Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 21
Filter
Add more filters










Type of study
Publication year range
1.
Br J Pharmacol ; 116(3): 2048-52, 1995 Oct.
Article in English | MEDLINE | ID: mdl-8640344

ABSTRACT

1. The role of 5-HT2 and 5-HT3 receptors in the mediation of direct and reflex vascular responses to intrapulmonary platelet activation was investigated. 2. Anaesthetized rabbits were challenged intravenously with an emulsion of autologous bone marrow that produced a sharp increase in pulmonary blood pressure, a fall in systemic blood pressure, platelet consumption and death. 3. Platelet depletion before the challenge nearly abolished all the cardiovascular effects and prevented death. Bilateral vagotomy prevented the fall in systemic blood pressure and death but did no prevent the increase in pulmonary pressure. The intravenous administration of the 5-HT2 antagonist, ketanserin, only reduced the increase in pulmonary pressure without affecting the systemic response or mortality. 4. The effects of intravenous 5-HT and of electrical stimulation of the cephalic ends of the cut vagi nerves were also explored. 5-HT injection increased the pulmonary vascular pressure but its effects on systemic blood pressure were variable. These response were modified by the 5-HT antagonists in a manner that resembles their effects on bone marrow embolism. Afferent vagal stimulation produced a fall in systemic blood pressure that was not prevented by MDL-7222. 5. This study indicates that a centrally mediated reduction of peripheral vascular tone is the cause of the potentially lethal circulatory collapse that follows the intrapulmonary entrapment of activated platelets. This reflex is initiated by the action of 5-HT on 5-HT3 receptors in the lung.


Subject(s)
Platelet Activation/drug effects , Receptors, Serotonin/metabolism , Serotonin Antagonists/pharmacology , Tropanes/pharmacology , Animals , Bone Marrow Transplantation , Injections, Intravenous , Lung/drug effects , Lung/metabolism , Male , Pulmonary Wedge Pressure/drug effects , Rabbits , Receptor, Serotonin, 5-HT2A , Receptors, Serotonin/drug effects , Receptors, Serotonin, 5-HT3 , Serotonin Antagonists/administration & dosage , Tropanes/administration & dosage , Vagus Nerve/physiology
2.
Arch Inst Cardiol Mex ; 64(3): 245-50, 1994.
Article in Spanish | MEDLINE | ID: mdl-7979814

ABSTRACT

The purpose of this study was to establish a blood platelet aggregation model that would permit "in vivo" (New Zealand rabbits) evaluation of hemodynamic and microscopic parameters. The platelet aggregation was induced by the administration of collagen I.V. 75 micrograms/kg/min, which produced a decrease of systolic arterial pressure from mean = 69 to mean = 55 mm Hg and diastolic pressure from mean = 43 to mean = 27 mm Hg, with ventricular increase from mean = 25 to mean = 41 mm Hg. Aspirin, dypiridamol or sulfinpyrazone was administered 10 mg/kg, half hour before the administration of collagen and prostacycline 100 mg/kg/min starting 3 minutes before until 10 minutes after the collagen injection. With the joint administration of collagen and aspirin, collagen and dypiridamol both systolic and diastolic arterial pressure were lowered with no modification in the ventricular values. No hemodynamic changes were observed with the joint administration of sulfinpyrazone-collagen or prostacycline-collagen. Histology demonstrated multiple vascular lung thrombosis with the administration of collagen and in less intensity when jointly administered with an antiaggregant drug. This model permits to measure hemodynamically and histologically pro and antiaggregant substances.


Subject(s)
Platelet Aggregation , Animals , Heart/drug effects , Hemodynamics/drug effects , Lung/drug effects , Lung/pathology , Models, Biological , Myocardium/pathology , Platelet Aggregation/drug effects , Rabbits
3.
Int J Cancer ; 56(5): 640-5, 1994 Mar 01.
Article in English | MEDLINE | ID: mdl-8314339

ABSTRACT

The level of amplification (copy number/cell) of HPV16 and HPV18 viral genomes and its correlation with the presence of E1/E2 genes were analyzed in a sample of 42 HPV16- and 21 HPV18-positive cervical carcinomas of different clinical stages and histological types. The viral copy number/cell was assessed by dot-blot hybridization and the presence of E1/E2 genes by PCR and Southern blot. The copy number/cell was significantly lower in HPV18-positive than in HPV16-positive tumours (23 +/- 8 and 457 +/- 191 respectively). Nearly half of the HPV16s (43%) were distributed similarly to the HPV18s in the ranges of 50 or less copies, having its peak at the group of 1 to 10 copies, whereas the remaining HPV16s (57%) spread over the groups of 51 or more copies, with another peak at the group of 101 to 500. The E1/E2 region was absent in all tumours positive for HPV18 and present in 64% of those positive for HPV16. The HPV16 tumours negative for E1/E2 had a much lower viral copy number (17 +/- 12) than the positive ones (582 +/- 212), thus resembling HPV18-positive tumours. Viral copy number was negatively correlated with the clinical stage of the tumours and directly associated with the degree of histological differentiation. However, these correlations are primarily attributable to the presence or absence of an intact E1/E2 region.


Subject(s)
DNA-Binding Proteins , Genes, Viral/genetics , Oncogene Proteins, Viral/genetics , Oncogene Proteins/genetics , Papillomaviridae/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/virology , Base Sequence , Blotting, Southern , Female , Gene Amplification , Humans , Immunoblotting , Molecular Sequence Data , Polymerase Chain Reaction
4.
Prostaglandins ; 42(6): 571-8, 1991 Dec.
Article in English | MEDLINE | ID: mdl-1801064

ABSTRACT

Prostacyclin (PGI2) and Thromboxane B2 (TxB2) production induced by thrombin in human umbilical veins (HUV) was studied. Successive stimulations of HUV segments were performed with and without restoration of arachidonic acid (AA). Thrombin consistently stimulated the production of both substances. The magnitude of the increment declined with progressive stimuli. The addition of exogenous AA could restore the production of TXB2 but not that of PGI2. These results suggest that sustained stimulation of AA release may lead to an imbalance in the TXA2/PGI2 ratio perhaps through an effect of unknown products of AA oxidation on PGI2 synthase.


Subject(s)
Epoprostenol/biosynthesis , Thrombin/pharmacology , Thromboxane B2/biosynthesis , Umbilical Veins/metabolism , Arachidonic Acid/pharmacology , Humans , Umbilical Veins/drug effects
6.
Br J Pharmacol ; 97(4): 1119-24, 1989 Aug.
Article in English | MEDLINE | ID: mdl-2790378

ABSTRACT

1. The role of nitric oxide (NO) in the regulation of the vascular tone of the coronary circulation of the Langendorff-perfused rabbit heart was investigated. 2. NG-monomethyl-L-arginine (L-NMMA; 10-100 microM), a specific inhibitor of NO formation from L-arginine (L-Arg), but not its D-enantiomer (D-NMMA; 100 microM) produced a dose-related, sustained increase in the coronary perfusion pressure (CPP). In addition, L-NMMA inhibited the vasodilator responses of acetylcholine (ACh), unmasking in some instances its direct vasoconstrictor effect. These effects of L-NMMA were attenuated by L-Arg. 3. L-NMMA (10 and 30 microM), but not D-NMMA (30 microM), caused a long-lasting inhibition of NO formation which was reversed by L-Arg (30 and 100 microM), but not by D-Arg (100 microM). 4. This study indicates that the formation of NO from L-Arg in the coronary circulation of the rabbit plays a role both as a regulator of vascular tone and as a mediator of the vasodilatation induced by ACh.


Subject(s)
Arginine/metabolism , Coronary Circulation/drug effects , Muscle, Smooth, Vascular/physiology , Nitric Oxide/pharmacology , Acetylcholine/pharmacology , Animals , Arginine/pharmacology , Heart/drug effects , In Vitro Techniques , Luminescent Measurements , Male , Muscle Relaxation/drug effects , Muscle, Smooth, Vascular/drug effects , Rabbits , Superoxide Dismutase/pharmacology , omega-N-Methylarginine
7.
Arch Invest Med (Mex) ; 20(3): 273-8, 1989.
Article in English | MEDLINE | ID: mdl-2517392

ABSTRACT

The mechanism of estrogen induced eosinophilia is not well understood. It has been proposed that type II estrogen receptors, present both in eosinophils and uterine tissues, can act as anchorage mechanism for the attachment of eosinophils within the uterus. However an explanation based on the existence of chemotactic mediators is more likely. We studied the effects of the lipoxygenase inhibitor BW755 and two different doses of indomethacin in a model of acute uterine eosinophilia promoted by 17-beta-estradiol in young rats; simultaneously estrogen receptors were studied with immunocytochemical methods using monoclonal antibodies. BW755 and a high dose of indomethacin sharply reduced the estrogen induced eosinophilia, whereas a low dose of indomethacin enhanced the steroid effect. No estrogen receptors were found with immunohistochemical methods neither in eosinophils nor in endothelial cells in any of the groups. A role for the lipoxygenase products of arachidonic acid, mainly leukotrine B4 as the chemical mediators responsible of eosinophil chemotaxis in be estrogen primed uterus is suggested.


Subject(s)
Arachidonate Lipoxygenases/antagonists & inhibitors , Cyclooxygenase Inhibitors , Eosinophilia/chemically induced , Estradiol/toxicity , Uterine Diseases/chemically induced , 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine/pharmacology , Animals , Arachidonic Acid , Arachidonic Acids/metabolism , Chemotaxis, Leukocyte/drug effects , Eosinophilia/metabolism , Female , Indomethacin/pharmacology , Rats , Rats, Inbred Strains , Uterine Diseases/metabolism
8.
Br J Pharmacol ; 95(3): 830-4, 1988 Nov.
Article in English | MEDLINE | ID: mdl-3061543

ABSTRACT

1. Acetylcholine (ACh, 0.03-3.0 microM) induced a dose-dependent vasodilatation in the isolated Langendorff-perfused heart of the rabbit. The vasodilatation was mimicked by exogenous nitric oxide (NO, 0.045-4.5 nmol). 2. There was no detectable vascular relaxing activity in the cardiac effluent when these concentrations of ACh or NO were injected through the heart, even in the presence of an infusion of superoxide dismutase (SOD). 3. Acetylcholine (0.03-3.0 microM), however, induced the release into the cardiac effluent of a material which produced a chemiluminescent signal when reacted with ozone, a response which could be mimicked with exogenous NO (0.045-4.5 nmol) injected through the heart. 4. The effects of ACh, but not those of NO, were antagonized by atropine (2 microM). Prostacyclin (1 microM) injected through the heart induced vasodilatation without the release of a biologically active or chemiluminescent material. 5. During passage through the heart, greater than 99% of the biological activity of exogenous NO disappeared, whereas there was approximately 50% reduction of its chemiluminescent response. This indicates complete transformation into a mixture containing approximately 50% NO2- and 50% of other non-chemiluminescent material(s), presumably NO3-. 6. This study suggests that ACh induces endothelium-dependent vasodilatation in the coronary circulation through the release of the endogenous nitrovasodilator, NO, which is rapidly converted to NO2- and NO3-.


Subject(s)
Acetylcholine/pharmacology , Heart/drug effects , Nitric Oxide/metabolism , Vasodilation , Acetylcholine/antagonists & inhibitors , Animals , Epoprostenol/pharmacology , In Vitro Techniques , Luminescent Measurements , Male , Rabbits , Sodium Nitrite/pharmacology
9.
J Appl Toxicol ; 8(5): 351-4, 1988 Oct.
Article in English | MEDLINE | ID: mdl-3230245

ABSTRACT

The effect of silymarin (100 mg/kg i.p.) on the biochemical indicators of liver damage induced by thallium (10 mg/kg p.o.) was studied in rats. The production of malondialdehyde and the content of reduced glutathione in the liver were measured as indicators of lipid peroxidation. Thallium intoxication increased the serum activities of glutamic pyruvic transaminase, gamma-glutamyl transpeptidase, alkaline phosphatase and the liver concentration of triglycerides. Thallium decreased the activity of alkaline phosphatase and increased that of gamma-glutamyl transpeptidase in the liver cell membrane. It also abolished the membrane activity of Na+/K+ ATPase. Lipid peroxidation was enhanced by thallium as malondialdehyde production was increased and the content of reduced glutathione was decreased in the liver. Silymarin completely prevented all these changes. It is suggested that thallium toxicity is due, at least in part, to the promotion of lipid peroxidation. The membrane stabilizing effect of silymarin observed in this and in other models of liver toxicity is due to some antioxidant property, possibly related to its ability to scavenge free oxygen radicals.


Subject(s)
Chemical and Drug Induced Liver Injury/prevention & control , Flavonoids/pharmacology , Silymarin/pharmacology , Thallium/toxicity , Animals , Chemical and Drug Induced Liver Injury/enzymology , Chemical and Drug Induced Liver Injury/metabolism , Liver/enzymology , Liver/metabolism , Male , Rats , Rats, Inbred Strains
10.
J Hepatol ; 6(3): 337-42, 1988 Jun.
Article in English | MEDLINE | ID: mdl-3392383

ABSTRACT

Pretreatment of rats with colchicine (10 micrograms/day) for 7 days protected against CCl4-induced acute liver damage. CCl4 intoxication was demonstrated histologically and by increased serum activities of glutamic-pyruvic transaminase, alkaline phosphatase and gamma-glutamyl transpeptidase. Furthermore, an increase in liver lipid peroxidation and a decrease in plasma membrane gamma-glutamyl transpeptidase activity were found. Colchicine increased the LD50 of CCl4 2.5-fold and prevented the release of intracellular enzymes, as well as the decrease in gamma-glutamyl transpeptidase activity in the plasma membrane. It also completely prevented the lipid peroxidation produced by CCl4 and limited the extent of the histological changes. Our results suggest that the protective effect of colchicine may be mediated through its action on an early toxic event, because treatment of the animals with colchicine produced a significant decrease in CCl4-induced lipid peroxidation.


Subject(s)
Carbon Tetrachloride Poisoning/pathology , Colchicine/therapeutic use , Liver/pathology , Animals , Liver/drug effects , Male , Rats , Rats, Inbred Strains , Time Factors
11.
J Appl Toxicol ; 7(6): 361-5, 1987 Dec.
Article in English | MEDLINE | ID: mdl-3429760

ABSTRACT

The profile of urinary salicylate metabolites was determined after an oral administration of acetylsalicylic acid (ASA) to: 1, control rats; 2, rats treated with CCl4 and 3, rats intoxicated with CCl4 and also pretreated with colchicine for 7 days. The following enzymatic activities were determined: liver and plasma ASA-esterase, liver UDP-glucuronyltransferase and liver aniline hydroxylase. The time course of plasma concentration of salicylates in similar groups were followed after the intraperitoneal administration of acetylsalicylic acid (ASA), salicylic acid (SA) or gentisic acid (GA). The animals acutely intoxicated with CCl4 showed a reduction in urinary excretion of glucuronates and an increased urinary excretion of gentisic and salicylic acids. The activities of plasma and liver ASA-esterases were significantly increased in CCl4-treated rats while the aniline hydroxylase was reduced and the UDP-glucuronyltransferase remained unchanged. The plasma half lives of salicylates were reduced in CCl4-treated rats regardless of the administered parent compound. Colchicine pre-treatment completely prevented the alterations produced by acute intoxication with CCl4. The heterogeneity of liver metabolic dysfunctions present in acute liver damage was evidenced. It is emphasized that the pharmacokinetic alterations produced by acute liver injury can be the result of complex factors that may involve changes in circulation, hepatic binding protein and other routes of elimination.


Subject(s)
Aspirin/pharmacokinetics , Carbon Tetrachloride Poisoning/metabolism , Animals , Carbon Tetrachloride Poisoning/enzymology , Carbon Tetrachloride Poisoning/pathology , Gentisates/blood , Half-Life , Liver/pathology , Male , Rats , Rats, Inbred Strains , Salicylates/blood
12.
Biochem Pharmacol ; 36(18): 3021-5, 1987 Sep 15.
Article in English | MEDLINE | ID: mdl-3115269

ABSTRACT

The profile of urinary salicylate metabolites was determined after the oral administration of acetylsalicylic acid (ASA) to CCl4-cirrhotic rats, CCl4-cirrhotic rats treated with colchicine for 1 month, and control groups. The following enzymatic activities were determined: liver and plasma ASA-esterase, liver UDP-glucuronyltransferase, and liver aniline hydroxylase. The time-course of plasma concentration of salicylates in similar groups was followed after the intraperitoneal administration of salicylic acid (SA) or gentisic acid (GA). The cirrhotic animals showed a lack of urinary glucuronates and an increase in urinary gentisic and salicylic acids. The activities of plasma and liver ASA-esterases were increased significantly in cirrhosis, whereas aniline hydroxylase was reduced and UDP-glucuronyltransferase remained unchanged. The plasma half-lives of salicylates were reduced in the cirrhotic animals regardless of the administered parent compound. Colchicine treatment reversed almost completely the alterations. The heterogeneity of liver metabolic dysfunctions present in chronic liver disease was demonstrated. It is emphasized that the pharmacokinetic alterations produced by liver damage are the result of a complex set of factors involving changes in the hepatic circulation, protein binding, and the existence of other routes of elimination.


Subject(s)
Aspirin/metabolism , Carbon Tetrachloride/toxicity , Gentisates , Liver Cirrhosis, Experimental/chemically induced , Salicylates/metabolism , Aniline Hydroxylase/metabolism , Animals , Carboxylic Ester Hydrolases/metabolism , Colchicine/pharmacology , Glucuronates/urine , Glucuronosyltransferase/metabolism , Hydroxybenzoates/metabolism , Kinetics , Liver/enzymology , Liver Cirrhosis, Experimental/metabolism , Male , Rats , Rats, Inbred Strains , Salicylates/blood , Salicylates/urine , Salicylic Acid
13.
Prostaglandins ; 33(6): 869-77, 1987 Jun.
Article in English | MEDLINE | ID: mdl-2890182

ABSTRACT

The effects of colchicine (10 g/day p.o. for 7 days) and rioprostil (2-decarboxy, 2-hydroxymethyl-15-deoxy-16-RS-hydroxy-16-methyl-prostaglandin-E1) (20 g/kg s.c., a single dose) on the enzymatic and histological markers of acute liver damage were studied in rats intoxicated with a single oral dose of CCl4. The rats were sacrificed 24 h after CCl4. The lipid composition of the liver plasma membranes was also determined. The increase in Alk. Phosp., GGTP and GPT activities and bilirubin concentration in serum as well as the histological images produced by CCl4 were equally prevented by the treatments with colchicine or rioprostil. CCl4 changed the lipid composition of the liver plasma membrane by increasing PI and PC and decreasing SM, PS and PEA. There was a decrease in the cholesterol/phospholipid ratio at the expense of a reduction of cholesterol/protein ratio and elevation in phospholipid/protein ratio. Colchicine and rioprostil also prevented these lipid alterations. The results suggest that the plasma membrane is an important site of action of CCl4 and of the 2 drugs studied. We postulate that the plasma membrane rather than other organelles is the target for the cytoprotective actions of prostaglandins.


Subject(s)
Carbon Tetrachloride , Colchicine/pharmacology , Liver Diseases/metabolism , Liver/metabolism , Membrane Lipids/metabolism , Prostaglandins E/pharmacology , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Animals , Bilirubin/metabolism , Cell Membrane/drug effects , Cell Membrane/metabolism , Chemical and Drug Induced Liver Injury , Liver/drug effects , Liver/pathology , Male , Phospholipids/metabolism , Rats , Rats, Inbred Strains , Rioprostil , gamma-Glutamyltransferase/blood
14.
Eur J Pharmacol ; 134(2): 175-80, 1987 Feb 10.
Article in English | MEDLINE | ID: mdl-2883011

ABSTRACT

We have compared the effects of BW755C, a dual inhibitor of the arachidonic acid cyclo-oxygenase and lipoxygenase, with the effects of colchicine and indomethacin on the reversion of the biochemical and histochemical signs of rat liver cirrhosis. This was induced by i.p. administration of CCl4 for 11 weeks. At this point the rats were divided into four groups (10 animals each). CCl4 administration was continued for one month along with either colchicine, BW755C or indomethacin. No additional treatment was given to the control group. BW755C consistently improved all the parameters studied. Although colchicine also improved all but two markers (serum ALT activity and serum proteins) it ranked lower than BW755C in most of them. Indomethacin only modified favourably serum alkaline phosphatase activity, serum proteins, cholesterol and bilirubins and liver collagen content. The effects of BW755C could be mainly attributed to the inhibition of the lipoxygenase pathway. A common feature of colchicine, adrenal steroids and BW755C was the ability to inhibit the formation of leukotriene and other lipoxygenase products. The possibility that this property might contribute to their anti-cirrhotic actions is discussed.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Arachidonate Lipoxygenases/antagonists & inhibitors , Carbon Tetrachloride Poisoning/enzymology , Liver Cirrhosis, Experimental/enzymology , Pyrazoles/pharmacology , 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine , Alanine Transaminase/metabolism , Alkaline Phosphatase/metabolism , Animals , Cell Membrane/enzymology , Colchicine/pharmacology , Collagen/metabolism , Indomethacin/pharmacology , Liver Cirrhosis, Experimental/chemically induced , Male , Rats , Rats, Inbred Strains , gamma-Glutamyltransferase/metabolism
15.
J Appl Toxicol ; 6(6): 401-4, 1986 Dec.
Article in English | MEDLINE | ID: mdl-3805567

ABSTRACT

Parathion toxicity has been attributed to its metabolic product paraoxon which is formed in the mammal liver through the multiple oxidase enzymes. These are induced by barbiturates and inhibited by SKF 525 A and cimetidine. We assessed the effects of these drugs on the acute toxicity of parathion in rats by measuring the rate of survival at 24 h after the administration of the oral LD50 of parathion to four groups of rats: control and pretreated with the aforementioned drugs. Additional rats of these groups were used to measure the capability of liver isolated microsomes to transform p-nitroanisole to p-nitrophenol. In the control and cimetidine groups we also measured the transformation of parathion to paraoxon and p-nitrophenol by the liver microsomes. Phenobarbital increased the survival 100% whereas cimetidine and SKF 525 A dramatically potentiated parathion toxicity. Phenobarbital increased the formation of p-nitrophenol but cimetidine and SKF-525 A produced the opposite effect. Paraoxon and p-nitrophenol from parathion were decreased by cimetidine. Our results strongly suggest that parathion itself is largely responsible of its toxicity and the inhibition of its metabolism is harmful rather than beneficial.


Subject(s)
Cimetidine/pharmacology , Parathion/toxicity , Phenobarbital/pharmacology , Animals , Drug Synergism , Liver/metabolism , Male , Parathion/antagonists & inhibitors , Parathion/metabolism , Proadifen/pharmacology , Rats , Rats, Inbred Strains
20.
Haemostasis ; 8(3-5): 252-65, 1979.
Article in English | MEDLINE | ID: mdl-389758

ABSTRACT

Prostacyclin and thromboxane A2 are products of arachidonic acid which play a role in the regulation of haemostatic plug and thrombus formation. Aspirin inhibits the synthesis of both compounds but is more active in blocking TXA2 formation; based on this, aspirin is suggested to have an anti-thrombotic effect. Other possible approaches to the development of anti-thrombotic drugs are discussed.


Subject(s)
Blood Platelets/physiology , Epoprostenol/metabolism , Prostaglandins/metabolism , Thrombosis/physiopathology , Thromboxane A2/metabolism , Thromboxanes/metabolism , Animals , Aspirin/pharmacology , Blood Platelets/metabolism , Dose-Response Relationship, Drug , Humans , Platelet Aggregation , Thrombosis/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...