Quantitative Histomorphometry of the Healthy Peritoneum

The peritoneum plays an essential role in preventing abdominal frictions and adhesions and can be utilized as a dialysis membrane. Its physiological ultrastructure, however, has not yet been studied systematically. 106 standardized peritoneal and 69 omental specimens were obtained from 107 patients (0.1-60 years) undergoing surgery for disease not affecting the peritoneum for automated quantitative histomorphometry and immunohistochemistry. The mesothelial cell layer morphology and protein expression pattern is similar across all age groups. Infants below one year have a thinner submesothelium; inflammation, profibrotic activity and mesothelial cell translocation is largely absent in all age groups. Peritoneal blood capillaries, lymphatics and nerve fibers locate in three distinct submesothelial layers. Blood vessel density and endothelial surface area follow a U-shaped curve with highest values in infants below one year and lowest values in children aged 7-12 years. Lymphatic vessel density is much lower, and again highest in infants. Omental blood capillary density correlates with parietal peritoneal findings, whereas only few lymphatic vessels are present. The healthy peritoneum exhibits major thus far unknown particularities, pertaining to functionally relevant structures, and subject to substantial changes with age. The reference ranges established here provide a framework for future histomorphometric analyses and peritoneal transport modeling approaches. © 2016, EDP Science. All rights reserved

Quercetin Suppresses Cyclooxygenase-2 Expression and Angiogenesis through Inactivation of P300 Signaling

Quercetin, a polyphenolic bioflavonoid, possesses multiple pharmacological actions including anti-inflammatory and antitumor properties. However, the precise action mechanisms of quercetin remain unclear. Here, we reported the regulatory actions of quercetin on cyclooxygenase-2 (COX-2), an important mediator in inflammation and tumor promotion, and revealed the underlying mechanisms. Quercetin significantly suppressed COX-2 mRNA and protein expression and prostaglandin (PG) E(2) production, as well as COX-2 promoter activation in breast cancer cells. Quercetin also significantly inhibited COX-2-mediated angiogenesis in human endothelial cells in a dose-dependent manner. The in vitro streptavidin-agarose pulldown assay and in vivo chromatin immunoprecipitation assay showed that quercetin considerably inhibited the binding of the transactivators CREB2, C-Jun, C/EBPβ and NF-κB and blocked the recruitment of the coactivator p300 to COX-2 promoter. Moreover, quercetin effectively inhibited p300 histone acetyltransferase (HAT) activity, thereby attenuating the p300-mediated acetylation of NF-κB. Treatment of cells with p300 HAT inhibitor roscovitine was as effective as quercetin at inhibiting p300 HAT activity. Addition of quercetin to roscovitine-treated cells did not change the roscovitine-induced inhibition of p300 HAT activity. Conversely, gene delivery of constitutively active p300 significantly reversed the quercetin-mediated inhibition of endogenous HAT activity. These results indicate that quercetin suppresses COX-2 expression by inhibiting the p300 signaling and blocking the binding of multiple transactivators to COX-2 promoter. Our findings therefore reveal a novel mechanism of action of quercetin and suggest a potential use for quercetin in the treatment of COX-2-mediated diseases such as breast cancers

Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009

Insulin resistance is a hallmark of type 2 diabetes mellitus and is associated with a metabolic and cardiovascular cluster of disorders (dyslipidaemia, hypertension, obesity [especially visceral], glucose intolerance, endothelial dysfunction), each of which is an independent risk factor for cardiovascular disease (CVD). Multiple prospective studies have documented an association between insulin resistance and accelerated CVD in patients with type 2 diabetes, as well as in non-diabetic individuals. The molecular causes of insulin resistance, i.e. impaired insulin signalling through the phosphoinositol-3 kinase pathway with intact signalling through the mitogen-activated protein kinase pathway, are responsible for the impairment in insulin-stimulated glucose metabolism and contribute to the accelerated rate of CVD in type 2 diabetes patients. The current epidemic of diabetes is being driven by the obesity epidemic, which represents a state of tissue fat overload. Accumulation of toxic lipid metabolites (fatty acyl CoA, diacylglycerol, ceramide) in muscle, liver, adipocytes, beta cells and arterial tissues contributes to insulin resistance, beta cell dysfunction and accelerated atherosclerosis, respectively, in type 2 diabetes. Treatment with thiazolidinediones mobilises fat out of tissues, leading to enhanced insulin sensitivity, improved beta cell function and decreased atherogenesis. Insulin resistance and lipotoxicity represent the missing links (beyond the classical cardiovascular risk factors) that help explain the accelerated rate of CVD in type 2 diabetic patients

Preoperative medical treatment in Cushing's syndrome : frequency of use and its impact on postoperative assessment : data from ERCUSYN

Background: Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial. Objective: (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS). Patients and methods: 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS). Results: Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (P < 0.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) (P < 0.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol (P < 0.01) and a lower remission rate (P < 0.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups. Conclusions: PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results

Molecular basis of the inflammation related to obesity

Almost two thousand millions of adults suffer from overweight or obesity in the world [1]. After decades of research, we understand that the solution to this problem is not easy, as the pernicious trend is still increasing. This disease is defined as an excessive fat accumulation together with a moderate but chronic inflammation. This accompanying proinflammatory status is considered the link between obesity and the development of its related comorbidities such as insulin resistance and type 2 diabetes, cardiovascular diseases, cancer, and nonalcoholic fatty liver disease

Hyperfine-structure measurements and new levels evaluation in singly ionized praseodymium

Results of systematic studies of the hyperfine structure of singly ionized praseodymium are presented. For many of the known energy levels the hyperfine constants A and B have been measured more precisely and found consistent with previous literature data. Identification of some new energy levels has also been performed. The hyperfine structure of some unclassified lines has been recorded by the method of laser induced fluorescence in a hollow cathode discharge. J quantum numbers and A-values for upper and lower levels have been determined. Identification has been achieved through comparison of the obtained results with those for known levels. Three new low-lying levels in singly ionized praseodymium have been discovered. Some of the recorded unclassified lines involve two new levels and their identification requires further investigations

The analysis of oral nutritional supplements related aspects among patients with digestive system cancer

OBJECTIVE: Malnutrition-related disease particularly occur in patients with digestive system cancer. The administration of oral nutritional supplements (ONSs) is one of the methods of nutritional support recommended for oncological patients. The primary aim of this study was to assess the consumption-related aspects of ONSs among patients with digestive system cancer. The secondary aim was to assess the impact of ONSs consumption on the quality of life of these patients. PATIENTS AND METHODS: The current study included 69 patients with digestive system cancer. The assessment of ONSs-related aspects among cancer patients was conducted using a self-designed questionnaire, which has been accepted by Independent Bioethics Committee. RESULTS: Among all patients, 65% of participants declared that they consumed ONSs. Patients consumed various types of ONSs. However, the most common were protein products (40%) and standard products (37.78%). Only 4.44% of patients consumed products with immunomodulatory ingredients. Nausea was the most commonly (15.56%) observed side effect after ONSs consumption. Considering particular types of ONSs, side effects were the most commonly declared by patients who consumed standard products (p=0.157). The easy product availability in the pharmacy was noted by 80% of participants. However, 48.89% of patients assessed the cost of ONSs as not acceptable (48.89%). 46.67% of studied patients did not observe the improvement of quality of life after ONSs consumption. CONCLUSIONS: We have demonstrated that patients with digestive system cancer consumed various period, amount, and types of ONSs. Side effects after ONSs consumption occur rarely. However, the improvement of quality of life related to ONSs consumption was not noted in almost half of participants. ONSs are easily available in pharmacy