The Effect of Dexamethasone Treatment on Murine Colitis

Background: Studies in developed countries would suggest that the immune response to Helicobacter pylori infection is a T helper cell 1 predominant response. Unlike subjects from developed countries, those resident in developing countries are subject to infection with a myriad of gastrointestinal pathogens from early in life. Given that H. pylori is acquired early in life, such infections may alter the immune response to H. pylori. The aim of this study was to compare the immune response to H. pylori in subjects from developed and developing countries. Methods: Using a previously validated IgG subclass ELISA, the H. pylori specific IgG1/IgG2 subclass ratio (a marker of the T helper cell response) in 58 adult and 21 paediatric symptomatic H. pylori positive Sowetan subjects was compared with that in 64 Australian and 45 German symptomatic H. pylori positive subjects. Results: An IgG1 predominant response (IgG1/IgG2 ratio >1) was observed in 81% of Sowetan adults and 90% of children compared with 4.7% of Australians and 4.4% of Germans. The IgG1/IgG2 ratio was significantly higher in Sowetans compared with Australians and Germans ( P < 0.001). In Australian and German subjects the IgG1/IgG2 ratio was significantly higher in NUD compared with DU. No significant difference was observed between NUD and other disease states in Sowetans. Conclusions: This study is the first to provide evidence that the host immune response to H. pylori infection in an African population differs to that observed in subjects from developed countries. Further studies are required to determine if this occurs in other developing countries.     

Does Ursodeoxycholic Acid Exert a Protective Effect on Liver Grafts in Orthotopic Liver Transplantation

No abstract available.     

Plant-Derived Polysaccharide Supplements Inhibit Dextran Sulfate Sodium-Induced Colitis in the Rat

Several plant-derived polysaccharides have been shown to have anti-inflammatory activity in animal models. Ambrotose complex and Advanced Ambrotose are dietary supplements that include aloe vera gel, arabinogalactan, fucoidan, and rice starch, all of which have shown such activity. This study was designed to evaluate these formulations against dextran sulfate sodium (DSS)-induced colitis in rats and to confirm their short-term safety after 14 days of daily dosing. Rats were dosed daily orally with vehicle, Ambrotose or Advanced Ambrotose. On day six groups of rats received tap water or 5% Dextran Sulfate sodium. Ambrotose and Advanced Ambrotose significantly lowered the disease scores and partially prevented the shortening of colon length. An increase in monocyte count was induced by dextran sulfate sodium and inhibited by Ambrotose and Advanced Ambrotose. There were no observable adverse effects after 14-day daily doses. The mechanism of action of the formulations against DSS-induced colitis may be related to its effect on monocyte count.     

Effect of Azithromycin on Acute Inflammatory Lesions and Colonic Bacterial Load in a Murine Model of Experimental Colitis

Background  

The aim of this study was to investigate the effect of the macrolide antibiotic azithromycin on mucosal changes and colonic bacterial load in a murine model of colitis.     

Protective Effect of Saffron in Mouse Colitis Models Through Immune Modulation

Digestive Diseases and Sciences - People with inflammatory bowel disease (IBD) including ulcerative colitis are at risk for colorectal cancer. Despite available effective drugs used to treat IBD,...     

Variable Impact of CD39 in Experimental Murine Colitis

Background

Dysregulation of immune responses in inflammatory bowel diseases (IBD) results in intestinal inflammation and vascular injury while exacerbating systemic disease. CD39 is an ectonucleotidase, expressed by T regulatory cells and dendritic cells, that hydrolyzes extracellular nucleotides to modify those cellular immune responses implicated in IBD. Genetic polymorphisms of CD39 have been linked to Crohn??s disease while gene deletion in mice exacerbates dextran sodium sulphate-induced colitis.

Aim

The aim of this study was to test how global deletion of CD39 in mice impacts other models of experimental colitis.

Methods

Colitis was induced in CD39-null and -wt mice, using trinitrobenzene sulfonic acid (TNBS, 125 mg/kg) administered intrarectally. Oxazolone colitis (1.5% oxazolone in 50% alcohol) was induced in comparable groups. Morphology, clinical and molecular parameters, and FACS analyses of lamina propria mononuclear cells (LPMC) were examined in CD39-null mice. CD39 expression was analyzed in human IBD biopsies.

Results

Paradoxically, TNBS colitis in CD39-null mice was characterized by improved survival, favorable clinical scores, and decreased MPO activity, when compared to wt mice (P < 0.05). LPMC from TNBS colitis contained significantly increased amounts of T-cells (CD3⁺ and CD4⁺) and TNF-?? mRNA expression were increased over those in CD39 null mice (P < 0.05). In contrast, oxazolone treated CD39-null and wt mice had comparable outcomes. In both ulcerative colitis and Crohn??s disease, CD39 is present at high levels in intestinal tissue biopsies.

Conclusions

TNBS colitis was attenuated in CD39-null mice whereas oxazolone-induced colitis was not impacted. Impaired adaptive cellular immune reactivity in the CD39-null environment appears protective in hapten-mediated Th1-type colitis. CD39 is expressed at high levels in clinical IBD tissues.     

Role of Interleukin-10 in a Murine Model of Dextran Sulfate Sodium-Induced Colitis

Background: Increased production of proinflammatory cytokines is characteristic of both animal models of experimental colitis and human inflammatory bowel disease. This study was designed to characterize the functional role of interleukin (IL)-10 in a murine model of experimental colitis. Methods: Cytokine profiles were analyzed in animals with dextran sulfate sodium-induced colitis. The effect of treatment with IL-10 or anti-IL-10 antibodies on colonic cytokine production in vitro and tissue damage in vivo were evaluated. Results     

Rectal Administration of Lipopolysaccharide and Ovalbumin Ameliorates Acute Murine Colitis

Background  

Repeated challenges of lipopolysaccharide (LPS) could reduce the expression of proinflammatory cytokines in vitro, and oral administration of ovalbumin (OVA) induces mucosal tolerance in vivo. However, the effect of local administration of LPS and OVA on experimental colitis in vivo remains unknown.     

Activating and Protective Capacities of a Purified Electrophoretic Fraction of Murine Leukemia Virus for Murine Leukemia Virus Infectivity

A highly purified gel electrophoretic fraction of murine leukemia virus (MuLV) can confer enhanced infectivity on MuLV derived from tissue culture and can protect MuLV from neutralization by specific antiserum. Of the known viral proteins tested, a purified electrophoretic fraction (14,000 daltons) is the only active fraction and seems to consist of the group-specific antigen I and an associated lipid moiety. The action of this fraction obtained from one type of MuLV is group-specific in that it can enhance and protect serologically different types of MuLV. The effect of this fraction is exerted on viruses and not on cells. MuLV derived from tumors was not enhanced by the fraction, but became amenable to its action after a single passage through tissue culture. Reconstruction experiments suggested that the fraction may consist of an exterior protein associated with some lipids. This complex, which apparently protrudes on the viral surface, is required for infectivity and shields the type-specific antigen containing the hemagglutinating site.     

Protective Effect of Comaruman, a Pectin of Cinquefoil Comarum palustre L., on Acetic Acid-Induced Colitis in Mice

The efficacy of comaruman CP, a pectin of marsh cinquefoil Comarum palustre L., was investigated using a model of acetic acid-induced colitis in mice. Mice were administered comaruman CP orally 2 days prior to rectal injection of 5% acetic acid and examined for colonic damage 24 hr later. Colonic inflammation was characterized by macroscopical injury, higher levels of myeloperoxidase activity, enhanced vascular permeability, and diminution of colonic mucus. Oral administration of comaruman CP was found to prevent progression of colitis. Colonic macroscopic scores and the total square of damage were significantly reduced in mice treated with CP compared with the vehicle-treated colitis group. Peroral pretreatment of mice with comaruman CP was shown to decrease tissue myeloperoxidase activity in colons compared with the colitis group. Comaruman CP was found to stimulate production of mucus by colons of normal and colitis mice. Comaruman CP decreased the inflammatory status of normal mice as elicited by reduction of vascular permeability and adhesion of peritoneal neutrophils and macrophages. Thus, a preventive effect of comaruman on acetic acid-induced colitis in mice was detected. Reduction of neutrophil infiltration and enhancement of colon-bound mucus may be implicated in the protective effect of comaruman.     

不同浓度脂联素通过减轻氧化应激损伤保护缺血再灌注心肌

目的观察不同浓度脂联素对大鼠心肌缺血再灌注损伤及其所引起的氧化应激的影响,以探讨脂联素保护缺血再灌注心肌是否与减轻氧化应激有关。方法将80只健康SD大鼠随机分成假手术组、缺血再灌注组、低浓度脂联素组(60 ng/g)、中浓度脂联素组(120 ng/g)和高浓度脂联素组(180 ng/g),每组16只。假手术组只穿线,不结扎,旷置225 m in;缺血再灌注组冠状动脉前降支结扎45 m in后,再灌注180 m in;各脂联素组于缺血前30m in经股静脉给予不同浓度脂联素,再进行缺血再灌注。各组进一步随机分为两个亚组。亚组1(8只)在缺血45m in再灌注180 m in后,用Evans b lue-TTC双染法测定心肌梗死面积;亚组2(8只)在大鼠再灌注180 m in后对左心室内压及单位时间左心室内压变化值(±dp/dt)等血流动力学指标进行检测。实验结束后,在心尖处取血并取心肌组织,测定大鼠血清超氧化物歧化酶活性、心肌组织总一氧化氮合酶及一氧化氮含量。结果与假手术组比较,缺血再灌注组大鼠血清中超氧化物歧化酶活性及心肌组织中总一氧化氮合酶和一氧化氮含量明显下降,心肌梗死面积增大;与缺血再灌注组比较,各浓度脂联素组心肌梗死面积减小,心肌舒缩功能有所改善,大鼠血清超氧化物歧化酶活性及心肌组织总一氧化氮合酶和一氧化氮含量显著增加,并随脂联素浓度增加而增加。结论脂联素对缺血再灌注心肌细胞有保护作用,减少缺血再灌注心肌的梗死面积,改善心脏舒缩功能;其作用机制可能是通过增加缺血再灌注心肌组织总一氧化氮合酶和一氧化氮含量及血清超氧化物歧化酶活性,从而减轻氧化应激损伤。     

脂联素在心房颤动中的保护作用及其研究进展

心房颤动是临床实践中最常见的心律失常。目前确切机制仍不清楚,病理生理机制复杂,且诸多可能的机制相互关联。近年来发现脂联素与心房颤动的发生及维持密切相关。由于脂联素具有减轻体重、逆转心肌重构、增强胰岛素敏感性、抗炎、抗动脉粥样硬化、抗高血压、保护血管内皮功能等作用。因此对心房颤动的保护作用具有巨大的潜力。     

Protective Effects of Lithium on Acetic Acid-Induced Colitis in Rats

Inflammatory bowel disease (IBD) is a multifactorial disease with unknown etiology characterized by oxidative stress, leukocyte infiltration, and rise in inflammatory cytokines such as tumor necrosis factor (TNF-α). Lithium, as a therapeutic agent for bipolar disorder, exerts some anti-inflammatory properties. In this study we have investigated the effects of lithium on acetic-acid-induced colitis in rats. Lithium (5, 10, and 20 mg/kg) was administered 1 h before the introduction of acetic acid. Colonic status was investigated 24 h following colitis induction through macroscopic, histological, and biochemical analyses. Lithium (20 mg/kg) ameliorated macroscopic and microscopic scores. These observations were accompanied by a reduction in the degree of both neutrophil infiltration, indicated by decreased myeloperoxidase activity, and lipid peroxidation, as measured by a decline in malondialdehyde content in inflamed colon as well as a decrease in TNF-α levels. These findings suggest that lithium exerts beneficial effects on experimental colitis and therefore might be useful in the treatment of IBD.     

The Protective Effect of the Recombinant 53-kDa Protein of Trichinella spiralis on Experimental Colitis in Mice

Background

Helminth infection has been proven to reduce the severity of experimental inflammatory bowel disease (IBD). The excretory-secretory proteins of helminths play an important role in the process of immunomodulation.

Aims

In the present study, we aimed to investigate the protective potential of recombinant Trichinella spiralis (TS) 53-kDa protein (rTsP53), a component of excretory-secretory proteins, on experimental colitis in mice.

Methods

BALB/c mice were treated subcutaneously with 50 ??g rTsP53 three times at an interval of 5 days. Colitis was induced by intrarectal administration of 5 mg trinitrobenzene sulfonic acid (TNBS). Disease activities and macroscopic and microscopic scores were evaluated. To determine immune response provoked by rTsP53, we measured specific IgG1 and IgG2a values against rTsP53 in sera of mice. We also detected cytokine profiles as well as the markers of alternatively activated macrophages (M2) in mice.

Results

RTsP53 ameliorated significantly the disease activity index (DAI) as well as the macroscopic and microscopic scores. IgG1 but not IgG2a was the predominant specific antibody detected in the sera of immunized mice, indicating the potential of stimulating T-helper (Th) 2 bias response by rTsP3. Pre-treatment with rTsP53 decreased serum Th1 cytokines (TNF-a, IFN-??) and elevated serum levels of serum Th2 cytokines (IL-4, IL-13); it also decreased colonic Th1 cytokines (TNF-??, IL-6) and colonic regulatory cytokines (IL-10, TGF-??1). RTsP53 increased colonic M2 markers, arginase-1 (Arg-1), and found in inflammatory zone 1 (FIZZ1), compared to mice without rTsP53 pretreatment.

Conclusions

RTsP53 is a potential protective agent for IBD.     

Adiponectin as a Protective Factor Against the Progression Toward Type 2 Diabetes Mellitus in Postmenopausal Women

Serum adiponectin levels have been suggested to be predictors of type 2 diabetes mellitus in diverse populations. However, the relationship between circulating adiponectin levels and the risk of development of type 2 diabetes in postmenopausal women has not been investigated.A total of 382 healthy postmenopausal women who participated in a prospective cohort study were followed for 5.8 years. Type 2 diabetes mellitus was defined according to the criteria set out by the American Diabetes Association. Adiponectin, osteoprotegerin (OPG), and high-sensitivity C-reactive protein (hs-CRP) levels were measured using ELISA.Of 195 women who did not have diabetes at baseline and who were reexamined in the second phase of the study for diabetic status, 35 subjects (17.9%) developed type 2 diabetes mellitus during the 5.8 years follow-up period. The women with type 2 diabetes had lower adiponectin levels than the healthy postmenopausal women. Multiple regression analysis showed that, after adjustments were made for age, cardiovascular risk factors, OPG, and hs-CRP levels, higher baseline adiponectin levels were associated with a lower relative risk (RR) of having type 2 (RR = 0.07, confidence interval [CI]: 0.01–0.66, P = 0.021).Higher baseline adiponectin levels functioned as a predictor of a lower risk of developing type 2 diabetes mellitus among postmenopausal women during a 5.8 years follow-up study. Therefore, it is suggested that elevated adiponectin levels may offer protection against the development of type 2 diabetes mellitus after the menopause.     

大蒜素对三硝基苯磺酸诱导大鼠结肠炎的保护作用及其机制研究

背景：溃疡性结肠炎（UC）是一种病因未明的结直肠炎症,大蒜素对其防治的作用目前尚未有结论。目的：探讨大蒜素对TNBS诱导的大鼠结肠炎的保护作用及其机制。方法：80只大鼠随机分为对照组、TNBS组、大蒜素预防组、大蒜素灌胃组、大蒜素灌肠组、地塞米松组、柳氮磺吡啶组、巴柳氮钠组。以含150mg／kgTNBS的50％乙醇溶液灌肠制备大鼠结肠炎模型。造模2周后处死大鼠。行大体评分和病理学评分,以ELISA法测定血清TNF-α、IL-1β、IL-10、IL4含量,蛋白质印迹法检测NF—κB表达。结果：与对照组相比,TNBS组大体和病理学评分均明显升高（P〈0．05）,体质量明显降低（P〈0．05）,血清TNF-α、IL-1B含量显著升高（P〈0．05）,血清IL-4、IL-10含量显著降低（P〈0．05）,NF-κB表达明显升高（P〈0．05）;给予大蒜素预防或治疗后,上述指标均明显改善（P〈0．05）,但疗效低于地塞米松组、柳氮磺吡啶组、巴柳氮钠组。结论：大蒜素对TNBS诱导的大鼠结肠炎有保护作用,可能是通过调控细胞因子和NF—κB而发挥作用的。     

The Anti-Inflammatory Effect and Intestinal Barrier Protection of HU210 Differentially Depend on TLR4 Signaling in Dextran Sulfate Sodium-Induced Murine Colitis

Background

Ulcerative colitis (UC) is strongly associated with inflammation and intestinal barrier disorder. The nonselective cannabinoid receptor agonist HU210 has been shown to ameliorate inflamed colon in colitis, but its effects on intestinal barrier function and extraintestinal inflammation are unclear.

Aims

To investigate the effects and the underlying mechanism of HU210 action on the UC in relation to a role of TLR4 and MAP kinase signaling.

Methods

Wild-type (WT) and TLR4 knockout (Tlr4 ^?/?) mice were exposed to 4% dextran sulfate sodium (DSS) for 7 days. The effects of HU210 on inflammation and intestinal barrier were explored.

Results

Upon DSS challenge, mice suffered from bloody stool, colon shortening, intestinal mucosa edema, pro-inflammatory cytokine increase and intestinal barrier destruction with goblet cell depletion, increased intestinal microflora accompanied with elevated plasma lipopolysaccharide, reduced mRNA expression of the intestinal tight junction proteins, and abnormal ratio of CD4⁺/CD8⁺ T cells in the intestinal Peyer’s patches. Pro-inflammatory cytokines in the plasma and the lung, as well as pulmonary myeloperoxidase activity, indicators of extraintestinal inflammation were increased. Protein expression of p38α and pp38 was up-regulated in the colon of WT mice. Tlr4 ^?/? mice showed milder colitis. HU210 reversed the intestinal barrier changes in both strains of mice, but alleviated inflammation only in WT mice.

Conclusions

Our study indicates that in experimental colitis, HU210 displays a protective effect on the intestinal barrier function independently of the TLR4 signaling pathway; however, in the extraintestinal tissues, the anti-inflammatory action seems through affecting TLR4-mediated p38 mitogen-activated protein kinase pathway.

     

Inhibition of Selectin Function and Leukocyte Rolling Protects Against Dextran Sodium Sulfate-Induced Murine Colitis

Background: The selectin family of adhesion molecules (P-, E- and L-selectin) plays an important role in inflammatory reactions by mediating interactions between leukocytes and activated endothelial cells. However, a recent study using gene-targeted mice has suggested that adhesion molecules (P- and Eselectin and ICAM-1) may not be relevant targets in intestinal inflammation. The objective of the present study was to re-evaluate the potential role of selectins in experimental colitis in wild-type mice using the polysaccharide fucoidan, which inhibits the function of P- and L-selectin. Methods: For this purpose, Balb/c mice were exposed to 5% dextran sodium sulfate (DSS) in the drinking water for 5 days with and without daily administration of fucoidan (25 mg/kg, i.v.). In separate experiments, the effect of fucoidan on leukocyte-endothelium interactions was examined by use of intravital microscopy. Results: