Aloísio Sales da Cunha

Influence of Saccharomyces boulardii on the intestinal permeability of patients with Crohn's disease in remission.

Objective. Crohns disease (CD) is characterized by a reduction in mucosal integrity that permits antigen penetration into the intestinal tissue. The administration of probiotics has been suggested to improve the barrier function of the mucosa. The objective of this study was to evaluate the influence of Saccharomyces boulardii on the intestinal permeability in CD. Material and methods. Thirty-four patients were randomized according to the Vienna classification for treatment with either placebo or Saccharomyces boulardii. Baseline medications (mesalamine, azathioprine, prednisone, metronidazole and/or thalidomide) were maintained. Intestinal permeability (lactulose/mannitol ratio) was evaluated immediately before the beginning of treatment and at the end of the first and third treatment month. Fifteen healthy volunteers were also submitted for the intestinal permeability test. Results. In volunteers, the lactulose/mannitol ratio was 0.005±0.0037, whereas this value was 0.021±0.01 in patients with CD (p=0.001). In the placebo group, there was an increase in lactulose/mannitol ratio by 0.004±0.010 (p=0.12) at the end of the third month. In the S. boulardii group, there was an improvement in intestinal permeability, with a decrease in the lactulose/mannitol ratio by 0.008±0.006 (p=0.0005) in the same period. Conclusions. Patients with CD in remission present alterations in the integrity of the intestinal mucosal barrier according to lactulose/mannitol ratio. S. boulardii added to baseline therapy improved intestinal permeability in these patients, even though complete normalization was not achieved.Objective. Crohns disease (CD) is characterized by a reduction in mucosal integrity that permits antigen penetration into the intestinal tissue. The administration of probiotics has been suggested to improve the barrier function of the mucosa. The objective of this study was to evaluate the influence of Saccharomyces boulardii on the intestinal permeability in CD. Material and methods. Thirty-four patients were randomized according to the Vienna classification for treatment with either placebo or Saccharomyces boulardii. Baseline medications (mesalamine, azathioprine, prednisone, metronidazole and/or thalidomide) were maintained. Intestinal permeability (lactulose/mannitol ratio) was evaluated immediately before the beginning of treatment and at the end of the first and third treatment month. Fifteen healthy volunteers were also submitted for the intestinal permeability test. Results. In volunteers, the lactulose/mannitol ratio was 0.005±0.0037, whereas this value was 0.021±0.01 in patients with CD (p=0....

Evaluation of inflammatory activity in Crohn’s disease and ulcerative colitis

Crohns disease and ulcerative colitis evolve with a relapsing and remitting course. Determination of inflammatory state is crucial for the assessment of disease activity and for tailoring therapy. However, no simple diagnostic test for monitoring intestinal inflammation is available. Noninvasive markers give only indirect assessments of disease activity. Histopathological or endoscopical examinations accurately assess inflammatory activity, but they are invasive, time consuming and expensive and therefore are unsuitable for routine use. Imaging procedures are not applicable for ulcerative colitis. The usefulness of ultrasound and Doppler imaging in assessing disease activity is still a matter of discussion for Crohns disease, and an increased interest in computed tomography enterograph (CTE) has been seen, mainly because it can delineate the extent and severity of bowel wall inflammation, besides detecting extraluminal findings. Until now, the available data concerning the accuracy of magnetic resonance enterography in detecting disease activity is less than CTE. Due to this, clinical activity indices are still commonly used for both diseases.

Spinal cord schistosomiasis: a prospective study of 63 cases emphasizing clinical and therapeutic aspects

A prospective study was conducted on 63 patients with schistosomal myeloradiculopathy admitted to a university hospital in Brazil. They were evaluated according to a protocol and treated with corticosteroid and praziquantel. The disease, in general, presented as a lower cord syndrome of acute progression characterized by motor, sensory and autonomic dysfunctions. The severity of the clinical picture was different among the patients, but the symptoms were quite constant. Cerebrospinal fluid examination showed an inflammatory pattern with or without eosinophils and/or IgG against schistosomal antigens. The most frequent alterations detected by imaging methods were enlargement of the medullary cone and of the roots of the cauda equina. Schistosome egg counts suggested a low parasite burden in 71.6% of the cases. Outcome was favorable in 38 (60.3%) patients and improvement usually started within the first 48 h after commencing on corticoid and was faster during the early period of treatment.

A cross-sectional study of 130 Brazilian patients with Crohn's disease and ulcerative colitis: analysis of articular and ophthalmologic manifestations.

This is a cross-sectional study that analyzed the pattern and frequency of articular and ophthalmologic manifestations in patients with Crohn’s disease (CD) and ulcerative colitis (UC), with or without signs of active bowel inflammation. One hundred and thirty consecutive patients with CD (n = 71) and UC (n = 59) were examined. Simple X-rays of lumbar spine, sacroiliac joints, and calcaneal bone were performed and human leukocyte antigen (HLA)-B27 was typed. Joint manifestations occurred in 41 (31.5%) patients, 27 (38%) with CD and 14 (23.7%) with UC. Peripheral involvement occurred in 22 patients, axial involvement in five, and mixed involvement in 14. The most frequently involved joints were knees (56.1%), ankles (29.3%), and hips (29.3%), while the predominant pattern was oligoarticular (84.6%) and asymmetrical (65.6%). Enthesitis was identified in seven (5.4%) patients and inflammatory lumbar pain in 13 (10%). Eight of these patients fulfilled the diagnostic criteria for ankylosing spondylitis (6.2%). Radiographic sacroiliitis occurred in 12 patients (9.2%). Ocular abnormalities were present in six patients (6.2%), and HLA-B27 was positive in five (5.8%). In conclusion, the articular manifestations in the present study were predominantly oligoarticular and asymmetric, with a low frequency of ophthalmologic involvement and positive HLA-B27.

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.

Dietary approach in the treatment of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) has been identified as one of the most prevalent chronic liver disease in adults and children populations. NAFLD is usually associated with the metabolic syndrome (MS), which is chiefly related to insulin resistance and its consequences. Insulin resistance has a crucial role in the pathogenesis of hepatic steatosis and potentially nonalcoholic steatohepatitis (NASH). Because of the contemporary epidemics of MS and obesity, the burden of NAFLD is also expected to rise. Unhealthy diets, such as the so-called western diet, are enriched in fructose, trans-fatty acids and saturated fat and seem to be associated with the development of NAFLD. In human studies, certain dietary sugars, particularly fructose, are used as a substrate for lipogenesis leading to hepatic fatty infiltration, inflammation, and possibly fibrosis. Other investigations have shown that fat consumption especially cholesterol and trans/saturated fatty acids are also steatogenic and seem to increase visceral adiposity. The identification of specific dietary components that favor the development of NASH could be important for the management of this disorder. This review focuses on the effects of different dietary approaches to prevent and treat NAFLD emphasizing the macronutrients and energy composition.

Therapeutical evaluation of different dose regimens of praziquantel in Schistosomiasis mansoni, based on the quantitative oogram technique

Uma pesquisa clinica compreendendo 80 pacientes de ambos os sexos, de 15 a 55 anos de idade, portadores de esquistossomose mansonica cronica, formas intestinal ou hepatintestinal, foi efetivada para avaliar a eficacia do praziquantel em diferentes esquemas posologicos. Os pacientes foram distribuidos aleatoriamente em quatro grupos, com igual numero de casos, sendo tratados com uma das seguintes dosagens: 60 mg/kg em um dia, 60 mg/kg diarios por dois dias, 60 mg/kg diarios por tres dias e 30 mg/kg diarios por seis dias. A avaliacao da cura parasitologica baseou-se na tecnica do oograma quantitativo mediante biopsias da mucosa retal, realizadas antes, bem como um, dois, quatro e seis meses apos o tratamento. Concomitantemente, efetuaram se exames de fezes segundo os metodos qualitativo de Hoffman, Pons & Janer e quantitativo de Kato-Katz. A melhor tolerabilidade foi verificada com 30 mg/kg diarios durante seis dias, enquanto a maior incidencia de efeitos colaterais, em especial tontura e nausea, ocorreu com 60 mg/kg diarios durante tres dias. Nenhuma reacao adversa grave foi observada com o medicamento. Alcancaram se os seguintes indices de cura: 25% com 60 mg/kg em um dia; 60% com 60 mg/kg diarios por dois dias; 89,5% com 60 mg/kg diarios por tres dias e 90% com 30 mg/kg diarios por seis dias. Paralelamente houve uma queda de, respectivamente, 64%, 73%, 87% e84% no numero mediano de ovos viaveis de S. mansoni por grama de tecido. Assim, constatou se uma correlacao direta entre dose e efeito. Os correspondentes indices de cura, segundo os exames de fezes, foram 39%, 80%, 100% e 95% com o metodo de Hoffman, Pons & Janer e com o de Kato-Katz 89%, 100%, 100% e 100%. A discrepância encontrada nos resultados entre os tres metodos parasitologicos decorre da desigualdade na precisao dos mesmos. Quando o numero de ovos viaveis por grama de tecido caiu abaixo de 5000, a diferenca no percentual de achados falso-negativos entre Hoffmann, Pons & Janer (28%) e Kato-Katz (80%) tornou-se significativa. Quando esse numero baixou para menos de 2000, a percentagem de resultados falso-negativos encontrada com Hoffman, Pons & Janer (49%) tambem passou a ser significativa em relacao ao oograma. Em conclusao, ficou provado que o praziquantel e altamente eficaz na infeccao pelo S. mansoni. Administrado na dose total de 180 mg/kg, dividida em tres ou seis dias, o praziquantel proporcionou 90% de cura. Provavelmente, poderia atingir 100% se a dose total fosse aumentada para 240 mg/kg. Ademais, confirmou-se que o oograma quantitativo consiste no metodo mais fidedigno para avaliar a eficacia terapeutica de novas drogas na esquistossomose mansonica.

Estimation of the local synthesis of immunoglobulin G (IgG) in the central nervous system of patients with spinal cord schistosomiasis by the IgG index

By analogy with other infections of the central nervous system (CNS), it is believed that schistosomal myeloradiculopathy (SMR) is an entity that may involve a mild-to-moderate degree of impairment of the blood-brain barrier along with intrathecal synthesis of antibodies. The first of these aspects is obvious but the second has not been clearly demonstrated. This study was undertaken in Brazil with the aim of investigating the production of immunoglobulin G (IgG) within the CNS in patients with SMR, by the determination of the cerebrospinal fluid (CSF) IgG index. The study population included 54 patients with SMR, evaluated prospectively. The CSF IgG index was increased in 43 of them (80%). Preliminary results from our laboratory suggest that these antibodies are reactive against Schistosoma mansoni antigens. Thus, this finding also suggests that this index may be useful in the differential diagnosis of SMR.

Double-blind therapeutical evaluation based on the quantitative oogram technique, comparing praziquantel and oxamniquine in human schistosomiasis mansoni

A total of 54 adult patients with chronic intestinal or hepato-intestinal schistosomiasis mansoni were included into a double-blind clinical trial to compare praziquantel and oxamniquine. Following a randomized allocation, 27 patients received praziquantel — 65 mg/kg bwt — and 27 oxamniquine — 18 mg/kg bwt — in a single oral dose divided into two intakes. The incidence, severity and duration of side-effects were similar for the two drugs. The assessment of therapeutical efficacy was based on the quantitative oogram technique via biopsy of the rectal mucosa, performed at the end of 1, 2, 4 and 6 months after treatment. At these same occasions, stool examinations according to Hoffman, Pons & Janer (HPJ) and Kato-Katz (K-K) methods were undertaken to confront their results with the oogram findings. In order to evaluate the immediate effect of the therapy upon the egg laying activity of the parasite, a limited number of patients was submitted to rectal biopsies on the 6th. and 18th. days subsequent to the drug administration. Both drugs proved to be active anti-schistosomal agents as their coefficients of variation, determined from the oograms made immediatly following the treatment, were above 60%. Furthermore, out of 27 patients in each group, 24 treated with praziquantel and 22 with oxamniquine have completed the required six months parasitological follow up period. The respective cure rates in accordance with the oogram, HPJ and K-K findings were: 29.2%, 50% and 91.7% for praziquantel; 22.7%, 50% and 86.3% for oxamniquine. Despite a quite low cure rate, a sharp fall (-83%) in the mean number of living eggs per gram of tissue was observed in the post-treatment oograms. These results indicated that both anti-schistosomal agents were similarly efficacious On the other hand, a striking difference in the cure rates amongst the three parasitological control methods became evident. The oogram was the most accurate one, followed by HPJ and lastly by K-K. Since there was a direct correlation between the number of living eggs in the oogram and the positivity of the stool examinations, the percentage of false-negative results has augmented remarkably after treatment reaching 47.3% with HPJ and 92.9% with K-K. Prior to therapy they were 0% and 64,8%, respectively. The authors infer that the different accuracy of the applied methodology to assess therapeutical efficacy may explain the discrepancy between the cure rate achieved in this clinical trial and those reported by other investigations with either praziquantel or oxamniquine.

Beneficial Effect of Synbiotic Supplementation on Hepatic Steatosis and Anthropometric Parameters, But Not on Gut Permeability in a Population with Nonalcoholic Steatohepatitis

Nonalcoholic fatty liver disease is the most prevalent chronic liver disease in Western countries; it can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocarcinoma. The importance of gut-liver-adipose tissue axis has become evident and treatments targeting gut microbiota may improve inflammatory and metabolic parameters in NASH patients. In a randomized, controlled clinical trial, involving 50 biopsy-proven NASH patients, we investigated the effects of synbiotic supplementation on metabolic parameters, hepatic steatosis, intestinal permeability, small intestinal bacterial overgrowth (SIBO) and lipopolysaccharide (LPS) serum levels. Patients were separated into two groups receiving Lactobacillus reuteri with guar gum and inulin for three months and healthy balanced nutritional counseling versus nutritional counseling alone. Before and after the intervention we assessed steatosis by magnetic resonance imaging, intestinal permeability by lactulose/mannitol urinary excretion and SIBO by glucose breath testing. NASH patients presented high gut permeability, but low prevalence of SIBO. After the intervention, only the synbiotic group presented a reduction in steatosis, lost weight, diminished BMI and waist circumference measurement. Synbiotic did not improve intestinal permeability or LPS levels. We concluded that synbiotic supplementation associated with nutritional counseling seems superior to nutritional counseling alone for NASH treatment as it attenuates steatosis and may help to achieve weight loss.