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 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies on intact and isolated blood vessels indicate that ethanol can exert depressant actions on vascular smooth muscle. This study, using isolated rat aortic strips and portal veins, was designed to ascertain whether acetaldehyde (ACT), a major metabolite of ethanol, could exert similar effects. The results indicate that ACT can: (a) inhibit spontaneous mechanical activity and lower baseline tension in aortic strips; (b) depending upon concentration, enhance (abolished by phentolamine) or inhibit such spontaneous contractions in portal veins; (c) dose-dependently attenuate contractions induced by epinephrine, vasopressin, serotonin and KCl; (d) cause non-competitive displacement of the contraction--effect curves of these vasoactive compounds; (e) relax drug-induced contractions of aortic and venous smooth muscle, (f) attenuate Ca2+-induced contractions of K+-depolarized aortas and portal veins. These profound depressant actions of ACT are not attenuated, prevented or mimicked by alpha-adrenergic histaminergic, cholinergic, or serotonergic blocking drugs, nor are they attributable to actions on beta-adrenoreceptors, or release of prostaglandin-like substance. The direct vasodepressant actions of ACT on vascular smooth muscles may play significant roles in alcohol-induced peripheral vasodilatation and hypotension, and cardiovascular collapse noted in the alcohol-Antabuse reaction.
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PMID:Acetaldehyde on vascular smooth muscle: possible role in vasodilator action of ethanol. 72 Mar 89

Various preparatory procedures were tested to preserve the ultrastructure of the sarcoplasmic reticulum (SR) by the best possible method within frog sino-atrial muscle fibres. These procedures were: conventional aldehyde fixation with or without tannic acid, cryofracture, metallic impregnation and quick-freezing followed by freeze-substitution. Our results illustrated that, when optimally preserved, the SR architecture and ultrastructure of frog sino-atrial fibres were not fundamentally different from those described in many other vertebrate muscle fibres, particularly cardiac fibres. The three-dimensional arrangement of the SR and the structure of its main compartments were situated in a precise fashion: the peripheral SR, located close to the plasma membrane, was made of a tight network of tubules and showed typical couplings; the juxtafibrillar SR was made of a loose network of tubules, small cisternae and some tubules near Z-lines; the intermediary SR, associated with the mitochondria, was made of tubules and fenestrated cisternae. Contacts between SR and mitochondrial membranes were also studied; cryofractures revealed no special intramembrane particles at this level. Collapsed portions of the SR were found after quick-freezing. Because of its relative importance and its three-dimensional arrangement, the SR of frog sino-atrial fibres may have comparable functional significance to the SR of other cardiac muscle fibres.
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PMID:Ultrastructure and architecture of the sarcoplasmic reticulum in frog sino-atrial fibres: a comparative study with various preparatory procedures. 388 16

The cardiovascular effects of ethanol ingestion after pretreatment with a new antialcohol drug, nitrefazole (2-methyl-4-nitro-1-(4-nitro-phenyl)imidazole, Altimol) were studied. Left ventricular function was examined by echocardiography and systolic time intervals in six healthy Finnish male volunteers who ingested 0.15-0.25 g of ethanol/kg, 24 hr after an 800 or 1600-mg peroral dose of nitrefazole. After ethanol ingestion, accumulation of acetaldehyde in blood (25-150 microM) was accompanied by a 1.5-2-fold increase in plasma noradrenaline, a 3-10-fold increase in plasma adrenaline, and a 0.5-2.0 degrees C rise in skin temperature. Heart rate increased by 70% and cardiac output by 107%. Diastolic blood pressure decreased by 30% and peripheral vascular resistance by 54%. Ejection fraction and maximum circumferential fiber-shortening velocity increased by 26 and 71%, respectively; the pre-ejection period/ejection time ratio decreased by 46%. An apparent vasovagal collapse was noticed in two nitrefazole-treated subjects after ethanol ingestion, and a third subject experienced a fainting attack shortly after the experiment. Thus, in subjects pretreated with nitrefazole, ingestion of rather small amounts of ethanol results in marked accumulation of acetaldehyde apparently due to aldehyde dehydrogenase inhibition. This causes elevation of plasma catecholamines and intense enhancement of cardiac performance. The marked cardiovascular changes demonstrate the potency of nitrefazole, suggesting that, particularly with alcoholics with occult myocardial diseases, its interaction with ethanol may be even more hazardous than that produced by other antialcohol drugs.
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PMID:The nitrefazole-ethanol interaction in man: cardiovascular responses and the accumulation of acetaldehyde and catecholamines. 389 93

Aldehyde-fixed rat tissues were variously dehydrated and impregnated in water-miscible 2-hydroxypropyl methacrylate (HPMA) containing 3 to 20 per cent water and 0.1 per cent alpha,alpha-azobisisobutyronitrile as catalyst for subsequent polymerization with ultraviolet light. Heat polymerization was also effective. Blocks of embedded tissue readily gave ultrathin sections, which required staining by uranyl acetate and/or lead stains to give adequate contrast for electron microscopy. The ultrastructure of pancreas, kidney, muscle, and intestine was well preserved by aldehyde fixation alone. Use of postfixation in osmium tetroxide or direct osmium tetroxide fixation was unsatisfactory. The fine structure of aldehyde-fixed liver from fasted rats was well preserved, whereas that from normal rats showed considerable disorganization and collapse, apparently because of extraction of glycogen during the embedding procedure. Enzymatic extraction of proteins by pepsin and of ribonucleic acid by ribonuclease after either formaldehyde or glutaraldehyde fixation was rapidly effected by direct treatment of ultrathin sections with solutions of the enzymes. In contrast, no digestion of chromatin by deoxyribonuclease could be detected. In spite of this present limitation, HPMA appears to have several advantages over earlier water-miscible embedding media for electron microscopy and to be particularly suitable for ultrastructural cytochemistry.
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PMID:Hydroxypropyl methacrylate, a new water-miscible embedding medium for electron microscopy. 585 16

19-Hydroxy[1 alpha-3H]androstenedione was synthesized and its specific activity was accurately determined. Upon aromatization of the above material by placental microsomal aromatase preparation, a process involving 1 beta hydrogen elimination, only 7.4% of the isotope was lost establishing the alpha orientation of the 3H at C-1 in the substrate. The 19-hydroxy[1 alpha]3H]androstenedione was used as the starting material in the synthesis of 2 beta-hydroxy-19-oxo[1 alpha-3H]androstenedione which therefore had the same specific activity and isotope orientation as its precursor. The nonenzymatic collapse of 2 beta-hydroxy-19-oxo[1 alpha-3H]androstenedione in pH 7.1 buffer to estrone was associated with the elimination of only 2.6% of the isotope indicating that this process proceeds also with stereospecific 1 beta hydrogen elimination. The stereochemistry of hydrogen loss in the nonenzymatic aromatization of the 2 beta-hydroxy-19-oxo derivative is therefore beta and identical with that of estrogen biosynthesis. This provides further evidence in support of the hypothesis that the final enzymatic hydroxylation of the aromatization sequence takes place at position 2 beta of the androgen substrate and that its product, the 2 beta-hydroxy-19-aldehyde, is the proximate precursor of estrogen with the final conversion occurring nonenzymatically.
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PMID:Mechanism of estrogen biosynthesis. Stereochemistry of C-1 hydrogen elimination in the aromatization of 2 beta-hydroxy-19-oxoandrostenedione. 701 54

In order to develop an intravenous formulation of all-trans-retinal (vitamin A aldehyde, VAA) for the treatment of night blindness, VAA and dipalmitoylphosphatidylcholine (DPPC) were sonicated and the dispersions in the VAA mole fraction range of 0.1-0.7 were stable at room temperature for 3 days. In order to clarify the dispersal mechanism, the dispersed particles were characterized and the interaction between VAA and DPPC was investigated using several physicochemical techniques. Dynamic light scattering measurements showed that the diameter of the dispersed particles was 50-70 nm. A limited amount of VAA is incorporated into DPPC bilayer membranes (approximately 5 mole%). The trapped aqueous volume inside the particles was determined fluorometrically using the aqueous space marker calcein and the volume in the VAA/DPPC particles was decreased remarkably with the addition of VAA into small unilamellar vesicles of DPPC. The decline in the fraction of vesicular particles was also confirmed by fluorescence quenching of N-dansylhexadecylamine in the DPPC membrane by the addition of the quencher CuSO(4). These results indicate that the excess VAA separated from the DPPC bilayers is stabilized as emulsion particles by the DPPC surface monolayer. The monolayer-bilayer equilibrium of VAA/DPPC mixtures was estimated by measurement of spreading and collapse pressures. The results showed that the coexistence of emulsion particles (surface monolayer of DPPC+core of VAA) with vesicular particles (bilayer) was critically important for the formation of the stably dispersed particles of the lipid mixture.
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PMID:Formation and structure of stably dispersed particles composed of retinal with dipalmitoylphosphatidylcholine: coexistence of emulsion particles with bilayer vesicles. 1047 32

Impairment of mitochondrial functions has been found in ethanol-induced liver injury. Ethanol can be oxidized to the 1-hydroxyethyl radical (HER) by rat liver microsomal systems. Experiments were carried out to evaluate the ability of HER to cause mitochondrial swelling as an indicator of the mitochondrial permeability transition (MPT). Electron spin resonance (ESR) spectroscopy was used to detect HER and to study its interaction with mitochondria. The ESR signal intensity of the spin adduct formed from alpha-(4-pyridyl-1-oxide) N-tert-butylnitrone (POBN) and HER generated from either a thermic decomposition of 1,1'-dihydroxyazoethane (DHAE) or a Fenton reaction system containing ethanol was markedly diminished by the addition of mitochondria, indicating an interaction between HER and mitochondria. Exposure of rat liver mitochondria to HER generated from either system caused swelling, as reflected by a decrease in absorbance at 540 nm, in a HER concentration-dependent and a cyclosporin A-sensitive manner. Mitochondrial swelling was also induced in the Fenton reaction system without ethanol. The DHAE-dependent generation of HER in mitochondrial suspension resulted in a decrease of membrane protein thiols and collapse of the membrane potential (delta psi). The swelling induced by HER was prevented by glutathione and vitamin E, but not by superoxide dismutase. Catalase did not prevent the swelling caused by the acetaldehyde/hydroxylamine O-sulfonate (HOS) system, but was inhibitory in the Fenton reaction system with or without ethanol. These results indicate that HER, as well as hydroxyl radical, can induce the MPT, and suggest the possibility that the collapse of delta psi caused by HER may, at least in part, contribute to impairment of mitochondrial function caused by ethanol and in ethanol-induced liver injury.
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PMID:Mitochondrial permeability transition induced by 1-hydroxyethyl radical. 1128 Dec 95

The pathogenesis of idiopathic Parkinson's disease (PD) remains to be elucidated. The discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suggests that neurotoxins in the human brain may cause selective depletion of striatal dopamine neurons, a hallmark of PD. An endogenous isoquinoline, N-methyl(R)salsolinol is a most promising neurotoxin candidate, and it was proved to be selectively toxic to dopamine neurons in the rat brain by in vivo experiments. The level of N-methyl(R)salsolinol in the cerebrospinal fluid obtained from PD patients was significantly higher than control. N-Methyl(R)salsolinol is synthesized by 2 enzymatic reactions from dopamine; condensation of dopamine with acetaldehyde into (R)salsolinol by (R)salsolinol synthase and N-methylation of (R)salsolinol by neutral(R)salsolinol N-methyltransferase. The second enzyme, which catabolizes the N-methylation of (R)salsolinol, was found to determine the level of the neurotoxin in the brain. The activity of neutral(R)salsolinol N-methyltransferase was examined using lymphocytes prepared from PD patients, normal controls and diseased controls as enzyme source. A significant increase in the activity was confirmed in lymphocytes from PD cases compared to normal- and diseased-control. Studies to clarify the environmental and genetic factors determining the activity of the enzyme are now under the way. The cytotoxicity of N-methyl(R)salsolinol was examined using a cultured cell model. N-Methyl(R)salsolinol was found to induce apoptotic cell death in a dose-dependent way. The mechanism of apoptosis was clarified to be mediated by collapse in mitochondrial membrane potential, activation of caspase 3 and fragmentation of nuclear DNA. In addition, propargylamines protected the cells from apoptosis. It was suggested that N-methyl(R)salsolinol and propargylamines have specific binding sites in mitochondria which regulate the death signal transduction. Propargylamines might be applicable as neuroprotective drugs, which can be orally administrated to PD patients.
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PMID:[Pathogenesis of idiopathic Parkinson's disease]. 1152 60

Incubation of rat liver mitochondria with 100-500 mM tyramine, a substrate for monoamine oxidases A and B (MAOs), in the presence of 30 mM Ca2+ induces matrix swelling, accompanied by collapse of membrane potential, efflux of endogenous Mg2+ and accumulated Ca2+ and oxidation of endogenous pyridine nucleotides. These effects are completely abolished in the presence of cyclosporin A, ADP, dithioerythritol and N-ethylmaleimide, thus confirming the induction of the mitochondrial membrane permeability transition (MPT). The observed partial protective effect exerted by catalase indicates the involvement of both MAO-derived hydrogen peroxide and aldehyde. Higher concentrations of tyramine (1-2 mM) are less effective or even completely ineffective. At these high concentrations tyramine has an inhibitory effect when the MPT is induced by 100 mM Ca2+. The MAO inhibitors clorgyline (50 mM) and pargyline (500 mM) completely protect against MPT induction by 100 mM tyramine but also inhibit the phenomenon, although with different efficacy, when it is induced by 100 mM Ca2+ in the absence of tyramine. Taken together, our data suggest that tyramine, clorgyline and pargyline act as modulators of the MPT either through a direct inducing/protective effect or by controlling hydrogen peroxide and aldehyde generation.
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PMID:Tyramine and monoamine oxidase inhibitors as modulators of the mitochondrial membrane permeability transition. 1217 44

Donor nerves of different origins, when transplanted onto a previously denervated adult crayfish abdominal superficial flexor muscle (SFM), regenerate excitatory synaptic connections. Here we report that an inhibitory axon in these nerves also regenerates synaptic connections based on observation of nerve terminals with irregular to elliptically shaped synaptic vesicles characteristic of the inhibitory axon in aldehyde fixed tissue. Inhibitory terminals were found at reinnervated sites in all 12 allotransplanted-SFMs, underscoring the fact that the inhibitory axon regenerates just as reliably as the excitatory axons. At sites with degenerating nerve terminals and at sparsely reinnervated sites, we observe densely stained membranes, reminiscent of postsynaptic membranes, but occurring as paired, opposing membranes, extending between extracellular channels of the subsynaptic reticulum. These structures are not found at richly innervated sites in allotransplanted SFMs, in control SFMs, or at several other crustacean muscles. Although their identity is unknown, they are likely to be remnant postsynaptic membranes that become paired with collapse of degenerated nerve terminals of excitatory and inhibitory axons. Because these two axons have uniquely different receptor channels and intramembrane structure, their remnant postsynaptic membranes may therefore attract regenerating nerve terminals to form synaptic contacts selectively by excitatory or inhibitory axons, resulting in postsynaptic specification.
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PMID:Allotransplanted nerves regenerate inhibitory synapses on a crayfish muscle: Possible postsynaptic specification. 1236 May 85


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