Does CA1 dopaminergic system play a role in cholestasis induced hypothermia?

ObjectiveThere is some of evidence describing that cholestasis induces hypothermia. Meanwhile, there is paucity of comprehensive data on the mechanism(s) governing this phenomenon. The present study was undertaken to determine the effect of CA1 dopaminergica system on cholestasis induced hypothermia.MethodsMale NMRI mice weighing 25–30 g, were used. Bilateral cannulae were implanted in dorsal hippocampi (CA1) for drug microinjection. Animals were randomly divided into non-operated control, sham-operated and bile duct-ligated (BDL) groups. Cholestasis was induced by means of main bile duct ligation. Body temperatures were measured before, two and four days after BDL.ResultsData indicated that, two and four days post BDL, the body temperature decreases as compared to the sham-operated animals, which indicates hypothermia. Intra-CA1 injection of different doses of sulpiride (SUL; 0.25, 0.5 and 0.75 μg/mouse), SCH23390 (SCH; 0.125, 025 and 0.5 μg/mouse), SKF38393 (SKF; 0.25, 0.5 and 1 μg/mouse) and quinpirole (QUI; 0.25, 05 and 0.75 μg/mouse) exerted no effect on body temperature in non-operated and sham operated mice, by themselves. Moreover, intra-CA1 injection of SUL, QUI or SKF blocked, whereas, SCH tended to increase BDL induced hypothermia.ConclusionsThe present data revealed that the CA1 dopaminergic system is possibly involved in the BDL induced impairment of thermoregulation.     

The prevalence of anxiety and depression among end-stage renal disease patients on hemodialysis in Saudi Arabia

Depression commonly overlaps with uremic symptoms, but anxiety is less commonly studied among renal patients. The symptoms of medical illness, along with the psychological and social stresses that often accompany a debilitating chronic disease, are thought to produce deleterious psychological consequences. We sought to determine the prevalence and predictors of anxiety and depression among Saudi dialysis patients in Makkah. A cross-sectional study of anxiety and depression among end-stage renal disease (ESRD) patients in Makkah was conducted in November 2011. The Hospital Anxiety and Depression Scale (HADS) was used to screen for anxiety and depression. Participants’ demographic data, possible stressors and past psychiatric history were obtained. All participants were Saudi ESRD patients on maintenance hemodialysis. According to HADS, 57 (21.1%) patients were probable cases of anxiety and 63 (23.3%) were probable cases of depression. Only 32 (11.3%) were diagnosed with depression or anxiety before ESRD onset. Age was a significant predictor of anxiety and depression diagnoses. Major family problems (p?=?0.001) were also a significant predictor of anxiety. Anxiety and depressive symptoms are prevalent among ESRD patients in Makkah, and anxiety can be predicted by family factors. Early detection, management and family support might improve clinical outcomes.     

Lipid metabolism in cachectic tumor‐bearing rats at different stages of tumor growth

Rates of lipogenesis and lipoprotein lipase (LPL) activity were measured in liver, adipose tissue, heart, and tumor at several stages during 10 days of palpable growth of a transplantable Leydig cell tumor in rats. This model showed the same characteristics as human cancer cachexia, including anorexia, weight loss, and muscle wasting. Comparison with pair‐fed controls showed that the rate of loss of body fat was greater than could be explained by anorexia alone.

The rate of lipogenesis tended to decrease during the later stages of tumor growth, particularly in the liver, where there was a statistically significant reduction on Days 5 and 10. This may be largely attributable to decreased availability of substrates caused by decreasing food intake and increasing glucose uptake by the tumor. There was a significant decrease in plasma glucose concentration by Day 10. In contrast, LPL activity in adipose tissue was depressed from the earliest stage of tumor growth, and this is likely to be a major cause of lipid depletion in cancer. There was no difference in adipose tissue LPL activity between the fed and postabsorptive states in the tumor‐bearing rats, indicating that the normal response to nutrient intake was impaired. Thus, treatment of cancer cachexia should concentrate on normalizing the metabolic response to nutrient ingestion.     

Cytokine expression profile in the bone‐anchored hearing system: 12‐week results from a prospective randomized,controlled study

Objective

To study the effect of implanting the percutaneous bone‐anchored hearing system (BAHS) itself and inflammation of the peri‐abutment skin warrant clarification. In this study, we aimed to acquire further insight into the immune responses related to BAHS surgery and peri‐implant skin inflammation.

Materials and Methods

During surgery and 12 weeks post‐implantation, skin biopsies were obtained. If applicable, additional biopsies were taken during cases of inflammation. The mRNA expression of IL‐1β, IL‐6, IL‐8, TNFα, IL‐17, IL‐10, TGF‐ß, MIP‐1α, MMP‐9, TIMP‐1, COL1α1, VEGF‐A, FGF‐2 TLR‐2, and TLR‐4 was quantified using qRT‐PCR.

Results

Thirty‐five patients agreed to the surgery and 12‐week biopsy. Twenty‐two patients had mRNA of sufficient quality for analysis. Ten were fitted with a BAHS using the minimally invasive Ponto surgery technique. Twelve were fitted with a BAHS using the linear incision technique with soft‐tissue preservation. Five biopsies were obtained during episodes of inflammation. The post‐implantation mRNA expression of IL‐1β (P = .002), IL‐8 (P = .003), MMP9 (P = .005), TIMP‐1 (P = .002), and COL1α1 (P < .001) was significantly up‐regulated. IL‐6 (P = .009) and FGF‐2 (P = .004) mRNA expression was significantly down‐regulated after implantation. Within patients, no difference between post‐implantation mRNA expression (at 12 weeks) and when inflammation was observed. Between patients, the expression of IL‐1β (P = .015) and IL‐17 (P = .02) was higher during cases of inflammation compared with patients who had no inflammation at 12‐week follow‐up.

Conclusions

As part of a randomized, prospective, clinical trial, the present study reports the molecular profile of selected cytokines in the soft tissue around BAHS. Within the limit of this study, the results showed that 12 weeks after BAHS implantation the gene expression of some inflammatory cytokines (IL‐8 and IL‐1β) is still relatively high compared with the baseline, steady‐state, expression. The up‐regulation of anabolic (COL1α1) and tissue‐remodeling (MMP‐9 and TIMP1) genes indicates an ongoing remodeling process after 12 weeks of implantation. The results suggest that IL‐1β, IL‐17, and TNF‐α may be interesting markers associated with inflammation.     

Feasibility of Ultrasound-Based Computational Fluid Dynamics as a Mitral Valve Regurgitation Quantification Technique: Comparison with 2-D and 3-D Proximal Isovelocity Surface Area-Based Methods

Current Doppler echocardiography quantification of mitral regurgitation (MR) severity has shortcomings. Proximal isovelocity surface area (PISA)-based methods, for example, are unable to account for the fact that ultrasound Doppler can measure only one velocity component: toward or away from the transducer. In the present study, we used ultrasound-based computational fluid dynamics (Ub-CFD) to quantify mitral regurgitation and study its advantages and disadvantages compared with 2-D and 3-D PISA methods. For Ub-CFD, patient-specific mitral valve geometry and velocity data were obtained from clinical ultrasound followed by 3-D CFD simulations at an assumed flow rate. We then obtained the average ratio of the ultrasound Doppler velocities to CFD velocities in the flow convergence region, and scaled CFD flow rate with this ratio as the final measured flow rate. We evaluated Ub-CFD, 2-D PISA and 3-D PISA with an in vitro flow loop, which featured regurgitation flow through (i) a simplified flat plate with round orifice and (ii) a 3-D printed realistic mitral valve and regurgitation orifice. The Ub-CFD and 3-D PISA methods had higher precision than the 2-D PISA method. Ub-CFD had consistent accuracy under all conditions tested, whereas 2-D PISA had the lowest overall accuracy. In vitro investigations indicated that the accuracy of 2-D and 3-D PISA depended significantly on the choice of aliasing velocity. Evaluation of these techniques was also performed for two clinical cases, and the dependency of PISA on aliasing velocity was similarly observed. Ub-CFD was robustly accurate and precise and has promise for future translation to clinical practice.     

A review of the effects of the cell environment physicochemical nanoarchitecture on stem cell commitment

Physicochemical features of a cell nanoenvironment exert important influence on stem cell behavior and include the influence of matrix elasticity and topography on differentiation processes. The presence of growth factors such as TGF-β and BMPs on these matrices provides chemical cues and thus plays vital role in directing eventual stem cell fate. Engineering of functional biomimetic scaffolds that present programmed spatio-temporal physical and chemical signals to stem cells holds great promise in stem cell therapy. Progress in this field requires tacit understanding of the mechanistic aspects of cell-environment nanointeractions, so that they can be manipulated and exploited for the design of sophisticated next generation biomaterials. In this review, we report and discuss the evolution of these processes and pathways in the context of matrix adhesion as they might relate to stemness and stem cell differentiation. Super-resolution microscopy and single-molecule methods for in vitro nano-manipulation are helping to identify and characterize the molecules and mechanics of structural transitions within stem cells and matrices. All these advances facilitate research toward understanding of stem cell niche and consequently to developing new class of biomaterials helping the “used biomaterials” for applications in tissue engineering and regenerative medicine.