Biochemical Evaluation of the Hypoglycemic Effects of Extract and Fraction of Cassia fistula Linn. in Alloxan-induced Diabetic Rats.

Various extracts of flowers of Cassia fistula Linn (Leguminosae) such as petroleum ether (60-80°), chloroform, acetone, ethanol, aqueous, and crude aqueous extracts and two fractions of ethanol extract were tested for antihyperglycemic activity in glucose-overloaded hyperglycemic rats. The effective antihyperglycemic extracts and fraction were tested for their hypoglycemic activity at two dose levels, 200 and 400 mg/kg, respectively. To confirm their utility in higher models, the effective extracts and fraction of C. fistula were subjected to antidiabetic study in an alloxan-induced diabetic model at two dose levels, 200 and 400 mg/kg, respectively. Biochemical parameters like glucose, urea, creatinine, serum cholesterol, serum triglyceride, high-density lipoprotein, low-density lipoprotein, hemoglobin, and glycosylated hemoglobin were also assessed in experimental animals. The petroleum ether and ethanol extracts of C. fistula and the water-soluble fraction of ethanol extract were found to exhibit significant antihyperglycemic activity. The extracts, at the given doses, did not produce hypoglycemia in fasted normal rats, and the fraction exhibited weak hypoglycemic effect after 2 h of the treatment. Treatment of diabetic rats with ethanol extract and water-soluble fraction of this plant restored the elevated biochemical parameters significantly (P<0.05) to the normal level. No activity was found in the petroleum ether extract of the plant. Comparatively, the water-soluble fraction of ethanol extract was found to be more effective than the ethanol extract, and the activity was comparable with that of the standard, glibenclamide (5 mg/kg).

The effect of uridine diphosphate glucuronosyltransferase (UGT)1A6 genetic polymorphism on valproic acid pharmacokinetics in Indian patients with epilepsy: a pharmacogenetic approach.

BACKGROUND AND OBJECTIVE: Sodium valproate is a widely prescribed broad-spectrum antiepileptic drug. It shows high inter-individual variability in pharmacokinetics and pharmacodynamics and has a narrow therapeutic range. We evaluated the effects of polymorphic uridine diphosphate glucuronosyltransferase (UGT)1A6 (541A>G, 552A>C) metabolizing enzyme on the pharmacokinetics of sodium valproate in the patients with epilepsy who showed toxicity to therapy. METHODS: Genotype analysis of the patients was made with polymerase chain-restriction fragment length polymorphism (RFLP) with sequencing. Plasma drug concentrations were measured with reversed phase high-performance liquid chromatography (HPLC) and concentration-time data were analyzed by using a non-compartmental approach. RESULTS: The results of this study suggested a significant genotypic as well as allelic association with valproic acid toxicity for UGT1A6 (541A>G) or UGT1A6 (552A>C) polymorphic enzymes. The elimination half-life (t ½ = 40.2 h) of valproic acid was longer and the clearance rate (CL = 917 ml/h) was lower in the poor metabolizers group of UGT1A6 (552A>C) polymorphism who showed toxicity than in the intermediate metabolizers group (t ½ = 35.5 h, CL = 1,022 ml/h) or the extensive metabolizers group (t ½ = 25.4 h, CL = 1,404 ml/h). CONCLUSION: Our findings suggest that the UGT1A6 (552A>C) genetic polymorphism plays a significant role in the steady state concentration of valproic acid, and it thereby has an impact on the toxicity of the valproic acid used in the patients with epilepsy.

Need for a national epilepsy control program.

This article briefly outlines the proposed national epilepsy control program. The content of the article is based on four meetings held by invitation of the Ministry of Health. Invitees by ministry - Drs. D. C. Jain, M. Gourie Devi, V. Saxena, S. Jain, P. Satish. Chandra, M. Gupta, K. Bala, V. Puri, K. S. Anand, S. Gulati, S. Johri, P. S. Chandra, M. Behari, K. Radhakrishnan, D. Bachani. Presentations were made by Dr. M. Tripathi.The program will involve all neurologists across the country in teaching and training at state levels and a central monitoring committee.

Genetic polymorphism of NAT2 metabolizing enzymes on phenytoin pharmacokinetics in Indian epileptic patients developing toxicity.

OBJECTIVE: To investigate the effects of NAT2 metabolizing enzymes on the pharmacokinetics of antiepileptic drug phenytoin in the epileptic patients showing toxicity. METHODS: Fifty epileptic individuals who had developed toxicity to phenytoin and 50 control epileptic subjects who had not developed toxicity to phenytoin were genotyped for NAT2 (NAT2*5A, NAT2*5C, NAT2*7, NAT2*6) polymorphisms by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP method). Phenytoin plasma levels were analyzed by reversed phase HPLC method and pharmacokinetic parameters such as area under the concentration curve (AUC), maximum concentration (C(max)), time to C(max) (t(max)) and half-life (t(1/2)) were estimated by noncompartmental analysis using PK Solutions® software. RESULTS: The NAT2 polymorphism was seen to be in Hardy-Weinberg equilibrium and showed significant genotypic as well as allelic association with phenytoin toxicity for NAT2*5A (481C>T) and NAT2*5C (803A>G). Pharmacokinetic parameters for phenytoin in toxicity group of poor metabolizers showed a longer elimination half-life of a drug (t(1/2) = 35.3 h) and less clearance rate (CL = 468 mL/h) compared to intermediate metabolizers (t(1/2) = 33.2 h, CL = 674 mL/h) and extensive metabolizer (t(1/2) = 20.7 h, CL = 977 mL/h) in NAT2*5A polymorphism. CONCLUSION: Our findings suggest that the NAT2*5A genetic polymorphisms plays a significant role in the steady-state concentrations of phenytoin and thereby have impact on toxicity in epileptic patients.

Tobacco control policies in India: implementation and challenges.

Tobacco use is a major public health challenge in India with 275 million adults consuming different tobacco products. Government of India has taken various initiatives for tobacco control in the country. Besides enacting comprehensive tobacco control legislation (COTPA, 2003), India was among the first few countries to ratify WHO the Framework Convention on Tobacco Control (WHO FCTC) in 2004. The National Tobacco Control Programme was piloted during the 11 th Five Year Plan which is under implementation in 42 districts of 21 states in the country. The advocacy for tobacco control by the civil society and community led initiatives has acted in synergy with tobacco control policies of the Government. Although different levels of success have been achieved by the states, non prioritization of tobacco control at the sub national level still exists and effective implementation of tobacco control policies remains largely a challenge.

Antidiabetic activity of medium-polar extract from the leaves of Stevia rebaudiana Bert. (Bertoni) on alloxan-induced diabetic rats.

OBJECTIVE: To investigate the medicative effects of medium-polar (benzene:acetone, 1:1, v/v) extract of leaves from Stevia rebaudiana (family Asteraceae) on alloxan-induced diabetic rats. MATERIALS AND METHODS: Diabetes was induced in adult albino Wistar rats by intraperitoneal (i.p.) injection of alloxan (180 mg/kg). Medium-polar extract was administered orally at daily dose of 200 and 400 mg/kg body wt. basis for 10 days. The control group received normal saline (0.9%) for the same duration. Glibenclamide was used as positive control reference drug against Stevia extract. RESULTS: Medium-polar leaf extract of S. rebaudiana (200 and 400 mg/kg) produced a delayed but significant (P < 0.01) decrease in the blood glucose level, without producing condition of hypoglycemia after treatment, together with lesser loss in the body weight as compared with standard positive control drug glibenclamide. CONCLUSIONS: Treatment of diabetes with sulfonylurea drugs (glibenclamide) causes hypoglycemia followed by greater reduction in body weight, which are the most worrisome effects of these drugs. Stevia extract was found to antagonize the necrotic action of alloxan and thus had a re-vitalizing effect on ß-cells of pancreas.

Bioassay-guided isolation of anti-inflammatory and antinociceptive compound from Plumbago zeylanica leaf.

Plumbago zeylanica Linn. (Plumbaginaceae) is used in the treatment of various inflammatory ailments in traditional medicines. In order to validate these ethnobotanical practices, the anti-inflammatory and antinociceptive activities of various leaf extracts (petroleum ether (60-80 degrees ), chloroform, acetone, ethanol, and aqueous) were studied using in vivo experimental models at two dose levels (200 and 400 mg/kg, p.o.). Anti-inflammatory activity was tested using the carrageenan induced rat hind paw edema method while analgesic activity was studied using the hot plate and formalin induced models. Diclofenac (100 mg/ kg) was used as the reference standard in both anti-inflammatory and analgesic models and morphine (10 mg/ kg, i.p.) was used as the reference standard in the formalin induced analgesic model. The acetone extract significantly (p < 0.01) reduced inflammation in the rats when compared to the control group. As for the analgesia effect, the acetone and petroleum ether extracts significantly (p < 0.01) decreased the pain stimulus only in the later phase of the formalin test, suggesting that the drug could be peripherally acting. Bioassay-guided fractionation of the acetone extract led to the isolation and identification of plumbagin. Structure elucidation of plumbagin confirmed it as 5-hydroxy-2-methyl-1,4-naphthoquinone, a naphthaquinone derivative, through spectral techniques.

Antiovulatory and estrogenic activity of Plumbago rosea leaves in female albino rats.

OBJECTIVE: To evaluate the effect of petroleum ether (60-80 degrees ), chloroform, acetone, ethanol and aqueous extracts of Plumbago rosea leaves on the estrous cycle and to identify the estrogenic activity of active acetone and ethanol extracts in female albino rats. METHODS: PLANT EXTRACTS WERE TESTED FOR THEIR EFFECT ON THE ESTROUS CYCLE AT TWO DOSE LEVELS: 200 and 400 mg/kg, respectively. The effective acetone and ethanol extracts were further studied on estrogenic activity in rats. Histological studies of the uterus were carried out to confirm their estrogenic activity. RESULTS: The acetone and ethanol extracts were most effective in interrupting the normal estrous cycle of the rats (P<0.05, <0.01, <0.001). These later exhibited prolonged diestrous stage of the estrous cycle with consequent temporary inhibition of ovulation. The antiovulatory activity was reversible on discontinuation of treatment. Both the extracts showed significant estrogenic and antiestrogenic activity. CONCLUSION: The acetone and ethanolic extracts of P. rosea leaves have an antifertility activity.

Antidiabetic activity of aqueous extract and non polysaccharide fraction of Cynodon dactylon Pers.

Petroleum ether (60 degrees-80 degrees C), chloroform, acetone, ethanol, aqueous and crude hot water extracts of the whole plant of C. dactylon and the two fractions of aqueous extract were tested for antihyperglycaemic activity in glucose overloaded hyperglycemic rats and in alloxan induced diabetic model at two-dose levels, 200 and 400 mg/kg (po) respectively. The aqueous extract of C. dactylon and the non polysaccharide fraction of aqueous extract were found to exhibit significant antihyperglycaemic activity and only the non polysaccharide fraction was found to produce hypoglycemia in fasted normal rats. Treatment of diabetic rats with aqueous extract and non polysaccharide fraction of the plant decreased the elevated biochemical parameters, glucose, urea, creatinine, serum cholesterol, serum triglyceride, high density lipoprotein, low density lipoprotein, haemoglobin and glycosylated haemoglobin significantly. Comparatively, the non polysaccharide fraction of aqueous extract was found to be more effective than the aqueous extract.

Antidiabetic activity of flower buds of Michelia champaca Linn.

OBJECTIVE: To identify the antihyperglycemic activity of various extracts, petroleum ether (60-80°), chloroform, acetone, ethanol, aqueous and crude aqueous, of the flower buds of Michelia champaca, and to identify the antidiabetic activity of active antihyperglycemic extract. MATERIALS AND METHODS: Plant extracts were tested for antihyperglycemic activity in glucose overloaded hyperglycemic rats. The effective antihyperglycemic extract was tested for its hypoglycemic activity at two-dose levels, 200 and 400 mg/kg respectively. To confirm its utility in the higher model, the effective extract of M. champaca was subjected to antidiabetic study in alloxan induced diabetic model at two dose levels, 200 and 400 mg/kg respectively. The biochemical parameters, glucose, urea, creatinine, serum cholesterol, serum triglyceride, high density lipoprotein, low density lipoprotein, hemoglobin and glycosylated hemoglobin were also assessed in the experimental animals. RESULTS: The ethanolic extract of M. champaca exhibited significant antihyperglycemic activity but did not produce hypoglycemia in fasted normal rats. Apart from this extract, the crude aqueous and petroleum ether extracts were found active only at the end of the first hour. Treatment of diabetic rats with ethanolic extract of this plant restored the elevated biochemical parameters significantly (P<0.05) (P<0.01) and the activity was found dose dependent. CONCLUSION: This study supports the traditional claim and the ethanolic extract of this plant could be added in traditional preparations for the ailment of various diabetes-associated complications.

A rare case of trypanosomiasis in a two month old infant in Mumbai, India.

Human Trypanosomiasis is a rare occurrence in India. In the cases reported so far the disease causative species have been the species infective to animals viz., Trypanosoma lewisi and Trypanosoma evansi. These animal species usually non pathogenic in humans can acquire the desired virulence and emerge as human pathogens causing serious disease, in the right combination of environmental, host related and organism related factors. We report here a case of trypanosomiasis caused by the rodent parasite T. lewisi in a two months old infant in urban Mumbai. Under the fastly changing environmental scenario there is an urgent need to be prepared for the emerging zoonoses. Any unusual disease occurrence in a given geographical area acquires a special significance in this context and should be reported to assess its public health importance and be prepared to deal with the consequent challenges posed, if any.

Chikungunya viral disease in district Bhilwara (Rajasthan) India.

An investigation of chikungunya outbreak cases was carried out in Bhilwara District, Rajasthan during Aug-Sep 2006. Fever with multiple joint pains was the first presenting feature. Aedes larval surveys indicate high Breteau index (78.6 to 200), House index (48.0 to 83.3) & Container index (41.1 to 73.6) above the critical index. Out of 40 sera samples tested, 12 showed HI antibodies for chikungunya virus in high titres and another five were positive for IgM antibodies against chikungunya. The clinico-epidemiological, laboratory and entomological investigations confirm that this episode of fever was due to chikungunya fever. Strengthening and intensification of surveillance along with educating the community were recommended for control of outbreak.

Epidemiological characteristics of rabies in Delhi and surrounding areas, 1998.

OBJECTIVE: To describe the epidemiological characteristics of rabies in Delhi in 1998. METHODS: Analysis of the records of hydrophobia cases admitted to the Infectious Diseases Hospital, Delhi (IDH) in 1998. RESULTS: About 46 percent (99/215) of the hydrophobia cases admitted to the IDH in 1998 belonged to Delhi. The remaining came from the adjoining states, both urban and rural areas. In Delhi residents, overall hospitalization rate was 0.81 per 100,000 population. It was significantly higher in 5-14 year old than in other age groups and in males than in females (p <0.0009). Cases occurred round the year. Almost 96 percent cases (206/215) gave history of animal exposure, 13 days to 10 years (median 60 days) before hospitalization. Majority (195/206) had class III exposure. Animals involved were stray dog (193/206 = 90 percent), pet dog, cat, jackal, mongoose, monkey and fox. Most of cases were never vaccinated (78 percent) or inadequately vaccinated (22 percent); only 1 percent each received appropriate wound treatment, or rabies immunoglobulin. CONCLUSIONS: Rabies is a major public health problem in Delhi. Its incidence is significantly higher in 5-14 year old children than in other age groups. The results indicate the need to educate the community and health care workers about the importance of immediate and adequate post-exposure treatment and to start an effective control program for dogs, the principal vector of rabies.

Bilateral cysticercosis of the optic nerve.

Bilateral cysticercosis of the optic nerves affected a man who presented with features suggestive of optic neuritis. Ultrasonography revealed bilateral sonolucent cystic lesions with central echo-dense, highly reflective structures behind the optic nerve heads. A subretinal cyst was present in one eye. Magnetic resonance imaging of the brain and orbit revealed multiple cysticerci in the brain, orbit, and eye. The subretinal cyst was removed by pars plana vitrectomy, and the other cysts resolved on treatment with albendazole.

Simultaneous measurement of XANES in halide-intercalated BSCCO(2212) using electron and fluorescence yield to compare their performance.

Total Yield with an escape depth of approximately 100-200 A is known to be rather surface sensitive. Fluorescence Yield, on the other hand, with an escape depth of approximately 1000-2000 A is relatively less prone to surface effects but necessitates some corrections to obtain the true signal. Both have their plus and minus points and, if used with care, yield reliable data. In the present experiment both the techniques have been simultaneously employed for measuring orientation dependent O K and the Cu L3 edges from an uncleaved surface of I(2)BSCCO(2212) single crystal to compare the performance of the two modes of detection. Despite glaring differences in intensities the results from the two appear to show reasonable agreement in respect of relative intensities of the spectral features.