Arenavirus Coinfections Are Common in Snakes with Boid Inclusion Body Disease.

Recently, novel arenaviruses were found in snakes with boid inclusion body disease (BIBD); these form the new genus Reptarenavirus within the family Arenaviridae. We used next-generation sequencing and de novo sequence assembly to investigate reptarenavirus isolates from our previous study. Four of the six isolates and all of the samples from snakes with BIBD contained at least two reptarenavirus species. The viruses sequenced comprise four novel reptarenavirus species and a representative of a new arenavirus genus.

Prophylactic potential of montelukast against mild colitis induced by dextran sulphate sodium in rats.

Cysteinyl leukotrienes play a part in inflammatory processes such as inflammatory bowel diseases. The present study aimed to evaluate the effects of the cys-LT-1 receptor antagonist montelukast on a mild colitis model in rats. Colitis was induced by administrating 4% dextran sulphate sodium (DSS, MW 45,000) in drinking water for 9 days. Montelukast (10 mg/kg/day) or vehicle was given by gastric gavage once daily simultaneously with DSS administration. A healthy control group receiving water as drinking fluid and vehicle by gastric gavage was included. Body weight loss, consistency of faeces (loose/diarrhoea) and occult blood in the faeces/ gross bleeding were assessed on days 6 - 9. After sacrifice, the following were assessed: colonic histology, the expression of inducible nitric oxide synthase, macrophage/monocyte marker ED1, cyclooxygenase-1 and cyclooxygenase-2, as well as the production of leukotriene B(4) and E(4), prostaglandin E(2), its metabolite bicyclic-prostaglandin E(2) and thromboxane B(2) in the colonic tissue incubation in vitro. Rats receiving DSS exhibited bloody diarrhoea from day 6 onwards. Montelukast significantly reduced the occult blood in the faeces/ gross bleeding, maintained normal body weight gain and tended to decrease the ratio of leukotriene B(4)/ prostaglandin E(2) production in the colon in vitro. The results indicate that montelukast has some potential to ameliorate mild experimental colitis induced by DSS.

Acute effects of the cys-leukotriene-1 receptor antagonist, montelukast, on experimental colitis in rats.

Cysteinyl leukotrienes play a part in inflammatory reactions such as inflammatory bowel diseases. The aim of the present study was to evaluate the acute effects of a cys-leukotriene-1 receptor antagonist, montelukast, on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Montelukast (5, 10 or 20 mg kg(-1) day(-1)), a 5-lipoxygenase inhibitor, zileuton (50 or 100 mg kg(-1) day(-1), a positive control), or the vehicle was administered intracolonically to the rats twice daily throughout the study, starting 12 h before the induction of colitis with TNBS. The severity of colitis (macroscopic and histological assessment, as well as myeloperoxidase activity), the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2, and eicosanoid production in colonic tissue incubation were assessed 24 and 72 h after colitis induction. Montelukast increased prostaglandin E(2) production at 24 h and tended to reduce the cyclooxygenase-2 protein expression at 72 h, but did not influence the severity of colitis. Zileuton failed to decrease the inflammatory reaction in spite of reduced leukotriene B(4) production at 72 h. The results suggest that drugs that block cysteinyl leukotriene receptors have limited potential to ameliorate acute TNBS-induced colitis, but that they exert some beneficial effects which make them capable of modulating the course of colitis.

Vascular changes in cyclosporine A-induced hypertension and nephrotoxicity in spontaneously hypertensive rats on high-sodium diet.

Functional and morphological changes of blood vessels in cyclosporine A (CsA)-induced hypertension and nephrotoxicity were studied in spontaneously hypertensive rats (SHR). The role of the L-arginine-nitric oxide (NO) pathway and the importance of oxidative stress in CsA toxicity were also assessed. SHR (7-8 week old) on a high-sodium diet were treated with CsA (5 mg kg(-1) d(-1) s.c.) for 6 weeks. A proportion of the rats were treated concomitantly with the NO precursor L-arginine (1.7 g kg(-1)d(-1) p.o.). CsA elevated blood pressure and caused renal dysfunction and morphological nephrotoxicity. CsA also impaired mesenteric and renal arterial function and caused structural damage to intrarenal and extrarenal small arteries and arterioles. Medial atrophy of the mesenteric resistance vessels and decreased viability of smooth muscle cells of the thoracic aorta were observed. Renal and arterial damage was associated with the presence of inflammatory cells. CsA did not affect markers of the L-arginine-NO pathway (urinary cyclic GMP excretion or endothelial or inducible NO synthase expression in kidney, aorta or heart) or oxidative stress (urinary excretion of 8-isoprostaglandin F2alpha, plasma urate concentration or total radical trapping capacity). Concomitant L-arginine treatment did not affect CsA-induced changes in blood pressure or histological findings but tended to alleviate the arterial dysfunction. The renal and cardiovascular toxicity of CsA was associated with arterial dysfunction and morphological changes in small arteries and arterioles in SHR on a high-sodium diet. The findings did not support the role of oxidative stress or a defect in the L-arginine-NO pathway.

Suppression of pro-inflammatory cytokine release by selective inhibition of inducible nitric oxide synthase in mucosal explants from patients with ulcerative colitis.

BACKGROUND: In ulcerative colitis (UC), inflammatory damage is associated with increased production of pro-inflammatory cytokines and nitric oxide through the inducible nitric oxide synthase (iNOS) pathway. In an animal model of acute experimental colitis we have previously shown amelioration of inflammation with the highly selective iNOS inhibitor 1400W. The aim of the present study was to investigate the effects of selective iNOS inhibition on the production of pro-inflammatory cytokines by the colon mucosa in UC. METHODS: Inflamed and uninflamed mucosa from patients with severe UC were incubated with a highly selective iNOS inhibitor N-[3-(aminomethyl)benzyl]acetamidine (1400W), with a relatively selective cNOS inhibitor N(G)-nitro-L-arginine-methyl-esther (L-NAME), or with an NO-donor, S-nitroso-acetylpenicillamine (SNAP). Cytokine concentrations in the incubation medium were quantitated with ELISA. RESULTS: Compared to uninflamed mucosa there was an increase in iNOS protein and nitrotyrosine levels in inflamed mucosal samples. Immunolocalization of iNOS and nitrotyrosine showed their expression in inflammatory cells in the lamina propria. Expression of iNOS was also found in the epithelial brush border. Selective inhibition of iNOS suppressed the release of tumour necrosis factor alpha (TNF-alpha, by 66%) and interleukin-6 (IL-6, by 27%). The NO-donor, SNAP, augmented the secretion of TNF-alpha, IL-6 and IL-1-beta (by 62%, 52% and 175%, respectively) and decreased the release of IL-1 receptor antagonist (IL-1Ra, by 34%) by the inflamed mucosa. Moreover, in uninflamed samples, 1400W suppressed the production of TNF-alpha (by 69%) and incubation with SNAP decreased IL-6 concentrations by 48%. The cNOS over iNOS selective inhibitor L-NAME had no significant effects on the accumulation of cytokines. CONCLUSION: Selective inhibition of iNOS suppresses mucosal TNF-alpha and IL-6 release in active UC, whereas NO seems to exacerbate the inflammatory response. These results suggest that selective iNOS inhibition may have therapeutic promise in the treatment of UC.

Effects of Lactobacillus rhamnosus GG and Lactobacillus reuteri R2LC on acetic acid-induced colitis in rats.

BACKGROUND: Certain lactobacilli reduce the severity of experimental colitis. The aim of this study was to compare the effects of a human strain Lactobacillus rhamnosus GG and a rat strain Lactobacillus reuteri R2LC on acetic acid-induced colitis in rats. METHODS: Lactobacillus rhamnosus GG, Lactobacillus reuteri R2LC or sulphasalazine were given orally to the rats. Colitis was assessed 72 h after induction with acetic acid. RESULTS: Lactobacillus reuteri R2LC significantly antagonized body weight loss caused by inflammation compared with Lactobacillus rhamnosus GG and sulphasalazine, and oedema formation in the colon compared with sulphasalazine. Lactobacillus reuteri R2LC reduced the median value of macroscopic ulceration and the protein content of inducible nitric oxide synthase by 50% and the median of the protein content of inducible cyclooxygenase by 30% compared with that of the colitis control group, and Lactobacillus rhamnosus GG reduced the median of inducible nitric oxide protein content by 40% and increased the median of inducible cyclooxygenase protein content by 30% compared with the median value of the colitis control group, but these differences were not statistically significant. CONCLUSIONS: The rat strain Lactobacillus reuteri R2LC, but not the human strain Lactobacillus rhamnosus GG, is of benefit in reducing the severity of acetic acid-induced colitis in rats. These results suggest that it is not the total amount of Lactobacillus but the particular species or strain of Lactobacillus that is important in attenuating experimental colitis.