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Intestinal permeability and liver disease.

Increased intestinal permeability has for many years been implicated as a possible contributory factor in the development of encephalopathy and spontaneous bacterial peritonitis (SBP) seen in patients with cirrhosis. The majority of studies indicate that there is an increase in small intestinal permeability in cirrhotic patients and there is also evidence of an increase in patients with acute liver failure. The cause of these changes is unknown and whether they are related to the development of SBP and encephalopathy is unclear.

Humans↗

Epithelial effects of proteinase-activated receptors in the gastrointestinal tract.

The intestinal epithelium plays a crucial role in providing a barrier between the external environment and the internal milieu of the body. A compromised mucosal barrier is characteristic of mucosal inflammation and is a key determinant of the development of intestinal diseases such as Crohn's disease and ulcerative colitis. The intestinal epithelium is regularly exposed to serine proteinases and this exposure is enhanced in numerous disease states. Thus, it is important to understand how proteinase-activated receptors (PARs), which are activated by serine proteinases, can affect intestinal epithelial function. This review surveys the data which demonstrate the wide distribution of PARs, particularly PAR-1 and PAR-2, in the gastrointestinal tract and accessory organs, focusing on the epithelium and those cells which communicate with the epithelium to affect its function. PARs have a role in regulating secretion by epithelia of the salivary glands, stomach, pancreas and intestine. In addition, PARs located on subepithelial nerves, fibroblasts and mast cells have important implications for epithelial function. Recent data outline the importance of the cellular site of PAR expression, as PARs expressed on epithelia may have effects that are countered by PARs expressed on other cell types. Finally, PARs and their ability to promote epithelial cell proliferation are discussed in terms of colon cancer.

Animals↗

Non-invasive investigation of inflammatory bowel disease.

The assessment of inflammatory activity in intestinal disease in man can be done using a variety of different techniques. These range from the use of non-invasive acute phase inflammatory markers measured in plasma such as C reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) (both of which give an indirect assessment of disease activity) to the direct assessment of disease activity by intestinal biopsy performed during endoscopy in association with endoscopic scoring systems. Both radiology and endoscopy are conventional for the diagnosis of inflammatory bowel disease (IBD). However these techniques have severe limitations when it comes to assessing functional components of the disease such as activity and prognosis. Here we briefly review the value of two emerging intestinal function tests. Intestinal permeability, although ideally suited for diagnostic screening for small bowel Crohn's disease, appears to give reliable predictive data for imminent relapse of small bowel Crohn's disease and it can be used to assess responses to treatment. More significantly it is now clear that single stool assay of neutrophil specific proteins (calprotectin, lactoferrin) give the same quantitative data on intestinal inflammation as the 4 day faecal excretion of 111Indium labelled white cells. Faecal calprotectin is shown to be increased in over 95% of patients with IBD and correlates with clinical disease activity. It reliably differentiates between patients with IBD and irritable bowel syndrome. More importantly, at a given faecal calprotectin concentration in patients with quiescent IBD, the test has a specificity and sensitivity in excess of 85% in predicting clinical relapse of disease. This suggests that relapse of IBD is closely related to the degree of intestinal inflammation and suggests that targeted treatment at an asymptomatic stage of the disease may be indicated.

Biomarkers↗

Comparative Study of the Efficacy and Tolerability of Secnidazole Suspension (single dose) and Tinidazole Suspension (two days dosage) in the Treatment of Amebiasis in Children.

Amebiasis caused by Entamoeba histolytica may be considered the most aggressive parasitic disease affecting human intestine, causing acute amoebic colitis and extra-intestinal diseases of high morbidity and mortality. 5-nitroimidazoles are the drugs of choice. In this multicenter, open and random clinical trial, the efficacy and tolerability of secnidazole suspension in a single oral dose of 1ml/kg was compared with 0.5ml/kg doses of tinidazole suspension given for 2 consecutive days to 303 Entamoeba histolytica-positive children aged 2 to 13. Patients with extra-intestinal complications were excluded from the study. Clinical and parasitological follow-up using the Faust and Kato-Katz method were carried out 7, 14, and 21 days after treatment. Clinical improvement/cure was observed in 93% of the patients in the secnidazole group and 91% in the tinidazole group. Parasitological success was reported for 77% and 63% of the secnidazole and tinidazole patients, respectively, showing a significant statistical difference between the two groups (p=0.007). Both drugs were well tolerated, and the adverse effects reported were mild, consisting mainly of digestive disturbances. This comparative study showed that a single oral dose of 1ml/kg of secnidazole produced a significantly higher parasitological cure rate than 2 doses of tinidazole. Secnidazole is a safe and effective drug for the treatment of uncomplicated intestinal amebiasis.

Journal Article↗

Preliminary report on isolation of mycobacteria from patients with Crohn's disease.

Several investigators have recently described the isolation of slow growing mycobacteria from the tissues of patients with Crohn's disease (CD). The primary purpose of this study was to culture and identify mycobacteria from the intestines of patients with CD and other intestinal diseases (control tissues). The culture methods were designed to eliminate most rapid-growing mycobacteria and to enhance the isolation of slow growing mycobacteria. Eighty-two surgically resected intestinal tissue samples were cultured over a four-year period: 27 tissues were from CD patients and 55 from patients with other intestinal diseases. After 4-12 months of culture, five mycobacteria were isolated, but only two have been identified thus far. Both of these organisms appeared to have initially grown as spheroplasts, but revertant bacteria were cultivated after transfer into fresh media. Four of the mycobacteria were from CD tissues, and one isolate was from a control tissue. Two of the isolates have been identified as M. chelonei subsp. abscessus, strain 390 and M. paratuberculosis strain 410. This M. paratuberculosis is similar to the previously identified M. paratuberculosis strains isolated from other human intestinal tissues from patients with CD. Both strains 390 and 410 were inoculated into neonatal goats, but they failed to reproduce a CD-like disease. The isolation of four mycobacteria from 27 CD tissues and only one from 55 control tissues strengthens the findings of previous investigators and supports the hypothesis that mycobacteria may be etiologically associated with some cases of Crohn's disease.

Animals↗

[Role of non spore-forming anaerobes in the formation of microbial landscape of the large intestine in patients with inflammatory processes at different sites].

Clinical microbiological techniques were used to study 300 patients with clinically verified urinary infections and chronic intestinal diseases. It was ascertained that examining the large intestinal content in average statistical groups of patients with inflammatory processes at various sites cannot objectively characterize the presence or absence of clinical manifestations of gastrointestinal diseases. The pathogenetic factors that predispose to the development of intestinal diseases are lower phagocytic activity, decreased complement and deficiency of B lymphocytes and IgA. The concentrations of IgM, IgG, secretory IgA and protein, as well as those of B. bifidum in the large intestinal content may serve as an additional diagnostic criterion for evaluating the mucosa of the ecological niche.

B-Lymphocytes↗

[Biochemical and serological characteristics of Escherichia belonging to the serological group 01].

A circulation at the territory of the country of various biochemical and serological variants of escherichia belonging to serological group O1, isolated in acute intestinal diseases of children and adults, was revealed. Nonhomogeneousness of the partial composition of the O-antigen was demonstrated; K-antigens were determined; new H-antigens were described. Of the 10 serological types of escherichia there proved to prevail O1 : K? : Hp and O1 : K1 : Hp; in group and sporadic acute intestinal diseases there were for the first time isolated O1 : K1 : H34, O1 : K1 : H20, O1 : K1 : Hp, O1 : K51 : H7, and O1 : K? : H20.

Acute Disease↗

Perianal Crohn disease: a new scoring system to evaluate and predict outcome of surgical intervention.

BACKGROUND: Conventional Crohn disease activity indices do not reflect perianal disease activity or allow prognostic implications from surgery. HYPOTHESIS: A new scoring system, based on the patient's disease history and physical examination findings, will allow more accurate use of surgical intervention for perianal Crohn disease. METHODS: A standardized scoring questionnaire was developed and applied to a consecutive group of patients before surgical treatment of perianal Crohn disease. The scoring system included abscess, fistula, ulcer and fissure, stenosis, incontinence, and concomitant disease. Weighted factors included acuity vs chronicity, de novo vs recurrent disease, and concomitant intestinal disease. The scoring system was validated against the surgical outcome, which was classified as poor, satisfactory, or good. RESULTS: Twenty-eight patients with Crohn disease who underwent 33 surgical procedures had a mean score of 16.5 (range, 3-37; possible range, 0-55). Using the Spearman nonparametric correlation test, the scoring system was accurate in predicting the outcome of surgical intervention (correlation coefficient, 0.78, 95% confidence interval, 0.57-0.89; P<.001) at mean follow-up of 20.8 months (range, 6-40 months). Correlation was further validated using a linear regression model (r = 0.75, slope best-fit value, 3.8; 95% confidence interval, 2.46-5.14; P<.001). All patients with a score of 10 or less had a good outcome, whereas all those with a score of 20 or greater had a poor outcome. CONCLUSIONS: The proposed scoring system correlated well with the short-term outcome of surgical intervention in patients with perianal Crohn disease and allowed prediction of surgical success. Ultimately, it may be possible to alter therapy based on preoperative prediction of the expected postoperative outcome.

Adult↗

W276 mutation in the endothelin receptor subtype B impairs Gq coupling but not Gi or Go coupling.

The mutation of W276 to cysteine within the human endothelin receptor subtype B (ET(B)R) is associated with Hirschsprung's disease, a congenital intestinal disease. The sequence surrounding W276 is highly conserved between the endothelin receptor subtypes A and B. We have introduced sets of mutations into W275 and W276 of the ET(B)R gene, and the corresponding W257 and W258 of the ET(A)R gene, and studied their coupling properties with G(i), G(o), and G(q) in reconstituted phospholipid vesicles. The prepared mutants all showed a similar affinity for endothelin-1. The W276C/ET(B)R and W276A/ET(B)R mutants had reduced activities in G(q) coupling but not in G(i)/G(o) coupling, while the W275A/ET(B)R displayed reduced activities in G(i)/G(q) coupling, with normal G(o) coupling. On the other hand, W257A/ET(A)R and W258A/ET(A)R exhibited wild-type activities in all examined G protein couplings. These results suggest that the defects in the G(q) signaling pathway by the ET(B)R are connected with Hirschsprung's disease and that the two conserved tryptophans play distinct roles in signal transduction by the two receptor subtypes. In addition, W275 and W276, which are thought to be located near the extracellular side of the transmembrane helix 5, play important roles in forming the active structure of ET(B)R.

Amino Acid Sequence↗

Acute autoimmune sensorineural hearing loss associated with Crohn's disease.

We report the sudden onset of bilateral hearing loss in a patient with Crohn's disease while the intestinal disease was quiescent. Antibodies directed against collagen type II were detected in the serum. Dramatic improvement of his hearing was observed under corticosteroid therapy. Diagnosis of autoimmune sensorineural hearing loss was established. This condition could be considered as an extraintestinal manifestation of Crohn's disease. Early diagnosis is mandated, as prompt and intensive treatment with corticosteroids and/or immunosuppressive drugs is effective and could prevent irreversible hearing loss.

Acute Disease↗

Reovirus type 1 is secreted into the bile.

Reovirus type 1, known to be a cause of systemic and intestinal disease in mice, is secreted into the bile of adult A/J mice after viremia. Virus found in the bile in concentrations higher than those in blood may indicate that reovirus type 1 is actively transported into the bile. The transport of virus was independent of levels of virus-specific immunoglobulin A antibody. Modifications of the virus that occurred during transport did not discernibly affect the infectivity of the virus. Entry of virus into the bile may be an important mechanism by which an enteric virus that produces systemic disease reenters the intestine for transmission.

Animals↗

Testosterone supplementation: why and for whom?

Androgen levels decline over a man's lifetime. In a proportion of men (increasing with age), levels fall below values that have been established by conventional laboratory criteria as indicative of hypogonadism. Testosterone has a wide range of non-reproductive actions: it preserves bone and muscle mass, it acts on non-sexual mental functioning and it stimulates red blood cell formation. Long-term androgen deficiency has a great impact on quality of life. The first intervention studies provide indications that androgen treatment of men with true androgen deficiency is helpful. Obviously, only men who are testosterone-deficient will benefit from androgen supplementation. The diagnosis of testosterone deficiency in old age is not unambiguous. Signs and symptoms of aging sometimes clinically overlap with those of testosterone deficiency. The groups that are at higher risk of testosterone deficiency are those men with disease (pulmonary disease, gastro-intestinal disease, rheumatoid disease, etc.). Usually, sex hormone binding globulin levels increase with aging, leading to lower levels of free, biologically available testosterone. For the time being, arbitrary criteria for testosterone deficiency in aging men have to be adopted. The best practical approach is to calculate the free testosterone level. The calculation can be found at www.issam.ch under 'Tools'.

Aged↗

[Evaluation of Fourier transform near-infrared spectrometer for determination of oxalate in standard urinary solution].

OBJECTIVES: The determination of oxalate in urine is required for the diagnosis and treatment of primary hyperoxaluria, idiopathic stone disease and various intestinal diseases. We examined the possibility of using Fourier transform near-infrared (FT-NIR) spectroscopy analysis to quantitate urinary oxalate. The practical advantages of this method include ease of the sample preparation and operation technique, the absence of sample pre-treatments, rapid determination and non-invasiveness. METHODS: The range of oxalate concentration in standard urine solutions was 0-221 mg/l. These 80 different samples were scanned in the region of 780-1,300 nm with a 0.5 nm data interval by a Spectrum One NTS FT-NIR spectrometer. PCR, PLSR and MLR regression models were used to calculate and evaluate the calibration equation. RESULTS: The PCR and PLSR calibration models were obtained from the spectral data and they are exactly same. The standard error of estimation (SEE) and the % variance were 10.34 mg/l and 97.86%, respectively. After full cross validation of this model, the standard error of estimation was 5.278 mg/l, which was much smaller than that of the pre-validation. Furthermore, the MCC (multiple correlation coefficient) was 0.998, which was compatible with the 0.923 or 0.999 obtained from the previous enzymatic methods. CONCLUSIONS: These results showed that FT-NIR spectroscopy can be used for rapid determination of the concentration of oxalate in human urine samples.

Calibration↗