Cell-Based Therapy for the Deficient Urinary Sphincter

When sterile culture techniques of mammalian cells first became state of the art, there was tremendous anticipation that such cells could be eventually applied for therapeutic purposes. The discovery of adult human stem or progenitor cells further motivated scientists to pursue research in cell-based therapies. Although evidence from animal studies suggests that application of cells yields measurable benefits, in urology and many other disciplines, progenitor-cell-based therapies are not yet routinely clinically available. Stress urinary incontinence (SUI) is a condition affecting a large number of patients. The etiology of SUI includes, but is not limited to, degeneration of the urinary sphincter muscle tissue and loss of innervation, as well as anatomical and biomechanical causes. Therefore, different regimens were developed to treat SUI. However, at present, a curative functional treatment is not at hand. A progenitor-cell-based therapy that can tackle the etiology of incontinence, rather than the consequences, is a promising strategy. Therefore, several research teams have intensified their efforts to develop such a therapy for incontinence. Here, we introduce candidate stem and progenitor cells suitable for SUI treatment, show how the functional homogeneity and state of maturity of differentiated cells crucial for proper tissue integration can be assessed electrophysiologically prior to their clinical application, and discuss the trophic potential of adult mesenchymal stromal (or stem) cells in regeneration of neuronal function.     

Excluding infections in arthroplasty using leucocyte esterase test

Purpose

Periprosthetic joint infections remain a major challenge for the surgeon in modern arthroplasty. The decision on how to handle a case is often difficult due to the variety of clinical presentations. The aim of this study was to establish the leucocyte esterase test as an intra-operative rapid diagnostic tool in an unclear infected or aseptic situation.

Methods

In the setting of 364 endoprosthetic joint procedures on knee, hip and shoulder, we aspirated synovial fluid before performing capsulotomy. We performed a leucocyte esterase test. The results were correlated with the pre-operative synovial fluid aspirations, the laboratory blood sample parameters (C-reactive protein, white blood cells) and the intra-operative histopathological and microbiological findings.

Results

The leucocyte esterase test has a sensitivity of 100 % and a specificity of 96.5 %. The positive predictive value was 82 % and the negative predictive value was 100 %. Correlation with conventional methods such as serum C-reactive protein and serum white blood cells is given. The histopathological evaluation confirmed the microbiological results in all but three cases.

Conclusions

Based on our results and the current literature, we recommend the leucocyte esterase test as a useful tool in the diagnosis of periprosthetic joint infection.     

The role of mechanotransduction in heart failure pathobiology—a concise review

Heart Failure Reviews - This review evaluates the role of mechanotransduction (MT) in heart failure (HF) pathobiology. Cardiac functional and structural modifications are regulated by biomechanical...     

Insulin Regulates the Unfolded Protein Response in Human Adipose Tissue

Endoplasmic reticulum (ER) stress is increased in obesity and is postulated to be a major contributor to many obesity-related pathologies. Little is known about what causes ER stress in obese people. Here, we show that insulin upregulated the unfolded protein response (UPR), an adaptive reaction to ER stress, in vitro in 3T3-L1 adipocytes and in vivo, in subcutaneous (sc) adipose tissue of nondiabetic subjects, where it increased the UPR dose dependently over the entire physiologic insulin range (from ∼35 to ∼1,450 pmol/L). The insulin-induced UPR was not due to increased glucose uptake/metabolism and oxidative stress. It was associated, however, with increased protein synthesis, with accumulation of ubiquitination associated proteins, and with multiple posttranslational protein modifications (acetylations, methylations, nitrosylations, succinylation, and ubiquitinations), some of which are potential causes for ER stress. These results reveal a new physiologic role of insulin and provide a putative mechanism for the development of ER stress in obesity. They may also have clinical and therapeutic implications, e.g., in diabetic patients treated with high doses of insulin.