ABSTRACT
BACKGROUND: A number of recent studies have demonstrated a protective effect of renin-angiotensin system (RAS) antagonism against immune mediated diseases such as myocarditis, chronic allograft rejection, and antiglomerular basement membrane nephritis. To our knowledge, there has been no report on the immunological contribution of the RAS in colonic tissue. AIMS: We evaluated the direct effect of angiotensin II (AII) on the pathogenesis of immune mediated colitis using angiotensinogen deficient homozygous (Atg-/-) mice. SUBJECTS: 2,4,6-Trinitrobenzene sulphonic acid (TNBS) colitis was induced in Atg-/- and wild-type (Atg+/+) mice. METHODS: Levels of proinflammatory cytokines in the colon were determined by enzyme linked immunosorbent assay. Histological analysis was performed simultaneously. RESULTS: Although Atg-/- mice developed colitis, the degree was much milder than that in Atg+/+ mice (p<0.05). Colonic cytokine analysis showed that the production of proinflammatory cytokines (interleukin (IL)-1beta, interferon gamma (IFN-gamma)) was impaired in Atg-/- mice. Furthermore, expression of cytokines such as IL-4 and IL-10 in the colon was predominant in Atg-/- compared with Atg+/+ mice after TNBS instillation (p<0.005, p<0.01, respectively). Similarly, subcutaneous infusion of losartan suppressed colitis (p<0.05) and the production of proinflammatory cytokines (IL-1beta, IFN-gamma). These results indicate that the RAS is directly involved in the pathogenesis of TNBS colitis through regulation of proinflammatory and anti-inflammatory cytokines in the colon. CONCLUSIONS: This study revealed that the RAS is involved in the immune system in the colon. Antagonism of the RAS is a potential prophylactic strategy for the treatment of human inflammatory bowel disease.
Subject(s)
Angiotensinogen/physiology , Colitis/prevention & control , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensinogen/deficiency , Angiotensinogen/genetics , Animals , Colitis/chemically induced , Colitis/immunology , Colitis/pathology , Colon/immunology , Cytokines/biosynthesis , Immunity, Mucosal , Intestinal Mucosa/immunology , Losartan/therapeutic use , Male , Mice , Mice, Inbred ICR , Mice, Knockout , Renin-Angiotensin System , Trinitrobenzenesulfonic Acid , Weight Loss/drug effects , Weight Loss/geneticsABSTRACT
A 56-year-old man developed severe lower gastrointestinal bleeding. He was classified as Child-Pugh grade C. Colonoscopy revealed multiple angiodysplasia-like lesions and mucosal friability throughout the entire colon (portal hypertensive colopathy, PHC). Haemostasis was immediately achieved with octreotide treatment, although melaena recurred after discontinuation of the infusion. Propranolol treatment before discontinuation of octreotide infusin prevented the recurrence of bleeding from PHC. Octreotide is a safe and effective treatment for severe acute bleeding from PHC, especially if the patient is not a candidate for transjugular intrahepatic portosystemic shunt (TIPS) or treatment with a beta-blocker due to the severity of liver disease or haemodynamic instability. However, a sufficient reduction of portal pressure by propranolol or other medical treatment may be needed in order to discontinue octreotide infusion without the recurrence of bleeding.
Subject(s)
Colonic Diseases/drug therapy , Gastrointestinal Hemorrhage/drug therapy , Hemostatics/administration & dosage , Hypertension, Portal/complications , Liver Cirrhosis/complications , Octreotide/administration & dosage , Acute Disease , Colonic Diseases/etiology , Colonoscopy , Dose-Response Relationship, Drug , Follow-Up Studies , Gastrointestinal Hemorrhage/etiology , Humans , Hypertension, Portal/diagnosis , Infusions, Intravenous , Liver Cirrhosis/diagnosis , Male , Middle Aged , Severity of Illness Index , Treatment OutcomeSubject(s)
Hepatitis/etiology , Syphilis/complications , Abdominal Pain/etiology , Acute Disease , Adult , Cholangitis/etiology , Humans , Male , RecurrenceABSTRACT
Tumor metastasis to the hypophyseal system has rarely been reported with either clinical or radiographic evidence. A 52-year-old woman presented with polydipsia, polyuria, and loss of appetite. She was diagnosed as having diabetes insipidus caused by pituitary micrometatasis of lung adenocarcinoma. After she had been treated with radiation therapy to the pituitary gland, the gland size was reduced as confirmed by magnetic resonance imaging, and her urine volume decreased. However, meningitis carcinomatosa appeared later. This was a rare case of secondary diabetes insipidus due to pituitary metastasis of lung cancer.
