Evidence of vascular growth associated with laser treatment of normal canine myocardium

BACKGROUND: Transmyocardial laser revascularization is a new therapy for patients with refractory angina. Although clinical studies suggest that transmyocardial laser revascularization decreases angina and may improve regional blood flow, the underlying mechanisms are not elucidated. We hypothesized that one mechanism may relate to stimulation of vascular growth in laser-treated regions. METHODS: Transmyocardial laser revascularization channels were made with holmium:yttrium-aluminum garnet or carbon dioxide lasers in eight normal canine hearts; animals were sacrificed 2 to 3 weeks later and examined for vascular density and for evidence of smooth muscle proliferation. RESULTS: The original channels were infiltrated by granulation tissue with associated vascularity. Vascular growth was stimulated immediately surrounding the channel remnant as evidenced by an increase in the number of vessels (approximately twice that of the control region) and an increase in the number of vascular cells staining positive for markers of cellular proliferation. CONCLUSIONS: Transmyocardial laser revascularization leads to local vascular growth as early as 2 weeks after treatment. It remains to be determined whether this mechanism contributes to increased regional blood flow or to clinical benefits associated with this novel form of therapy.     

Unique natriuretic properties of the ATP-sensitive K(+)-channel blocker glyburide in conscious rats

Small-conductance, ATP-sensitive K(+)-channels (KATP) localized in apical membranes of both thick ascending limb of the loop of Henle and cortical collecting duct cells may be involved in Na+ reabsorption and K+ secretion in the mammalian kidney. Possible pharmacologic tools to evaluate such an hypothesis may be the antidiabetic sulfonylureas which block K(+)-channels in pancreatic beta-cells. In saline-loaded conscious rats, glyburide (GLY) dose-dependently increased urinary Na+ excretion with little change in urinary K+ excretion after i.p. administration (10-100 mg/kg). In renal clearance studies, GLY at 25 mg/kg i.v. increased Na+ excretion 350% during the first hour post-treatment without affecting K+ excretion, glomerular filtration rate, mean arterial pressure or heart rate. GLY at 50 mg/kg was no more natriuretic than the 25 mg/kg dose, whereas 12.5 mg/kg of GLY increased Na+ excretion 200%. The change in Na+ excretion produced by 25 mg/kg of GLY in streptozotocin-induced diabetic rats was significantly greater than the change after drug vehicle in these animals. It is unlikely that the natriuresis produced by GLY is secondary to changes in plasma insulin and/or glucose because the doses used were far above GLY's insulin-releasing action (i.e., all natriuretic doses would have produced maximal insulin release) and GLY was natriuretic in streptozotocin-induced diabetic rats. It is possible that GLY interferes with reabsorption of Na+ by blocking KATP and thereby interrupting K+ recycling and Na(+)-2Cl(-)-K+ cotransport in the loop of Henle.     

THE FATIGUE RESISTANCE OF PEENED 7050-T7451 ALUMINIUM ALLOY—REPAIR AND RE-TREATMENT OF A COMPONENT SURFACE

Abstract— Metal and glass-bead peening treatments, widely used throughout the aircraft industry to enhance the fatigue performance of many steels and titanium alloys, are now being routinely applied to high-strength aluminium-alloy components. This paper describes the effects of peening on the fatigue life of 7050 aluminium alloy material, which is representative of alloys used for many components in modern military aircraft. Using simulated service loading, two proposed peening/re-peening procedures were evaluated and compared with both the original peened surface and a simple hand-polished surface. The results show that optimisation of peening parameters to reduce surface damage can provide a substantial improvement in fatigue life over both the original peening treatment and the polished surface treatment, however, poor control of peening procedures, or unnecessary "overpeening" can lead to a relatively poor fatigue life. For re-peened surfaces, a procedure incorporating a polishing step, designed to repair any damage from the severe peening applied initially, gave the best fatigue performance. Results are discussed in relation to the stability of the residual surface stresses under fatigue loading, the surface roughness, and the number and types of defects introduced by the peening treatments.     

Mitochondrial myopathy. Biochemical studies revealing a deficiency of NADH--cytochrome b reductase activity

This paper presents biochemical data upon a young male with a mitochondrial myopathy characterised by weakness, severe exercise intolerance, muscle wasting and exercise-induced lactic acidaemia. Two similar cases have been previously documented (Morgan-Hughes et al. 1979). This report more precisely locates the mitochondrial defect. In vitro mitochondrial studies show markedly decreased respiratory rates with all NAD-linked substrates whilst that with flavin-linked succinate is normal. Oxidative phosphorylation is normally coupled. Mitochondrial cytochrome components as determined by low temperature spectroscopy are normal. NADH-ferricyanide reductase and primary dehydrogenase activities are present at levels far in excess of that required to support normal NAD-linked substrate oxidation rates. Intramitochondrial NAD levels are similar to those found in other mammalian muscle. It is proposed therefore that the mitochondrial defect is situated between NADH dehydrogenase and the CoQ--Cytochrome b complex; possibly being a derangement of a non-haem iron sulphur centre.     

Dynamic mechanical properties of polystyrene-polydimethylsiloxane blends

It was found that commercial silicone grease incorporated accidentally into polystyrene bars yields a major dynamic mechanical loss peak at ca. ?128°C. This finding was followed up with a study of various polydimethylsiloxanes and silicone rubber, in which up to three peaks were found. In order of increasing temperature (at 1 Hz) these are the glass transition (T_g; ca. ?128°C), crystallization (T_c; ca. ?110°C) and melting peaks (T_m; ca. ?50°C). Hydrocarbon-based greases were also investigated. The results indicate that the methods employed may be of use for the investigation of the dynamic mechanical properties of small amounts of material of varying particle sizes, such as powders of cross-linked polymers, that need not be compatible with, or soluble in, the host matrix. The sensitivity of the method is such at a 1 percent by weight contamination of silicone grease in polystyrene gives a loss tangent peak of at least 0.002 above background, and emphasizes the necessary care to be taken during sample preparation to exclude unwanted substances.     

CypScore: Quantitative Prediction of Reactivity toward Cytochromes P450 Based on Semiempirical Molecular Orbital Theory

CypScore predicts the reactivity of competing positions in the same and different molecules to a variety of cytochrome P450 metabolic reactions on a single reactivity scale.

     

Homology Model Adjustment and Ligand Screening with a Pseudoreceptor of the Human Histamine H4 Receptor

A new pseudoreceptor modeling method (PRPS) was applied to the refinement of a homology model of the human histamine H₄ receptor (H₄R), the prediction of a ligand binding site, and virtual screening. Retrieval of two new H₄R ligands demonstrates the biological relevance of the pseudoreceptor model and provides a means for finding new hits and leads in the early phases of drug discovery.

     

The production of yellow pigments from (+)-catechin and dihydroxyfumaric acid in a model wine system

The oxidation of tartaric acid by hydroxyl radicals, produced by gamma-irradiation of aqueous solutions of tartaric acid, was shown to generate dihydroxyfumaric acid. To confirm the importance of this oxidative degradation pathway in wine oxidation, dihydroxyfumaric acid was itself reacted with (+)-catechin in a wine-like solution and the yellow pigments formed were identified by liquid chromatography mass spectrometry (LC-MS) studies as xanthylium cations. The concentration of these pigments increased if the wine-like system also contained 0.6 mg/L copper(II). The results clearly demonstrate a link between the production of yellow xanthylium cation pigments from (+)-catechin and the degradation of tartaric acid by hydroxyl radicals.