Determination of Mesenchymal Stem Cell Fate by Pigment Epithelium-Derived Factor (PEDF) Results in Increased Adiposity and Reduced Bone Mineral Content.

Determination of mesenchymal stem cell fate by pigment epithelium-derived factor (PEDF) results in increased adiposity and reduced bone mineral content.

FASEB J. 2013 Jul 25;
Gattu AK, Swenson ES, Iwakiri Y, Samuel VT, Troiano N, Berry R, Church CD, Rodeheffer MS, Carpenter TO, Chung C

Pigment epithelium-derived factor (PEDF), the protein product of the SERPINF1 gene, has been linked to distinct diseases involving adipose or bone tissue, the metabolic syndrome, and osteogenesis imperfecta (OI) type VI. Since mesenchymal stem cell (MSC) differentiation into adipocytes vs. osteoblasts can be regulated by specific factors, PEDF-directed dependency of murine and human MSCs was assessed. PEDF inhibited adipogenesis and promoted osteoblast differentiation of murine MSCs, osteoblast precursors, and human MSCs. Blockade of adipogenesis by PEDF suppressed peroxisome proliferator-activated receptor-? (PPAR?), adiponectin, and other adipocyte markers by nearly 90% compared with control-treated cells (P<0.001). Differentiation to osteoblasts by PEDF resulted in a common pathway that involved PPAR? suppression (P<0.01). Canonical Wnt-?-catenin signaling results in a MSC differentiation pattern analogous to that seen with PEDF. Thus, adding PEDF enhanced Wnt-?-catenin signal transduction in human MSCs, demonstrating a novel Wnt agonist function. In PEDF knockout (KO) mice, total body adiposity was increased by >50% compared with controls, illustrating its systemic role as a negative regulator of adipogenesis. Bones from KO mice demonstrated a reduction in mineral content recapitulating the OI type VI phenotype. These results demonstrate that the human diseases associated with PEDF reflect its ability to modulate MSC differentiation.-Gattu, A. K., Swenson, E. S., Iwakiri, Y., Samuel, V. T., Troiano, N., Berry, R., Church, C. D., Rodeheffer, M. S., Carpenter, T. O., Chung, C. Determination of mesenchymal stem cell fate by pigment epithelium-derived factor (PEDF) results in increased adiposity and reduced bone mineral content. HubMed – rehab

[Ethnoterritorial heterogeneity of alcohol dependence formation in the native population of Siberia.]

Zh Nevrol Psikhiatr Im S S Korsakova. 2013; 113(6 Vypusk 2 Alkogolizm): 9-13
Bokhan NA, Mandel’ AI, Peshkovskaia AG, Badyrgy IO, Aslanbekova NV

Clinical-dynamic parameters of heterogeneity of alcohol dependence in 155 tuvinian and russian patients with lucid and psychotic forms of the disease have been studied. A highly progressive form of alcoholism with late onset of systematic consumption of alcohol has been identified in tuvinians as compared with russians. The formation of withdrawal syndrome occurs at later age than in russians (37.7 and 29.6 years; p=0.00004), but its development is more rapid – in average 2-2.5 years of systematic alcohol consumption. Psychotic forms of alcoholism are more frequent in tuvinians with the earlier onset of systematic consumption of alcohol and manifestation of basic disease syndromes (by 7 and 5 years, respectively) than in those with lucid alcoholism. In conclusion, treatment and rehabilitation of patients of different ethnic groups should be based on clinical and social features of the disease. HubMed – rehab

Thiamine, Cobalamin, Locally Injected Alone or Combination for Herpetic Itching: A Single-Center Randomized Controlled Trial.

Clin J Pain. 2013 Jul 24;
Xu G, Lv ZW, Xu GX, Tang WZ

The present study was designed to explore the efficacy of locally injected thiamine or cobalamin in relieving itch or pain and improving the daily living activities among patients with herpetic itching.Eighty eligible patients with herpetic itching with a worst itching score of ?4 were randomized to receive locally injected thiamine (B1 group), cobalamin (B12 group), lidocaine (LD group), or combination of thiamine and cobalamin (COB group) for 4 weeks. The treatment efficacy was assessed based on the patients’ pruritus and pain severity, global impression of change, and activities of daily living and quality of life.After 7 days, thiamine yielded a significant itch relief, cobalamin yielded a significant pain relief, and their combination significantly relieved both pain and itch; which all continued till the endpoint (all Ps<0.001). However, lidocaine did not provide significant itch or pain relief than the other groups. Sixteen patients in the thiamine group achieved ?30% itch reduction; 18 patients in the cobalamin group obtained ?30% pain reduction; and 18 patients achieved ?30% itch reduction and 19 patients obtained ?30% pain reduction in the combination group. The activities of daily living and quality of life data at the endpoint were consistent with a significant benefit in the thiamine (P<0.05), cobalamin, and combination groups (both Ps<0.001).Locally injected thiamine had a significant antipruritic effect, cobalamin had an analgesic effect, and their combination had the dual effect with no obvious synergies. This intervention was efficacious, tolerable, and safe for herpetic itching. HubMed – rehab

Less Efficacious Conditioned Pain Modulation and Sensory Hypersensitivity in Chronic Whiplash-associated Disorders in Singapore.

Clin J Pain. 2013 Jul 24;
Ng TS, Pedler A, Vicenzino B, Sterling M

Cultural differences in pain perception exist. Although chronic whiplash-associated disorder (WAD) is well investigated in western countries, little is known about its presentation in Singapore. We studied the neck motion and pain sensitivity in people with chronic WAD in Singapore.Thirty chronic WAD participants [>3 mo, Neck Disability Index: 40% (SD 17%)] were age, sex, and ethnicity matched with 30 pain-free controls. All 60 participants underwent the following tests: active neck motion, pain thresholds [pressure, brachial plexus provocation test (BPPT), cold], cold pain tolerance, and conditioned pain modulation (CPM). The test stimulus of contact heat and conditioning stimulus of cold water immersion was used to assess CPM. Data were evaluated to determine differences between WAD and control groups.Active neck motion (F1,29=80.02), pain thresholds of blunt pressure (F1,29=20.84), BPPT (F1,29=54.56), and cold (Z=-4.31) were significantly lower in participants with WAD (P<0.0001). Cold pressor pain tolerance was significantly lower in participants with WAD (Z=-2.89, P=0.02). A less efficacious CPM was also demonstrated in participants with WAD (F1,29=9.20, P=0.03). A combination of BPPT and cold hyperalgesia best predicted the WAD group (sensitivity=96.7%, specificity=96.7%).These findings of sensory hypersensitivity and decreased neck motion in Singaporeans with chronic WAD are consistent with physical impairments reported in western populations. HubMed – rehab

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