Deficiency of folate and vitamin B12 increases oxidative stress in chronic pancreatitis patients.

BACKGROUND: Folate and vitamin B12 are involved in metabolic reactions for combating oxidative stress. We measured erythrocyte folate and plasma vitamin B12 and compared these with blood antioxidants - erythrocyte glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and plasma vitamin C - and marker of lipid peroxidation, thiobarbituric acid reactive substance (TBARS), in chronic pancreatitis (CP) patients. METHODS: One hundred and seventy-five CP patients (91 tropical, 84 alcoholic) and 113 healthy controls were recruited. Erythrocyte folate and plasma vitamin B12 were measured using microbiological assay, and antioxidant levels and erythrocyte TBARS by spectrophotometry. RESULTS: Erythrocyte folate and plasma vitamin B12 were significantly lower in CP patients than controls (225.4 ± 9.13 vs. 380.38 ± 17.29 nmol/L, p < 0.001 and 233.23 ± 10.4 vs. 338.84 ± 19.01 pmol/L, p < 0.001), and in diabetic- vs. non-diabetic CP patients. Blood antioxidant levels were significantly lower and TBARS was higher in CP patients as compared to controls. Low folate level correlated with low GSH levels (r = 0.314, p < 0.001). CP patients with low folate and vitamin B12 had low GSH and GPx levels as compared to patients with normal folate and vitamin B12 levels. Low vitamin B12 level was associated with 3.24 (95% CI 1.11-9.46, p < 0.05) fold increased risk of pancreatic insufficiency. Smoking was associated with 9.82 (95% confidence interval [CI] 3.3-29.22, p < 0.05) fold increased risk of having low folate levels. CONCLUSION: Low folate and vitamin B12 levels were associated with increased oxidative stress in CP patients.

Time trends in the etiology of chronic pancreatitis in South India.

BACKGROUND: Recent reports indicate a decline in prevalence of classical tropical chronic pancreatitis (TCP). We studied the etiologies and risk factors over a 14-year period at a tertiary care university hospital. METHODS: We compared the etiology in chronic pancreatitis (CP) patients presenting and followed-up in our Pancreas Clinic over two time periods (2000-06 and 2007-13). RESULTS: Idiopathic chronic pancreatitis (ICP) was the predominant etiology seen over the two time periods. However an increase in prevalence of alcoholic chronic pancreatitis (ACP) during the latter time period suggests that it may be emerging as a dominant etiology over recent years. Hypertriglyceridemia and hyperparathyroidism were uncommon causes of non-alcoholic CP. Autoimmune pancreatitis was noted only during 2007-13, but remains a rare cause of CP. There are multiple risk factors for CP in our population. CONCLUSIONS: The high prevalence of ICP indicates need closer examination of risk factors and ICP pathogenesis. ACP appears to be emerging as a dominant cause of CP which suggests a need to reorient preventive strategies.

Assessment of cassava toxicity in patients with tropical chronic pancreatitis.

BACKGROUND AND AIM: There have been conflicting reports on the role of cassava ingestion in tropical pancreatitis (TCP). In this study we aimed to estimate cyanogens detoxifying enzyme rhodanese, thiocyanate and sulfur containing amino acids in cassava consumer as well as cassava non-consumer TCP patients and healthy controls and compare the same. METHODS: Eighty-six TCP patients and 90 healthy controls were recruited. Serum rhodanese, thiocyanate, plasma amino acids, urinary inorganic sulfate/creatinine were measured. RESULTS: There was significant reduction in serum rhodanese activity in both cassava consumer- and non-consumer TCP patients as compared to controls but no significant difference between cassava consumer- and non-consumer TCP patients was observed. Serum thiocyanate was significantly lower in cassava consumer TCP patients as compared to cassava consumer controls but not significantly different from cassava non-consumer TCP patients. Plasma methionine, cysteine and urinary inorganic sulfate / creatinine ratio was significantly lower in both cassava consumer and non-consumer TCP patients as compared to controls but were comparable among cassava consumers and non-consumers. CONCLUSIONS: Significant reduction in rhodanese activity with concomitant decrease in sulfur containing amino acids and antioxidants such as glutathione suggests that TCP patients are at higher risk of defective detoxification of cyanogens. However there was no difference between cassava consumers and non-consumers. Low levels of sulfur amino acids may contribute to the development of pancreatitis.

Assessment of oxidative status in chronic pancreatitis and its relation with zinc status.

BACKGROUND: Oxidative stress-induced free radicals have been implicated in the pathology of chronic pancreatitis (CP). AIM: We aimed to estimate oxidative stress and antioxidant status in tropical chronic pancreatitis (TCP) and alcoholic chronic pancreatitis (ACP) and correlate with zinc status. METHODS: One hundred and seventy-five CP patients (91 TCP, 84 ACP) and 113 healthy subjects were prospectively studied. Disease characteristics and imaging features were recorded. Erythrocyte reduced glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), plasma vitamin C, and erythrocyte thiobarbituric acid reactive substance (TBARS) were estimated by spectrophotometry. Erythrocyte zinc was estimated by flame atomic absorption spectrophotometry. RESULTS: Enhanced lipid peroxidation with concomitant decrease in antioxidant status was observed in both TCP and ACP patients (p < 0.05). The findings were comparable in both diabetic and non-diabetic CP patients. Significantly, lower plasma vitamin C and elevated levels of erythrocyte TBARS was noted in TCP as compared to ACP patients. The erythrocyte zinc significantly correlated with SOD activity (r = 0.450, p < 0.001). CONCLUSIONS: Our study corroborates the role of oxidative stress in CP and suggests some differences in oxidative status in TCP and ACP patients. Zinc deficiency appears to affect oxidative status in CP patients.

Alterations in plasma amino acid levels in chronic pancreatitis.

CONTEXT: Dietary proteins and amino acids can modulate pancreatic function. OBJECTIVE: Our aim was to estimate the levels of plasma amino acids in chronic pancreatitis patients and study their relationship with disease characteristics as well as exocrine and endocrine insufficiency. PATIENTS: One hundred and seventy-five consecutive adult patients with chronic pancreatitis: 84 patients with alcoholic chronic pancreatitis and 91 patients with tropical chronic pancreatitis. One hundred and thirteen healthy controls were also studied. DESIGN: Prospective study. MAIN OUTCOME MEASURES: Disease characteristics and imaging features were recorded. Plasma-free amino acid levels were estimated using reverse-phase high-performance liquid chromatography. Polyclonal antibody ELISA was used to assess pancreatic fecal elastase-1. RESULTS: The majority of the plasma free amino acid levels decreased in chronic pancreatitis patients whereas glutamate, glycine, proline and lysine were elevated as compared to the controls. Multivariate logistic regression analysis revealed that the decrease in branched chain amino acid concentration was significantly associated with the presence of diabetes and low fecal elastase-1. In addition, a significant positive correlation was observed between branched chain amino acids and pancreatic elastase-1 (rs=0.724, P<0.001). CONCLUSION: Reductions of plasma amino acid levels are seen in chronic pancreatitis, particularly sulphur containing amino acids and branched chain amino acids. Selective amino acid deficiencies seem to correlate with exocrine and endocrine insufficiency.

Chronic pancreatitis is associated with hyperhomocysteinemia and derangements in transsulfuration and transmethylation pathways.

OBJECTIVES: Homocysteine has been implicated in vascular dysfunction and thrombosis, as well as inflammatory conditions. This study was aimed to find out whether chronic pancreatitis (CP) is associated with hyperhomocysteinemia and derangements of transmethylation and transsulfuration pathways. METHODS: We estimated homocysteine and its metabolites in 45 alcoholic CP patients, 45 tropical CP patients, and 48 healthy controls. RESULTS: Significant increases in plasma total homocysteine and decreases in red blood cell folate, reduced glutathione, plasma methionine, cysteine, and urinary inorganic sulfate/creatinine ratio were observed in both alcoholic and tropical CP patients in comparison with healthy controls. Red blood cell glutathione and plasma cysteine levels were significantly lower in alcoholic than in tropical CP patients. However, plasma vitamin B12 levels were comparable between CP patients and controls. No significant differences in these parameters were observed between diabetic patients and nondiabetic patients. Multivariate regression analysis showed a significant negative correlation between homocysteine and folate (r = -0.415, P = 0.001) and a positive correlation between glutathione and cysteine levels (r = 0.37, P = 0.003). CONCLUSIONS: Chronic pancreatitis is associated with hyperhomocysteinemia and derangements in transmethylation and transsulfuration pathways. Low folate levels observed in these patients seem to have a key role in this derangement.

Zinc status in chronic pancreatitis and its relationship with exocrine and endocrine insufficiency.

CONTEXT: A major role of the pancreas in zinc homeostasis has been suggested. OBJECTIVE: To assess erythrocyte zinc status in chronic pancreatitis and to correlate it with pancreatic exocrine and endocrine insufficiency. PATIENTS: One hundred and one patients with chronic pancreatitis (34 alcoholic chronic pancreatitis, 67 tropical chronic pancreatitis) were prospectively studied. MAIN OUTCOME MEASURE: Disease characteristics and imaging features were recorded. Erythrocyte zinc was estimated by flame atomic absorption spectrophotometry. Exocrine insufficiency was assessed using polyclonal antibody ELISA for pancreatic stool elastase1. Endocrine insufficiency was assessed by serum glucose levels and insulin requirement. RESULTS: Erythrocyte zinc was significantly lower in chronic pancreatitis patients than in the controls (26.5+/-9.5 microg/g Hb vs. 38.0+/-6.6 microg/g Hb; P<0.001), and in tropical chronic pancreatitis than in alcoholic chronic pancreatitis (25.0+/-10.4 microg/g Hb vs. 29.6+/-6.5 microg/g Hb, P=0.001). In chronic pancreatitis patients who had exocrine insufficiency, erythrocyte zinc positively correlated with stool elastase1 (r=0.587, P<0.001). Erythrocyte zinc levels were significantly lower in diabetic patients as compared to non-diabetics (P=0.036). CONCLUSIONS: This study demonstrates zinc deficiency in chronic pancreatitis patients, and that zinc deficiency correlates with exocrine and endocrine insufficiency. Further studies may clarify the possible benefits of zinc supplementation in chronic pancreatitis.

Fecal elastase1 and acid steatocrit estimation in chronic pancreatitis.

BACKGROUND: Measurement of pancreatic exocrine function and steatorrhea in chronic pancreatitis in the clinical setting has not received much attention. AIM: To assess pancreatic exocrine function and fecal fat excretion in a cohort of patients with chronic pancreatitis. METHODS: Stool elastase1 levels were measured in 101 patients using polyclonal ELISA and acid steatocrit was measured in 86 chronic pancreatitis patients. Associations with etiology, clinical and radiological features, and diabetic status were examined. RESULTS: Low pancreatic stool elastase1 (<200 microg/g stool) was observed in two-thirds of chronic pancreatitis patients and correlated with ductal dilatation, pancreatic atrophy and calcification (p<0.05). Diabetes was more prevalent in chronic pancreatitis patients with low elastase1 (p=0.045). There was no difference in mean acid steatocrit between diabetics and non-diabetics (p=0.069). Elastase1 levels had a negative correlation with acid steatocrit (r=-0.606, p<0.001), and a positive correlation (r=0.412) with body mass index (p=0.013). Fifty-three percent of chronic pancreatitis patients with normal BMI had low elastase1. CONCLUSIONS: Fecal elastase1 levels correlated with fecal fat excretion and BMI. Fecal elastase1 estimation may be helpful in early detection of malabsorption in chronic pancreatitis.