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1.
D B Saprygin R A Serov L S Kashtélian S P Smotrov P M Ashirov 《Biulleten' eksperimental'no? biologii i meditsiny》1984,98(8):175-177
Experiments on an isolated rat heart were made to compare the damaging action on the myocardium of catecholamines (noradrenaline, adrenaline and isoproterenol) differing in the affinity for beta-receptors. The damage to myocardial cells was evaluated from the release into the perfusate of intracellular enzymes (creatine phosphokinase and lactate dehydrogenase) and the number of contracture damaged myocytes. Noradrenaline exerted the most powerful damaging action on the myocardium at a concentration of 10(-6) M. Perfusion of the heart with isoproterenol at concentrations of 10(-6) M and 10(-5) M did not lead to the affection of cardiomyocytes. It was isoproterenol concentration exceeding noradrenaline concentration 100 times that produced an increase in the rate of the release of the enzymes to the perfusate and a rise of the number of contractures in the myocardium, with the above increase being less than that provoked by adrenaline and noradrenaline (10(-6) M). It is concluded that the mechanism of the cardiotoxic effect of catecholamines cannot be reduced only to their effect on myocardial beta-receptors. 相似文献
2.
Isolation, purification, and antibiotic activity of o-methoxycinnamaldehyde from cinnamon. 总被引:2,自引:1,他引:1
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S Morozumi 《Applied microbiology》1978,36(4):577-583
o-Methoxycinnamaldehyde has been isolated and purified from powdered cinnamon. The compound inhibits the growth and toxin production of mycotoxin-producing fungi. The substance completely inhibited the growth of Aspergillus parasiticus and A. flavus at 100 microgram/ml and A. ochraceus and A. versicolor at 200 microgram/ml. It inhibited the production of aflatoxin B1 by over 90% at 6.25 microgram/ml, ochratoxin A at 25 microgram/ml, and sterigmatocystin at 50 microgram/ml. The substance also displayed a strong inhibitory effect on the growth of five dermatophytoses species, e.g., Microsporum canis (minimum inhibitory concentration, 3.12 to 6.25 microgram/ml). However, no antibacterial effect was observed at concentrations as high as 50 microgram/ml. 相似文献
3.
L-carnitine prevents doxorubicin-induced apoptosis of cardiac myocytes: role of inhibition of ceramide generation. 总被引:6,自引:0,他引:6
N Andrieu-Abadie J P Jaffrezou S Hatem G Laurent T Levade J J Mercadier 《FASEB journal》1999,13(12):1501-1510
Besides the well-documented effect of the chemotherapeutic drug doxorubicin on free radical generation, the exact signaling mechanisms by which it causes cardiac damage remain largely unknown and are of fundamental importance in understanding anthracycline cardiotoxicity. In this study, we describe that a 1 h treatment of isolated adult rat cardiac myocytes with doxorubicin (0.5 microM) induced DNA fragmentation associated with the classical morphological features of apoptosis observed after 7 days of culture. The doxorubicin toxicity was preceded by an increase in intracellular ceramide levels with a concurrent decrease in sphingomyelin. Anthracycline-induced ceramide accumulation resulted from the activation of a sphingomyelinase assayed under acidic conditions, an effect related to an increase in V(max). Pretreatment of cardiac myocytes with L-carnitine (200 microgram/ml), a compound known for its protective effect on cardiac metabolic injuries, was found to dose-dependently inhibit the doxorubicin-induced sphingomyelin hydrolysis and ceramide generation as well as subsequent cell death. However, L-carnitine did not protect cardiac myocytes from apoptosis induced by exogenous cell-permeant ceramide. L-carnitine pretreatment did not affect the sphingomyelinase basal activity but abolished the doxorubicin-induced increase in V(max). Moreover, in vitro studies conducted on cell extracts or with purified acid sphingomyelinase demonstrated that L-carnitine exerted a dose-dependent, sphingomyelinase inhibitory effect (through V(max) reduction). Taken together, these findings show that by inhibiting a (perhaps novel) drug-activated acid sphingomyelinase and ceramide generation, L-carnitine can prevent doxorubicin-induced apoptosis of cardiac myocytes. 相似文献
4.
E V YoungLai 《Hormone research》1978,9(1):31-40
Prostaglandins of the F and E series at concentrations from 1 to 100 microgram/ml had no effect on steroidogenesis by isolated rabbit follicles. Indomethacin and 7-oxa-13-prostynoic acid at doses lower than 100 microgram/ml failed to prevent the LH-induced increase in testosterone accumulation by follicles. At 1 mg/ml these inhibitors prevented the LH effects. Prostaglandin E2 and F2alpha had no effect on testosterone accumulation. However, prostaglandin E2 seemed to enhance the LH-induced accumulation of androstenedione and progesterone by the follicles. These data suggest that prostaglandins play a minor role in steroidogenesis by isolated rabbit ovarian follicles. 相似文献
5.
N Frisina G Costa M Buemi R Scamardi A Trovato G Squadrito 《Bollettino della Società italiana di biologia sperimentale》1979,55(23):2431-2437
Angiotensin II increases aldosterone production of isolated and superfused bovine adrenal glands. Indomethacin shows a bi-phasic effect on the production of the above-mentioned hormone, inhibitory at low doses (0,2 microgram/ml), stimulatory at high doses (5.0 microgram/ml). Preincubation with this drug impedes the increase of aldosterone production induced by angiotensin II. It is likely that the steroidogenetic effect of angiotnesin II is carried out through the PGs. 相似文献
6.
Y Lessard S Desbrousses G Paulet 《Comptes rendus des séances de la Société de biologie et de ses filiales》1977,171(6):1270-1282
Inhalation of gas mixtures containing different concentrations of FC 12 by anesthetized and normally oxygenated dogs produces blood levels of FC 12 which are stable and proportional to the rate of FC 12 in the mixture. From the arterial concentration of 40 microgram/ml FC 12 (5 % FC 12 mixture) and over, FC 12 alone causes effects proportional to doses: arterial pressure decrease with tachycardia. At high rates of FC 12 tachypnoea and slight morphological alterations of the electrocardiogram can be recorded. Arhythmia never occurs under the action of FC 12 alone even at maximum arterial concentration reached here : 230 microgram/ml (40 % FC 12 mixture). Recorded disturbances are always reversible. The intravenous perfusion of epinephrine alone evokes the appearance of premature contractions at the only dose of 5 microgram/kg/mn. The presence of FC 12 in blood conjoined with epinephrine induces the inhibition of the hypertensive action of epinephrine at high concentration and lowers the arhythmogenic threshold. The dog is clearly more sensitive than the rabbit to the arhythmogenic action of epinephrine and FC 12. The required rates of epinephrine and FC 12 validate the hypothesis of cardiac sensitization by FC 12 to the arhythmogenic action of circulating adrenaline to explain the cases of sudden "sniffing" deaths in man. 相似文献
7.
The effect of Indian red scorpion (Mesobuthus tamulus concanesis, Pocock; MBT) venom was investigated on isolated rat right atrial preparations. MBT venom (0.001-3.0 micrograms/ml) exhibited a peculiar concentration-response pattern with respect to rate. The venom concentrations between 0.001-0.01 microgram/ml increased the atrial rate (phase I), followed by a relative decrease with 0.03-0.3 microgram/ml (phase II), and then an abrupt increase with 0.6-3.0 micrograms/ml (phase III). On the other hand, the force was unaltered by venom at phases I and II, while an increase was seen at phase III (3.0 micrograms/ml). Propranolol (0.1 microM) completely blocked the cardiostimulant action of venom at phase III. Further, this stimulant action of venom was absent in atria obtained from reserpinized animals. Pretreatment with atropine (0.3 microM), produced tachycardia at concentrations 0.1-0.3 microgram/ml of venom. But, hexamethonium (30 microM) had no influence on the venom (0.1 microgram/ml)-induced alterations in rate. However, MBT venom increased the acetylcholinesterase (AChE) activity (2-3 fold) in a concentration-dependent manner. Tetrodotoxin (2 microM), did not block the increase in rate produced by 0.01 microgram/ml of venom. Results suggest that, MBT venom-induced alterations of cardiac rhythmicity are mediated through cholinergic as well as adrenergic mechanisms depending upon the concentrations. The modulation of atrial rate at very low concentrations may be due to the direct action of venom on the atrium. 相似文献
8.
The effect of three concentrations of sarcolysine (0.5 micrograms/ml, 1 microgram/ml and 2 micrograms/ml) on the sister chromatid exchanges (SCE) was investigated in human lymphocytes in vitro. A dose related increase in SCEs frequencies was observed after sarcolysine administration and also a delayed development of cell cycle has been induced by the two last concentrations. The variation range of SCEs per cell was dose-dependent and it was considered to represent the acquired genetic instability induced by the drug. 相似文献
9.
The effect of intracerebroventricular (i.c.v.) injection of the alpha 2-adrenoceptor agonists clonidine and B-HT 920 on mean arterial pressure (MAP), heart rate (HR), and plasma concentrations of noradrenaline and adrenaline was examined in conscious unrestrained rats. The injection of 1.0 microgram clonidine significantly decreased MAP and slightly decreased HR. Plasma noradrenaline and adrenaline levels were slightly but not significantly decreased after the injection of 1 microgram clonidine. In contrast, the injection of 0.1-10.0 micrograms B-HT 920 increased MAP and decreased HR. Plasma noradrenaline and adrenaline levels were slightly increased after the injection of the 1- and 10-micrograms doses. The i.c.v. injection of the alpha 2-antagonist rauwolscine slightly but not significantly increased MAP and plasma noradrenaline and adrenaline levels. The responses to i.c.v. injection of clonidine and B-HT 920 were not changed by prior administration of rauwolscine. Neither the pressor response to B-HT 920 nor the depressor response to clonidine was abolished by rauwolscine, suggesting that neither response was mediated by alpha 2-adrenoceptors. 相似文献
10.
Prevention of experimental coronary thrombosis by hirudin 总被引:1,自引:0,他引:1
The antithrombotic activity of hirudin was studied in a rat coronary thrombosis model. The thrombus formation was induced by external application of silver nitrate solution onto the left anterior descending coronary artery. Following subcutaneous injection, hirudin in doses of 0.25, 0.5 and 1.0 mg/kg reduced the development of coronary thrombosis in a dose-dependent manner. The most pronounced antithrombotic effect of hirudin in the described model was related with plasma concentrations between 0.20 and 0.35 microgram hirudin/ml. 相似文献
11.
The preparation of isolated adult rat heart myocytes able to tolerate physiological calcium concentrations is described. The use of tissue culture medium as the buffer for the enzymic perfusion and digestion of the heart and, subsequently, not exposing isolated myocytes to temperatures below room temperature, proved necessary for the preparation of isolated myocytes able to maintain integrity in the presence of 2 mM calcium. After 60 minutes, 85 percent of the myocytes incubated at 37° with 2 mM calcium exclude the dye trypan blue. Levels of ATP and related compounds, although depressed, were maintained for an extended period. Oxidation of glucose and pyruvate was greater and succinate oxidation lower in calcium-resistant mycoytes compared to myocytes not resistant to calcium. The two types of myocytes were equally rapid in converting succinate to malate. Oxygen utilization increased following the addition of calcium. Myocytes demonstrated both Pasteur and Randle effects and responded to plasma levels of insulin by increasing glucose oxidation. This is the first report of isolated adult rat heart myocytes able to tolerate millimolar calcium concentrations in physiologic medium. 相似文献
12.
Brain natriuretic peptide (BNP) affects the regulation of myocardial metabolism through the production of cGMP and these effects may be altered by cardiac hypertrophy. We tested the hypothesis that BNP would cause decreased metabolism and function in the heart and cardiac myocytes by increasing cGMP and that these effects would be disrupted after thyroxine-induced cardiac hypertrophy (T4). Open-chest control and T4 rabbits were instrumented to determine local effects of epicardial BNP (10(-3) M). Function of isolated cardiac myocytes was examined with BNP (10(-8)-10(-7) M) with or without KT5823 (10(-6) M, cGMP protein kinase inhibitor). Cyclic GMP levels were measured in myocytes. In open-chest controls, O2 consumption was reduced in the BNP area of the subepicardium (6.6+/-1.3 ml O2/min/100 g versus 8.9+/-1.4 ml O2/min/100 g) and subendocardium (9.4+/-1.3 versus 11.3+/-0.99). In T4 animals, functional and metabolic rates were higher than controls, but there was no difference between BNP-treated and untreated areas. In isolated control myocytes, BNP (10(-7) M) reduced percent shortening (PSH) from 6.5+/-0.6 to 4.3+/-0.4%. With KT5823 there was no effect of BNP on PSH. In T4 myocytes, BNP had no effect on PSH. In control myocytes, BNP caused cGMP levels to rise from 279+/-8 to 584+/-14 fmol/10(5) cells. In T4 myocytes, baseline cGMP levels were lower (117+/-2 l) and were not significantly increased by BNP. Thus, BNP caused decreased metabolism and function while increasing cGMP in control. These effects were lost after T4 due to lack of cGMP production. These data indicated that the effects of BNP on heart function operated through a cGMP-dependent mechanism, and that this mechanism was disrupted in T4-induced cardiac hypertrophy. 相似文献
13.
To measure cholinergic, adrenergic and tryptaminergic receptor activity of formaldehyde (HCHO) in rat uterus, albino rats were treated with 5 and 10 mg/kg, ip HCHO for 30 days. Acetylcholine (ACh) in doses 1.33, 2 and 3 micrograms/ml produced mild to moderate contraction of isolated rat uterus in control group. HCHO had no effect on isolated rat uterus per se, however it reduced ACh and carbachol induced contraction and presence of adrenaline influences in respect of ACh and carbachol activity. Adrenaline per se had no effect in control preparations, but reduced carbachol induced contraction. Propranolol had no effect on rat uterus; but its presence in the bathing medium increased activity of adrenaline. 5-Hydroxytryptamine (5-HT) had no effect of its own on isolated rat uterus but its presence in the bathing medium enhanced contractions of carbachol and oxytocin. 相似文献
14.
M Orsetti M C Cassone 《Bollettino della Società italiana di biologia sperimentale》1982,58(6):289-294
The modification of the synergism acetylcholine-eserine induced by two different concentrations of morphine (0.2 and 8 microgram/ml) was studied on the frog rectus abdominis muscle. Morphine increases the Ach-potentiating action of low concentrations of eserine (from 3 to 40 ng/ml). On the contrary at higher eserine concentrations (from 0.1 to 1.0 microgram/ml), morphine reduces the potentiation of Ach effects caused by eserine. It is concluded that in amphibian muscle eserine and morphine potentiate the effects of exogenous Ach by acting on the same population of receptors. 相似文献
15.
The effect of corticosterone (CC, 0.4 and 1 microgram/ml) and of hydrocortisone (HC, 20 and 40 micrograms/ml) on the spontaneous motility and on prostaglandin (PG) generation in the uterus from ovariectomized rats, was studied. Both concentrations of CC depressed significantly the frequency of contractions but the isometric developed tension was affected only by the higher dose. HC significantly inhibited the isometric developed tension at both concentrations whereas the contractile frequency was only depressed by the higher one. The CC-inhibited motility was accompanied by a reduction in the amount of PGs released from the uterus into the bath solution. In addition, the influences of arachidonic acid (AA), linoleic acid (LA) and gamma-linolenic acid (alpha-LA) - 1 or 2 micrograms/ml - on the depression evoked by CC, were also explored. The fatty acids had no effect on the spontaneous uterine motility except in the case of alpha-LA at 1 microgram/ml. alpha-LA completely blocked the CC-evoked reduction of both tension and frequency; AA (1 microgram/ml) elicited a reversion only on frequency whereas LA had no effect at all. This reversion by a fatty acid PG-precursor might indicate that CC is able to diminish substrate availability for PG synthesis in the rat uterus. 相似文献
16.
P J Battista J P Poff D R Deaver W A Condon 《Journal of reproduction and fertility》1987,80(2):517-522
Biogenic amines were administered using osmotic pumps placed subcutaneously in the neck region of regularly cycling, non-lactating dairy cows on Days 9-11 (oestrus = Day 0) of the oestrous cycle. Blood samples were collected using indwelling jugular catheters and the plasma progesterone concentrations were measured. Samples were collected at 4-h intervals for the first 12 h of treatment and thereafter at 12-h intervals for the remainder of the 72-h treatment period. After administration of various doses of noradrenaline, adrenaline and serotonin (0.5-2.0 micrograms/kg/h) significant elevation of plasma progesterone was achieved at a dosage of 2.0 micrograms/kg/h (P less than 0.01). The response to adrenaline was greater than that observed for noradrenaline and serotonin (P less than 0.05). Within-treatment comparison to pretreatment samples showed plasma progesterone concentrations to increase within 4 h after the administration of noradrenaline, adrenaline and serotonin (P less than 0.05) and this enhancement was maintained throughout the treatment period (P less than 0.05). The elevation in plasma progesterone concentrations induced by noradrenaline, adrenaline and serotonin was independent of changes in circulating concentrations of luteinizing hormone. These results support a physiological role for endogenous biogenic amines in the control of bovine luteal progesterone production. 相似文献
17.
Experiments were conducted on albino rats; a study was made of hyperplastic processes in the mitochondria of the myocytes of the heart with the action of toxic adrenaline doses. A solution of adrenaline chloride was injested intramuscularly (3 mg/kg). Three types of mitochondria were revealed in electron microscopic study. Mitochondria of the first type were of the size and structure characteristic of the muscle cells of the myocardium. Mitochondria of the second type had a very dense, finegrained matrix and a great number of cristae per unit of the area. Mitochondria of the third type had two "sections" under the common external membrane, differing from one another by the matrix density, distribution and number of cristae. It is supposed that the ultrastructural peculiarities of each of the types reflected their functional condition. 相似文献
18.
Regulation of pyruvate dehydrogenase activity in rat epididymal fat-pads and isolated adipocytes by adrenaline. 总被引:2,自引:2,他引:0
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1. Dose-dependent effects of adrenaline on PDHa activity were investigated with both incubated rat epidiymal fat-pads and isolated adipocytes. 2. Adrenaline (10nM- 5 micrometer) decreased PDHa activity in fat-pads incubated with 5 mM-[U-14C]glucose + insulin (20 munits/ml). Changes in [U-14C]glucose incorporation into fatty acids in these tissues correlated only loosely with changes in PDHa activity. There was a good inverse relationship between adrenaline-induced changes in PDHa activity and increases in lipolysis (glycerol release). 3. Adrenaline (10nM - 0.5 micrometer) decreased PDHa activity in fat-pads incubated with 5 mM-[U-14C]pyruvate + insulin (20 munits/ml), whereas 1 micrometer- and 5 micrometer-adrenaline slightly increased PDHa activity. All concentrations of adrenaline tested decreased [U-14C]pyruvate incorporation into fatty acids. Between 10nM- and 0.5 micrometer-adrenaline percentage decreases in PDHa activity paralleled decreases in faty acid synthesis. 4. Effects of adrenaline on PDHa activity and fatty acid synthesis in fat-pads incubated with 5mM-[U-14C]pyruvate + insulin (20 munits/ml) could not be mimicked by addition of albumin-bound palmitate. 5. The response of PDHa activity to adrenaline (0.1 nM - 1 micrometer) in isolated adipocytes differed with the carbohydrate substrate used in the incubations. With 5 mM-glucose + insulin (20 munits/ml), PDHa activity was significantly increased by 10 nM-adrenaline, but not by 1 micrometer-adrenaline, the response to adrenaline being biphasic. There was some correlation between PDHa activity and accumulation of non-esterified fatty acids. With 5 mM-glucose alone adrenaline (0.1 nM - 1 micrometer) had no effect on PDHa activity even though lipolysis was increased by adrenaline (0.1 micrometer - 1 micrometer). With 5mM-fructose in the presence and absence of insulin, lipolytic doses of adrenaline decreased PDHa activity. No tested concentrations of adrenaline increased PDHa with this substrate. 6. In the presence of 5 mM-fructose, palmitate was significantly more effective than adrenaline with respect to the maximum decrease in PDHa activity that could be elicited. 4. The relationship of changes in PDHa activity to changes in lipogenesis and the likelihood of adrenaline-induced changes in PDHa activity being secondary to changes in non-esterified fatty acid metabolism are discussed. 相似文献
19.
Effects of glucagon and N6O2''-dibutyryladenosine 3'':5''-cyclic monophosphate on calcium transport in isolated rat liver mitochondria.
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1. The administration of glucagon to fed rats by intraperitoneal injection, or the perfusion of livers from fed rats with glucagon by the method of Mortimore [Mortimore (1963) Am.J. Physiol. 204, 699--704] was associated with increases of 15- and 5-fold respectively, in the time for which a given load of exogenous Ca2+ is retained by mitochondria subsequently isolated from the liver. This effect of glucagon was (a) also induced by N6O2'-dibutyryl cyclic AMP, (b) completely blocked by cycloheximide, (c) relatively slow in onset (15--60 min) and (d) associated with a stimulation of about 20% in the rates of ADP-stimulated oxygen utilization and Ca2+ transport measured in the presence of succinate. 2. Perfusion of livers with glucagon resulted in the isolation of mitochandria which showed a 50% increase, no significant change and a 40% increase in the concentrations of endogenous Ca, Mg and Pi respectively, when compared with mitochondria isolated from control perfused livers. 3. The administration of insulin or adrenaline to fed rats induced increases of 10- and 8-fold respectively, in the time for which Ca2+ is retained by isolated liver mitochondria. Perfusion of livers with insulin had no effect on mitochondrial Ca2+ retention time. 4. The perfusion of livers from starved rats with glucagon, or the administration of either glucagon or insulin to starved rats, increased by about 2.5- and 15-fold respectively, the time for which isolated mitochondria retain Ca2+. 5. Mechanisms which may be responsible for the observed alterations in Ca2+-retention time are discussed. 相似文献