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Bruha R Vitek L Marecek Z Pospisilova L Nevsimalova S Martasek P Petrtyl J Urbanek P Jiraskova A Malikova I Haluzik M Ferenci P 《Journal of inherited metabolic disease》2012,35(3):541-548
Background &; Aims
Wilson disease (WD) is an inherited disorder of copper disposition caused by an ATP7B transporter gene mutation, leading to copper accumulation in predisposed tissues. In addition to a genetic predisposition, other factors are likely to contribute to its clinical manifestation. The aim of the study was to assess whether oxidative stress affects the phenotypic manifestation of WD.Methods
In 56 patients with WD (29 men; 26 with the hepatic form, 22 with the neurologic form, and eight asymptomatic; mean age 38.5?±?12 years), total serum antioxidant capacity (TAC) and inflammatory parameters (hs-CRP, IL-1??, IL-2, IL-6, IL-10, and TNF-??) were analyzed and related to the clinical manifestation, and mutations of the ATP7B gene. The control group for the TAC and inflammatory parameters consisted of 50 age- and gender-matched healthy individuals.Results
WD patients had a significantly lower TAC (p?0.00001), lower IL-10 levels (p?=?0.039), as well as both higher IL-1?? (p?=?0.019) and IL-6 (p?=?0.005) levels compared to the control subjects. TNF-??, hs-CRP, and IL-2 did not differ from the controls. Patients with the neurological form of WD had a significantly lower TAC than those with the hepatic form (p?0.001). In addition, the lower TAC was associated with the severity of the neurological symptoms (p?=?0.02). No relationship between the inflammatory parameters and clinical symptoms was found.Conclusions
Data from our study suggest that the increased oxidative stress contributes significantly to the clinical manifestation of WD; as a lower TAC is associated with the neurological symptoms in WD patients. 相似文献93.
Dubessy AL Ursu R Maillet D Augier A Le Guilloux J Carpentier AF Belin C 《Age and ageing》2012,41(2):275-277
A 75-year-old patient was evaluated for dementia. His past medical history included an ischaemic cardiomyopathy treated with aspirin daily. His neurological examination showed mild ataxia syndrome and central deafness. The neuropsychological examination did not suggest Alzheimer's disease. No specific aetiology was found from biological investigations, but MRI scans revealed a superficial siderosis, which was further confirmed with CSF exams. This case highlights the interest of MRI with echo-gradient-T2 weighted sequences in patients investigated for memory disorders. Once the diagnosis is known, specific preventive measures have to be taken: searching for a treatable source of bleeding and the interruption of antiplatelet aggregation or anticoagulant treatments. 相似文献
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Jansa P Becvar R Ambroz D Palecek T Tomcik M Skacelova S Aschermann M Linhart A 《Clinical rheumatology》2012,31(3):557-561
Background
Systemic sclerosis (SSc) is an important cause of pulmonary arterial hypertension (PAH), with an estimated prevalence of 7.85–26.7%. 相似文献96.
Nikpay M ?eda O Tremblay J Petrovich M Gaudet D Kotchen TA Cowley AW Hamet P 《Hypertension research》2012,35(6):585-591
Links between substance use habits, obesity, stress and the related cardiovascular outcomes can be, in part, because of loci with pleiotropic effects. To investigate this hypothesis, we performed genome-wide mapping in 119 multigenerational families from a population in the Saguenay-Lac-St-Jean region with a known founder effect using 58,000 single-nucleotide polymorphisms and 437 microsatellite markers to identify genetic components of the following factors: habitual alcohol, tobacco and coffee use; response to mental and physical stress; obesity-related traits; and heart rate (HR) and blood pressure (BP) measures. Habitual alcohol and/or tobacco users had attenuated HR responses to mental stress compared with non-users, whereas hypertensive individuals had stronger HR and systolic BP responses to mental stress and a higher obesity index than normotensives. Genetic mappings uncovered numerous shared genes among substance use, stress response, obesity and hemodynamic traits, including CAMK4, CNTN4, DLG2, FHIT, GRID2, ITPR2, NOVA1 and PRKCE, forming network of interacting proteins, sharing synaptic function and display higher and patterned expression profiles in brain-related tissues; moreover, pathway analysis of shared genes pointed to long-term potentiation. Subgroup genetic mappings uncovered additional shared synaptic genes, including CAMK4, CNTN5 and DNM3 (hypertension-specific); CNTN4, DNM3, FHIT and ITPR1 (sex-specific), having protein interactions with genes driven from general analysis. In summary, consistent with the observed phenotypic correlations, we found substantial overlap among genomic determinants of these traits in synapse, which supports the notion that the neural synapse may be a shared interface behind substance use, stress, obesity, HR, BP as well as the observed sex- and hypertension-specific genetic differences. 相似文献
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