review of literature on clinical pancreatology - The Pancreapedia

for the first time the significance <strong>of</strong> PRSS1, SPINK1 mutations and genetic variants <strong>of</strong> AAT ina group <strong>of</strong> Spanish patients with chronic pancreatitis. One hundred and four consecutivepatients with chronic pancreatitis were included, as well as 84 healthy control subjects. TheR122H and N29I mutations in the PRSS1 gene, the N34S mutation in the SPINK1 gene andPiS and PiZ mutations in the AAT gene were analyzed by RFLP-PCR methods. No R122Hmutation was found in the PRSS1 gene, and N29I mutation was detected in 8 percent <strong>of</strong>chronic pancreatitis patients. A N29I mutation was observed in 4 percent <strong>of</strong> patients withalcohol-related pancreatitis. A total <strong>of</strong> 6 percent <strong>of</strong> chronic pancreatitis patients wereidentified with the N34S mutation. Genotype MS, SS and MZ were detected in 18.3, 3.8 and1.3 percent <strong>of</strong> patients, respectively. It was concluded that the percentage <strong>of</strong> N29I mutationsin alcohol-related pancreatitis patients was higher than that reported in other studies, whilethe percentage <strong>of</strong> N34S and AAT mutations in alcohol-related pancreatitis and idiopathicchronic pancreatitis patients was similar [250].Possible etiological factorsChronic pancreatitis is an inflammatory disease followed by structural alterations –inflammation, fibrosis and acinar atrophy – pain emergence, exocrine and endocrinepancreatic insufficiency, severe alteration <strong>of</strong> quality <strong>of</strong> life. The pathogenetic mechanismscharacteristic to this disease are not thoroughly known, but the identification <strong>of</strong> some geneticand autoimmune factors in certain entities has elucidated several pathogenetic links. Theetiologic risk factors for chronic pancreatitis may associate each other and may causedifferent evolutions to the disease. By tracing out the risk factors and their typical workingmechanisms, further pathogenetic treatments may occur, taking place precociously andpreventing the evolution <strong>of</strong> the disease towards exocrine and endocrine pancreaticinsufficiency [251].HomocysteinemiaHomocysteine has been implicated in vascular dysfunction and thrombosis, as well asinflammatory conditions. One study was aimed to find out whether chronic pancreatitis isassociated with hyperhomocysteinemia and derangements <strong>of</strong> transmethylation andtranssulfuration pathways. It was estimated homocysteine and its metabolites in 45 alcoholicchronic pancreatitis patients, 45 tropical chronic pancreatitis patients, and 48 healthycontrols. Significant increases in plasma total homocysteine and decreases in red blood cellfolate, reduced glutathione, plasma methionine, cysteine, and urinary inorganicsulfate/creatinine ratio were observed in both alcoholic and tropical chronic pancreatitispatients in comparison with healthy controls. Red blood cell glutathione and plasma cysteinelevels were significantly lower in alcoholic than in tropical chronic pancreatitis patients.However, plasma vitamin B12 levels were comparable between chronic pancreatitis patientsand controls. No significant differences in these parameters were observed between diabeticpatients and nondiabetic patients. Multivariate regression analysis showed a significantnegative correlation between homocysteine and folate and a positive correlation betweenglutathione and cysteine levels. It was concluded that pancreatitis is associated withhyperhomocysteinemia and derangements in transmethylation and transsulfurationpathways. Low folate levels observed in these patients seem to have a key role in thisderangement [252].Changes in neurohormonesIt was measured content <strong>of</strong> neuromediators (acetylcholine, serotonin) and gastrointestinalhormones (cholecystokinine and secretin) in the blood serum <strong>of</strong> patients with chronicpancreatitis to study protective properties <strong>of</strong> the mucus in the duodenum. In alcoholic