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Biomedical subjects

F V DeFeudis

Publications and source records attributed to F V DeFeudis.

At least 19 recordsLinked to original sources

Coronary atherosclerosis: current therapeutic approaches and future trends.

Invasive cardiovascular procedures, such as percutaneous translumenal coronary angioplasty (PTCA) and aorto-coronary bypass surgery (ACBS), that are currently employed in treating the coronary stenosis or occlusion caused by atherosclerosis represent a major therapeutic advance for managing coronary heart disease (CHD). However, the cellular proliferative response and associated intimal hyperplasia that can follow the damage to blood vessels that occurs with these procedures leads to late complications which cannot be effectively controlled by presently available drugs. Hence, a new approach is required for managing these complications, termed "restenosis" (in the case of PTCA) or "stenosis" (in the case of ACBS). Existing drug therapy is reviewed and some new approaches to this problem are provided herein. Further studies of growth factors and other substances that influence the cellular proliferative response that follows injury to the blood vessel wall could lead to the development of effective therapy. Inhibition of intimal hyperplasia and/or acceleration of endothelial cell re-growth provide a basis for such new approaches. Platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), as well as endothelium-derived relaxing factor(s) (EDRF) and calcitonin gene-related peptide (CGRP) are among the substances discussed. Modification of certain currently available drugs (e.g. Ca(2+)-antagonists) could also be of value in meeting this therapeutic demand.

Calcitonin Gene-Related Peptide

Pharmacological studies of somatostatin and somatostatin-analogues: therapeutic advances and perspectives.

This article is aimed at reviewing and analyzing studies that are related to the possible therapeutic use of a potent and ubiquitously-distributed hormone--somato-statin (SS-14), and its analogues. Administration of these substances has provided beneficial effects in treating acromegaly, gastro-intestinal hemorrhagic and hypersecretory disorders, acute pancreatitis, diabetes mellitus, and certain types of cancer. Further studies with SS-14-analogues might provide new therapies for treating certain life-threatening disorders of man.

Acromegaly

Studies on endothelium-dependent vasorelaxation.

Recent studies on endothelium-dependent vasorelaxation have been briefly reviewed and analyzed. This mechanism, which might involve the release of metabolite(s) termed "endothelium-derived relaxing factor(s)" (EDRF), could play a major role in the regulation of vascular tone.

Animals

Effects of antidepressants on receptor-activated and Ca2+-activated contractions of rabbit isolated aorta.

Helically-cut strips of rabbit aorta were used to examine the inhibitory effects of some antidepressants on the contractile responses produced by norepinephrine (NE), serotonin (5-HT) or K+. The order of potency of antidepressants in antagonizing 5-HT-induced responses was: mianserin greater than amitriptyline greater than imipramine (IMI) greater than desipramine greater than or equal to nomifensine. With NE as agonist, the order of potency was: amitriptyline greater than mianserin greater than IMI greater than desipramine greater than or equal to nomifensine. Viloxazine (10(-5) M) was ineffective on 5-HT- or NE-induced contractions. For K+-induced contraction (which is mediated by Ca2+ entry into smooth muscle cells) tricyclic antidepressants were about equipotent with mianserin; nomifensine and viloxazine were relatively ineffective. These results indicate that certain antidepressants have multiple effects on arterial smooth muscle. Such effects could underlie not only the side-effects, but also the therapeutic actions of these agents.

Animals

Verapamil as an apparent competitive antagonist of the serotonin receptor of rabbit isolated aorta.

The actions of four Ca2+-antagonists (verapamil, diltiazem, nifedipine and flunarizine) were tested on serotonin- (5-HT-) induced contraction of rabbit isolated aorta. Verapamil produced a dose-dependent, parallel shift to the right of the concentration-response curve for 5-HT (pA2 approximately equal to 7.13; Schild slope approximately equal to 1.01), indicative of competitive antagonism. The effects of diltiazem, nifedipine and flunarizine were much less pronounced and best characterized as non-competitive interactions. The effect of verapamil, which likely involves its antagonism of smooth muscle 5-HT2-receptors, might be useful in explaining its therapeutic actions and/or its side-effects.

Animals

Endothelium-derived relaxing factor (EDRF).

Recent studies on endothelium-dependent vasorelaxation have been briefly reviewed and analyzed. The following processes appear to subserve this mechanism: In the endothelial cell: receptor activation, activation of phospholipases, mobilization of intracellular Ca2+, synthesis and release of 'endothelium-derived relaxing factor(s) (EDRF); In the smooth muscle cell: activation of guanyl cyclase and protein kinase, protein phosphorylation/dephosphorylation, relaxation. Alterations of this mechanism could be involved in certain cardiovascular disorders.

Animals

Comparison of the contractile effects of an extract of Ginkgo biloba and some neurotransmitters on rabbit isolated vena cava.

Dose-related contractions were elicited in strips of rabbit isolated vena cava by norepinephrine (NE, IC50 approximately equal to 2.3 X 10(-7) M), dopamine (IC50 approximately equal to 6.9 X 10(-6) M), histamine (IC50 approximately equal to 2.1 X 10(-6) M) and extract of Ginkgo biloba (Gb, IC50 approximately equal to 86 micrograms/ml). Serotonin and tyramine elicited very weak contractile effects in this preparation. Phenoxybenzamine (10(-7) M) abolished the contractions elicited by NE, and blocked the effect of Gb by about 50%. Further support is provided for the therapeutic action of Gb in cardiovascular disorders.

Animals

Are vascular mechanisms involved in antidepressant action?

Recent studies of the mechanisms of action of certain antidepressants, anti-migraine agents, and Ca2+ entry blockers have been briefly reviewed and analyzed. It is postulated that a thorough explanation of the therapeutic effects of antidepressants should include discussion of their actions on the cardiovascular (cerebrovascular) system. The inhibitory actions of antidepressants on Ca2+- and serotonin (5-HT)-mediated processes of vascular smooth muscle seem to be particularly important.

Animals

Mechanism of endothelium-dependent vasorelaxation.

A sequential mechanism for endothelium-dependent vasorelaxation is proposed. The following events appear to be involved: Endothelial cell: activation of a receptor----activation of membrane phospholipases----increase in intracellular free Ca2+----formation of endothelium-derived relaxing factor(s) (EDRF) via a cytochrome P450-dependent epoxygenase or non-enzymatic lipid peroxidation pathway----release of EDRF----diffusion of EDRF to the smooth muscle cell; Smooth muscle cell: activation of guanyl cyclase----activation of protein kinase----protein phosphorylation----dephosphorylation of myosin light chain----relaxation. Relationships between endothelium-dependent and endothelium-independent vasorelaxation are indicated. EDRF-candidates include aldehydes and epoxides.

Animals

Ligand-binding studies on GABA receptors--relation to physiology and behavior.

Some studies that have been conducted with ligand-binding methods support the contention that activation of cerebral GABA-receptors is involved in the control of certain behaviors. Further study of the changes in GABA-receptors that are associated with altered physiology and behavior in experimental animals and in man might lead to the development of new therapies for certain neuropsychiatric, cardiovascular, and endocrinological disorders.

Aging

gamma-Aminobutyric acid-ergic analgesia: implications for gamma-aminobutyric acid-ergic therapy for drug addictions.

Recent in vivo and in vitro studies regarding the involvement of gamma-aminobutyric acid (GABA)-ergic systems in analgesia and in opiate dependence have been reviewed and analyzed. It seems evident that GABA-ergic systems play a role in mediating the effects of opiates and that some interplay might exist between endogenous opioid systems and GABA-ergic systems. Systemic administration of GABA-agonists, GABA uptake blockers and inhibitors of GABA-alpha-oxoglutarate transaminase (GABA-T) can produce potent analgesic actions in experimental animals and in man. Further study of such agents might lead to the development of new analgesics and/or new drugs for treating certain types of drug addiction.

Animals

Endothelium-dependent relaxations of rabbit isolated aorta produced by carbachol and by Ginkgo biloba extract.

Spirally-cut strips of rabbit aorta were used to examine the relaxations produced by carbachol and extract of Ginkgo biloba (Gb) under isometric conditions. After precontracting the strips with phenylephrine (10(-7) M), carbachol produced a dose-related relaxation (PD2 congruent to 6.2 +/- 0.1) and this effect was antagonized competitively by atropine (PA2 congruent to 9.4 +/- 0.1). Gb (0.2 or 0.3 mg/ml) also relaxed the strips. Removal of the endothelium or a 30-min pre-treatment of the strips with a substance that has lipoxygenase-inhibitor activity (nordihydroguaiaretic acid, NDGA, 10(-5) M) abolished the relaxant effect of carbachol and partially blocked the relaxant effect of Gb. Thus, at least part of the relaxant effect of Gb is mediated by a factor(s) (e.g., EDRF) that is released from endothelial cells.

Animals

gamma-Aminobutyric acid and cardiovascular function.

Evidence supporting the hypothesis that GABA-ergic mechanisms are involved in controlling mammalian cardiovascular function has been reviewed and analyzed. In vivo and in vitro studies with GABA-agonists and GABA-antagonists have revealed that activation of GABA-receptors is involved in the control of blood pressure and heart rate. Further studies conducted with agents that modify central and/or peripheral GABA-ergic systems could lead to the discovery of drugs that might be useful for treating certain cardiovascular disorders in man, such as hypertension and stroke, and should increase our understanding of the pathophysiological bases of such disorders.

Animals