New Approach To Determine the Healthy Immune Variations by Combining Clustering Methods

peer reviewedDataGreen - Fédération Wallonie Bruxelle

Blunted anti-inflammatory response to adenosine in alcoholic cirrhosis

Background/Aim: Adenosine is an endogenous nucleoside that is released under metabolically unfavourable circumstances such as ischaemia or infection. It exerts potent anti-inflammatory effects by decreasing tumour necrosis factor release and costimulating interleukin-10 production by human monocytes. The aim of this study was to assess the cytokine response to adenosine in whole blood cultures from alcoholic cirrhotic patients. Methods: Whole blood from 17 patients and 17 healthy controls stimulated with lipopolysaccharide was cultured in the presence of adenosine at different concentrations and, in some experiments, with the adenosine deaminase inhibitor deoxycoformycin. Peripheral blood mononuclear cell response was compared to whole blood, and plasma adenosine deaminase activity was measured. Results: Adenosine (100 μM) significantly inhibited TNF release and increased IL-10 production in whole blood cultures from controls stimulated with lipopolysaccharide, but not from cirrhotic patients. However, the response to adenosine was restored in peripheral mononuclear cells of patients in the absence of autologous plasma. To test the hypothesis that plasma adenosine deaminase, which was increased in the patients' plasma, was actually involved in this blunted response to adenosine in alcoholic cirrhosis, we performed adenosine dose-response experiments and pharmacologically blocked adenosine deaminase activity with deoxycoformycin. In both kinds of experiment, adenosine-induced inhibition of TNF release could be restored in alcoholic cirrhotic patients. Conclusions: These data indicate that increased circulating adenosine deaminase activity blunts the antiinflammatory properties of adenosine in alcoholic cirrhotic patients.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

N-acetylcysteine and glycyrrhizin combination: Benefit outcome in a murine model of acetaminophen-induced liver failure

BACKGROUND Acetaminophen overdose is the most frequent cause of drug-induced liver failure in developed countries. Substantial progress has been made in understanding the mechanism of hepatocellular injury, but N-acetylcysteine remains the only effective treatment despite its short therapeutic window. Thus, other hepatoprotective drugs are needed for the delayed treatment of acetaminopheninduced hepatotoxicity. Our interest focused on glycyrrhizin for its role as an inhibitor of high mobility group box 1 (HMGB1) protein, a member of the family of damage-associated molecular pattern, known to play an important pathological role in various diseases. AIM To investigate the efficacy of the N-acetylcysteine/glycyrrhizin combination compared to N-acetylcysteine alone in the prevention of liver toxicity. METHODS Eight-week-old C57BL/6J wild-type female mice were used for all our experiments. Mice fasted for 15 h were treated with acetaminophen (500 mg/kg) or vehicle (phosphate-buffered saline) by intraperitoneal injection and separated into the following groups: Glycyrrhizin (200 mg/kg); N-acetylcysteine (150 mg/kg); and N-acetylcysteine/glycyrrhizin. In all groups, mice were sacrificed 12 h following acetaminophen administration. The assessment of hepatotoxicity was performed by measuring plasma levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase. Hepatotoxicity was also evaluated by histological examination of hematoxylin and eosin-stained tissues sections. Survival rates were compared between various groups using Kaplan-Meier curves. RESULTS Consistent with data published in the literature, we confirmed that intraperitoneal administration of acetaminophen (500 mg/kg) in mice induced severe liver injury as evidenced by increases in alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase but also by liver necrosis score. Glycyrrhizin administration was shown to reduce the release of HMGB1 and significantly decreased the severity of liver injury. Thus, the co-administration of glycyrrhizin and N-acetylcysteine was investigated. Administered concomitantly with acetaminophen, the combination significantly reduced the severity of liver injury. Delayed administration of the combination of drugs, 2 h or 6 h after acetaminophen, also induced a significant decrease in hepatocyte necrosis compared to mice treated with N-acetylcysteine alone. In addition, administration of N-acetylcysteine/glycyrrhizin combination was associated with an improved survival rate compared to mice treated with only N-acetylcysteine. CONCLUSION We demonstrate that, compared to N-acetylcysteine alone, co-administration of glycyrrhizin decreases the liver necrosis score and improves survival in a murine model of acetaminophen-induced liver injury. Our study opens a potential new therapeutic pathway in the prevention of acetaminophen hepatotoxicity.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Dynamic behavior analysis of in vitro cancerous cells by means of an automatic image processing device

SCOPUS: cp.pinfo:eu-repo/semantics/publishe

KATP channel subunits are expressed in the epididymal epithelium in several mammalian species.

Adenosine triphosphate-sensitive K(++) (K(ATP)) channels are poorly characterized in the reproductive tract. The present study was designed to evaluate the putative expression of K(ATP) channel subunits (Kir6.x and SURx) in the epididymis from different mammalian species. Immunohistochemical, Western blot, and RT-PCR techniques were used. A positive immunostaining for Kir6.2 (KCNJ11) and SUR2 (ABCC9) was observed by immunoenzymatic and immunofluorescent approaches in the principal epithelial cells throughout all regions of the rat and mouse epididymis. Double labeling with anti-aquaporin 9 (AQP9) and anti-Kir6.2 (KCNJ11) confirmed their colocalization in the principal cells. No immunostaining could be demonstrated for Kir6.1 (KCNJ8) and SUR1 (ABCC8) subunits. Under higher magnification, the immunostaining for Kir6.2 (KCNJ11) exhibited a cytoplasmic labeling that was more intense at the level of the Golgi apparatus along the whole epididymis. A similar pattern was observed for SUR2 (ABCC9), although in the latter case, the Golgi labeling appeared to be region specific. Spermatozoa in epididymal tubules from rodents also immunostained for Kir6.2 (KCNJ11) and SUR2 (ABCC9). Western blot analysis of epididymal total protein and crude membrane extracts from adult and prepubertal rats confirmed the presence of Kir6.2 (KCNJ11). SUR2 (ABCC9) protein expression was detected in adult epididymal extracts. Furthermore, RT-PCR established the presence of Kir6.2 (KCNJ11) and SUR2 (ABCC9) mRNA in prepubertal and adult mouse epididymis. Indirect immunofluorescence also documented the presence of Kir6.2 (KCNJ11) and SUR2 (ABCC9) in the epididymal epithelium, as well as in spermatozoa, of canine, feline, bovine, and human origin. These data demonstrate the presence of the K(ATP) channel subunits, Kir6.2 (KCNJ11) and SUR2 (ABCC9), in epididymal epithelial cells and spermatozoa from several mammalian species. Although their physiological roles need to be fully characterized, it is tempting to propose that such types of K(++) channels might be involved in protein secretion and fluid-electrolyte transport occurring along the epididymal epithelium, leading to spermatozoa maturation.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Intestinal bacteria as a key factor for alcoholic steatosis in mice

info:eu-repo/semantics/publishe

Lack of the Chemokine Receptor Ccr5 Exacerbates Acute Pancreatitis in Mice

info:eu-repo/semantics/publishe