RESUMEN
Previous studies have demonstrated that enalapril and verapamil seem to attenuate the cyclosporine nephrotoxicity. However, the mechanisms have not been completely understood, especially on molecular events. The aim of this study was to examine the effect of individual or combined treatment on osteopontin, TGF-beta, endothelin-1 and procollagen alpha 1(I) mRNA expressions. Enalapril (50 mg/L in drinking water) and verapamil (0.5 mg/kg/day, subcutaneously), alone or in combination, were administered to rats with chronic cyclosporine nephrotoxicity (cyclosporine, 25 mg/kg/day, subcutaneously) (n = 5 each). Five rats treated with olive oil vehicle were used as control. After 4 weeks, biochemical parameters were measured, and renal cortical mRNA levels were evaluated by Northern blot analysis. Cyclosporine reduced renal creatinine clearance significantly and induced renal cortical osteopontin, TGF-beta, endothelin-1 and procollagen alpha 1(I) gene expressions around 13.5 +/- 1.3, 2.4 +/- 0.2, 1.5 +/- 0.1, 1.9 +/- 0.1 folds, respectively. Individual treatment with enalapril or verapamil significantly suppressed the osteopontin and TGF-beta mRNA expression, but not endothelin-1 and procollagen alpha 1(I). Combined treatment also inhibited the osteopontin and TGF-beta mRNA expression but there was no difference between combined and individual treatment. In conclusion, enalapril or verapamil significantly blunted the cyclosporine-induced osteopontin and TGF-beta gene expressions. However, combined treatment did not show any additive effect.
Asunto(s)
Masculino , Ratas , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Bloqueadores de los Canales de Calcio/uso terapéutico , Ciclosporina/efectos adversos , Quimioterapia Combinada , Enalapril/uso terapéutico , Enalapril/administración & dosificación , Endotelina-1/metabolismo , Endotelina-1/genética , Regulación de la Expresión Génica/efectos de los fármacos , Inmunosupresores/efectos adversos , Corteza Renal/metabolismo , Nefritis/tratamiento farmacológico , Nefritis/inducido químicamente , Procolágeno/metabolismo , Procolágeno/genética , ARN Mensajero/análisis , Ratas Wistar , Sialoglicoproteínas/metabolismo , Sialoglicoproteínas/genética , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/genética , Verapamilo/uso terapéutico , Verapamilo/administración & dosificaciónRESUMEN
Time to antagonism induced by pyridostigmine from different levels of neuromuscular blockade was evaluated in 45 patients anesthetized with nitrous oxide, fentanyl, and vecuronium. Neuromuscular blockade, as monitered by train-of-four count, was antagonized at varing degrees of spontaneous recovery. Train-of-four ratio was used as an index of the ability of the patients to maintain adequate spontaneous ventil'ation, and maximum inspiratory pressure as an index of the ability of the patients to protect their airways against aspiration or obstruction. We measured time from administration of pyridostigmine to train-of-four ratio of 70% indicating the recovery of the ability to maintain adquate spontaneous ventilation, and time to maximum inspiratory pressure of -45 cmH2O indicating the recovery of the ability to protect the patients airways against aspiration or obstruction. For a train-of-four count level of 0-1, reversal time to train-of-four ratio of 70% was 22.73+/-3.00 minutes and that to maximum inspiratory pressure of -45 cmH2O was 30.33+/-2.69 minutes. For a train-of-four count level of 2- 3, reversal time to train-of-four ratio of 70% was 17.33+/-3.18 minutes and that to maximum inspiratory pressure of -45cmH2O was 22.27+/-2.91 minutes. For a train-of-four count level of 4, reversal time to train-of-four ratio of 70% was 8.40+/-3.58 minutes and that to maximum inspiratory pressure of -45 cmH2O was 14.60+/-3.11 minutes. It is concluded that the more shallow is the neuromuscular blockade, the more rapid and the safer is the reversal of neuromuscular blockade, although the dose of reversal drug was determined according to the depth of neuromuscular blockade. Moreover, it should take more than 30 minutes to antagonixe profaund neuromuacular hlock- ade induced by vecuronium to such a degree that not only can the patients maintain adequate spontaneous ventilation, but they can maintain the airways and protect them against aspiration as well.
Asunto(s)
Humanos , Fentanilo , Bloqueo Neuromuscular , Óxido Nitroso , Bromuro de Piridostigmina , Bromuro de Vecuronio , VentilaciónRESUMEN
Intrathecal meperidine produces a profound analgesia, because meperidine has a high lipid solubility and a structure similar to local anesthetics. This study was undertaken to evaluate the anesthetic effect and complications of intrathecal meperidine anesthesia and the effect of added epinephrine. Two percent meperidine 30 mg (Group I) and 2% meperidine 30 mg with 0.3 mg epinephrine (Group II) in 20% D/W were injected intrathecally in each of 30 cases scheduled for simple and short surgical procedures. The results are as follows: 1) Systolic blood pressure and pulse rate decreased significantly from 10 minutes to 1 hour after intrathecal meperidine injection, compared with the value before anesthetic administration, but did not require special medical treatment. 2) The onset time of block of T, sensory dermatome in the meperidine injection group (Group 1) and the added epinephrine mixed injection group (Group II), were 5.3+/-1.4 minutes and 6.6+/-2.1 minutes, and duration were 58.5+/-10.5 minutes and 74.1+/-16.4 minutes respectively. Therefore, the onset time of motor nerve blok were 5.5+/-2.6 minutes and 8.9+/-1.6 minutes, and then their duration were 65.7+/-11.4 minutes and 79.7+/-13.4 minutes respectively. 3) PaO decreased and PaCO2 increased significantly 1 hour after meperidine injection without any serious problem. 4) Complications, such as nausea, pruritus and urinary retention, were observed in many patients without any serious problem.
Asunto(s)
Humanos , Analgesia , Anestesia , Anestésicos , Anestésicos Locales , Presión Sanguínea , Epinefrina , Frecuencia Cardíaca , Meperidina , Náusea , Prurito , Solubilidad , Retención UrinariaRESUMEN
The hemodynamic changes during the induction and maintenance of anesthesia, the rapidity of postanesthetic recovery, and side effects were measured and compared in 60 patients receiving either morphine, meperidine, or fentanyl as supplements to balanced anesthesia. Blood pressure, measured through an indwelling arterial catheter, was recorded continuously, as were electrocardiogram and heart rates. The narcotics, made up in equipotent concentration, were given as indicated by hemodynamic and clinical signs. After induction, hemodynamic reponses to laryngoscopy and intubation were more suppressed in patients receiving fentanyl than in patients receiving morphine or meperidine. Meperidine, unilke morphine or fentanyl, significantly increased heart rates. Intraoperatively, mean arterial blood pressure and rate-pressure product were lowest in patients receiving fentanyl. Because of the increase in blood pressure, hart rate, or both to greater than 20% above preanesthetic values, supplementation with a potent inhalatinal agent was necessary, in 25%, 10%, and 10% of the patients given meperidine, morphine, and fentanyl, respectively. Side effects, including histamine release accompanied by tachycardia and hypotension, were most frequent and most severe in patients who received meperidine. Postoperatively, there was more rapid recovery of consciousness with fentanyl than meperidine and morphine and the incidence of postoperative respiratory depression was least with fentanyl. The authors concluded that a moderate dose of fentanyl was a better supplement to balanced anesthesia than morphine or meperidine.