Chronic peripheral ouabain treatment affects the brain endothelin system of rats.

Background: Chronically administered ouabain increases the content of ouabain in several brain areas that are closely related to central cardiovascular regulation. However, the pattern of central changes induced by chronic infusion of ouabain is not completely understood.

Objectives: To investigate whether chronic peripheral ouabain treatment affects the brain endothelin system.

ETA endothelin receptors are involved in the ouabain-induced haemodynamic effects in the periaqueductal gray area of rats.

The aim of the present study was to asses the effects on blood pressure and vascular resistances elicited by microinjections of ouabain (OUA) within the periaqueductal gray area (PAG). We also tested whether peripheral vascular responses caused by exogenous intra-PAG ouabain involve activation of the PAG-endothelin system. In normotensive Sprague-Dawley rats the basal mean arterial blood pressure (MABP) was 114 +/- 3 mmHg.

Microsatellite instability in a population of sporadic colorectal cancers: correlation between genetic and pathological profiles.

Background: Tumours with high-frequency microsatellite instability exhibit unique genotype and phenotype features, whereas the difference between low-frequency microsatellite instability and apparently stable tumours is far from being clear.

Aims: To identify distinctive genetic and pathological characteristics of low-frequency microsatellite instability tumours.

Methods: Microsatellite instability status of 57 sporadic colorectal cancers and its correlation with genetic, pathological and clinical features was analysed.

Mutations of the APC gene in human sporadic colorectal cancers.

Background: Mutations of the APC gene are reported to occur frequently in sporadic colorectal adenomas and adenocarcinomas. We studied APC gene mutations in cases of human sporadic colorectal cancer in order to evaluate their correlation with pathologic characteristics and clinical prognosis.

Methods: Most of the mutations of the APC gene (95%) are nonsense or frame shift mutations, encoding for truncated APC proteins.

Myocardial infarction in diabetic rats: role of hyperglycaemia on infarct size and early expression of hypoxia-inducible factor 1.

Aims/hypothesis: This study aimed to evaluate the effects of hyperglycaemia on the evolution of myocardial infarction and the expression of the transcriptional factor for angiogenesis hypoxia-inducible factor 1alpha (HIF-1alpha) in the rat.

Methods: We studied the effects of streptozotocin induced diabetes on infarct size and HIF-1 alpha gene expression. These parameters were also evaluated in isolated hearts of non-diabetic rat, in condition of high glucose concentration.

Endothelin-1 receptor antagonists reduce cardiac electrical instability induced by high glucose in rats.

Endothelin-1 (ET-1) influences the electrical activity of the heart by causing arrhythmias associated with lengthening of the QT interval in the electrocardiogram. Recent results from our laboratory have shown a primary role for a high plasma glucose concentration in determining cardiac QT prolongation. Since high glucose up-regulates the ET-1 system, the aim of the present study was to determine whether the increase of the QT interval and coronary vascular tone induced by high glucose in the heart involves increased activity of the ET system.

Local administration of ETA (but not ETB) blockers into the PAG area of the brain decreases blood pressure of DOCA-salt rats.

The present study investigated the role possibly played by ET-receptor antagonism at periaqueductal grey (PAG) area level in decreasing the arterial blood pressure and heart rate values reached in DOCA-salt hypertensive rats. A 3-week DOCA-salt treatment induced an increase in blood pressure of up to 174+/-3 mmHg in Sprague-Dawley (SD) rats. This was paralleled by a significant increase in heart rate (HR), and endothelin-1 (ET-1) levels throughout the brain, as assessed by specific EIA ( P<0.

Photopheresis in cutaneous T-cell lymphoma: five-year experience.

Background: Cutaneous T-cell lymphoma (CTCL) includes several lymphoproliferative disorders involving mature T-lymphocyte proliferation initially confined to the cutis. These affections, after variable periods, may progress to the blood, limph nodes and visceral organs. Mycosis fungoides (MF) is the most frequent form of CTCL and has an indolent clinical course.

An immunogenetic map of Lombardy (Northern Italy).

For this study we consulted the Bone Marrow Donors' Registry of Lombardy (Italy) and analyzed 43937 HLA-A,B phenotypes and 13922 HLA-A,B,DR phenotypes. We estimated the HLA-A,B and HLA-A,B,DR haplotype frequencies via the maximum-likelihood method. We analyzed the genetic structure of the 11 provinces of Lombardy by means of Principal Component Analysis and Correspondence Analysis, and estimated the variety of the different haplotypes at provincial level and the percentage of unique phenotypes at village level.

Acute hyperglycemia induces nitrotyrosine formation and apoptosis in perfused heart from rat.

This study investigated coronary perfusion pressure, nitric oxide (NO) and superoxide production, nitrotyrosine (NT) formation, and cardiac cell apoptosis in isolated hearts perfused with high glucose concentration. Coronary perfusion pressure; NO and superoxide anion generation; immunostaining for NT, inducible NO synthase (iNOS), and the constitutive type of NO synthase (NOS) eNOS; iNOS and eNOS mRNA expression by Western blot and RT-PCR; and apoptosis of cardiac cells were studied in hearts perfused for 2 h with solutions containing D-glucose at a concentration of 11.1 mmol/l (control), D-glucose at the concentration of 33.

Annexin 1 peptides protect against experimental myocardial ischemia-reperfusion: analysis of their mechanism of action.

Myocardial reperfusion injury is associated with the infiltration of blood-borne polymorphonuclear leukocytes. We have previous described the protection afforded by annexin 1 (ANXA1) in an experimental model of rat myocardial ischemia-reperfusion (IR) injury. We examined the 1) amino acid region of ANXA1 that retained the protective effect in a model of rat heart IR; 2) changes in endogenous ANXA1 in relation to the IR induced damage and after pharmacological modulation; and 3) potential involvement of the formyl peptide receptor (FPR) in the protective action displayed by ANXA1 peptides.

Antioxidant and pro-oxidant capacity of catecholamines and related compounds. Effects of hydrogen peroxide on glutathione and sphingomyelinase activity in pheochromocytoma PC12 cells: potential relevance to age-related diseases.

The antioxidant and pro-oxidant capacity of catecholamines (CA) and related compounds were analyzed using the oxygen radical absorbance capacity (ORAC) assay. In the assay 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH), a peroxyl radical generator, ROO*; H2O2-Cu2+, mainly a hydroxyl radical generator, *OH; and Cu2+ a transition metal were used. The antioxidant effect of CA and its related compounds were in the order: neurotransmitters: dopamine (DA), norepinephrine (NE) > metabolites > amino acid precursors as measured by using AAPH.

High glucose induces ventricular instability and increases vasomotor tone in rats.

Aims/hypothesis: To investigate cardiac repolarization time in streptozotocin-induced diabetic rats and isolated hearts perfused with high glucose concentration.

Methods: We studied the effects of streptozotocin-induced diabetes on the cardiac repolarisation time (Q-T interval) in Sprague-Dawley rats during a 4-day period of hyperglycaemia and a subsequent 4-day period of normoglycaemia. The Q-T interval was also evaluated in isolated hearts of non-diabetic rats, in condition of high glucose concentration.

Slow-release pellets of sodium butyrate do not modify azoxymethane (AOM)-induced intestinal carcinogenesis in F344 rats.

Butyrate exerts anti-tumour effects in vitro, but not consistently in vivo. We previously demonstrated that the administration of slow-release gastro-resistant pellets of sodium butyrate increases apoptosis in the colon mucosa of rats, an effect which may protect against carcinogenesis. Therefore, we studied whether the administration of butyrate pellets could protect rats against experimental colon carcinogenesis.

Effect of complex polyphenols and tannins from red wine on DNA oxidative damage of rat colon mucosa in vivo.

Background: Dietary polyphenols have been reported to have a variety of biological actions, including anti-carcinogenic, antioxidant and anti-inflammatory activities.

Aim Of The Study: In the present study we have evaluated the effect of an oral treatment with complex polyphenols and tannins from red wine and tea on DNA oxidative damage in the rat colon mucosa.

Methods: Isolated colonocytes were prepared from the colon mucosa of rats treated for ten days with either wine complex polyphenols (57.

Haemophilus influenzae porin contributes to signaling of the inflammatory cascade in rat brain.

In the present study we observed that the Haemophilus influenzae type b (Hib) porin, among the different surface bacterial components, is involved in the pathophysiology of bacterial meningitis. This study demonstrates that inoculation of Hib porin into the fourth cerebral ventricle causes the simultaneous expression of interleukin-1alpha (IL-1alpha), tumor necrosis factor alpha (TNF-alpha), and macrophage inflammatory protein 2 (MIP-2) at 6 h after inoculation. At 24 h, the expression of MIP-2 decreases while the expression of IL-1alpha and TNF-alpha increases.

Effects of black tea, green tea and wine extracts on intestinal carcinogenesis induced by azoxymethane in F344 rats.

We investigated whether polyphenolic extracts from black tea, green tea or red wine affect azoxymethane (AOM)-induced intestinal carcinogenesis. Male F344 rats were treated 10 times (1 week apart) with AOM (7.4 mg/kg, s.

Inhibition of 1,2-dimethylhydrazine-induced oxidative DNA damage in rat colon mucosa by black tea complex polyphenols.

The effect of black tea polyphenols on 1,2-dimethylhydrazine (DMH)-induced oxidative DNA damage in rat colon mucosa has been investigated. Fischer 344 rats were treated orally with thearubigin (TR) or theafulvin (TFu) for 10 days (40 mg/kg), injected ip with DMH (20 mg/kg) or saline and sacrificed 24 hr after DMH administration. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured in colonic mucosa DNA and expressed as a ratio relative to 2'-deoxyguanosine (2dG).

Lipocortin 1 reduces myocardial ischemia-reperfusion injury by affecting local leukocyte recruitment.

We assessed here the effect of the glucocorticoid-regulated protein lipocortin 1 (LC1) in a model of rat myocardial ischemia reperfusion. Treatment of animals with human recombinant LC1 at the end of a 25-min ischemic period significantly reduced the extent of infarct size in the area at risk as measured 2 h later, with approximately 50% inhibition at the highest dose tested of 50 microg per rat (equivalent to 5.4 nmol/kg).

Detection of somatic DNA alterations in azoxymethane-induced F344 rat colon tumors by random amplified polymorphic DNA analysis.

Colon carcinogenesis induced in rats by azoxymethane (AOM) is a useful experimental model as it mimics the human adenoma-carcinoma sequence and allows the study of dietary variation and of the effects of chemopreventive substances. Alterations of specific oncogenes and tumor suppressor genes (APC and K-ras) play roles at different stages of this carcinogenesis process. Recently, it has been suggested that genomic instability is the necessary step for the generation of multiple mutations underlying the occurrence of cancer.

Clinicopathologic features and FHIT gene expression in sporadic colorectal adenocarcinomas.

Background: The putative tumour suppressor gene FHIT (fragile histidine triad) spans the common fragile site FRA3B, which is highly susceptible to breaks and deletions induced by genotoxic agents. Tumours associated with exposure to carcinogens, such as colorectal adenocarcinomas, should be particularly susceptible to alterations in the FHIT gene. We studied the frequency of FHIT alterations and their correlations with clinicopathologic features in sporadic colon carcinomas.

Aortic valve replacement via ministernotomy: early results of a two-center study.

Background: The reversed T ministernotomy has been proposed by Gundry to perform different congenital and common acquired heart valve operations. In this study we assessed the technical aspects of this approach for aortic valve replacement before starting a prospective randomized study. We evaluated the results of a two-Center study on the technical feasibility of aortic valve replacement via the reversed T ministernotomy according to the Gundry's approach.

Endothelin receptor antagonists reduce the pressor effects of angiotensin II into the periaqueductal gray area of rats.

Injection of ANGII (0.01, 0.1 and 1 nmol/rat) into the periaqueductal gray (PAG) area significantly (P<0.

Injection of endothelin-1 into the raphe obscurus of rats induces depressor responses predominantly through endothelin ET(A) receptors.

We used in vitro autoradiography to identify the endothelin-1 receptor subtype(s) in the nucleus raphe obscurus of rats. These studies showed dense binding of [125I]PD 151242 (for endothelin ET(A) receptors), while tissues incubated with [125I]BQ3020 (for endothelin ET(B) receptors) had low binding. In addition, we examined the effects of the endothelin receptor antagonists FR 139317 (endothelin ET(A) receptor-selective antagonist), SB 209670 (endothelin ET(A)/ET(B) receptor-non-selective antagonist) and BQ-788 (endothelin ETB receptor-selective antagonist) on the blood pressure responses following administration of endothelin-1 into the nucleus raphe obscurus.

Arrhythmias induced by myocardial ischaemia-reperfusion are sensitive to ionotropic excitatory amino acid receptor antagonists.

We have investigated the effects of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK801), a non-competitive N-methyl-D-aspartate (NMDA) ionotropic excitatory amino acid receptor antagonist, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA ionotropic excitatory amino acid receptor antagonist, ketamine and memantine, NMDA receptor channel blockers, on ventricular arrhythmias induced by myocardial ischaemia and myocardial ischaemia-reperfusion. Coronary artery occlusion caused 100 +/- 2% ventricular tachycardia, in saline treated group, and 60 +/- 3% ventricular fibrillation. 66 +/- 6% of the animals recovered from ventricular fibrillation, while in 34 +/- 4% of animals the ventricular fibrillation caused mortality.