Effects of octreotide in acute hemorrhagic necrotizing pancreatitis in rats

BACKGROUND AND AIM: Octreotide is considered to reduce exocrine pancreatic secretion in acute hemorrhagic necrotizing pancreatitis decreasing pancreatic autodigestion. The aim of this study was to determine whether octreotide also has antioxidative effects in acute pancreatitis. Additionally time and dose of application were of interest. METHOD: Ninety male Sprague-Dawley rats were randomized into six groups (n = 15). Group 1 underwent a laparotomy, and animals in groups 2-6 received intraductal glycodeoxycholic acid followed by intravenous cerulein. Groups 3 and 4 were injected with 0.5 mg octreotide, while groups 5 and 6 received continuous intravenous infusion of 0.05 mg octreotide/h for 10 h. Treatment was initiated 6 hours after induction of pancreatitis (IP) in groups 3 and 5, and 14 h after IP in groups 4 and 6. At 24 h after IP all animals were killed and each pancreas was analyzed histopathologically. In addition, levels of pancreatic lipid peroxidation protective enzymes glutathione-peroxidase (GSH-Px) and superoxide dismutase (SOD) as well as lipid peroxidation via thiobarbituric acid reactive substances (TBARS) were determined. RESULTS: Early bolus application of octreotide reduced severity of histopathological changes in acute pancreatitis and decreased lipid peroxidation in pancreatic tissue samples; however, late bolus application and continuous intravenous infusion did not influence pancreatitis or lipid peroxidation. CONCLUSION: Octreotide seems to have a dose- and time-dependent effect on histopathology and lipid peroxidation in a model of pancreatitis in rats.     

Adiponectin is a novel humoral vasodilator

OBJECTIVES: Perivascular adipose tissue secretes an adipocyte-derived relaxing factor(s) (ADRF) that opens K(v) channels in rat arteries. Visceral fat accumulation causes adipocyte dysfunction, including hyposecretion of adiponectin. We tested the hypothesis that ADRF might be adiponectin and that adiponectin plays a role in the paracrine control of vascular tone by perivascular adipose tissue. METHODS AND RESULTS: We studied Sprague-Dawley rats, wild-type and adiponectin gene-deficient (Apn 1-/-) mice, and New Zealand obese (NZO) mice. In rat aortas, recombinant adiponectin at serum levels (2-5 microg/ml) inhibited serotonin-induced contractions. The effects were abolished by K(v) channel inhibition with 4-aminopyridine (4-AP, 2 mM). Similar effects were observed in NZO mouse mesenteric arteries. To study vascular function in Apn 1-/- mice, the mesenteric vascular bed was isolated, cannulated, and perfused at a constant 4-5-ml/min flow in the absence and presence of serotonin. 4-AP (2 mM) induced a similar increase in perfusion pressure in the Apn 1-/- perfused isolated mesenteric vascular bed, compared to wild-type mice. Removal of perivascular fat increased the vasoconstrictor responses, but abolished the 4-AP effects. The anti-contractile effects of perivascular fat were similar in mesenteric artery and aortic rings from Apn 1-/- and wild-type mice. Despite high adiponectin levels, the anti-contractile effects of perivascular fat were diminished in mesenteric arteries of NZO mice with age. CONCLUSION: Adiponectin is a novel humoral vasodilator that relaxes aortic and mesenteric rings by opening K(v) channels. Similar to the rat, perivascular adipose tissue of the mouse harbors an ADRF, which is malfunctional in NZO mice and is not adiponectin.     

Kinetics of soluble TNF-receptors and soluble adhesion molecules ICAM-1, E-selectin and VCAM-1 under systemic rhTNFα therapy

Cytostatic as well as cytotoxic effects of tumour necrosis factor alpha (TNF-α) therapy have been shown in vitro and in experimental in vivo models. Nevertheless, the mechanism of anti-tumour activity in humans in vivo remains unclear. To determine the role of the vascular lining endothelial cells as important mediators of several immunological interactions, we investigated changes in the levels of the soluble endothelial cell adhesion molecules intercellular adhesion molecule 1, E-selectin and vascular cell adhesion molecule 1 as well as of soluble TNF receptors I and II during systemic therapy with recombinant human rhTNF-α (rhTNF-α). All tests were performed by enzyme-linked immunosorbent assays (ELISAs). The clinical efficacy of the intravenous rhTNF-α therapy was poor. Only one patient with isolated intra-arterial limb perfusion had a delayed, marked, but only temporary necrosis of tumour cells. In contrast, we found a marked, significant and (during therapy) undulating augmented increase in the levels of soluble adhesion molecules as well as of the soluble TNF receptors. Taken together, these data support the hypothesis that a sufficient tumour-specific cellular immunity is required to achieve a clinically apparent efficacy of systemic rhTNF-α therapy in addition to cytokine-dependent inducible activation mechanisms. In this context, the vascular lining endothelial cells might play an important role as mediators of the complex immunological antitumoral activity.     

Renal oncocytosis: imaging considerations

Renal oncocytosis is a very rare entity. Although it has been described in pathology and surgery literature, the imaging findings of renal oncocytosis have not yet been described in the radiology literature. We present three cases of renal oncocytosis. The imaging features and clinical considerations are discussed.     

Pro- and anti-inflammatory cytokine production by autoimmune T cells against preproinsulin in HLA-DRB1*04, DQ8 Type 1 diabetes

Aims/hypothesis Preproinsulin is a target T cell autoantigen in human Type 1 diabetes. This study analyses the phenotype and epitope recognition of preproinsulin reactive T cells in subjects with a high genetic risk of diabetes [HLA-DRB1*04, DQ8 with Ab+ (autoantibody-positive) or without islet autoantibodies (control subjects)], and in HLA-matched diabetic patients.Methods A preproinsulin peptide library approach was used to screen for cytokine profiles and epitope specificities in human peripheral blood lymphocytes, and CD4⁺CD45RA^– and CD4⁺CD45RA⁺ T cell subfractions, representing memory and naive and recently primed T cells respectively.Results In CD4⁺ T cell subsets we identified immunodominant epitopes and cytokine production patterns that differed profoundly between patients, Ab+ subjects and non-diabetic HLA-matched control subjects. In Ab+ subjects, a C-peptide epitope C13–29 and insulin B-chain epitope B11–27 were preferentially recognised, whereas insulin-treated Type 1 diabetic patients reacted to native insulin and B-chain epitope B1–16. In peripheral blood lymphocytes of Ab+ subjects, an increase in T helper (Th) 1 (IFN, IL-2) and Th2 (IL-4) cytokines was detectable, wheras in CD45RA⁺ and CD45RA^– subsets, IL-4 and IL-10 phenotypes dominated, compatible with the contribution of non-CD4 cells to IFN content. In insulin-treated Type 1 diabetic patients, naive and recently primed CD4⁺ cells were characterised by increasd IFN, TNF, and IL-5.Conclusions/interpretation Our data show that T cell reactivity to preproinsulin in CD45RA subsets is Th2-dominant in Ab+ subjects, challenging the Th1 paradigm in Type 1 diabetes. Characteristic immunodominant epitopes and cytokine patterns distinguish diabetic patients and Ab+ subjects from HLA-matched healthy individuals. This could prove useful in monitoring of T-cell immunity in clinical diabetes intervention trials.Abbreviations PPI Preproinsulin - PBMC peripheral blood mononuclear cells - Th T helper cells - Ab+ autoantibody-positive - ICA islet cell antibodies - IA-2A islet thyrosine phosphatase - SI stimulation index - Tr T regulatory cells W. Karges and B.O. Boehm contributed equally to this article     

Sexual function and quality of life after surgical treatment for anal fistulas in Crohn’s disease

Background

The aim of this study was to assess sexual function and quality of life (QoL) in patients after surgery for perianal Crohn’s disease.

Methods

Eighty-eight consecutive patients with perianal Crohn’s disease, operated on at the Medical University of Vienna, completed a self-administered questionnaire including the International Index of Erectile Function (IIEF), Female Sexual Function Index (FSFI), Short Form-12 Health Survey (SF-12), and the Inflammatory Bowel Disease Questionnaire (IBDQ). Patients with a current stoma were excluded from further analysis. The median follow-up time was 104 months (range 3–186 months). Healthy subjects served as controls for each case and were matched by age (±6 years) and gender. Forty-seven (68 %) female and 22 male patients with a median age of 46.5 years (range 18–64 years) were analyzed. Eleven (16 %) patients had simple and 58 (84 %) complex anal fistulas.

Results

The median SF-12 physical health score of the patients was significantly lower (47.9 (range 25.5–57.2)) than that of the controls (54.3 (range 34.6–61.8); p = 0.03). Not surprisingly, the median total sore of the IBDQ of the controls was significantly better than that of the patients (controls: 188.5 (range 125–206.5), patients: 157 (range 60–199.5); p < 0.0001). Analysis with the multiple logistic regression test showed that type of operation, >1 perianal fistula opening, and active Crohn’s disease were independent risk factors for a worse IBDQ (p = 0.03, p = 0.015 and p < 0.0001). Interestingly, the median FSFI and IIEF score were not found to be significant different in any domain.

Conclusions

QoL but not sexual function is significantly influenced by surgery for perianal Crohn’s disease.     

Obesity is a significant susceptibility factor for idiopathic AA amyloidosis

Background: To investigate obesity as susceptibility factor in patients with idiopathic AA amyloidosis.

Methods: Clinical, biochemical and genetic data were obtained from 146 patients with AA amyloidosis. Control groups comprised 40 patients with long-standing inflammatory diseases without AA amyloidosis and 56 controls without any inflammatory disease.

Findings: Patients with AA amyloidosis had either familial Mediterranean fever (FMF) or long-standing rheumatic diseases as underlying inflammatory disease (n?=?111, median age 46 years). However, in a significant proportion of patients with AA amyloidosis no primary disease was identified (idiopathic AA; n?=?37, median age 60 years). Patients with idiopathic AA amyloidosis were more obese and older than patients with AA amyloidosis secondary to FMF or rheumatic diseases. Serum leptin levels correlated with the body mass index (BMI) in all types of AA amyloidosis. Elevated leptin levels of more than 30?µg/l were detected in 18% of FMF/rheumatic?+?AA amyloidosis and in 40% of patients with idiopathic AA amyloidosis (p?=?.018). Finally, the SAA1 polymorphism was confirmed as a susceptibility factor for AA amyloidosis irrespective of the type of the disease.

Conclusions: Obesity, age and the SAA1 polymorphism are susceptibility factors for idiopathic AA amyloidosis. Recent advances in treatment of FMF and rheumatic disorders will decrease the incidence of AA amyloidosis due to these diseases. Idiopathic AA, however, might be an emerging problem in the ageing and increasingly obese population.