Biomedical subjects

B Ventura

Publications and source records attributed to B Ventura.

15 recordsLinked to original sources

PubMed2001

The site of production of superoxide radical in mitochondrial Complex I is not a bound ubisemiquinone but presumably iron-sulfur cluster N2.

The mitochondrial respiratory chain is a powerful source of reactive oxygen species, considered as the pathogenic agent of many diseases and of aging. We have investigated the role of Complex I in superoxide radical production in bovine heart submitochondrial particles and found, by combined use of specific inhibitors of Complex I and by Coenzyme Q (CoQ) extraction from the particles, that the one-electron donor in the Complex to oxygen is a redox center located prior to the binding sites of three different types of CoQ antagonists, to be identified with a Fe-S cluster, most probably N2 on the basis of several known properties of this cluster. Short chain CoQ analogs enhance superoxide formation, presumably by mediating electron transfer from N2 to oxygen. The clinically used CoQ analog, idebenone, is particularly effective in promoting superoxide formation.

Animals↗

PubMed2001

Highly luminescent Cu(I)-phenanthroline complexes in rigid matrix and temperature dependence of the photophysical properties.

We synthesized new [Cu(NN)(2)](+)-type complexes where NN = 2-5 and denotes a 2,9-disubstituted-1,10-phenanthroline ligand (related complexes of 1 and 6 ligands are used for reference purposes). For 2, 3, and 4 the ligand substituents are long alkyl-type fragments, whereas in 5 a phenyl ring is directly attached to the chelating unit. At 298 K the four complexes display relatively intense metal-to-ligand-charge-transfer (MLCT) emission bands with maxima around 720 nm, Phi(em) approximately 1 x 10(-)(3) and tau > 100 ns in deaerated CH(2)Cl(2). The emission behavior at 77 K in a CH(2)Cl(2)/MeOH matrix is quite different for complexes of alkyl- (2-4) versus phenyl-substituted (5) ligands. The former exhibit very intense emission bands centered around 642 nm and hypsochromically shifted with respect to 298 K, whereas the luminescence band of [Cu(5)(2)](+) is faint and shifted toward the infrared side. These results prompted us to study in detail the temperature dependence of luminescence properties of [Cu(2)(2)](+) and [Cu(5)(2)](+) in the 300-96 K range. For both complexes the excited state lifetimes increase monotonically by decreasing temperatures, and the trend is well described by an Arrhenius-type treatment involving two equilibrated MLCT excited levels. The emission bands show a similar behavior for the two compounds (intensity decrease and red-shift) only in the 300-120 K range, when the solvent is fluid. In the frozen regime (T </= 120 K), the emission intensity of [Cu(5)(2)](+) continues to drop, whereas that of [Cu(2)(2)](+) exhibits a dramatic intensity increase. We interpret this different behavior in terms of structural factors, suggesting that long alkyl-chains in the 2,9-phenanthroline positions are optimal to prevent significant ground- and excited-state distortions in rigid matrix. We show that our results do not contradict current models describing the photophysics of [Cu(NN)(2)](+) but, instead, bring further evidence to support their validity. They also suggest guidelines for the design of Cu(I)-phenanthroline complexes showing optimized luminescence performances both in fluid and in rigid matrix, an elusive goal for over two decades.

Journal Article↗

PubMed2000

Mitochondrial bioenergetics in aging.

Mitochondria are strongly involved in the production of reactive oxygen species, considered as the pathogenic agent of many diseases and of aging. The mitochondrial theory of aging considers somatic mutations of mitochondrial DNA induced by oxygen radicals as the primary cause of energy decline; experimentally, complex I appears to be mostly affected and to become strongly rate limiting for electron transfer. Mitochondrial bioenergetics is also deranged in human platelets upon aging, as shown by the decreased Pasteur effect (enhancement of lactate production by respiratory chain inhibition). Cells counteract oxidative stress by antioxidants; among lipophilic antioxidants, coenzyme Q is the only one of endogenous biosynthesis. Exogenous coenzyme Q, however, protects cells from oxidative stress by conversion into its reduced antioxidant form by cellular reductases.

Aging↗

PubMed1997

Detection of coronary collaterals using dipyridamole PET myocardial perfusion imaging with rubidium-82.

UNLABELLED: This study evaluated the ability of dipyridamole PET myocardial perfusion imaging to detect coronary collaterals. A previous study showed an association between dipyridamole-induced coronary steal on PET imaging and the presence of coronary collaterals on angiography. METHODS: Dipyridamole PET myocardial perfusion imaging using 82Rb was performed in 45 patients who had recent coronary angiography. The stress/rest count ratio (rubidium activity with stress divided by activity at rest)-was used to express the change in regional tracer uptake with dipyridamole and was calculated manually and automatically. The accuracy of the stress/rest count ratio for detecting coronary collaterals was determined. RESULTS: A manual stress/rest count ratio < or = 0.80 identified coronary collaterals with 81% sensitivity, 92% specificity and 90% accuracy (p < 0.0001). An automated ratio < or = 0.80 had 90% sensitivity, 88% specificity and 90% accuracy (p < 0.0001). Vascular beds incorrectly identified by PET as having collaterals had an increased frequency of severe stenoses and abnormal wall motion. CONCLUSION: PET perfusion imaging using the stress/rest count ratio can serve as a unique imaging method to identify coronary collaterals noninvasively.

Collateral Circulation↗

PubMed1995

Serial myocardial perfusion imaging with dipyridamole and rubidium-82 to assess restenosis after angioplasty.

UNLABELLED: The purpose of this study was to determine whether patients at high risk for clinical restenosis, following coronary angioplasty, could be identified by myocardial perfusion imaging performed with dipyridamole- 82Rb PET. METHODS: Forty-five patients (34 men, 11 women; mean age 58.5 yr) who had successful single-vessel angioplasty and were asymptomatic had dipyridamole-82Rb PET at 1 and 3 mo after the procedure. Abnormal flow reserve in the distribution of the angioplasty artery on PET was considered to be a decrease of > or = 1 perfusion grade in response to dipyridamole (assessed qualitatively from tomographic images and polar coordinate maps). Follow-up was performed for 6 mo postangioplasty. Clinical restenosis was defined as recurrent angina similar to that occurring before angioplasty and/or > or = 50% stenosis at the angioplasty site documented angiographically. We analyzed abnormal flow reserve in the distribution of the angioplasty vessel to identify which patients were at high risk for clinical restenosis. RESULTS: Fourteen patients developed clinical restenosis between 1 and 6 mo postangioplasty. Abnormal relative flow reserve in the distribution of the angioplasty vessel was present prior to the development of symptoms in 13 of 14 patients with clinical restenosis and in 8 of 31 patients without clinical restenosis (sensitivity 93%, specificity 74%, p < 0.0001). PET imaging successfully separated postangioplasty patients into groups with high (62%) and low (4%) risk of clinical restenosis. CONCLUSION: Abnormal relative flow reserve in the distribution of the angioplasty vessel on dipyridamole PET identifies asymptomatic postangioplasty patients at risk for clinical restenosis.

Angioplasty, Balloon, Coronary↗

PubMed1993

Left ventricular cavity-to-myocardial count ratio: a new parameter for detecting resting left ventricular dysfunction directly from tomographic thallium perfusion scintigraphy.

Patients with reduced left ventricular function or aneurysms have cavities that appear dark on SPECT thallium scintigrams. We hypothesized that a quantitative index, which relates thallium activity in the left ventricular cavity to that in the myocardium (C/M ratio), could provide information on left ventricular function. A group of 80 patients who had both exercise SPECT thallium imaging and cardiac catheterization were studied. The C/M ratio was obtained from the short-axis tomogram on both exercise and rest images. Counts in a 2 x 2 pixel region of interest in the left ventricular cavity were divided by the number of counts in the "hottest" area of the myocardium. Plotting the angiographically determined ejection fraction against the C/M exercise and rest ratios, we observed a linear correlation between ejection fraction and both C/M ratios, r = 0.65 for C/M exercise and r = 0.67 for C/M rest ratio (p < 0.00001). Using data from 12 normal cardiac catheterization patients, we established the lower limit of normal; 50% for ejection fraction and 0.40 for the C/M ratios. A C/M exercise ratio < or = 0.40 identified 26 of 31 patients with an ejection fraction < or = 50%. A C/M exercise ratio > 0.40 identified 39 of 49 patients with an ejection fraction > 50%. These calculations yielded a sensitivity of 83% and specificity of 78% for the C/M exercise ratio. A similar analysis for C/M rest ratio revealed sensitivity of 61% and specificity of 92%. The present study shows that an abnormal C/M ratio correctly distinguishes patients with abnormal from normal ejection fractions with an accuracy of 81%. The C/M ratio is easily obtained, requires minimal processing time and is highly reproducible. These attributes may enable this index to add supplementary information regarding left ventricular function in addition to perfusion from thallium imaging.

Adult↗

PubMed1990

Findings on the efficacy and safety of thrombolytic therapy. An analysis of key clinical trials.

This past decade has seen remarkable progress in the use of thrombolytic agents to increase survival after AMI. Early IC strategies and several reperfusion trials of thrombolytic therapy visually demonstrated the efficacy of these agents. The life-saving benefits of thrombolysis have been illustrated by the large multicenter mortality trials with decreases in mortality from 15% to 8%. Mortality rates in AMI treated with rt-PA has been shown to be much lower in studies using full-dose IV heparin: TIMI IIB 4.9% (6 weeks), ASSET 7.2% (1 month), ECSG 3.7% (21 days). SK and APSAC are most effective at achieving thrombolysis when administered early in the course of AMI; rt-PA retains its superior efficacy on the older thrombus. When patients are properly screened for contraindications, IV-thrombolytic therapy is a safe and highly effective treatment for AMI. The choice of agent remains that of personal or institutional preference. Only when definitive results of ongoing and future head-to-head clinical trials are published can the effectiveness of the agents be compared accurately. Until these data are available, the most important lesson is to treat and treat quickly.

Clinical Trials as Topic↗

PubMed1990