Mechanism of Fecal Bacteriotherapy in Treating Clostridium Difficile Infection and GI Tract Disorders

Clostridium difficile infection, an increasingly prevalent and virulent condition, is often resistant to treatment. Standard antibiotic therapy is rarely efficient when used to treat recurrent C. difficile infection. Fecal microbiota transplantation (FMT) is a safe, effective and inexpensive treatment that has a cure rate of about 90%, according to clinical trials and reports. This approach may also be applicable in treating ulcerative colitis, a type of inflammatory bowel disease, on the basis of the restoration of flora imbalances. Additionally, recent data suggests that a disproportion in composition of the gut microbiome may contribute to obesity. FMT, may restore a healthy balance. Using information from Touro College’s database, this article discusses the reason behind the success of fecal microbiota transplantation when used to treat Clostridium difficile infection and ulcerative colitis. The effect of diet, environment and geography on the bacterial flora is also explored

Statin-induced expression of CD59 on vascular endothelium in hypoxia: a potential mechanism for the anti-inflammatory actions of statins in rheumatoid arthritis

Hypoxia, which leads to dysfunctional cell metabolism, and complement activation both play central roles in the pathogenesis of rheumatoid arthritis (RA). Recent studies have reported that mice deficient for the complement-inhibitory protein CD59 show enhanced susceptibility to antigen-induced arthritis and reported that statins have anti-inflammatory effects in RA. We hypothesized that the anti-inflammatory effect of statins in RA relates in part to their ability to increase CD59 expression in hypoxic conditions and therefore to reduce complement activation. Flow-cytometric analysis showed that CD59 expression on endothelial cells (EC) was unaffected by atorvastatin in normoxia (21% O(2)), whereas in hypoxic conditions (1% O(2)) an up to threefold dose-dependent increase in CD59 expression was seen. This effect of hypoxia was confirmed by treatment of EC with chemical mimetics of hypoxia. The upregulation of CD59 protein expression in hypoxia was associated with an increase in steady-state mRNA. L-Mevalonate and geranylgeraniol reversed the response, confirming a role for inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase and geranylgeranylation. Likewise, inhibition by N(G)-monomethyl-L-arginine and N(G)-nitro-L-arginine methyl ester confirmed that CD59 upregulation in hypoxia was nitric oxide dependent. The expression of another complement-inhibitory protein, decay-accelerating factor (DAF), is known to be increased by atorvastatin in normoxia; this response was also significantly enhanced under hypoxic conditions. The upregulation of CD59 and DAF by atorvastatin in hypoxia prevented the deposition of C3, C9 and cell lysis that follows exposure of reoxygenated EC to serum. This cytoprotective effect was abrogated by inhibitory anti-CD59 and anti-DAF mAbs. The modulation of EC CD59 and DAF by statins under hypoxic conditions therefore inhibits both early and late complement activation and may contribute to the anti-inflammatory effects of statins in RA

Atorvastatin-induced CD59 and decay-accelerating factor in hypoxia enhance endothelial cell cytoprotection

<p><b>Copyright information:</b></p><p>Taken from "Statin-induced expression of CD59 on vascular endothelium in hypoxia: a potential mechanism for the anti-inflammatory actions of statins in rheumatoid arthritis"</p><p>Arthritis Research & Therapy 2006;8(4):R130-R130.</p><p>Published online 21 Jul 2006</p><p>PMCID:PMC1779384.</p><p></p> Human umbilical vein endothelial cells (HUVEC) were cultured under normoxic or hypoxic conditions with and without atorvastatin (0.25 μM) for 48 hours followed by 3 hours reoxygenation. Harvested endothelial cells (EC) were incubated with 20% C5-deficient (C5 D) serum (filled bars) or heat-inactivated (HI) normal human serum (NHS) (open bars) for 2 hours. C3 binding was analysed by flow cytometry and results are expressed as the percentage of C3 binding relative to that on EC exposed to C5 D in normoxia (shown as 100%). *< 0.05 (= 4), difference between levels of cell surface C3 deposition on EC cultured under hypoxic conditions in the presence or absence of atorvastatin HUVEC were cultured under normoxic or hypoxic conditions with and without atorvastatin (0.5 μM) for 48 hours followed by 3 hours of reoxygenation. C9 binding was analysed by flow cytometry following incubation with 20% NHS (filled bars) or HI serum (open bars). Results are expressed as the percentage of C9 binding relative to that on EC exposed to NHS in normoxia (shown as 100%). *< 0.05 (= 4), difference between statin-treated and untreated EC in hypoxia.HUVEC were incubated in 1% Owith or without atorvastatin (At) 0.5 μM for 48 hours followed by 3 hours of reoxygenation. EC were preincubated with the inhibitory mAbs Bric229 (CD59) and 1H4 (decay-accelerating factor) (20 μg/ml) or veronal buffered saline + 1% gelatin at 4°C. EC were then incubated with 20% rabbit serum or 20% HI rabbit serum at 37°C for 1 hour and propidium iodide (PI) was added prior to analysis by flow cytometry. The percentage EC lysis was calculated as the number of PI-positive cells expressed as a percentage of the total number of cells. **< 0.001 (= 4), difference between statin-treated and untreated EC

Hypoxia increases atorvastatin-induced decay-accelerating factor expression

<p><b>Copyright information:</b></p><p>Taken from "Statin-induced expression of CD59 on vascular endothelium in hypoxia: a potential mechanism for the anti-inflammatory actions of statins in rheumatoid arthritis"</p><p>Arthritis Research & Therapy 2006;8(4):R130-R130.</p><p>Published online 21 Jul 2006</p><p>PMCID:PMC1779384.</p><p></p> Analysis of decay-accelerating factor expression on human umbilical vein endothelial cells (HUVEC) following 48 hours culture in 21% O(open bars) or 1% O(filled bars) in the presence or absence of atorvastatin (0.25 μM). and HUVEC were treated with increasing concentrations of atorvastatin for 48 hours in the presence (filled bars) or absence (open bars) of (b) cobalt chloride (CoCl) (100 μM) or (c) desferrioxamine (DFO) (100 μM). Decay-accelerating factor expression was measured by flow cytometry using the mAb 1H4. Bars represent the mean ± standard error of the mean (= 4). *< 0.05, **< 0.01 compared with untreated controls

Mechanisms involved in atorvastatin-induced decay-accelerating factor expression

<p><b>Copyright information:</b></p><p>Taken from "Statin-induced expression of CD59 on vascular endothelium in hypoxia: a potential mechanism for the anti-inflammatory actions of statins in rheumatoid arthritis"</p><p>Arthritis Research & Therapy 2006;8(4):R130-R130.</p><p>Published online 21 Jul 2006</p><p>PMCID:PMC1779384.</p><p></p> Human umbilical vein endothelial cells (HUVEC) were cultured for 48 hours under hypoxia (1% O) and were treated with atorvastatin (At) (0.5 μM) in the presence or absence of mevalonate (200 μM), -monomethyl-L-arginine (L-NMMA) (500 μM), -nitro-L-arginine methyl ester (L-NAME) (100 μM) and geranylgeraniol (GGOH) (20 μM). Endothelial cell CD59 expression was measured by flow cytometry using the mAb BRIC 229. Results are expressed as the percentage increase in relative fluorescence intensity above the hypoxic control (US) (= 4). *< 0.5, **< 0.01 compared with untreated controls