Obese reproductive-age women exhibit a proatherogenic inflammatory response during hyperglycemia

Objective: The objective was to determine if physiological hyperglycemia induces a proatherogenic inflammatory response in mononuclear cells (MNCs) in obese reproductive‐age women. Research Methods and Procedures: Seven obese and 6 age‐matched lean women (20 to 39 years of age) underwent a 2‐hour 75‐g oral glucose tolerance test. The release of interleukin‐6 (IL‐6) and interleukin‐1β (IL‐1β) from MNCs cultured in the presence of lipopolysaccharide (LPS) was measured after isolation from blood samples drawn fasting and 2 hours after glucose ingestion. Reactive oxygen species (ROS) generation and intra‐nuclear nuclear factor κB (NFκB) from MNCs were quantified from the same blood samples. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA‐IR). Total body fat and truncal fat were determined by DXA. Results: Obese women had a higher (p < 0.03) total body fat (42.2 ± 1.1 vs. 27.7 ± 2.0%), truncal fat (42.1 ± 1.2 vs. 22.3 ± 2.4%), and HOMA‐IR (3.3 ± 0.5 vs. 1.8 ± 0.2). LPS‐stimulated IL‐6 release from MNCs was suppressed during hyperglycemia in lean subjects (1884 ± 495 vs. 638 ± 435 pg/mL, p < 0.05) but not in obese women (1184 ± 387 vs. 1403 ± 498 pg/mL). There was a difference (p < 0.05) between groups in the hyperglycemia‐induced MNC‐mediated release of IL‐6 (?1196 ± 475 vs. 219 ± 175 pg/mL) and IL‐1β (?79 ± 43 vs. 17 ± 12 pg/mL). In addition, the obese group exhibited increased (p < 0.05) MNC‐derived ROS generation (39.3 ± 9.9 vs. ?1.0 ± 12.8%) and intra‐nuclear NFκB (9.4 ± 7.3 vs. ?23.5 ± 13.5%). Truncal fat was positively correlated with the MNC‐derived IL‐6 response (ρ = 0.58, p < 0.05) and intra‐nuclear NFκB (ρ = 0.64, p < 0.05). Discussion: These data suggest that obese reproductive‐age women are unable to suppress proatherogenic inflammation during physiological hyperglycemia. Increased adiposity may be a significant contributor to this pro‐inflammatory susceptibility.     

Increasing trends in waist circumference and abdominal obesity among US adults

Objective: Some studies have shown that abdominal obesity may be a better predictor than overall obesity for disease risks and all‐cause mortality. This study sought to examine the recent trends in waist circumference (WC) among adults in the United States. Research Methods and Procedures: Data from the National Health and Nutrition Examination Survey during 1988–1994, 1999–2000, 2001–2002, and 2003–2004 were analyzed to estimate the trends in the mean WC and the prevalence of abdominal obesity. Pooled t tests were used to test the differences in estimates between two time periods. Results: Between the periods of 1988–1994 and 2003–2004, the age‐adjusted mean WC increased from 96.0 cm to 100.4 cm among men (p < 0.001) and from 89.0 cm to 94.0 cm among women (p < 0.001); the age‐adjusted prevalence of abdominal obesity increased from 29.5% to 42.4% among men (p < 0.001) and from 47.0% to 61.3% among women (p < 0.001). Between the periods of 1999–2000 and 2003–2004, a significant increase occurred in mean WC only among men (from 99.0 cm to 100.4 cm; p = 0.03) and in the prevalence of abdominal obesity among both men (from 37.0% to 42.2%; p = 0.03) and women (from 55.3% to 61.3%; p = 0.04). People with a BMI of 25 to 29 kg/m² had a greater relative increase in abdominal obesity. Discussion: The mean WC and the prevalence of abdominal obesity among U.S. adults have increased continuously during the past 15 years. Over one‐half of U.S. adults had abdominal obesity in the period of 2003–2004.     

Anatomical patterning of visceral adipose tissue: race, sex, and age variation

Objective: We tested sex, race, and age differences in the patterning of visceral adipose tissue (VAT) and subcutaneous adipose tissue. Research Methods and Procedures: Contiguous 1‐cm‐thick magnetic resonance (MR) images of the abdomen were collected from 820 African‐American and white adults. Repeated‐measures ANOVA was used to examine the effects of image location, sex, race, and age (≥50 vs. <50 years) on adipose tissue areas. Maximum VAT area was identified for each subject from the raw data. Results: Compared to women, men had greater total VAT volume (p < 0.0001), and their maximum VAT area occurred higher in the abdomen (p < 0.0001). Among white men, maximim VAT area most frequently occurred 5 to 10 cm above L4‐L5, whereas in the other groups, maximim VAT area most frequently occurred 1 to 4 cm above L4‐L5 (p < 0.0001). African‐American men had greater total VAT volume than African‐American women (p < 0.01), but this sex difference was only significant using single images cranial to L4‐L5 + 2 cm. Age‐related increases in VAT tended to be greatest 5 to 10 cm above L4‐L5 in men and near L4‐L5 in women. Discussion: A single MR image 5 to 10 cm above L4‐L5 may allow more accurate conclusions than the L4‐L5 image regarding group differences in visceral adiposity.     

Formulation and optimization of porous osmotic pump-based controlled release system of oxybutynin

The aim of the current study was to design a porous osmotic pump-based drug delivery system for controlled release of oxybutynin. The porous osmotic pump contains pore-forming water-soluble additives in the coating membrane, which after coming in contact with water, dissolve, resulting in an in situ formation of a microporous structure. The dosage regimen of oxybutynin is one 5-mg tablet 2 to 3 times a day. The plasma half-life ranges from ∼2 to 3 hours. Hence, oxybutynin was chosen as a model drug with an aim to develop a controlled release system for a period of 24 hours. Linear and reproducible release similar to that of Ditropan XL was achieved for optimized formulation (f2>50) independent of hydrodynamic conditions. The effect of different formulation variables, namely, ratio of drug to osmogent, membrane weight gain, and level of pore former on the in vitro release was studied. Cellulose acetate (CA) was used as the semipermeable membrane. It was found that drug release rate increased with the amount of osmogent because of the increased water uptake, and hence increased driving force for drug release. Oxybutynin release was inversely proportional to the membrane weight gain; however, directly related to the level of pore former, sorbitol, in the membrane. This system was found to deliver oxybutynin at a zero-order rate for 20 hours. The effect of pH on drug release was also studied. The optimized formulations were subjected to stability studies as per International Conference on Harmonisation (ICH) guidelines and formulations were stable after a 3 month study. Published: July 13, 2007     

The pore-forming action of polyenes: From model membranes to living organisms

The incidence of resistant fungal pathogens has been increasing, especially in immuno-compromised people. As such, considerable research has been focused on discovering anti-fungal agents with new mechanisms of action and on optimizing the use of existing agents. In this context, interest in the polyene group of anti-fungals has recently been renewed, since they are known to be effective against a broad spectrum of fungal pathogens that only rarely develop a resistance to them. In the past 10?years considerable efforts have been made to improve their efficacy and, simultaneously, to reduce their toxicity. Knowledge about the basic mechanisms of their action will be of crucial importance to further optimizing their use. The mechanisms of polyene action at the membrane level are reviewed here, focusing primarily on their pore-forming activity and on the resulting osmotic responses of artificial lipid vesicles and different eukaryotic cells.     

Research on circadian clock genes in common abdominal malignant tumors

Circadian rhythm describes the 24-h oscillation in physiology and behavior of living organisms and presents a timing controller for life activity. Studies in recent years have reported that the abnormal expression of clock genes is closely related to the development of common abdominal malignant tumors. The expression of the 14 kinds of clock genes in 6 abdominal malignant tumors from Cancer Genome Atlas (TCGA) data was integrated and analyzed using R and Perl programming languages to show the association between clock gene expression and prognosis of cancer patients. Analysis of TCGA data indicated that the overexpression of Per1-3, Cry2, CLOCK, NR1D2 and RORA with underexpression of Timeless and NPAS2 was associated with a favorable prognosis in kidney cancer. In liver cancer, high expressions of Cry2 and RORA were correlated with prolonged overall survival (OS) in patients, while high expressions of NPAS2 and Timeless were correlated with a poor survival. High expression of CLOCK was positively correlated with OS in colon cancer patients. High expression of Cry2 and low expression of DEC1 were associated with a favorable prognosis in pancreatic cancer patients, respectively. Most of these clock-genes expressions were closely related to the clinical stage and degree of tumor differentiation of patients. Aberrant clock gene expression is related to the biological characteristics of abdominal malignant tumors, which likely has a causal role in cancer development and survival.     

The effects of the muscular contraction on the abdominal biomechanics: a numerical investigation

Abdominal wall biomechanics is strongly affected by muscular contraction and intra-abdominal pressure (IAP) which characterize different physiological functions and daily tasks. However, the active muscular behavior is generally not considered in current computational models of the abdominal wall. The aim of this study is to develop a numerical model mimicking muscular activation and IAP.

A three dimensional Finite Element model of a healthy abdominal wall is developed detailing the principal abdomen components reconstructed upon anatomical data and medical images. Fascial tissues, aponeuroses and linea alba are modelled as hyperelastic fiber-reinforced materials, while a three-element Hill’s model is assumed for muscles. Numerical analyses are performed increasing the IAP up to 100?mmHg and simultaneously activating the muscular structures.

The obtained abdominal behavior is compared to a similar model with same IAPs, but passive muscles conditions. Abdomen stiffness and strength are computed in regions in which hernias can potentially occur. A global stiffening of the abdominal wall is found corresponding to a low abdomen deformation and the membrane force on fascial structures is reduced by muscular contraction.

Representing active muscular contraction leads to advanced findings, otherwise membrane force results overestimated considering a purely passive behavior for the abdominal wall.     

基于网络药理学的益母草治疗产后腹痛的潜在分子机制研究

本文通过网络药理学方法探讨益母草治疗产后腹痛的潜在分子机制。首先根据TCMSP数据库和文献挖掘益母草的活性成分,在TCMSP、Swiss Target Prediction、Similarity ensemble approach平台上检索活性成分靶点,在OMIM、GeneCards上检索产后腹痛靶点,得到益母草-产后腹痛交集靶点。利用STRING数据库构建蛋白互作(PPI)网络,接着利用Cytoscape软件对PPI网络进行拓扑分析,并对拓扑分析筛选出的核心靶点进行基因本体论(Gene Ontology,GO)分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析。最后利用免疫组化实验验证益母草对流产大鼠模型子宫组织中PGF2αR、MMP9、TIMP1、VEGFA、VEGFR2蛋白表达水平的影响。最终得到益母草活性成分10种,与产后腹痛相关靶点144个;通过PPI网络分析筛选出118个靶点,进一步拓扑分析后得到98个节点;然后对这98个节点进行GO和KEGG注释。GO分析得到1151个生物过程(BP)条目,97个细胞组成(CC)条目,122个分子功能(MF)条目;KEGG分析得到41条通路,主要涉及雌激素、PI3K-Akt、MAPK、HIF-1信号通路等。最后免疫组化实验证明益母草可显著抑制流产模型大鼠子宫组织中PGF2αR、MMP9蛋白上调和TIMP1、VEGFR2蛋白下调。本研究通过网络药理学和免疫组化实验验证,显示益母草治疗产后腹痛是多成分、多靶点、多途径相互作用的结果,为益母草的临床应用提供了一定的理论依据。     

超声引导下腹横肌平面阻滞联合舒芬太尼、右美托咪定镇痛对肝部分切除术后患者疼痛因子、应激反应和细胞免疫功能的影响

摘要 目的：探讨超声引导下腹横肌平面阻滞（TAPB）联合舒芬太尼、右美托咪定镇痛对肝部分切除术后患者疼痛因子、应激反应和细胞免疫功能的影响。方法：选择我院2020年4月~2021年8月期间收治的行肝部分切除术的患者70例。根据随机数字表法将患者分为A组（超声引导下TAPB联合舒芬太尼镇痛,35例）和B组（超声引导下TAPB联合舒芬太尼、右美托咪定镇痛,35例）,对比两组镇静、镇痛效果,观察两组疼痛因子、应激反应和细胞免疫功能变化,对比两组围术期间不良反应发生率。结果：两组术后12 h、术后24 h、术后48 h视觉模拟评分法（VAS）下降,且B组低于A组（P<0.05）。两组术后12 h、术后24 h、术后48 h Ramsay镇静评分下降,但B组高于A组（P<0.05）。两组术后1 d血清前列腺素E2（PGE2）、血清P物质（SP）、降钙素基因相关肽（CGRP）水平均升高,但B组低于A组（P<0.05）。两组术后1 d血清肾上腺素（E）、皮质醇（Cor）、C反应蛋白（CRP）水平均升高,但B组低于A组（P<0.05）。两组术后1 d CD8⁺升高,但B组低于A组;CD3⁺、CD4⁺、CD4⁺/CD8⁺下降,但B组高于A组（P<0.05）。两组不良反应发生率对比无统计学差异（P>0.05）。结论：超声引导下TAPB联合舒芬太尼、右美托咪定镇痛用于肝部分切除术后患者,可有效减轻术后疼痛和应激反应,改善机体免疫功能,安全可靠。     

Mitochondrial Ca<Superscript>2+</Superscript> cycle mediated by the palmitate-activated cyclosporin a-insensitive pore

Earlier we found that in isolated rat liver mitochondria the reversible opening of the mitochondrial cyclosporin A-insensitive pore induced by low concentrations of palmitic acid (Pal) plus Ca²⁺ results in the brief loss of Δψ [Mironova et al., J Bioenerg Biomembr (2004), 36:171–178]. Now we report that Pal and Ca²⁺, increased to 30 and 70 nmol/mg protein respectively, induce a stable and prolonged (10 min) partial depolarization of the mitochondrial membrane, the release of Ca²⁺ and the swelling of mitochondria. Inhibitors of the Ca²⁺ uniporter, ruthenium red and La³⁺, as well as EGTA added in 10 min after the Pal/Ca²⁺-activated pore opening, prevent the release of Ca²⁺ and repolarize the membrane to initial level. Similar effects can be observed in the absence of exogeneous Pal, upon mitochondria accumulating high [Sr²⁺], which leads to the activation of phospholipase A₂ and appearance of endogenous fatty acids. The paper proposes a new model of the mitochondrial Ca²⁺ cycle, in which Ca²⁺ uptake is mediated by the Ca²⁺ uniporter and Ca²⁺ efflux occurs via a short-living Pal/Ca²⁺-activated pore.