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991.
992.
Karen A. Nunley Caterina Rosano Christopher M. Ryan J. Richard Jennings Howard J. Aizenstein Janice C. Zgibor Tina Costacou Robert M. Boudreau Rachel Miller Trevor J. Orchard Judith A. Saxton 《Diabetes care》2015,38(9):1768-1776
OBJECTIVE
The aim of this study was to investigate the presence and correlates of clinically relevant cognitive impairment in middle-aged adults with childhood-onset type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS
During 2010–2013, 97 adults diagnosed with T1D and aged <18 years (age and duration 49 ± 7 and 41 ± 6 years, respectively; 51% female) and 138 similarly aged adults without T1D (age 49 ± 7 years; 55% female) completed extensive neuropsychological testing. Biomedical data on participants with T1D were collected periodically since 1986–1988. Cognitive impairment status was based on the number of test scores ≥1.5 SD worse than demographically appropriate published norms: none, mild (only one test), or clinically relevant (two or more tests).RESULTS
The prevalence of clinically relevant cognitive impairment was five times higher among participants with than without T1D (28% vs. 5%; P < 0.0001), independent of education, age, or blood pressure. Effect sizes were large (Cohen d 0.6–0.9; P < 0.0001) for psychomotor speed and visuoconstruction tasks and were modest (d 0.3–0.6; P < 0.05) for measures of executive function. Among participants with T1D, prevalent cognitive impairment was related to 14-year average A1c >7.5% (58 mmol/mol) (odds ratio [OR] 3.0; P = 0.009), proliferative retinopathy (OR 2.8; P = 0.01), and distal symmetric polyneuropathy (OR 2.6; P = 0.03) measured 5 years earlier; higher BMI (OR 1.1; P = 0.03); and ankle-brachial index ≥1.3 (OR 4.2; P = 0.01) measured 20 years earlier, independent of education.CONCLUSIONS
Clinically relevant cognitive impairment is highly prevalent among these middle-aged adults with childhood-onset T1D. In this aging cohort, chronic hyperglycemia and prevalent microvascular disease were associated with cognitive impairment, relationships shown previously in younger populations with T1D. Two additional potentially modifiable risk factors for T1D-related cognitive impairment, vascular health and BMI, deserve further study. 相似文献993.
Low birth weight and later development of insulin resistance and biochemical/clinical features of polycystic ovary syndrome 总被引:1,自引:0,他引:1
Pandolfi C Zugaro A Lattanzio F Necozione S Barbonetti A Colangeli MS Francavilla S Francavilla F 《Metabolism: clinical and experimental》2008,57(7):999-1004
Reduced insulin sensitivity in adult life has been reported in subjects born at term small for gestational age (SGA) and in those born prematurely with very low birth weight (LBW) (<1,500 g). We assessed whether LBW (<2,500 g) young women, irrespective of whether they were born SGA or adequate for gestational age (premature AGA), exhibited a reduction in insulin sensitivity through a prospective historical design. The risk of developing biochemical and clinical features of polycystic ovary syndrome was also investigated. The study population included 35 LBW women (19 SGA [BW range, 1,000-2,400 g] and 16 premature AGA [BW range, 1,700-2,440 g]) aged 21.8 +/- 1.8 years and 35 term AGA controls, of similar age, recruited from a neonatal registry. All women underwent clinical, ultrasonographic, hormonal, and metabolic evaluations, including the composite insulin sensitivity index. Women under hormonal contraception (21.4%) were excluded from hormonal and metabolic analyses. Composite insulin sensitivity index was significantly lower in LBW women even when the 2 LBW subgroups, SGA and premature AGA, were analyzed separately (4.4 +/- 2.2 and 4.0 +/- 1.7, respectively) than in controls (6.9 +/- 4.4). The LBW women showed a significantly higher incidence proportion of irregular menses (14/35 [40%] vs 2/35 [5.7%]) and a significantly higher free androgen index (5.8 +/- 3.5 vs 3.9 +/- 3.2). They also showed a nonsignificantly higher proportion of hirsutism, acne, and polycystic ovaries. In conclusion, LBW (<2,500 g) young women, irrespective of whether they were SGA and premature AGA, exhibited a reduction in insulin sensitivity as compared with born at term AGA women. Furthermore, they exhibited an increased risk of developing clinical and biochemical features of polycystic ovary syndrome. 相似文献
994.
Boccia S Cadoni G Sayed-Tabatabaei FA Volante M Arzani D De Lauretis A Cattel C Almadori G van Duijn CM Paludetti G Ricciardi G 《Journal of cancer research and clinical oncology》2008,134(1):93-100
Purpose As risk-modifiers of alcohol and tobacco effects, metabolic genes polymorphisms were investigated as susceptibility candidates
for squamous cell carcinoma of the head and neck (SCCHN).
Methods A total of 210 cases and 245 hospital controls, age and gender matched, were genotyped for CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms. A measurement of the biological interaction among two risk factors was estimated by the attributable proportion
(AP) due to interaction and its 95% confidence interval (CI).
Results SCCHN risk was associated with high-levels of alcohol intake [OR = 3.50 (95%CI: 1.93–6.35) and OR = 6.47 (95%CI: 2.92–14.35)
for 19–30 g/day and >30 g/day, respectively], cigarette smoking [OR = 3.47 (95%CI: 1.88–6.41) and OR = 7.65 (95%CI: 4.20–13.90)
for 1–25 and >25 pack-years of smoking, respectively] and low-fruit and vegetables consumption (OR = 2.45; 95%CI: 1.53–3.92).
No differences were observed for the genotypes or haplotypes distributions among cases and controls, and no biological interaction
emerged from gene–gene and gene–environment interaction analyses. An attributable proportion (AP) due to biological interaction
of 0.65 (95%CI: 0.40–0.90) was detected for heavy drinkers with a low intake of fruit and vegetables, and an AP of 0.40 (95%CI:
0.10–0.72) resulted forever smokers with low fruit and vegetables consumption.
Conclusions Even in presence of high alcohol consumption or cigarette smoking, a high intake of fruit and vegetables might prevent the
development of around one quarter of SCCHN cases. The lack of interaction between the studied polymorphisms and the environmental
exposures suggests that chronic consumption of tobacco and alcohol overwhelm enzyme defences, irrespective of genotype. 相似文献
995.
996.
Simoncini T De Caterina R Genazzani AR 《The Journal of clinical endocrinology and metabolism》1999,84(2):815-818
Selective estrogen receptors modulators (SERMs) are a series of new compounds exerting estrogenic or anti-estrogenic effects in different tissues. 17Beta-estradiol is known to inhibit endothelial vascular cell adhesion molecule (VCAM)-1 expression. We studied the relative effects of the raloxifene analogue LY117018 and of tamoxifen on lipopolysaccharide (LPS)-induced VCAM-1 expression in cultured human saphenous vein endothelial cells (HSVEC) and on HSVEC adhesiveness towards U937 monocytoid cells. We here demonstrate a concentration-dependent inhibitory action on VCAM-1 protein expression both for 17beta-estradiol and LY117018. The action of both compounds was blocked by the pure anti-estrogen ICI 182,780. LY117018 did not antagonize 17beta-estradiol activity. On the contrary, tamoxifen had no effects of his own. Both 17beta-estradiol and LY117018 inhibited HSVEC VCAM-1 expression at the mRNA level, while tamoxifen was ineffective. Finally, 17beta-estradiol and LY117018, but not tamoxifen, inhibited HSVEC adhesiveness towards U937 monocytoid cells induced by LPS stimulation. Therefore, only some SERMs have potential anti-atherogenic actions exerted directly at the vascular level through the regulation of endothelial cell adhesion molecules expression and of endothelial-leukocyte interactions. 相似文献
997.
Petronio AS Amoroso G Limbruno U Baglini R Paterni G Pinori E Ferdeghini M Balbarini A De Caterina R Mariani M 《The American journal of cardiology》1999,84(9):1085-8, A9
To assess the effects of percutaneous transluminal coronary angioplasty on endothelin-1 (ET-1) release, we assessed ET-1 concentrations at different sites of the coronary circulation in patients submitted to elective procedures. ET-1 levels immediately downstream from the plaque and ET-1 aortocoronary gradient increased significantly after the procedure, which was related to mechanical wall stress in patients only receiving balloons, but not in those undergoing stent percutaneous transluminal coronary angioplasty. No changes were found in the coronary sinus; these results suggest ET-1 release from the plaque rather than an ischemia/reperfusion-related production from the distal myocardium. 相似文献
998.
Aims/hypothesis Although hyperinsulinaemia in Type 2 diabetes in states of insulin resistance is a risk factor for atherosclerotic vascular disease, underlying mechanisms are poorly understood. We tested the hypothesis that insulin increases monocyte-endothelial interactions, which are implicated in atherosclerosis.Methods We treated human umbilical vein endothelial cells with insulin (10–10 to 10–7 mol/l) for 0 to 24 h. To dissect potentially implicated signal transduction pathways, we treated endothelial cells with known pharmacological inhibitors of two distinct insulin signalling pathways: the phosphatidylinositol-3-kinase (PI3-kinase) inhibitor wortmannin (3×10–8 to 10–6 mol/l), involved in insulin-induced endothelial nitric oxide synthase stimulation, and the p38 mitogen-activated protein (p38MAP) kinase inhibitor SB-203580 (10–7 to 2×10–6 mol/l). We measured adhesion molecule expression by cell surface enzyme immunoassays and U937 monocytoid cell adhesion in rotational adhesion assays.Results At pathophysiological concentrations (10–9 to 10–7 mol/l), insulin concentration-dependently induced vascular cell adhesion molecule (VCAM)-1 (average increase: 1.8-fold) peaking at 16 h. By contrast, the expression of intercellular adhesion molecule-1 and E-selectin were unchanged. The effect on VCAM-1 was paralleled by increased U937 cell adhesion. In the absence of cytotoxicity, wortmannin significantly potentiated the effect of insulin alone on VCAM-1 surface expression and monocytoid cell adhesion, whereas SB-203580 (10–6 mol/l) completely abolished such effects.Conclusions/interpretation These observations indicate that insulin promotes VCAM-1 expression in endothelial cells through a p38MAP-kinase pathway, amplified by the PI3-kinase blockage. This could contribute to explaining the increased atherosclerosis occurring in subjects with hyperinsulinaemia, or in states of insulin resistance, which feature a defective PI3-kinase pathway.Abbreviations VCAM-1
vascular cell adhesion molecule-1
- ICAM-1
intercellular adhesion molecule-1
- PI3-kinase
phosphatidylinositol 3-kinase
- MAP
mitogen-activated protein
- NO
nitric oxide
- EIA
enzyme immunoassays 相似文献
999.
Menaquinone‐4 enhances osteogenic potential of human amniotic fluid mesenchymal stem cells cultured in 2D and 3D dynamic culture systems
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Domitilla Mandatori Letizia Penolazzi Caterina Pipino Pamela Di Tomo Sara Di Silvestre Natalia Di Pietro Sara Trevisani Marco Angelozzi Mariangela Ucci Roberta Piva Assunta Pandolfi 《Journal of tissue engineering and regenerative medicine》2018,12(2):447-459
Menaquinones, also known as Vitamin K2 family, regulate calcium homeostasis in a ‘bone‐vascular cross‐talk’ and recently received particular attention for their positive effect on bone formation. Given that the correlation between menaquinones and bone metabolism to date is still unclear, the objective of our study was to investigate the possible role of menaquinone‐4 (MK‐4), an isoform of the menaquinones family, in the modulation of osteogenesis. For this reason, we used a model of human amniotic fluid mesenchymal stem cells (hAFMSCs) cultured both in two‐dimensional (2D) and three‐dimensional (3D; RCCS?bioreactor) in vitro culture systems. Furthermore, to mimic the ‘bone remodelling unit’ in vitro, hAFMSCs were co‐cultured in the 3D system with human monocyte cells (hMCs) as osteoclast precursors. The results showed that in a conventional 2D culture system, hAFMSCs were responsive to the MK‐4, which significantly improved the osteogenic process through γ‐glutamyl carboxylase‐dependent pathway. The same results were obtained in the 3D dynamic system where MK‐4 treatment supported the osteoblast‐like formation promoting the extracellular bone matrix deposition and the expression of the osteogenic‐related proteins (alkaline phosphatase, osteopontin, collagen type‐1 and osteocalcin). Notably, when the hAFMSCs were co‐cultured in a 3D dynamic system with the hMCs, the presence of MK‐4 supported the cellular aggregate formation as well as the osteogenic function of hAFMSCs, but negatively affected the osteoclastogenic process. Taken together, our results demonstrate that MK‐4 supported the aggregate formation of hAFMSCs and increased the osteogenic functions. Specifically, our data could help to optimize bone regenerative medicine combining cell‐based approaches with MK‐4 treatment. 相似文献
1000.
Dondorp AM Fanello CI Hendriksen IC Gomes E Seni A Chhaganlal KD Bojang K Olaosebikan R Anunobi N Maitland K Kivaya E Agbenyega T Nguah SB Evans J Gesase S Kahabuka C Mtove G Nadjm B Deen J Mwanga-Amumpaire J Nansumba M Karema C Umulisa N Uwimana A Mokuolu OA Adedoyin OT Johnson WB Tshefu AK Onyamboko MA Sakulthaew T Ngum WP Silamut K Stepniewska K Woodrow CJ Bethell D Wills B Oneko M Peto TE von Seidlein L Day NP White NJ;AQUAMAT group 《Lancet》2010,376(9753):1647-1657