Vedolizumab in patients with concurrent primary sclerosing cholangitis and inflammatory bowel disease does not improve liver biochemistry but is safe and effective for the bowel disease.

BACKGROUND: Blocking of lymphocyte trafficking to bile ducts is a potential mechanism to alter the disease course of patients with primary sclerosing cholangitis (PSC). AIM: To describe the effect of the α4 ß7 integrin antibody, vedolizumab, on liver biochemistry and disease activity in patients with PSC and inflammatory bowel disease (IBD). METHODS: This is a retrospective multi-centre study of adult patients with a diagnosis of both IBD and PSC. The primary outcome was change in serum alkaline phosphatase level at weeks 14 and 30. Secondary outcomes included changes in other liver biochemistries and in clinical outcomes for the bowel disease. A safety analysis for adverse events was performed. RESULTS: Thirty-four patients (16 Crohn's disease, 18 ulcerative colitis) were included. Nine (26%) had a history of liver transplant. Median follow-up on vedolizumab was 9 months (IQR: 7-16). There was no overall change in serum alkaline phosphatase level with vedolizumab therapy (median 268 [IQR: 105-551] IU/L at baseline versus 249 [IQR: 183-634] IU/L, P = 0.99 at week 30). No significant changes in other liver biochemistries or the Mayo PSC Risk Score were demonstrated at week 30. Clinical remission was achieved at week 30 in 55% of Crohn's disease and 29% of ulcerative colitis patients. Seven (21%) patients ceased vedolizumab; six patients stopped therapy due to persistent IBD activity and one for worsening of liver biochemistries. CONCLUSION: Vedolizumab treatment in patients with PSC and IBD did not improve liver biochemistry but was associated with improvement in bowel disease and a favourable safety profile.

Glutamine and alanyl-glutamine accelerate the recovery from 5-fluorouracil-induced experimental oral mucositis in hamster.

INTRODUCTION: Mucositis induced by anti-neoplastic drugs is an important, dose-limiting and costly side effect of cancer therapy. AIM: To evaluate the effect of oral glutamine and alanyl-glutamine, a more stable glutamine derivative, on 5-FU-induced oral mucositis in hamsters. MATERIALS AND METHODS: Oral mucositis was induced by two intraperitoneal (i.p) administrations of 5-FU on the first and second days of the experiment (60 and 40 mg/kg, respectively) followed by mechanical trauma on the fourth day in male hamsters. Animals received saline, glutamine or alanyl-glutamine suspension (100 mM) 1 h before the injections of 5-FU and daily until sacrifice, on the 10th or 14th day. Macroscopic and histopathological analyses were evaluated and graded. Tissues from the cheek pouches were harvested for measurement of myeloperoxidase activity and glutathione stores. For investigation of serum concentration of glutamine, blood was obtained by heart puncture from anesthetized animals before sacrifice, on day 10. RESULTS: Treatment with glutamine and alanyl-glutamine reduced macroscopic and histological parameters of oral mucositis, and reduced the myeloperoxidase activity on day 14, but not on day 10. The 5-FU-induced oral mucositis significantly decreased the serum glutamine levels as well as the cheek pouch glutathione stores observed on day 10. Glutamine or alanyl-glutamine administration reversed the 5-FU effects, restoring serum glutamine levels and cheek pouch glutathione stores, observed on day 10, but did not prevent oral mucositis on the tenth day. CONCLUSION: Glutamine or alanyl-glutamine accelerated the mucosal recovery increasing mucosal tissue glutathione stores, reducing inflammatory parameters and speeding reepithelization.

Role of nitric oxide on pathogenesis of 5-fluorouracil induced experimental oral mucositis in hamster.

INTRODUCTION: Mucositis induced by antineoplastic drugs is an important, dose-limiting, and costly side effect of cancer therapy. AIM: To investigate the role of nitric oxide (NO) on the pathogenesis of 5-fluorouracil (5-FU)-induced oral mucositis. MATERIALS AND METHODS: Oral mucositis was induced by two intraperitoneal (i.p) administrations of 5-FU on the first and second days of the experiment (60 and 40 mg/kg, respectively) in male hamsters. Animals were treated subcutaneously with saline (0.4 ml), 1,400 W (1 mg/kg), aminoguanidine (5 or 10 mg/kg) or Nphi-Nitro-L-Arginine Methyl Ester (L-NAME) (5, 10, or 20 mg/kg) 1 h before the injections of 5-FU and daily until sacrifice, on the tenth day. Macroscopic and histopathological analyses were evaluated and graded. Tissues from the cheek pouches were harvested for measurement of myeloperoxidase (MPO) activity, nitrite level, and immunohistochemistry for induced nitric oxide synthase (iNOS). RESULTS: Treatment with 1,400 W or aminoguanidine reduced macroscopic and histological parameters of oral mucositis, and reduced the inflammatory cell infiltration as detected by histopathology and by MPO activity. In contrast, the administration of L-NAME did not significantly reverse the inflammatory alterations induced by experimental mucositis. Increased NOS activity, nitrite level and immunostaining for iNOS were detected on the check pouch tissue of animals submitted to 5-FU-induced oral mucositis on the tenth day. CONCLUSION: These results suggest an important role of NO produced by iNOS in the pathogenesis of oral mucositis induced by 5-FU.

Ecodopplercardiograma na avaliação de sinais precoces de comprometimento cardíaco decorrente de diferentes níveis de hipertensão arterial sistêmica em pacientes de 18 a 40 anos / Dopplerechocardiography evaluation of early signs of cardiac involvement induced by several levels of systemic hypertension in individuals aged 18 to 40 years old

Objetivo: Avaliar as alterações precoces na função diastólica e morfologia cardíaca em pacientes com nível de hipertensão arterial primária entre 18 e 40 anos. Métodos: 110 pacientes normotensos e 130 hipertensos: 83 no estágio I (PAS - Pressão Arterial Sistólica de 140 a 159 mmHg e PAD (Pressão Arterial Diastólica de 90 a 99 mmHg); no estágio II (PAS de 160 a 179 mmHg, PAD de 100 a 109 mmHg) e 22 no estágio III (PAS acima de 180 mmHg e PAD acima de 110 mmHg) foram submetidos a exame físico e exames complementares (bioquímica, eletrocardiograma, raios-X de tórax e ecodopplercardiograma). Resultados: Nos hipertensos, a espessura do septo interventricular não foi significativamente maior, inclusive no estágio III (p maior 0,05). A espessura relativa da PP (parede posterior) definido pela relação PP / raio do VE (ventriculo esquerdo) em diastóle e a fração de ejeção só foram maiores em pacientes no estágio III (P menor 0,05). A massa do ventriculo esquerdo (MVE) e índice de massa do VE(IMVE) foram maiores em todos os grupos com hipertensão quando comparados aos normotensos. Pelo fluxograma da valva mitral, 92 por cento de pacientes com hipertensão estágio I, 83,9 por cento estágio II e 81,9 por cento estágio III tiveram uma relação E/A maior 1, como um dos indicadores de relaxamento VE normal. Hipertrofia concêntrica do VE foi significativamente maior em pacientes com hipertensão estágio III. Porém, hipertrofia excêntrica do VE foi maior em pacientes nos estágios II e I. Conclusão: A MVE e o IMVE foram as alterações mais frequentes em todos os estágios de hipertensão quando comparados aos normotensos, sugerindo ser a alteraçãio mais precoce e o achado mais sensível na avaliação de danos cardíacos a hipertensão entre 18 e 40 anos. A hipertrofia precede as alterções no relaxamento medida pela relação E/A no fluxograma da valva mitral, sugerindo ser não somente relacionada diretamente com idade e tempo de diagnóstico, ma também com o nível de pressão arterial.