Quinolinyl Pyrimidines: Potent Inhibitors of NDH-2 as a Novel Class of Anti-TB Agents

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Evaluation of immune responses to an oral typhoid vaccine,Ty21a,in children from 2 to 5 years of age in Bangladesh

Young children are very susceptible to typhoid fever, emphasizing the need for vaccination in under five age groups. The parenteral Vi polysaccharide vaccine is not immunogenic in children under 2 years and the oral Ty21a vaccine (Vivotif) available in capsular formulation is only recommended for those over 5 years.     

Randomized controlled trial of effectiveness of lafutidine versus pantoprazole in uninvestigated dyspepsia

Objectives:

Lafutidine is a new H₂-blocker in India claimed to be more potent and effective than existing H₂-blockers. Proton pump inhibitors (PPIs), by virtue of their mechanism of action, have greater efficacy than H₂-blockers in gastric acid suppression. However, clinical trials comparing H₂-blockers directly with PPIs are limited. We carried out a head-to-head comparison of the effectiveness of lafutidine versus the PPI pantoprazole in uninvestigated dyspepsia [CTRI/2013/12/004261].

Materials and Methods:

A prospective, open label, randomized, controlled trial was conducted in a tertiary care hospital. Ambulatory adult patients with dyspepsia, not yet subjected to endoscopy, were recruited if they had at least moderately severe symptoms, defined as a score of ≥ 4 on a 7-point Global Overall Symptom (GOS) Scale. Those with alarm features or significant comorbidity were excluded. Subjects received either once daily lafutidine 10 mg or pantoprazole 40 mg, orally, for 8 weeks. Reflux, dysmotility and pain scores were assessed by Modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (mFSSGERD), and quality of life (QoL) by SF-8 scale. The latter had physical and mental components summarized by physical component summary score (PCS) and a mental component summary score (MCS).

Results:

Of 122 patients enrolled, data of 57 on lafutidine and 60 on pantoprazole were analyzed. At 4 weeks, proportion of subjects responding (GOS score ≤ 2) in the two arms (lafutidine 45.61% vs. pantoprazole 48.33%, P = 0.854) or showing symptom resolution (GOS score ≤ 1) (lafutidine 12.28% vs. pantoprazole 5.00%; P = 0.197) were comparable. Similarly at 8 weeks, both responder (lafutidine 52.63% vs. pantoprazole 56.67%; P = 0.712) and symptom resolution proportions (lafutidine 33.33% vs. pantoprazole 30%; P = 0.843) were comparable. Total score on mFSSGERD scale, as well as all its three component scores, and PCS and MCS scores on QoL SF-8 scale showed improvement but no statistically significant difference between the two arms. Tolerability of both drugs was excellent.

Conclusions:

Lafutidine is well-tolerated and there is no clinically worthwhile difference between the two drugs in the empirical treatment of uninvestigated dyspepsia.KEY WORDS: Dyspepsia, lafutidine, pantoprazole, randomized controlled trial     

Osteoarthritis: Prognosis and emerging therapeutic approach for disease management

Osteoarthritis (OA), a disorder of joints, is prevalent in older age. The contemporary cure for OA is aimed to confer symptomatic relief, consisting of temporary pain and swelling relief. In this paper, we discuss various modalities responsible for the onset of OA and associated with its severity. Inhibition of chondrocytes receptors such as DDR2, SDF‐1, Asporin, and CXCR4 by specific pharmacological inhibitors attenuates OA, a critical step for finding potential disease modifying drugs. We critically analyzed recent OA studies with an emphasis on intermediate target molecules for OA intervention. We also explored some novel and safe treatments for OA by considering disease prognosis crosstalk with cellular signaling pathways.     

Randomized controlled trial for smoking cessation among city office employees

To evaluate the effect of a smoking cessation program by health professionals, a randomized intervention study was carried out in the Omihachiman city office in 1993. Participants (n = 53), volunteers from current smokers in the city office, were randomly divided into intervention and control groups. The intervention group received intensive education for five months (i.e., the effect of smoking on health, the beneficial aspects of quitting smoking, how to stop smoking and how to deal with the withdrawal symptoms). Group lectures (two times) and individual counseling (three times) were used for health education. After five months, the control group was also given the same advice on smoking cessation. Comparison of smoking cessation rates between the two groups was performed at the end of the intervention period. Follow-up of all participants occurred at six and 12 months post intervention. After the five months of intervention, smoking cessation rate in the intervention group (19.2%) tended to be higher than that in the control group (7.4%), but was not significant (chi 2 = 1.62). Over all smoking cessation rates of all participants (n = 53) at the end of the 10 month intervention was 32.1% and at six months and 1 year after the end of the 10 month intervention were 24.5% and 13.2%, respectively. Comparison of participants who successfully stopped smoking and those who did not, it was revealed that younger age, lower expired air CO concentration (p < 0.01), and attitude for smoking cessation at the beginning were significantly related to smoking cessation. In our study, after five months, smoking cessation rate in the intervention group was about two times that of the control group, although the effectiveness of our smoking cessation program could not be validated due to small sample size. Taking into account the rate of smoking cessation after one year, We believe that programs by health professionals are effective for smoking cessation.     

Evaluation of Gum of Moringa oleifera as a Binder and Release Retardant in Tablet Formulation

The present study was undertaken to find out the potential of gum from Moringa oleifera to act as a binder and release retardant in tablet formulations. The effect of calcium sulphate dihydrate (water insoluble) and lactose (water soluble) diluent on the release of propranolol hydrochloride was studied. The DSC thermograms of drug, gum and mixture of gum/drug indicated no chemical interaction. Tablets (F1, F2, F3, and F4) were prepared containing calcium sulphate dihydrate as diluent, propranolol hydrochloride as model drug using 10%, 8%, 6% and 4% w/v of gum solution as binder. Magnesium stearate was used as lubricant. Physical and technological properties of granules and tablets like flow rate, Carr index, Hausner ratio, angle of repose, hardness, friability and disintegration time were determined and found to be satisfactory. Tablets were prepared by wet granulation method containing calcium sulphate dihydrate as excipient, propranolol hydrochloride as model drug using 10%, 20% and 30% of gum as release retardant, magnesium stearate was used as lubricant. Similarly tablets were prepared replacing lactose with calcium sulphate dihydrate. Despite of the widely varying physico-chemical characteristics of the excipients, the drug release profiles were found to be similar. The drug release increased with increasing proportions of the excipient and decreased proportion of the gum irrespective of the solubility characteristics of the excipient. The values of release exponent 'n' are between 0.37 and 0.54. This implies that the release mechanism is Fickian. There is no evidence that the dissolution or erosion of the excipient has got any effect on the release of the drug. The t(50%) values for tablets containing calcium sulphate dihydrate were on an average 10%-15% longer than the tablets containing lactose as excipient. These relatively small differences in t(50%) values suggest that the nature of excipient used appeared to play a minor role in regulating the release, while the gum content was a major factor.     

Immunofluorescence test for the epidemiological monitoring of acute haemorrhagic conjunctivitis cases

An epidemic of acute haemorrhagic conjunctivitis (AHC) occurred in and around Chandigarh, north India, during June, July and August 1981. Considering the difficulty of virus isolation, the indirect immunofluorescence test was used for the demonstration of virus-specific antigen in the cytoplasm of exfoliated conjunctival cells, using reference antisera. The epidemic appeared to be primarily due to enterovirus type 70. The method was found suitable for the rapid diagnosis of AHC cases and for detecting subclinical infection among healthy subjects and convalescent carriers. During follow-up, it was observed that some of the AHC cases were shedding virus-infected conjunctival cells for a prolonged period, even after clinical recovery and during convalescence, before they became free from virus. In the absence of virus isolation, this method can be considered as suitable for the epidemiological monitoring of AHC.     

Indian Council of Medical Research. Task Force on Hormonal Contraception: Phase II randomized clinical trial with norethisterone oenanthate 50 mg alone and in combination with 5 mg or 2.5 mg of either estradiol valerate or cypionate as a monthly injectable contraceptive

A Phase II multicentric study was carried out to compare the different contraceptive treatment schedules of the monthly injectable consisting of norethisterone oenanthate (NET OEN) 50 mg either given alone or in combination with estrogen esters, 2.5 or 5 mg of estradiol valerate (E2 Val.) or estradiol cypionate (E2 Cyp.). A total of 364 women were observed for 1686 months of use. Analysis of the bleeding pattern data indicated that NET OEN 50 mg when given alone gave rise to delayed cycles and/or amenorrhoea. However, the addition of estrogen esters in a dose of either 2.5 or 5 mg provided significantly better bleeding patterns. Of the different treatment schedules investigated, the combination of NET OEN 50 mg with E2 Val. 5 mg provided more consistent and better cycle control. These findings however need further validation on a larger study sample.