RESUMEN
OBJECTIVE: To report the surgical experience in the management of patients with synchronous primary lung cancer and solitary brain metastasis. DESIGN: Retrospective cohort study. SETTING: Regional hospital, Hong Kong. PATIENTS: Seventeen patients with synchronous primary lung cancer and solitary brain metastasis were treated by pulmonary resection and neurosurgical intervention between 1994 and 2007. RESULTS: Median patient survival was 52 months (95% confidence interval, 9-95 months) and the 5-year survival was 27%. The univariate analysis yielded no significant prognostic factor. Four out of six patients who had lymph node metastases developed tumour recurrence. CONCLUSION: In view of encouraging survival results, aggressive therapy including pulmonary resection and neurosurgical intervention should be recommended for patients with synchronous presentation with primary lung cancer and solitary brain metastasis.
Asunto(s)
Neoplasias Encefálicas/cirugía , Neoplasias Pulmonares/cirugía , Neoplasias Primarias Múltiples/cirugía , Carcinoma Pulmonar de Células Pequeñas/cirugía , Adulto , Anciano , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/secundario , Diagnóstico por Imagen , Femenino , Hong Kong , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/patología , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/diagnóstico , Carcinoma Pulmonar de Células Pequeñas/patología , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Bis(7)-tacrine was evaluated for efficacy on memory retention in mice 17 days of age and 30 days of age. The tests used were a passive-avoidance response test and a measure of spontaneous motor activity. Also, possible drug-induced hepatotoxicity and acute drug toxicity were evaluated. Behavioral studies were performed using a step-through task and an open-field test with a 24-h interval between training and evaluation tests. Bis(7)-tacrine (0.06-20 micromol/kg) was subcutaneously injected 30 min prior to the first session of both test types. During the training session of the step-through task, bis(7)-tacrine treatment reduced (by 46%, P<0.01) the number of avoidable electric shocks (footshocks) only at a high dose of 20 micromol/kg in mice 17 days of age, but dose-dependently decreased the number of footshocks (10-56%, P<0.001) in mice 30 days of age. Bis(7)-tacrine treatment at all doses tested did not produce any detectable changes in retention latency in mice 17 days of age, but the drug significantly prolonged retention latency at low doses (1.25 and 2.50 micromol/kg), and not high doses (5-20 micromol/kg), in mice 30 days of age. In the open-field test, bis(7)-tacrine decreased spontaneous motor activity in the acquisition session only at a high dose of 20 micromol/kg in mice 17 days of age and 30 days of age (by 28 and 45%, respectively), but did not affect spontaneous motor activity in the recall session. Bis(7)-tacrine treatment at a dose of 20 micromol/kg produced a more potent hepatotoxic effect in mice 30 days of age than in mice 17 days of age, (P<0.05), and the drug caused acute toxicity with comparable potencies in mice of both age groups. In conclusion, mice 30 days of age seemed to be more sensitive than mice 17 days of age to bis(7)-tacrine-induced cognitive function enhancement and hepatotoxicity. Bis(7)-tacrine appears to be more potent and more selective as a cognitive function-enhancing agent than tacrine.
Asunto(s)
Conducta Animal/efectos de los fármacos , Tacrina/análogos & derivados , Factores de Edad , Animales , Reacción de Prevención/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Dosificación Letal Mediana , Hígado/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Actividad Motora/efectos de los fármacos , Nootrópicos/administración & dosificación , Nootrópicos/farmacología , Nootrópicos/toxicidad , Tacrina/administración & dosificación , Tacrina/farmacología , Tacrina/toxicidadRESUMEN
The potential of tacrine in altering cognitive/behavioral function as well as in causing toxicity was evaluated in mice of 17 and 30 days of age. Cognitive and behavioral studies were performed using a step-through passive avoidance task and a habituation open-field test with a 24-h retention interval. Tacrine was subcutaneously injected (1.25-80 micro mol/kg) 30 min prior to the first session of both tests. During the training session in step-through task, tacrine treatment dose-dependently decreased the number of footshocks, with IC(50) values being 7.8 and 23.3 micro mol/kg in 17- and 30-day-old mice, respectively. Treatment with tacrine at a low dose (5 micro mol/kg) significantly prolonged the retention latency in 17-day-old mice only, but it shortened the retention latency at high doses of 20 and 40 micro mol/kg in 17- and 30-day-old, respectively. During the acquisition session in the open-field test, tacrine treatment dose-dependently decreased the locomotor activity in 17- and 30-day-old mice, with IC(50) values being 15.1 and 24.7 micro mol/kg, respectively. High doses of tacrine invariably increased the locomotor activity during the recall session. Tacrine treatment at a dose of 40 micro mol/kg caused a significant increase in serum alanine aminotransferase activity in 17- and 30-day-old mice at 6 h post-dosing, with the extent of stimulation in 30-day-old mice being more prominent. In conclusion, tacrine was more potent in enhancing/disrupting the cognitive function, inhibiting locomotor activity as well as in causing hepatotoxicity in 17-day-old than in 30-day-old mice.
Asunto(s)
Reacción de Prevención/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Tacrina/toxicidad , Animales , Defecación/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Hígado/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos ICRRESUMEN
We report three cases of benign metastasising leiomyoma, which is a rare cause of multiple lung nodules, in three Hong Kong Chinese females. One patient presented with pleuritic chest pain, another was asymptomatic, while the last presented with haemoptysis. All three patients had previously undergone surgical resection of uterine leiomyomas. Multiple lung nodules mimicking lung metastases were demonstrated on chest radiographs, and all three diagnoses were obtained from lung biopsies. Hormonal therapy was given to two patients with variable responses. To the best of our knowledge, this is the first report of benign metastasising leiomyoma in Hong Kong Chinese population. It highlights the importance of considering this rare and benign disease in premenopausal females presenting with multiple lung nodules.
Asunto(s)
Leiomioma/patología , Neoplasias Pulmonares/secundario , Neoplasias Uterinas/patología , Adulto , Dolor en el Pecho/etiología , Diagnóstico Diferencial , Femenino , Hong Kong , Humanos , Leiomioma/complicaciones , Leiomioma/cirugía , Pulmón/patología , Persona de Mediana Edad , Tomografía por Rayos X , Neoplasias Uterinas/complicaciones , Neoplasias Uterinas/cirugíaRESUMEN
Previous studies in our laboratory have demonstrated the effect of Schisandrin B (Sch B),an active ingredient of the fruit of Schisandra chinensis, on enhancing the hepatic glutathione antioxidant system in mice, as evidenced by the hepatoprotection against carbon tetrachloride (CCl4) toxicity. In the present study, the mechanism involved in the hepatoprotection afforded by Sch B treatment was investigated. Treating female Balb/c mice with 1, 3-bis(2-chloroethyl)-1-nitrosourea, an inhibitor of glutathione reductase (GRD), at a dose of 2 mmol/kg (i.p.) did not abrogate the hepatoprotective action of Sch B in CCl4-treated mice. The result indicates that the increased activity of hepatic GRD is not ascribable to the hepatoprotective action of Sch B. In control mice, the same Sch B treatment regimen caused an enhancement in hepatic mitochondrial glutathione redox status, as indicated by the significant increase and decrease in reduced and oxidized glutathione levels, respectively. While the CCl4 intoxication greatly impaired mitochondrial glutathione redox status, the beneficial effect of Sch B treatment became more evident after CCl4 challenge. Our results strongly suggest that the mechanism of hepatoprotection afforded by Sch B treatment may involve the enhancement of mitochondrial glutathione redox status.
Asunto(s)
Antioxidantes/farmacología , Tetracloruro de Carbono/antagonistas & inhibidores , Tetracloruro de Carbono/toxicidad , Glutatión/metabolismo , Lignanos , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Compuestos Policíclicos/farmacología , Alanina Transaminasa/sangre , Animales , Ciclooctanos , Inhibidores Enzimáticos/farmacología , Femenino , Radicales Libres/metabolismo , Glutatión/análogos & derivados , Disulfuro de Glutatión , Glutatión Reductasa/antagonistas & inhibidores , Ratones , Ratones Endogámicos BALB C , Oxidación-ReducciónRESUMEN
Although the protection against myocardial ischemia-reperfusion injury by allopurinol has previously been attributed to inhibition of xanthine oxidase, the demonstration of protective effects in species devoid of detectable myocardial xanthine oxidase activity argues against this hypothesis. In the present study, the effects of allopurinol pretreatment in a model of heart-lung transplantation were examined in swine, a species devoid of myocardial xanthine oxidase activity. Twenty-eight experiments were performed utilizing the heart-lung transplantation model--seven controls (14 animals, 7 donors and 7 recipients) with no preoperative pharmacological intervention, and twenty-one in the experimental group (42 animals, 21 donors and 21 recipients) with donor and recipient pretreated with allopurinol 50 mg/kg/day for 3 days. The effect of allopurinol was determined on day 2 blood samples assessing red cell antioxidant status by measurement of malondialdehyde (MDA) formation in response to in vitro peroxidative challenge. The experimental group was divided into subgroups--namely, nonresponders (8 pairs of animals) and responders (13 pairs of animals) based on the range (mean +/- 2 SD) of erythrocyte MDA levels in the control group. Heart-lung transplantation was performed in the three groups (control [7], nonresponders [8], and responders [13]) on day 3 following the final dose of allopurinol administration in the experimental group. Based on postsurgical assessments of cardiac and pulmonary function integrity, animals showing the greatest red cell antioxidant response following allopurinol treatment showed significantly better recovery compared with the control group. In contrast, animals that did not respond to allopurinol pretreatment showed results similar to those of the control (i.e., untreated) group. Furthermore, red cell MDA levels in all the allopurinol-treated animals were found to correlate positively (P < 0.001) with the extent of myocardial and lung dysfunction, as indicated by cardiac index and lung water measurements, respectively. The present study suggests that allopurinol protection against ischemia-reperfusion injury may involve generalized alterations in tissue antioxidant status, and that the measurement of erythrocyte susceptibility to oxidative challenge could provide a useful approach to optimizing the effectiveness of therapeutic interventions undertaken prior to surgery in order to minimize the risk of damage resulting from postischemic tissue reperfusion.
Asunto(s)
Alopurinol/farmacología , Antioxidantes/metabolismo , Eritrocitos/metabolismo , Trasplante de Corazón-Pulmón/fisiología , Corazón/fisiología , Pulmón/fisiología , Animales , Eritrocitos/efectos de los fármacos , Femenino , Corazón/efectos de los fármacos , Pulmón/efectos de los fármacos , Malondialdehído/sangre , Oxidantes/farmacología , Peróxidos/farmacología , Análisis de Regresión , Porcinos , terc-ButilhidroperóxidoRESUMEN
Allopurinol and its metabolite oxypurinol inhibited basal oxidation of ascorbate and exerted comparable concentration-dependent inhibitory effects on the oxidation of ascorbate catalysed by cupric ion, but the stimulation produced by ferric ion was affected minimally. UV spectral analysis suggested the formation of an allopurinol-ascorbate-copper ion complex. The oxidation of erythrocyte membrane lipids by ferric ion and cupric ion-t-butylhydroperoxide was also inhibited by allopurinol and oxypurinol, by the metal chelators EDTA and uric acid, and by the antioxidant butylated hydroxytoluene. The metal chelating actions of allopurinol and oxypurinol may be relevant to their protective actions against ischemia/reperfusion injury.
Asunto(s)
Alopurinol/farmacología , Ácido Ascórbico/metabolismo , Cobre/farmacología , Hierro/farmacología , Peroxidación de Lípido/efectos de los fármacos , Oxipurinol/farmacología , Pirimidinas/farmacología , Hidroxitolueno Butilado/farmacología , Ácido Edético/farmacología , Membrana Eritrocítica/metabolismo , Humanos , Lípidos de la Membrana/metabolismo , Oxidación-Reducción , Ácido Úrico/farmacologíaRESUMEN
A comparison between the effects of schisandrin B (Sch B) and butylated hydroxytoluene (BHT) treatments on hepatic antioxidant status was made to identify the critical antioxidant action of Sch B involved in hepatoprotection in mice. Whereas Sch B treatment (3 mmol/kg/day x 3, p.o.) increased the hepatic mitochondrial-reduced glutathione (GSH) level, BHT treatment at the same dosage regimen decreased it. However, both Sch B and BHT increased, albeit to a different extent, the activity of mitochondrial glutathione reductase. The differential effect of Sch B and BHT treatment on hepatic mitochondrial glutathione status became more apparent after carbon tetrachloride (CCl4) challenge. Pretreatment with Sch B could sustain the hepatic mitochondrial GSH level in CCl4-intoxicated mice and protect against CCl4 hepatotoxicity. BHT pretreatment did not produce any protective effect on CCl4-induced GSH depletion in mitochondrion and hepatocellular damage. Although both Sch B and BHT treatments increased hepatic ascorbic acid (VC) level in control animals, only Sch B pretreatment sustained a high hepatic VC level in CCl4-intoxicated mice. Moreover, Sch B pretreatment prevented the CCl4-induced decrease in the hepatic alpha-tocopherol (VE) level. However, Sch B inhibited NADPH oxidation in mouse liver microsomes incubated with CCl4 in vitro, whereas BHT stimulated this oxidation. The ensemble of results suggests that the ability to sustain the hepatic mitochondrial GSH level and the hepatic VC and VE levels may represent the crucial antioxidant action of Sch B in protection against CCl4 hepatotoxicity. The possible inhibition of CCl4 metabolism by Sch B may also contribute to its hepatoprotective action.
Asunto(s)
Antioxidantes/farmacología , Hidroxitolueno Butilado/farmacología , Tetracloruro de Carbono/toxicidad , Lignanos , Hígado/efectos de los fármacos , Compuestos Policíclicos/farmacología , Alanina Transaminasa/sangre , Animales , Ciclooctanos , Femenino , Ratones , Ratones Endogámicos BALB C , NADP/metabolismoRESUMEN
As a preliminary investigation to exploring whether the methylenedioxy group and the cyclooctadiene ring of the dibenzo[a,c]cyclooctadiene (schisandrin) molecule plays an important role in the protection against myocardial ischemia-reperfusion (IR) injury, we examined the effects of three schisandrins, namely schisandrin A (Sch A), schisandrin B (Sch B), and schisandrin C (Sch C), and the effect of dimethyl-4,-4'-dimethoxy-5,6,5',6'-dimethylene-dioxy-biphenyl-2,2' -bicarboxylate (DDB), an intermediate compound derived from the synthesis of Sch C, on myocardial IR injury in isolated Langendorff-perfused rat hearts. While pretreating rats with Sch A or DDB at a daily oral dose of 1.2 mmol/kg for 3 days did not protect the isolated-perfused hearts against IR-induced damage, pretreatment with Sch B or Sch C at the same dosage regimen produced cardioprotective action. The extent of cardioprotection afforded by Sch B or Sch C pretreatment correlated well with the degree of enhancement in myocardial glutathione antioxidant status, as indicated by significant increases in the tissue-reduced glutathione level and Se-glutathione peroxidase (EC 1.11.1.9), glutathione transferases (EC 2.5.1.18), and glutathione reductase (EC 1.6.4.2) activities in ischemic-reperfused hearts when compared with the unpretreated IR control. Our results indicate that both the methylenedioxy group and the cyclooctadiene ring of the schisandrin molecule are important structural determinants in mediating the protection against myocardial IR injury.
Asunto(s)
Antioxidantes/farmacología , Ciclooctanos , Depuradores de Radicales Libres/farmacología , Lignanos , Daño por Reperfusión Miocárdica/prevención & control , Compuestos Policíclicos/farmacología , Animales , Antioxidantes/química , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Depuradores de Radicales Libres/química , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Glutatión Transferasa/metabolismo , Corazón/efectos de los fármacos , Técnicas In Vitro , L-Lactato Deshidrogenasa , Masculino , Conformación Molecular , Estructura Molecular , Miocardio/metabolismo , Compuestos Policíclicos/química , Ratas , Ratas Sprague-DawleyRESUMEN
As a preliminary approach to exploring whether the methylenedioxy group of the dibenzocyclooctadiene skeleton of schisandrins plays an important role in hepatic mitochondrial-reduced glutathione (GSH) stimulatory activity, we examined the effects of three schisandrins, namely schisandrin A (Sch A), schisandrin B (Sch B), and schisandrin C (Sch C), on carbon tetrachloride (CCl4) hepatotoxicity and hepatic mitochondrial GSH status in mice. Pretreating mice with Sch A at a daily oral dose of 1 mmol/kg for 3 days did not protect against CCl4 hepatotoxicity, whereas pretreatment with Sch B or Sch C at the same dosage regimen produced almost complete protection. The hepatoprotection afforded by Sch B or Sch C pretreatment was associated with significant increases in the hepatic mitochondrial GSH level and glutathione reductase (EC 1.6.4.2) activity. Our results indicate that the methylenedioxy group of the dibenzocyclooctadiene skeleton of schisandrin is an important structural determinant in the stimulation of hepatic mitochondrial GSH, particularly under conditions of CCl4 intoxication.
Asunto(s)
Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Ciclooctanos , Lignanos , Compuestos Policíclicos/administración & dosificación , Alanina Transaminasa/sangre , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Medicamentos Herbarios Chinos/administración & dosificación , Femenino , Glutatión/metabolismo , Ratones , Ratones Endogámicos BALB C , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Compuestos Policíclicos/química , Relación Estructura-ActividadRESUMEN
A homologous radioreceptor assay was developed to determine the epidermal growth factor (EGF) contents of the shrew submaxillary glands. The results supported previous findings by heterologous radioreceptor assay that this gland in the shrew contained a high level of EGF. This EGF was also found to be a powerful mitogen in two fibroblast cell lines.
Asunto(s)
Factor de Crecimiento Epidérmico/análisis , Mitosis/efectos de los fármacos , Glándula Submandibular/análisis , Animales , Bioensayo , Línea Celular , Factor de Crecimiento Epidérmico/farmacología , Fibroblastos/efectos de los fármacos , Masculino , Ensayo de Unión Radioligante , MusarañasRESUMEN
Tumor necrosis factor-alpha (TNFalpha) could cause apoptosis in hepatic tissue of D-galactosamine sensitized mice, as evidenced by the increase in the extent of DNA fragmentation. The hepatic apoptosis induced by TNFalpha was associated with hepatocellular damage as assessed by plasma alanine aminotransferase activity. Schisandrin B (Sch B) pretreatment at daily doses ranging from 0.5 to 2 mmol/kg for 3 days caused a dose-dependent protection against TNFalpha-induced apoptosis in mice. The hepatoprotection was accompanied by a parallel reduction in the extent of hepatocellular damage. The same Sch B pretreatment regimens increased hepatic Hsp70 level in a dose-dependent manner. The relevance of Sch B-induced increase in Hsp70 expression to the prevention of TNFalpha-triggered hepatic apoptosis remains to be elucidated.
Asunto(s)
Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Proteínas HSP70 de Choque Térmico/biosíntesis , Lignanos , Hígado/efectos de los fármacos , Compuestos Policíclicos/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Animales , Antioxidantes/química , Western Blotting , Ciclooctanos , Relación Dosis-Respuesta a Droga , Proteínas HSP70 de Choque Térmico/análisis , Hígado/metabolismo , Hígado/patología , Hepatopatías/metabolismo , Hepatopatías/patología , Ratones , Compuestos Policíclicos/químicaRESUMEN
The few reports in the literature on thoracoscopic anatomic lung resections were almost exclusively for early primary lung cancers. We report our combined experience on video-assisted thoracoscopic (VAT) lobectomy for benign diseases from two major hospitals in Hong Kong over a 20-month period. From August 1993 to March 1995, 66 VAT lobectomies were performed; of this number, 10 cases (15%) were for benign diseases (5 tuberculosis, 2 organized pneumonia, 1 bronchiectasis, 1 sclerosing hemangioma, 1 infected bronchogenic cyst). There was no mortality or incidence of intraoperative complications. Postoperative complications occurred in one patient with tuberculosis and consisted of persistent air leak and subsequent wound infection. There were no long-term complications after a mean follow-up of 11 months. The mean duration of chest tube drainage was 6.7 days and that of hospital stay was 9.8 days. These results were not statistically different from those achieved in VAT lobectomies performed for malignant tumors (5.0 days for drainage and 6.8 days for hospital stay) despite the fact that hilar dissection was sometimes more difficult in the former because of inflammatory changes. We conclude that VAT lobectomy for benign diseases is technically feasible even though its role in thoracic surgery remains to be defined.
Asunto(s)
Enfermedades Pulmonares/cirugía , Neumonectomía , Adulto , Anciano , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Toracoscopía , Grabación en VideoRESUMEN
We report our combined experience on video-assisted thoracoscopic (VAT) anatomic lung resections from two major hospitals in Hong Kong over a 17-month period. From August 1993 to December 1994, 82 cases of major lung resections were attempted using the VATS approach, of which 60 were successfully completed (55 lobectomies, 2 bilobectomies, 2 pneumonectomies, and 1 segmentectomy). Of these 60 cases, there were 43 men and 17 women with a mean age of 66 years (range, 37 to 85 years). The final pathologies were 52 primary lung cancers (37 adenocarcinoma, 11 squamous cell carcinoma, 2 bronchoalveolar carcinoma, 1 adenosquamous carcinoma, and 1 undifferentiated carcinoma); 1 pulmonary metastasis (from nasopharyngeal carcinoma); and 7 benign lesions (3 tuberculosis, 1 bronchiectasis, 1 sclerosing hemangioma, 2 organizing pneumonia). There was one postoperative death (mortality rate, 1.8%). Complications include persistent air leak over 10 days (four), wound infection (two), supraventricular tachycardia (three), and recurrence of tumor over the utility thoracotomy scar (one). All the patients were followed up from 8 weeks to 19 months (mean, 10 months). The mean duration of chest drainage was 5.4 days (range, 2 to 25 days). The mean hospital stay was 7.2 days (range, 4 to 35 days). The average postoperative parenteral narcotic (meperidine hydrochloride [Pethidine]) requirement by patient-controlled analgesia was 275 mg (range, 75 to 800 mg). This compared favorably with an age- and sex-matched historic group of patients who underwent posterolateral thoracotomy and had a hospital stay of 10.4 days (statistically non-significant) and narcotic requirement of 950 mg (statistically significant by paired t test). We conclude that VAT anatomic lung resection is technically feasible. However, there are some specific complications associated with major lung resection through minimal access. Refinement of our present technique and attention to details are important to improve our results.
Asunto(s)
Endoscopía , Neumonectomía , Toracoscopía , Grabación en Video , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Analgesia Controlada por el Paciente , Analgésicos Opioides/administración & dosificación , Carcinoma de Células Escamosas/cirugía , Estudios de Casos y Controles , Drenaje , Endoscopía/efectos adversos , Endoscopía/métodos , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Hong Kong , Humanos , Tiempo de Internación , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Masculino , Meperidina/administración & dosificación , Persona de Mediana Edad , Dolor Postoperatorio/prevención & control , Neumonectomía/efectos adversos , Neumonectomía/métodos , Neumonía/cirugía , Neumotórax/etiología , Taquicardia Supraventricular/etiología , Toracoscopía/efectos adversos , Toracoscopía/métodos , Tuberculosis Pulmonar/cirugíaRESUMEN
A progressive impairment in antioxidant status of rabbit hearts was observed when a fixed period (40 mins) of ischemia produced by coronary artery ligation was followed by increasing periods of reperfusion. This was reflected in a reduction in myocardial glutathione levels and an increase in glutathione depletion and production of thiobarbituric acid-reactive substances following in vitro oxidative challenge with t-butylhydroperoxide. Correlation analysis, in which activities of antioxidant enzymes were viewed in relation to biochemical indices of antioxidant status, indicated the functionally relevant suppression of Cu,Zn-superoxide dismutase and glutathione reductase activities in ischemic/reperfused tissues. These results and the demonstration of significant decreases in the activity of glutathione-dependent antioxidant enzymes under acidotic conditions suggest that transient impairment in the functioning of antioxidant enzymes may be involved in the triggering of irreversible myocardial ischemia-reperfusion injury.
Asunto(s)
Antioxidantes/farmacología , Daño por Reperfusión Miocárdica/enzimología , Animales , Radicales Libres , Glutatión/metabolismo , Glutatión Reductasa/metabolismo , Peróxidos Lipídicos/metabolismo , Masculino , Miocardio/metabolismo , Peróxidos/farmacología , Conejos , Superóxido Dismutasa/metabolismo , Tiobarbitúricos/antagonistas & inhibidores , terc-ButilhidroperóxidoRESUMEN
The role of allopurinol in the prevention of ischemia-reperfusion injury was assessed in a model of heart-lung transplantation. Fourteen swine were divided into two groups (seven donors and seven recipients). All heart and lung blocks were placed in hypothermic storage after perfusion with cold iso-osmolar cardioplegic solution and modified Collins solution, respectively (t = 8-10 degrees C for heart and t = 16-18 degrees C for lungs). The total ischemic time including the orthotopic transplantation was 6 h. Animals (donors and recipients) were pretreated with allopurinol given orally at a dosage of 50 mg/kg for 4 days. Animals were assessed by monitoring heart and lung function, including extravascular lung water at three time intervals, which included pretransplantation (donor), and 30 min and 2 h posttransplantation (recipient). Erythrocyte peroxidation susceptibility was assessed for 3 days, and surgery was performed on day 4. The malondialdehyde levels determined from erythrocyte exposure to in vitro peroxidative challenge classified three paired donor and recipient animals as responders and four paired donor and recipient animals as nonresponders to the allopurinol pretreatment. A persistent deterioration of lung function was observed over time in nonresponders (p less than .05) (increase of lung water, decrease of partial pressure of oxygen, increase in alveolar-arterial gradient, and decrease in arterial-alveolar tension ratio). Responders showed no significant alterations in lung function. This study in swine, a species devoid of myocardial xanthine oxidase activity, indicates that allopurinol may have a mechanism of action other than xanthine oxidase inhibition in the prevention of ischemia-reperfusion injury. The parallelism between protection of lung function and of red blood cells suggests the involvement of a generalized increase in tissue antioxidant capacity.
Asunto(s)
Alopurinol/farmacología , Trasplante de Corazón-Pulmón/métodos , Daño por Reperfusión/prevención & control , Animales , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Corazón/efectos de los fármacos , Trasplante de Corazón-Pulmón/fisiología , Peroxidación de Lípido/efectos de los fármacos , Pulmón/irrigación sanguínea , Pulmón/efectos de los fármacos , Peróxidos/farmacología , Premedicación , Porcinos , Resistencia Vascular/efectos de los fármacos , terc-ButilhidroperóxidoRESUMEN
Synthesized 5-arylamino-2-methyl-4,7-dioxobenzothiazoles 3a-3o were evaluated for modulation of NAD(P)H: quinone oxidoreductase (NQO1) activity with the cytosolic fractions derived from cultured human lung cancer cells and their cytotoxicity in cultured several human solid cancer cell lines. The 4,7-dioxobenzothiazoles affected the reduction potential by NQO1 activity and showed a potent cytotoxic activity against human cancer cell lines. The tested compounds 3a, 3b, 3g, 3h, 3n and 3o were considered as more potent cytotoxic agents, and comparable modulators of NQO1 activity.
Asunto(s)
Antineoplásicos/farmacología , Equinomicina/análogos & derivados , Inhibidores Enzimáticos/farmacología , NAD(P)H Deshidrogenasa (Quinona)/antagonistas & inhibidores , Quinona Reductasas/síntesis química , Tiazoles/síntesis química , Antineoplásicos/síntesis química , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/síntesis química , Humanos , Quinona Reductasas/farmacología , Tiazoles/farmacología , Células Tumorales CultivadasRESUMEN
Sheng-Mai-San (SMS), a traditional Chinese formulation used for the treatment of coronary heart disease, is comprised of Radix Ginseng, Fructus Schisandrae and Radix Ophiopogonis. Pretreatment with a lignan-enriched SMS (17 g/kg/day x 3, p.o.) was found effective in protection against isoproterenol-induced myocardial injury in rats, and in ischemia-reperfusion injury in isolated perfused hearts prepared from pretreated animals. Results obtained from pretreatment studies using extracts prepared by mixing various combinations of the three component herbs indicate that the major myocardial protective component in SMS is the lignan-enriched extract of Fructus Schisandrae.
Asunto(s)
Corazón/efectos de los fármacos , Medicina Tradicional China , Isquemia Miocárdica/tratamiento farmacológico , Animales , Femenino , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
The aim of this study was to assess whether the Streamlined Liner of the Pharynx Airway (SLIPA) performed as well as an endotracheal tube for positive pressure ventilation in gynaecological laparoscopic surgery in the Trendelenburg position. Forty patients (American Society of Anesthesiologists physical status I to III) were randomly divided into two groups: SLIPA (n = 20) or endotracheal tube group (n = 20). Lung mechanics and severity of postoperative sore throat were assessed in both groups. In the SLIPA group, the oropharyngeal leak pressure was also measured. There were no significant differences between groups in the lung mechanics. In the SLIPA group, oropharyngeal leak pressure and peak inspiratory pressure increased significantly after gas insufflation compared to 10 minutes after patient positioning in the lithotomy position (P < 0.05). The difference between oropharyngeal leak pressure and peak inspiratory pressure (approximately 10 cmH2O throughout the procedure) remained suitable for airway maintenance. The incidence of sore throat was similar in both groups but the severity was less in the SLIPA group 24 hours after surgery (P < 0.05). There were no other complications such as regurgitation noted in either group. In the study population, the SLIPA performed as well as an endotracheal tube in allowing positive pressure ventilation without gas leak during gynaecological laparoscopy. The way in which the SLIPA increases its resistance to gas leak as the inspiratory pressure rises may account for this.
Asunto(s)
Procedimientos Quirúrgicos Ginecológicos/métodos , Ventilación con Presión Positiva Intermitente/métodos , Laparoscopía/métodos , Máscaras Laríngeas , Adyuvantes Anestésicos/administración & dosificación , Adyuvantes Anestésicos/farmacología , Adolescente , Adulto , Anciano , Femenino , Glicopirrolato/administración & dosificación , Glicopirrolato/farmacología , Inclinación de Cabeza , Humanos , Intubación Intratraqueal , Reflujo Laringofaríngeo/epidemiología , Persona de Mediana Edad , Monitoreo Intraoperatorio , Faringitis/epidemiología , Complicaciones Posoperatorias/epidemiología , Tamaño de la Muestra , Adulto JovenRESUMEN
The effects of VI-28 (a Yang-invigorating Chinese herbal formula) treatment on the renal mitochondrial antioxidant system and susceptibility to gentamicin-induced nephrotoxicity were investigated in rats. VI-28 treatment (80 or 240 mg/kg/day x 12) enhanced the renal mitochondrial antioxidant system, as indicated by dose-dependent increases in the level/activities of reduced glutathione, Mn-superoxide dismutase, Se-glutathione peroxidase and glutathione S-transferases. VI-28 treatment protected against nephrotoxicity induced by gentamicin administration (100 mg/kg/day x 8) and the nephroprotection was associated with an enhancement in the renal mitochondrial antioxidant system. In conclusion, VI-28 treatment enhanced the renal mitochondrial antioxidant system, thereby protecting against gentamicin nephrotoxicity.