Transplantation of Placenta-Derived Mesenchymal Stem Cells in the EAE Mouse Model of MS

Stem cell-based regenerative medicine raises great hope for the treatment of multiple sclerosis (MS). Bone marrow-derived mesenchymal stem cells (BM-MSCs) are being tested in clinical trials. Bone marrow is the traditional source of human MSCs, but human term placenta appears to be an excellent alternative because of its availability, without ethical issues. In this study, the therapeutic effect of human placental MSCs (PL-MSCs) was evaluated in experimental autoimmune encephalomyelitis (EAE), the mice model of MS. EAE mice were transplanted intra-cerebrally with PL-MSCs or with the vehicle saline 5 or 10 days after first MOG injection. The mice were monitored for a month after therapy. A daily EAE score revealed a decrease in disease severity in the transplanted animals when compared to saline. Survival was significantly higher in the transplanted animals. In vitro experiments demonstrated that conditioned media from LPS-activated astrocytes stimulated PL-MSCs to express the gene TNF-α-stimulated gene/protein 6 (TSG-6). The same mRNA expression was obtained when PL-MSCs were exposed to TNF-α or IL1-β. These results demonstrate that PL-MSCs have a therapeutic effect in the EAE mice model. We assume that this effect is caused by reduction of the anti-inflammatory protein, TSG-6, of the inflammatory damage.     

Angiotensin 1-7 as Means to Prevent the Metabolic Syndrome: Lessons From the Fructose-Fed Rat Model

We studied the effects of chronic angiotensin 1-7 (Ang 1-7) treatment in an experimental model of the metabolic syndrome, i.e., rats given high-fructose/low-magnesium diet (HFrD). Rats were fed on HFrD for 24 weeks with and without Ang 1-7 (576 µg/kg/day, s.c., Alzet pumps). After 6 months, Ang 1-7–treated animals had lower body weight (−9.5%), total fat mass (detected by magnetic resonance imaging), and serum triglycerides (−51%), improved glucose tolerance, and better insulin sensitivity. Similar metabolic effects were also evident, albeit in the absence of weight loss, in rats first exposed to HFrD for 5 months and then subjected to short-term (4 weeks) treatment with Ang 1-7. Six months of Ang 1-7 treatment were associated with lower plasma renin activity (−40%) and serum aldosterone (−48%), less hepatosteatatitis, and a reduction in epididymal adipocyte volume. The marked attenuation of macrophage infiltration in white adipose tissue (WAT) was associated with reduced levels of the pP65 protein in the epididymal fat tissue, suggesting less activation of the nuclear factor-κB (NFκB) pathway in Ang 1-7–treated rats. WAT from Ang 1-7–treated rats showed reduced NADPH-stimulated superoxide production. In single muscle fibers (myofibers) harvested and grown ex vivo for 10 days, myofibers from HFrD rats gave rise to 20% less myogenic cells than the Ang 1-7–treated rats. Fully developed adipocytes were present in most HFrD myofiber cultures but entirely absent in cultures from Ang 1-7–treated rats. In summary, Ang 1-7 had an ameliorating effect on insulin resistance, hypertriglyceridemia, fatty liver, obesity, adipositis, and myogenic and adipogenic differentiation in muscle tissue in the HFrD rats.The metabolic syndrome (MetSyn) encompasses cardiometabolic risk determinants including visceral obesity, insulin resistance, glucose intolerance, dyslipidemia, nonalcoholic fatty liver disease, and hypertension (1). Ectopic fat accumulating in the liver, muscle, and pancreas may play an important role, presumably by releasing adipocytokines, which decrease sensitivity to insulin (2) and promote inflammation (3).Blockade of the renin-angiotensin system, by inhibiting the formation of angiotensin II (Ang II) with angiotensin-converting enzyme inhibitors or by angiotensin receptor blockers, yields a significant (25%) reduction in the incidence of new-onset type 2 diabetes (4). The renin-angiotensin system may also be involved in hepatic inflammation and fibrogenesis (5) and to adversely affect insulin-mediated glucose uptake in skeletal muscles (6). In cultured myofibers, Ang II was shown to induce insulin resistance via impaired insulin signaling, independent of its vascular effects (7). Skeletal muscles are lost in diabetic patients (8), possibly due to local accumulation of adipocytes that potentially replace muscle cells (9). Moreover, the skeletal muscle stem cells, satellite cells, of obese Zucker rats apparently display increased adipogenic potential (10,11). This may account, at least in part, for the inter- and intramuscular adipocyte accumulation characteristics of obesity and the MetSyn and even the sarcopenia associated with aging.Angiotensin 1-7 (Ang 1-7) opposes many of the adverse cardiovascular effects of Ang II (12), including hypertension, pregnancy-induced hypertension (preeclampsia), renal disease, heart failure, and cardiac arrhythmia (13–15). The best-studied effects of Ang 1-7 are its vasodilator, blood pressure–lowering, and antiproliferative actions in the cardiovascular system. These effects are apparently mediated through Mas, a specific G protein–coupled receptor for Ang 1-7 (16–22). Santos et al. (23) showed that Mas is expressed in the adipose tissue and that Mas-deficient mice develop a MetSyn-like state. In the current study, we evaluated the effect of long-term activation of the Mas receptor by chronic Ang 1-7 treatment on MetSyn in rats fed a high-fructose diet.     

Cellular phone use and risk of benign and malignant parotid gland tumors--a nationwide case-control study

The objective of this nationwide study was to assess the association between cellular phone use and development of parotid gland tumors (PGTs). The methods were based on the international INTERPHONE study that aimed to evaluate possible adverse effects of cellular phone use. The study included 402 benign and 58 malignant incident cases of PGTs diagnosed in Israel at age 18 years or more, in 2001-2003, and 1,266 population individually matched controls. For the entire group, no increased risk of PGTs was observed for ever having been a regular cellular phone user (odds ratio = 0.87; p = 0.3) or for any other measure of exposure investigated. However, analysis restricted to regular users or to conditions that may yield higher levels of exposure (e.g., heavy use in rural areas) showed consistently elevated risks. For ipsilateral use, the odds ratios in the highest category of cumulative number of calls and call time without use of hands-free devices were 1.58 (95% confidence interval: 1.11, 2.24) and 1.49 (95% confidence interval: 1.05, 2.13), respectively. The risk for contralateral use was not significantly different from 1. A positive dose-response trend was found for these measurements. Based on the largest number of benign PGT patients reported to date, our results suggest an association between cellular phone use and PGTs.