15 research outputs found

    Alterations to cerebral perfusion, metabolite profiles, and neuronal morphology in the hippocampus and cortex of male and female mice during chronic exposure to a high-salt diet

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    Excess dietary salt reduces resting cerebral blood flow (CBF) and vascular reactivity, which can limit the fueling of neuronal metabolism. It is hitherto unknown whether metabolic derangements induced by high-salt-diet (HSD) exposure during adulthood are reversed by reducing salt intake. In this study, male and female mice were fed an HSD from 9 to 16 months of age, followed by a normal-salt diet (ND) thereafter until 23 months of age. Controls were continuously fed either ND or HSD. CBF and metabolite profiles were determined longitudinally by arterial spin labeling magnetic resonance imaging and magnetic resonance spectroscopy, respectively. HSD reduced cortical and hippocampal CBF, which recovered after dietary salt normalization, and affected hippocampal but not cortical metabolite profiles. Compared to ND, HSD increased hippocampal glutamine and phosphocreatine levels and decreased creatine and choline levels. Dietary reversal only allowed recovery of glutamine levels. Histology analyses revealed that HSD reduced the dendritic arborization and spine density of cortical and hippocampal neurons, which were not recovered after dietary salt normalization. We conclude that sustained HSD exposure throughout adulthood causes permanent structural and metabolic alterations to the mouse brain that are not fully normalized by lowering dietary salt during aging

    Association between Immunofluorescence Pattern and Mucosal Involvement in Patients with Bullous Pemphigoid

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    Bullous pemphigoid is an acquired autoimmune subepidermal blistering disease which is associated with mucocutaneous lesions. The type and amount of autoantibody deposition may have a role in mucosal lesions. We studied the association between mucosal involvement and direct immunofluorescence pattern in cutaneous lesions of patients with bullous pemphigoid. In this retrospective analytical cross-sectional study, we studied the demographic data, clinical presentations, and immunopathological findings of 69 patients with bullous pemphigoid admitted to our hospital 2008-2016. Patients were allocated into two groups on the basis of the mucosal involvement, and direct immunofluorescence patterns were evaluated. The data were analyzed using SPSS version18. The mean age of patients was 70.9±14.97 (mean ± Standard Deviation) years old. In our study, 56.5% of patients were women. All patients showed deposition of IgG and C3 in the dermoepidermal junction, with different severity. Patients with mucosal involvement (40.6% of cases) had a more prominent deposition of IgG, IgA, and C3 at the dermoepidermal junction compared with patients without mucosal involvement, which represented a statistically significant difference (P&lt;0.05). Logistic regression analysis showed that lower age, IgA, and C3 deposition (P&lt;0.05) were associated with mucosal involvement. Deposition of IgA and C3 (in addition to IgG) at the dermoepidermal junction seems to be a marker of mucosal involvement in patients with bullous pemphigoid. Attention to direct immunofluorescence pattern in patients with bullous pemphigoid may be helpful in prediction of mucosal involvement in these patients. </p

    Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

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    Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

    EFFECT OF KIDNEY STEM CELLS ON BIOCHEMICAL ANALAYSIS AND SMAD2/3 PHOSPHORYLATION IN RATS WITH DIABETIC NEPHROPATHY

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    Introduction: Mesenchymal stem cells (MSCs) were proposed as a critical therapeutic candidate in diabetic nephropathy (DN). Renal stem cells as a source for repairing are controversial. The purpose of the present study was to evaluate the effect of kidney rat stem cells on DN. Materials and methods: After separation of renal stem cells from rat kidney, the surface Stem cell markers were assessed by flow cytometry analysis. To establish the diabetic nephropathy rat model STZ(60mg/kg) was used. The cells were injected to experimental groups via tail vein (2×106cells/rat). Biochemical and histological parameters were evaluated in order to determining the impact of stem cells on kidney structure. Phosphorylation of Smad2/3 two weeks after induction of early diabetic nephropathy was evaluated by using standard western blotting.Result: The cells significantly reduced blood nitrogen (BUN), serum creatinine (Scr) and 24 urinary proteins. The phosphorylation of smad2 and smad3 significantly down-regulated. PAS staining showed in the presence of adult kidney stem cells histopathological changes were improved.Conclusion: Adult kidney stem cells may be a candidate for treatment of early DN to improve the kidney function and regenerating kidney tissues in DN rats

    Dietary acid load and its interaction with CETP TaqB1 polymorphisms on lipid profile among patients with Type 2 diabetes mellitus

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    Abstract Objective Gene-diet interaction plays a key role in the inter-individual differences in lipid abnormalities as a major risk factor for cardiovascular diseases (CVDs). Thus, we explored the interaction between CETP TaqB1 polymorphism with dietary acid load (DAL) on lipid profile among type 2 diabetes mellitus (T2DM). Method This cross-sectional study conducted on 220 Iranian patients with T2DM. Dietary acid load (PRAL and NEAP) was calculated via a validated food-frequency questionnaire (FFQ). The polymerase chain reaction (PCR) used for genotyping Taq1B polymorphism. Biochemical markers were measured by standard protocol. The interaction between CETP Taq1B polymorphism and DAL (PRAL and NEAP) on lipid profile was performed by a generalized linear regression model (GLM). Results The overall prevalence of rs708272 genotypes was 8.6%, 72.7% and 18.6% for B1B1, B1B2 and B2B2 genotype respectively. This study showed that people with the B1B1 genotype had greater LDL, TC, LDL/HDL, and TG when they consumed diets that scored higher on the NEAP and PRAL indexes than those with the B1B2 and B2B2 genotypes. Besides, carriers of the B1B1 allele who were in the highest tertile of NEAP, had lower HDL (P Interaction < 0.05). Conclusions In summary, the lipid profile might be improved in B1B1 homozygotes by less adherence to DAL indexes, however, the findings should be validated in high-quality interventional studies

    A Nutrigenetic Approach to Investigate ApoB EcoR1 Polymorphism–Dietary Acid Load Interactions on Lipid and Anthropometric-Related Outcomes in Adults with Dyslipidemic Type 2 Diabetes

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    Introduction: Despite multiple studies which have considered the role of dietary acid load (DAL) or Apolipoprotein B (ApoB) EcoR1 polymorphism in diabetes, none have assessed their interplay effect on metabolic markers. Therefore, this study aimed to determine the interaction of EcoR1 and DAL on metabolic markers among adults with Type 2 diabetes mellitus (T2DM). Methods: 492 randomly selected individuals with T2DM were recruited for this cross-sectional study. Dietary intake was evaluated by a validated food frequency questionnaire. DAL was assessed as net-endogenous acid production (NEAP) and potential renal acid load (PRAL). Real-time-PCR was used to genotype EcoR1. Metabolic markers were also assessed. The interaction effect of the polymorphism and DAL indexes was analyzed by analysis of covariance (ANCOVA). Result: The frequency of EcoR1 genotypes was not different between dyslipidemic and normolipidemic participants (P>0.05). Among participants with dyslipidemia, those with the GG genotype and who consumed a higher level of NEAP had higher body mass index (BMI) (p=0.03) and waist circumference (WC; p =0.02). Moreover, triglyceride (TG) concentration (P=0.007), the LDL/HDL ratio (P=0.03) and the TG/HDL (P=0.03) ratio were significantly higher in A allele carriers with higher than the median intake of NEAP, in comparison with GG homozygotes. Finally, GA/AA carriers who had a higher intake of PRAL had a higher TG concentration (P=0.006) and TG/HDL ratio (P=0.01) compared to lower median intake in the dyslipidemia group. Discussion/Conclusion: In the dyslipidemic group, there was a higher TG concentration among individuals with the GA/AA genotype and a higher intake of NEAP/ PRAL. Also, in this group, a higher intake of NEAP may be considered as a risk factor for increased levels of BMI and WC among participants with the GG genotype

    Alterations to Cerebral Perfusion, Metabolite Profiles, and Neuronal Morphology in the Hippocampus and Cortex of Male and Female Mice during Chronic Exposure to a High-Salt Diet

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    Excess dietary salt reduces resting cerebral blood flow (CBF) and vascular reactivity, which can limit the fueling of neuronal metabolism. It is hitherto unknown whether metabolic derangements induced by high-salt-diet (HSD) exposure during adulthood are reversed by reducing salt intake. In this study, male and female mice were fed an HSD from 9 to 16 months of age, followed by a normal-salt diet (ND) thereafter until 23 months of age. Controls were continuously fed either ND or HSD. CBF and metabolite profiles were determined longitudinally by arterial spin labeling magnetic resonance imaging and magnetic resonance spectroscopy, respectively. HSD reduced cortical and hippocampal CBF, which recovered after dietary salt normalization, and affected hippocampal but not cortical metabolite profiles. Compared to ND, HSD increased hippocampal glutamine and phosphocreatine levels and decreased creatine and choline levels. Dietary reversal only allowed recovery of glutamine levels. Histology analyses revealed that HSD reduced the dendritic arborization and spine density of cortical and hippocampal neurons, which were not recovered after dietary salt normalization. We conclude that sustained HSD exposure throughout adulthood causes permanent structural and metabolic alterations to the mouse brain that are not fully normalized by lowering dietary salt during aging
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