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1.
Eur Endod J ; 3(2): 73-76, 2018.
Article in English | MEDLINE | ID: mdl-32161859

ABSTRACT

OBJECTIVE: The current pulp diagnostic techniques based on subjective patient response to electrical or thermal stimuli are unable to assess tooth vascularization, which is a true indicator of pulp vitality. The present study evaluates thermography as a pulp vitality test, assessing tooth recovery following thermal stimulation. METHODS: A model simulating intrapulpal circulation was developed. Superficial thermographic measurements were obtained from teeth with and without elevation of the intracoronal temperature before and after applying thermal stress with cold. The data were analyzed using analysis of variance (ANOVA), and the level of significance was set at P<0.05. RESULTS: The model obtained could help differentiate between teeth with and without simulated pulp circulation. Recovery following application of thermal stress showed significant differences between the two types of teeth. CONCLUSION: Thermography has the potential to be used as a diagnostic tool for the vascularity status of the dental pulp.

2.
Biol Sport ; 32(3): 219-23, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26424925

ABSTRACT

The use of graduated compression stockings (GCS) in sport has been increasing in the last years due to their potential positive effects for athletes. However, there is little evidence to support whether these types of garments actually improve cardiorespiratory performance. The aim of this study was to examine the cardiorespiratory responses of GCS during running after three weeks of regular use. Twenty recreational runners performed three tests on different days: test 1) - a 5-min maximal effort run in order to determine the participants' maximal aerobic speed; and tests 2) and 3) - a fatigue running test of 30 minutes at 80% of their maximal aerobic speed with either GCS or PLACEBO stockings at random. Cardiorespiratory parameters (minute ventilation, heart rate, relative oxygen consumption, relative carbon dioxide production, ventilatory equivalents for oxygen and carbon dioxide, and oxygen pulse) were measured. Before each test in the laboratory, the participants trained with the randomly assigned stockings (GCS or PLACEBO) for three weeks. No significant differences between GCS and PLACEBO were found in any of the cardiorespiratory parameters. In conclusion, the present study provides evidence that running with GCS for three weeks does not influence cardiorespiratory parameters in recreational runners.

3.
Rev. chil. cir ; 60(5): 418-423, oct. 2008. tab
Article in Spanish | LILACS | ID: lil-549986

ABSTRACT

Introducción: A pesar del gran avance que ha experimentado la cirugía laparóscopica en los últimos años, no ha sido hasta hace dos, cuando el Programa Nacional de la Especialidad en Cirugía General y Digestivo se ha hecho eco de esta evolución y en su formato ha especificado el número y el tipo de intervenciones que debería efectuar un residente durante su período de formación para adquirir la destreza quirúrgica necesaria en el dominio de esta nueva técnica quirúrgica. Objetivos: Evaluar la adecuación de la docencia en cirugía laparóscopica en nuestro hospital en relación al Programa Nacional de la Especialidad y al programa específico del Hospital Ramón y Cajal, examinando el número de cirugías laparoscópicas en las que el residente ha participado tanto como cirujano como ayudante durante el período comprendido entre 2000-2005. Resultados: La primera cirugía laparóscopica que realiza el residente de cirugía general es la colecistectomía, y ésta se realiza en general en el 2º año de residencia. Un residente de 5º año, cuando termina su formación, ha realizado una media de 49 colecistecomías laparoscópicas como primer cirujano y ha ayudado a una media de 56,4 cirugías (incluyendo cirugía laparóscopica avanzada). Conclusión: No existe consenso en la literatura acerca de cuál es el número ni el tipo de cirugías laparoscópicas que debe realizar el residente tras acabar su período de formación. En base al Programa Nacional de la Especialidad y al del Hospital Ramón y Cajal, pensamos que nuestros residentes reciben una correcta formación en cirugía laparóscopica.


Introduction: In spite of significant advancements in laparoscopic surgery in the last years, it was two years ago when the Spanish General Surgery Programme showed this evolution, and specified the number and the kind of interventions a resident should realize in his formation period to obtain the necessary ability in this new surgical technique. Purpose: Evaluate the training of residents in laparoscopic surgery in relation to the Spanish General Surgery Programme, and to the Ramón y Cajal specific Programme, investigating the number of laparoscopic surgeries in which the resident took part as surgeon or assistant during the period of 2000-2005. Results: The first laparoscopic surgery realized by the resident is the cholecistectomy, generally in the second year of residence. A resident of fifth year, when finished his formation, has realized approximately 49 laparoscopic cholecistectomies as first surgeon, and has assisted 56,5 surgeries (advanced laparoscopic surgery is included) Conclusion: There is no assent in the literature about the number and the kind of laparoscopic surgeries a resident has to realize in his formation period. In relation to the Spanish General Surgery Programme and the Ramón y Cajal Programme, we think our residents received a correct training in laparoscopic surgery.


Subject(s)
Humans , Educational Technology , Internship and Residency , Laparoscopy , Digestive System Surgical Procedures/education , Clinical Competence , Specialties, Surgical/education , Spain
4.
Rev. chil. cir ; 60(3): 246-248, jun. 2008. ilus
Article in Spanish | LILACS | ID: lil-504099

ABSTRACT

Las lesiones quísticas localizadas en la línea media de la glándula prostética presentan una incidencia difícil de estimar, debido a que la mayoría son asintomáticas y suelen ser un hallazgo casual durante el estudio de otra patología urológica. Presentamos el caso de un varón de 85 años que en el transcurso de un episodio de retención aguda de orina es diagnosticado de un quiste de retención prostético, y realizamos una revisión de la literatura.


The incidence of medial prostatic cysts is unknown, since most of them are asymptomatic, and usually appear as an incidental finding during the study of other urological disease. We report an 85 years oíd man with a urinary obstruction. Rectal palpation disclosed a mass that was adjacent to the prostate. Magnetic resonance showed a cystic lesión of the right seminal vesicle. The cyst was drained, obtaining 250 mi of fluid and urinary obstruction subsided. After three months of follow up, the patient remains asymptomatic.


Subject(s)
Humans , Male , Aged, 80 and over , Prostatic Diseases/surgery , Prostatic Diseases/diagnosis , Cysts/surgery , Cysts/diagnosis , Urinary Retention/etiology , Prostatic Diseases/complications , Cysts/complications
5.
Rev. chil. cir ; 59(5): 379-381, oct. 2007. ilus
Article in Spanish | LILACS | ID: lil-477314

ABSTRACT

Presentamos el caso clínico de una mujer de 54 años que consulta por una gran tumoración infraclavicular de dos años de evolución. Los resultados de la punción-aspiración de la lesión son compatibles con un tumor de células granulares. La lesión es extirpada y el estudio histológico confirma el diagnóstico. Realizamos una revisión sobre el origen del tumor, su biología, histología, diagnóstico y tratamiento.


The case reported is a 54 years-old woman with a great mass below the clavicle for two years. The results of fine-needle aspiration biopsy were compatible with granular cell tumour. The mass was removed and the histopathological study confirmed the diagnosis. The present report reviews some aspects about the origin, biology, histology, diagnosis and treatment of this tumour.


Subject(s)
Humans , Female , Middle Aged , Clavicle , Granular Cell Tumor/surgery , Granular Cell Tumor/pathology , Treatment Outcome
6.
Rev. chil. cir ; 59(3): 223-228, jun. 2007. ilus
Article in Spanish | LILACS | ID: lil-465001

ABSTRACT

Introducción: Aunque el cáncer de mama metastatiza con mayor frecuencia en ganglios linfáticos, hueso, pulmón e hígado, también se puede extender hacia el tracto gastrointestinal, peritoneo y órganos ginecológicos. Material y Método: Describimos tres casos de carcinomatosis peritoneal secundaria a la diseminación metastásica de un carcinoma lobulillar infiltrante de mama. En los tres casos el diagnóstico se hizo varios años después del descubrimiento del tumor primario y en dos de ellos se observa remisión de la enfermedad al año y cuatro años respectivamente tras la administración de quimio y hormonoterapia postoperatoria. Conclusión: La carcinomatosis peritoneal en cáncer de mama es poco frecuente, pero cuando aparece casi siempre es secundaria a un carcinoma lobulillar infiltrante con receptores hormonales positivos. Los síntomas son inespecíficos y normalmente existe un intervalo largo desde el diagnóstico inicial del tumor, de ahí que en muchos casos sea difícil diferenciar entre un tumor primario de la cavidad peritoneal y la presencia de metástasis de un carcinoma de mama, no solo a nivel clínico, sino también histológico. El diagnóstico resulta fundamental para el oncólogo, pues con tratamiento quimio y hormo-noterápico se han descrito remisiones parciales o completas del tumor durante períodos prolongados de tiempo.


Subject(s)
Female , Middle Aged , Humans , Carcinoma, Lobular/pathology , Carcinoma/diagnosis , Carcinoma/secondary , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/secondary , Breast Neoplasms/pathology , Carcinoma/therapy , Neoplasm Metastasis/pathology , Peritoneal Neoplasms/surgery
7.
Inorg Chem ; 44(16): 5770-7, 2005 Aug 08.
Article in English | MEDLINE | ID: mdl-16060629

ABSTRACT

Reaction between cationic units of carboxylate-bridged diruthenium complexes [Ru(2)(mu-O(2)CR)(4)](+) (R = Me, CMePh(2), CMe(3), CH(2)CH(2)OMe, C(Me)=CHEt, C(6)H(4)-p-OMe, Ph) and tetrabutylammonium perrhenate gives complexes with different arrangements in the solid state. Thus, the compounds Ru(2)(mu-O(2)CR)(4)(ReO(4)) [R = Me (1), CMePh(2) (2), CMe(3) (3), CH(2)CH(2)OMe (4), C(Me)=CHEt (5), C(6)H(4)-p-OMe (6), Ph (7)] have polymeric structures with the diruthenium units linked by perrhenate ligands in the axial positions. The structures of complexes 3.THF and 4 were established by single-crystal X-ray diffraction. The tetrahedral geometry of the ReO(4)(-) anion permits the formation of a chain close to the linearity. In contrast to the polymeric chains observed in complexes 1-7, the reaction of [Ru(2)(mu-O(2)CPh)(4)](+) with NBu(4)ReO(4) also affords the compounds Ru(2)(mu-O(2)CPh)(4)(ReO(4))(H(2)O) (8) and NBu(4)[Ru(2)(mu-O(2)CPh)(4)(ReO(4))(2)] (9) depending on the reaction conditions. The structure of 8 consists of cationic and anionic units, [Ru(2)(mu-O(2)CPh)(4)(H(2)O)(2)](+) and [Ru(2)(mu-O(2)CPh)(4)(ReO(4))(2)](-), linked by hydrogen bonds, which give a three-dimensional net. The structure of complex 9.0.5H(2)O has an anionic unit similar to that of 8, whose counterion is NBu(4)(+). The Ru-Ru bond distances are slightly longer in [Ru(2)(mu-O(2)CPh)(4)(ReO(4))(2)](-) than in the polymeric compounds Ru(2)(mu-O(2)CR)(4)(ReO(4)). The magnetic behavior owes to the existence of zero-field splitting (ZFS) and a weak antiferromagnetic coupling. The experimental data are fitted with a model that considers the ZFS effect using the Hamiltonian (D) = SDS. The weak antiferromagnetic coupling is introduced as a perturbation, using the molecular field approximation.

8.
Chemistry ; 7(18): 3890-900, 2001 Sep 17.
Article in English | MEDLINE | ID: mdl-11596931

ABSTRACT

The study of a variety of substituted sulfoxides as chiral auxiliaries in intermolecular Heck reactions of sulfinyldihydrofurans and sulfinylcyclopentenes with different iodoarenes is reported. In the presence of [Pd(OAc)2]/Ag2CO3 and a bidentate phosphine ligand, synthetically useful yields and asymmetric inductions were obtained. By far the best diastereoselectivities were obtained by the use of the palladium-coordinating O-(N,N-dimethylamino)phenylsulfinyl group. By final removal of the chiral auxiliary, these sulfoxide-stereocontrolled asymmetric Heck processes were applied to the enantioselective synthesis of 1-aryl-substituted and 1,3-diaryl-substituted dihydrofurans and cyclopentenes.

9.
Chem Commun (Camb) ; (19): 2026-7, 2001 Oct 07.
Article in English | MEDLINE | ID: mdl-12240272

ABSTRACT

A ready access to a new family of planar chiral ferrocenes, the (RFc,RS)-2-amino substituted 1-tert-butylsulfinylferrocenes, is described; in the case of the sulfonamide series enantioselectivities of up to 96% were obtained in the addition of Et2Zn to aromatic aldehydes.

10.
Inorg Chem ; 39(1): 65-70, 2000 Jan 10.
Article in English | MEDLINE | ID: mdl-11229036

ABSTRACT

The reaction of Ru2Cl(mu-O2CMe)4 with 2,4-hexadienoic and 2-methoxyacetic acids affords the compounds Ru2Cl(mu-O2CR)4 [R = CH=CHCH=CHCH3 (1), CH2OMe (2)]. The structures of both complexes have been determined by X-ray crystallography. 1 crystallizes in the triclinic space group P-1 with a = 9.264(1) A, b = 12.661(8) A, c = 12.839(5) A, alpha = 106.09(3) degrees, beta = 77.89(2) degrees, gamma = 97.73(3) degrees, and Z = 2. 2 crystallizes in the nonstandard monoclinic space group P2(1)/c with a = 12.132(4) A, b = 11.570(2) A, c = 13.674(2) A, beta = 91.18(2) degrees, and Z = 4. Complexes 1 and 2 show [Ru2(mu-O2CR)4]+ units linked by chloride ions, giving zigzag chains with Ru-Cl-Ru angles of 119.43(4) degrees and 110.11(7) degrees, respectively. The Ru-Ru bond distances are 2.2857(9) A (1) and 2.290(1) A (2). A magnetic study, in the 2-300 K temperature range, of the new compounds and the previously described Ru2Cl(mu-O2CR)4 [R = CHMe2 (3), CMe3 (4), C4H4N (5)] is described. The polymeric complexes 1 and 2 and the nonpolymeric 3-5 show a large zero-field splitting which varies from 53.9 to 68.1 cm-1. These complexes also show a weak, but not negligible, through-space intermolecular antiferromagnetic coupling not observed in the previous magnetic studies carried out on these types of compounds.

12.
Farmaco ; 52(3): 147-55, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9212449

ABSTRACT

A series of 1H-Imidazo and 1H-[1,2,3]-Triazolo fused derivatives have been obtained and tested as non peptide AII receptor antagonists. Modification of the classical biphenyl moiety to a 4-arylthienyl fragment afforded interesting activities.


Subject(s)
Angiotensin Receptor Antagonists , Imidazoles/pharmacology , Triazoles/pharmacology , Animals , Guinea Pigs , Imidazoles/chemistry , In Vitro Techniques , Molecular Structure , Rabbits , Receptors, Angiotensin/chemistry , Structure-Activity Relationship , Triazoles/chemistry
13.
J Med Chem ; 38(15): 2830-41, 1995 Jul 21.
Article in English | MEDLINE | ID: mdl-7636844

ABSTRACT

The synthesis and pharmacological activities of the four stereoisomers of methyl tetrahydrofuran-2-ylmethyl 2,6-dimethyl-4-(2'-nitrophenyl)-1,4-dihydropyridine-3,5- dicarboxylate(furnidipine) are reported. The four isomers were synthesized by a modified Hantzsch synthesis by reaction of (-)- or (+)-tetrahydrofuran-2-ylmethyl 3-aminocrotonate and methyl 2-[(2'-nitrophenyl)methylene]acetoacetate or, alternatively, by reaction of (-)- or (+)-tetrahydrofuran-2-ylmethyl 2-[(2'-nitrophenyl)methylene]acetoacetate and methyl 3-aminocrotonate. The 1:1 diastereomeric mixtures thus obtained were separated by chromatography, using poly(D-phenylglycine) as the chiral stationary phase. The enantiomeric purity of the stereoisomers was determined by a high-performance liquid chromatography-chiral stationary phase technique (HPLC-CSP). Attempts to obtain crystals of a single stereoisomer failed in different solvents, while methanol crystallization of the product obtained from (+/-)-tetrahydrofuran-2-ylmethyl 2-[(2'-nitrophenyl)methylene]acetoacetate and methyl 3-aminocrotonate yielded good-quality crystals of the most insoluble racemate which proved to be a mixture of the (SS)/(RR) enantiomers by X-ray crystallography. Conformational analysis of the stereoisomers, assuming rotation of the aryl substituent and ester groups, shows small energy differences (about 4 kcal.mol-1) between the most and the least favorable conformations. Binding studies were performed using [3H]isradipine as a reference ligand. The results showed stereospecificity of the furnidipine isomers in brain, ileum, and cardiac tissues, the (SS)- and (SR)-isomers clearly being more potent than their (RR)- and (RS)-enantiomers. The (SS)- and (SR)-isomers were also more selective on cerebral tissue when compared with ileal and cardiac preparations.


Subject(s)
Calcium Channel Blockers/chemistry , Calcium Channel Blockers/pharmacology , Dihydropyridines/chemistry , Dihydropyridines/pharmacology , Animals , Binding, Competitive , Brain/drug effects , Brain/metabolism , Calcium Channel Blockers/chemical synthesis , Chemical Phenomena , Chemistry, Physical , Crystallography, X-Ray , Dihydropyridines/chemical synthesis , Drug Evaluation, Preclinical , Guinea Pigs , Heart/drug effects , In Vitro Techniques , Isradipine/metabolism , Kinetics , Molecular Conformation , Molecular Structure , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Myocardial Contraction/drug effects , Myocardium/metabolism , Rats , Rats, Sprague-Dawley , Stereoisomerism , Structure-Activity Relationship , Tritium
14.
Bioorg Med Chem ; 2(5): 323-9, 1994 May.
Article in English | MEDLINE | ID: mdl-7922143

ABSTRACT

Several bicyclic dihydropyrimidines were synthesized and evaluated for their calcium antagonistic activities by comparison with the usual 1,4-dihydropyridine calcium antagonist reference compound nifedipine. The solid-state structure of the isopropyl 2-methyl-4-(3'-nitrophenyl)-1,4-dihydrobenzo[4,5]imidazo[1,2- a]pyrimido-3-carboxylate shows that these compounds can adopt the most important structural features of the 1,4-dihydropyridine and 1,4-dihydropyrimidine calcium channel blockers. The high-potassium depolarized rat aorta assay was used for testing the compounds as calcium channel blockers. Some compounds showed interesting vasorelaxant activity.


Subject(s)
Calcium Channel Blockers/pharmacology , Pyrimidines/pharmacology , Animals , Aorta, Thoracic/drug effects , Calcium Channel Blockers/chemical synthesis , Calcium Channel Blockers/chemistry , Crystallography, X-Ray , Drug Evaluation, Preclinical , In Vitro Techniques , Magnetic Resonance Spectroscopy , Male , Models, Molecular , Molecular Structure , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Rats , Rats, Sprague-Dawley , Vasodilator Agents/chemical synthesis , Vasodilator Agents/chemistry , Vasodilator Agents/pharmacology
16.
Eur J Pharmacol ; 243(1): 25-34, 1993 Oct 12.
Article in English | MEDLINE | ID: mdl-7504630

ABSTRACT

PCA 50941 is a novel 1,4-dihydropyridine derivative. Its vasoconstricting effects prompted a systematic comparison with the prototypic Ca2+ channel activator, Bay K 8644. The two compounds exhibit marked analogies and differences in their cardiovascular profiles. PCA 50941 exhibits a pronounced vascular over cardiac selectivity while Bay K 8644 has both potent vasoconstrictor effects and strong cardiac positive inotropic actions. PCA 50941 exhibits either poor positive inotropic effects (isolated guinea-pig atria) or clear negative inotropic effects (isolated perfused rat heart). Both compounds reduced by 10-40% the coronary flow in the perfused rat heart. However, PCA 50941 had slight vasoconstrictor effects in pig coronary arteries, causing their relaxation at nanomolar/micromolar concentrations; this contrasts with the almost pure, marked vasoconstrictor effects of Bay K 8644 in coronary arteries. In the rat aorta PCA 50941 exhibited a biphasic pattern of vasoconstriction and vasorelaxation, and in portal vein it markedly reduced the Ca(2+)-evoked contractions; Bay K 8644 behaved as a pure vasoconstrictor in these two preparations. It is concluded that the racemic compound, PCA 50941, exhibits different degrees of Ca2+ agonism and Ca2+ antagonism by acting upon 1,4-dihydropyridine receptors of different cardiovascular tissues. Its tissue selectivity and its prolonged duration of action give PCA 50941 a cardiovascular profile more favourable than that of other 1,4-dihydropyridine Ca2+ agonist existing to date.


Subject(s)
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology , Calcium Channel Agonists/pharmacology , Cardiovascular System/drug effects , Dihydropyridines/pharmacology , Thiazoles/pharmacology , Vasoconstriction/drug effects , Animals , Aorta/drug effects , Heart Atria/drug effects , In Vitro Techniques , Isradipine/metabolism , Mesenteric Arteries/drug effects , Muscles/metabolism , Nitrendipine/metabolism , Rabbits , Rats , Rats, Sprague-Dawley , Swine
17.
Eur J Pharmacol ; 235(1): 101-8, 1993 Apr 22.
Article in English | MEDLINE | ID: mdl-7686102

ABSTRACT

The intravenous (i.v.) or oral administration of the platelet-activating factor (PAF) antagonist, PCA-4248, to guinea-pigs blocked selectively the bronchoconstriction induced by PAF, as well as the accompanying thrombocytopenia and leucopenia. In addition, PCA-4248 i.v. or intratracheal (i.t.) administration blocked the bronchoconstriction caused by the i.t. instillation of PAF. As in the case of other PAF antagonists, bronchoconstriction caused by the i.t. instillation of antigen was only inhibited by PCA-4248 in guinea-pigs that did not receive a booster injection of antigen during sensitization whereas the booster injection of antigen made anaphylactic bronchoconstriction resistant to the compound. In vitro, when lungs from non-sensitized guinea-pigs were perfused with Krebs-bovine serum albumin (BSA) solution supplemented with PCA-4248, bronchoconstriction and the formation of thromboxane A2 by PAF were blocked. In this in vitro model of perfused lungs, active sensitization with a booster injection of antigen leads to bronchopulmonary hyperresponsiveness to PAF and failure of other PAF antagonists to inhibit the effects of PAF itself. Surprisingly, in lungs isolated from actively sensitized and boosted guinea-pigs, PCA-4248 blocked the effects of PAF, indicating that this compound possesses additional original properties in this model.


Subject(s)
Anaphylaxis/prevention & control , Bronchial Hyperreactivity/prevention & control , Bronchoconstriction/drug effects , Dihydropyridines/pharmacology , Platelet Activating Factor/antagonists & inhibitors , Animals , Blood Cell Count/drug effects , Dihydropyridines/administration & dosage , Female , Guinea Pigs , Histamine Release/drug effects , Immunization , In Vitro Techniques , Injections, Intravenous , Lung/drug effects , Lung/metabolism , Male , Platelet Activating Factor/pharmacology , Radioimmunoassay , Thromboxane B2/metabolism
18.
Haemostasis ; 22(4): 202-10, 1992.
Article in English | MEDLINE | ID: mdl-1468723

ABSTRACT

The effects of a new antithrombotic compound, PCA-4230, versus ticlopidine were investigated using an experimental thrombosis and vascular endothelial injury model in rats. Both PCA-4230 and ticlopidine protected rat arteries from the formation of prominent thrombi and most of microthrombi without modifying the formation of a first platelet monolayer. Neither coagulation parameters nor fibrinolysis were modified by these antithrombotic drugs. Neither PCA-4230 nor ticlopidine affected thromboxane A2 production in rats, whereas unlike PCA-4230, ticlopidine inhibited ex vivo fibrinogen binding to the fibrinogen receptor found on the platelet membrane. In conclusion, PCA-4230 and ticlopidine inhibited thrombus formation in vivo by a platelet-dependent mechanism which may be different for one or the other drug in spite of the fact that the protective effect measured in this thrombosis model is quite similar for either PCA-4230 or ticlopidine. The above-mentioned results clearly show that PCA-4230 is a new potent agent with both antivascular-damaging and antiplatelet activities, and devoid of effects on coagulation and fibrinolytic systems.


Subject(s)
Blood Platelets/metabolism , Carotid Arteries/metabolism , Dihydropyridines/pharmacology , Fibrinolytic Agents/pharmacology , Animals , Blood Platelets/drug effects , Carotid Arteries/ultrastructure , Dihydropyridines/administration & dosage , Fibrinogen/metabolism , Fibrinolytic Agents/administration & dosage , Male , Platelet Membrane Glycoproteins/drug effects , Platelet Membrane Glycoproteins/metabolism , Rats , Rats, Sprague-Dawley , Thrombosis/prevention & control , Thromboxane B2/analysis , Ticlopidine/pharmacology
19.
J Med Chem ; 33(12): 3205-10, 1990 Dec.
Article in English | MEDLINE | ID: mdl-2175357

ABSTRACT

A new series of 4-alkyl-1,4-dihydropyridines (1,4-DHP) were synthesized and evaluated for their ability to inhibit washed rabbit platelet aggregation induced by PAF-acether (1-O-hexadecyl/octadecyl-2-O-acetyl-sn-glycero-3-phosphorylcholine) and to reverse PAF-induced hypotension in anesthetized rats. Additionally, compounds were evaluated for their ability to inhibit the binding of radiolabeled PAF to its receptor on rabbit platelets. Among these compounds, 6I and 6L were the most potent and specific antagonists. At concentrations up to 100 microM, neither compound 6I nor compound 6L caused platelet aggregation nor did they inhibit platelet aggregation induced by collagen or adenosine diphosphate. Compound 6L did not show in vitro calcium channel blocker activity measured on vascular smooth muscle preparations of rabbit aorta and on [3H]nitrendipine binding assays. The compound did not show any cardiovascular effects in anesthetized rat at iv doses up to 1000 micrograms/kg, and the Ki value was 568.62 nmol. These results indicate that compound 6L is a potent and specific PAF antagonist with 1,4-dihydropyridine structure but devoid of a significant cardiovascular activity related to calcium-antagonist properties.


Subject(s)
Dihydropyridines/pharmacology , Platelet Activating Factor/antagonists & inhibitors , Platelet Membrane Glycoproteins , Receptors, G-Protein-Coupled , Adenosine Triphosphate/blood , Animals , Aorta, Thoracic/drug effects , Aorta, Thoracic/physiology , Blood Platelets/drug effects , Blood Platelets/metabolism , Blood Pressure/drug effects , Chemical Phenomena , Chemistry , Dihydropyridines/chemical synthesis , Heart Rate/drug effects , Ileum/ultrastructure , Male , Microsomes/metabolism , Molecular Structure , Muscle Contraction/drug effects , Myocardial Contraction/drug effects , Nitrendipine/metabolism , Nitrendipine/pharmacology , Platelet Activating Factor/pharmacology , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Rabbits , Rats , Rats, Inbred Strains , Receptors, Cell Surface/metabolism
20.
J Pharmacol Exp Ther ; 255(1): 28-33, 1990 Oct.
Article in English | MEDLINE | ID: mdl-2170624

ABSTRACT

PCA 4233 [2-(phenylthio)ethyl-5-ethoxycarbonyl-2,4,6-trimethyl- 1,4-dihydropyridine-3-carboxylate] and PCA 4248 [2-(phenylthio) ethyl-5-methoxycarbonyl-2, 4, 6-trimethyl-1, 4-dihydropyridine-3-carboxylate], two compounds developed from a series of 1,4-dihydropyridines that lack pharmacologic effects on voltage-operated calcium channels, were found to block selectively rabbit operated calcium channels, were found to block selectively rabbit and human platelet aggregation and secretion, and binding of [3H]-labeled platelet-activating factor (PAF) to human platelet and polymorphonuclear PAF receptors. Rabbit platelet aggregation was tested with 1.9 nM PAF, i.e., a concentration producing maximal response, and was completely blocked with 10 microM PCA 4233 and 3 microM 4248 (IC50 values, 2.55 and 1.05 microM, respectively). Human platelet aggregation in platelet-rich plasma was studied with 1 microM PAF, a concentration that caused a response comparable with that of 1.9 nM PAF in rabbit platelets. The IC50 of PCA 4248 for ATP release under these conditions was 3.6 microM. PCA 4248 behaved as a competitive and selective antagonist in [3H]serotonin secretion studies on rabbit platelets, since it displaced rightwards log dose-response curves and lacked any effect on thrombin- and ionophore A23187-induced platelet secretion. A pA2 value of 7.5 was obtained from Schild plots on [3H]serotonin secretion studies. PCA 4248 also produced a dose-dependent inhibition of [3H]PAF binding to human platelets and to human polymorphonuclear leukocytes. These data indicate that PCA 4233 and PCA 4248 belong to a new class of selective PAF-receptor antagonists.


Subject(s)
Dihydropyridines/pharmacology , Platelet Activating Factor/antagonists & inhibitors , Platelet Membrane Glycoproteins , Receptors, Cell Surface/drug effects , Receptors, G-Protein-Coupled , Animals , Blood Platelets/metabolism , Humans , In Vitro Techniques , Neutrophils/metabolism , Platelet Activating Factor/metabolism , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Rabbits , Serotonin/metabolism
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