Assessment of prescribing pattern of drugs and completeness of prescriptions as per the World Health Organization prescribing indicators in various Indian tertiary care centers: A multicentric study by Rational Use of Medicines Centers-Indian Council of Medical Research network under National Virtual Centre Clinical Pharmacology activity.

OBJECTIVE: The rational use of medicines as per the World Health Organization (WHO) should be practiced globally. However, data regarding the completeness of the prescriptions and their rational use is lacking from developing countries like India. Thus, the aim of this study was to assess the prescribing patterns of drugs and completeness of prescriptions as per WHO core drug use and complementary indicators to provide real-life examples for the Indian Council of Medical Research (ICMR) online prescribing skill course for medical graduates. METHODS: Prescriptions of the patients, fulfilling inclusion criteria, attending Outpatient Departments of various specialties of tertiary care hospitals, were collected by thirteen ICMR Rational use of medicines centers located in tertiary care hospitals, throughout India. Prescriptions were evaluated for rational use of medicines according to the WHO guidelines and for appropriateness as per standard treatment guidelines using a common protocol approved by local Ethics committees. RESULTS: Among 4838 prescriptions, an average of about three drugs (3.34) was prescribed to the patients per prescription. Polypharmacy was noted in 83.05% of prescriptions. Generic drugs were prescribed in 47.58% of the prescriptions. Further, antimicrobials were prescribed in 17.63% of the prescriptions and only 4.98% of prescriptions were with injectables. During the prescription evaluation, 38.65% of the prescriptions were incomplete due to multiple omissions such as dose, duration, and formulation. CONCLUSION: Most of the parameters in the present study were out of the range of WHO-recommended prescribing indicators. Therefore, effective intervention program, like training, for the promotion of rational drug use practice was recommended to improve the prescribing pattern of drugs and the quality of prescriptions all over the country.

Prevalence of risk factors for coronary artery disease in an urban Indian population.

OBJECTIVE: The objective of this study was to assess the prevalence of risk factors for coronary artery disease (CAD) in government employees across India. METHODS: The study population consisted of government employees in different parts of India ({n=10,642 men and n=1966 women; age 20-60 years}) and comprised various ethnic groups living in different environmental conditions. Recruitment was carried out in 20 cities across 14 states, and in one union territory. All selected individuals were subjected to a detailed questionnaire, medical examinations and anthropometric measurements. Blood samples were collected for blood glucose and serum lipid profile estimation, and resting ECG was recorded. Results were analysed using appropriate statistical tools. RESULTS: The study revealed that 4.6% of the study population had a family history of premature CAD. The overall prevalence of diabetes was 16% (5.6% diagnosed during the study and the remaining 10.4% already on medication). Hypertension was present in 21% of subjects. The prevalence of dyslipidemia was significantly high, with 45.6% of study subjects having a high total cholesterol/high density lipoprotein ratio. Overall, 78.6% subjects had two or more risk factors for CAD. CONCLUSIONS: The present study demonstrates a high prevalence of CAD risk factors in the Indian urban population. Therefore, there is an immediate need to initiate measures to raise awareness of these risk factors so that individuals at high risk for future CAD can be managed.

Recent advances in the pathophysiology and pharmacological treatment of obesity.

WHAT IS KNOWN AND OBJECTIVE: The increasing prevalence of obesity and associated morbidity present unmet medical needs for safe and effective new drug therapies. Our aim is to review the diverse targets and compounds that are in clinical development. METHODS: Literature searches were conducted using the PUBMED database for studies published in English from January 1985 to December 2011 using combinations of key words, including obesity, overweight, weight loss and treatment in addition to the clinical trials website. Bibliographies of selected references were also evaluated for relevant articles. Press/news releases were also utilized. The collection of information for this review was limited to the most recently available human and animal data. RESULTS AND DISCUSSION: Weight loss drugs in development include compounds that act centrally (neuropeptide Y, AgRP and MCH1 receptors) to limit food intake or reduce the absorption of fat from the gastrointestinal tract (lipase inhibitors) or increase energy expenditure or reduce adipose tissue formation. Among the existing therapy, new combinations (topiramate plus phentermine, bupropion plus naltrexone) offer greater efficacy with reduced adverse effects. WHAT IS NEW AND CONCLUSION: Despite recent setbacks in the pharmacotherapy of obesity (withdrawal of rimonabant and sibutramine), many compounds are in phase II/III trials. The future holds promise for a new drug that alone or in combination with an existing agent could target the initial pathophysiology and morbidities associated with obesity.

Cloning of gag gene of HIV-1 subtype C (Indian strain) into a mammalian expression vector and in vitro expression studies.

PURPOSE: Acquired immunodeficiency syndrome caused by HIV-1 is one of the biggest health problems we are facing today. It is required to concentrate efforts towards designing a safe, effective and affordable vaccine candidate in the context of the growing epidemic worldwide. Recently the approach of DNA based immunogen has evoked a lot of enthusiasm in the preclinical models. METHODS: This study was designed towards a subtype C based gag DNA construct in the expression vector pJW4304. The gag and protease genes of HIV-1 subtype C were cloned into a mammalian expression vector pJW4304. The cloning strategy was designed so as to express a naturally processed form of the protein. Expression of gag protein by the construct pJWgagprotease49587 was evaluated by western blotting, p24 antigen capture ELISA and electron microscopy. RESULTS: Gag p24 was detected both in the supernatant and in the transfected cells. Extra cellular p24 protein was estimated by p24 antigen capture ELISA. Immunoblotting using HIV positive polyclonal sera further confirmed the expression and processing of gag gene. The 24kDa band has been observed in cell lysates, which indicates that the proper processing is taking place in the presence of protease. Virus like particles were seen budding from the cell membrane 24 and 48 hours post transfection by transmission electron microscopy. CONCLUSIONS: The recombinant construct pJWgagprotease49587 has shown good expression in vitro and therefore is a good candidate to study immunogenicity of the construct. Immunogenicity testing in mice is being carried out currently with this construct.

Topical amiloride accelerates healing and delays neovascularization in mechanically produced corneal ulcers in rabbits.

The present investigation was undertaken to explore the ulcer healing and antiangiogenic efficacy of two dosage schedules of topically administered amiloride in mechanically produced corneal ulcers in rabbits and to compare its effect with the conventional topical antiinflammatory angiostatic agent flurbiprofen. The epithelium and superficial lamellae of the stroma of both eyes of each rabbit were cut through by a corneal trephine (8 mm diameter) up to a depth of 0.3 mm and removed after local anesthesia. The animals were randomly divided in groups of 4 rabbits each. In the eyes of 2 groups of animals, amiloride (4%) was instilled either q.i.d. or b.i.d.; in another, flurbiprofen (0.03%) was instilled twice daily whereas the saline-treated group served as control. The healing of ulcer was followed on a slit lamp regarding its size, depth, slough formation, infiltration and neovascularization on alternate days up to the 10th day with and without fluorescein staining. Healing of corneal ulcers was significantly accelerated by both dosage schedules of topical amiloride (4%) but more so following q.i.d. instillation. Topical flurbiprofen, on the other hand, delayed the healing process. Instillation of amiloride four times daily or flurbiprofen twice daily inhibited angiogenesis significantly. However, appearance of new vessels was completely prevented when amiloride (4%) was instilled twice daily. Thus topical amiloride (4%) may prove to be a cheap and better antineovascularization as well as ulcer healing agent with no apparent side effects. Inhibition of uPA by amiloride appears to be responsible for these effects.

Predictor of outcome of hyperthyroidism due to Graves disease: serum triiodothyronine/thyroxine ratio.

There is a proportionally greater increase in the serum T3 than Serum T4 concentration in patients with hyperthyroidism due to Grave's disease which results in an elevation of serum T3 to T4 ratio. The study was undertaken to investigate the alteration of serum T3 to T4 ratio in relation to the outcome of antithyroid drug therapy. 98 patients of hyperthyroid Grave's disease were studied and 78 patients had T3 to T4 ratio greater than 20 ng/microgram before therapy (normal range 14-20; mean 16.0) In 16 out of 78 patient T3 to T4 ratio remained high during a 18 months course of antithyroid drug therapy and in 13 of them (81%) hyperthyroidism recurred after stoppage of treatment. In the remaining 62 patients, the initial high T3 to T4 ratio became normal (< 20) during treatment and 34 of them (54.9%) had a remission of the disease after stoppage of the drug. Of the 20 patients in whom the initial T3 to T4 ratios were within normal range, the ratio remained normal during treatment and 16(80%) had a remission. Goiter size was larger in patients with high serum T3 to T4 ratio and reduction of goiter size occurred in some patients (59%) with decreasing T3 to T4 ratios. It is concluded that serum T3 to T4 ratio is a single and a useful predictor of the outcome of antithyroid drug therapy in patients with hyperthyroidism due to Grave's disease. A ratio greater than 20 throughout therapy indicates that the chances of relapse is high and a ratio below 20 either initially or during therapy is an indication of prolonged remission.

Evaluation of long-term results of two schedules of treatment for toxic multinodular goitre with radioiodine therapy (I 131).

Results of the long term effects of two schedules of radioine therapy (I131) in 130 toxic multinodular goitre patients were evaluated. Seventy five patients (group I) were treated with low doses and 55 patients (group II) with calculated high doses adjusted for thyroid weight (0.5-1 mu ci/g) and radioiodine uptake. Follow up (mean +/- SEM) was 4.5 +/- 0.4 years and 4.8 +/- 0.6 years respectively (p > 0.1). At the end of followup hyperthyroidism was successfully reversed in 87% (Group I) and 82% (Group II). In group I hypothyroidism was present in 5% of patients while it was 12.5% in group II patients. The total dose per gram of thyroid tissue was not significantly different in both the groups (0.058 mu ci +/- 0.0054 VS 0.073 +/- 0.0054 ci/g.) However in group II the number of I131 administration was significantly lower (1.5 +/- 0.2) than in group I (3.2 +/- 0.4) and the percentage of patients who were adequately treated in Group II with single dose was more as compared in group I (62% in group II versus 49% in group I) Hypothyroidism was reached in a shorter time after treatment in group II (median time 0.8 year in group II Vs 1.1 yrs in group I). Patients with positive thyroid antibodies showed a significant earlier development of hypothyroidism within six months. It is concluded that radioiodine is an effective treatment for toxic multinodular goitre with a significant low incidence of post therapy hypothyroidism in patients treated with low doses as compared to higher doses of radioiodine therapy.

Long-term results of two schedules of treatment for toxic multinodular goitre with radioiodine therapy.

Results of the long-term effects of two schedules of radioiodine therapy I131 in 130 toxic multinodular goitre patients were evaluated. Seventy five patients (group I) were treated with low doses and 55 patients (group II) with calculated high doses adjusted for thyroid weight (0.5-1 mci/g) and radioiodine uptake. Follow up (mean +/- SEM) was 4.5 +/- 0.4 years and 4.8 +/- 0.6 years respectively (P > 0.1). At the end of follow up, hyperthyroidism was successfully reversed in 78% (Group I) and 82% (Group II). In group I hypothyroidism was present in 5% of patients, while it was 12.5% in group II patients. The total dose per gram of thyroid tissue was not significantly different in both the groups (.058 mci +/- .0054 VS .073 +/- .0054 mci/g). However in group II the number of I131 administration was significantly lower (1.5 +/- 0.2) than in group I (3.2 +/- 0.4). The percentage of patients who were adequately treated in Group II with single dose was more as compared in group I (62% in group II versus 40% in group I). Euthyroidism was reached in a shorter time after treatment in group II (median time 0.8 year in group II Vs 1.1 yrs in group I) It is concluded that radioiodine is an effective treatment for toxic multinodular goitre with a significant low incidence of post therapy hypothyroidism in patients treated with low doses as compared to higher doses of radioiodine therapy.

Nitric oxide synthase expression in glial cells: suppression by tyrosine kinase inhibitors.

Rat brain glial cells have the capacity to express a calcium-independent form of nitric oxide synthase (iNOS). To test if iNOS induction required tyrosine kinase activity, we made use of genistein, a selective inhibitor of tyrosine kinases. In both primary astrocyte cultures and C6 glioma cells, the presence of genistein prevented both lipopolysaccharide- and cytokine-induced NOS activity in a dose-dependent manner. The presence of tyrphostin-25 (10 microM), which is highly specific for tyrosine kinases, also blocked iNOS induction. Additional characterization showed that genistein blocked iNOS induction in a dose-dependent manner (IC50 of approximately 40 microM), that the continuous presence of genistein was not necessary to observe inhibition, and that preincubation with genistein led to higher levels of inhibition than the simultaneous addition of genistein and inducers. The decrease in iNOS activity due to genistein was accompanied by a decrease in iNOS mRNA level as detected by a specific PCR assay. These results indicate that induction of astroglial iNOS expression requires tyrosine kinase activity.

Induction of protective immunity to experimental hepatic amoebic infection in hamsters.

Immunisation of hamsters with the Sephadex G-200 chromatographed Fraction-I of the crude amoebic extract afforded protection in 58% of the animals against an intrahepatic challenge with a virulent subline of axenic Entamoeba histolytica NIH-200 (V). The protected animals had variable levels of anti-FI antiamoebic antibodies, while none of the infected controls had such antibodies. Findings suggest that chromatographed FI of crude amoebic extract might function as a potent immunogen affording protection in amoebic infection.