RESUMEN
AIMS: Human serum paraoxonase (PON1) is associated with high-density lipoprotein, and inhibits oxidative modification of low-density lipoprotein. Therefore, PON1 is supposed to contribute to the prevention of atherosclerosis. We and other investigators have shown that the enzymatic activities and concentrations of PON1 were decreased in maintenance hemodialysis (HD) patients. However, the effect of PON1 status on the long-term outcome of HD patients has not been reported. In this study, we examined the association between baseline PON 1 status and cardiovascular mortality in an observation study of an outpatient HD population. PATIENTS AND METHODS: The relation between baseline cardiovascular risk factors and clinical events was investigated, during 6 years of follow-up, in 81 HD patients (50 males and 31 females) whose enzymatic activities, concentrations and genetic polymorphisms of PON1 had been determined in a previous study. RESULTS: During follow-up for 6 years, we recorded 42 deaths, including 24 fatal cardiovascular events. In univariate analyses, baseline PON1 concentration was associated with not only cardiovascular mortality (p < 0.005), but also all-cause mortality (p < 0.001) during the period of follow-up, as were age, preexisting cardiovascular disease (CVD) and hemoglobin concentration. In a multivariate Cox regression analysis, PON1 concentration retained significant associations with cardiovascular mortality (p < 0.05) and all-cause mortality (p < 0.005) even after correction of known risk factors for CVD or mortality in HD patients. Using Kaplan-Meier survival curves, we assessed the association between low and high concentrations of PON1 divided according to the median value (7.52 U/ml). Significantly increased cardiovascular mortality (log rank 6.125, p = 0.01) and all-cause mortality (log rank 7.113, p < 0.01) were detected in the patients with low PON1 concentrations. CONCLUSIONS: These data suggest that low PON 1 concentration may be an independent predictor of cardiovascular mortality in maintenance HD patients.
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Arildialquilfosfatasa/sangre , Enfermedades Cardiovasculares/mortalidad , Diálisis Renal , Insuficiencia Renal/terapia , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Análisis de SupervivenciaRESUMEN
To investigate the prevalence and clinical relevance of immunoglobulin (Ig) isotypes of antimyeloperoxidase (MPO) and antilactoferrin (LF) antibodies in collagen diseases, enzyme-linked immunosorbent assay was employed to detect the Ig isotypes of both antibodies. The purified proteins of MPO and LF were used as two major representative antigens for anti-neutrophil cytoplasmic antibodies (ANCA) with a perinuclear staining pattern by an indirect immunofluorescent technique. We examined 131 serum samples from 79 patients with rheumatoid arthritis (RA), 32 with systemic lupus erythematosus (SLE), 14 with progressive systemic sclerosis (PSS), 6 with polymyositis/dermatomyositis (PM/DM), and 5 with idiopathic crescentic glomerulonephritis who served as positive controls and 36 healthy subjects who served as controls. A limited number of patients with RA (4-10%), SLE (6-9%), and PSS (7-14%) but not PM/DM showed positive IgG or IgA anti-MPO antibody (MPO-ANCA) but not IgM MPO-ANCA. However, 10-20% of RA, 40-60% of SLE, 20-36% of PSS but none of the PM/DM patients showed positive IgG, IgA, or IgM anti-LF antibody (LF-ANCA). MPO- and LF-ANCA positivity in RA patients was correlated with markers of disease activity such as the erythrocyte sedimentation rate, C-reactive protein, and serum Ig levels. IgG LF-ANCA but not MPO-ANCA positivity in SLE patients also was correlated with the disease activity index but not with clinical features. Neither MPO- nor LF-ANCA positivity in PSS patients was correlated with any clinical features. Overall, both MPO- and LF-ANCA were found mainly in RA, SLE, and PSS patients but not in PM/DM patients. The Ig isotypes of MPO- and LF-ANCA frequently belonged to both IgG and IgA and rarely to the IgM class. Both MPO- and LF-ANCA positivity reflected disease activity in RA and SLE rather than specific organ involvement.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Autoantígenos/inmunología , Enfermedades Autoinmunes/inmunología , Enfermedades del Colágeno/inmunología , Isotipos de Inmunoglobulinas/sangre , Lactoferrina/inmunología , Peroxidasa/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Especificidad de Anticuerpos , Artritis Reumatoide/inmunología , Dermatomiositis/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Glomerulonefritis/inmunología , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Especificidad de Órganos , Polimiositis/inmunología , Esclerodermia Sistémica/inmunologíaRESUMEN
BACKGROUND: Nitric oxide (NO) is synthesized by endothelial cell NO synthase (ecNOS) on vascular endothelium, and it plays a key role in the regulation of blood flow and pressure. A polymorphism of the ecNOS gene was recently shown to be associated with the development of cardiovascular disease. PATIENTS AND METHODS: We investigated the ecNOS gene polymorphism in 68 Japanese patients with IgA nephropathy (IgAN) and 134 normal controls. RESULTS: The genotype distributions were not different between the normal controls and the IgAN patients (ecNOS4b/b: ecNOS4b/a: ecNOS4a/a = 106:27:1 and 50:18:0, respectively). There was no significant difference in the renal histopathological grading between the patients with ecNOS4b/a and ecNOS4b/b. However, among the subgroup of patients whose duration of illness was two or more years, the advanced histopathological grading was more frequent in the patients with the ecNOS4b/a genotype (than in those with the ecNOS4b/b (p = 0.04)). The incidence of hypertension was also higher in the patients with the ecNOS4b/a genotype (50% in ecNOS4b/a versus 12% in ecNOS4b/b, p = 0.04). CONCLUSION: These results suggest that the ecNOS4b/a genotype (or ecNOS4a allele) of the ecNOS gene polymorphism may be involved in the progression of IgAN.
Asunto(s)
Glomerulonefritis por IGA/genética , Óxido Nítrico Sintasa/genética , Polimorfismo Genético , Adulto , Biopsia , Estudios de Casos y Controles , Femenino , Genotipo , Glomerulonefritis por IGA/enzimología , Glomerulonefritis por IGA/patología , Humanos , Riñón/patología , Masculino , Óxido Nítrico Sintasa de Tipo III , Peptidil-Dipeptidasa A/genética , Factores de TiempoRESUMEN
The rectal absorption of a platinum anti-tumor agent, [bis (acetato) ammine dichloro (cyclohexylamine) platinum(IV)] (BMS-182751), was investigated in rats. BMS-182751 was co-ground with various carriers to improve its poor aqueous solubility. The highest drug dissolution was observed for the co-ground mixture of BMS-182751 and low molecular (LM) gelatin (1:9, w/w), followed by beta-cyclodextrin and polyvinylpyrrolidone. The influence of a suppository base or additive on the rectal absorption of BMS-182751 in the drug state of crystalline powder or co-ground mixture was examined in vitro using excised rat rectum. A macrogol base gave much higher BMS-182751 permeation across the rat rectum than that from a Pharmasol base. The addition of sodium caprylate or caprylic acid to the macrogol base markedly enhanced the drug permeation, and a 3% addition of sodium caprylate to the base afforded maximum drug permeation. Two rectal formulations, the co-ground mixture with LM-gelatin plus 3% sodium caprylate in macrogol and the crystalline drug alone plus 3% sodium caprylate in macrogol, as well as an oral aqueous drug suspension, were administered to rats. The Cmax and AUC0-24h values for platinum from the former suppository were 5.1- and 4.1-fold greater than those from the oral suspension, respectively. The values from the latter suppository were almost comparable to those from the suspension. These results suggest that the suppository may provide a promising therapeutic means for cancer treatment using this platinum agent.
Asunto(s)
Antineoplásicos/farmacocinética , Absorción Intestinal , Compuestos Organoplatinos/farmacocinética , Recto/metabolismo , Administración Rectal , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Masculino , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/química , Ratas , Ratas Sprague-Dawley , Solubilidad , Difracción de Rayos XRESUMEN
Antineutrophil cytoplasmic antibodies (ANCA) for two antigens, i.e. myeloperoxidase (MPO) and lactoferrin (LF) in sera from 19 IgA nephropathy (IgAN), 3 adult Henoch-Schönlein purpura (HSP) and 8 child HSP patients were examined by enzyme-linked immunoabsorbent assay (ELISA) for immunoglobulin isotypes. All of child HSP patients showed negative ANCA. On the other hand, one IgAN patient and two adult HSP patients showed weak positivity for IgA class anti-MPO antibody. There was no patients who showed positivity for IgG and IgM class anti-MPO antibody. In anti-LF antibody, one IgAN and one adult HSP showed positivity in IgG class; 2 IgAN and 2 HSP in IgA class and 2 IgAN and one HSP in IgM class. These results indicate that adult HSP patients have higher prevalence of IgA class anti-MPO antibody and anti-LF antibody than IgAN or child HSP.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/análisis , Glomerulonefritis por IGA/inmunología , Vasculitis por IgA/inmunología , Lactoferrina/inmunología , Peroxidasa/inmunología , Adulto , Niño , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulinas/análisis , Masculino , Persona de Mediana EdadRESUMEN
The incidence, specificity and clinical significance of positivity for serum antineutrophil cytoplasmic antibody (ANCA) was investigated in 60 patients with primary Sjögren's syndrome (SjS). The indirect immunofluorescence (IIF) technique and an enzyme-linked immunosorbent assay (ELISA) were used to measure ANCA. Purified myeloperoxidase (MPO), lactoferrin (LF), cathepsin-G (CTG) and elastase (HLE) served as ANCA antigens for the ELISA. Ten (16.7%) of the 60 SjS patients showed positivity by IIF for perinuclear, but not cytoplasmic, ANCA. Four of the 60 sera were shown to be positive for LF, four for MPO, 0 for CTG and 0 for HLE by ELISA. There was no correlation between ANCA positivity and clinical features. ANCA in patients with SjS might be an epiphenomenon of polyclonal B-cell activation.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos , Síndrome de Sjögren/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Anticitoplasma de Neutrófilos/análisis , Catepsina G , Catepsinas/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Lactoferrina/inmunología , Masculino , Persona de Mediana Edad , Elastasa Pancreática/inmunología , Peroxidasa/inmunología , Serina Endopeptidasas , Síndrome de Sjögren/inmunologíaRESUMEN
A 61-year-old Japanese woman was hospitalized because of general malaise. The patient demonstrated hypertension, hypokalemia and chronic renal failure (CRF). Plasma aldosterone concentration and urinary excretion of aldosterone were elevated. Abdominal computed tomographic scan revealed right adrenal tumor and multiple cysts in both kidneys. Adrenal scintigram using 131I-adosterol disclosed uptake of the isotope in the area corresponding to the adrenal tumor. Plasma aldosterone concentration and renin activity (PRA) in an upright posture and daily variations in adrenocorticotropic hormone, cortisol, aldosterone levels and PRA were compatible with aldosterone-producing adrenocortical adenoma. After administration of spironolactone and manidipine hydrochloride, a calcium antagonist, general malaise disappeared, and blood pressure and serum potassium level returned to the normal range without adrenalectomy. Although adrenalectomy is known to be effective for the treatment of aldosterone-producing adrenocortical adenoma, several papers reporting cases of aldosterone-producing adrenocortical adenoma with CRF indicated that surgical therapy was not always optimal in terms of postoperative conditions. Taken together, the conservative therapy may be one of the choices considering the prognoses of hypertension and renal dysfunction in patients with aldosterone-producing adrenocortical adenoma with CRF.
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Neoplasias de la Corteza Suprarrenal/complicaciones , Adenoma Corticosuprarrenal/complicaciones , Aldosterona/metabolismo , Fallo Renal Crónico/complicaciones , Neoplasias de la Corteza Suprarrenal/diagnóstico , Neoplasias de la Corteza Suprarrenal/metabolismo , Neoplasias de la Corteza Suprarrenal/terapia , Adenoma Corticosuprarrenal/diagnóstico , Adenoma Corticosuprarrenal/metabolismo , Adenoma Corticosuprarrenal/terapia , Hormona Adrenocorticotrópica/sangre , Aldosterona/sangre , Femenino , Humanos , Hidrocortisona/sangre , Persona de Mediana Edad , Renina/sangreRESUMEN
A 46 year-old female presented with dry eyes and a dry mouth which she had been experiencing for about 15 years. She also began to notice dizziness (orthostatic hypotension) during the last 5 years. The symptoms gradually increased whereupon she began to have polyarthralgia, facial flashing, hyper and hyposweating in some areas on the face and trunk. Her sialography showed a damaged parotid gland. Minor salivary gland biopsy revealed chronic sialoadenitis. The Sirmer test was low, and the Rosebengal test indicated keratoconjunctivitis sicca. Her serological tests showed hypocomplementemia and were positive for antinuclear antibody and SS-A antibody. The diagnosis of primary Sjögren's syndrome (SjS) was made based on these findings. Prednisolone, at a dose of 15 mg per day, was given orally. As a result of this therapy, arthralgia disappeared immediately, although it had no effect on the neuropathy found in this patient. This is a rare case of SjS associated with peripheral neuropathy and severe dysautonomia.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/etiología , Enfermedades del Sistema Nervioso Periférico/etiología , Síndrome de Sjögren/complicaciones , Femenino , Glucocorticoides/uso terapéutico , Humanos , Hipohidrosis/etiología , Hipotensión Ortostática/etiología , Persona de Mediana Edad , Prednisolona/uso terapéutico , Síndrome de Sjögren/tratamiento farmacológicoRESUMEN
The established antitumor efficacy of paclitaxel against a variety of human tumors has led to pre-clinical and clinical studies to develop the paclitaxel-based combination regimens. We examined in vivo the antitumor activity and toxicity of the combination of paclitaxel and each of 8 antitumor agents, currently in clinical use, against M-109 murine lung carcinoma implanted subcutaneously into male CDF1 mice. Paclitaxel given intravenously at 24 mg/kg/day on a schedule of consecutive daily injections for 5 days (d1-5) induced reproducibly, in 6 experiments, a significant (37-82%) increase in the survival time of tumor-bearing mice over saline-treated control mice. Cisplatin at 4 and 2 mg/kg/day given intravenously on the same treatment schedule showed no significant antitumor activity when given alone; however, the combination of paclitaxel at 24 mg/kg/day (d1-5) followed by cisplatin at a dose of 2 mg/kg/day (d6-10) induced a significant (P < 0.05) prolongation of the survival time of tumor-bearing mice compared with the group given paclitaxel alone. On the other hand, treatment with these drugs on the reverse sequence caused toxic deaths of all mice. Such sequence-dependent toxic death of mice was also observed with the combination of paclitaxel and carboplatin, etoposide or methotrexate. The combination of paclitaxel and adriamycin, cyclophosphamide, ranimustine or vinblastine (VLB) showed a sequence-independent antitumor activity and a more-than-additive therapeutic effect was observed with the combination of paclitaxel and either VLB or ranimustine. Although the drug administration schedules used here may not be directly applicable to the clinic, knowledge of the nature of the sequence-dependency in paclitaxel-based combination chemotherapy should be useful in the design of clinical trials.
Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Paclitaxel/administración & dosificación , Animales , Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos Fitogénicos/toxicidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Carboplatino/administración & dosificación , Carboplatino/toxicidad , Carcinoma/patología , Cisplatino/administración & dosificación , Cisplatino/toxicidad , Ciclofosfamida/administración & dosificación , Ciclofosfamida/toxicidad , Doxorrubicina/administración & dosificación , Doxorrubicina/toxicidad , Esquema de Medicación , Ensayos de Selección de Medicamentos Antitumorales , Sinergismo Farmacológico , Etopósido/administración & dosificación , Etopósido/toxicidad , Femenino , Inyecciones Intravenosas , Neoplasias Pulmonares/patología , Masculino , Metotrexato/administración & dosificación , Metotrexato/toxicidad , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Compuestos de Nitrosourea/administración & dosificación , Compuestos de Nitrosourea/toxicidad , Paclitaxel/uso terapéutico , Paclitaxel/toxicidad , Vinblastina/administración & dosificación , Vinblastina/toxicidadRESUMEN
We report a rare case of Cushing's syndrome due to bilateral adrenocortical adenomas in a 45-year-old female. She suffered from diabetes mellitus and hypertension for a decade, but her appearance was not Cushingoid. The plasma cortisol level in the morning was at the upper limit of the normal range, but did not show a diurnal rhythm or was suppressed by 1 mg of dexamethasone. The plasma level of ACTH was undetectable, and it failed to respond to human CRH (hCRH). Plasma cortisol responded well to synthetic ACTH. The urinary 17-OHCS level was high, and was not suppressed by 4 mg of dexamethasone. While these findings were consistent with a diagnosis of adrenocortical adenoma, computed tomography showed several nodules in both adrenal glands that suggested the presence of huge nodular adrenocortical hyperplasia or bilateral adrenocortical adenomas. Bilateral adrenalectomy demonstrated the presence of three adenomas, two in the right and one in the left adrenal. Analysis of the extract from each adenoma revealed that two of the three produced an excess amount of cortisol. Magnetic resonance imaging (MRI) of the brain suggested the presence of pituitary adenoma. Prior to adrenalectomy, TSH, GH or LH showed a low response to TRH, GHRH or LHRH, respectively. Since normal responses were restored after bilateral adrenalectomy, these abnormalities were attributed to hypercortisolemia.
Asunto(s)
Neoplasias de la Corteza Suprarrenal/complicaciones , Adenoma Corticosuprarrenal/complicaciones , Síndrome de Cushing/etiología , Neoplasias de la Corteza Suprarrenal/diagnóstico , Neoplasias de la Corteza Suprarrenal/cirugía , Adrenalectomía , Adenoma Corticosuprarrenal/diagnóstico , Adenoma Corticosuprarrenal/cirugía , Hormona Adrenocorticotrópica , Anciano , Ritmo Circadiano/fisiología , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/cirugía , Dexametasona , Femenino , Humanos , HidrocortisonaRESUMEN
To investigate the incidence, the specificity and clinical significance of positivity for serum anti-neutrophil cytoplasmic antibody (ANCA) in 31 patients with systemic lupus erythematosus (SLE), the indirect immunofluorescence (IIF) technique and enzyme-linked immunosorbent assay (ELISA) were used to measure ANCA. Purified myeloperoxidase (MPO), lactoferrin (LF), cathepsin-G (CTG) and elastase (HLE) served as ANCA antigens for ELISA. Thirteen (42%) of the 31 SLE patients showed positivity for perinuclear, but not cytoplasmic, ANCA by IIF. Five of 31 sera were positive for MPO, 10 for LF, 1 for CTG and 0 for HLE by ELISA. Patients positive for ANCA had a higher score of SLE disease activity index (SLEDAI) than those without ANCA. There was no correlation between ANCA positivity, clinical manifestations, or organic involvement. While the ANCA in patients with SLE reflected disease activity, it was unrelated to organic involvement.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/análisis , Lupus Eritematoso Sistémico/inmunología , Adolescente , Adulto , Biomarcadores/análisis , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Masculino , Persona de Mediana Edad , Pronóstico , Valores de Referencia , Sensibilidad y Especificidad , Vasculitis/inmunologíaRESUMEN
We examined paclitaxel for anti-tumor activity against human lung cancer xenografts in nude mice and compared its efficacy with that of cisplatin, currently a key drug for lung cancer chemotherapy. Five non-small cell lung cancers (A549, NCI-H23, NCI-H226, NCI-H460 and NCI-H522) and 2 small cell lung cancers (DMS114 and DMS273) were chosen for this study, since these cell lines have been well characterized as regards in vitro and in vivo drug sensitivity. These cells were exposed to graded concentrations of paclitaxel (0.1 to 1000 nM) for 48 h. The 50% growth-inhibitory concentrations (GI50) for the cell lines ranged from 4 to 24 nM, which are much lower than the achievable peak plasma concentration of paclitaxel. In the in vivo study, 4 cell lines (A549, NCI-H23, NCI-H460, DMS-273) were grown as subcutaneous tumors xenografts in nude mice. Paclitaxel was given intravenously as consecutive daily injections for 5 days at the doses of 24 and 12 mg/kg/day. Against every xenograft, paclitaxel produced a statistically significant tumor growth inhibition compared to the saline control. Paclitaxel at 24 mg/kg/day was more effective than cisplatin at 3 mg/kg/day with the same dosing schedule as above, although the toxicity of paclitaxel was similar to or rather lower than that of cisplatin, in terms of body weight loss. In addition, paclitaxel showed potent activity against 2 other lung cancer xenografts (NCI-H226 and DMS114). Therefore, paclitaxel showed more effective, wider-spectrum anti-tumor activity than cisplatin in this panel of 6 lung cancer xenografts. These findings support the potential utility of paclitaxel in the treatment of human lung cancer.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Paclitaxel/uso terapéutico , Animales , División Celular/efectos de los fármacos , Femenino , Humanos , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante Heterólogo , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
Some patients with rheumatoid arthritis (RA) as well as those with other collagen diseases are positive for antinuclear antibody (ANA). We investigated the frequency of positivity for ANA in 104 patients with RA and evaluated the clinical features and laboratory data in the ANA-positive and -negative groups. The presence of ANA in sera was studied by indirect immunofluorescence using HEp-2 cells as the antigen substrate. Sera with a positive fluorescence at a dilution of 1:20 were considered to be positive for ANA. Of the 104 patients, 39 (37.5%) were positive for ANA. The staining pattern in the positive cases varied, but most were speckled (64.1%) and homogeneous (48.7%). A small number showed a nucleolar (20.5%) or a centromere (10.3%) pattern. None showed a shaggy pattern. The ANA titer was lower in RA patients compared with those with other collagen-related diseases such as systemic lupus erythematosus or progressive systematic sclerosis. None of the patients positive for ANA with either a nucleolar or centromere staining pattern had progressive systemic sclerosis or the CREST syndrome. One patient each had Raynaud's phenomenon and pulmonary fibrosis. There was no correlation between ANA positivity and indicators of joint inflammation. The prevalence of ANA positivity in patients with advanced or prolonged disease was higher than those with early stages or short durations. There was no correlation with drug therapy.
Asunto(s)
Anticuerpos Antinucleares/sangre , Artritis Reumatoide/inmunología , Adulto , Anciano , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
Titrations of anti-hepatitis C core (anti-HCc) immunoglobulin G (IgG) antibodies and its subclasses were studied in 90 patients with acute and chronic hepatitis C virus (HCV) infection, including 27 patients who underwent interferon (IFN) therapy. The positivity rates for each anti-HCc subclass were as follows: 95.2% for IgG1, 12.0% for IgG2, 69.9% for IgG3 and 19.3% for IgG4. The total anti-HCc IgG titre correlated well with the IgG1, titre, indicating that IgG1 was the main virus-specific IgG. Changes of IgG1 production mainly contributed to fluctuations of the anti-HCc IgG titre and corresponded well to positivity for HCV-RNA during and after IFN therapy. IgG3 was detected prior to IgG1 during the early phase of acute hepatitis in some cases and also appeared with relapse after IFN therapy. The serial assay of anti-HCc subclasses showed the patients' humoral immune response to HCV infection, and might be useful for evaluation of anti-viral immunity influenced by IFN therapy.
Asunto(s)
Anticuerpos contra la Hepatitis C/biosíntesis , Hepatitis C/inmunología , Inmunoglobulina G/biosíntesis , Proteínas del Núcleo Viral/inmunología , Enfermedad Aguda , Adulto , Enfermedad Crónica , Estudios de Evaluación como Asunto , Femenino , Hepacivirus/genética , Hepacivirus/inmunología , Hepatitis C/terapia , Humanos , Inmunoglobulina G/clasificación , Interferones/uso terapéutico , Masculino , Persona de Mediana Edad , ARN Viral/biosíntesis , Resultado del TratamientoRESUMEN
Immunoglobulin A class antibody to hepatitis C virus core antigen (IgA anti-HCc) was measured in the serum of 128 patients with type C chronic liver disease. Fifty-eight patients (45.3%) were seropositive. IgA anti-HCc was detected in only one of 20 patients with chronic persistent hepatitis; however, 52.3% (46/88) of patients with chronic active hepatitis and 55% (11/20) of patients with liver cirrhosis were seropositive. Histological examination revealed that 22 (71.0%) of 31 patients with severe disease activity were seropositive compared to 35 (44.9%) of 78 patients with moderate (P < 0.05) and one (5.3%) of 19 patients with mild (P < 0.01) histological changes. IgA anti-HCc was measured sequentially in 65 patients who underwent interferon therapy. There was a significant difference between responders and other patients in the mean ratio of IgA anti-HCc titers one month after therapy. Three months after therapy, IgA anti-HCc was detectable in only two of 15 responders who were IgA anti-HCc seropositive at the start of therapy. In contrast, IgA anti-HCc reappeared three months after therapy despite a temporary decrease to undetectable levels in all nonresponders. We conclude that IgA anti-HCc is a useful marker to identify the presence of active type C liver disease and that the disappearance of IgA anti-HCc three months after interferon therapy predicts a good response in treated patients.
Asunto(s)
Anticuerpos Antivirales/sangre , Hepacivirus/inmunología , Hepatitis C/inmunología , Inmunoglobulina A/sangre , Proteínas del Núcleo Viral/inmunología , Adolescente , Adulto , Anciano , Biopsia , Enfermedad Crónica , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Hepatitis C/patología , Hepatitis C/terapia , Humanos , Interferones/uso terapéutico , Hígado/patología , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
Paclitaxel, an antineoplastic agent, was given to Crj: CD (SD) rats of both sexes at 38, 50, 65 and 85 mg/kg by single intravenous administration to investigate its acute toxicity. The results obtained are summarized as follows: 1. Tachypnea and decreased activity with prone position were noted for vehicle and all paclitaxel groups, and alopecia for all paclitaxel groups. 2. Deaths occurred for one out of 5 males and 2 out of 5 females at 85 mg/kg. One female died of respiratory insufficiency induced by vehicle on Day 0. One female and one male died of the systemic toxicity of paclitaxel such as hypoplasia of the bone marrow and lymphoid depletion of lymphatic organs on Days 6 and 12, respectively. 3. On Days 4 and 5, all paclitaxel groups showed decreases of reticulocyte and white blood cell counts, as well as decrease of differential count of neutrophils. These changes were generally recovered by a week after dosing. 4. Histopathological examinations revealed atrophy of the thymic medulla, hypoplasia of the bone marrow and lymphoid depletion of the spleen for a few males at 85 mg/kg, and hypospermatogenesis and tubular atrophy of the testes for all paclitaxel groups. Based on these results, 85 mg/kg of paclitaxel was lethal to rats, and hematopoietic, lymphoid and male reproductive systems were primarily affected under this condition.
Asunto(s)
Paclitaxel/toxicidad , Alopecia/inducido químicamente , Animales , Atrofia , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Femenino , Inyecciones Intravenosas , Masculino , Neutropenia/inducido químicamente , Paclitaxel/administración & dosificación , Ratas , Ratas Sprague-Dawley , Espermatogénesis/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/patología , Testículo/efectos de los fármacos , Testículo/patología , Timo/efectos de los fármacos , Timo/patologíaRESUMEN
Paclitaxel, an antineoplastic agent, was intravenously given to Crj:CD (SD) rats of both sexes at 0 (saline), 0 (vehicle), 1.0 (low dose), 3.3 (intermediate dose) and 10.0 (high dose) mg/kg at five-day interval over one-month period (6 times in total) to investigate its repeated dose toxicity and the reversibility of toxic effects. The results obtained are summarized as follows: 1. Decreased activity with prone position was observed for high dose and vehicle groups, and alopecia was seen for many high dose rats. Body weight gain and food intake were suppressed for high and intermediate dose groups. No deaths occurred. 2. Red blood cell count, hemoglobin, hematocrit, white blood cell count, relative neutrophil count, platelet count and reticulocyte count were decreased for high dose groups. Red blood cells count was also decreased for intermediate dose groups. 3. Thymic atrophy, splenic hematopoiesis, bone marrow hypoplasia, testicular atrophy with suppression of spermatogenesis and tubular atrophy, and epididymal atrophy were observed for high dose rats. 4. Above-described changes excluding the findings on the testis and epididymis for high dose rats were shown to be generally reversible. Based on these results, the no-toxic effect dose of paclitaxel was estimated to be 1.0 mg/kg in rats under this study condition.
Asunto(s)
Paclitaxel/toxicidad , Alopecia/inducido químicamente , Animales , Atrofia , Recuento de Células Sanguíneas/efectos de los fármacos , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Esquema de Medicación , Ingestión de Alimentos/efectos de los fármacos , Femenino , Hematopoyesis/efectos de los fármacos , Inyecciones Intravenosas , Masculino , Paclitaxel/administración & dosificación , Ratas , Ratas Sprague-Dawley , Espermatogénesis/efectos de los fármacos , Bazo/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/patología , Timo/efectos de los fármacos , Timo/patología , Aumento de Peso/efectos de los fármacosRESUMEN
Paclitaxel, an antineoplastic agent, was intravenously given to Crj:CD (SD) rats of both sexes at 0 (saline), 0 (vehicle), 0.3 (low dose), 1.0 (intermediate dose) and 3.3 (high dose) mg/kg at seven-day interval over a six-month period (total of 27 doses) to investigate its repeated dose toxicity. The results obtained are summarized as follows: 1. No deaths occurred in this study. Vehicle-related salivation was seen for some high dose and vehicle control rats. Soiling of the perigenital region was observed for some high dose females. 2. Red blood cell count, hemoglobin, hematocrit and white blood cell count were decreased for high dose rats. Reticulocyte count was increased and relative neutrophil count was decreased for high dose males. 3. Relative erythroid and myeloid cell count were decreased for high dose rats in bone marrow smear examinations. 4. Bone marrow hypoplasia and splenic hemosiderosis were observed for high dose rats, and thymic atrophy and lymphoid depletion were seen for some high dose males. Based on the these results, the no-toxic effect dose of paclitaxel was estimated to be 1.0 mg/kg in rats under this study condition.
Asunto(s)
Paclitaxel/toxicidad , Animales , Atrofia , Recuento de Células Sanguíneas/efectos de los fármacos , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Recuento de Células/efectos de los fármacos , Esquema de Medicación , Femenino , Hemosiderosis/inducido químicamente , Inyecciones Intravenosas , Tejido Linfoide/efectos de los fármacos , Masculino , Paclitaxel/administración & dosificación , Ratas , Ratas Sprague-Dawley , Enfermedades del Bazo/inducido químicamente , Timo/efectos de los fármacos , Timo/patologíaRESUMEN
Paclitaxel, an antineoplastic agent, was administered intravenously to Crj: CD (SD) rats daily at dose levels of 0 (saline and vehicle), 0.1, 0.3 and 1.0 mg/kg for 63 days prior to mating and during the mating period in males, and for 14 days prior to mating and during the mating period as well as day 0 to day 7 of gestation in females. Results were as follows: 1. Body weight gains were shown a tendency to hasten in vehicle-treated male rats associated with the increased food consumption. However, the vehicle-treated group had no effect in the other parameters that were measured in this study when compared to the saline-treated group. 2. 1.0 mg/kg paclitaxel caused suppression of the body weight gains accompanied by the decreased food consumption in either male or female rats. 3. Adrenal and ovarian weights were decreased in 1.0 mg/kg dams at term. 4. The fertility indices in both sexes of 1.0 mg/kg were lower than the saline-treated group. However, the copulation indices in both sexes in 1.0 mg/kg rats were comparable to those of the saline-treated group. 5. Decreases in the number of corpora lutea, implantations and live fetuses or increases in the number of empty implantation sites and total embryo-fetal deaths were observed in 1.0 mg/kg dams. However, the fetal weights, crown-rump distances and tail lengths in live fetuses were not affected by paclitaxel treatment. Based on the reproductive and developmental indices, the no toxic-effect dose level of paclitaxel is 0.3 mg/kg/day for parent animals and their fetuses.