ramipril and Pancreatitis

Autoimmune pancreatitis is a rare form of pancreatitis characterized by responsiveness to steroid therapy and an often relapsing disease course. The mainstay of therapy is oral corticotherapy. Associations of interstitial nephritis with various autoimmune disorders have been described. We hereby report the case of a 69-year-old Caucasian man with a 2-year history of autoimmune pancreatitis, who presented with impairment of kidney function, proteinuria, and hypertension. Renal histopathology showed severe diffuse interstitial nephritis. With oral prednisone and ACE inhibitor therapy, complete recovery of kidney function was not achieved and proteinuria persisted. Therefore, mycophenolate mofetil was initiated. After 8 weeks, serum creatinine decreased, and a nearly complete and sustained resolution of proteinuria was seen, while tapering oral steroid doses. With autoreactive T cells playing a major role in the pathogenesis of both diseases, a common etiology of pancreatitis and interstitial nephritis can be assumed, and the beneficial effects of an inhibitor of lymphocyte proliferation, such as mycophenolate mofetil, can be explained. We infer from our case that mycophenolate mofetil can be effective in the control of simultaneous autoimmune pancreatitis and interstitial nephritis.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Autoimmune Diseases; Cortisone; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Nephritis, Interstitial; Pancreatitis; Prednisolone; Ramipril

Drug-induced acute pancreatitis is considered to be a rare diagnosis. The incidence of drug-induced acute pancreatitis is usually estimated from case reports.. The aim of this study was to determine the incidence, etiology, and severity of drug-induced pancreatitis during a 2-year period in a tertiary hospital.. The study was conducted as a retrospective analysis of all cases of pancreatitis in the University Hospital in Olomouc (1,432 beds) in 2006-2007. All cases of acute pancreatitis were re-evaluated and divided according to the causative factor. In drug-induced cases, the WHO Probability Scale for the evaluation of causality relationship was used.. The inclusion criteria were met by 170 medical files. There were 91 (53%) cases in men and 79 (47%) in women, and mean age was 57 years old (5-91 years old). The etiology was in 53% biliary, 31% alcohol-induced, 12% other determined, and in 4% the cause could not be established. The proportion of drug-induced acute pancreatitis was 5.3% and it was the third most frequent cause of the AP. Azathioprine was the most frequent causative factor (three cases in two patients); all the other causative drugs were documented only in single cases: mesalazine, dexamethasone, ramipril, mycophenolate mofetil, cytarabine, and valproate.. The diagnosis of drug-induced acute pancreatitis seems to be underestimated because of the difficulties in determining the causative agent and the need for a retrospective re-evaluation of the suspected causative factors. The disease is more probable in younger persons, women, and patients suffering from Crohn's disease.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Azathioprine; Child; Child, Preschool; Crohn Disease; Cytarabine; Dexamethasone; Female; Humans; Immunosuppressive Agents; Incidence; Male; Mesalamine; Middle Aged; Mycophenolic Acid; Pancreatitis; Ramipril; Retrospective Studies; Risk Factors; Severity of Illness Index; Valproic Acid; Young Adult

Pancreatic stellate cells (PSCs) are involved in pancreatic inflammation and fibrosis. Recent studies have shown that blocking the renin-angiotensin system (RAS) attenuates pancreatic inflammation and fibrosis. However, there are few data about the direct effects of high glucose on extracellular matrix (ECM) protein synthesis and angiotensin II (Ang II) induction in PSCs. PSCs were isolated from male Sprague-Dawley rats and cultured in medium containing 5.5 mM (LG group) or 27 mM D-glucose (HG group). Levels of Ang II and transforming growth factor-beta (TGF-beta) in culture media were measured and Ang II-positive cells were counted. We used real-time polymerase chain reaction (PCR) to detect Ang II receptor expression and Western blot analysis for the expression of ECM proteins such as connective-tissue growth factor (CTGF) and collagen type IV. Cells were also treated with an Ang II-receptor antagonist (candesartan, 10 microM) or angiotensin-converting enzyme (ACE) inhibitor (ramiprilat, 100 nM). Thymidine uptake by PSCs increased fourfold with high glucose treatment. Ang II levels and the proportion of Ang II-positive PSCs were significantly increased after 6 h under high-glucose conditions. TGF-beta concentrations also increased significantly with high glucose. After 72 h, the expression of CTGF and collagen type IV proteins in high-glucose cultures increased significantly and this increase was effectively attenuated by the candesartan or the ramiprilat. All together, high glucose induced PSCs proliferation and ECM protein synthesis, and these effects were attenuated by an Ang II-receptor antagonist. The data suggest that pancreatic inflammation and fibrosis aggravated by hyperglycemia, and Ang II play an important role in this pathogenesis.

Topics: Angiotensin I; Angiotensin II; Animals; Benzimidazoles; Biphenyl Compounds; Collagen; Connective Tissue Growth Factor; Dose-Response Relationship, Drug; Extracellular Matrix; Extracellular Matrix Proteins; Fibronectins; Fibrosis; Glucose; Immediate-Early Proteins; Intercellular Signaling Peptides and Proteins; Male; Pancreas; Pancreatitis; Ramipril; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Tetrazoles; Transforming Growth Factor beta

Few data exist about the incidence of drug induced acute pancreatitis in the general population. Drugs are related to the aetiology of pancreatitis in about 1.4%-2% of cases. Although angiotensin converting enzymes are generally well tolerated, acute pancreatitis has been reported in a few subjects treated with captopril, enalapril, and lisinopril. A 85 year old man with a long standing history of hypertension, who was treated with ramipril 5 mg once daily, presented with acute pancreatitis. Other causes of the disease were ruled out. After cessation of ramipril his condition improved and amylase level decreased. This was his third episode of acute pancreatitis since ramipril was started in 2000. To the authors' knowledge ramipril induced pancreatitis has not previously been reported.

Topics: Acute Disease; Aged; Aged, 80 and over; Antihypertensive Agents; Humans; Hypertension; Male; Pancreatitis; Ramipril

Acute pancreatitis is an inflammatory disease characterized by pancreatic tissue edema, acinar cell necrosis, hemorrhage and inflammation of the damaged gland. It is believed that acinar cell injury is initiated by the activation of digestive zymogens inside the acinar cells, leading finally to the autodigestion of the pancreas. Previous study in our laboratory demonstrated that cerulein-induced acute pancreatitis was associated with an up-regulation of local renin-angiotensin system (RAS) in rat pancreas. Therefore, the utilization of RAS inhibitors may provide a novel and alternative treatment for acute pancreatitis. By means of a rat model of cerulein-induced acute pancreatitis, results from the present study showed that an intravenous injection of saralasin, an antagonist for angiotensin II receptors, at a dose of 40 microg/kg 30 min before the induction of acute pancreatitis significantly attenuated pancreatic edema. Results from the biochemical measurements showed that pretreatment with saralasin at a dose of 20 microg/kg markedly reduced pancreatic injury, as evidenced by the decreased activities of alpha-amylase and lipase in plasma. However, the same recipe of ramiprilat, a specific inhibitor for angiotensin-converting enzyme, at a dose of 20 microg/kg did not provide any protective effect against acute pancreatitis. On the contrary, pretreatment with ramiprilat at a dose 40 microg/kg enhanced cerulein-induced pancreatic injury. Results from histopathological analysis of these RAS inhibitors further confirmed with those results as obtained from biochemical analysis. These data indicate that administration of saralasin but not ramiprilat could be protective against acute pancreatitis and that activation of pancreatic RAS in acute pancreatitis may play a role in pancreatic tissue injury.

Topics: Acute Disease; alpha-Amylases; Angiotensin Receptor Antagonists; Animals; Ceruletide; Disease Models, Animal; Edema; Injections, Intravenous; Lipase; Necrosis; Pancreatitis; Ramipril; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; Saralasin

Topics: Acute Disease; Aged; Angiotensin-Converting Enzyme Inhibitors; Fatal Outcome; Humans; Male; Pancreatitis; Ramipril