脂质代谢异常对儿童过敏性紫癜肾损伤预测价值的Meta分析

背景　过敏性紫癜（HSP）是儿童最常见的血管炎之一,部分可累及肾脏发展为紫癜性肾炎（HSPN）,影响预后。因此在HSP的发病早期寻找肾脏损伤的预测因子十分必要,近年来越来越多的研究表明脂质代谢异常可能是HSP肾脏损伤的危险因素,然而未见系统的循证研究。目的　全面搜集相关文献,评估HSP发病早期脂质代谢异常是否能作为HSPN的预测因子。方法　计算机检索PubMed、EMBase、The Cochrane Library、中国知网、万方数据知识服务平台、维普网、中国生物医学文献数据库,检索时间为建库至2020-02-10。收集第一作者、发表年份、国家、诊断标准、性别、年龄、例数（HSPN组/非HSPN组）、观察指标〔两组人群起病时的总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、载脂蛋白M（ApoM）〕、研究类型、发生情况（初发/复发）、病程、随访时间,运用纽卡斯尔-沃太华量表（NOS）对纳入文献进行质量评估,Stata 15.1软件进行Meta分析。结果　共纳入16篇文献5 312例患者,失访26例,纳入HSP患儿5 286例,其中1 997例发展为HSPN,NOS评分均≥6分。Meta分析结果显示：HSPN组患者起病时的TC水平〔WMD=0.72,95%CI（0.51,0.92）〕、TG水平〔WMD=0.61,95%CI（0.45,0.77）〕、LDL水平〔WMD=0.65,95%CI（0.41,0.89）〕高于非HSPN组,ApoM水平〔OR=0.32,95%CI（0.12,0.85）〕低于非HSPN组。结论　高水平的TC、TG和LDL可能是HSP发展为HSPN的预测因子,HDL水平与HSPN关系尚不明确,有待进一步研究证实,ApoM有望成为HSPN的新独立预测因子。     

Long-Term Lithium Treatment Reduces Glucose Metabolism in the Cerebellum and Hippocampus of Nondemented Older Adults: An [18F]FDG-PET Study

相似文献   

Quantitative tissue pH measurement during cerebral ischemia using amine and amide concentration-independent detection (AACID) with MRI

Tissue pH is an indicator of altered cellular metabolism in diseases including stroke and cancer. Ischemic tissue often becomes acidic due to increased anaerobic respiration leading to irreversible cellular damage. Chemical exchange saturation transfer (CEST) effects can be used to generate pH-weighted magnetic resonance imaging (MRI) contrast, which has been used to delineate the ischemic penumbra after ischemic stroke. In the current study, a novel MRI ratiometric technique is presented to measure absolute pH using the ratio of CEST-mediated contrast from amine and amide protons: amine/amide concentration-independent detection (AACID). Effects of CEST were observed at 2.75 parts per million (p.p.m.) for amine protons and at 3.50 p.p.m. for amide protons downfield (i.e., higher frequency) from bulk water. Using numerical simulations and in vitro MRI experiments, we showed that pH measured using AACID was independent of tissue relaxation time constants, macromolecular magnetization transfer effects, protein concentration, and temperature within the physiologic range. After in vivo pH calibration using phosphorus (³¹P) magnetic resonance spectroscopy (³¹P-MRS), local acidosis is detected in mouse brain after focal permanent middle cerebral artery occlusion. In summary, our results suggest that AACID represents a noninvasive method to directly measure the spatial distribution of absolute pH in vivo using CEST MRI.     

Double deletion of orexigenic neuropeptide Y and dynorphin results in paradoxical obesity in mice

Objective

Orexigenic neuropeptide Y (NPY) and dynorphin (DYN) regulate energy homeostasis. Single NPY or dynorphin deletion reduces food intake or increases fat loss. Future developments of obesity therapeutics involve targeting multiple pathways. We hypothesised that NPY and dynorphin regulate energy homeostasis independently, thus double NPY and dynorphin ablation would result in greater weight and/or fat loss than the absence of NPY or dynorphin alone.

Design and methods

We generated single and double NPY and dynorphin knockout mice (NPYΔ, DYNΔ, NPYDYNΔ) and compared body weight, adiposity, feeding behaviour, glucose homeostasis and brown adipose tissue uncoupling protein-1 (UCP-1) expression to wildtype counterparts.

Results

Body weight and adiposity were significantly increased in NPYDYNΔ, but not in NPYΔ or DYNΔ. This was not due to increased food intake or altered UCP-1 expression, which were not significantly altered in double knockouts. NPYDYNΔ mice demonstrated increased body weight loss after a 24-h fast, with no effect on serum glucose levels after glucose injection.

Conclusions

Contrary to the predicted phenotype delineated from single knockouts, double NPY and dynorphin deletion resulted in heavier mice, with increased adiposity, despite no significant changes in food intake or UCP-1 activity. This indicates that combining long-term opioid antagonism with blockade of NPY-ergic systems may not produce anti-obesity effects.     

The ontogeny of drug metabolism enzymes and implications for adverse drug events

Profound changes in drug metabolizing enzyme (DME) expression occurs during development that impacts the risk of adverse drug events in the fetus and child. A review of our current knowledge suggests individual hepatic DME ontogeny can be categorized into one of three groups. Some enzymes, e.g., CYP3A7, are expressed at their highest level during the first trimester and either remain at high concentrations or decrease during gestation, but are silenced or expressed at low levels within one to two years after birth. SULT1A1 is an example of the second group of DME. These enzymes are expressed at relatively constant levels throughout gestation and minimal changes are observed postnatally. ADH1C is typical of the third DME group that are not expressed or are expressed at low levels in the fetus, usually during the second or third trimester. Substantial increases in enzyme levels are observed within the first one to two years after birth. Combined with our knowledge of other physiological factors during early life stages, knowledge regarding DME ontogeny has permitted the development of robust physiological based pharmacokinetic models and an improved capability to predict drug disposition in pediatric patients. This review will provide an overview of DME developmental expression patterns and discuss some implications of the data with regards to drug therapy. Common themes emerging from our current knowledge also will be discussed. Finally, the review will highlight gaps in knowledge that will be important to advance this field.     

Abnormal lipid metabolism down‐regulates adenosine triphosphate synthase β‐subunit protein expression in corpus cavernosum smooth muscle in vitro and in vivo

Metabolic syndrome is closely related to erectile dysfunction (ED), and hyperlipidaemia is considered a major risk factor for ED. Adenosine triphosphate (ATP) synthase is believed to play an important role in metabolic syndrome; it has been hypothesised that ATP synthase contributes to ED development. We have verified this hypothesis using primary cultured human corpus cavernosum smooth muscle (HCCSM) cells treated with excessive free fat acid (FFA) and a high‐fat diet (HFD) mouse model. Our results showed that high fatty factors could cause lipid accumulation in HCCSM cells, which could result in abnormal lipid metabolism, such as high levels of triglycerides, cholesterol and glucose in the HFD mice. There was a remarkable down‐regulation of ATP synthase and p‐Akt after in vivo and in vitro excessive FFA treatments. These results indicated that abnormal lipid metabolism could induce ATP synthase down‐regulation via the Akt phosphorylation pathway and that ATP synthase may be a target of lipotoxicity in corpus cavernosum smooth muscle cells.