Mechanisms of myocardial protection produced by chronic ethanol consumption.

Recent evidence suggests that chronic ingestion of small quantities of ethanol may protect myocardium from ischemic injury by activating many of the endogenous signal transduction elements that have been implicated during other forms of preconditioning. Studies conducted in a variety of animal models in vitro and in vivo have indicated that chronic ethanol consumption improves functional recovery after global ischemia, reduces biochemical markers of ischemic injury, and decreases myocardial infarct size. Many of these beneficial actions appear to occur independent of alterations in systemic and coronary hemodynamics and transmural myocardial perfusion. To date, adenosine type 1 (A(1)) receptors, alpha(1)-adrenoceptors, the epsilon isoform of protein kinase C (PKC), and adenosine triphosphate-dependent potassium (K(ATP)) channels have been shown to mediate cardioprotection associated with chronic ethanol ingestion. These data suggest another mechanism by which chronic, intermittent consumption of ethanol may reduce overall cardiovascular mortality, decrease the incidence of coronary artery disease, and improve survival after myocardial infarction in humans. In this brief review, we discuss current evidence supporting a role for endogenous signaling in chronic ethanol-induced myocardial protection against ischemic injury.     

Increased extrajunctional acetylcholine sensitivity produced by chronic acetylcholine sensitivity produced by chronic post-synaptic neuromuscular blockade.

1. Anaesthetized rats were paralysed for periods of up to 3 days by chronic administration of D-tubocurarine (DTC), succinylcholine or alpha-bungarotoxin. 2. After 3 days of treatment with DTC, the phrenic nerve remained active. Neuromuscular transmission and spontaneous miniature end-plate potentials (m.e.p.p.s) were restored after removal of the DTC. Resting potentials and input resistances of muscle fibres that had been paralysed for 3 days were similar to those in denervated fibers. 3. Chronic neuromuscular blockade increased the binding of [125-I]-alpha-bungarotoxin by extrajunctional regions of muscle. The time course of the increase was similar to that seen after denervation. Binding to muscles from animals that were anaesthetized and respirated, but not paralysed, was not increased. 4. Three days of paralysis increased the sensitivity of the extrajunctional muscle membrane to acetylcholine (ACh) applied by iontophoresis. 5. Approximately the same proportion of muscle fibres from muscles paralysed for 3 days gave overshooting action potentials in the presence of tetrodotoxin 10-minus 6 g/ml. as did fibres form muscles denervated for 3 days. 6. Chronic paralysis did not change the accumulation of acetylcholinesterase above a ligation in the sciatic nerve. 7. These results are consistent with the idea that extrajunctional ACh sensitivity is normally controlled by muscle activity.     

Adaptation to periodic hypoxia reduces ethanol consumption and abstinence-related visceral damage during alcohol withdrawal in chronic alcoholic animals

Research Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow. Orenburg Medical Institute. (Presented by Academician of the Russian Academy of Medical Sciences G. N. Kryzhanovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 12, pp. 574–578, December, 1992.     

Rabbit corneal damage produced by Pseudomonas aeruginosa infection.

Gross, light microscopic, and electron microscopic examination of the rabbit corneal destruction produced by experimental Pseudomonas aeruginosa infections revealed a combination of acute inflammation and liquefaction necrosis of the cornea. Degeneration of the epithelial cells and the start of polymorphonuclear leukocyte infiltration of the cornea occurred initially. These changes were followed by loss of the epithelium, degeneration and loss of the keratocytes and endothelium, loss of the characteristic weblike pattern of the proteoglycan ground substance, dispersal of ultrastructurally normal collagen fibrils, extensive accumulation followed by degeneration of polymorphonuclear leukocytes, and accumulation of plasma proteins and fibrin in the necrotic cornea. Histochemical examination of the cornea suggested a loss of the proteoglycan ground substance but not of collagen. Rabbit corneas injected with Clostridium histolyticum collagenase showed gross and cellular changes similar to those observed during the pseudomonal infections; however, histochemical examination suggested a loss of collagen, and electron microscopy revealed ultrastructurally abnormal collagen fibrils. The results support the idea (i) that a bacterial or host-derived collagenase is not required for extensive corneal damage during a P. aeruginosa corneal infection, and (ii) that a P. aeruginosa corneal infection may severly damage the cornea by producing extensive corneal edema and by causing the loss of the corneal proteoglycan ground substance, thus resulting in dispersal of undamaged collagen fibrils, weakening of the cornea, and subsequent descemetocele formation and corneal perforation by the anterior chamber pressure.     

Muscle damage induced by electrical stimulation

Electrical stimulation (ES) induces muscle damage that is characterised by histological alterations of muscle fibres and connective tissue, increases in circulating creatine kinase (CK) activity, decreases in muscle strength and development of delayed onset muscle soreness (DOMS). Muscle damage is induced not only by eccentric contractions with ES but also by isometric contractions evoked by ES. Muscle damage profile following 40 isometric contractions of the knee extensors is similar between pulsed current (75 Hz, 400 μs) and alternating current (2.5 kHz delivered at 75 Hz, 400 μs) ES for similar force output. When comparing maximal voluntary and ES-evoked (75 Hz, 200 μs) 50 isometric contractions of the elbow flexors, ES results in greater decreases in maximal voluntary contraction strength, increases in plasma CK activity and DOMS. It appears that the magnitude of muscle damage induced by ES-evoked isometric contractions is comparable to that induced by maximal voluntary eccentric contractions, although the volume of affected muscles in ES is not as large as that of eccentric exercise-induced muscle damage. It seems likely that the muscle damage in ES is associated with high mechanical stress on the activated muscle fibres due to the specificity of motor unit recruitment (i.e., non-selective, synchronous and spatially fixed manner). The magnitude of muscle damage induced by ES is significantly reduced when the second ES bout is performed 2–4 weeks later. It is possible to attenuate the magnitude of muscle damage by “pre-conditioning” muscles, so that muscle damage should not limit the use of ES in training and rehabilitation.     

慢性酒精中毒引起的脑神经损害与Aβ蛋白变化的相关性

慢性酒精中毒会对脑神经造成损伤,并且这种损伤与Aβ蛋白变化有着密切的关系。慢性酒精中毒会促进Aβ蛋白的产生,而Aβ蛋白可以激活星形胶质细胞和小神经胶质细胞,产生过多的炎症细胞因子间接损害神经,亦可通过影响线粒体的功能而损害神经元。Aβ蛋白对脑神经的损伤可表现为认知、记忆功能障碍,引发阿尔兹海默病(AD)。     

Fluctuating odontometric asymmetry and maternal alcohol consumption.

Fluctuating asymmetry was evaluated in the dental arcades of 112 children (60 male, 52 female) of alcoholic mothers. Only individuals who showed no signs of the fetal alcohol syndrome were included. When these results were compared with those of a control group of 120 normal children, the former group was found to be significantly more asymmetric. The present study showed that canines were the least asymmetric whilst lateral incisors showed the greatest levels of asymmetry. It is suggested that the elevated levels of fluctuating odontometric asymmetry in children of alcoholic mothers may be ascribed to prenatal stress, especially during the soft tissue stage of odontogenesis.     

Microscopic characterization of ocular damage produced by Pseudomonas aeruginosa toxin A.

The ocular damage in young adult mice produced by purified Pseudomonas aeruginosa exotoxin A was microscopically characterized at 1 and 5 h and at 1, 3, 5, 7, 10, 14, and 21 days after toxin A challenge, using light, transmission, and scanning electron microscopic techniques. Similarly to previously described infection with viable organisms, toxin A killed both epithelial and endothelial cells and induced stromal cell swelling within 5 to 24 h after application onto the nonpenetrating wounded corneal surface. Other toxin-induced damage similar to the damage produced by infection with the viable bacteria was production of electron-dense particles within the corneal stroma, dispersal of undamaged collagen fibrils, and apparent loss of stromal proteoglycan ground substance. Toxin A damage differed from infection with the viable bacteria in essentially two ways. First, more purulent exudate and more polymorphonuclear neutrophilic leukocyte (PMN) infiltration of the corneal stroma were produced by infection with the viable organisms than by the toxin. Additionally, PMN did not appear within the toxin-treated corneas until 3 days after treatment, whereas in corneas infected with the viable organisms, PMN were numerous by 18 h. Secondly, toxin A produced cataract of the ocular lens, whereas infection with the viable organisms did not.     

Microscopic characterization of rabbit lung damage produced by Pseudomonas aeruginosa proteases.

The intratracheal administration of highly purified Pseudomonas aeruginosa proteases (ca. 10 to 100 microgram) elicited extensive, grossly observable rabbit lung damage by 3 h postinjection. Light and electron microscopic characterization of the lesions revealed: (i) progressive injury and necrosis of type I epithelial cells and capillary endothelial cells from 3 h to 1 day postinjection, and progressively increasing accumulations of erythrocytes, plasma proteins, fibrin, and released type II epithelial cell lamellar bodies in alveolar lumina during that time period; (ii) progressively increasing accumulations of macrophages, but not of polymorphonuclear leukocytes, in alveolar lumina from 3 h to 6 days postinjection; (iii) progressive hyperplasia of type II epithelial cells from 12 h to 4 days postinjection; (iv) progressive infiltration of alveolar septa by mononuclear inflammatory cells (interstitial pneumonitis) from 2 to 6 days postinjection; (v) no loss of alveolar septal connective tissue and no damage to pulmonary arterioles and venules; and (vi) almost normal alveolar structure by ca. 8 days postinjection. The study revealed that the intra-alveolar hemorrhage, the injury and necrosis of alveolar septal cells, and the infiltration by mononuclear cells that have been reported to occur during human pseudomonas pneumonia can also be elicited by the experimental administration of pseudomonas proteases. Thus, the results support the idea that in vivo production and activity of P. aeruginosa proteases is important, at least in part, in eliciting the lung damage characteristic of pseudomonas pneumonia.     

Mismatch negativity impairment associated with alcohol consumption in chronic alcoholics: a scalp current density study.

Previous studies, based on amplitude and latency measurements of auditory event-related brain potentials, yielded inconclusive results about the status of mismatch negativity (MMN) in chronic alcoholics. The present study explores scalp current density (SCD) dynamics during MMN latency range in alcoholics, and correlates electrical SCD results with clinical data of the patients. SCD was computed from 30 electrodes in 16 abstinent chronic alcoholics and 16 healthy control volunteers in a paradigm on MMN elicited by duration changes. Reduced activity was observed in left frontal and right anterior and posterior temporal areas during MMN in alcoholics. Alcohol consumption correlated negatively with SCD intensity in these regions. Delayed activation was observed in the left posterior temporal area in the patients. Alcohol abstinence duration correlated positively with SCD intensity in this region. These results point to an impairment of automatic brain processing mechanisms associated with auditory change detection in chronic alcoholism. The present results suggest a reorganization of the computational neurodynamics of automatic auditory change detection linked to the amount of alcohol consumed in abstinent chronic alcoholics.     

Blood-derived phagocytes in the cerebellar cortex of the rat after chronic alcohol consumption

Past work showed that chronic alcohol consumption induces massive degeneration in the rat cerebellar cortex. To study the subsequent process of nervous tissue repair, followed itself by a remodelling activity, groups of alcohol-treated rats for 3 and 6 months were used and the results compared with the respective age-matched controls. From the wide variety of cells which display phagocytic activity in the mammalian brain it was found, based on qualitative observations, that two types were clearly involved in the removal of the alcohol-induced degenerated debris: the resident microglial cells and the non-resident brain macrophages. This assumption was corroborated by the study of their origin, using carbon particles and latex beeds intravenously injected, which showed that brain macrophages were the sole population to be labelled. These observations fit with the multiple origin concept for neural phagocytosis which postulates that different cell types can be recruited for the removal of the damaged neural tissue depending on the severity of the lesions and on the extension of the blood vessels damage.     

Giant multivesicular bodies in the rat hippocampal pyramidal cells after chronic alcohol consumption

Multivesicular bodies (MVBs) with diameters up to 4.5 microns were observed in the hippocampal pyramidal cells of rats submitted to chronic alcohol consumption. A significant increase in the volumetric density (Vv) of these organelles was found in CA1 pyramidal cells. Transitional forms of MVBs towards lysosomes were seen. A failure in MVB's enzymatic hydrolytic mechanisms, due to the prolonged alcohol aggression, could underlie its formation.     

Platelet consumption by polyvinyl alcohol coated tubing in canines

Polyvinyl alcohol (PVA)-coated polyethylene tubing, with or without immobilized heparin, caused severe thrombocytopenia and enhanced the production of new platelets when inserted in a chronic arteriovenous shunt in canines. A similar length of uncoated polyethylene tubing neither lead to thrombocytopenia nor significantly enhanced platelet regeneration, relative to the shunt only without a test section. Platelet regeneration was monitored by the malondialdehyde assay, which was assumed to make a distinction between "new" and "old" platelets. This distinction was combined with the platelet count values to enable calculation of the cumulative consumption curve and the initial fractional consumption rate in the presence of a non constant platelet count. The resulting initial fractional consumption rates were: 34%/day for PVA, 20.5%/day for polyethylene, and 18%/day for the shunt only blank.