Oxidative damage to the myocardium: the protective action of exogenous phosphocreatine

Oxidative damage of the isolated perfused rat heart was caused by addition of 90 microM H2O into Krebs-Henseleit solution. After 20 min of H2O2 addition an elevation of diastolic pressure (irreversible contracture) was observed followed by decrease of developed tension and heart work. Addition of phosphocreatine (10 mM) at constant total sodium concentration prevented the development of contracture and diminished the decrease of cardiac work. This protective effect is probably related to the elevation of structural order of phospholipids by phosphocreatine.     

丹皮多糖-2b对肾上腺素模型小鼠降血糖作用研究

目的　观察丹皮多糖-2b(PSM-2b)对肾上腺素模型小鼠血糖的影响。方法　采用300μg·kg-1肾上腺素腹腔注射复制小鼠高血糖模型。将小鼠随机分为三大组,各大组分别连续灌胃1周、2周或3周。每大组又分为六小组:对照组、模型组、阳性(降糖灵)组、PSM-2b大剂量(90mg·kg-1)组、中剂量(60mg·kg-1)组、小剂量(30mg·kg-1)组。按葡萄糖氧化酶法测血糖,按苯酚-硫酸法测肝糖元含量。结果　PSM-2b能够显著降低肾上腺素模型小鼠的高血糖,且其降血糖作用呈一定的量效关系。PSM-2b还能够促进血糖转化为糖元,显著提高模型小鼠肝糖元的含量。结论　PSM-2b可以通过抑制肾上腺素升血糖作用而降低血糖。     

Anti-arrhythmic action of adenosine and the cyclic nucleotide content of the myocardium of rats with ischemia

In anesthetized rats a 30-min intravenous infusion of adenosine (2.5 mg/kg/min) performed after the coronary artery ligation significantly decreased the incidence and severity of early ischemic arrhythmias. After the infusion of adenosine, there was an increase in cGMP level in the left ventricular myocardium, cAMP content remained unchanged.     

The similarity and difference in the action of adriamycin and hydrogen peroxide on the myocardium

The oxidative stress in cardiomyocytes is a component of cardiotoxic action of adriamycin. To distinguish the importance of this component we have compared initial effects of hydrogen peroxide and adriamycin on the contractile function and a tone of coronary vessels of the isolated rat heart. Adriamycin in concentration 3 mcM distinctly reduced developed pressure and heart rate, but raised coronary vessel tone. The concentration 1 mcM was inefficient at usual perfusion rate, but practically prevented rise in developed pressure and rates of its rise and fall at increased perfusion rate. Hydrogen peroxide also dose-dependently reduced developed pressure, but rates of its rise and fall were reduced to a lesser degree, while the heart rate slightly raised, and coronary vessel tone was reduced. Thus, the initial actions of hydrogen peroxide and adriamycin on the heart considerably differ. It suggests that the oxidative stress is not the main component of cardiotoxic action of adriamycin, at least, in its application in concentrations close to therapeutic ones.     

The structuro-functional state of the ischemic myocardium under the action of a terrilitin-nicotinic acid mixture in animal experiments

Histochemical evidence of the activity and distribution of glycolysis redox enzymes, tissue respiration and terminal oxidation pattern (dehydrogenase of lactic, malic, succinic and isocitric acids, NAD-N- and NADPh-N-ase, cytochrome oxidase) as well as the levels of the major carbohydrates (glycogen, neutral aminopolysaccharides, glucose) were experimentally studied in the cardiomyocytes of myocardial necrotic, perinecrotic and intact areas in the control and in the experimental material under the administration of terrilitin-nicotinic acid mixture. It was stated that the use of aforementioned mixture contributed to the retention of enzymatic activity and optimal levels of energy formation in the cardiomyocytes of the marginal infarction zone and noticeably prevented the destructive involvement of the considered area as well as the impairment of functional activity of oscillating cardiomyocytes. Therefore, the application of the mixture improved the outcome prognosis in acute myocardial infarction.     

Comparative evaluation of the action of prostanoid inhibitors on uterine contractile function

Indomethacin and substance BW-755C in experiments on isolated myometrium striae of pregnant white rats exert an inhibiting effect on the contractile uterus function due to inhibition of cyclooxygenase or lipoxygenase ways of the arachidonic acid transformation. Prostaglandin F2 alpha is sensitive to functioning of the cyclooxygenase and lipoxygenase ways of the arachidonic acid transformation, while oxytocin--only lipoxygenase one. Conclusions rest on results from multiparametric analysis of the contractile uterus function suggested by authors and confirmed by the pattern recognition method--the Karunen-Loev orthogonal decomposition.     

PACAP and a novel stable analog protect rat brain from ischemia: Insight into the mechanisms of action

Pituitary adenylate cyclase-activating polypeptide (PACAP) shows potent protective effects in numerous models of neurological insults. However, the use of PACAP as a clinically efficient drug is limited by its poor metabolic stability. By combining identification of enzymatic cleavage sites with targeted chemical modifications, a metabolically stable and potent PACAP38 analog was recently developed. The neuroprotective activity of this novel compound was for the first time evaluated and compared to the native peptide using a rat model of middle cerebral artery occlusion (MCAO). Our results show that as low as picomolar doses of PACAP38 and its analog strongly reduce infarct volume and improve neurological impairment induced by stroke. In particular, these peptides inhibit the expression of Bcl-2-associated death promoter, caspase 3, macrophage inflammatory protein-1α, inducible nitric oxide synthase 2, tumor necrosis factor-α mRNAs, and increase extracellular signal-regulated kinase 2, B-cell CLL/lymphoma 2 and interleukin 6 mRNA levels. These results indicate that the neuroprotective effect of PACAP after MCAO is not only due to its ability to inhibit apoptosis but also to modulate the inflammatory response. The present study highlights the potential therapeutic efficacy of very low concentrations of PACAP or its metabolically stable derivative for the treatment of stroke.     

Preventive action of Ginkgo biloba in stress- and corticosterone-induced impairment of spatial memory in rats

In this study, we tested preventive effects of a natural medicine the extract of Ginkgo biloba (EGB 761) on post-stress cognitive dysfunction. Exposure to chronic restraint stress in rats and psychosocial stress in humans has been shown to alter cognitive functions such as learning and memory and have been linked to the pathophysiology of mood and anxiety disorders.Our findings indicate that chronic restraint stress impaired egocentric spatial memory as observed in the eight-arm radial maze but it did not alter the allocentric spatial memory in the Morris water maze. In control rats EGB 761 (100 mg/kg, orally) improved spatial memory in these two tests. Also, EGB 761 normalized cognitive deficits seen in rats chronically stressed or treated with an ‘equivalent’ dose of exogenous corticosterone (5 mg/kg, subcutaneously).We conclude that, in rats, repeated administration of EGB 761 prevents stress- and corticosterone-induced impairments of spatial memory.     

Changes in the content of glycolysis products in the myocardium of adult and older rats under stress]

The experiments on adult (8-10 months) and old (24-26 months) male rats have been performed to determine the glucose content in myocardium as well as the content of pyruvic and lactic acid after the stress impact. Findings show that the maximum accumulation of glycolysis products and the reduction of glucose content occur 18-60 hours after the stress, the effect being more pronounced in old animals.     

The myosin-activating protein kinases in human myocardium: localization and content

Using the immunofluorescence approach, we have determined that the recently detected protein kinases, among which are RhoA-activated kinase, integrin-linked kinase, zipper interacting protein kinase, and death-associated protein kinase, which are capable of phosphorylating myosin, are localized in the Z-lines sarcomeres of human myocardium. Additionally, we studied the content of integrin-linked and zipper interacting protein kinases in human embryonic myocardium, as well as in normal and hypertrophic adult human heart. The content of these protein kinases in adult normal myocardium increases in comparison with the embryonic heart. The content of integrin-linked and zipper interacting protein kinases in hypertrophic myocardium is higher compared with the normal adult heart. The data obtained suggest the involvement of these protein kinases in the development and hypertrophy of human heart.     

On the mechanism of action of thyroxin, an amino acid analog of tyrosine

The concept of a hormone inevitably carries with it a set of specific connotations and prejudices which in the case of thyroxin may obscure rather than elucidate its mechanism of action. Viewed as a hormone, the very number and broad range of thyroxin effects defy resolution. Viewed as an amino acid analog, the behavior of this molecule becomes coherent, in that it resembles the behavior of amino acids in general and tyrosine in particular, with distinguishing characteristics appropriate to its own structure and its analog status.Thyroxin is only one of a number of amino acids appearing in the course of phylogeny, derived from modifications of aminoacyl residues in protein. Comparative physiologic studies suggest that the biogenesis of iodine-modified tyrosines long preceded their useful biological function. Eventually their presence in threatened aquatic forms may have provided survival advantage with regard to terrestrial adaptation.Both structure and function of the vertebrate thyroid gland reflect its foregut ancestry. Iodoproteins within the lumen of the thyroid follicle are subject to a process similar to gastric digestion of ordinary dietary proteins. Free iodoamino acids together with other amino acid constituents of the digest are then absorbed into the blood stream. As expected of an amino acid, thyroxin leaving the extracellular space enters into and influences the function of almost all cells and subcellular organelles, including the nucleus. Its analog properties are reflected in the fact that only small fractions of the available thyroxin pools participate at any one time in biological reactions.The diverse actions of thyroxin are compatible with the model set by the parent amino acid tyrosine, which is notably active at a number of branch points in its own metabolism. Thyroxin effects on growth and development conform with the known alterations in genetic response which occur in the presence of false protein amino acids and are also consistent with the rapid turnover and remodelling of protein systems which follow the incorporation of false amino acid residues into protein. Its effects on overall metabolic processes are consistent with the known propensity of tyrosine-like compounds to become converted to false transmitters in the adrenergic nervous system, which in the case of thyroxin, would result in the development of iodothyronine-derived adrenergic transmitter substances. Altered pigment metabolism in patients with thyroid disease and localization of iodoamino acids in pigment-bearing cells of many vertebrate species suggest that thyroxin may be an alternate substrate in the melanin biosynthetic pathway.Since thyroxin is required for normal body function, it may be classified as an indispensable amino acid along with the other biologically more ancient members of its class.