RESUMEN
BACKGROUND: Gastrointestinal toxicity is one of the most serious side effects in the methotrexate (MTX) treatment. However, the mechanism of the toxicity has not been completely clarified, which may be the reason why symptomatic therapy is carried out. On the other hand, the oxidative stress is known to play an important role in various diseases and drug-induced side effects. In this study the focus was on the oxidative stress in order to clarify the mechanism of MTX-induced small intestinal damage, especially neutrophil infiltration. METHODS: MTX (20 mg/kg body wt) was administered to rats intravenously. Mucosal homogenates were prepared from the small intestine and used for assay of biochemical parameters, by which induction of oxidative stress and neutrophil infiltration were evaluated. N-acetylcysteine (NAC; 80 mg/kg body wt), an antioxidant or sodium tungstate (tungsten; 0.7 g/kg body wt), an inhibitor of xanthine dehydrogenase (XD)/xanthine oxidase (XO) known as an important source of reactive oxygen species (ROS) was given to rats with MTX to investigate the contribution of ROS to neutrophil infiltration. RESULTS: The MTX treatment of rats induced the oxidative stress in the small intestine. The ROS production was seen preceding an increase of myeloperoxidase activity, which suggested neutrophil infiltration. Both treatments of NAC and tungsten prevented the MTX-induced ROS production and neutrophil infiltration. CONCLUSIONS: These results suggest that oxidative stress plays an important role in the MTX-induced small intestinal damage, especially neutrophil infiltration. Thus, the modulation of oxidative stress would be useful in reducing intestinal damage in MTX treatment.
Asunto(s)
Intestino Delgado/efectos de los fármacos , Metotrexato/toxicidad , Estrés Oxidativo/efectos de los fármacos , Acetilcisteína/farmacología , Animales , Antioxidantes/farmacología , Catalasa/análisis , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Intestino Delgado/metabolismo , Intestino Delgado/patología , Mediciones Luminiscentes , Masculino , Infiltración Neutrófila , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/análisis , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Compuestos de Tungsteno/farmacología , Xantina Deshidrogenasa/antagonistas & inhibidores , Xantina Deshidrogenasa/metabolismoRESUMEN
BACKGROUND: The induction of tumour-specific immunity is important for advanced cancer therapy. There are many molecules, including costimulatory molecules, that have been identified as the activator for tumour-specific T cells. METHODS: To induce autologous tumour-specific cytotoxic T lymphocytes (CTL) more effectively, we studied whether the expression of the B7 gene may render human colon cancer cells able to stimulate autologous peripheral blood mononuclear cells (PBMC) to become tumour-specific cytotoxic T cells. After the establishment of a B7.1 gene transfected tumour cell line, Cw2/B7.1, we first examined its stimulatory effect on autologous PBMC and subsequently, its effect on the induction of parental cell (Cw2)-specific CTL. RESULTS: The results showed that Cw2/B7.1 had a more potent stimulatory effect on PBMC for the induction of both proliferation and cytotoxicity than Cw2. By adding a low dose of interleukin-2, Cw2/B7.1-activated killer cell activity was significantly increased. The specificity of Cw2/B7.1-activated killer cells was demonstrated by the absence of their cytotoxicity to either human lymphocyte antigen (HLA)-A33 identical (ORF) or HLA-non-identical (MT) allogenic colon cancer cell lines. Furthermore, such Cw2-specific cytotoxic activity was significantly reduced by the deletion of CD8+ cells but not CD4+ cells, indicating that these killer cells were mainly CD8+ T cells. CONCLUSIONS: Thus, our results demonstrate that, by using B7.1 gene-transfected tumour cell lines, we effectively induced autologous tumour-specific CTL. These results will provide us with new tools for adoptive immunotherapy for colon cancer patients.
Asunto(s)
Antígeno B7-1/genética , Neoplasias del Colon/genética , Neoplasias del Colon/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos T Citotóxicos/inmunología , Antígeno B7-1/biosíntesis , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , División Celular/efectos de los fármacos , División Celular/inmunología , Células Cultivadas , Neoplasias del Colon/patología , Pruebas Inmunológicas de Citotoxicidad , Epítopos , Femenino , Citometría de Flujo , Antígenos de Histocompatibilidad Clase I/biosíntesis , Humanos , Molécula 1 de Adhesión Intercelular/biosíntesis , Interleucina-2/farmacología , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Activación de Linfocitos/genética , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Persona de Mediana Edad , TransfecciónRESUMEN
To investigate the features of erythrocyte metabolism in extremely immature infants, we assayed 21 enzyme activities and glutathione level in cord erythrocytes from 28 extremely low-birth-weight infants (ELBWI; defined as birth weight <1,000 g). The results were compared with those from normal adults and non-neonatal reticulocyte-rich controls. Statistical analysis revealed that activities of six enzymes (glucosephosphate isomerase, phosphoglycerate kinase, monophosphoglycerate mutase, enolase, glucose-6-phosphate dehydrogenase (G6PD), and glutathione reductase) were significantly higher, and those of eight other enzymes (phosphofructokinase, 6-phosphogluconate dehydrogenase (6PGD), glutathione peroxidase, adenylate kinase, adenosine deaminase, acetylcholinesterase, NADH methemoglobin reductase, and catalase) were lower in ELBWI taking their marked reticulocytosis into consideration. The 6PGD/G6PD ratio, which is consistently unchanged under various physiological and pathological conditions, was markedly reduced in ELBWI. Our results support the previous reports that neonatal erythrocytes have a unique metabolic pattern which is different from that of adult erythrocytes, and also suggest that the 6PGD/G6PD ratio might be an index for the developmental immaturity of fetal erythrocytes. This is the first report describing the pattern of erythrocyte enzyme activities in ELBWI.
Asunto(s)
Eritrocitos/enzimología , Sangre Fetal/enzimología , Recién Nacido de muy Bajo Peso/sangre , Reticulocitos/enzimología , Acetilcolinesterasa/sangre , Adenosina Desaminasa/sangre , Adenilato Quinasa/sangre , Adulto , Peso al Nacer , Catalasa/sangre , Citocromo-B(5) Reductasa/sangre , Glucosa-6-Fosfato Isomerasa/sangre , Glucosafosfato Deshidrogenasa/sangre , Glutatión Peroxidasa/sangre , Glutatión Reductasa/sangre , Humanos , Recién Nacido , Fosfogluconato Deshidrogenasa/sangre , Valores de Referencia , Recuento de ReticulocitosAsunto(s)
Acromegalia/complicaciones , Hormonas/uso terapéutico , Hipofaringe/patología , Laringe/patología , Apnea Obstructiva del Sueño/complicaciones , Acromegalia/tratamiento farmacológico , Acromegalia/patología , Acromegalia/cirugía , Bromocriptina/uso terapéutico , Antagonistas de Hormonas/uso terapéutico , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Octreótido/uso terapéutico , Apnea Obstructiva del Sueño/patologíaRESUMEN
There have been few studies on adenosine triphosphate (AT) stress echocardiography. The AT stress test may have fewer adverse effects than the adenosine stress test. The addition of atropine to AT echocardiography may enhance the sensitivity for detection of coronary artery disease (CAD). The purpose of this study was to determine the utility of AT-atropine echocardiography for detection of CAD. The group studied consisted of 112 patients with suspected CAD. Sixty-one patients did not have a history of prior myocardial infarction (group I) and 51 patients did (group II). AT was infused intravenously at 180 microg/kg/min for 14 minutes. Atropine (0.25 mg intravenously, repeated up to maximum total dose of 1 mg) was administered starting after 8 minutes of AT infusion. Ischemic response was defined as new or worsening wall motion abnormality occurring during the infusion. The sensitivity and specificity for detection of CAD were assessed using the representative echocardiograms during single AT infusion and AT-atropine infusion. Sixty-two patients had CAD. Fifty-eight patients (52%) developed minor side effects that resolved promptly. The rate-pressure product (10(3)/mm Hg beats/min) was significantly increased at 12 minutes of infusion (12.4+/-3.2) compared with that at baseline (9.1+/-2.3) and that at 6 minutes of infusion (9.4+/-2.1). The sensitivity for detection of CAD was 45% for AT echocardiography and 74% for AT-atropine echocardiography. The specificity was 94% for AT echocardiography and 90% for AT-atropine echocardiography. The sensitivity and specificity of AT-atropine echocardiography was 78% and 93%, respectively, in group I, and 70% and 86%, respectively, in group II. In conclusion, AT-atropine stress echocardiography seems to be well tolerated, safe, and useful for detection of CAD.
Asunto(s)
Adenosina Trifosfato , Atropina , Enfermedad Coronaria/diagnóstico por imagen , Ecocardiografía , Adenosina Trifosfato/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Atropina/administración & dosificación , Angiografía Coronaria , Enfermedad Coronaria/fisiopatología , Electrocardiografía , Prueba de Esfuerzo , Femenino , Hemodinámica , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Seguridad , Sensibilidad y EspecificidadRESUMEN
A highly water soluble disulfonated tetrazolium salt, 4-[3-(2-methoxy-4-nitrophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate sodium salt, was synthesized. The compound is reduced by NADH in good yields at neutral pHs in the presence of 1-methoxy PMS to produce the corresponding formazan dye that absorbs at 460 nm. The formazan is soluble to water at concentrations higher than 0.1 M. The tetrazolium salt thus proved to be useful as a sensitive chromogenic indicator for NADH. It is also applicable to cell proliferation assays as a cell viability indicator.
RESUMEN
We present a patient with continuous melena, diagnosed as rectal varices bleeding. She had a history of esophageal varices, which was treated by endoscopic ligation therapy. Eight years after the treatment of esophageal varices, the continuous melena began. Colonoscopic examination showed that the melena was caused by rectal varices, which were so severe that they could not be treated by either endoscopic sclerotherapy or surgical devascularization. Taking into considering the overall risk of treating rectal varices, we chose the approach of double balloon-occluded embolotherapy (DBOE) with 5% ethanolamine oleate with iopamodol as a liquid embolic material. DBOE is one of the interventional radiology techniques (Morita et al., Acta Hepatol Jpn 1994;35:109-120), but in this case was a completely new and novel clinical procedure for rectal varices. After the DBOE therapy, the condition of rectal varices was markedly improved. Thus, DBOE might be a new tool for treating inoperable rectal varices.
Asunto(s)
Embolización Terapéutica/instrumentación , Embolización Terapéutica/métodos , Enfermedades del Recto/terapia , Várices/terapia , Anciano , Quimioembolización Terapéutica/instrumentación , Quimioembolización Terapéutica/métodos , Femenino , Humanos , Yopamidol/uso terapéutico , Ácidos Oléicos/uso terapéutico , Enfermedades del Recto/diagnóstico por imagen , Soluciones Esclerosantes/uso terapéutico , Tomografía Computarizada por Rayos X , Várices/diagnóstico por imagenRESUMEN
Few reports exist on the changes in systolic and diastolic coronary flow velocities (CFVs) at baseline and during coronary vasodilation in patients with chronic aortic regurgitation (AR). We examined the left anterior descending CFVs in 21 patients with AR (11 patients with mild AR and 10 patients with moderate to severe AR), 9 patients without AR (no AR group), and 6 patients who had undergone surgery for moderate to severe AR (postoperation group) with transesophageal Doppler echocardiography. Adenosine triphosphate (ATP) was infused into a peripheral right arm vein at four different doses (35, 70, 100, and 140 micrograms/kg/min). Coronary flow velocity response in systole and diastole was calculated as the ratio of systolic peak and mean and diastolic peak and mean CFVs during maximal ATP infusion to those at baseline. The systolic peak and mean CFVs and the diastolic peak and mean CFVs at baseline were significantly increased in the moderate to severe group compared with those in the other groups (p < 0.05, respectively). Systolic and diastolic CFVs were significantly increased during ATP infusions in the four groups. No significant differences of systolic and diastolic CFVs were observed among the four groups during maximal ATP infusion. The coronary flow velocity response calculated from the peak and mean diastolic CFVs were significantly decreased in the moderate to severe group (1.6 +/- 0.3 and 1.7 +/- 0.4) compared with those in the other three groups (3.6 +/- 0.7 and 3.2 +/- 1.1 in the no AR group, 2.6 +/- 0.6 and 2.5 +/- 0.4 in the mild group, and 2.5 +/- 0.7 and 2.4 +/- 0.6 in the postoperation group) (p < 0.05, respectively). In conclusion, the systolic and diastolic left CFVs at baseline appeared to be significantly increased in patients with moderate to severe chronic AR. However, the velocities during coronary vasodilation by ATP were equal to those in other groups, resulting in a decrease of coronary flow velocity response in systole and diastole.
Asunto(s)
Adenosina Trifosfato/farmacología , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/fisiopatología , Circulación Coronaria , Ecocardiografía Doppler de Pulso , Ecocardiografía Transesofágica , Vasodilatación/efectos de los fármacos , Velocidad del Flujo Sanguíneo , Enfermedad Crónica , Factores de Confusión Epidemiológicos , Diástole , Femenino , Humanos , Masculino , Persona de Mediana Edad , SístoleRESUMEN
Assessment of systolic and diastolic coronary blood flow velocities (FVs) in patients with aortic regurgitation (AR) has remained a clinical challenge. We recorded left anterior descending coronary blood FV in 21 patients with chronic AR an in 6 control subjects using transesophageal pulsed Doppler echocardiography. In 7 patients FV was measured 4.0 +/- 5.2 months after aortic valve replacement. Peak and mean FVs during systole and diastole and systolic/diastolic ratios of these FVs were determined. Left ventricular (LV) mass index was calculated by means of standard M-mode echocardiography. In patients with severe AR, peak and mean systolic FVs were significantly increased (34 +/- 8 cm/sec and 21 +/- 6 cm/sec, respectively) compared with FVs in the control group (15 +/- 4 and 12 +/- 3 cm/sec, respectively) and in patients with mild AR (17 +/- 3 cm/sec and 13 +/- 2 cm/sec, respectively). Peak and mean systolic FVs were also significantly increased in severe AR (54 +/- 13 cm/sec and 33 +/- 9 cm/sec, respectively) compared with FVs in the control (30 +/- 8 cm/sec and 21 +/- 5 cm/sec, respectively) and mild AR groups (30 +/- 5 cm/sec and 21 +/- 4 cm/sec, respectively). Peak systolic and diastolic FVs were correlated significantly with LV mass index (r = 0.72 and r = 0.73, respectively). Systolic and diastolic FVs and LV mass index were significantly decreased, normalized or both after aortic valve surgery. In conclusion, LV mass seems to have an effect on the significantly increased systolic and diastolic left coronary blood FV pattern in patients with chronic, severe AR. Increased systolic and diastolic FV appears to be normalized in the late period after surgery.
Asunto(s)
Insuficiencia de la Válvula Aórtica/fisiopatología , Circulación Coronaria , Vasos Coronarios/fisiopatología , Ecocardiografía Doppler de Pulso , Ecocardiografía Transesofágica , Adulto , Anciano , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/cirugía , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Gasto Cardíaco , Enfermedad Crónica , Vasos Coronarios/diagnóstico por imagen , Diástole , Ecocardiografía , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Sístole , Función Ventricular IzquierdaRESUMEN
The mechanism(s) of an inappropriate secretion of insulin is poorly understood. We report a case of reactive hypoglycemia associated with an unusually exaggerated insulin secretion. The patient, a 32-year-old man, developed frequent episodes of postprandial hypoglycemia after interferon treatment was begun for chronic type C hepatitis. Oral glucose challenge test confirmed the patient's extremely high plasma IRI response, i.e., more than 1000 microU/ml, and that of plasma C-peptide 56.9 ng/ml at 90 min, followed by symptomatic hypoglycemia (plasma glucose 34 mg/dl) at 240 min. The plasma proinsulin level also was high, but the molar ratio of immuno reactive insulin (IRI)/plasma C-peptide and IRI/proinsulin was within the normal range. Antibodies to insulin or insulin-receptor were negative. Plasma IRI response was apparently greater when the glucose was given orally than when given intravenously. The response of plasma glucagon-like-peptide (GLP)-1 to oral glucose was quite high (from baseline of 45.5 to 303.2 pmol/L) and showed a close parallel with the change in the plasma IRI concentration. The greatly enhanced insulin secretion leading to reactive hypoglycemia in this patient may therefore be attributed to the increased secretion of GLP-1.
Asunto(s)
Alimentos , Hipoglucemia/etiología , Insulina/metabolismo , Fragmentos de Péptidos/metabolismo , Adulto , Péptido C/sangre , Ayuno , Glucagón , Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Prueba de Tolerancia a la Glucosa , Humanos , Secreción de Insulina , Masculino , Proinsulina/sangreRESUMEN
This study was designed to investigate whether the left ventricular filling profile during preceding control beats significantly affects the pulse deficit caused by ventricular premature contractions (VPCs). The study group consisted of 18 patients (10 men, eight women, 15-85 years old) who underwent electrophysiological catheterization because of sinus bradycardia. Using a temporary pacing lead inserted in the right ventricular apex, isolated VPCs with various coupling intervals were produced by electrical stimulation of the right ventricle. During the production of the VPCs, the mitral filling flow velocity using pulsed wave Doppler echocardiography, the femoral arterial pressure curve and the electrocardiogram were simultaneously recorded. The right ventricle was stimulated 800, 750, 700, 650, 600, 550, 500, 450 and 400 ms after the triggered control beat QRS complex. Pulse pressures during VPCs gradually decreased in relation to the shortening of the extrasystolic beat coupling interval. The longest coupling interval for each subject, which caused complete abolition of the pressure pulse during the VPC, was defined as the pulse deficit coupling interval. The early to late diastolic velocity-time integral ratio (Ei/Ai ratio) of the mitral filling flow velocity during the control beats which precede the VPC was obtained as an index expressing the left ventricular filling profile. The Ei/Ai ratio of the mitral filling flow velocity ranged from 0.7 to 4.5 (1.8 +/- 1.0). The pulse deficit coupling interval ranged from 440 to 640 ms (510 +/- 60 ms).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Complejos Cardíacos Prematuros/fisiopatología , Hemodinámica/fisiología , Pulso Arterial/fisiología , Función Ventricular Izquierda/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Velocidad del Flujo Sanguíneo/fisiología , Bradicardia/fisiopatología , Cateterismo Cardíaco , Complejos Cardíacos Prematuros/diagnóstico por imagen , Diástole/fisiología , Ecocardiografía Doppler , Femenino , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/fisiopatología , Contracción Miocárdica/fisiología , Estudios Prospectivos , Sístole/fisiologíaRESUMEN
A single subcutaneous injection of capsaicin (50 mg/kg) to neonatal Wistar rats induced prominent corneal changes consisting of initial edematous lesions and late degenerative opacities in the epithelium and stroma, with disintegrated epithelial cells on histologic sections. Qualitative and quantitative analyses of the corneal nerves by means of gold chloride impregnation revealed a marked degeneration of the intraepithelial terminal fibers, resulting in a significant decrease in neural density by over 70% of the normal value at 4 and 6 weeks after neonatal capsaicin treatment. Thereafter, regeneration of nerve fibers occurred, but the neural density did not return to the normal level at 6 months after treatment.