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Mangialardi G Oikawa A Reni C Madeddu P 《Endocrine, metabolic & immune disorders drug targets》2012,12(2):159-167
Diabetes mellitus is considered a cardiovascular disease owing to its prevalent association with cardiovascular morbidity and mortality. Cardiovascular events are not only more frequent but also complicated with more severe outcomes in diabetic patients as compared with non-diabetic patients. One mechanism accounting for this difference consists of the impairment of the regenerative cellular machinery, which contributes to tissue healing. Recent evidence indicates the contribution of resident progenitor cells in post-ischemic tissue remodeling. In addition, a wide spectrum of cells from distant sources, including the bone marrow, is attracted and home to the healing tissue. Diabetes affects the process of mobilization and recruitment as well as intrinsic functional properties of bone marrow-derived progenitor cells. This review highlights current evidence for diabetes-induced damage of bone marrow hematopoietic progenitor cells in the endosteal and vascular niches. 相似文献
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Objective
To investigate the association between serum levels of 25-hydroxyvitamin D and the occurrence of simultaneous fractures of the upper limb in older women who sustain a fall-related fracture of the hip.Study design
Cross-sectional study.Main outcome measures
We investigated 472 of 480 white women consecutively admitted to a rehabilitation hospital because of a fall-related hip fracture. Twenty-seven (5.7%) of the 472 women sustained a concomitant upper-limb fracture of either distal radius (20 women) or proximal humerus (seven women). We assessed serum levels of 25-hydroxyvitamin D 14.2 ± 4.1 (mean ± SD) days after surgical repair of the hip fracture in the 472 women by an immunoenzymatic assay.Results
Twenty-five-hydroxyvitamin D levels were significantly lower in the 27 women with concomitant fractures of both hip and upper limb than in the remaining 445 hip-fracture women: mean ± SD values were 6.5 ± 5.0 ng/ml and 11.7 ± 10.4 ng/ml respectively in the two groups (mean difference between groups 5.2 ng/ml: 95% CI 1.2–9.2; p = 0.011). Low levels of 25-hydroxyvitaimn D were significantly associated with concomitant fractures of the upper limb (p = 0.017), after adjustment for eight potential confounders including age, height, weight, hip-fracture type, cognitive impairment, neurologic impairment, previous hip fracture, and previous upper-limb fracture.Conclusions
Low levels of 25-hydroxyvitamin D were significantly associated with concomitant upper-limb fractures in our sample of older women with a fall-related fracture of the hip. Preventing vitamin D deficiency may lower the incidence of simultaneous fractures due to a singe fall in elderly women. 相似文献75.
Kuylenstierna C Björkström NK Andersson SK Sahlström P Bosnjak L Paquin-Proulx D Malmberg KJ Ljunggren HG Moll M Sandberg JK 《European journal of immunology》2011,41(7):1913-1923
Invariant NKT cells are important in the activation and regulation of immune responses. They can also function as CD1d-restricted killer cells. However, the role of activating innate NK-cell receptors expressed on NKT cells in triggering cytolytic function is poorly characterized. Here, we initially confirmed that the cellular stress-ligand receptor NKG2D is expressed on CD4- NKT cells, whereas most CD4+ NKT cells lack this receptor. Interestingly, NKG2D+ NKT cells frequently expressed perforin, and both NKG2D and perforin localized at the site of contact with NKG2D ligand-expressing target cells. CD4- NKT cells degranulated in response to NKG2D engagement in a redirected activation assay independent of stimulation via their invariant TCR. NKT cells killed P815 cells coated with anti-NKG2D mAb and CD1d-negative K562 tumor target cells in an NKG2D-dependent manner. Furthermore, NKG2D engagement co-stimulated TCR-mediated NKT-cell activation in response to endogenous CD1d-presented ligands or suboptimal levels of anti-CD3 triggering. These data indicate that the CD4- subset of human NKT cells can mediate direct lysis of target cells via NKG2D engagement independent of CD1d, and that NKG2D also functions as a co-stimulatory receptor in these cells. NKG2D thus plays both a direct and a co-stimulatory role in the activation of NKT cells. 相似文献
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Campa D Hüsing A Chang-Claude J Dostal L Boeing H Kröger J Tjønneland A Roswall N Overvad K Dahm CC Rodríguez L Sala N Pérez MJ Larrañaga N Chirlaque MD Ardanaz E Khaw KT Wareham N Allen NE Travis RC Trichopoulou A Naska A Bamia C Palli D Sieri S Tumino R Sacerdote C van Kranen HJ Bas Bueno-de-Mesquita H Stattin P Johansson M Chajes V Rinaldi S Romieu I Siddiq A Norat T Riboli E Kaaks R Canzian F 《European journal of cancer (Oxford, England : 1990)》2011,47(3):420-427
A western lifestyle, characterised by low rates of energy expenditure and a high-energy diet rich in animal protein, saturated fats and refined carbohydrates, is associated with high incidence of prostate cancer in men. A high-energy nutritional status results in insulin/IGF signalling in cells, which in turn stimulates synthesis of fatty acids. We investigated whether the genetic variability of the genes belonging to the fatty acid synthesis pathway is related to prostate cancer risk in 815 prostate cancer cases and 1266 controls from the European Prospective Investigation on Cancer (EPIC). Using a tagging approach and selecting 252 SNPs in 22 genes, we covered all the common genetic variation of this pathway. None of the SNPs reached statistical significance after adjusting for multiple comparisons. Common SNPs in the fatty acid synthase pathway are not major contributors to prostate cancer risk. 相似文献
78.
Tepongning RN Lucantoni L Nasuti CC Dori GU Yerbanga SR Lupidi G Marini C Rossi G Esposito F Habluetzel A 《Journal of ethnopharmacology》2011,137(1):743-751
Ethnopharmacological relevance
The decoction of the combined stem barks of Khaya ivorensis A. Chev. (Meliaceae) and Alstonia boonei De Wild (Apocynaceae) has a history of use in traditional medicine of central Cameroon for malaria treatment but also for the prevention of the disease.Aim of the study
The purpose of this investigation was to determine the antiplasmodial activity of Khaya ivorensis (K) and Alstonia boonei (A) preparations in the murine malaria model Plasmodium berghei/Anopheles stephensi, to estimate their prophylactic potential and to assess acute and sub-acute toxicity of the formulations prepared according to the traditional recipes.Materials and methods
Aqueous extracts from the stem-bark of the two plants were prepared and tested separately and in combination. BALB/c mice were treated for 9 days and challenged on day 3 by exposure to mosquitoes infected with Plasmodium berghei. Treatment doses ranged between 200 and 400 mg/kg/day, corresponding approximately to the dosage applied by traditional healers to cure malaria patients or prevent the disease. Parasitemia reduction in treated animals was calculated from Giemsa smear counts, of two replicate experiments. To estimate acute toxicity in terms of median lethal dose (LD50), geometrically increasing doses were administered to mice. Sub-acute toxicity of the herbal combination (KA) was investigated by administering the same doses as in the antiplasmodial activity test for a period of 14 days, followed by 14 days of recovery observation. Locomotor activity (Open Field Test), body weight, liver and kidney morphology were monitored.Results
The combination KA was found to exhibit antiplasmodial activity in the murine malaria model. In mice treated with the combination remedy at a dosage of 200 mg/kg/day, parasitemia values of 6.2% ± 1.7 and 6.5% ± 0.8 were recorded, compared to 10.8% ± 1.3 and 12.0% ± 4.0 in controls (p < 0.01). Doubling the dosage of the extracts did not significantly increase parasite suppression. When extracts of K and A were administered separately at a dosage of 400 mg/kg, a reduction in parasitemia was still obtained, but it did not reach statistical significance. Toxicity studies yielded comforting results: the LD50 was estimated to be greater than 2779.5 mg/kg. Moreover, mice exposed to the fourteen-day repeated-dose toxicity test (sub-acute toxicity test) did not display weight loss, liver or kidney morphological modifications, significant alterations in locomotor activity or any other sign of illness.Conclusion
The antiplasmodial activity and the wide dose interval between the therapeutic dosage and the toxic dosage exhibited by the KA herbal combination in the murine malaria model argue in favor of its use as an antimalarial prophylactic remedy. It remains to be demonstrated by human clinical trials whether the combination remedy, when taken by inhabitants during malaria transmission season, can reduce parasite density and lead to a reduction of malaria episodes in the community. 相似文献79.
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