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1.
Pharmacogenomics ; 17(2): 133-45, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26566055

RESUMEN

AIMS: Opioids are widely used as effective analgesics, but opioid sensitivity is well known to vary widely among individuals and the underlying genetic factors are not fully understood, thus hampering efficient pain treatment. We explored the genetic factors that contribute to individual differences in opioid sensitivity by performing a genome-wide association study. METHODS: We conducted a multistage genome-wide association study in subjects who underwent laparoscopic-assisted colectomy (LAC). RESULTS: A nonsynonymous SNP in the LAMB3 gene region, rs2076222, was strongly associated with postoperative opioid requirements. The C allele of this best-candidate SNP was associated with lower opioid sensitivity and/or higher pain sensitivity in the patient subjects. CONCLUSION: Our findings provide valuable information for personalized pain treatment after LAC, in which the C allele of the rs2076222 SNP is associated with lower opioid sensitivity and requires more opioid analgesic after LAC.


Asunto(s)
Analgésicos Opioides/administración & dosificación , Neoplasias del Colon/genética , Fentanilo/administración & dosificación , Sitios Genéticos , Dolor Postoperatorio/tratamiento farmacológico , Neoplasias del Recto/genética , Analgésicos Opioides/uso terapéutico , Colectomía , Neoplasias del Colon/cirugía , Femenino , Fentanilo/uso terapéutico , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Neoplasias del Recto/cirugía
2.
Masui ; 64(7): 772-4, 2015 Jul.
Artículo en Japonés | MEDLINE | ID: mdl-26422948

RESUMEN

BACKGROUND: We studied the stability of the continuous arterial pressure line (A line) achieved by using a catheter securement device. METHODS: A total of 100 patients requiring an arterial catheter were divided into 2 groups of fixation: (1) fixation achieved by using the SorbaView SHIELD (Centurion Medical Products Corporation, USA) and (2) fixation by using Tegaderm 3 M (TEGADERM 3 M, Japan). We analyzed the stability of the fixation, presence or absence of skin disorders, and the preference by nurses. RESULTS: The SorbaView SHIELD was superior judged by nurses and was found to render more stability to the fixation of the A line as compared to Tegaderm 3 M, especially when transferring a patient into the intensive care unit after surgery. CONCLUSIONS: We conclude that stability of the A line maintained by the use of the SorbaView SHIELD is more effective in maintaining the stability of the A line.


Asunto(s)
Adhesivos , Cateterismo Periférico/instrumentación , Atención Perioperativa/instrumentación , Anciano , Humanos
3.
Masui ; 64(10): 1065-7, 2015 Oct.
Artículo en Japonés | MEDLINE | ID: mdl-26742411

RESUMEN

A 75-year-old man with abdominal aortic aneurysm underwent Y-graft replacement under combination of general anesthesia and epidural anesthesia. Although we inserted an epidural catheter at first attempt from T11-12, nurse cut the epidural catheter accidently. We re-inserted from the same place. Postoperatively, we found hemopneumothorax in the chest Xp. The patient was transferred to ICU and mechanical ventilation was continued. The next day, he showed motor disturbance of both legs after waking up from sedation. The surgeon pulled out the epidural catheter. At that time, APTT was 41.5 sec, PT-INR was 1.32, PLT was 80,000. After one hour, he could move leg but had numbness of the left leg. MRI revealed epidural hematoma from T8 to T10. Although the cause of epidural hematoma remains unclear, we should have proposed to check anticoagulant data when catheter was pulled out from epidural space.


Asunto(s)
Anestesia Epidural/efectos adversos , Aneurisma de la Aorta Abdominal/cirugía , Trastornos de la Coagulación Sanguínea/complicaciones , Cateterismo/efectos adversos , Hematoma Espinal Epidural/etiología , Anciano , Aneurisma de la Aorta Abdominal/complicaciones , Humanos , Imagen por Resonancia Magnética , Masculino
4.
Masui ; 63(8): 921-3, 2014 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-25199334

RESUMEN

A 31-year-old female, with 22 weeks of pregnancy, presented with sudden onset of severe headache. CT scan showed diffuse subarachnoid hemorrhage. A cerebral angiogram showed dissecting aneurysm of right cerebral artery. To obliterate the aneurysm and prevent rupture, the patient underwent coil embolization via an endovascular approach under general anesthesia because the procedure under sedation with local anesthesia was too risky for re-bleeding. The patient has been diagnosed as PAPA syndrome. Although the arthritis was now stable and she was taking no drug, remarkable osteoarthritis was observed. The cervical spine X ray demonstrated no cervical ankylosis. As patient was sedated with propofol, airway examination could not be done except noticing thyromental distance of seven centimeters. Patient's trachea was intubated using Macintosh size #3 laryngoscope blade and a 7.0 non-styletted tracheal tube at the first attempt without any problems (Cormack grade I). Anesthesia was maintained with sevoflurane, fentanyl and remifentanil. After the end of endovascular surgery, the patient was transferred to the intensive care unit under mechanical ventilation. She was weaned from mechanical ventilation 2 days later but consciousness was unclear. Right incomplete paralysis was also observed. MRI revealed vasospasm on the bilateral internal carotid artery. The patient underwent percutaneous tansluminalangioplasty coil and intraarterial injection of fasudil hydrochloride under local anesthesia. The consciousness recovered fully and the paralysis was improved. The patient delivered the baby by Caesarean sections under combined spinal and epidural anesthesia at 36 weeks without any problems with both the mother and baby.


Asunto(s)
Acné Vulgar , Anestesia General , Anestesia Obstétrica , Disección Aórtica/terapia , Artritis Infecciosa , Aneurisma Intracraneal/terapia , Complicaciones del Embarazo , Piodermia Gangrenosa , Adulto , Anestesia Epidural , Anestesia Raquidea , Aneurisma Roto/prevención & control , Angioplastia/métodos , Cesárea , Embolización Terapéutica/métodos , Procedimientos Endovasculares/métodos , Femenino , Humanos , Recién Nacido , Atención Perioperativa , Embarazo , Resultado del Embarazo , Síndrome
6.
Masui ; 63(5): 545-7, 2014 May.
Artículo en Japonés | MEDLINE | ID: mdl-24864577

RESUMEN

A 71-year-old male was scheduled for a laparoscopic cholecystectomy. The plan was to intubate him using direct laryngoscopy. After induction of anesthesia and analgesia direct laryngoscopy was performed but it was difficult to get a good view of epiglottis, and at 2nd attempt there was laryngeal edema, which made the procedure more difficult. The patient was then ventilated with a facemask and it was decided to intubate him with an Ambu Laryngeal Mask Angle Type-i (Aura-i) and a bronchofiberscope. The procedure worked, and the patient was successfully intubated. We did not want to remove the Aura-i due to concerns about losing the airway. Therefore, we decided to place the gastric tube with the Aura-i still inserted. Therefore the cuff of the Aura-i was deflated and we were able to easily pass a gastric tube behind the Aura-i type easily. After the operation, the patient was extubated from the trachea with the Aura-i still in place. When sufficient respiration returned, the Aura-i was removed. There was no bleeding in the mouth after removal of the Aura-i.


Asunto(s)
Intubación Gastrointestinal/métodos , Máscaras Laríngeas , Anciano , Colecistectomía , Humanos , Intubación Intratraqueal/métodos , Masculino
7.
Masui ; 63(5): 561-3, 2014 May.
Artículo en Japonés | MEDLINE | ID: mdl-24864581

RESUMEN

We report the successful combined use of continuous epidural anesthesia and transversus abdominis plane block for the management of postoperative pain following a cesarean delivery in a patient whose paralysis and pain were not well controlled after two previous cesarean deliveries. A 28-year-old female patient with no remarkable medical history was scheduled to undergo cesarean delivery at 38 weeks and 3 days of pregnancy. She had undergone cesarean deliveries twice previously, at 23 and 25 years of age. Both of these procedures were concluded using combined spinal-epidural anesthesia. However, in both procedures, the continuous epidural catheter could not be removed within 12 hours because of paralysis of the right leg and sharp pain. Therefore, during the third operation, the concentration of the continuous epidural anesthesia infusion was decreased to prevent complications, and a transversus abdominis plane block was added. The patient experienced no postoperative pain and fewer complications. We think that the combined use of these blocks provided good postoperative pain control with fewer complications.


Asunto(s)
Anestesia Epidural/métodos , Cesárea Repetida , Bloqueo Nervioso/métodos , Adulto , Femenino , Humanos , Dolor Postoperatorio/prevención & control , Cuidados Posoperatorios , Embarazo
8.
Masui ; 63(5): 564-7, 2014 May.
Artículo en Japonés | MEDLINE | ID: mdl-24864582

RESUMEN

A 19-year-old male was admitted with diabetic ketoacidosis. A central venous catheter for fluid loading and insulin administration was inserted from the right femoral vein. The catheter was placed for 4days and was removal. Three days after removal thrombus was pointed out with echocardiography. Cardiac ultrasound revealed floating thrombi in the right atrium. Venography demonstrated a large thrombus from the right femoral vein to the end of the inferior vena cava. Emergency surgery was performed. A tubular thrombus was trapped from the inferior vena cava departure at the right atrium under cardiopulmonary bypass. The surgeon also implanted an inferior vena caval filter. The patient was weaned from ventilator assist next day and was discharged from the hospital 13 days later. This case suggests that deep vein thrombosis should be checked in diabetic ketoacidosis even after removal of a central venous catheter implanted at the femoral vein.


Asunto(s)
Cateterismo Venoso Central/efectos adversos , Cetoacidosis Diabética/complicaciones , Atrios Cardíacos , Trombosis , Vena Cava Inferior , Trombosis de la Vena/etiología , Puente Cardiopulmonar , Cetoacidosis Diabética/terapia , Vena Femoral , Humanos , Masculino , Trombosis de la Vena/terapia , Adulto Joven
9.
Masui ; 63(11): 1269-71, 2014 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-25731062

RESUMEN

In a 54-year-old man, at the time of anesthesia administration during the Bentall re-operation, a preoperative ultrasound scan showed right internal jugular vein thrombosis before insertion of a pulmonary artery catheter into the right internal jugular vein. Therefore, we performed the insertion after confirming that the left internal jugular vein was safe via a preoperative ultrasound and chest computed tomography (CT). Although we could insert the catheter sheath, contrast imaging revealed that the pulmonary artery catheter had advanced no further than approximately 15 cm into the left internal jugular vein. Similar advancement was noted when inserting the pulmonary artery catheter under fluroscopic guidance. This indicated an obstruction in the confluence of the left internal jugular vein and the brachiocephalic vein. A postoperative chest contrast CT showed thrombosis in the confluence of the left internal jugular vein and the brachiocephalic vein. Considering that the chest CT scan was performed 2 months before the surgery, it is necessary to perform imaging again before surgery.


Asunto(s)
Cateterismo de Swan-Ganz , Venas Yugulares , Insuficiencia Venosa/diagnóstico , Humanos , Venas Yugulares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Ultrasonografía
10.
Masui ; 62(12): 1422-5, 2013 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-24498774

RESUMEN

Although tracheal laceration during surgical procedure is a rare complication, it can be life-threating. Its immediate recognition and treatment are important. A 72-year-old man with aortic valve regurgitation was scheduled for aortic valve replacement. At anesthetic induction an endotracheal tube was smoothly inserted and the tidal volume was set at 500 ml with ventilator rate of 12 min-1. After electrocautery maneuver of the upper sterna region, end-tidal carbon-oxide curve suddenly became flat. Immediately after the completion of median sternotomy air bubble was seen in the surgical field. An 8-mm longitudinal tracheal laceration at the fourth tracheal cartilage was identified. The tracheal laceration was repaired with interrupted suture and the mediastinal tissue was used to cover the suture line. Air leaks were no longer present. After surgical repair, the aortic valve replacement was performed. The postoperative courses of both tracheal laceration repair and aortic valve replacement were uneventful.


Asunto(s)
Electrocoagulación/efectos adversos , Complicaciones Intraoperatorias/etiología , Laceraciones/etiología , Esternotomía/efectos adversos , Tráquea/lesiones , Anciano , Anestesia General , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Complicaciones Intraoperatorias/cirugía , Laceraciones/cirugía , Masculino , Técnicas de Sutura , Resultado del Tratamiento
12.
J Anesth ; 24(5): 801-2, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20640451

RESUMEN

The Starfish heart positioning device allows excellent cardiac positioning and hemodynamic stability during off-pump coronary artery bypass graft surgery. Herein, we present a patient in whom the use of this device caused epicardial hematoma as the result of an injured epicardial vein, an uncommon complication of this device. In this patient, regional left ventricular wall motion abnormality on transesophageal echocardiography and a ST-T change on electrocardiogram occurred secondary to the development of the epicardial hematoma. These signs completely disappeared upon removal of the hematoma. These findings suggested that the hematoma resulted in reversible myocardial ischemia.


Asunto(s)
Hematoma/etiología , Complicaciones Intraoperatorias/etiología , Isquemia Miocárdica/etiología , Pericardio , Instrumentos Quirúrgicos/efectos adversos , Anciano , Angina Inestable/cirugía , Puente de Arteria Coronaria Off-Pump , Vasos Coronarios/lesiones , Ecocardiografía Transesofágica , Electrocardiografía , Hematoma/diagnóstico por imagen , Humanos , Complicaciones Intraoperatorias/diagnóstico por imagen , Masculino , Isquemia Miocárdica/diagnóstico por imagen
13.
J Anesth ; 24(2): 293-6, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20101512

RESUMEN

This study was conducted to examine whether pretreatment with intravenous atropine could prevent bradycardia and hypotension during induction of total intravenous anesthesia with propofol and remifentanil in a prospective randomized placebo-controlled manner. Seventy patients, aged 24-78 years, were randomly divided into two groups, and received 0.5 mg atropine or placebo saline 1 min before induction of intravenous anesthesia with remifentanil at 0.4 microg/kg/min, propofol at a target blood concentration of 3 microg/ml, and vecuronium 1.5 mg/kg. Immediately after tracheal intubation, the infusion rate of remfentanil and the target concentration of propofol were reduced to and kept at 0.1 microg/kg/min and 2 microg/ml, respectively, for 10 min. Noninvasive blood pressure (BP) and heartrate (HR) were measured and recorded every minute. Intravenous atropine could prevent a fall in HR, but not a fall in BP, during induction of intravenous anesthesia with propofol and remifentanil of our dosing regimen. Our data suggested that a fall in HR induced by propofol-remifentanil anesthesia was mainly caused by centrally mediated sympatholytic and/or vagotonic actions of propofol and remifentanil, whereas a fall in BP was mainly the result of their direct vasodilating actions.


Asunto(s)
Anestesia Intravenosa/métodos , Atropina/uso terapéutico , Bradicardia/prevención & control , Hipotensión/prevención & control , Parasimpatolíticos/uso terapéutico , Adulto , Anciano , Anestésicos Intravenosos , Atropina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Parasimpatolíticos/administración & dosificación , Piperidinas , Propofol , Estudios Prospectivos , Remifentanilo , Resultado del Tratamiento , Adulto Joven
14.
J Anesth ; 24(1): 143-5, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20052499

RESUMEN

We report on a patient who presented with recurrent severe shock during general anesthesia. The patient was a man scheduled for lung surgery whose first attack was a coronary spasm, which was followed by a second shock with severe bronchospasm and hypotension 4 weeks later. An elevated serum tryptase concentration was observed, and subsequent skin testing revealed negative reactions to some drugs administered in this case. This case serves to alert anesthetists to the possibility of some different forms of allergy and highlights the importance of rigorous investigation of all the reagents and phenomena.


Asunto(s)
Anafilaxia/etiología , Anestesia General/efectos adversos , Complicaciones Intraoperatorias , Anciano , Espasmo Bronquial/inmunología , Vasoespasmo Coronario/inmunología , Hipersensibilidad a las Drogas/etiología , Humanos , Hipotensión/inmunología , Pulmón/cirugía , Masculino , Prevención Secundaria , Choque/etiología , Pruebas Cutáneas
15.
J Clin Anesth ; 21(6): 408-13, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19833273

RESUMEN

STUDY OBJECTIVE: To compare the influence of baricity and patient positioning during onset of subarachnoid block in patients placed in the prone, jackknife position with head-down tilt of 15 degrees . DESIGN: Randomized study. SETTING: Operating room of Tonami General Hospital. PATIENTS: 180 ASA physical I and II patients (134 men and 46 women), aged 18 to 54 years, scheduled for elective perianal surgery. INTERVENTIONS: Patients were randomly divided into 6 groups (n = 30 each) based on baricity (hyperbaric or isobaric) of 0.5% bupivacaine (5 mg) and duration of the sitting position (two, 5, or 10 min) after injection. MEASUREMENTS: Sensory block levels were examined by pinprick at 0, 5, 10, 20, and 60 minutes after jackknife positioning. Systolic blood pressure and heart rate were also recorded. MAIN RESULTS: After jackknife positioning, sensory block levels progressively increased until 15 or 20 minutes in all groups. Regardless of baricity of bupivacaine, sensory block levels were higher at 10 through 60 minutes in the two-minute sitting groups than in the 5-minute or 10-minute sitting groups (P < 0.01 and P < 0.01, respectively), and in the 5-minute sitting groups than in the 10-minute sitting groups (P < 0.05). The mean highest sensory block levels were T5, T9, and T11 in the two-minute, 5-minute, and 10-minute sitting groups, respectively. CONCLUSION: Patient positioning, not baricity of bupivacaine, significantly affected the cephalad spread of spinal anesthesia, and a 10-minute period in the sitting position limits the maximum cephalad spread to T11.


Asunto(s)
Anestesia Raquidea/métodos , Anestésicos Locales/administración & dosificación , Bupivacaína/administración & dosificación , Bloqueo Nervioso/métodos , Adolescente , Adulto , Femenino , Inclinación de Cabeza , Humanos , Masculino , Persona de Mediana Edad , Postura , Posición Prona , Recto/cirugía , Factores de Tiempo , Adulto Joven
16.
J Clin Anesth ; 21(8): 567-73, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20122588

RESUMEN

STUDY OBJECTIVE: To identify risk factors for reversible psychomotor dysfunction after prolonged sedation with isoflurane during mechanical ventilation in the intensive care unit (ICU). DESIGN: Retrospective case series. SETTING: General ICU at Tonami General Hospital. MEASUREMENTS: The records of 335 patients, aged from 10 months to 93 years, who were sedated with isoflurane for more than 12 hours, were reviewed. The presence or absence of reversible psychomotor dysfunction after weaning from mechanical ventilation during isoflurane sedation, and its type and duration, if present, were recorded. Data on patients' demographics, duration of isoflurane inhalation, minimum alveolar concentration (MAC)-hours of isoflurane, and concomitant medical treatments were recorded. RESULT: Twelve patients (3.6%) developed reversible psychomotor dysfunction, including systemic or localized tremor, chorea, and hallucination, which lasted 10 minutes to 6 days after weaning from mechanical ventilation during isoflurane sedation. Such psychomotor dysfunction occurred in 42% (8 of 19) of patients aged 4 years or less, while only in 1.3% (4 of 316) of those older than 4 years (P < 0.0001). It occurred in 0% (none of 167) of patients receiving isoflurane for 24 hours or less, while in 7.1% (12 of 168) of patients receiving it for more than 24 hours (P = 0.0004). Other factors examined, including gender, MAC-hours, and drugs co-administrated with isoflurane, did not affect its incidence. CONCLUSION: Four years of age or less and isoflurane inhalation for more than 24 hours were considered to be significant risk factors for the development of reversible psychomotor dysfunction after prolonged sedation with isoflurane.


Asunto(s)
Anestésicos por Inhalación/efectos adversos , Unidades de Cuidados Intensivos , Isoflurano/efectos adversos , Trastornos Psicomotores/inducido químicamente , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anestésicos por Inhalación/administración & dosificación , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Isoflurano/administración & dosificación , Masculino , Persona de Mediana Edad , Trastornos Psicomotores/epidemiología , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
17.
Masui ; 57(2): 209-12, 2008 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-18277574

RESUMEN

We experienced a case of pulseless electrical activity (PEA) during posture change after epidural anesthesia. A 79-year-old man was scheduled for open reduction of left femoral neck fracture. Past history included severe diabetes, which is hardly controlled even by hypodermic injection of insulin before surgery. We performed epidural anesthesia at L3-4 level in right lateral position. Shortly after turning the patient to supine position, the patient became unconscious and blood pressure was unmeasurable. ECG showed sinus rhythm and he was diagnosed as PEA. Loss of consciousness was prolonged even after recovery of blood pressure by intravenous injection of epinephrine 1 mg. The patient underwent therapeutic hypothermia (target temperature 34 degrees C) over a period of 48 hours. The patient showed no neurological dysfunction after recovery from therapeutic hypothermia. We consider that the cause of PEA is blood pressure decrease associated with epidural anesthesia and diabetic autonomic neuropathy.


Asunto(s)
Anestesia Epidural/efectos adversos , Postura/fisiología , Pulso Arterial , Inconsciencia/etiología , Anciano , Enfermedades del Sistema Nervioso Autónomo/complicaciones , Neuropatías Diabéticas/complicaciones , Electrocardiografía , Fracturas del Cuello Femoral/cirugía , Humanos , Hipotensión Ortostática/etiología , Hipotermia Inducida , Masculino , Inconsciencia/fisiopatología , Inconsciencia/terapia
18.
Masui ; 56(4): 418-20, 2007 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-17441449

RESUMEN

An 88-year-old man was admitted to the intensive care unit after the ingestion of 150 mg of dehydrocodeine. The ECG showed severe brodycardia and he was diagnosed as sick sinus syndrome. The recovering of sinus node function took 5 days after the ingestion. The complication observed suggests that transient hypoxia induced by ingestion of high dose DHC had affected sinus node.


Asunto(s)
Analgésicos Opioides/efectos adversos , Codeína/análogos & derivados , Neuralgia Posherpética/tratamiento farmacológico , Síndrome del Seno Enfermo/inducido químicamente , Anciano de 80 o más Años , Analgésicos Opioides/administración & dosificación , Codeína/administración & dosificación , Codeína/efectos adversos , Electrocardiografía , Humanos , Masculino , Síndrome del Seno Enfermo/diagnóstico , Síndrome del Seno Enfermo/terapia
19.
Arch Biochem Biophys ; 402(1): 149-57, 2002 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-12051692

RESUMEN

We examined the paraquat detoxicative system in mouse livers. The survival rate of mice receiving 50 mg/kg paraquat was 41% at 7 days and significantly rose to 88, 64, 69% with pretreatment with phenytoin, phenobarbital, and rifampicin, respectively. Phenytoin induced activity in NADPH-cytochrome P450 reductase, CYP3A, CYP2B, and CYP2C that was 3 to 4 times higher than that of the controls. Phenobarbital induced CYP2B and rifampicin induced CYP3A, respectively, in addition to NADPH-cytochrome P450 reductase. 3-Methylcholanthrene did not induce these enzymes and did not alter the survival rate. All the mice pretreated with CoCl(2) (a CYP synthesis inhibitor) or SKF 525-A (a CYP inhibitor) were dead after 5 days, and troleandomycin (a CYP3A-specific inhibitor) also reduced the survival rate. When cell homogenates were incubated with paraquat and NADPH, paraquat decreased and its metabolic intermediate paraquat-monopyridone was formed. Troleandomycin inhibited the decrease in paraquat and increased the monopyridone. After making a subfraction of the homogenate, monopyridone was produced in the postmicrosomal 105,000g supernatant, but not in the microsomes. The pretreatment of mice with phenytoin decreased the monopyridone in the postmitochondrial fraction, but did not affect the supernatant. These results indicated that paraquat was first metabolized in the postmicrosomal supernatant into monopyridone, and that may have been subsequently hydroxylated by the microsomes. Repeated intravenous injections of alpha-tocopherol to paraquat-loaded mice significantly reduced the paraquat mortality and when these mice were pretreated with rifampicin, 100% of them survived. These studies demonstrate that postmitochondrial fractions play an important role in paraquat detoxication metabolism, and that the combination of CYP induction and alpha-tocopherol administration is highly useful for the survival of paraquat-exposed mice.


Asunto(s)
Hidrocarburo de Aril Hidroxilasas , Hígado/metabolismo , Paraquat/toxicidad , Animales , Cromatografía Líquida de Alta Presión , Cobalto/farmacología , Citocromo P-450 CYP2B6 , Citocromo P-450 CYP3A , Sistema Enzimático del Citocromo P-450/biosíntesis , Sistema Enzimático del Citocromo P-450/metabolismo , Inducción Enzimática , Inhibidores Enzimáticos/farmacología , Hígado/efectos de los fármacos , Hígado/ultraestructura , Masculino , Metilcolantreno/farmacología , Ratones , Ratones Endogámicos ICR , NADPH-Ferrihemoproteína Reductasa/biosíntesis , NADPH-Ferrihemoproteína Reductasa/metabolismo , Oxidorreductasas N-Desmetilantes/biosíntesis , Oxidorreductasas N-Desmetilantes/metabolismo , Paraquat/metabolismo , Fenobarbital/farmacología , Fenitoína/farmacología , Proadifeno/farmacología , Conejos , Rifampin/farmacología , Troleandomicina/farmacología , Vitamina E/farmacología
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