Acute pancreatitis in inflammatory bowel disease, with special reference to azathioprine-induced pancreatitis

Background  Pancreatitis is a potentially severe condition. Patients with inflammatory bowel disease (IBD) seem to be at increased risk for acute pancreatitis.
Aim  To describe the incidence, main causes and possible predictive factors of acute pancreatitis in inflammatory bowel disease.
Methods  Information was retrospectively extracted from the clinical records of patients followed in the IBD Units of nine hospitals in Madrid ( n  = 5073).
Results  A total of 82 acute pancreatitis episodes were diagnosed (cumulative incidence, 1.6%); 98% of them were mild. Recurrent acute pancreatitis developed in 13% of patients. Most cases of acute pancreatitis (63.4%) were attributed to drug exposure [azathioprine/mercaptopurine (AZA/MP) n  = 46, mesalazine (mesalamine) n  = 6]; 20.7% were idiopathic, and 12.2% were biliary. Incidence of acute pancreatitis in patients treated with AZA/MP was 3.1%. In patients with acute pancreatitis, female gender (OR 3.4 95% CI: 1.3–9.3; P  = 0.012) and Crohn's disease (CD) (OR 5.8 95% CI: 1.6–20.6; P  = 0.007) were risk factors for AZA/MP-associated acute pancreatitis, the latter also when analysed only in patients treated with AZA/MP ( n  = 1477) (OR 5.2 95% CI: 1.8–14; P  = 0.002).
Conclusions  The incidence of acute pancreatitis in our IBD patients (1.6%) is similar to that previously described. Drugs, mainly AZA/MP, are the leading cause. AZA-induced acute pancreatitis is always mild. Patients with CD are at a higher risk for AZA/MP-associated acute pancreatitis. The frequency of idiopathic acute pancreatitis is higher than expected, suggesting that part of these cases could be extraintestinal manifestations of IBD.     

Review article: malignancy on thiopurine treatment with special reference to inflammatory bowel disease

Aliment Pharmacol Ther 2010; 32: 119–130

Summary

Background Immunosuppression is a risk factor for carcinogenesis. Thiopurines specifically contribute to this. As thiopurines are used more aggressively in the treatment of IBD, it is likely that we will see more thiopurine‐related malignancy. Aim To review the literature, exploring how immunosuppression, thiopurines specifically, might cause cancer and which malignancies occur in practice, placing specific emphasis on IBD cohorts. Methods Search terms included ‘malignancy’‘cancer’‘azathioprine’‘mercaptopurine’‘tioguanine (thioguanine)’‘thiopurine’ and ‘inflammatory bowel disease’‘Crohn’s disease’‘ulcerative colitis’. We also searched for specific cancers (lymphoma, colorectal cancer, skin cancer, cervical cancer) and reviewed the reference lists of the articles detected. Results Immunosuppression is associated with an increased risk of cancer. Thiopurines are associated with specific additional risks. In IBD cohorts, very few thiopurine‐related malignancies have been reported. However, studies suggest a relative risk of 4–5 for lymphoma. This still translates into a low actual risk, (one extra lymphoma in every 300–1400 years of thiopurine treatment). Conclusions Whilst we must be aware of this risk and counsel our patients appropriately, thiopurines remain a mainstay of IBD therapy. We present practical advice aimed at minimizing our patients’ risk of developing malignancy, whilst optimizing the benefits that thiopurines can provide.     

Fabry disease with special reference to neurological manifestations

Fabry's disease is an X-linked recessive Lysosomal Storage disease. The underlying metabolic defect is deficiency of lysosomal enzyme ceramidetrihexosidase. The disease has multisystem involvement. Neurological manifestations include small-fiber polyneuropathy manifested as painful distal extremities and anhidrosis. Fabry's disease also presents with both small-vessel and cortical multiple cerebral infarcts. Enzyme-replacement therapy has been found effective but expensive. Gene therapy could evolve as the ultimate therapeutic strategy.     

Quality control of antibodies with special reference to prostaglandins

Sources of error in the immunoassay of prostaglandins are reviewed. First, the specificity of the antibody, in terms of cross-reactions with structurally related substances, is often tested against irrelevant compounds, i.e. available compounds that do not occur in the biological material under study; major metabolises occurring in much larger amounts are overlooked. Hence, the reported high specificity of some antibodies may be apparent only. Second, many eicosanoids occur in two or more chemical forms in equilibrium in aqueous media. Antibodies may recognize one form preferentially; thus comparison of data from different laboratories is difficult. In addition numerous factors may interfere with the antigen-antibody binding in a non-immunological way. The most common effect is inhibition of antigen-antibody binding, but enhancement of binding sometimes occurs.     

Chitosan induced hepato-nephrotoxicity in mice with special reference to gender effect in glycolytic enzymes activities

Chitosan is an antilipidemic dietary supplement used as a diet aide. The present study investigated the effect of sex-toxicity relationship between male and female mice orally given two dose levels (150 and 300 mg/kg) for 35 days. Chitosan treatment caused significant elevation in transaminases (ALT, AST) and alkaline phosphatase (ALP) in liver and in serum urea and creatinine in dose dependent manner; no sex differences between-treated groups. Lipid profile parameters significantly decreased and significant increase in glycolytic enzymes activities in all treatment groups. Female mice treated with chitosan (300 mg/kg) had significant reduction in lipid profile parameters than the same dose of male group. Phosphofructokinase (PFK) and lactate dehydrogenase (LDH) activities significantly enhanced without sex differences, while glucose phosphate isomerase (GPI) and hexokinase (HK) significantly elevated in the higher dose of females than male. Histopathological study of liver and kidney tissues showed moderate to severe histopathological changes depend on the dose and gender difference. Image analysis resulted significant depletion in glycogen and protein contents especially in female more than male. These results indicated that female mice were more susceptible to the toxic effect of chitosan than males when administered with the higher dose for a long period.