The effect of nicotine in vitro on the integrity of tight junctions in Caco-2 cell monolayers

Ulcerative colitis is characterised by impairment of the epithelial barrier and tight junction alterations resulting in increased intestinal permeability. UC is less common in smokers with smoking reported to decrease paracellular permeability. The aim of this study was thus to determine the effect of nicotine, the major constituent in cigarettes and its metabolites on the integrity of tight junctions in Caco-2 cell monolayers. The integrity of Caco-2 tight junctions was analysed by measuring the transepithelial electrical resistance (TER) and by tracing the flux of the fluorescent marker fluorescein, after treatment with various concentrations of nicotine or nicotine metabolites over 48 h. TER was significantly higher compared to the control for all concentrations of nicotine 0.01-10 M at 48 h (p < 0.001), and for 0.01 mu M (p < 0.001) and 0.1 mu M and 10 M nicotine (p < 0.01) at 12 and 24 h. The fluorescein flux results supported those of the TER assay. TER readings for all nicotine metabolites tested were also higher at 24 and 48 h only (p <= 0.01). Western blot analysis demonstrated that nicotine up-regulated the expression of the tight junction proteins occludin and claudin-l (p < 0.01). Overall, it appears that nicotine and its metabolites, at concentrations corresponding to those reported in the blood of smokers, can significantly improve tight junction integrity, and thus, decrease epithelial gut permeability. We have shown that in vitro, nicotine appears more potent than its metabolites in decreasing epithelial gut permeability. We speculate that this enhanced gut barrier may be the result of increased expression of claudin-l and occludin proteins, which are associated with the formation of tight junctions. These findings may help explain the mechanism of action of nicotine treatment and indeed smoking in reducing epithelial gut permeability. (c) 2007 Elsevier Ltd. All rights reserved.

Escala de coping religioso-espiritual (escala CRE) : tradução, adaptação e validação da escala rcope, abordando relações com saúde e qualidade de vida

OBJETIVOS: A importância do coping religioso espiritual (CRE) nas áreas da saúde e qualidade de vida (QV), e a falta de instrumentos brasileiros para avalia-lo são apontadas pela literatura científica. Este estudo objetivou realizar a versão brasileira da RCOPE Scale, gerando a Escala de Coping Religioso Espiritual (Escala CRE), e examinar a relação entre CRE, saúde e QV. MÉTODO: A primeira fase deste estudo compreendeu: tradução por especialistas da RCOPE, adaptação à cultura brasileira, teste piloto com 50 estudantes de nível médio e superior. A segunda abrangeu teste de campo e processo de validação. Os 616 participantes [65% mulheres, 13-DQRV p=18,44)], foram acessados em um dos seguintes locais que freqüentavam: instituições religiosas ou grupos espirituais (74,4%), universidades (13,5%), clínicas para tratamento de saúde (9,1%) e Web Mail (2,9%). Eles completaram vários instrumentos: Consentimento Livre/Esclarecido, Questionário Geral (questões demográficas, socioeconômicas, religiosas, de saúde), Escala CRE, Escala de Atitude Religiosa e WHOQOL-bref. RESULTADOS: Análises fatoriais geraram uma Escala CRE com duas dimensões: CRE Positivo (CREP) (8 fatores, 66 itens) e CRE Negativo (CREN) (4 fatores, 21 itens). Foram criados quatro índices principais para avaliar os respondentes: as médias CREP e CREN, os escores de CRE TOTAL e Razão CREN/CREP. A Escala CRE demonstrou validade de construto, critério, conteúdo e bons níveis de fidedignidade. Testes Qui-quadrado para Classificação Subjetiva de Saúde (7categorias) mostraram problemas de saúde (PS) físicos relacionados a altos escores de CRE TOTAL e baixos de Razão CREN/CREP; PS emocionais, acrescidos ou não de PS físicos, mostraram resultado inverso. Ainda, QV e CRE TOTAL estiveram positiva e significativamente correlacionados. O CREN esteve negativamente correlacionado à QV em grau maior do que o CREP esteve positivamente correlacionado com QV. Usando Testes t de Student, aqueles que tiveram altos escores de CRE TOTAL mostraram maiores níveis de QV em todos os domínios do WHOQOL-bref, além de maior Classificação Objetiva de Saúde (Likert 5-pontos). Ademais, aqueles que tiveram altos níveis de QV demonstraram maior uso de CREP e menor de CREN. CONCLUSÕES: A Escala CRE é válida e fidedigna, permite aplicação clínica e em pesquisas em locais para tratamento de saúde públicos ou privados. PS físicos podem ser motivadores e educadores do uso do CRE. PS emocionais podem dificultar um melhor uso do CRE, sugerindo que intervenções psicológicas poderiam facilitar o processo. Além disso, CRE e QV são construtos correlacionados. Uma proporção mínima de 2CREP:1CREN (Razão CREN/CREP menor/igual 0,5) foi proposta para se obter um efeito benéfico geral do CRE na QV. Evidências sugerem que intervenções focadas no processo de CRE poderiam ser benéficas e efetivas para agentes de saúde pública pelo seu potencial de reduzir custos de intervenções e pelo seu impacto significante na saúde e QV da população. Os próximos passos seriam: utilização de metodologias experimentais longitudinais para melhor avaliar os efeitos do CRE na saúde e na QV, elaboração de uma Escala CRE Abreviada, investigação aprofundada da influência da variável idade na relação CRE-Saúde e testes de proporção e causais, para verificar a direção da correlação, entre CRE e QV.

Role of phospholipase A(2) and tyrosine kinase in Clostridium difficile toxin A-induced disruption of epithelial integrity, histologic inflammatory damage and intestinal secretion

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Decreased oxidative stress in patients with ulcerative colitis supplemented with fish oil omega-3 fatty acids

OBJECTIVE: the potential pathogenicity of free radicals may have a pivotal role in ulcerative colitis. Fish oil omega-3 fatty acids exert anti-inflammatory effects on patients with ulcerative colitis (UC), but the precise mechanism of the action of fish oil on oxidative stress is still controversial. The aim of the present work was to verify the blood oxidative stress in patients with UC and determine whether the association of sulfasalazine to fish oil omega-3 fatty acids is more effective than isolated use of sulfasalazine to reduce the oxidative stress.METHODS:, Nine patients (seven female and two male; me. an age = 40 +/- 11 y) with mild or moderate active UC were studied in a randomized crossover design. In addition to their usual medication (2 g/d of sulfasalazine), they received fish oil omega-3 fatty acids (4.5 g/d) or placebo for 2-mo treatment periods that were separated by 2 mo, when they only received sulfasalazine. Nine healthy individuals served as control subjects to study the oxidative stress status. Disease activity was assessed by laboratory indicators (C-reactive protein, alpha(1)-acid glycoprotein, alpha(1)-antitrypsin, erythrocyte sedimentation rate, albumin, hemoglobin, and platelet count), sigmoidoscopy, and histology scores. Analysis of oxidative stress was assessed by plasma chemiluminescence and erythrocyte lipid peroxidation, both induced by tert butyl hydroperoxide (t-BuOOH) and by plasma malondialdehyde. Antioxidant status was assayed by total plasma antioxidant capacity (TRAP) and microsomal lipid peroxidation inhibition (LPI). Superoxide dismutase (SOD) and catalase erythrocyte enzymatic activities were also determined.RESULTS: No significant changes were observed in any laboratory indicator or in the sigmoidoscopy or histology scores, with the exception of erythrocyte sedimentation rate, which decreased with both treatments. Oxidative stress was demonstrated by significant decreases in TRAP and LPI levels, increased chemiluminescence induced by t-BuOOH, and higher SOD activity in patients with UC. Treatment with fish oil omega-3 fatty acids reverted the chemiluminescence induced by t-BuOOH and LPI to baseline levels but that did not occur when patients received only sulfasalazine. Levels of plasma malondialdehyde, erythrocyte lipid peroxidation, and catalase were not different from those in the control group.CONCLUSIONS: the results indicated that plasma oxidative stress occurs in patients with UC, and there was a significant decrease when the patients used sulfasalazine plus fish oil omega-3 fatty acids. However, there was no improvement in most laboratory indicators, sigmoidoscopy, and histology scores. The results suggested that omega-3 fatty acids may act as free radical scavengers protecting the patients against the overall effect of oxidative stress. (C)Elsevier B.V. 2003.

Comparison of omega-3 fatty acids and sulfasalazine in ulcerative colitis

Fish oil omega-3 fatty acids exert antiinflammatory effects on patients with ulcerative colitis. However, a comparative study in patients with mild to moderate ulcerative colitis receiving only sulfasalazine or omega-3 fatty acids has not been performed. We sought to detect changes in the inflammatory disease activity with the use of either fish oil omega-3 fatty acids or sulfasalazine in patients with ulcerative colitis. Ten patients (five male, five female; mean age = 48 +/- 12 y) with mild to moderate active ulcerative colitis were investigated in a randomized cross-over design. They received either sulfasalazine (2 g/d) or omega-3 fatty acids (5.4 g/d) for 2 mo. Disease activity was assessed by clinical and laboratory indicators, sigmoidoscopy, histology, and whole-body protein turnover (with N-15-glycine). Treatment with w-3 fatty acids resulted in greater disease activity as detected by a significant increase in platelet count, erythrocyte sedimentation rate, C-reactive protein, and total fecal nitrogen excretion. No major changes in protein synthesis and breakdown were observed during either treatment. In conclusion, treatment with sulfasalazine is superior to treatment with omega-3 fatty acids in patients with mild to moderate active ulcerative colitis. Nutrition 2000;16:87-901 (C) Elsevier B.V. 2000.

Dietary intervention with narrow-leaved cattail rhizome flour (Typha angustifolia L.) prevents intestinal inflammation in the trinitrobenzenesulphonic acid model of rat colitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Suppression of TNBS-induced colitis in rats by 4-methylesculetin, a natural coumarin: Comparison with prednisolone and sulphasalazine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Intestinal anti-inflammatory activity of esculetin and 4-methylesculetin in the trinitrobenzenesulphonic acid model of rat colitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Properties of l=1 B-1 and B*(2) Mesons

This Letter presents the first strong evidence for the resolution of the excited B mesons B-1 and B-2(*) as two separate states in fully reconstructed decays to B+(*())pi(-). The mass of B-1 is measured to be 5720.6 +/- 2.4 +/- 1.4 MeV/c(2) and the mass difference Delta M between B-2* and B-1 is 26.2 +/- 3.1 +/- 0: 9 MeV/c(2), giving the mass of the B-2* as 5746.8 +/- 2.4 +/- 1.7 MeV/c(2). The production rate for B-1 and B-2* mesons is determined to be a fraction (13.9 +/- 1.9 +/- 3.2)% of the production rate of the B+ meson.

Anti-inflammatory intestinal activity of Abarema cochliacarpos (Gomes) Barneby & Grimes in TNBS colitis model

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Intestinal anti-inflammatory activity of coumarin and 4-hydroxycoumarin in the trinitrobenzenesulphonic acid model of rat colitis

Coumarins represent an important class of phenolic compounds with multiple biological activities, including inhibition of lipidic peroxidation and neutrophil-dependent anion superoxide generation, anti-inflammatory and immunosuppressor actions. All of these proprieties are essential for that a drug may be used in the treatment of inflammatory bowel disease. The present study examined intestinal anti-inflammatory activity of coumarin and its derivative, the 4-hydroxycoumarin on experimental ulcerative colitis in rats. This was performed in two different experimental settings, i.e. when the colonic mucosa is intact or when the mucosa is in process of recovery after an initial insult. The results obtained revealed that the coumarin and 4-hydroxycoumarin, at doses of 5 and 25 mg/kg, significantly attenuated the colonic damage induced by trinitrobenzenesulphonic acid (TNBS) in both situations, as evidenced macroscopically, microscopically and biochemically. This effect was related to an improvement in the colonic oxidative status, since coumarin and 4-hydroxycoumarin prevented the glutathione depletion that occurred as a consequence of the colonic inflammation. © 2008 Pharmaceutical Society of Japan.

Biological therapy in the treatment of moderate-to-severe ulcerative colitis patients: Can colectomy be prevented?

Ulcerative colitis treatment intends to induce remission, and its maintenance. Biological drugs, such as infliximab, have been indicated in moderate and severe cases of the disease, which are unresponsive to conventional medication. Randomized controlled trials proved the efficacy of biological treatment with high rates of sustained disease remission and mucosal healing. Recently, the concept of mucosal healing has been inversely associated with surgical treatment. Patients treated with infliximab have lower colectomy rates than those receiving conventional therapies. We suppose that earlier use of biological drugs in disease's course would lead to better clinical control and mucosal healing, with a consequent reduction in colectomy rates. To support this hypothesis, a literature review from January, 1996 to April, 2011 was performed.

Bone healing around titanium implants in two rat colitis models

Objective: Crohn's disease is a chronic inflammatory process that has recently been associated with a higher risk of early implant failure. Herein we provide information on the impact of colitis on peri-implant bone formation using preclinical models of chemically induced colitis. Methods: Colitis was induced by intrarectal instillation of 2,4,6-trinitro-benzene-sulfonic-acid (TNBS). Colitis was also induced by feeding rats dextran-sodium-sulfate (DSS) in drinking water. One week after disease induction, titanium miniscrews were inserted into the tibia. Four weeks after implantation, peri-implant bone volume per tissue volume (BV/TV) and bone-to-implant contacts (BIC) were determined by histomorphometric analysis. Results: Cortical histomorphometric parameters were similar in the control (n = 10), DSS (n = 10) and TNBS (n = 8) groups. Cortical BV/TV was 92.2 ± 3.7%, 92.0 ± 3.0% and 92.6 ± 2.7%. Cortical BIC was 81.3 ± 8.8%, 83.2 ± 8.4% and 84.0 ± 7.0%, respectively. No significant differences were observed when comparing the medullary BV/TV and BIC (19.5 ± 6.4%, 16.2 ± 5.6% and 15.4 ± 9.0%) and (48.8 ± 12.9%, 49.2 ± 6.2 and 41.9 ± 11.7%), respectively. Successful induction of colitis was confirmed by loss of body weight and colon morphology. Conclusions: The results suggest bone regeneration around implants is not impaired in chemically induced colitis models. Considering that Crohn's disease can affect any part of the gastrointestinal tract including the mouth, our model only partially reflects the clinical situation. © 2012 John Wiley & Sons A/S.

Anti-inflammatory intestinal activity of Arctium lappa L. (Asteraceae) in TNBS colitis model

Ethnopharmacological relevance: In Brazilian traditional medicine, Arctium lappa (Asteraceae), has been reported to relieve gastrointestinal symptoms. Aim of the study: In the present study, we investigated the effects of the lactone sesquiterpene onopordopicrin enriched fraction (ONP fraction) from Arctium lappa in an experimental colitis model induced by 2,4,6 trinitrobenzene sulfonic acid and performed experiments to elucidate the underlying action mechanisms involved in that effect. Materials and methods: ONP fraction (25 and 50 mg/kg/day) was orally administered 48, 24 and 1 h prior to the induction of colitis and 24 h after. The inflammatory response was assessed by gross appearance, myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-α) levels and a histological study of the lesions. We determined cyclooxygenase (COX)-1 and -2 protein expressions by western blotting and immunohistochemistry assays. Results: TNBS group was characterized by increased colonic wall thickness, edema, diffuse inflammatory cell infiltration, increased MPO activity and TNF-α levels. On the contrary, ONP fraction (25 and 50 mg/kg) treatment significantly reduced the macroscopic inflammation scores (p<0.05 and p<0.01, respectively) and morphological alterations associated with an increase in the mucus secretion. Similarly, the degree of neutrophil infiltration and the cytokine levels were significantly ameliorated. Moreover, COX-2 expression was up regulated in TNBS-treated rats. In contrast, ONP fraction (50 mg/kg) administration reduced COX-2 overexpression. Conclusions: We have shown that the ONP fraction obtained from Arctium lappa exert marked protective effects in acute experimental colitis, confirming and justifying, at least in part, the popular use of this plant to treat gastrointestinal diseases. © 2013 Elsevier B.V. All rights reserved.

Nutritional intake according to injury extent in ulcerative colitis patients

Background: Ulcerative colitis (UC) is often associated with nutritional deficiency, which appears to contribute to the progression of UC severity. The present study aimed to evaluate nutritional status and dietary intake in UC remission patients. Methods: The present study comprised a cross-sectional study in which variables such as extent of disease (distal colitis, left-sided colitis, pancolitis), remission period, sex and age were recorded. Extent of disease was assessed by the results of a colonoscopy and dietary intake was evaluated by using 3-day, 24-h recalls. A Kruskall-Wallis test was used to compare the intake of macro- and micronutrients among the three study groups. The analysis was complemented by the Mann-Whitney test. A logistic regression analysis was performed to identify predictive factors of extent of disease (pancolitis versus left-sided colitis versus distal colitis). Results: The median (range) age of the 59 patients was 49.0 (37.0-63.0) years and 53.3% were female. Twenty-six (44.1%) patients had distal colitis, 11 (18.6%) patients had left-sided colitis and 22 (37.3%) patients had pancolitis. A high probability of an inadequate intake of fibre (100%), fat soluble vitamins (>40% for vitamin A and >95% for vitamin E), vitamin C (>34%), calcium (>90%) and magnesium (>50%) was identified in the study group. Vitamin D intake (odds ratio = 0.60; 95% confidence interval = 0.39-0.94; P < 0.05) was significantly associated with increased intestinal damage. Conclusions: A large number of individuals showed an inadequate intake of nutrients. In addition, the consumption of vitamin D was significantly associated with extent of disease. © 2013 The British Dietetic Association Ltd.