Gopalakrishna Rajesh

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

BackgroundOxidative stress-induced free radicals have been implicated in the pathology of chronic pancreatitis (CP).AimWe aimed to estimate oxidative stress and antioxidant status in tropical chronic pancreatitis (TCP) and alcoholic chronic pancreatitis (ACP) and correlate with zinc status.MethodsOne 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.ResultsEnhanced 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).ConclusionsOur 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.

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.

Fecal elastase1 and acid steatocrit estimation in chronic pancreatitis

BackgroundMeasurement of pancreatic exocrine function and steatorrhea in chronic pancreatitis in the clinical setting has not received much attention.AimTo assess pancreatic exocrine function and fecal fat excretion in a cohort of patients with chronic pancreatitis.MethodsStool 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.ResultsLow pancreatic stool elastase1 (<200 μg/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). Fiftythree percent of chronic pancreatitis patients with normal BMI had low elastase1.ConclusionsFecal elastase1 levels correlated with fecal fat excretion and BMI. Fecal elastase1 estimation may be helpful in early detection of malabsorption in chronic pancreatitis.

Alcoholic chronic pancreatitis and alcoholic liver cirrhosis: differences in alcohol use habits and patterns in Indian subjects.

Objectives Alcohol abuse is a risk factor for both liver cirrhosis and chronic pancreatitis. However, less than 15% of heavy drinkers develop these complications. Coexistence of cirrhosis and pancreatitis in the same patient is considered uncommon. We compared drinking patterns and related patient factors in patients with alcoholic liver cirrhosis and alcoholic chronic pancreatitis. Methods A prospective evaluation of 307 patients (all men: 188 with alcoholic liver cirrhosis and 119 with alcoholic chronic pancreatitis) was conducted over a 7-year period using a detailed alcohol assessment proforma. Assessment of demographic features, diet, and other habits like tobacco smoking were recorded. Results Patients with alcoholic liver cirrhosis were older. The mean ± SD age in alcoholic liver cirrhosis was 52.4 ± 9.16 years and 47.1 ± 9.78 years (P < 0.001) in alcoholic chronic pancreatitis. The mean ± SD age when they started drinking was similar in both groups (22.8 ± 5.32 years and 24.3 ± 6.94; P > 0.05). The mean ± SD duration of drinking was higher in the cirrhosis group (29.5 ± 10.25 years) than in the pancreatitis group (21.5 ± 9.61 years) (P < 0.001). Fifty-nine percent of cirrhosis and 75% of pancreatitis were heavy tobacco smokers (P = 0.004). Conclusions There are distinct differences in drinking patterns and related patient factors between alcoholic liver cirrhosis and alcoholic chronic pancreatitis, suggesting the need to orient different interventional strategies.

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.

Genotype-phenotype correlation in 9 patients with tropical pancreatitis and identified gene mutations.

The etiopathogenesis of tropical chronic pancreatitis (TCP) remains unclear. Malnutrition, dietary toxins like cyanogens in cassava and micronutrient deficiency are proposed factors. The description and characterization of genetic factors in TCP has added a new dimension to the understanding of pathogenesis of the disease. However, there is sparse data on the association of TCP with cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. We report 8 patients of TCP with CFTR gene mutations, including one with a novel mutation, and describe the clinical profile of these patients. Further prospective genetic studies on the association of CFTR gene mutations are essential in order to unravel the genetic basis of TCP.