Hepatic alterations are accompanied by changes to bile acid transporter-expressing neurons in the hypothalamus after traumatic brain injury

Annually, there are over 2 million incidents of traumatic brain injury (TBI) and treatment options are non-existent. While many TBI studies have focused on the brain, peripheral contributions involving the digestive and immune systems are emerging as factors involved in the various symptomology associated with TBI. We hypothesized that TBI would alter hepatic function, including bile acid system machinery in the liver and brain. The results show activation of the hepatic acute phase response by 2 hours after TBI, hepatic inflammation by 6 hours after TBI and a decrease in hepatic transcription factors, Gli 1, Gli 2, Gli 3 at 2 and 24 hrs after TBI. Bile acid receptors and transporters were decreased as early as 2 hrs after TBI until at least 24 hrs after TBI. Quantification of bile acid transporter, ASBT-expressing neurons in the hypothalamus, revealed a significant decrease following TBI. These results are the first to show such changes following a TBI, and are compatible with previous studies of the bile acid system in stroke models. The data support the emerging idea of a systemic influence to neurological disorders and point to the need for future studies to better define specific mechanisms of action

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

An Evaluation of the Effects of the Potato Starch on the Biogas Produced from the Anaerobic Digestion of Potato Wastes

Anaerobic digestion (AD) has undergone many developments since its first appearance. Despite that, there are still some environmental and economical obstacles that are limiting its sustainability. On the other hand, different types of starch have proven their effectiveness in some different applications. Food processing industries are considered one of the largest generators of waste in the environment. With an aid of the response surface methodology (RSM), the proposed study aimed to find an optimised way to overcome the obstacles by studying the impacts of the starch isolated from the potato peels on the biogas produced from the AD of potato peels before and after starch separation. The study found that potato peels represented approximately 12.5% of the potato total weight. The starch has only a slight influence on the quantity of the biogas produced and much lower influences on its quality. This finding suggests further investigation is required on the production of starch bio-based products simultaneously with the biogas and bio-slurry, which may mitigate environmental influences and economical obstacles of AD and make it more commercially attractive. The study showed also that the highest energy gain by the g-VS/0.2 L of potato peels was 62.9% at 35 °C, 1.62 g-VS/0.2 L organic concentration and 50% sludge concentration, which yielded a maximum CH4 of 72.4%

SREBP2 mediates the modulation of intestinal NPC1L1 expression by curcumin

Curcumin, the major phenolic compound in the spice turmeric, exhibits numerous biological effects, including lowering plasma cholesterol and preventing diet-induced hypercholesterolemia. The mechanisms underlying the hypocholesterolemic effect of curcumin are not fully understood. In this regard, intestinal Niemann-Pick C1-like 1 (NPC1L1) cholesterol transporter, the molecular target of intestinal cholesterol absorption inhibitor ezetimibe, plays an essential role in the maintenance of cholesterol homeostasis. The current studies were designed to investigate the effect of curcumin on NPC1L1 function, expression, and promoter activity in intestinal Caco-2 monolayers. NPC1L1 function was evaluated by the measurement of ezetimibe-sensitive [3H]cholesterol esterification. Relative abundance of NPC1L1 mRNA and protein was evaluated by real-time PCR and Western blotting, respectively. Luciferase assays were used to measure NPC1L1 promoter activity. Our results showed that curcumin significantly inhibited ezetimibe-sensitive cholesterol esterification in a dose-dependent manner with a maximum decrease (by 52% compared with control) occurring at 50 μM concentration. Curcumin treatment of Caco-2 monolayers also significantly decreased NPC1L1 mRNA and protein expression. Similarly, the promoter activity of the NPC1L1 gene was inhibited significantly (55%) by 50 μM curcumin. The decrease in NPC1L1 promoter activity by curcumin was associated with a reduction in the expression and the DNA-binding activity of the sterol response element-binding protein 2 (SREBP2) transcription factor. Furthermore, the overexpression of active SREBP2 protected NPC1L1 from the inhibitory effect of curcumin. Our studies demonstrate that curcumin directly modulates intestinal NPC1L1 expression via transcriptional regulation and the involvement of SREBP2 transcription factor

Chronische Bauchschmerzen – Folge einer seltenen gastrointestinalen Fehlbildung?

<jats:title>Zusammenfassung</jats:title><jats:p>Es wird über eine 15-jährige Patientin mit chronischen Bauchschmerzen, Übelkeit, stuhlig riechendem Aufstoßen und Durchfällen nach dem Trinken berichtet. Endoskopisch wurden 3 gastrokolische Fisteln entdeckt. Weder laborchemisch noch histologisch ergab sich ein Hinweis auf das Vorliegen eines M. Crohn oder anderer Grunderkrankungen. Histologisch fanden sich in Schleimhautbiopsaten der größten Fistel Zeichen einer geringgradigen chronischen und floriden Gastritis. Nach Therapiebeginn mit Omeprazol kam es zur deutlichen Beschwerdebesserung. Alle Fisteln wurden in einer laparoskopischen Operation mithilfe eines Staplers durchtrennt.</jats:p&gt