TNF-α signalling and inflammation: interactions between old acquaintances

Introduction

Inflammation is a very important part of innate immunity and is regulated in many steps. One such regulating step is the cytokine network, where tumor necrosis factor α (TNF-α) plays one of the most important roles.

Methods

A PubMed and Web of Science databases search was performed for studies providing evidences on the role of TNF-α in inflammation, apoptosis, and cancer.

Results and Conclusion

This review concisely summarizes the role of this pro-inflammatory cytokine during inflammation. It is focused mainly on TNF-α intracellular signaling and its influence on the typical inflammatory features in the organism. Being one of the most important pro-inflammatory cytokines, TNF-α participates in vasodilatation and edema formation, and leukocyte adhesion to epithelium through expression of adhesion molecules; it regulates blood coagulation, contributes to oxidative stress in sites of inflammation, and indirectly induces fever. The connection between TNF-α and cancer is mentioned as well.     

RNA interference microarrays: high-throughput loss-of-function genetics in mammalian cells

RNA interference (RNAi) is a biological process in which a double-stranded RNA directs the silencing of target genes in a sequence-specific manner. Exogenously delivered or endogenously encoded double-stranded RNAs can enter the RNAi pathway and guide the suppression of transgenes and cellular genes. This technique has emerged as a powerful tool for reverse genetic studies aimed toward the elucidation of gene function in numerous biological models. Two approaches, the use of small interfering RNAs and short hairpin RNAs (shRNAs), have been developed to permit the application of RNAi technology in mammalian cells. Here we describe the use of a shRNA-based live-cell microarray that allows simple, low-cost, high-throughput screening of phenotypes caused by the silencing of specific endogenous genes. This approach is a variation of "reverse transfection" in which mammalian cells are cultured on a microarray slide spotted with different shRNAs in a transfection carrier. Individual cell clusters become transfected with a defined shRNA that directs the inhibition of a particular gene of interest, potentially producing a specific phenotype. We have validated this approach by targeting genes involved in cytokinesis and proteasome-mediated proteolysis.     

Effect of clopidogrel pretreatment on angiographic and clinical outcomes in patients undergoing primary percutaneous coronary intervention for ST-elevation acute myocardial infarction

Pretreatment with clopidogrel before elective primary percutaneous coronary intervention (PCI) has been shown to reduce ischemic complications. There are limited data about the value of clopidogrel pretreatment in the setting of PCI for ST-elevation myocardial infarction (STEMI). We aimed to examine the effect of clopidogrel preloading on angiographic and clinical outcomes in patients with STEMI who were treated with PCI. We conducted a prospective registry of all patients treated with primary PCI for STEMI from March 2003 to June 2006. Excluded were patients with cardiogenic shock. For the current analysis, patients (n = 292) were allocated into 2 groups. One group received clopidogrel loading dose before PCI (in the emergency department or coronary care unit, n = 165); the other,immediately after PCI (n = 127). TIMI myocardial perfusion (TMP) grade at the end of PCI and 30-day and 6-month clinical outcomes were assessed. Clinical characteristics were similar among the groups. However, patients pretreated with clopidogrel were more likely to receive aspirin and beta blockers before the current admission. TMP grade 3 occurred in a higher proportion of patients in the clopidogrel pretreatment group than in the no-pretreatment group (85% vs 71%, p = 0.01). Multivariate logistic regression analysis showed that clopidogrel pretreatment was associated with an odds ratio of 2.2 for TMP grade 3 (1.2 to 3.9, p = 0.01). Furthermore, the incidence of reinfarction at 30 days was lower in the pretreatment group (0% vs 3.2%, respectively, p = 0.04). In conclusion, these findings support the early use of clopidogrel in patients with STEMI who are treated with primary PCI.     

Outcomes of a type 2 diabetes education program adapted to the cultural contexts of Saudi women: A pilot study

Objective:

To explore the outcomes of a pilot intervention of a type 2 diabetes (T2D) education program, based on international standards, and adapted to the cultural and religious contexts of Saudi women.

Methods:

This study is an experiment of a pilot intervention carried out between August 2011 and January 2012 at the primary health clinics in Dammam. Women at risk of or diagnosed with T2D (N=35 including dropouts) were assigned to one of 2 groups; an intervention group participated in a pilot intervention of T2D education program, based on international standards and tailored to their cultural and religious contexts; and a usual care group received the usual care for diabetes in Saudi Arabia. Outcomes included blood glucose, body composition, 6-minute walk distance, life satisfaction, quality of life, and diabetes knowledge. The intervention group participated in a focus group of their program experience. Data analysis was based on mixed methods.

Results:

Based on 95% confidence interval comparisons, improvements were noted in blood sugar, 6-minute walk distance, quality of life, and diabetes knowledge in participants of the intervention group. They also reported improvements in lifestyle-related health behaviors after the education program.

Conclusion:

Saudi women may benefit from a T2D education program based on international standards and adapted to their cultural and religious contexts.Saudi women have a higher prevalence of obesity than men, which increases their risk of type 2 diabetes (T2D).1 The reporting of diabetes is higher in women compared to men in all provinces of Saudi Arabia.1 Diabetes education programs in Saudi Arabia do not target people at risk of diabetes with emphasis on diabetes prevention and feasible changes to lifestyle behaviors.2 Scientific evidence suggests that diabetes education programs based on international standards of lifestyle behaviors, are more effective when tailored to the cultures and religions of targeted groups.3-6 The aim of this study was to explore the outcomes of a pilot intervention of a T2D education program based on international standards and adapted to the cultural and religious contexts of Saudi women. Specifically, whether such a program can impact health outcomes (for example, physical health measures, diabetes knowledge, life satisfaction, and health-related quality of life, diabetes knowledge) in comparison with the usual care of T2D in Saudi Arabia.     

Dorsal costo-vertebral joint as a rare localization of Staphylococcus aureus sepsis

Background

Septic arthritis of the costovertebral thoracic joint is a rare site infection. We report an isolated case of septic arthritis of the 10th costo-vertebral right joint with osteitis due to Staphylococcus aureus.