Joint analysis of individual participants’ data from 17 studies on the association of the IL6 variant -174G>C with circulating glucose levels,interleukin-6 levels,and body mass index

Background. Several studies have investigated associations between the -174G>C single nucleotide polymorphism (rs1800795) of the IL6 gene and phenotypes related to type 2 diabetes mellitus (T2DM) but presented inconsistent results.

Aims. This joint analysis aimed to clarify whether IL6 -174G>C was associated with glucose and circulating interleukin-6 concentrations as well as body mass index (BMI).

Methods. Individual-level data from all studies of the IL6-T2DM consortium on Caucasian subjects with available BMI were collected. As study-specific estimates did not show heterogeneity (P>0.1), they were combined by using the inverse-variance fixed-effect model.

Results. The main analysis included 9440, 7398, 24,117, or 5659 non-diabetic and manifest T2DM subjects for fasting glucose, 2-hour glucose, BMI, or circulating interleukin-6 levels, respectively. IL6 -174 C-allele carriers had significantly lower fasting glucose (?0.091 mmol/L, P=0.014). There was no evidence for association between IL6 -174G>C and BMI or interleukin-6 levels, except in some subgroups.

Conclusions. Our data suggest that C-allele carriers of the IL6 -174G>C polymorphism have lower fasting glucose levels on average, which substantiates previous findings of decreased T2DM risk of these subjects.     

Effects of kinesiologic taping on epidermal–dermal distance,pain, edema and inflammation after experimentally induced soft tissue trauma

Abstract

Purpose: In sports medicine, the use of kinesiologic tape has recently gained popularity. Although widely used, there is no study examining the effects of kinesiologic tape on soft tissue after a contusion injury. The aim of this study was to examine the effects of kinesiologic taping on epidermal–dermal distance, edema, pain and inflammation after experimentally induced contusion injury. Methods: Twelve adult female Wistar albino rats were divided into two groups: (1) 30?min group: n?=?6, weight range: 182.0–199.4?g; and (2) 6?h group: n?=?6, weight range: 186.9–200.8?g. After soft-tissue trauma, tape was applied to the right sides of each rat. In one group, tape was applied for 30?min while 6?h in the other. To assess the epidermal–dermal distance and edematous area, tissue sections were stained with hematoxylin and eosin and examined. Tissue sections were stained with nerve growth factor (NGF) and B-cell lymphoma 2 (Bcl-2) immunohistochemically to evaluate the effect of taping on pain and inflammation respectively. Results: Epidermal–dermal distances were found to be significantly higher than controls’ in both groups (p?<?0.05). Notable decreases were seen in edematous areas in both groups (p?<?0.05). NGF and Bcl-2 immune reactivity were decreased in all tape applied sides. Conclusions: After soft-tissue trauma, it was histologically shown that kinesiologic taping increases epidermal–dermal distance, and may reduce the sensation of pain, edema and inflammation. For better, faster and comfortable tissue healing with protection of soft-tissue integrity, kinesiologic taping may be a valuable treatment after contusion injury. However, these results should be supported by clinical studies.     

A Guide to Performing Pelvic Speculum Exams: A Patient-Centered Approach to Reducing Iatrogenic Effects

Purpose: Current training in the United States for pelvic speculum examinations (PSEs) has a primary focus on the physician-centered goal of visualizing the cervix but may not inform practitioners of potential iatrogenic effects. Such oversight leaves trainees unprepared and unskilled in preventing and addressing adverse outcomes. This article incorporates a literature review into a step-by-step guide to aid the teaching of PSEs. Summary: Iatrogenic effects of PSEs may include mild discomfort, extreme pain, anxiety, psychological (re)traumatization, and sexual pain disorders. A literature-based guide is presented to identify patients at risk for adverse outcomes, set up the exam room, set up the patient, perform the exam, calm distressed patients, and avoid exam-interfering behaviors. Conclusions: Although PSEs can lead to adverse outcomes, awareness of the iatrogenic effects allows clinicians to utilize techniques to prevent or reduce negative effects. A method of incorporating techniques described in this article into teaching is provided.     

Update on reslizumab for eosinophilic asthma

The cellular uptake of oligomeric nucleic acid-based tools and drugs including small-interfering RNA (siRNA) represents a major technical hurdle for the biologic effectiveness and therapeutic success in vivo. Subsequent to cellular delivery it is crucial to direct siRNA to the cellular location where it enters the RNA interference pathway. Here the authors summarise evidence that functionally active siRNA represents a minor fraction in the order of 1% of total siRNA inside a given target cell. Exploiting possibilities of steering intracellular release or trafficking of siRNA bears the potential of substantially increasing the biological activity of siRNA. The recently described phosphorothioate stimulated cellular delivery of siRNA makes use of the caveolar system ending in the Golgi apparatus, which contrasts all other known delivery systems. Therefore, it represents an attractive alternative to study whether promoted intracellular release is related to increased target suppression and, thus, increased phenotypic biologic effectiveness.     

Drotrecogin alfa: a new approach in the treatment of severe sepsis

Severe sepsis is a common and frequently fatal condition. Evidence showing a link between the coagulation system and the inflammatory response to sepsis led to the development of drotrecogin alfa (activated) as an agent in the treatment of sepsis. This recombinant form of the natural protein, activated protein C (Xigris^TM, Eli Lilly & Co.), has been shown to significantly reduce mortality in a large randomised, controlled Phase III study involving 1690 patients. The exact mode of action of drotrecogin alfa (activated) remains uncertain, although it clearly combines anticoagulant and anti-inflammatory properties. Although associated with an increased risk of bleeding, this is usually procedure-related rather than spontaneous. Although costly, this is a drug that effectively reduces mortality rates in patients with severe sepsis.     

Antibodies as therapeutic agents: vive la renaissance!

Until recently, the concept of antibodies as in vivo therapeutics was still considered to be an exceedingly ambitious goal. However, in 2003, the situation has been completely transformed, with 14 FDA-approved monclonal antibodies (mAbs), 70 in late stage clinical (Phase II+) trials and > 1000 in preclinical development. The driving force behind this reversal in fortune has been advances in antibody engineering and the emergence of novel discovery techniques which overcame stability and immunogenicity issues that had blighted previous clinical trials of murine antibodies. For indications as diverse as inflammation, cancer and infectious disease, it is clear that unique properties of antibodies make them safe, effective and versatile therapeutics. These drugs can be used to neutralise pathogens, toxins and endogenous mediators of pathology. As cell targeting reagents, antibodies can be used to modulate cytoplasmic cascades or to ‘tag’ specific cells for complement- or effector-mediated lysis. Antibodies can also be modified to deliver toxic or modulatory payloads (small molecules, radionuclides and enzymes) and engineered to bind multiple epitopes (bispecifics) or even to have novel catalytic activity (abzymes). The modular structure of immunoglobulins and the availability of antibody fragment libraries also make it possible to produce variable-domain therapeutics (Fab, single-chain and domain antibodies). Although exhibiting less favourable kinetics in vivo, these fragments are simple to express and have an increased tissue penetration, making them especially useful as neutralising agents or in the delivery of payload. The number of approved antibodies is expected to increase arithmetically in the near term, as the platform is adopted as a valid alternative to small molecule discovery. This review provides an introduction to the antibody discovery process and discusses the past, present and future applications of therapeutic antibodies, with reference to several FDA-approved precedents.     

Vascular protectants for the treatment of atherosclerosis

AGI1067, the monosuccinic acid ester of probucol, is a phenolic antioxidant member of a novel class of agents termed vascular protectants. It has strong antioxidant properties, equipotent to those of probucol, and anti-inflammatory properties. It inhibits gene expression of vascular cell adhesion molecule-1 and monocyte chemotactic protein1 and has been effective at preventing atherosclerosis in all tested animal models. It also improved luminal dimensions of reference segments in the percutaneous coronary intervention (PCI) vessels in the CART1 clinical trial, which suggests a direct anti-atherosclerosis effect. Two important trials that test the antioxidant/anti-inflammatory hypothesis are ongoing with AGI1067: the Canadian Atherosclerosis and Restenosis Trial, which assesses its value for the reduction of both atherosclerosis progression in non-PCI vessels and post-PCI restenosis, and the Aggressive Reduction of Inflammation Stops Events trial, which is evaluating the effects of AGI1067 on hard cardiovascular outcomes.     

T1 mapping in myocarditis – headway to a new era for cardiovascular magnetic resonance

Myocarditis is a major cause of cardiac morbidity and mortality, particularly in young patients. A spectrum of challenges besets this condition, from establishing the diagnosis to effective treatment. Endomyocardial biopsy remains the diagnostic gold standard, despite its invasiveness, low diagnostic yield and a paucity of consequential management pathways. Cardiac magnetic resonance by Lake Louise criteria has contested to become the non-invasive diagnostic alternative by providing confirmation of disease. The advent of T1 mapping now allows a high diagnostic accuracy in confirmation and exclusion of disease, discrimination of stages and activity of disease. Alongside the research into the mechanisms and potential therapeutic targets, cardiac magnetic resonance confidently claims a prime role within a modern diagnostic pathway in clinically stable patients with suspected myocarditis.