Mathematical and Pharmacokinetic Approaches for the Design of New 3D Printing Inks Using Ricobendazole

Pharmaceutical Research - 3D printing (3DP) makes it possible to obtain systems that are not achievable with current conventional methods, one of them, sustained release floating systems. Floating...     

石榴皮活性成分治疗痤疮作用机制的网络药理学预测及实验研究＊

目的 采用网络药理学及实验验证的方法，探索皮类中药石榴皮治疗痤疮的作用机制。方法 利用网络药理学技术筛选石榴皮治疗痤疮的活性成分和作用靶点，采用String数据库对活性成分靶点与痤疮疾病靶点进行蛋白互作网络分析，并通过David数据库对其结果进行KEGG通路富集分析。基于以上结果，采用Cytoscape3.6.1软件构建石榴皮治疗痤疮的“成分-靶点-通路”网络关系图。通过动物实验，观察石榴皮多酚乳膏对金黄地鼠皮脂腺斑面积及PI3K蛋白表达情况的影响。结果 本研究共获得药效成分31个，药物靶点193个，痤疮靶点1371个，药效成分与疾病的交集靶点79个。石榴皮治疗痤疮的主要成分为槲皮素、山奈酚、木犀草素等；核心靶点为Akt1、IL-6、VEGFA和PTSG2；关键信号通路可能包括PI3K-Akt信号通路、TNF信号通路、T细胞受体信号通路、FoxO信号通路等。体内实验证实，石榴皮能够降低金黄地鼠皮脂腺斑PI3K蛋白表达水平，抗皮脂腺斑增生。结论 本研究预测了石榴皮治疗痤疮可能的作用机制，为“以皮治皮”理论在中医皮肤科的应用提供现代理论依据。     

A novel p.Gly417Valfs*12 mutation in the MTTP gene causing abetalipoproteinemia: Presentation of the first patient in Mexico and analysis of the previously reported cases

BackgroundOur aims were to describe the first Mexican patient with abetalipoproteinemia and to perform a comparative analysis of biochemical, clinical, and genetic characteristics of 100 cases reported in the literature.MethodsWe performed biochemical and molecular screenings in a Mexican girl with extremely low lipid levels and in her family. Further, we integrated and evaluated the characteristics of the cases with abetalipoproteinemia described in the literature.ResultsOur patient is a six‐year‐old girl who presented vomiting, chronic diarrhea, failure to thrive, malabsorption, acanthocytosis, anemia, transaminases elevation, and extremely low lipid levels. MTTP gene sequencing revealed homozygosity for a novel mutation p.Gly417Valfs*12 (G deletion c.1250). With the analysis of the reported cases, 60 clinical features (14 classical and 46 non‐classical) were observed, being the most common acanthocytosis (57.5%), malabsorption (43.7%), and diarrhea (42.5%); 48.8% of the patients presented only classic clinical features, while the remaining 51.2% developed secondary effects due to a fat‐soluble vitamin deficiency. An odds ratio analysis disclosed that patients diagnosed after 10 years of age have an increased risk for presenting clinical complications (OR = 18.0; 95% CI 6.0‐54.1, p < 0.0001). A great diversity of mutations in MTTP has been observed (n = 76, being the most common p.G865X and p.N139_E140) and some of them with possible residual activity.ConclusionThe first Mexican patient with abetalipoproteinemia presents a novel MTTP mutation p.Gly417Valfs*12. Three factors that could modulate the phenotype in abetalipoproteinemia were identified: age at diagnosis, treatment, and the causal mutation.     

Genomic damage as a biomarker of chronic kidney disease status

Patients suffering from chronic kidney disease (CKD) exhibit a high incidence of cancer and cardiovascular diseases, as well as high levels of genomic damage. To confirm the association of CKD with genomic damage we have carried out the largest study to date addressing this issue, using a total of 602 subjects (187 controls, 206 pre‐dialysis CKD patients and 209 CKD patients in hemodialysis). DNA oxidative damage was measured in all individuals using the comet assay. Our results indicate that CKD patients have significantly higher levels of DNA damage than controls, but no significant differences were observed between pre‐hemodialysis (pre‐HD) and hemodialysis (HD) patients. When oxidative damage was measured, no differences were observed between patients and controls, although HD patients showed significantly higher levels of oxidative damage than pre‐HD patients. In addition, a positive relationship was demonstrated between genomic damage and all‐cause mortality. Our study confirms that genomic damage can be predictive of prognosis in CKD patients, with high levels of DNA damage indicating a poor prognosis in HD patients. Environ. Mol. Mutagen. 56:301–312, 2015. © 2014 Wiley Periodicals, Inc.     

Emergency department visits involving opioids in Connecticut, 2011–2015

Background: Opioid abuse has demonstrated an unwavering elevation in the past decade. This study examined emergency department (ED) utilization for this growing public health problem in the state of Connecticut.

Methods: We evaluated the ED discharges involving opioids in individuals treated in Connecticut EDs from 2011 to 2015. International Classification of Disease, 9th Revision, Clinical Modification and external cause of injury codes were used to identify cases.

Results: There were 38,003 ED visits involving opioids during the study period. Visits were most prevalent in males (63.4%) and in those aged 18–44 years (71.8%). The rate of visits (per 10,000 ED visits) in whites (72.7) was more than three times that of blacks (24.7) and nearly double that of individuals of Hispanic ethnicity (37.7). The rate of visits for females under the age of 18 was slightly greater than that for males in the same age groups (2.7 vs. 2.4/10,000 ED visits, respectively).

Conclusion: Manual labor work and racial stereotyping are possible causal factors for higher rates of opioid-related ED visits among white males between the ages of 18 and 44, while higher levels of emotional distress may be contributing to similar rates among females under the age of 18 and over the age of 65.     

徐州市儿童青少年超重和肥胖及其对血压的影响

目的 了解徐州市儿童青少年超重和肥胖情况及其对血压的影响。方法 采用分层整群抽样方法,在徐州市随机抽取小学、初中、高中、大学共12 所学校,共计抽取2 147人。采用Excel录入数据,使用SPSS 19.0进行统计分析。结果 徐州市儿童青少年超重检出率为17.9%,肥胖检出率为13.3%,不同性别超重肥胖检出率差异均有统计学意义(χ2=83.745,P<0.01);高血压检出率为 8.2%,不同性别高血压检出率差异有统计学意义(χ2=5.225,P<0.05);正常组、超重组、肥胖组高血压检出率分别为 6.6%、9.4%、15.0%;多因素logistics回归分析结果显示:性别、年龄、超重和肥胖是儿童青少年高血压的危险因素。结论 徐州市儿童青少年超重、肥胖检出率较高;超重肥胖组高血压检出率比体质量正常组高。