Artemether: a new therapeutic strategy in experimental rheumatoid arthritis

The current research was designed to determine the effect of artemether in treatment of experimental rheumatoid arthritis. Collagen-induced arthritis was induced in Lewis rats. The intramusculary administration of artemether (ART) and intraperitoneally injection of methotrexate (MTX) were started on day 25 postimmunization and continued until final assessment on day 35. During this period, clinical examination was taken intermittently. The anticollagen type II antibody (CII Ab) and nitric oxide synthesis were measured. The paws and kness were then removed for histopathology and radiography assay.The biocompatibility of ART and MTX were assessed using fibrosarcoma cell line. Data showed that i.m. injection of ART to arthritic rats induced a significant reduction in paw edema. This beneficial effect was associated with a significant decrease in anti-CII antibody response compared with untreated rats. Histopathological assessment showed a reduced inflammatory cell infiltrate in joints of treated rats; tissue edema, and bone erosion in the paws were markedly reduced following ART therapy. Furthermore, our radiography results paralleled our histological findings. Cytotoxicity analysis of ART showed greater tolerability compared with MTX. Treatment with ART significantly diminished NO formation in treated rats compared with nontreated controls. Our data shed light on the therapeutic efficacy of artemether in experimental rheumatoid arthritis compared with a choice drug (methotrexate), and it may be offered as a second-line drug in treatment of rheumatoid arthritis.     

Co-administration of Salvia miltiorrhiza and verapamil inhibits detrimental effects of torsion/detorsion on testicular tissue in rats

Testicular torsion/detorsion is one of the important emergencies that requires fast surgical intervention. This study aimed to investigate the effects of Salvia miltiorrhiza hydroalcoholic extract combined with verapamil on testicular ischaemia/reperfusion damage in Wistar albino rats. All animals were distributed in 3 groups (n = 8), including the sham-operated group, torsion/detorsion (TD) group and torsion/detorsion + pretreatment with 200 mg/kg Salvia miltiorrhiza extract combined with 0.3 mg/kg verapamil (SMV) group. Oxidative stress biomarkers (MDA, GPx, CAT and TAC) both in plasma and testicular tissue, sperm parameters (motility, vitality, concentration and morphology) and histopathological parameters (MSTD, GECT, Johnson's score, Cosentino's score and testicular cell thickness) were assessed in all groups. Ischaemia/reperfusion significantly increased MDA and decreased GPx, CAT and TAC levels (p < .05). Pretreatment with SMV significantly increased GPx, CAT and TAC levels (p < .05). SMV group increased progressive sperm motility and vitality and reduced non-progressive motility of spermatozoon (p < .05). Testicular torsion significantly decreased all histopathological parameters compared to the sham group (p < .05). SMV pretreatment remarkably increased MSTD, GECT and Cosentino's score in comparison with the TD group (p < .05). A combination of Salvia miltiorrhiza with verapamil could reduce damages triggered by testicular torsion detorsion and improve sperm functionality parameters and oxidative stress defence systems.     

Effects of cartilage impact with and without fracture on chondrocyte viability and the release of inflammatory markers

Post‐traumatic arthritis (PTA) frequently develops after intra‐articular fracture of weight bearing joints. Loss of cartilage viability and post‐injury inflammation have both been implicated as possible contributing factors to PTA progression. To further investigate chondrocyte response to impact and fracture, we developed a blunt impact model applying 70%, 80%, or 90% surface‐to‐surface compressive strain with or without induction of an articular fracture in a cartilage explant model. Following mechanical loading, chondrocyte viability, and apoptosis were assessed. Culture media were evaluated for the release of double‐stranded DNA (dsDNA) and immunostimulatory activity via nuclear factor kappa B (NF‐κB) activity in Toll‐like receptor (TLR) ‐expressing Ramos‐Blue reporter cells. High compressive strains, with or without articular fracture, resulted in significantly reduced chondrocyte viability. Blunt impact at 70% strain induced a loss in viability over time through a combination of apoptosis and necrosis, whereas blunt impact above 80% strain caused predominantly necrosis. In the fracture model, a high level of primarily necrotic chondrocyte death occurred along the fracture edges. At sites away from the fracture, viability was not significantly different than controls. Interestingly, both dsDNA release and NF‐κB activity in Ramos‐Blue cells increased with blunt impact, but was only significantly increased in the media from fractured cores. This study indicates that the mechanism of trauma determines the type of chondrocyte death and the potential for post‐injury inflammation. (c) 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1283–1292, 2013     

Prevalence of haptic feedback in robot-mediated surgery: a systematic review of literature

With the successful uptake and inclusion of robotic systems in minimally invasive surgery and with the increasing application of robotic surgery (RS) in numerous surgical specialities worldwide, there is now a need to develop and enhance the technology further. One such improvement is the implementation and amalgamation of haptic feedback technology into RS which will permit the operating surgeon on the console to receive haptic information on the type of tissue being operated on. The main advantage of using this is to allow the operating surgeon to feel and control the amount of force applied to different tissues during surgery thus minimising the risk of tissue damage due to both the direct and indirect effects of excessive tissue force or tension being applied during RS. We performed a two-rater systematic review to identify the latest developments and potential avenues of improving technology in the application and implementation of haptic feedback technology to the operating surgeon on the console during RS. This review provides a summary of technological enhancements in RS, considering different stages of work, from proof of concept to cadaver tissue testing, surgery in animals, and finally real implementation in surgical practice. We identify that at the time of this review, while there is a unanimous agreement regarding need for haptic and tactile feedback, there are no solutions or products available that address this need. There is a scope and need for new developments in haptic augmentation for robot-mediated surgery with the aim of improving patient care and robotic surgical technology further.     

Cartilage tissue engineering using differentiated and purified induced pluripotent stem cells

The development of regenerative therapies for cartilage injury has been greatly aided by recent advances in stem cell biology. Induced pluripotent stem cells (iPSCs) have the potential to provide an abundant cell source for tissue engineering, as well as generating patient-matched in vitro models to study genetic and environmental factors in cartilage repair and osteoarthritis. However, both cell therapy and modeling approaches require a purified and uniformly differentiated cell population to predictably recapitulate the physiological characteristics of cartilage. Here, iPSCs derived from adult mouse fibroblasts were chondrogenically differentiated and purified by type II collagen (Col2)-driven green fluorescent protein (GFP) expression. Col2 and aggrecan gene expression levels were significantly up-regulated in GFP+ cells compared with GFP− cells and decreased with monolayer expansion. An in vitro cartilage defect model was used to demonstrate integrative repair by GFP+ cells seeded in agarose, supporting their potential use in cartilage therapies. In chondrogenic pellet culture, cells synthesized cartilage-specific matrix as indicated by high levels of glycosaminoglycans and type II collagen and low levels of type I and type X collagen. The feasibility of cell expansion after initial differentiation was illustrated by homogenous matrix deposition in pellets from twice-passaged GFP+ cells. Finally, atomic force microscopy analysis showed increased microscale elastic moduli associated with collagen alignment at the periphery of pellets, mimicking zonal variation in native cartilage. This study demonstrates the potential use of iPSCs for cartilage defect repair and for creating tissue models of cartilage that can be matched to specific genetic backgrounds.     

Cluster of Middle East Respiratory Syndrome Coronavirus Infections in Iran, 2014

During January 2013–August 2014, a total of 1,800 patients in Iran who had respiratory illness were tested for Middle East respiratory syndrome coronavirus. A cluster of 5 cases occurred in Kerman Province during May–July 2014, but virus transmission routes for some infections were unclear.     

2D Statistical Lung Shape Analysis Using Chest Radiographs: Modelling and Segmentation

Journal of Digital Imaging - Accurate information of the lung shape analysis and its anatomical variations is very noticeable in medical imaging. The normal variations of the lung shape can be...     

Development of mitral and tricuspid regurgitation in right ventricular apex versus right ventricular outflow tract pacing

Purpose

This study aimed at comparing the development of tricuspid and mitral regurgitation between the right ventricular outflow tract (RVOT) and right ventricular apex (RVA) pacing.

Methods

We prospectively enrolled 164 patients for permanent pacemaker implantation due to sick sinus syndrome or atrioventricular block and randomly divided them into two equal groups to receive either RVOT or RVA pacing. Patients with heart failure or valvular disease were excluded. The post-procedural echocardiographic evaluations were performed 1 year after the pre-procedural echocardiography, and the results were compared with respect to the development of mitral and tricuspid regurgitation and probable changes in the ejection fraction (EF).

Results

Age, gender, pacing mode, and baseline cardiac rhythm did not significantly differ between the RVOT and RVA pacing groups. The incidence of mitral regurgitation was significantly higher in the RVA group (p?=?0.03), but the incidence of tricuspid regurgitation was similar in both groups. There was a trend toward less tricuspid regurgitation in the RVOT group; however, it was not statistically significant. The mean EF was not significantly different between the study groups.

Conclusion

It seems that the incidence of mitral regurgitation in RVA pacing is significantly higher than that in RVOT pacing. The formation of tricuspid regurgitation needs to be discussed in the future.

Clinical trial registration number

IRCT201103146061N1     

Differential regulation of EHD3 in human and mammalian heart failure

Electrical and structural remodeling during the progression of cardiovascular disease is associated with adverse outcomes subjecting affected patients to overt heart failure (HF) and/or sudden death. Dysfunction in integral membrane protein trafficking has long been linked with maladaptive electrical remodeling. However, little is known regarding the molecular identity or function of these intracellular targeting pathways in the heart. Eps15 homology domain-containing (EHD) gene products (EHD1-4) are polypeptides linked with endosomal trafficking, membrane protein recycling, and lipid homeostasis in a wide variety of cell types. EHD3 was recently established as a critical mediator of membrane protein trafficking in the heart. Here, we investigate the potential link between EHD3 function and heart disease. Using four different HF models including ischemic rat heart, pressure overloaded mouse heart, chronic pacing-induced canine heart, and non-ischemic failing human myocardium we provide the first evidence that EHD3 levels are consistently increased in HF. Notably, the expression of the Na/Ca exchanger (NCX1), targeted by EHD3 in heart is similarly elevated in HF. Finally, we identify a molecular pathway for EHD3 regulation in heart failure downstream of reactive oxygen species and angiotensin II signaling. Together, our new data identify EHD3 as a previously unrecognized component of the cardiac remodeling pathway.