The pancreatic beta cell surface proteome

The pancreatic beta cell is responsible for maintaining normoglycaemia by secreting an appropriate amount of insulin according to blood glucose levels. The accurate sensing of the beta cell extracellular environment is therefore crucial to this endocrine function and is transmitted via its cell surface proteome. Various surface proteins that mediate or affect beta cell endocrine function have been identified, including growth factor and cytokine receptors, transporters, ion channels and proteases, attributing important roles to surface proteins in the adaptive behaviour of beta cells in response to acute and chronic environmental changes. However, the largely unknown composition of the beta cell surface proteome is likely to harbour yet more information about these mechanisms and provide novel points of therapeutic intervention and diagnostic tools. This article will provide an overview of the functional complexity of the beta cell surface proteome and selected surface proteins, outline the mechanisms by which their activity may be modulated, discuss the methods and challenges of comprehensively mapping and studying the beta cell surface proteome, and address the potential of this interesting subproteome for diagnostic and therapeutic applications in human disease.     

Subarachnoid haemorrhage WFNS grade V: is maximal treatment worthwhile?

Background

Aneurysmal subarachnoid haemorrhage (SAH) WFNS grade V is commonly known to be associated with high mortality and a very poor prognosis for survivors. Therefore, maximal invasive therapy is frequently delayed until any spontaneous improvement with or without an external ventricular drainage occurs. The aim of the study was to verify possible predictive factors and the probability of a favourable outcome in maximally treated patients.

Methods

One hundred and thirty-eight consecutive patients with WFNS grade V SAH were admitted between 03/2006 and 12/2010. Thirty-five patients died before aggressive therapy could proceed. One hundred and three patients received maximal treatment and were retrospectively evaluated. The outcome was assessed at discharge and in the follow-up with the Glasgow Outcome Scale. Univariate and multivariate linear regression models were performed to find predictors for an unfavourable outcome.

Results

Despite treatment, early mortality was 30 % (n?=?31). At discharge, the rate of both vegetative and severely disabled patients was 27 % (n?=?28). Favourable outcome at discharge was observed in 16 % (n?=?16) of cases, whereas in the follow-up it rose to 26 % (n?=?27). Multivariate full model regression identified intraventricular haematoma (IVH) and increasing age as independently predictive for poor outcome.

Conclusions

Despite treatment, initial mortality and severe disability remain high. Nevertheless, a favourable outcome was achieved in 26 % of aggressively treated patients, rendering the withdrawal of maximal therapy for WFNS grade V SAH patients unacceptable today. In cases of old patients with IVH, the indication for aggressive therapy should be put in place more carefully due to a very poor prognosis.     

Nucleotide metabolic mismatches in mammalian hearts: implications for transplantation

Introduction

Human donor organ shortages have led surgeons and scientists to explore the use of animals as alternative organ sources. Acute thrombovascular rejection (AVR) is the main hurdle in xenotransplantation. Disparities in nucleotide metabolism in the vessels of different species may contribute significantly to the microvascular component of AVR.

Methods

We evaluated the extent of nucleotide metabolism mismatch in selected organs and endothelial cells of different mammals with particular focus on the changes in activity of ecto-5’-nucleotidase (E5’N) elicited by exposure of porcine hearts or endothelial cells to human blood (ex vivo) or human plasma (in vitro).

Results

E5’N activity in the rat heart was significantly higher than in other species. We noted a significant difference (p<0.001) in E5’N activity between human and pig endothelial cell lines. Initial pig aortic endothelial E5’N activity decreased in vitro after a three-hour exposure to human and porcine plasma while remaining constant in controls. Ex vivo perfusion with fresh human blood for four hours resulted in a significant decrease of E5’N activity in both wild type and transgenic pig hearts overexpressing human decay accelerating factor (p<0.001).

Conclusions

This study provides evidence that mismatches in basal mammalian metabolic pathways and humoral immunity interact in a xenogeneic environment. Understanding the role of nucleotide metabolism and signalling in xenotransplantation may identify new targets for genetic modifications and may lead to the development of new therapies extending graft survival.     

Laminar flow reduces cases of surgical site infections in vascular patients

Introduction

Numerous strategies are employed routinely in an effort to lower rates of surgical site infections (SSIs). A laminar flow theatre environment is generally used during orthopaedic surgery to reduce rates of SSIs. Its role in vascular surgery, especially when arterial bypass grafts are used, is unknown.

Methods

A retrospective review of a prospectively maintained database was undertaken for all vascular procedures performed by a single consultant over a one-year period. Cases were performed, via random allocation, in either a laminar or non-laminar flow theatre environment. Demographic data, operative data and evidence of postoperative SSIs were noted. A separate subgroup analysis was undertaken for patients requiring an arterial bypass graft. Univariate and multivariate logistical regression was undertaken to identify significant factors associated with SSIs.

Results

Overall, 170 procedures were analysed. Presence of a groin incision, insertion of an arterial graft and a non-laminar flow theatre were shown to be predictive of SSIs in this cohort. In the subgroup receiving arterial grafts, only a non-laminar flow theatre environment was shown to be predictive of an SSI.

Conclusions

This study suggests that laminar flow may reduce incidences of SSI, especially in the subgroup of patients receiving arterial grafts.     

Population-based trends in ambulatory surgery for urinary incontinence

Introduction and hypothesis

Surgical procedures for stress urinary incontinence (SUI) have become progressively less invasive and easier to perform with the development of new technologies such as the midurethral sling. For these reasons, it seems logical to conclude that midurethral slings would supplant other surgical treatments for incontinence. The purpose of this study was to assess the impact of this technology on trends in ambulatory surgery for incontinence over the past decade.

Methods

We searched Current Procedure Terminology codes and the State Ambulatory Surgery Database from 2001 through 2009 to identify all ambulatory procedures for incontinence. Next, we calculated age-adjusted rates separately for each procedure. We then fit a multilevel model to characterize patient and regional factors associated with the preferential use of midurethral slings over alternative treatments.

Results

Midurethral slings and submucosal injections comprised >90 % of all ambulatory procedures for SUI during the time period examined. Age-adjusted rates of midurethral slings increased dramatically, from 2.36 to 9.45/10,000 population (p?<?0.001), whereas rates of submucosal injections remained relatively stable, from 1.75 to 1.41/10,000 population (p?=?0.226). Not surprisingly, older ([odds ratio (OR) 0.61; 95 % confidence interval (CI) 0.56–0.66] and more infirm patients (OR 0.60; CI 0.44–0.83) were more likely to receive submucosal injection therapy than to receive midurethral slings.

Conclusions

Rates of midurethral slings have increased significantly by fourfold. Rates of submucosal injections, however, have remained fairly stable during this time period, suggesting that sling dissemination has led to an increase in rates of incontinence procedures as opposed to replacing old technologies in the ambulatory setting.     

Kinder mit Kunstherzunterstützungssystemen im häuslichen Bereich

Introduction

Due to miniaturization of ventricular assist devices (VADs) application in children is feasible. As waiting time for a suitable organ increases worldwide, discharging children on intracorporeal VAD to enhance quality of life should be aimed for. Emphasis for discharge are on besides extensive training of the child, parents and family doctor to train emergency services (EMS) as well as school maits and teaching staff. Paramedics have to be aware of the problems that might occur and should know how to monitor a left VAD (LVAD) patient and how to handle life threatening device failure.

Methods

We report a preclinical algorithm for emergency care in children provided with an intracorporeal VAD plus our joint established training concept with local EMS staff. Main focus besides a theoretical part are hands-on training workshops and cardiac arrest simulation training (CAST) and establishing an alarm plan including local medical organization and specialists of the Children’s Hospital Zurich.

Conclusion

Specifics for treatment for children on VAD support are discussed.     

Efficacy of Crocus sativus L. on reduction of cadmium‐induced toxicity on spermatogenesis in adult rats

Cadmium is a toxic heavy metal element, which probably cause infertility by impairment in spermatogenesis. The present work aimed (i) to study the toxic effect of cadmium on spermatogenesis in rat, as well as (ii) the protective effect of Crocus sativus L. on cadmium‐intoxicated rats. Cadmium chloride was administered intraperitoneally during 16 days at intervals of 48 h between subsequent treatments. Crocus sativus L. was pre‐treated in both of control and cadmium‐injected rats. Animals were sacrificed on day 17 after the first treatment. The left cauda epididymis was removed and immediately immersed into Hank's balanced salt solution for the evaluation of sperm count and viability, and left testis was fixed in 10% formalin for histological evaluation. Following contamination with cadmium, a decrease was observed in the number and viability of cauda epididymis sperm, which were increased by Crocus sativus L. pre‐treatment (P < 0.05). In addition, cadmium decreased both cell proliferation and Johnsen Scores in the seminiferous tubules, which were reversed by Crocus sativus pre‐treatment (P < 0.05). Furthermore, cadmium‐induced decrease in the amount of free serum testosterone as well as an increase in lipid peroxidation activity in the testicular tissue was reversed by Crocus sativus L. (P < 0.05). These findings may support the concept that Crocus sativus L. can improve the cadmium toxicity on spermatogenesis.