Preventive and therapeutic effects of Lactobacillus paracasei B21060-based synbiotic treatment on gut inflammation and barrier integrity in colitic mice.

BACKGROUND: Although gut microbiota perturbation is recognized as a main contributing factor to the pathogenesis of inflammatory bowel disease, synbiotic therapies, as prevention or treatment, have remained overlooked. OBJECTIVE: To verify whether Lactobacillus paracasei B21060-based synbiotic therapy could prevent or repair colon damage in a mouse model of colitis, we performed treatments before and after colitis induction. METHODS: The experimental study lasted 19 d. Experimental colitis was induced in BALB/c mice by giving them dextran sodium sulfate (DSS, 2.5%) in drinking water (days 7-12) followed by DSS-free water (days 13-19) (DSS group). L. paracasei B21060 (2.5 × 10(7) bacteria/10 g body weight) was orally administered 7 d before DSS [synbiotic as preventive treatment (P-SYN) group] or 2 d after DSS [synbiotic as therapeutic treatment (T-SYN) group] until day 19. Another group was not treated with DSS or synbiotic and was given tap water (control group), for a total of 4 groups. RESULTS: Compared with the DSS group, both synbiotic-treated groups had significantly less pronounced weight loss and colon damage. Consistently, mRNA levels of chemokine (C-C motif) ligand 5 in the colon were reduced in both P-SYN and T-SYN mice compared with the DSS group (51%, P < 0.05 and 72%, P < 0.001, respectively). In the P-SYN and T-SYN groups, neutrophil elastase transcription was also reduced (51%, P < 0.01 and 59%, P < 0.001, respectively). Accordingly, oxidative/nitrosative stress was lower in P-SYN and T-SYN mice than in the DSS group. In P-SYN and T-SYN mice, colonic gene expression of tumor necrosis factor (47%, P < 0.01 and 61%, P < 0.001, respectively) and prostaglandin-endoperoxide synthase 2 (45%, P < 0.01 and 35%, P < 0.05, respectively) was lower, whereas interleukin 10 mRNA was doubled compared with the DSS group (both P < 0.5). Remarkably, epithelial barrier integrity (zonulin and occludin) and gut protection (ß-defensin and mucin expression) were completely restored in P-SYN and T-SYN mice. CONCLUSIONS: Our data highlight the beneficial effects of this synbiotic formulation in acutely colitic mice, suggesting that it may have therapeutic and possibly preventive efficacy in human colitis.

13C-aminopyrine breath test accurately predicts long-term outcome of chronic hepatitis C.

BACKGROUND & AIMS: Although numerous non-invasive tests are currently available to explore liver function and disease activity in patients with HCV-related chronic diseases, none of these indicate the likelihood of disease progression in the individual patient. We aimed at assessing the prognostic ability of (13)C(2)-aminopyrine breath test ((13)C-ABT) in the prediction of liver fibrosis progression in patients with HCV chronic hepatitis who prospectively entered a long-term follow-up. METHODS: Fifty patients with HCV-related chronic disease who underwent paired liver biopsy (at baseline and after a mean period of 86 months) were included in the study. (13)C-ABT was carried out at baseline and every 3 years. Histological progression was defined as increase of at least 2 fibrosis units according to Ishak score. RESULTS: Fourteen patients progressed of at least 2 fibrosis units during the follow-up. These patients were more frequently infected with a HCV-1b genotype and had, at baseline, a significantly older age, higher BMI, AST levels, and AST to platelet ratio index (APRI). (13)C-ABT was altered in 57% of cases at baseline and in 100% of the cases at 3-year follow-up. In the univariate analysis, age (p=0.005), BMI (p=0.006), platelet count (p=0.03), AST (p=0.012) and ALT (p=0.04) levels, APRI (p=0.03), and baseline (13)C-ABT results (p<0.0001) were all independently associated with progression of liver fibrosis. By Cox's multiple regression analysis, the (13)C-ABT was the only covariate that significantly predicted liver fibrosis progression (HR 6.7; 95% CI 2.3-20.1; p<0.001). CONCLUSIONS: (13)C-ABT accurately predicts the risk of disease progression in patients with HCV-related chronic hepatitis.

Topical treatment of distal active ulcerative colitis with beclomethasone dipropionate or mesalamine: a single-blind randomized controlled trial.

GOALS: Therapy for active ulcerative colitis (UC) usually involves rectal formulations of corticosteroids (CS), which are characterized by the risk of systemic steroid-related adverse effects. BACKGROUND: To compare the efficacy and safety of the topically acting CS beclomethasone dipropionate (BDP) versus mesalamine (5-ASA) in the treatment of active UC. STUDY: Patients with mild to moderate distal active UC were randomized to a 6-week treatment with BDP 3 mg enema o.d. or 5-ASA 1 g enema daily in a single-blind, multicenter, parallel-group, controlled study. The primary efficacy variable was the decrease in Disease Activity Index (DAI) score. Safety variables were adrenal function, monitoring of adverse events, vital signs, and laboratory parameters. RESULTS: A total of 217 patients were enrolled and treated with BDP (n = 111) or 5-ASA (n = 106). A significant decrease in the DAI score (P < 0.05) was observed in both treatment groups, with a clinical remission rate of 36.7% in the BDP group and of 29.2% in the 5-ASA group. Both treatments were well tolerated. No changes from baseline in morning cortisol levels were observed in the BDP group. CONCLUSIONS: BDP administered as a rectal enema over a 6-week treatment period was efficacious and safe in patients with active UC, without interference with pituitary adrenal axis.

Per-rectal portal scintigraphy is complementary to ultrasonography and endoscopy in the assessment of portal hypertension in children with chronic cholestasis.

UNLABELLED: We evaluated the clinical usefulness of 99mTc-pertechnetate per-rectal portal scintigraphy (PPS) in the assessment of portal circulation in children with chronic cholestasis. METHODS: PPS percentage shunt index (%SI) (the amount of radionuclide that shunts the liver and reaches the systemic blood after injection in the rectum) was measured in 22 children (mean age, 7.2 +/- 4.9 y) and compared with established clinical, laboratory, and endoscopic and imaging parameters of portal hypertension (PH). Fourteen children had surgically treated biliary atresia, and 8 had chronic intrahepatic cholestasis. Six clinically well children served as control subjects. RESULTS: The %SI was 14.3 +/- 3.1 and 34.7 +/- 18.8 in controls and in patients, respectively (P < 0.01). A cutoff of 19% correctly allocated 100% of controls and 86% of patients. Mean %SI values were significantly higher in patients with biliary atresia, a high risk of pretransplantation death, esophageal varices (EV) at endoscopy, and an abnormal value for the ratio of lesser omentum thickness to abdominal aorta diameter (LO/Ao) at ultrasonography. Correlations between %SI values and several ultrasonographic continuous variables were statistically significant only for LO/Ao ratios (r = 0.51; P = 0.005) and spleen longitudinal diameters (r = 0.53; P = 0.01). The presence of EV could correctly be predicted only when values of %SI were greater than 30% (100% specificity; 56% sensitivity). Endoscopic and PPS findings agreed for a diagnosis of PH with EV in 3 of 7 patients with normal or borderline ultrasonographic LO/Ao ratios. PPS patterns and %SI values became normal in 3 children who underwent liver transplantation. CONCLUSION: In children with chronic cholestasis, PPS may be an advantageous, minimally invasive tool complementary to ultrasonography and endoscopy for better assessment and follow-up of PH before and after liver transplantation.

Clinical and genetic aspects of psoriatic arthritis "sine psoriasis".

OBJECTIVE: To characterize the clinical pattern of psoriatic arthritis (PsA) sine psoriasis. METHODS: Fifty-seven patients (31 men, 26 women, mean age 46.32 +/- 14.12 yrs) with undifferentiated spondyloarthropathy (SpA) were studied. Two subsets were defined: (1) 21 patients with familial psoriasis (12 men, 9 women, mean age 49.29 +/- 14.17 yrs); (2) 36 patients without familial psoriasis (19 men, 17 women, mean age 44.58 +/- 14.00 yrs). The prevalence of the following clinical variables was evaluated: low back pain, enthesopathy, dactylitis, distal interphalangeal (DIP) arthritis, spinal involvement, and discitis. In all patients the following HLA haplotypes were tested: B7, B13, B17, B18, B27, B38, Cw6, and DR7. RESULTS: Dactylitis and DIP arthritis were markedly present in the articular subset with familial psoriasis (p < 0.0001) that also showed a high frequency rate of HLA-Cw6 (p < 0.0001 vs controls and patients without familial psoriasis). HLA-B27 was markedly frequent in patients without familial psoriasis (p < 0.0001 vs controls and p = 0.019 vs patients with familial psoriasis). In addition, in patients with familial psoriasis the log-linear model showed that the presence of HLA-Cw6 was related to the presence of DIP arthritis as well as dactylitis (likelihood ratio chi-square change of 5.891 and p = 0.015). CONCLUSION: A subset of patients with PsA "sine psoriasis" is identified by the occurrence of a SpA with dactylitis and/or DIP arthritis, presence of HLA-Cw6, and familial psoriasis in first or second-degree relatives.