (ER) subtypes, ER alpha and ER beta. An aryl-substituted pyrazole is an ER alpha potency-selective agonist, showing higher binding affinity for ER alpha and 120-fold higher potency in stimulation of ER alpha vs. ER beta in transactivation assays in cells. A tetrahydrochrysene (THC) has a 4-fold preferential binding affinity for ER beta; it is an agonist on ER alpha, but a complete antagonist on ER beta. Intriguingly, the antagonist activity of THC is associated with the R,R-enantiomer (R,R-THC). The S,S-enantiomer (S,S-THC) is an agonist on both ER alpha and ER beta but has a 20-fold lower affinity for ER beta than R,R-THC. This difference in binding affinity accounts for the full ER beta antagonist activity of the THC racemate (a 1:1 mixture of R,R-THC and S,S-THC). These compounds should be useful in probing the conformational changes in these two ERs that are evoked by agonists and antagonists, and in evaluating the distinct roles that ER beta and ER alpha may play in the diverse target tissues in which estrogens act.

Animals↗

Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers.

The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02), and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.

Adult↗

Binding of heterocyclic amines by lactic acid bacteria from miso, a fermented Japanese food.

Miso, a widely used Japanese fermented food was analysed for its lactic acid bacterial count on bromocresol purple agar. The binding of eight different foodborne carcinogenic heterocyclic amines to 25 bacterial isolates from miso were investigated. The heterocyclic amines used were 3-amino-1,4-dimethyl[5H]pyrido(4,3-b)indole (Trp-P-1), 3-amino-1-methyl[5H]pyrido(4,3-b)indole (Trp-P-2), 2-amino-6-methyldipyrido(1,2-a:3'2'-d)imidazole (Glu-P-1), 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), 2-amino-dimethylimidazo(4,5f)quinoline (IQ), 2-amino-3,4-dimethylimidazo(4,5-f) quinoline (MeIQ), 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx), and 2-amino-3-methyl-9H-pyrido(2,3)indole (MeA alpha C). The lyophilized cells of all of the isolates exhibited high binding activity towards Trp-P-1, Trp-P-2, MeA alpha C, and PhIP, while Glu-P-1 and IQ were not effectively bound. Of the isolates tested, the strongest and weakest binders were identified as Pediococcus acidilactici 1 and 2, respectively. Lyophilized cell wall fractions, heat-treated cells, and the cytoplasmic contents of P. acidilactici 1 and 2 were analysed for their ability to bind to different mutagens. Pure cell wall and peptidoglycan showed greater binding activity than the bacterial cells. Cytoplasmic content also showed some binding, but it was much less effective. The impact of enzymes (amylase, protease, cellulase, chitinase, muraminase, and peptidase) and acetylation of Trp-P-1 and IQ on the binding action of bacteria and cell wall material were also analysed to understand the possible processes involved in the binding of lactic acid bacteria to carcinogenic heterocyclic amines.

Amines↗

A comparison between emergency diagnostic and treatment unit and inpatient care in the management of acute asthma.

BACKGROUND: Emergency diagnostic and treatment units (EDTUs) may provide an alternative to hospitalization for patients with reversible diseases, such as asthma, who fail to adequately respond to emergency department therapy. OBJECTIVE: To evaluate the medical and cost-effectiveness, patient satisfaction, and quality of life of patients receiving EDTU care for acute asthma compared with inpatient care. METHODS: A prospective, randomized clinical trial performed at 2 urban public hospitals enrolled patients with acute asthma (age range, 18-55 years) not meeting discharge criteria after 3 hours of emergency department therapy. Patients were treated with inhaled adrenergic agonists and steroids in an EDTU for up to 9 hours after randomization or with routine therapy in a hospital ward. Patients were followed up for 8 weeks. MAIN OUTCOME MEASURES: Discharge rate from the EDTU, length of stay, relapse rates, days missed from work or school, days incapacitated during waking hours, symptom-free days and nights, nocturnal awakenings, direct medical costs, patients satisfaction, and patient quality of life. RESULTS: The study consisted of 222 patients with asthma. Sixty-five patients (59%) treated in an EDTU were discharged home; the remainder were admitted to the hospital. There were no differences during the follow-up period in relapse rates (P = .74) or in any other morbidities between the EDTU and inpatient groups. There were significant differences in the length of stay, patient satisfaction, and quality of life favoring EDTU care. The mean (+/-SD) cost per patient in the EDTU group was $1202.79 +/- $1343.96, compared with $2247.32 +/- $1110.18 for the control group (P < .001). CONCLUSIONS: Treatment of selected patients with asthma in an EDTU results in the safe discharge of most such patients. This study suggests that quality gains and cost-effective measures can be achieved by the use of such units.

Acute Disease↗