Schiff base complexes of copper and zinc as potential anti-colitic compounds.

The design, synthesis and activity of polymodal compounds for the treatment of inflammatory bowel disease are reported. The compounds, being based on a metal-Schiff base motif, are designed to degrade during intestinal transit to release the bioactive components in the gut. The compounds have been developed sequential with the biomodal compounds combining copper or zinc with a salicylaldehyde adduct.

C-reactive protein velocity to distinguish febrile bacterial infections from non-bacterial febrile illnesses in the emergency department.

Introduction: C-reactive protein (CRP) is a real-time and low-cost biomarker to distinguish febrile bacterial infections from non-bacterial febrile illnesses. We hypothesised that measuring the velocity of the biomarker instead of its absolute serum concentration could enhance its ability to differentiate between these two conditions.

Methods: We prospectively recruited adult patients (age >or= 18 years) who presented to the emergency department with fever.

Expanding circle of inhibition: small-molecule inhibitors of Bcl-2 as anticancer cell and antiangiogenic agents.

The specific targeting of diseases, particularly cancer, is a primary aim in drug development, as specificity reduces unwelcome effects on healthy tissue and increases drug efficacy at the target site. Drug specificity can be increased by improving the delivery system or by selecting drugs with affinity for a molecular ligand specific to the disease state. The role of the prosurvival Bcl-2 protein in maintaining the normal balance between apoptosis and cellular survival has been recognized for more than a decade.

Degradation of bradykinin, a cardioprotective substance, during a single passage through isolated rat-heart.

Angiotensin converting enzyme (ACE) inhibitors have cardioprotective effects in different species including human. This cardioprotective effect is mainly due to the inhibition of bradykinin (BK) degradation rather than inhibition of the conversion of angiotensin I to angiotensin II. Bradykinin, a nonapeptide, has been considered to be the potential target for various enzymes including ACE, neutral endopeptidase 24.

The release and vascular action of bradykinin in the isolated perfused bovine udder.

It has been postulated that the mammary kinin system may play a role in modulating mammary blood flow. Until the present study, the local release of bradykinin (BK) or other kinin system constituents into the mammary vasculature had not been reported and there were also conflicting findings on the action of BK on udder vasculature. Udders were removed from healthy lactating cows at slaughter.

The anti-inflammatory compounds of Polygonum bistorta: isolation and characterisation.

A bioassay-guided technique has been used to isolate anti-inflammatory compounds from the dried rhizomes of Polygonum bistorta, for structural identification. Anti-inflammatory activity was detected using the carrageenan-induced rat paw oedema. Two compounds were isolated which significantly suppressed the inflammatory response.

The release of bradykinin in bovine mastitis.

The kinin peptides are released during inflammation and are amongst the most potent known mediators of vasodilatation, pain and oedema. Despite early reports of the presence of kinins in milk, no previous study has investigated the role of the kinin system in bovine mastitis. The present study indicated that mastitis was accompanied by raised levels of bradykinin (BK) in milk and the increased levels of BK correlated with the severity of mastitis.

The involvement of plasma kinins in the cardiovascular effects of Leiurus quinquestriatus scorpion venom in anaesthetised rabbits.

The present study was undertaken to investigate the involvement of kinins in the cardiovascular- and respiratory effects of LQQ venom. Blood pressure, heart rate, electrocardiogram (ECG) and respiration were studied in anaesthetised rabbits, in the presence and absence of aprotinin and icatibant, a B2 bradykinin antagonist. Plasma bradykinin concentrations were also measured following venom injection.

Modulation of endothelin-1 release by a transmissible factor from ischemic myocardium.

The aim of this study was to detect the possible release from the ischemic rabbit myocardium of a factor capable of modulating the release of endothelin-1 (ET-1) from the peripheral vasculature. Isolated rabbit hearts were perfused on a Langendorff apparatus so that part of the coronary effluent was pumped directly into the arterial supply of isolated ears. Mean ET-1 outflow from ears perfused with fresh Krebs was 4.

Bradykinin and endothelial-cardiac myocyte interactions in ischemic preconditioning.

Myocardial ischemia results in the release of a variety of vasoactive substances from coronary vascular endothelial cells and/or from cardiac myocytes. Some of these substances appear to be protective and include nitric oxide and bradykinin. One hypothesis for the pronounced antiarrhythmic effects of preconditioning involves the early generation of bradykinin and, subsequently, nitric oxide.

The release of kininase from rat isolated hearts during myocardial ischaemia.

BK destroying activity was observed in rat isolated heart perfusates. BK was optimally degraded at pH 8.4 in rat heart.

Kinin release from normally perfused and ischaemic isolated rat hearts: effect of strain.

The release of kinin during 30 min of left descending coronary artery was observed in WKY, SHR and SD rat isolated hearts. The kinin levels were compared with the ECG abnormalities in these strains. It was observed that low level of kinin could not be a reason for increased ECG abnormalities.

Modulation of kinin outflow from isolated perfused rat hearts by endothelin-1.

Bradykinin has previously been shown to suppress ET-1 secretion by endothelial cells. In the present study, rat isolated hearts have been perfused with Krebs solution using the Langendorff method. Immunoreactive bradykinin (IRBK) was measured in the perfusate and the basal level was found to be constant for up to 3 h.

An acidic kininogenase in rat ventricular myocardium.

Background: Canine ventricles have been reported to contain a cathepsin D-like kininogenase, which might confer protection on the heart during ischaemia. The aim of this study was to investigate the presence and levels of a similar kininogenase in normal and ischaemic rat hearts.

Methods: Aqueous extracts of rat ventricles were tested for the ability to release bradykinin-like immunoreactivity from human low-molecular-weight kininogen and high-molecular-weight kininogen at acidic pHs.

Effects of endothelin-1 and the ETA-receptor antagonist, BQ123, on ischemic arrhythmias in anesthetized rats.

The effects of intravenous (i.v.) infusions of exogenous endothelin-1 (ET-1, 0.

Anti-inflammatory activity of Polygonum bistorta, Guaiacum officinale and Hamamelis virginiana in rats.

The aqueous ethanolic extracts of Polygonum bistorta L. Polygonaceae, Guaiacum officinale L. Zygophyllaceae and Hamamelis virginiana L.

Anti-inflammatory activity of resins from some species of the plant family Burseraceae.

The anti-inflammatory activities of extracts from the resins of four species of the plant family Burseraceae, Boswellia dalzielli, Boswellia carteri (gum olibanum), Commiphora mukul, and Commiphora incisa, were studied. The aqueous extracts of the resins of B. dalzielli, C.

A method for the simultaneous and continuous monitoring of vascular tone and protein leakage in the synovium.

A technique has been developed to monitor changes in synovial vascular tone and leakage of macromolecules, two of the cardinal features of inflammation. The technique permits not only quantitative sequential measurements of the leakage of 125I-albumin from the circulation into the synovium, but also semiquantitative continuous monitoring of the leakage changes. It allows simultaneous continuous monitoring of changes in synovial vascular tone as well.

Acid optimum kininogenases in canine myocardium and aorta.

Objective: Canine coronary artery was recently reported to contain a cathepsin like acid optimum enzyme and a kallikrein like alkaline optimum enzyme which cleaved from a crude kininogen preparation a vasodilator uterus contracting substance. The aim of this study was to seek the presence of similar acid optimum enzymes in canine ventricular myocardium and in a large systemic artery, the aorta.

Methods: Aqueous canine tissue extracts were tested for the ability at different pHs to release uterus contracting substance (using rat isolated oestrous uterus) from a kininogen preparation.

Inhibition of butyric acid-induced colitis in mice by 16,16-dimethyl prostaglandin E2.

A standard colitic lesion was induced in male BKA mice by intrarectal administration of butyric acid (7.5%, 0.1 ml, 10 sec contact).

The effect of inhibitors of prostaglandin formation on contraction of the rat, rabbit and human vas deferens.

1. The rat vas deferens releases both PGE2 and PGF2 alpha under basal conditions in vitro but the human vas deferens synthesizes prostaglandins only when arachidonic acid is supplied exogenously. 2.

Coronary vessels contain enzymes that liberate kinin-like vasodilator substances.

The presence of an acid optimum (pH 6) enzyme capable of generating a spasmogenic, vasodilator polypeptide from human plasma kininogen has been demonstrated in dog coronary arteries, veins and in the wall of the left ventricle. This enzyme also cleaved the tripeptide kallikrein substrate Val-Leu-Arg-pNA. Highest amounts were present in the coronary arteries.