RESUMEN
The likely effect of oral and subcutaneous meperidine on maximal electroshock seizure (MES) in mice was studied. Convulsive current fifty (CC50) was assessed to be 46m A, an electrical pulse causing seizure in 50% of test animals. Doses of 15, 30, 60, or 120 mg/kg meperidine given orally or subcutaneously increased the convulsion threshold of MES as evidenced by a significant dose-dependent reduction of MES below control value (p < .05). An initial hyperactivity reaction that was worsened by noisy and tactile stimuli and tail erection followed by sedation was observed after s.c. injection of 60 or 120 mg/kg meperidine. No significant difference was found between meperidine-induced reductions of control MES values obtained one and two hours after oral doses; the depressed MES values obtained one hour after oral administration of meperidine were significantly different and more powerful than those obtained two hours after s.c. drug administrations (p < .05). Combining previous literature information with the present results, we conclude that such an effect of meperidine can be attributed to cerebellar stimulation.
Asunto(s)
Meperidina/farmacología , Narcóticos/farmacología , Convulsiones/prevención & control , Administración Oral , Animales , Corteza Cerebelosa/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Electrochoque , Femenino , Inyecciones Subcutáneas , Masculino , Meperidina/administración & dosificación , Meperidina/metabolismo , RatonesRESUMEN
The direct cardiac effects of morphine, alfentanil, ketamine, etomidate, thiopentone, midazolam and propofol were measured in isolated Wistar rat hearts. Experiments were performed using a multiple columnar Langendorff apparatus and the hearts were perfused with a modified Tyrode solution under constant pressure. Each drug was applied from a different column in rising concentrations at 5-min intervals. Dose ranges were chosen to compare effects at sub-clinical, clinically relevant and more than clinical concentrations. Six rat hearts were chosen at random for each drug. Only thiopentone reduced contractile force at a clinically relevant concentration: measured as g contractility per g heart weight-1 (mean +/- standard deviation), base-line contractility was 8.8 +/- 2.4, and contractility at 10(-4) mol litre-1 thiopentone was 7.1 +/- 1.5 (P < 0.01). Alfentanil was the only drug to have no significant effect on the isolated heart at any concentration. Propofol was not cardiodepressant at clinically relevant concentrations, but had a lower therapeutic range than the other drugs.
Asunto(s)
Analgésicos Opioides/farmacología , Anestésicos Intravenosos/farmacología , Corazón/efectos de los fármacos , Alfentanilo/administración & dosificación , Alfentanilo/farmacología , Analgésicos Opioides/administración & dosificación , Anestésicos Disociativos/administración & dosificación , Anestésicos Disociativos/farmacología , Anestésicos Intravenosos/administración & dosificación , Animales , Circulación Coronaria/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Etomidato/administración & dosificación , Etomidato/farmacología , Femenino , Fentanilo/administración & dosificación , Fentanilo/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Ketamina/administración & dosificación , Ketamina/farmacología , Masculino , Midazolam/administración & dosificación , Midazolam/farmacología , Morfina/administración & dosificación , Morfina/farmacología , Contracción Miocárdica/efectos de los fármacos , Propofol/administración & dosificación , Propofol/farmacología , Distribución Aleatoria , Ratas , Ratas Wistar , Tiopental/administración & dosificación , Tiopental/farmacologíaRESUMEN
1. The aim of this study was to investigate the possible anticonvulsant effect of a dihydropyridine calcium antagonist, isradipine, which easily crosses the blood-brain barrier displaying high affinity and specificity for the brain L-type voltage-sensitive calcium channel, on maximal electroshock seizures in mice. 2. Isradipine at i.p. doses of 2.5 mg/kg and 5.0 mg/kg was found to cause a statistically significant increase in the convulsion threshold of maximal electroshock seizures in a dose-dependent manner (P = 0.047 and P = 0.022, respectively). 3. It was concluded that the mode of action of the anticonvulsant effect of isradipine is related to blockade of the intraneuronal calcium currents, which play an important role in epileptic activity.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Barrera Hematoencefálica , Bloqueadores de los Canales de Calcio/uso terapéutico , Isradipino/uso terapéutico , Convulsiones/tratamiento farmacológico , Animales , Anticonvulsivantes/farmacocinética , Bloqueadores de los Canales de Calcio/farmacocinética , Evaluación Preclínica de Medicamentos , Electrochoque , Femenino , Isradipino/farmacocinética , Masculino , Ratones , Convulsiones/etiologíaRESUMEN
In open heart surgery it is very important to protect the heart during the ischaemic period in terms of mortality and morbidity. Many different cardioplegic solutions are in clinical use without being tested experimentally. In this study we intended to investigate the effects of albumin addition to St. Thomas Hospital cardioplegic solution on cardiac protection to ischaemia. Rat hearts were isolated and perfused in Langendorff apparatus (n = 6 for each group). After the stabilisation period, the hearts in the control group were arrested with St. Thomas Hospital cardioplegic solution for 3 min then subjected to 30 min of global ischaemia in cardioplegic solution, this is followed by reperfusion for 10 min. In albumin groups, the experimental protocol was the same but 2.25%, 4.5% or 9% human albumin was added to the cardioplegic solution. All of the hearts were compared for their pre-ischaemic and post-ischaemic contractility, heart rate, coronary flow, LDH and CK enzyme leakage, and wet/dry weight ratio values. The contraction, heart rate (P < 0.01 for both), and coronary flow (only for the 9% albumin group, P < 0.05) values in the albumin group were less than the control group during the reperfusion period. There was no difference between groups in LDH, and CK leakage, and wet/dry weight ratio. The circulation of ischaemic hearts in the albumin group were diminished, possibly due to protein precipitation. This condition negatively affected the performance of the heart. The fact that there is no difference in enzyme leakage and wet/dry weight ratio, indicates that this event is not irreversible.
Asunto(s)
Albúminas/toxicidad , Soluciones Cardiopléjicas/toxicidad , Daño por Reperfusión Miocárdica/inducido químicamente , Animales , Bicarbonatos/toxicidad , Cloruro de Calcio/toxicidad , Circulación Coronaria/efectos de los fármacos , Femenino , Humanos , Técnicas In Vitro , Magnesio/toxicidad , Masculino , Contracción Miocárdica/efectos de los fármacos , Isquemia Miocárdica/tratamiento farmacológico , Isquemia Miocárdica/etiología , Miocardio/enzimología , Perfusión , Cloruro de Potasio/toxicidad , Ratas , Ratas Wistar , Cloruro de Sodio/toxicidadRESUMEN
This study was undertaken to compare aqueous humor penetration of topical 0.3% ciprofloxacin, 0.3% norfloxacin and 0.3% ofloxacin in 63 patients undergoing cataract surgery. The patients were divided into two groups. Group 1 (long-term treatment) involved 30 patients undergoing cataract extraction who received either 0.3% ciprofloxacin, 0.3% norfloxacin or 0.3% ofloxacin topical drops. Each patient was preoperatively given a single drop per hour six times. At the time of surgery, 0.1 ml aqueous fluid was aspirated from the anterior chamber and immediately stored at -70 degrees C. Topically applied ciprofloxacin, ofloxacin and norfloxacin achieved mean aqueous humor levels of 2.80 +/- 1.07, 2.95 +/- 1.19 and 1.50 +/- 0.48 micrograms/ml respectively. There was no statistically significant difference in intraocular mean aqueous levels of ciprofloxacin versus ofloxacin. Topical ciprofloxacin and ofloxacin achieved mean aqueous humor levels significantly higher than norfloxacin (p < 0.001 and p < 0.0008 respectively). Group 2 (short-term treatment) involved 33 patients undergoing cataract extraction who received 0.3% ciprofloxacin, 0.3% ofloxacin and 0.3% norfloxacin topical drops. These patients were given one drop at 90 minutes and one drop 30 minutes preoperatively. At the time of surgery, 0.1 ml aqueous fluid was aspirated from the anterior chamber and immediately stored at -70 degrees C. Topically applied ciprofloxacin, ofloxacin and norfloxacin achieved mean aqueous humor levels of 1.11 +/- 0.50, 1.50 +/- 0.62 and 1.20 +/- 0.43 micrograms/ml respectively. There was no statistically significant difference in intraocular mean aqueous humor levels of ofloxacin versus norfloxacin and ciprofloxacin versus norfloxacin. Topical ofloxacin achieved a significantly higher mean aqueous humor level than ciprofloxacin (p < 0.03). All levels were above the minimum inhibitory concentrations of ciprofloxacin, ofloxacin and norfloxacin for most of the sensitive organisms.
Asunto(s)
Antiinfecciosos/uso terapéutico , Profilaxis Antibiótica , Humor Acuoso/efectos de los fármacos , Extracción de Catarata , Ciprofloxacina/uso terapéutico , Norfloxacino/uso terapéutico , Ofloxacino/uso terapéutico , Administración Tópica , Anciano , Anciano de 80 o más Años , Antiinfecciosos/administración & dosificación , Humor Acuoso/metabolismo , Ciprofloxacina/administración & dosificación , Ciprofloxacina/metabolismo , Infecciones del Ojo/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Norfloxacino/administración & dosificación , Norfloxacino/metabolismo , Ofloxacino/administración & dosificación , Ofloxacino/metabolismo , Soluciones OftálmicasRESUMEN
Cardiac transplantation is a prominent development in the treatment of patients with severe cardiac diseases. If it is not possible to transplant the heart immediately after removing it from the donor, procedures for preparing, protecting, storing and transferring of the heart constitute a major portion of this study. Selecting the best method among those used for cardioprotection is still been debated. This experimental study investigated whether isocolloidoosmotic solution in addition to St. Thomas Hospital cardioplegic solution would give better cardioprotection. Wistar rat hearts were isolated and perfused by the Langendorff method (n = 6 for each group). In the control group after stabilisation, the hearts were arrested while perfused with St. Thomas Hospital cardioplegic solution for 3 min, then they were placed in cardioplegic solution at 4 degrees C for 6 h. Afterwards the hearts were reperfused. In the experimental groups, modified gelatin fluid (30 g/l) or HES 200/0.5 (50 g/l) or dextran 70 (25 g/l) was added to the cardioplegic solution. Maximum contractility, +dF/dtmax, -dF/dtmax, heart rate, contractility rate product, coronary flow and lactate dehydrogenase, creatine phosphokinase enzyme leakage were measured in all groups during pre-ischemic and post-ischemic periods (10 min after reperfusion). At the end of each experiment, the hearts were weighted and tissue levels of lipid peroxide, expressed in terms of thiobarbituric acid reactive substances, malondialdehyde, glutathione (an important intracellular antioxidant) and ATP were measured. Non-ischemic tissue levels of malondialdehyde, glutathione and ATP were also measured in another group (n = 6). There was no statistically significant difference among the simultaneous experimental and control groups in any criteria evaluated (P > 0.05). The addition of synthetic colloids to the standard cardioplegic solution did not provide further protection except for the gelatin group in which recovered contractile force was not significantly different from the group's initial values. This effect may be explained by its degradation to amino acids which may play a substrate role.
Asunto(s)
Soluciones Cardiopléjicas/farmacología , Corazón , Preservación de Órganos/métodos , Adenosina Trifosfato/metabolismo , Animales , Bicarbonatos/farmacología , Cloruro de Calcio/farmacología , Coloides , Circulación Coronaria/efectos de los fármacos , Creatina Quinasa/metabolismo , Femenino , Gelatina , Glutatión/metabolismo , Técnicas In Vitro , L-Lactato Deshidrogenasa/metabolismo , Magnesio/farmacología , Masculino , Malondialdehído/metabolismo , Contracción Miocárdica/efectos de los fármacos , Isquemia Miocárdica/metabolismo , Reperfusión Miocárdica , Miocardio/enzimología , Miocardio/metabolismo , Cloruro de Potasio/farmacología , Ratas , Ratas Wistar , Cloruro de Sodio/farmacologíaRESUMEN
The tear pharmacokinetic profiles of 0.3% ciprofloxacin, 0.3% ofloxacin, and 0.3% norfloxacin ophthalmic solutions after a single drop topically administrations in the eyes of 30 healthy volunteers were evaluated. Tear samples collected at 30, 120, 180, and 240 minutes, were analyzed for drug concentrations by high performance liquid chromatography (HPLC) with fluorometric detection. Topically applied ciprofloxacin, ofloxacin, and norfloxacin achieved the mean tear concentrations (mean +/- SD) of 11.28 +/- 6.98, 6.52 +/- 4.06, and 13.28 +/- 8.78 micrograms/g at 30 min, and then fell to 3.52 +/- 1.30, 4.82 +/- 1.80, and 5.79 +/- 4.80 micrograms/g at 240 min, respectively. Topical norfloxacin achieved mean tear level significantly higher than ofloxacin at 30 min (p = 0.031). There were no statistically significant differences in the mean tear levels of ciprofloxacin versus ofloxacin (at 30, 120, 180, and 240 min), ciprofloxacin versus norfloxacin (at 30, 120, 180, and 240 min) and ofloxacin versus norfloxacin (at 120, 180, and 240 min). However, the mean tear levels, 240 min after dosing ciprofloxacin and norfloxacin, fell to the statistically significant concentrations (p = 0.02 and p = 0.01, respectively). But, it is concluded that concentrations of ciprofloxacin, ofloxacin, and norfloxacin in tears were still significantly greater than the minimum inhibitory concentrations for the most sensitive organisms, 240 min after a single drop application.
Asunto(s)
Antiinfecciosos/farmacocinética , Ciprofloxacina/farmacocinética , Norfloxacino/farmacocinética , Ofloxacino/farmacocinética , Lágrimas/metabolismo , Administración Tópica , Adulto , Antiinfecciosos/administración & dosificación , Cromatografía Líquida de Alta Presión , Ciprofloxacina/administración & dosificación , Ojo/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Norfloxacino/administración & dosificación , Ofloxacino/administración & dosificación , Soluciones Oftálmicas , Espectrofotometría Ultravioleta , Lágrimas/químicaRESUMEN
A simple HPLC assay was evaluated for analysis of ofloxacin in biological fluids. Mobile phase contained methanol (40%) and phosphate buffer (pH 3.5, 60 mmol/l) and a common C18 column was used. Detection was set at 280 nm (UV). Biological fluids (50 microliters) were prepared for assay by protein precipitation with acetonitrile (1/1, vol/vol). The assay is linear from 2000 to 10 ng/ml and sensitive to 10 ng/ml. The mean recovery of ofloxacin from serum was 99.4%. The coefficient of variation was < or = 4.0% for same-day precision and < or = 6.8% for assay-to-assay precision. Because the assay requires only small specimens volumes and minimal sample preparation, this assay provides a simple to use, sensitive and specific method for quantification of ofloxacin in biological fluids.
Asunto(s)
Ofloxacino/análisis , Humor Acuoso/química , Cromatografía Líquida de Alta Presión/métodos , Humanos , Técnicas In VitroRESUMEN
Twenty-two subjects complaining of cough, chest tightness and/or shortness of breath with normal chest radiograph and normal pulmonary function test results were challenged with methacoline. Venous histamine levels were measured before and just after methacoline challenge. For comparison, a single blood sample was obtained from 10 normal subjects. Blood histamine levels were significantly higher in subjects with respiratory symptoms regardless of methacoline challenge being positive or negative (p less than 0.001). After methacoline challenge, blood histamine increased significantly in methacoline challenge positive group (p less than 0.05). Thereafter, terfenadine, a H1 antagonist, 120 mg/day were given to patients for one month. After terfenadine therapy, there was a subjective improvement of symptoms, methacoline provocation dose (PD20) increased and there was no significant change in blood histamine level. It is concluded that nonspecific challenge increases blood histamine levels and blood histamine levels seems to be a sensitive index of bronchial hyperreactivity in subjects with respiratory symptoms of unknown origin and that terfenadine is effective in the treatment of bronchial hyperreactivity.
Asunto(s)
Hiperreactividad Bronquial/sangre , Histamina/sangre , Terfenadina/farmacología , Adulto , Hiperreactividad Bronquial/tratamiento farmacológico , Hiperreactividad Bronquial/fisiopatología , Pruebas de Provocación Bronquial , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Masculino , Flujo Espiratorio Medio Máximo/efectos de los fármacos , Cloruro de Metacolina , Capacidad Vital/efectos de los fármacosRESUMEN
The bronchodilator, respiratory center and respiratory muscle effects of oral sustained release theophylline are investigated with a placebo controlled double-blind study in 34 patients with chronic obstructive lung disease (COLD). The first 3 days were a theophylline washout period and the patients did not receive theophylline and on the 4th day, serum theophylline concentration was negligible. Initial pulmonary function tests were performed. Twenty-four of the patients took 350 mg oral sustained release theophylline twice a day. Ten of the patients were given placebo. On day 7, serum theophylline concentrations of the study group were in therapeutic doses and the tests were repeated. Bronchodilator effect was assessed by spirometry, flow-volume loops and measuring airway resistance (Raw). Respiratory muscle function was assessed by measuring maximal inspiratory (PImax) and expiratory pressures (PEmax) and the effect on respiratory center was evaluated by minute ventilation, mouth occlusion pressure index and inspiratory duty ratio. Forced vital capacity in one second (p less than 0.001), maximal mid expiratory flow rate (p less than 0.05), maximal expiratory flow at 50 percent of vital capacity (p less than 0.001), maximal inspiratory pressure (p less than 0.01) increased, while airway resistance (p less than 0.05) decreased significantly. Mouth occlusion pressure and minute ventilation mouth occlusion pressure index did not change after theophylline therapy. In placebo group, there was no significant change in airway obstruction assessed by spirometry and flow volume loops or in respiratory muscle function assessed by maximal respiratory pressures. It is therefore, concluded that oral sustained release theophylline has a bronchodilator effect in irreversible chronic obstructive lung disease, increases respiratory muscle function, but in therapeutic doses has no effect on respiratory center.
Asunto(s)
Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Teofilina/uso terapéutico , Administración Oral , Adulto , Anciano , Preparaciones de Acción Retardada , Método Doble Ciego , Humanos , Persona de Mediana Edad , Centro Respiratorio/efectos de los fármacos , Pruebas de Función Respiratoria , Músculos Respiratorios/efectos de los fármacos , Músculos Respiratorios/fisiopatología , Espirometría , Teofilina/administración & dosificación , Teofilina/sangreRESUMEN
Our study has clearly shown that the oral administration of choline ascorbate, which contains approximately 500 mg of ascorbic acid to the volunteers causes an increase in the blood levels of ascorbic acid. This increase is statistically significant (p less than 0.01) compared with the basal level each time. In the control group, vitamin C tablet also causes an increase in the blood level of ascorbic acid. However, this increase is less than that of the test group. Our results indicate that ascorbic acid, as a part of choline ascorbate molecule, reaches the blood circulation without losing its activity.
Asunto(s)
Ácido Ascórbico/farmacología , Administración Oral , Adulto , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/sangre , Femenino , Humanos , MasculinoRESUMEN
The aim of this study was to determine the possible effect of propranolol, a beta-adrenoceptor blocker, on maximal electroshock seizures (MES) in mice. It was found that doses of 5, 10 and 20 mg/kg propranolol caused an increase in the convulsion threshold of maximal electroshock seizures (MES) proportional to the dose and, that the mode of the anticonvulsant action of propranolol used doses in this study is related to membrane stabilization.