Assessment of changes in biochemical parameters associated with kidney function in patients with multiple sclerosis while taking the drug

زمینه و هدف: بیماری مولتیپل اسکلروزیس، یکی از شایع ترین بیماری های مغز و اعصاب محسوب می گردد. هدف از این مطالعه، بررسی تغییرات پارامترهای بیوشیمیایی مرتبط با عملکرد کلیه شامل اوره، اوریک اسید و کراتینین در بیماران مبتلا به ام اس در حین مصرف دارو و مقایسه آن ها با گروه کنترل است. روش بررسی: در این مطالعه، سطح سرمی اوره، اوریک اسید و کراتینین در 52 بیمار مبتلا به ام اس اندازه گیری شد و با 52 فرد سالم که از نظر سنی و جنسی و BMI با گروه بیمار هماهنگ بودند، مقایسه گردید. در نهایت داده ها با استفاده از روش تی تست، شاخص های میانگین و انحراف معیار توسط نرم افزار SPSS تحلیل شدند. یافته ها: میانگین سطح سرمی اوره در گروه بیمار و سالم به ترتیب 58/4±38/14 و 33/4±86/13 میلی گرم بر دسی لیتر مشاهده شد. میانگین غلظت اسید اوریک در گروه بیمار 99/0±66/4 و در گروه سالم 06/1±64/4 میلی گرم بر دسی لیتر و میانگین غلظت کراتینین نیز در گروه بیمار و سالم به ترتیب 10/0±85/0 و 11/0±78/0 میلی گرم بر دسی لیتر به دست آمد. نتیجه گیری: یافته های این تحقیق نشان داد که سطح سرمی اوره، اسید اوریک و کراتینین هیچ تفاوت آماری معنی داری بین گروه بیمار و کنترل نداشت

Increased expression of heme-binding protein 1 early in Alzheimer's disease is linked to neurotoxicity.

Alzheimer's disease is the most prevalent neurodegenerative disorder leading to progressive cognitive decline. Despite decades of research, understanding AD progression at the molecular level, especially at its early stages, remains elusive. Here, we identified several presymptomatic AD markers by investigating brain proteome changes over the course of neurodegeneration in a transgenic mouse model of AD (3×Tg-AD). We show that one of these markers, heme-binding protein 1 (Hebp1), is elevated in the brains of both 3×Tg-AD mice and patients affected by rapidly-progressing forms of AD. Hebp1, predominantly expressed in neurons, interacts with the mitochondrial contact site complex (MICOS) and exhibits a perimitochondrial localization. Strikingly, wildtype, but not Hebp1-deficient, neurons showed elevated cytotoxicity in response to heme-induced apoptosis. Increased survivability in Hebp1-deficient neurons is conferred by blocking the activation of the mitochondrial-associated caspase signaling pathway. Taken together, our data highlight a role of Hebp1 in progressive neuronal loss during AD progression

A genetic polymorphism in the CYP1B1 gene in patients with squamous cell carcinoma of the esophagus: an Iranian Mashhad cohort study recruited over 10 years

Background: Esophageal-cancer is the seventh most common-cause of cancer-related-deaths in men. Cytochrome-P450-family-1-subfamily-B-polypeptide-1 (CYP1B1) plays a role in the metabolism of xenobiotics, and is associated with several cancers. Here we investigated the association between a genetic-variant, CYP1B1-rs1056836, with the clinical-characteristics of patients with esophagus-squamous-cell-carcinoma (ESCC). Method: 117-patients with ESCC and 208 healthy-subjects were recruited. DNA was extracted and genotyped. Kaplan-Meier curves were utilized to assess overall and progression-free survival. The relationship between clinicopathological-data, disease-prognosis, and survival, were evaluated with the genotypes. Results: the genotypic frequency for GG, GC, and CC were 58.6%, 29.8%, 11.5% respectively in the healthy subjects and 51.8%, 36.14% and 12% in the ESCC group. An association between the GG genotype and stage of ESCC was found. Conclusion: Our findings suggest a relationship between the CYP1B1-rs1056836 genetic polymorphism and clinical features of ESCC, supporting further studies in larger-populations in different-ethnic groups, taking into account potentially important environmental-factors

Changes in lung function in European adults born between 1884 and 1996 and implications for the diagnosis of lung disease:a cross-sectional analysis of ten population-based studies

Background: During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements. Methods: In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20-94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV1, forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV1 and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV1/FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV1 and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year. Findings: Across the ten included studies, we included 243 465 European participants (mean age 51·4 years, 95% CI 51·4-51·5) in our analysis, of whom 136 275 (56·0%) were female and 107 190 (44·0%) were male. After full adjustment, FEV1 increased by 4·8 mL/birth year (95% CI 2·6-7·0; p<0·0001) and FVC increased by 8·8 mL/birth year (5·7-12·0; p<0·0001). Birth year-related increases in the FEV1 and FVC values predicted by published reference equations corroborated these findings. This height-independent increase in FEV1 and FVC across the last century will have caused mean population values to progressively exceed previously predicted values. However, the population mean adjusted FEV1/FVC ratio decreased by 0·11 per 100 birth years (95% CI 0·09-0·14; p<0·0001). Interpretation: If current diagnostic criteria remain unchanged, the identified shifts in European values will allow the easier fulfilment of diagnostic criteria for lung diseases such as chronic obstructive pulmonary disease, but the systematic underestimation of lung disease severity. Funding: The European Respiratory Society, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, and Sanofi-Genzyme

E pluribus plurima: Multidimensional indices and clinical phenotypes in COPD

as the picture of COPD becomes more complex and the results from large studies generate the need of further research, it is clear the close link between the definition of clinical phenotypes and the validation of either single or multidimensional indices

Spirometric phenotypes from early childhood to young adulthood : a Chronic Airway Disease Early Stratification study

Acknowledgements Cohort-specific acknowledgements are presented in the supplementary material. We also acknowledge collaboration with the EXPANSE consortium (funded by the EU H2020 programme, grant number 874627). We thank Elise Heuvelin, European Respiratory Society, Lausanne, Switzerland, for her assistance on the current project.Peer reviewedPublisher PD

Systematic review of the evidence relating FEV1 decline to giving up smoking

<p>Abstract</p> <p>Background</p> <p>The rate of forced expiratory volume in 1 second (FEV₁) decline ("beta") is a marker of chronic obstructive pulmonary disease risk. The reduction in beta after quitting smoking is an upper limit for the reduction achievable from switching to novel nicotine delivery products. We review available evidence to estimate this reduction and quantify the relationship of smoking to beta.</p> <p>Methods</p> <p>Studies were identified, in healthy individuals or patients with respiratory disease, that provided data on beta over at least 2 years of follow-up, separately for those who gave up smoking and other smoking groups. Publications to June 2010 were considered. Independent beta estimates were derived for four main smoking groups: never smokers, ex-smokers (before baseline), quitters (during follow-up) and continuing smokers. Unweighted and inverse variance-weighted regression analyses compared betas in the smoking groups, and in continuing smokers by amount smoked, and estimated whether beta or beta differences between smoking groups varied by age, sex and other factors.</p> <p>Results</p> <p>Forty-seven studies had relevant data, 28 for both sexes and 19 for males. Sixteen studies started before 1970. Mean follow-up was 11 years. On the basis of weighted analysis of 303 betas for the four smoking groups, never smokers had a beta 10.8 mL/yr (95% confidence interval (CI), 8.9 to 12.8) less than continuing smokers. Betas for ex-smokers were 12.4 mL/yr (95% CI, 10.1 to 14.7) less than for continuing smokers, and for quitters, 8.5 mL/yr (95% CI, 5.6 to 11.4) less. These betas were similar to that for never smokers. In continuing smokers, beta increased 0.33 mL/yr per cigarette/day. Beta differences between continuing smokers and those who gave up were greater in patients with respiratory disease or with reduced baseline lung function, but were not clearly related to age or sex.</p> <p>Conclusion</p> <p>The available data have numerous limitations, but clearly show that continuing smokers have a beta that is dose-related and over 10 mL/yr greater than in never smokers, ex-smokers or quitters. The greater decline in those with respiratory disease or reduced lung function is consistent with some smokers having a more rapid rate of FEV₁decline. These results help in designing studies comparing continuing smokers of conventional cigarettes and switchers to novel products.</p

Age-related decreased inhibitory vs. excitatory gene expression in the adult autistic brain

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