Bone marrow mesenchymal stem cells undergo nemosis and induce keratinocyte wound healing utilizing the HGF/c-Met/PI3K pathway

We previously showed cell–cell contacts of human dermal fibroblasts to induce expression of the hepatocyte growth factor/scatter factor (HGF) in a process designated as nemosis. Now we report on nemosis initiation in bone marrow mesenchymal stem cells (BMSCs). Because BMSCs are being used increasingly in cell transplantation therapy we aimed to demonstrate a functional effect and benefit of BMSC nemosis for wound healing. Nemotic and monolayer cells were used to stimulate HaCaT keratinocyte migration in a scratch-wound healing assay. Both indicators of nemosis, HGF production and cyclooxygenase-2 expression, were induced in BMSC spheroids. When compared with a similar amount of cells as monolayer, nemotic cells induced keratinocyte in vitro scratch-wound healing in a concentration-dependent manner. The HGF receptor, c-Met, was rapidly phosphorylated in the nemosis-stimulated keratinocytes. Nemosis-induced in vitro scratch-wound healing was inhibited by an HGF-neutralizing antibody as well as the small molecule c-Met inhibitor, SU11274. HGF-induced in vitro scratch-wound healing was inhibited by PI3K inhibitors, wortmannin and LY294002, while LY303511, an inactive structural analogue of LY294002, had no effect. Inhibitors of the mitogen-activated protein kinases MEK/ERK1/2 (PD98059 and U0126), and p38 (SB203580) attenuated HGF-induced keratinocyte in vitro scratch-wound healing. We conclude that nemosis of BMSCs can induce keratinocyte in vitro scratch-wound healing, and that in this effect signaling via HGF/c-Met is involved.     

A modern approach to tuberculous pericarditis

The human immunodeficiency virus (HIV) epidemic has been associated with an increase in all forms of extrapulmonary tuberculosis including tuberculous pericarditis. Tuberculosis is responsible for approximately 70% of cases of large pericardial effusion and most cases of constrictive pericarditis in developing countries, where most of the world's population live. However, in industrialized countries, tuberculosis accounts for only 4% of cases of pericardial effusion and an even smaller proportion of instances of constrictive pericarditis. Tuberculous pericarditis is a dangerous disease with a mortality of 17% to 40%; constriction occurs in a similar proportion of cases after tuberculous pericardial effusion. Early diagnosis and institution of appropriate therapy are critical to prevent mortality. A definite or proven diagnosis is based on demonstration of tubercle bacilli in pericardial fluid or on histologic section of the pericardium. A probable or presumed diagnosis is based on proof of tuberculosis elsewhere in a patient with otherwise unexplained pericarditis, a lymphocytic pericardial exudate with elevated biomarkers of tuberculous infection, and/or appropriate response to a trial of antituberculosis chemotherapy. Treatment consists of 4-drug therapy (isoniazid, rifampicin, pyrazinamide, and ethambutol) for 2 months followed by 2 drugs (isoniazid and rifampicin) for 4 months regardless of HIV status. It is uncertain whether adjunctive corticosteroids are effective in reducing mortality or pericardial constriction, and their safety in HIV-infected patients has not been established conclusively. Surgical resection of the pericardium is indicated for those with calcific constrictive pericarditis or with persistent signs of constriction after a 6 to 8 week trial of antituberculosis treatment in patients with noncalcific constrictive pericarditis.     

Potential determinants of obesity among children and adolescents in Germany: results from the cross-sectional KiGGS study

Background  

Obesity among children and adolescents is a growing public health problem. The aim of the present paper is to identify potential determinants of obesity and risk groups among 3- to 17-year old children and adolescents to provide a basis for effective prevention strategies.     

Association of dietary calcium with mortality from all causes,cardiovascular disease and cancer in people with hypertension

Association between calcium intake and premature mortality in the general population has been well studied, but little is known about the association among specific populations. The authors aim to evaluate the association among people with hypertension and to provide a proper reference range of dietary calcium intake. This prospective cohort study included 8534 US adults with hypertension from National Health and Nutrition Examination Survey cycles 2003–2014. Dietary calcium intakes were self-reported and mortality status was ascertained by National Death Index records. During a median follow-up of 5.9 years, 1357 death occurred. Compared with participants of dietary calcium intake in quintile 1, participants in quintiles 2 and 4 had a 27% (HR: 0.73, 95% CI: 0.60–0.89) and a 29% lower risk (HR: 0.71, 95% CI: 0.57–0.88) of all-cause mortality respectively. The authors also observed a 34% lower risk (HR: 0.66, 95% CI: 0.45–0.97) of CVD death among participants in quintile 3 and a 37% lower risk (HR: 0.63, 95% CI: 0.40–0.99) of cancer-related death in participants in quintile 4 respectively. Restricted cubic spline (RCS) regression revealed a consistent protective effect of dietary calcium in participants with a daily intake of over 1000 mg, but a daily intake over 1200 mg fails to show further protective effect. Our findings suggest that elevated dietary calcium was associated with lower mortality risk from all-causes, cardiovascular disease (CVD) and cancer, and supplying sufficient dietary calcium intake, between 1000 and 1200 mg per day, in people with hypertension may be considered cost-effective to decrease risk of premature death.     

Lithium toxicity

We report a case of severe lithium toxicity precipitated by a thiazide diuretic and compounded by an angiotensin converting enzyme inhibitor. There was severe vasodilatation refractory to noradrenaline.