Ubiquitin-proteasomal degradation of COX-2 in TGF-β stimulated human endometrial cells is mediated through endoplasmic reticulum mannosidase I

Cyclooxygenase (COX)-2 is a key regulatory enzyme in the production of prostaglandins (PG) during various physiological processes. Mechanisms of COX-2 regulation in human endometrial stromal cells (human endometrial stromal cells) are not fully understood. In this study, we investigate the role of TGF-β in the regulation of COX-2 in human uterine stromal cells. Each TGF-β isoform decreases COX-2 protein level in human uterine stromal cells in Smad2/3-dependent manner. The decrease in COX-2 is accompanied by a decrease in PG synthesis. Knockdown of Smad4 using specific small interfering RNA prevents the decrease in COX-2 protein, confirming that Smad pathway is implicated in the regulation of COX-2 expression in human endometrial stromal cells. Pretreatment with 26S proteasome inhibitor, MG132, significantly restores COX-2 protein and PG synthesis, indicating that COX-2 undergoes proteasomal degradation in the presence of TGF-β. In addition, each TGF-β isoform up-regulates endoplasmic reticulum (ER)-mannosidase I (ERManI) implying that COX-2 degradation is mediated through ER-associated degradation pathway in these cells. Furthermore, inhibition of ERManI activity using the mannosidase inhibitor (kifunensine), or small interfering RNA-mediated knockdown of ERManI, prevents TGF-β-induced COX-2 degradation. Taken together, these studies suggest that TGF-β promotes COX-2 degradation in a Smad-dependent manner by up-regulating the expression of ERManI and thereby enhancing ER-associated degradation and proteasomal degradation pathways.     

A study of clinical presentation and delays in management of acute myocardial infarction in community

To assess the medico social demographics of acute myocardial infarction (AMI) in our community we studied 609 patients presenting between January 2008 to December 2008 with a detailed questionnaire in four centres of UP. Medical attention was sought late (> 6 hours) in 316 (51.6%), thrombolysis was obtained in 45.2% (275) and presentation was atypical in 16.3% (99). 36.2% (221) had pre-monitory symptoms of which 68% (150) ignored the same while of 32% (71) who did seek medical attention 47.9% (37) were brushed away as non-cardiac in origin. 20.3% (46/226) of hypertension, 23.2% (43/185) of diabetes and 83.4% (91/109) of hyperlipidaemia was diagnosed post event. We conclude that at least half of patients with AMI do not get definitive therapy, at least one in 10 patients do not have the classical symptoms, reasonable proportion are unaware of their risk factors, and a good majority have pre-monitory symptoms which get overlooked.     

Atrial fibrillation in a tertiary care institute – A prospective study

ObjectiveAtrial fibrillation is the commonest sustained arrhythmia. In western countries the common causes of atrial fibrillation are hypertensive heart disease, dilated cardiomyopathy, and coronary heart disease. Rheumatic heart disease being still common in India, we studied its contribution to atrial fibrillation.Material and methods137 consecutive patients of atrial fibrillation coming to our hospital were subjected to echocardiography to determine the cause.ResultsOut of 137 patients with atrial fibrillation, 76 were female (55.47%) and 61 were male (44.43%). Mean age was 51.24 ± 15.36 years. Commonest cause of AF was rheumatic heart disease found in 84 (61.31%) patients. Next common causes were hypertensive heart disease in 14 (10.2%) patients and chronic obstructive pulmonary disease (COPD) in 14 (10.2%) patients. Mean left atrial size was 47.8 ± 12.25 mm.ConclusionIn our study of patients coming from a rural back ground of North India, more than 60% patients of AF are due to RHD. Hypertensive heart disease and COPD are the next common causes.     

Bleeding-avoidance strategies and outcomes in patients ≥80 years of age with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (from the NCDR CathPCI Registry)

The purpose of our study was to evaluate the use of bleeding-avoidance strategies (BAS) and risk-adjusted bleeding over time in patients ≥80 years of age undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction. We analyzed data from the CathPCI Registry from July 1, 2006 through June 30, 2009. Patients were included if they were ≥80 years old, presented with ST-segment elevation myocardial infarction, and underwent primary PCI. We evaluated trends in use of BAS (direct thrombin inhibitors, vascular closure devices, and radial access) and risk-adjusted bleeding over time. Of 10,469 patients ≥80 years old undergoing primary PCI, 1,002, (9.6%) developed a bleeding complication. Use of direct thrombin inhibitors and vascular closure devices increased over time (12.8% to 24.9% and 29.2% to 32.7%, p <0.01 and <0.05 for trends, respectively). Radial access was extremely uncommon (<1%) and did not change over the course of the study. In multivariable analyses, use of BAS was associated with lower bleeding. However, over the course of the study period, overall risk-adjusted bleeding did not decrease significantly (9.9% to 9.4%, p = 0.14 for trend). In conclusion, patients ≥80 years old undergoing primary PCI are at high risk of bleeding, and despite significant increases in use of BAS, the overall rate of bleeding complications remains high.     

Assessment of dental anxiety and its correlation with denture satisfaction in edentulous patients

Objective: The objectives of this study were to measure the level of dental anxiety and its correlation with dental history, denture satisfaction and other variables. Materials and methods: A cross-sectional study was conducted on 150 completely edentulous patients reporting to the Department of Prosthodontics, KLES's Institute of Dental Sciences, Belgaum, over a period of 17 months (August 2005 to March 2007). The anxiety level of the patients was assessed with the help of a questionnaire, after obtaining an informed consent. Reliability of the dental anxiety scale was assessed by means of coefficient alpha. Results: The results of this study concluded that dental anxiety scale for edentulous patients was a reliable scale for measuring dental anxiety. The anxiety score was higher for female than male patients. A significant correlation was found between denture satisfaction score and anxiety. Discussion: Anxiety plays a major role in denture satisfaction. The variables included: Previous denture experience, occupation, medical history, age, gender, dental anxiety scale, period of edentulousness, age of previous dentures, number of complete dentures, denture satisfaction score, and the score on the Hamilton anxiety scale Conclusion: The study indicated that gender correlates significantly with dental anxiety. Patients with medical history were found to be more anxious than normal patients. Patients with higher anxiety values were less satisfied with the treatment. Lastly, subjects with higher general anxiety showed greater values on the dental anxiety scale. Clinical significance: The assessment of dental anxiety will help the prosthodontist in the management of anxious patients and secondly to provide evidence-based research into this psychological construct which has been shown to predict dental avoidance. Keywords: Dental anxiety, Denture satisfaction, Completely edentulous patients. How to cite this article: Shrivastava R, Srivastava R, Shigli K, Prashanth MB, Kumaraswamy BN, Nethravathi TD. Assessment of Dental Anxiety and its Correlation with Denture Satisfaction in Edentulous Patients. J Contemp Dent Pract 2012;13(3):257-260. Source of support: Nil Conflict of interest: None declared.