Comparison of Observational and Controlled Clinical Trials of Diltiazem in the Treatment of Chronic Anal Fissure

Diltiazem has been extensively studied in the treatment of chronic anal fissures, but efficacy in clinical practice is not fully established. The aim of the present study was to evaluate the safety and efficacy of topical application diltiazem in observational studies as well as in controlled clinical trials in the treatment of chronic anal fissures. A systematic literature search was carried out from 1966 to 31 December, 2007 on PubMed, Medline, Embase and Cochrane database, using the appropriate search words. We found six observational studies with 392 patients and five controlled clinical trials with 289 patients in which topical diltiazem treatment was given. Efficacy was found to be very high in observational studies (56.88%), whereas it was found to be modest in controlled clinical trials (29.41%). In observational studies, most of the patients reported complete healing of fissures within 6–12 weeks, whereas in controlled trials healing was reported within 8 weeks, with tolerable adverse effects of diltiazem. On the basis of the above studies, it can be concluded that topical application of diltiazem is useful in the treatment of chronic anal fissure, but to fully establish its efficacy, larger prospective double-blind study is required in the near future.     

Therapeutic potential of sulindac against ischemia-reperfusion-induced myocardial infarction in diabetic and nondiabetic rats

BACKGROUND

Diabetes mellitus is an independent risk factor for cardiovascular disease and is also associated with increased susceptibility to cardiovascular complications. It has been suggested that alterations in glucose metabolism and glucose flux via the aldose reductase pathway make the diabetic heart more sensitive to ischemic-reperfusion injury. Previous studies have found sulindac to have inhibitory and anti-inflammatory effects on aldose reductase. The use of aldose reductase inhibitors for the protection of ischemic myocardium is still in an exploratory state.

OBJECTIVES

To evaluate the therapeutic potential of sulindac in an in vivo rat model of acute ischemia (30 min) and reperfusion (4 h) in diabetic and nondiabetic rats.

METHODS

Diabetes was induced in rats by administering streptozotocin (45 mg/kg, intravenously). Myocardial infarction was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Sorbitol dehydrogenase levels in heart tissue, as well as lipid peroxide levels in serum and heart tissue, were estimated spectrophotometrically.

RESULTS

Infarct size was increased in diabetic rats in comparison with normal rats. Pretreatment with sulindac significantly reduced infarct size, lipid peroxidation and sorbitol dehydrogenase levels in both diabetic and nondiabetic rats. The degree of cardioprotection was greater in diabetic rats than in nondiabetic rats.

CONCLUSIONS

The present study indicates that the observed cardioprotection provided by sulindac in terms of reducing infarct size in normal rats may be due to its combined antioxidant and anti-inflammatory activities. The inhibition of aldose reductase may be responsible for the enhanced cardioprotection observed in diabetic rats treated with sulindac.     

Magnetic resonance imaging evaluation of myocardial perfusion and viability in congenital and acquired pediatric heart disease

This study examined the feasibility and potential clinical utility of magnetic resonance imaging (MRI) evaluation of myocardial perfusion (first-pass contrast enhancement) and viability (myocardial delayed enhancement) in 30 patients with congenital and acquired pediatric heart disease. Good agreement was found between MRI evaluation of myocardial perfusion and viability and analysis of segmental wall motion as well as coronary angiography (n = 10) and single photon emission computed tomography (n = 6).     

FEV1/FEV6 is effective as a surrogate for FEV1/FVC in the diagnosis of chronic obstructive pulmonary disease

Background and objectiveChronic Obstructive Pulmonary Disease (COPD) causes substantial morbidity and mortality across the globe. Diagnosis of COPD requires post-bronchodilator FEV1/FVC <0.70 as per GOLD Guidelines. FVC maneuver requires a minimum of 6 seconds of forceful expiration with no flow for 1 second for an accepted effort, which lacks any fixed cut-off point. This leads to discomfort, especially in advanced COPD and old aged population. We conducted this study to find the utility of FEV1/FEV6 as a surrogate for FEV1/FVC, the correlation between the two ratios, and the fixed cut-off value of FEV1/FEV6 for COPD diagnosis.MethodsThis was a prospective, cross-sectional study approved by the institutional ethics committee conducted from January 2017 to November 2018. Consented patients above 18 years suspected of COPD underwent Spirometry as per ATS guidelines. FEV1, FEV6, FEV1/FEV6 and FEV1/FVC ratios were recorded from the best acceptable maneuver.ResultsOut of 560 screened patients, 122 diagnosed as COPD. The correlation coefficient between the post-bronchodilator FEV1/FVC ratio and FEV1/FEV6 ratio was 0.972 (p < 0.01). The relationship between the post-bronchodilator FEV1/FVC ratio and FEV1/FEV6 ratio (linear regression analysis) was found out as: FEV1/FVC = ?1.845 + 1.009(FEV1/FEV6). Using this formula, the post-bronchodilator FEV1/FEV6 value of 71.845 was obtained corresponding to the post-bronchodilator FEV1/FVC value of 70.00.ConclusionWe found a positive correlation coefficient (r = 0.972, p < 0.001) between the FEV1/FEV6 and FEV1/FVC ratios and the cut off value of 71.845 (p < 0.01) for the post-bronchodilator FEV1/FEV6 ratio for the diagnosis of COPD. Thus FEV1/FEV6 should be used as a surrogate for FEV1/FVC for the diagnosis of COPD.     

Concomitant parasitism: bancroftian filariasis and intestinal helminths and response to albendazole

Subjects in an disease-endemic area in Orissa, India concomitantly infected with filariasis and intestinal helminths had significantly lower intensity of filarial infection in comparison with those who were infected only with filariasis. Administration of albendazole resulted in a significant decrease in the prevalence of filarial antigenemia in subjects concomitantly infected with intestinal helminths, but produced little change in this infection measure in subjects infected only with Wuchereria bancrofti. These results indicate that intestinal helminths could play a role in the anti-filarial activity of albendazole, most probably by depressing filarial infection intensity in co-infected individuals. Confirmation of these findings in a larger cohort may yield important new insights regarding the role of using albendazole in the ongoing intervention programs for the control of lymphatic filariasis.     

Management practices of tuberculosis in children among pediatric practitioners in Mangalore,South India

Introduction

In spite of having BCG vaccination and tuberculosis control program for the last 50 years, prevalence of tuberculosis continues to be high in India. Inadequate diagnostic methods, suboptimal treatment and monitoring, and the lack of vigilant reporting system are some of the contributing factors for the failure of TB control.

Regulation of polymerase exchange between Poleta and Poldelta by monoubiquitination of PCNA and the movement of DNA polymerase holoenzyme

To ensure efficient and timely replication of genomic DNA, organisms in all three kingdoms of life possess specialized translesion DNA synthesis (TLS) polymerases (Pols) that tolerate various types of DNA lesions. It has been proposed that an exchange between the replicative DNA Pol and the TLS Pol at the site of DNA damage enables lesion bypass to occur. However, to date the molecular mechanism underlying this process is not fully understood. In this study, we demonstrated in a reconstituted system that the exchange of Saccharomyces cerevisiae Poldelta with Poleta requires both the stalling of the holoenzyme and the monoubiquitination of proliferating cell nuclear antigen (PCNA). A moving Poldelta holoenzyme is refractory to the incoming Poleta. Furthermore, we showed that the Poleta C-terminal PCNA-interacting protein motif is required for the exchange process. We also demonstrated that the second exchange step to bring back Poldelta is prohibited when Lys-164 of PCNA is monoubiquitinated. Thus the removal of the ubiquitin moiety from PCNA is likely required for the reverse exchange step after the lesion bypass synthesis by Poleta.     

Polydiacetylene Nanotubes in Heterogeneous Catalysis: Application to the Gold‐Mediated Oxidation of Silanes

A layer‐by‐layer approach is used to anchor small gold nanoparticles onto organic nanotubes resulting from the self‐assembly and polymerization of diacetylene‐containing nitrilotriacetic amphiphiles. The obtained nanotube–gold hybrid is used as a catalyst for the aerobic oxidation of various silanes. With minimal gold loading (0.05 mol%), all substrates are converted into the corresponding silanols with hydrogen gas as the only by‐product. The catalyst operates under mild conditions and can be easily recycled, losing neither activity nor selectivity.