Adipose‐derived stem cells and keratinocytes in a chronic wound cell culture model: the role of hydroxyectoine

Chronic wounds represent a major socio‐economic problem in developed countries today. Wound healing is a complex biological process. It requires a well‐orchestrated interaction of mediators, resident cells and infiltrating cells. In this context, mesenchymal stem cells and keratinocytes play a crucial role in tissue regeneration. In chronic wounds these processes are disturbed and cell viability is reduced. Hydroxyectoine (HyEc) is a membrane protecting osmolyte with protein and macromolecule stabilising properties. Adipose‐derived stem cells (ASC) and keratinocytes were cultured with chronic wound fluid (CWF) and treated with HyEc. Proliferation was investigated using MTT test and migration was examined with transwell‐migration assay and scratch assay. Gene expression changes of basic fibroblast growth factor (b‐FGF), vascular endothelial growth factor (VEGF), matrix metalloproteinases‐2 (MMP‐2) and MMP‐9 were analysed by quantitative real‐time polymerase chain reaction (qRT‐PCR). CWF significantly inhibited proliferation and migration of keratinocytes. Addition of HyEc did not affect these results. Proliferation capacity of ASC was not influenced by CWF whereas migration was significantly enhanced. HyEc significantly reduced ASC migration. Expression of b‐FGF, VEGF, MMP‐2 and MMP‐9 in ASC, and b‐FGF, VEGF and MMP‐9 in keratinocytes was strongly induced by chronic wound fluid. HyEc enhanced CWF induced gene expression of VEGF in ASC and MMP‐9 in keratinocytes. CWF negatively impaired keratinocyte function, which was not influenced by HyEc. ASC migration was stimulated by CWF, whereas HyEc significantly inhibited migration of ASC. CWF induced gene expression of VEGF in ASC and MMP‐9 in keratinocytes was enhanced by HyEc, which might partly be explained by an RNA stabilising effect of HyEc.     

Effects of vitamins C and E on oxidative stress markers and endothelial function in patients with systemic lupus erythematosus: a double blind, placebo controlled pilot study

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) experience excess morbidity and mortality due to coronary artery disease (CAD) that cannot be fully explained by the classical CAD risk factors. Among emerging CAD risk factors, oxidative stress is currently being emphasized. We evaluated the effects of longterm antioxidant vitamins on markers of oxidative stress and antioxidant defense and endothelial function in 39 patients with SLE. METHODS: Patients were randomized to receive either placebo or vitamins (500 mg vitamin C and 800 IU vitamin E daily) for 12 weeks. Markers of oxidative stress included malondialdehyde (MDA) and allantoin. Antioxidants measured included erythrocyte superoxide dismutase and glutathione peroxidase, plasma total antioxidant power (as FRAP value), and ascorbic acid and vitamin E concentrations. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery and plasma concentration of von Willebrand factor (vWF) and plasminogen activator inhibitor type 1 (PAI-1). Primary outcome of the study included the change in lipid peroxidation as revealed by MDA levels. Secondary outcomes included changes in allantoin and antioxidant levels and change in endothelial function. RESULTS: After treatment, plasma ascorbic acid and alpha-tocopherol concentrations were significantly (p < 0.05) increased only in the vitamin-treated group, associated with a significant decrease (p < 0.05) in plasma MDA. Other oxidative stress markers and antioxidant levels remained unchanged in both groups. FMD and vWF and PAI-1 levels remained unchanged in both groups. CONCLUSION: Combined administration of vitamins C and E was associated with decreased lipid peroxidation, but did not affect endothelial function in patients with SLE after 3 months of therapy.     

Effects of high-intensity exercise on leptin and testosterone concentrations in well-trained males

Objective: A number of investigations have examined the effect of exercise on leptin concentrations, because leptin is associated with obesity, satiety, and reproductive function. High-intensity exercise is known to increase testosterone, an inhibitor of leptin. The objective of the study was to determine whether the leptin responses to a progressive, intermittent exercise protocol were related to serum testosterone concentrations. Most previous studies have examined leptin responses to low or moderately high exercise intensities. A second objective was to determine whether leptin responses were different than previous experiments using intermittent moderate and high-intensity exercise. Methods: Well-trained runners completed strenuous intermittent exercise consisting of treadmill running at 60, 75, 90, and 100% VO _2max and a subsequent resting control trial was also conducted. Results: There were significant increases in mean serum levels of leptin and testosterone with both quickly returning to baseline during recovery, but no relationship between the two hormones was found. After examining individual data for both hormones, it was discovered that subjects could be classified as leptin responders or nonresponders, whereas testosterone increased in all subjects. Responders had elevated serum leptin levels at baseline and exhibited increases after high-intensity exercise, whereas nonresponders did not show changes in leptin during exercise. Conclusions: Data suggest testosterone levels do not acutely affect leptin responses to exercise or 1-h of recovery. Moreover, varied leptin responses to intense exercise in comparable well-trained runners was observed and was associated with baseline leptin concentrations.     

Physician empathy and subjective evaluation of medical treatment outcome in trauma surgery patients

Objective

To analyze whether patients’ perception of their medical treatment outcome is higher among patients who experienced a higher empathy by trauma surgeons during their stay in hospital.

Methods

127 patients were surveyed six weeks after discharge from the trauma surgical general ward. Subjective evaluation of medical treatment outcome was measured with the corresponding scale from the Cologne Patient Questionnaire. Clinical empathy was assessed by using the CARE measure. The influence of physician empathy and control variables on a dichotomized index of subjective evaluation of medical treatment outcome was identified with a logistic regression.

Results

120 patients were included in the logistic regression analysis. Compared to patients with physician empathy ratings of less than 30 points, patients with ratings of 41 points or higher have a 20-fold higher probability to be in the group with a better medical treatment outcome on the CPQ-scale (α-level < .001, R² 46.9).

Conclusion

Findings emphasize the importance of a well-functioning relationship between physician and patient even in a surgical setting where the focus is mostly on the bare medical treatment.

Practice implications

Communication trainings i.e. in surgical education can be an effective way to improve the ability to show empathy with patients’ concerns.     

Schistosoma mansoni Morbidity among School-Aged Children: A SCORE Project in Kenya

Schistosomiasis control programs aim to reduce morbidity but are evaluated by infection prevalence and intensity reduction. We present baseline cross-sectional data from a nested cohort study comparing indicators of morbidity for measuring program impact. Eight hundred twenty-two schoolchildren 7–8 years of age from Nyanza Province, Kenya, contributed stool for diagnosis of Schistosoma mansoni and soil-transmitted helminths (STH) and blood smears for malaria, and were evaluated for anemia, quality of life, exercise tolerance, anthropometry, and ultrasound abnormalities. Schistosoma mansoni, STH, and malaria infection prevalence were 69%, 25%, and 8%, respectively. Only anemia and S. mansoni infection (adjusted odds ratio [aOR] = 1.70; confidence interval [CI] = 1.03–2.80), and hepatomegaly and heavy S. mansoni infection (aOR = 2.21; CI = 1.19–4.11) were associated. Though anemia and hepatomegaly appeared most useful at baseline, additional morbidity indicators may be sensitive longitudinal measures to evaluate schistosomiasis program health impact.     

IFN-γ and indoleamine 2,3-dioxygenase signaling between donor dendritic cells and T cells regulates graft versus host and graft versus leukemia activity

Allogeneic hematopoietic stem cell transplantation (HSCT) can eradicate chemorefractory leukemia through the graft-versus-leukemia (GVL) activity of donor T cells. However, the clinical success of allo-HSCT is limited by the graft-versus-host disease (GVHD) activity of donor T cells. We have reported previously that donor bone marrow precursors of plasmacytoid dendritic cells (pre-pDCs) can activate donor T cells toward T-helper 1 immune polarization in murine allogeneic HSCT. To optimize the GVL activity of these activated donor T cells and limit their graft versus host activity, we engineered the cellular constituents of an allogeneic hematopoietic stem cell graft with highly purified hematopoietic stem cells, T cells, and pre-pDCs and studied their GVL and GVHD activities in a murine model of allogeneic HSCT. Transplanted donor pre-pDCs expanded in vivo for 2 weeks after transplant, and they markedly augmented the activation and GVL activity of donor T cells while attenuating their GVHD activity, leading to an improved therapeutic index. Bidirectional signaling between donor T cells and donor pDCs with IFN-γ synthesis by donor T cells inducing indoleamine 2,3-dioxygenase synthesis by donor pDCs limited GVHD by altering the balance between donor T-reg and inflammatory T cells. Manipulating the content of donor DC precursors in allogeneic HSCT is a novel method to optimize the balance between GVL and GVHD.