Drynaria quercifolia suppresses paracetamol­induced hepatotoxicity in mice by inducing Nrf-2.

Paracetamol is a popular and safe drug preferred by victims of pain or pyrexia; however, its overdose or abuse is a growing concern worldwide. Here the hepatoprotective effect of an ethnomedicinal plant Drynaria quercifolia against paracetamol­induced toxicity in murine model is demonstrated. This fern, native to tropical countries including the Northeast India, is used by local tribes to treat inflammatory conditions. Paracetamol 500 mg/kg body weight was orally administered on alternate days for a period of 21days to mimic a chronic overdose. Drynaria quercifolia acetone extract (DQA) treatment interspaced with paracetamol significantly decreased serum biomarkers of hepatotoxicity (ALT, AST and ALP) renal toxicity (urea, creatinine), lipid peroxidation level, histological damage in liver and kidney. The protein and mRNA expressions of the transcription factor, Nrf2, and its target antioxidant genes (SOD1, CAT and GST) as well as activities of these antioxidant enzymes were downregulated by paracetamol administration but significantly recovered following the DQA treatment (Tab. 3, Fig. 5, Ref. 31). Keywords: acetaminophen/paracetamol, Drynaria quercifolia, renal toxicity, hepatotoxicity, Nrf-2.

Evaluation of genotoxic responses of Chaetoceros tenuissimus and Skeletonema costatum to water accommodated fraction of petroleum hydrocarbons as biomarker of exposure.

Genotoxic responses towards chronic exposure of Chaetoceros tenuissimus and Skeletonema costatum to water accommodated fraction of petroleum hydrocarbons (WAF-P) were evaluated as biomarkers of petroleum hydrocarbons pollution. The DNA damage caused by water accommodated fraction of petroleum hydrocarbons was assessed in terms of the DNA integrity measured by alkaline unwinding assay. The comparative study of the growth pattern of C. tenuissimus with respect to DNA integrity and the DNA strand breaks in different concentrations of WAF-P showed sufficient tolerance. However, its toxicity increased proportionately with exposure to elevated levels of WAF-P. Although DNA damage in S. costatum was similar to C. tenuissimus, its tolerance level to WAF-P was at least 5 times lower than that of C. tenuissimus indicating its high sensitivity to petroleum hydrocarbons. Active growth was exhibited by C. tenuissimus between 10 and 20% WAF-P (ranging from 0.59 to 1.18mg/L petroleum hydrocarbons) which can be related to the polluted regions only, suggesting the tolerant nature of this organism. Considering the degree of sensitivity to petroleum products and good growth under laboratory conditions, these two diatoms could be recommended as model species for evaluating ecogenotoxic effects of wide range of petroleum hydrocarbon pollutants using alkaline unwinding assays.

Outcomes of different subgroups of smear-positive retreatment patients under RNTCP in rural West Bengal, India.

INTRODUCTION: This record-based study was undertaken at Bagula Tuberculosis Unit, Nadia, West Bengal, India to compare outcomes among sputum-positive TB retreatment patient groups (relapse, failure and treatment after default) at completion of therapy, under the Revised National Tuberculosis Control Program (RNTCP). METHODS: A total of 234 registered cases of TB retreatment (category II) between January 1999 and June 2005 were analysed and compared by Z-test for proportion. RESULTS: There was a uniform distribution in terms of age, grades of sputum positivity and sputum conversion at 2 and 3 months among the three groups. In spite of this, a favourable outcome was most likely for relapse cases, and cases with a low grade of sputum positivity in all three subgroups. Unfavourable outcome was most likely among the treatment failure subgroup and those with high grades of sputum positivity. CONCLUSION: The results are likely to be due to an increased incidence of multi-drug resistant TB in these patients. In rural areas of the developing world, as in India, there is a heavy burden of TB and resources are limited. Culture and drug sensitivity patterns prior to commencing therapy should be performed for failure and default patients who present with an initially high load of bacilli in their sputum.

Ecotoxicological effect of grounded MV River Princess on the intertidal benthic organisms off Goa.

The ecotoxicological effects of oil spill from the grounded vessel MV River Princess on the intertidal benthic organisms of Sinquerim-Candolim beach at Goa were investigated. An intertidal expanse of 1 km on either side of the grounded vessel was selected to evaluate the concentration of total petroleum hydrocarbon (TPH) in the sediment and its effects on the composition, abundance and diversity of micro-, meio- and macrobenthos. TPH in the intertidal sediment ranged from 7.8 to 89 microg g(-1) (mean 35.44+/-26.35 SD). Microbenthos comprised of microalgae, protozoans and juvenile forms of meiobenthos. Apart from juvenile nematodes, which were abundant, Coscinodiscus spp., Navicula spp., and Nitzschia spp. representing microalgae were also observed in microbenthic samples. Meiobenthos was represented by 13 taxa and their total density ranged between 92 and 1057 nos. 10 cm(-2). Maximum meiobenthic abundance of 1057 nos. 10 cm(-2) was observed at Sinquerim. Nematodes were the dominant meiobenthic taxa followed by turbellarians and harpacticoid copepods. The macrobenthos was numerically dominated by polychaetes, followed by crustaceans whereas bivalve molluscs were less represented. There was substantial increase in the petroleum concentration in the beach sediment compared to the previously reported values and highest TPH (89 microg g(-1) sediment) values were in the vicinity of the grounded vessel. The polychaete/amphipod ratio and cumulative and partial dominance abundance-biomass curves showed significant negative impact of TPH on macrofauna. The benthic community structure also showed measurable changes, as there was significant decrease (60%) in the number of species. Given that the microalgal counts were low in sediment, it is assumed that the intertidal meiofauna was possibly using oil-degrading bacteria as alternate food source. In conclusion, the results reported here suggest that the grounded ore carrier is not only detrimental to the beach community, that may take longer time for recovery, but also affects the beach morphology which may have long-term impact on local fishery.

Black tea is a powerful chemopreventor of reactive oxygen and nitrogen species: comparison with its individual catechin constituents and green tea.

Production of black tea [BT] results in biotransformation of catechins of green tea [GT] to theaflavins and thearubigins. BT was found to be more efficient than GT and its individual catechin constituents in proportionate amounts in abrogating production of NO and O2(-) in activated murine peritoneal macrophages. In a reconstitution system of BT that is free of all catechins, stepwise addition of catechins showed that though all the constituents contributed to the overall effect of BT, theaflavin was the most powerful in abrogating NO production. RT-PCR analysis also showed theaflavin to be the most important constituent in down-regulating synthesis of iNOS. Clearly, BT containing theaflavin is an excellent chemopreventor against reactive oxygen and nitrogen species.

Study of impact of nutrition & health day strategy on the coverage rates of supplementary nutrition and health interventions among the ICDS beneficiaries in a rural block of Madhya Pradesh.

To study the trends of beneficiary coverage (pregnant and lactating women and children less than two years of age) for utilization of supplementary nutrition and health services in a rural block before and after the launch of a strategy to converge Health & Integrated Child Development Services (ICDS) on a single day christened "Nutrition and Health Day" (NHD). It is a before and after intervention design in rural ICDS block Amarwada in district Chhindwada. As a part of intervention, NHD were organised on which convergent services of Health & ICDS were made available to the beneficiaries. On the weekly NHDs, uncooked supplementary nutrition for the week was distributed to pregnant and lactating mothers and children under two. The Health worker visited the Anganwadi Centre (AWC) and immunized children and pregnant women, distributed IFA, Vitamin A and provided health and nutrition education. The study assessed the impact of these interventions on the coverage rates of the services. Study was conducted between May 97 and March 98. The routine monitoring reports of the ICDS and Health System of the state government were used as study tools. The study sample comprised of AWC beneficiaries in the project area. The total population of the block was 89,476. Participation in the supplementary nutrition program (SNP) increased two to three folds in all categories of the target population. Immunization and Vitamin A coverage levels for children also showed an increase of about 3 and 5-8 times from baseline status respectively in a year's time. Among pregnant women, Tetanus Toxoid (TT) and Iron and Folic Acid (IFA) utilization rates have also shown two and five fold increase respectively.

Beta-carotene inhibits rat liver chromosomal aberrations and DNA chain break after a single injection of diethylnitrosamine.

Beta-carotene (BC) has recently been found to possess potent anti-tumour activity in chemically induced rat liver carcinogenesis. In the present study, attempts have been made to understand the basic cytogenetic and molecular mechanism of the anti-tumour effect of BC by monitoring its effect on rat liver chromosomal aberrations (CAs) and DNA chain breaks during the early preneoplastic stage of diethylnitrosamine (DEN)-induced hepatocarcinogenesis in male rats. DNA chain breaks, however, can be detected with great sensitivity by exposing crude cell lysates to alkaline solutions and monitoring the rate of strand unwinding so that one strand break per chromosome can easily be detected. Supplementary BC, in basal diet (120 mg kg[-1]), was given to rats 15 days before carcinogenic threat with DEN. Under these experimental conditions, BC was found to afford a unique protection against DEN-induced CAs 96 h after DEN injection. Long-term treatment with BC also triggered a protective effect on induction of CAs 15, 30 or 45 days after DEN treatment, which was maximal on structural aberrations followed by numerical and physiological types. BC treatment for 15 days before DEN injection was found to offer a significant (P < 0.001) protection in the generation of single-strand breaks compared with DEN control. Thus, BC ranks as a potential chemopreventive agent for the future so far as chemical rat liver carcinogenesis is concerned.

Biochemical basis of selenomethionine-mediated inhibition during 2-acetylaminofluorene-induced hepatocarcinogenesis in the rat.

Supplementation of selenium in the form of selenomethionine (8 ppm) in drinking water daily has been found to be highly effective in reducing cancer incidence in male Sprague-Dawley rats fed 2-acetylaminofluorine (2-AAF) (0.05%) in the basal diet daily for 16 weeks. Selenomethionine treatment before initiation, during initiation or during the selection/promotion phases of hepatocarcinogenesis has been found to be effective in elevating hepatic microsomal cytochrome b5, cytochrome P-450 contents, triphosphopyridine nucleotide-cytochrome c-reductase and cytosolic aryl hydrocarbon hydroxylase activities to a statistically significant level measured either in the hyperplastic nodules or in the non-nodular surrounding liver parenchyma compared with 2-AAF control rats. Moreover, selenomethionine treatment throughout the study also decreased the cytosolic 1-chloro-2,4-dinitrobenzene conjugated glutathione-S-transferase and microsomal UDP-glucuronyl transferase activities to a significant level when compared with 2-AAF control rats. Furthermore, direct correlations between hyperplastic nodules and non-nodular liver areas were observed with the hepatic selenium content and also with the rates and patterns of hepatic drug metabolism. Selenomethionine was also found to protect and improve the histopathological indices without any toxic side effects as revealed from the haematoxylin and eosin staining. Our results establish the fact that selenium is particularly protective in limiting the action of 2-AAF during the initiation phase of hepatocarcinogenesis.

Hepatoprotective activity of carrot (Daucus carota L.) against carbon tetrachloride intoxication in mouse liver.

The effect of carrot extract on carbon tetrachloride (CCl4)-induced acute liver damage was evaluated. The increased serum enzyme levels (viz., glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase, alkaline phosphatase, sorbitol and glutamate dehydrogenase) by CCl4-induction were significantly lowered due to pretreatment with the extract. The extract also decreased the elevated serum bilirubin and urea content due to CCl4 administration. Increased activities of hepatic 5'-nucleotidase, acid phosphatase, acid ribonuclease and decreased levels of succinic dehydrogenase, glucose-6-phosphatase and cytochrome P-450 produced by CCl4 were reversed by the extract in a dose-responsive way. Results of this study revealed that carrot could afford a significant protective action in the alleviation of CCl4-induced hepatocellular injury.

Changes in the blood lipid profile after administration of Ocimum sanctum (Tulsi) leaves in the normal albino rabbits.

Administration of fresh leaves of Ocimum sanctum (Tulsi) mixed as 1 g and 2 g in 100 gms of diet given for four weeks, brought about significant changes in the lipid profile of normal albino rabbits. This resulted in significant lowering in serum total cholesterol, triglyceride, phospholipid and LDL-cholesterol levels and significant increase in the HDL-cholesterol and total faecal sterol contents.

Preparation of anti-polysaccharide antiserum using liposomes as immunological adjuvant.

Bovine serum albumin (BSA) was coupled to dextran by controlled periodate oxidation followed by sodium borohydride reduction. The conjugate was entrapped in negatively charged, multilamellar phosphatidylcholine (lecithin) liposomes in which the polysaccharide remained surface-exposed, at least partially. Liposome-entrapped conjugate elicited in rabbits an appreciable anti-dextran response when compared with the sera raised in saline or in Freund's adjuvant. The anti-dextran antibodies belonged to both the IgM and IgG classes. The precipitin reaction of dextran with the antiserum raised in liposomes was determined.

Effect of chronic hypo and hypervitaminosis C on the brush border enzymes and the intestinal uptake of glucose and alanine.

Brush border sucrase and alkaline phosphatase activities are considerably enhanced in the intestine of ascorbic acid deficient guinea-pigs. Similar increase in the uptake of D-glucose and L-alanine also occurs in chronic vitamin C deficiency. However the permeability of D-glucose and L-alanine in the intestine of animals fed with large doses of vitamin C is severely depressed, with a reduction in the levels of sucrase and alkaline phosphatase activities.

A new non-steroidal drug for long-acting contraception.

A new contraceptive compound had been prepared with the common ingredients and it was applied in female rats. The efficacy and toxicity tests of this compound showed that this drug has along-acting contraceptive value not causing any side-effects.

Effect of adrenalin and acetylcholine on the hypothalamic neurosecretory system in the garden lizard, Calotes versicolor.

Injection of adrenalin or acetylcholine led to enhanced elaboration and release of neurosecretory materials (hyperactivity) in the hypothalamic neurosecretory system of the garden lizard. The hyperactivity apparently came down to the control level of activity at the 120 h stage of the experiment.