Radicals in the reaction between peroxynitrite and uric acid identified by electron spin resonance spectroscopy and liquid chromatography mass spectrometry.

Peroxynitrite is a reactive oxidant produced in vivo in response to oxidative and other stress by the diffusion-limited reaction of nitric oxide and superoxide. This article is focused on the identification of free radical intermediates of uric acid formed during its reaction with peroxynitrite. The experimental approach included the ESR spin trapping of the radical generated from the reaction between uric acid and peroxynitrite at pH 7.

Reactions of peroxynitrite with uric acid: formation of reactive intermediates, alkylated products and triuret, and in vivo production of triuret under conditions of oxidative stress.

Hyperuricemia is associated with hypertension, metabolic syndrome, preeclampsia, cardio-vascular disease and renal disease, all conditions associated with oxidative stress. We hypothesized that uric acid, a known antioxidant, might become prooxidative following its reaction with oxidants; and, thereby contribute to the pathogenesis of these diseases. Uric acid and 1,3-(15)N(2)-uric acid were reacted with peroxynitrite in different buffers and in the presence of alcohols, antioxidants and in human plasma.

Inactivation of nitric oxide by uric acid.

The 1980 identification of nitric oxide (NO) as an endothelial cell-derived relaxing factor resulted in an unprecedented biomedical research of NO and established NO as one of the most important cardiovascular, nervous and immune system regulatory molecule. A reduction in endothelial cell NO levels leading to "endothelial dysfunction" has been identified as a key pathogenic event preceding the development of hypertension, metabolic syndrome, and cardiovascular disease. The reduction in endothelial NO in cardiovascular disease has been attributed to the action of oxidants that either directly react with NO or uncouple its substrate enzyme.

Does Tamm-Horsfall protein-uric acid binding play a significant role in urate homeostasis?

Background: Mutations in Tamm-Horsfall protein (THP), also known as uromodulin, lead to a group of diseases known as the uromodulin storage disorders. Clinically, these diseases present with tubulo-interstitial damage, progressive renal dysfunction, hyperuricaemia, and gout. However, it remains unclear how a mutation in THP, a protein produced in the thick ascending limb, can cause hyperuricaemia when most of the uric acid transport is believed to occur in the proximal tubule.

Blocking of monocyte chemoattractant protein-1 during tubulointerstitial nephritis resulted in delayed neutrophil clearance.

The chemokine monocyte chemoattractant protein (MCP)-1 has been implicated in the monocyte/macrophage infiltration that occurs during tubulointerstitial nephritis (TIN). We investigated the role of MCP-1 in rats with TIN by administering a neutralizing anti-MCP-1 antibody (Ab). We observed significantly reduced macrophage infiltration and delayed neutrophil clearance in the kidneys of TIN model rats treated with the anti-MCP-1 Ab.

Th1 inflammatory response with altered expression of profibrotic and vasoactive mediators in AT1A and AT1B double-knockout mice.

AT(1) double receptor (AT(1A) and AT(1B)) knockout mice have lower blood pressure, impaired growth, and develop early renal microvascular disease and tubulointerstitial injury. We hypothesized that there would be an increased expression of vasoactive, profibrotic, and inflammatory mediators expressed in the kidneys of AT(1) double-knockout mice. We examined the renal expression of various mediator systems in control (n = 6) vs.

Of mice and dogs: species-specific differences in the inflammatory response following myocardial infarction.

Large animal models have provided much of the descriptive data regarding the cellular and molecular events in myocardial infarction and repair. The availability of genetically altered mice may provide a valuable tool for specific cellular and molecular dissection of these processes. In this report we compare closed chest models of canine and mouse infarction/reperfusion qualitatively and quantitatively for temporal, cellular, and spatial differences.

Mast cells and macrophages in normal C57/BL/6 mice.

Mast cells and macrophages have an important role in immunity and inflammation. Because mice are used extensively for experimental studies investigating immunological and inflammatory responses, we examined mast cell and macrophage distribution in normal murine tissues. Mast cells were abundant in the murine dermis, tongue, and skeletal muscle but were rarely found in the heart, lung, spleen, kidney, liver, and the bowel mucosa.

Active interstitial remodeling: an important process in the hibernating human myocardium.

Objectives: The purpose of this study is to investigate the morphologic characteristics of the cardiac interstitium in the hibernating human myocardium and evaluate whether active remodeling is present and is an important determinant of functional recovery.

Background: Myocardial hibernation is associated with structural myocardial changes, which involve both the cardiomyocytes and the cardiac interstitium.

Methods: We evaluated 15 patients with coronary disease with two-dimensional echocardiography and thallium-201 ((201)Tl) tomography before coronary bypass surgery.