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Byline: Zoltan Jambrik (1), Mariann Gyongyosi (2), Peter Hegyi (3), Laszlo Czako (3), Tamas Takacs (3), Andras Farkas (4), Yvette Mandy (5), Csaba Gog (3), Dietmar Glogar (2), Miklos Csanady (1) Keywords: Plasma levels IL-6 Hemodynamic abnormalities Acute pancreatitis Rabbits Abstract: Abstract Objective. To examine the relationship between plasma cytokine levels and cardiac and hemodynamic function. Design. Measurement of cytokines and the systolic (left ventricular dimensions, heart rate, and cardiac output) and diastolic (early and late transmitral peak flow velocity: E and A-waves and their ratio) functions of the left ventricle (assessed by echocardiography) in rabbits. Setting and interventions. Laboratory and echocardiographic analyses were performed at baseline and at 1, 3, 6, 12, and 24 h after acute necrotizing pancreatitis induction (Group ANP), in rabbits after somatostatin pretreatment (Group S-ANP) and in sham-operated controls (Group C). Measurements and results. Left ventricular dilatation occurred at 6 h and cardiac output was increased 3 h after induction of acute necrotizing pancreatitis. Somatostatin pretreatment mitigated the left ventricular enlargement and filling abnormalities. Plasma level of IL-6 was increased significantly 3 h after pancreatitis induction, but to a lesser extent in Group S-ANP, while somatostatin prevented TNF[alpha] release (IL-6: Group ANP: 0, 0, 518+-139, 956+-125, 373+-48, and 122+-37 pg/ml Group S-ANP: 0, 0, 191+-68, 261+-49, 23+-13, and 0 pg/ml TNF[alpha]: Group ANP: 88+-42, 371+-40, 2963+-291, 276+-30, 197+-106, and 23+-14 U/l Group S-ANP: 91+-34, 41+-25, 68+-42, 25+-9, 0, and 0 U/ml). The increase in plasma level of IL-6 correlated significantly with left ventricular end-diastolic diameter and volume, cardiac output, and diastolic dysfunction. Conclusions Plasma levels of IL-6, but not TNF[alpha] correlate with cardiac output and left ventricular filling characteristics in acute pancreatitis. Somatostatin pretreatment improves the cardiac and hemodynamic changes, probably through the decrease in cytokine release. Author Affiliation: (1) 2nd Dept of Int. Medicine and Cardiological Center, University of Szeged, Hungary (2) Division of Cardiology, University of Vienna Medical Center, Wahringer Gurtel 18--20, 1090, Vienna, Austria (3) 1st Dept. of Int. Medicine, University of Szeged, Hungary (4) Dept. of Pharmacology and Pharmacotherapy, University of Szeged, Hungary (5) Dept. of Microbiology, University of Szeged, Hungary Article History: Received Date: 11/03/2002 Accepted Date: 19/09/2002 Article note: Electronic Publication

Genetic polymorphisms of the genes involved in angiogenesis, the inflammatory cascade or apoptosis control can influence the chronic complications of diabetic patients. Parallel evaluation of multiple genetic polymorphisms became available with the development of DNA resequencing arrays. We aimed to develop a 16-gene, 18,859-nucleotide resequencing array to analyze the genetic background of uremic and gastrointestinal complications. DNA was isolated from 10 ml of peripheral blood of 41 non-uremic and 37 uremic patients with type II diabetes mellitus (DM); 32 suffering from gastric erosion complications. An Affymetrix Customseq Resequencing array was developed containing a total of 37 PCR products of selected genes. Confirmatory analysis was performed for 5 known polymorphisms by RFLP and for 4 others by capillary sequencing. Statistical analysis was performed using the Fisher's exact test. Correlations between the DNA resequencing array and the confirmatory methods were 96% for RFLP and 99.4% for capillary sequencing. The genetic polymorphisms of the ApoE, HSD3B1, IL-1beta and p53 genes were found to be significantly different (p<0.05) between the uremic and non-uremic diabetes group. In regards to the gastric erosion complications of the diabetic uremic patients, the A17708T polymorphism of the p53 intron 10 was found to have a statistically significant (p<0.05) role. In conclusion, DNA sequencing arrays can contribute to a multiparameter genetic analysis yielding highly correlating results using a single method in patients suffering type II DM.