Mycobacterium avium subsp. paratuberculosis and Crohn's disease: characterization of the interaction with different aspects of the disease.

Crohn's disease (CD) is a chronic granulomatous inflammatory bowel disease with no fully understood etiology and cure. Mycobacterium avium subspecies paratuberculosis (MAP), the etiologic agent of paratuberculosis, is also isolated from samples from human patients with CD. Paratuberculosis is characterized by persistent diarrhea and progressive weight loss and primarily affects ruminants, which eliminate the agent via feces and milk. The involvement of MAP in the pathogenesis of CD and other intestinal diseases is unclear. Thus, the present study aimed to analyze immunological, socioepidemiological, biochemical, and therapeutic variables that may be related to the occurrence of MAP in blood samples and CD patients. The sampling was random, and the population of origin was the patients from the Bowel Outpatient Clinic of the Alpha Institute of Gastroenterology (IAG), Hospital das Clínicas, Universidade Federal de Minas Gerais (HC-UFMG). Blood samples were collected from 20 patients with CD, eight with ulcerative rectocolitis (UCR), and 10 control patients without inflammatory bowel diseases. Samples were subjected to real-time PCR for detection of MAP DNA, oxidative stress analyses, and socioepidemiological variables. MAP was detected in 10 (26.3%) of the patients, seven (70%) were CD patients, 2 (20%) were URC patients, and one (10%) was a non-IBD patient. MAP was found more frequently among CD patients, but not restricted to CD patients. The presence of MAP in the blood of these patients occurred simultaneously with an inflammatory response with an increase in neutrophils and significant alterations in the production of antioxidant enzymes such as catalase and GST.

Gut permeability to lactulose and mannitol differs in treated Crohn's disease and celiac disease patients and healthy subjects

The gut barrier monitors and protects the gastrointestinal tract from challenges such as microorganisms, toxins and proteins that could act as antigens. There is evidence that gut barrier dysfunction may act as a primary disease mechanism in intestinal disorders. The aim of the present study was to evaluate the barrier function towards sugars after the appropriate treatment of celiac disease and Crohn's disease patients and compare the results with those obtained with healthy subjects. Fifteen healthy volunteers, 22 celiac disease patients after 1 year of a gluten-free diet, and 31 Crohn's disease patients in remission were submitted to an intestinal permeability test with 6.0 g lactulose and 3.0 g mannitol. Six-hour urinary lactulose excretion in Crohn's disease patients was significantly higher than in both celiac disease patients (0.42 vs 0.15 percent) and healthy controls (0.42 vs 0.07 percent). Urinary lactulose excretion was significantly higher in celiac disease patients than in healthy controls (0.15 vs 0.07 percent). Urinary mannitol excretion in Crohn's disease patients was the same as healthy controls (21 vs 21 percent) and these values were significantly higher than in celiac disease patients (10.9 percent). The lactulose/mannitol ratio was significantly higher in Crohn's disease patients in comparison to celiac disease patients (0.021 vs 0.013) and healthy controls (0.021 vs 0.003) and this ratio was also significantly higher in celiac disease patients compared to healthy controls (0.013 vs 0.003). In spite of treatment, differences in sugar permeability were observed in both disease groups. These differences in the behavior of the sugar probes probably reflect different mechanisms for the alterations of intestinal permeability.

Gut permeability to lactulose and mannitol differs in treated Crohn's disease and celiac disease patients and healthy subjects.

The gut barrier monitors and protects the gastrointestinal tract from challenges such as microorganisms, toxins and proteins that could act as antigens. There is evidence that gut barrier dysfunction may act as a primary disease mechanism in intestinal disorders. The aim of the present study was to evaluate the barrier function towards sugars after the appropriate treatment of celiac disease and Crohn's disease patients and compare the results with those obtained with healthy subjects. Fifteen healthy volunteers, 22 celiac disease patients after 1 year of a gluten-free diet, and 31 Crohn's disease patients in remission were submitted to an intestinal permeability test with 6.0 g lactulose and 3.0 g mannitol. Six-hour urinary lactulose excretion in Crohn's disease patients was significantly higher than in both celiac disease patients (0.42 vs 0.15%) and healthy controls (0.42 vs 0.07%). Urinary lactulose excretion was significantly higher in celiac disease patients than in healthy controls (0.15 vs 0.07%). Urinary mannitol excretion in Crohn's disease patients was the same as healthy controls (21 vs 21%) and these values were significantly higher than in celiac disease patients (10.9%). The lactulose/mannitol ratio was significantly higher in Crohn's disease patients in comparison to celiac disease patients (0.021 vs 0.013) and healthy controls (0.021 vs 0.003) and this ratio was also significantly higher in celiac disease patients compared to healthy controls (0.013 vs 0.003). In spite of treatment, differences in sugar permeability were observed in both disease groups. These differences in the behavior of the sugar probes probably reflect different mechanisms for the alterations of intestinal permeability.

Efficacy of oxamniquine and praziquantel in the treatment of Schistosoma mansoni infection: a controlled trial.

OBJECTIVE: To evaluate the therapeutic efficacy of oxamniquine and praziquantel, the two most clinically important schistosomicide drugs, and to compare the accuracy of faecal examination with the accuracy of oogram in testing for Schistosoma mansoni infection. METHODS: In a triple-masked and randomized controlled trial, 106 patients infected with S. mansoni were randomly allocated to one of three statistically homogeneous groups. One group was given 60 mg/kg praziquantel per day for three consecutive days, another was given two daily doses of 10 mg/kg oxamniquine, and the placebo group received starch. Faecal examinations (days 15, 30, 60, 90, 120, 150, and 180 after treatment) and biopsy of rectal mucosa by quantitative oogram (days 30, 60, 120, and 180) were used for the initial diagnosis and for evaluating the degree of cure. The chi2 test and the Kruskal-Wallis test were used to compare variables in the three groups. Survival analysis (Kaplan-Meier) and the log-rank test were used to evaluate the efficacy of the treatments. FINDINGS: The sensitivity of stool examinations ranged from 88.9% to 94.4% when patients presented with >5000 S. mansoni eggs per gram of tissue (oogram); when the number of eggs dropped to <1000 eggs per gram, sensitivity was reduced (range, 22.7-34.0%). When cure was evaluated by stool examination, oxamniquine and praziquantel had cure rates of 90.3% and 100%, respectively. However, when the oogram was used as an indicator of sensitivity, the oxamniquine cure rate dropped dramatically (to 42.4%), whereas the rate for praziquantel remained high, at 96.1%. CONCLUSIONS: Praziquantel was significantly more effective than oxamniquine in treating S. mansoni infection. The oogram was markedly more sensitive than stool examinations in detecting S. mansoni eggs and should be recommended for use in clinical trials with schistosomicides.

The value of an enzyme-linked immunosorbent assay for the diagnosis of schistosomiasis mansoni myeloradiculopathy.

The role of serological tests on cerebrospinal fluid (CSF) in the diagnosis of neuroschistosomiasis has not been fully elucidated; the condition is essentially diagnosed on the basis of circumstantial evidence, which may lead to an erroneous diagnosis, especially in highly endemic areas. We therefore carried out a prospective case-control study in which we compared the concentrations of immunoglobulin G (IgG) specific for schistosome soluble egg antigen (SEA) present in the CSF of 54 patients with schistosomiasis mansoni myeloradiculopathy (SMMR) with those observed in a control group consisting of 41 patients with epidemiological and serological evidence of exposure to schistosomes, and with other neurological disorders that result in mild to moderate impairment of the blood-brain barrier. Anti-SEA IgG was estimated by an enzyme-linked immunosorbent assay. The sensitivity, specificity and positive and negative predictive values were 56%, 95%, 94% and 62% respectively. Likelihood ratios and the corresponding post-test probabilities were determined for 4 levels of anti-SEA IgG in CSF. A value below 0.1 micrograms/mL practically excluded the possibility of SMMR (post-test probability < 5%), a value above 1.4 micrograms/mL practically confirmed the diagnosis of SMMR (post-test probability > 96%), values of 0.1 to 0.5 microgram/mL had no diagnostic value (post-test probability approximately 45%), and values of 0.6 to 1.4 micrograms/mL were useful in some situations (post-test probability approximately 70%). We conclude that the estimation of anti-SEA IgG in the CSF is useful for the diagnosis of SMMR.

Toxicological profile of FCE 22101 and its orally available ester FCE 22891.

LD50 values of FCE 22101 iv were 3872 mg/kg and 4392 mg/kg in male and female mice, and 2000 mg/kg and 2201 mg/kg in male and female rats respectively. Oral LD50s of FCE 22891 were 4363 mg/kg in male and 6167 mg/kg in female mice; in the rat this value was over 5000 mg/kg in both males and females. FCE 22101, given iv for two consecutive days was less nephrotoxic in rabbits than cephaloridine and imipenem alone, but more nephrotoxic than imipenem/cilastatin. Dose ranging studies carried out in rats and 13-week studies in rats and monkeys indicated that the kidney was a target organ for both penem compounds. Renal lesions appeared beginning with doses higher than 300 mg/kg/day and were morphologically similar to those induced by cephaloridine and imipenem. Possible targets at high doses were the urinary bladder in rats and the haemopoietic system in monkeys given FCE 22101. The toxicity data available for iv FCE 22101 and oral FCE 22891 in the rat and monkey indicated an adequate tolerance of these compounds, comparable with other beta-lactam antibiotics, including imipenem/cilastatin.

Thyroid-stimulating hormone and prolactin responses to thyrotropin-releasing hormone in common migraine.

Intravenous administration of 50 micrograms or 200 micrograms thyrotropin-releasing hormone (TRH) to men with common migraine elicited blunted prolactin (PRL) responses, when compared with healthy controls. The thyroid-stimulating hormone (TSH) response was enhanced after 50 micrograms TRH in the migraineurs, but not after 200 micrograms. The physiologic TSH dose-response relationship was abolished in migraine sufferers. The data may be interpreted in the light of dopaminergic and noradrenergic supersensitivity, for PRL and TSH, respectively. The TSH response in migraine differs from the one that occurs in depression.

Toxicity of 2-methyl-4-chlorophenoxyacetic acid to the adult crested newt.

The toxicity of the herbicide Agroxone 3, a commercial formulation of the sodium salt of 2-methyl-4-chlorophenoxyacetic acid (MCPA), in the adult newt (Triturus cristatus carnifex) was tested after percutaneous exposure. At the concentration of 3200 ppm, the LT50 values were 17 and 21 hr for male and female newts. At 1600 ppm, the LT50 values were 35 and 45.5 hr. At 800 ppm, most of the animals were still alive after the 3 months of experimentation. There were no deaths at 400 and 200 ppm. Severe neuromuscular disorders were observed in animals exposed to lethal concentrations.

Experimental studies on peripheral nerve repair following early or delayed suture.

Early suture of the sciatic nerve in rats was compared with delayed suture performed after 2 weeks. The distal tract of the nerve was studied morphologically using semifine sections and computerised measurements of the number and diameters of regenerated fibres, and electrophysiologically by the measurement of nerve velocity conduction. The morphological examination did not reveal any substantial difference, while the velocity conduction tests showed better reinnervation following early suture.