RESUMEN

The aim of this study was to determine the effects of an acrylic-based resilient liner (ARL) on masticatory ability by verifying the null hypothesis that masticatory performance and mandibular movements do not differ between people who wear mandibular complete dentures with ARL and those who wear complete dentures with conventional acrylic resin (CAR). From April 2004 to July 2006, we conducted a randomized controlled trial study at two centres. After written informed consent was obtained from 74 edentulous patients, they were randomly allocated to either the ARL group or CAR group. Masticatory performance and mandibular movement at the lower incisal point during chewing were measured as the outcomes. We did not observe significant differences in both outcomes between the groups. The chewing cycles were significantly different during the initial, middle, and final phases of mastication. Within the limitations of the current study, the results indicate that the acrylic-based resilient denture liners used have no clinical impact on the masticatory ability of complete denture wearers.

Asunto(s)

Resinas Acrílicas/química , Materiales Dentales/química , Alineadores Dentales , Dentadura Completa Inferior , Masticación/fisiología , Anciano , Anciano de 80 o más Años , Proceso Alveolar/patología , Índice de Masa Corporal , Diseño de Dentadura , Dentadura Completa Superior , Femenino , Estudios de Seguimiento , Humanos , Arcada Edéntula/patología , Masculino , Mandíbula/patología , Mandíbula/fisiopatología , Persona de Mediana Edad , Movimiento , Factores de Tiempo

RESUMEN

OBJECTIVES: :We present a novel method of scanning for intra-abdominal fat volume by helical computed tomography (CT), and describe the clinical significance of measuring the volumes of intra-abdominal visceral fat (V(vol)) and subcutaneous fat (S(vol)) vs these respective areas determined by conventional slice-by-slice CT at the umbilical level. METHOD: Subjects with obesity or hyperlipidemia (79 men, 74 women) were recruited for this study. We obtained helical CT scans with a tube current of 150 mA, voltage of 120 kV and 2:1 pitch (table speed in relation to slice thickness), starting at the upper edge of the liver and continuing until the pelvis. The intra-abdominal visceral fat volume was measured by drawing a line within the muscle wall surrounding the abdominal cavity. The abdominal subcutaneous fat volume was calculated by subtracting the visceral fat volume from the total abdominal fat volume. By comparison, the intra-abdominal visceral and subcutaneous fat areas were determined at the umbilical level by the established slice-by-slice CT scanning technique. RESULTS: V(vol) was correlated positively with visceral fat area (V(area)) measured by conventional CT in both genders (in men (n=79) V(vol) vs V(area), r=0.81 P<0.0001; in women (n=74) V(vol) vs V(area), r=0.85, P<0.0001). S(vol) also showed a positive correlation with subcutaneous fat area (S(area)) in both genders (in men (n=78) S(vol) vs S(area), r=0.95, P<0.0001; in women (n=74) S(vol) vs S(area), r=0.92, P<0.0001). CONCLUSION: We have reported a novel method for measuring intra-abdominal fat volume by the use of helical CT.

Asunto(s)

Abdomen , Tejido Adiposo/diagnóstico por imagen , Composición Corporal , Hiperlipidemias/diagnóstico por imagen , Obesidad/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Índice de Masa Corporal , HDL-Colesterol/sangre , Femenino , Humanos , Leptina/sangre , Lípidos/sangre , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Caracteres Sexuales , Triglicéridos/sangre , Vísceras

RESUMEN

BACKGROUND: Atorvastatin is a recently introduced statin that lowers LDL-cholesterol (LDL-C) and triglycerides more than some of the older statins. METHODS: Twenty-one Japanese hyperlipidemic subjects were treated with atorvastatin (10 mg/day) for 6 weeks. Plasma lipid concentrations and pre-heparin plasma LPL mass before and after oral administration were evaluated using an open crossover trial format. LPL mass in the pre-heparin plasma was measured by a sandwich enzyme immunoassay. RESULTS: Atorvastatin decreased plasma triglyceride (TG) concentration (-21%, p<0.05), as well as plasma total and LDL-cholesterol concentrations. LPL mass in the pre-heparin plasma did not change significantly by this treatment during this period. Both apolipoprotein (apo) B and E decreased considerably (-33%, p<0.001 for apo B; -29% p<0.001 for apo E), while apo A-I concentration did not change. Other clinical parameters such as body mass index, blood pressure, and fasting plasma glucose concentration of these subjects did not change during this treatment. CONCLUSIONS: Atorvastatin is effective in reducing plasma TG, which did not appear to be associated with an increased LPL mass.

Asunto(s)

Ácidos Heptanoicos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/enzimología , Lipoproteína Lipasa/sangre , Pirroles/uso terapéutico , Anciano , Apolipoproteínas B/metabolismo , Apolipoproteínas E/metabolismo , Atorvastatina , Glucemia/metabolismo , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Triglicéridos/sangre

RESUMEN

A 61-year-old Japanese woman with heterozygous familial hypercholesterolemia (FH), type 2 diabetes mellitus and coronary artery disease underwent coronary artery bypass grafting (CABG) utilizing a saphenous vein graft at the age of 46, in June 1984, 6 months before low density lipoprotein (LDL) apheresis was started. She had received LDL apheresis every two weeks, along with combined drug treatment since the age of 47 (December 1984). She had bilateral xanthelasma and Achilles tendon xanthomas. Her fasting baseline serum total cholesterol and triglyceride level were 464 mg/dl and 57 mg/dl, respectively at the age of 47 when she visited our hospital for the first time. Analysis of the genomic DNA from the patient revealed heterozygous amino acid substitution of Leu for Pro664 in the LDL receptor gene. She was diagnosed as type 2 diabetes mellitus at the age of 53. Combined treatment in the steady state yielded a pretreatment LDL cholesterol level of 230+/-14 mg/dl and a posttreatment level of 57+/-7.6. All grafts were widely patent after as long as 14 years since CABG, suggesting that LDL apheresis combined with drug therapy is highly effective in preventing the occlusion of bypass grafts in a patient with heterozygous FH and type 2 diabetes mellitus.

Asunto(s)

Eliminación de Componentes Sanguíneos , Puente de Arteria Coronaria , Oclusión de Injerto Vascular/prevención & control , Hiperlipoproteinemia Tipo II/terapia , Lipoproteínas LDL/sangre , Mutación Puntual , Receptores de LDL/genética , Vena Safena/trasplante , Aorta/cirugía , Angiografía Coronaria , Enfermedad Coronaria/sangre , Enfermedad Coronaria/cirugía , Vasos Coronarios/cirugía , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Estudios de Seguimiento , Oclusión de Injerto Vascular/sangre , Humanos , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/genética , Persona de Mediana Edad , Resultado del Tratamiento

RESUMEN

Type 1 diabetes mellitus in nonobese diabetic (NOD) mice, a well-known model of human type 1 diabetes, has been considered to be caused by the destruction of insulin-producing beta cells in the islets of the pancreas by self-reactive T cells. Antigen-presenting cells like dendritic cells (DCs) and macrophages are expected to be involved in the processes from their role in generating regulatory or effector T cells. These immunohistochemical studies revealed that CD11c-positive DCs already appeared in the islets of NOD mice as early as 4 weeks old when lymphocytes were not yet infiltrated in the islet, and thus insulitis was not developed. DCs were first observed to locate around swollen parainsular vessels. From age 7 weeks onward to age 13 weeks, more DCs were present in parainsular areas where lymphocytes had also accumulated, and the number of DCs in the islets as well as lymphocytes increased. However, at the end stage of insulitis from age approximately 17 weeks onward, the number of DCs in the islets decreased. In contrast, accumulation of DCs in the para- and periislets was not observed in 7- and 17-week-old ICR female mice that do not develop type 1 diabetes. Double-staining studies using confocal laser scanning microscopy showed that the CD11c-positive DCs coexpress both major histocompatibility (MHC) class II and costimulatory molecules, CD80 and CD86. Electron-microscopy studies further demonstrated that cell bodies and processes of the DCs make close contact with lymphocytes. These results suggest that DCs infiltrated into the pancreatic islets are capable of stimulating T cells by the MHC class II-antigenic peptide complex, together with costimulatory molecules, which eventually lead to the beta-cell destruction in NOD mice.

Asunto(s)

Células Dendríticas/patología , Diabetes Mellitus Tipo 1/patología , Islotes Pancreáticos/patología , Animales , Anticuerpos Monoclonales , Antígenos CD11/análisis , Comunicación Celular , Gránulos Citoplasmáticos/ultraestructura , Células Dendríticas/inmunología , Femenino , Linfocitos/patología , Ratones , Ratones Endogámicos ICR , Ratones Endogámicos NOD , Microscopía Electrónica , Microvellosidades/ultraestructura , Linfocitos T/patología

RESUMEN

In order to test whether a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor has an anti-atherogenic activity, the effects of carvastatin, a newly developed potent inhibitor, and pravastatin were examined on the intimal thickening of the artery after the endothelial denudation induced by balloon catheter injury. Rabbits were divided into four groups; control, pravastatin-treated (20 mg kg(-1) day(-1)) and two of carvastatin-treated groups (10 or 20 mg kg(-1) day(-1)). Two weeks after balloon catheter injury, the areas of intima and media of the injured carotid arteries were determined, and the ratios of intima to media (I/M) were calculated as an index of intimal thickening. Average I/M ratios of the injured artery were 0.42+/-0.05 for control, 0.49+/-0.07 for pravastatin, 0.19+/-0.03 (10 mg kg(-1) day(-1)) and 0.20+/-0.04 (20 mg kg(-1) day(-1)) for carvastatin-treated rabbits, respectively. Thus, carvastatin reduced I/M ratio of the injured artery to approximately half versus control, but pravastatin failed to suppress the intimal thickening. For in vitro study, vascular smooth muscle cells (SMC) from rabbit aorta were explanted, then cultured, and the effects of carvastatin on SMC migration and SMC proliferation were also examined. Carvastatin inhibited dose-dependently SMC migration and SMC proliferation with IC50 values of 0.5 microM and 1 microM, respectively. These inhibitory effects of carvastatin were cancelled by the coexistence of mevalonate, a metabolite of cholesterol synthesis. Our results suggest that carvastatin may be useful in rabbits as an anti-atherogenic drug by means of the inhibition of SMC migaration or SMC proliferation.

Asunto(s)

Arterias Carótidas/efectos de los fármacos , Cateterismo/efectos adversos , Movimiento Celular/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Músculo Liso Vascular/citología , Naftalenos/farmacología , Piranos/farmacología , Animales , Anticoagulantes/farmacología , Arteriosclerosis/tratamiento farmacológico , Arteriosclerosis/patología , Becaplermina , Carcinoma Hepatocelular , Arterias Carótidas/patología , División Celular/efectos de los fármacos , LDL-Colesterol/biosíntesis , Humanos , Masculino , Ácido Mevalónico/farmacología , Músculo Liso Vascular/química , Músculo Liso Vascular/metabolismo , Naftalenos/química , Factor de Crecimiento Derivado de Plaquetas/farmacología , Pravastatina/farmacología , Proteínas Proto-Oncogénicas c-sis , Piranos/química , Conejos , Receptores de LDL/biosíntesis , Células Tumorales Cultivadas , Túnica Íntima/efectos de los fármacos

RESUMEN

The NOD mouse has been used to explore the many features of insulin-dependent diabetes mellitus (IDDM) that is caused by the destruction of insulin-producing beta cells in the islets of Langerhans of the pancreas. Self-reactive T cells have been considered to mediate IDDM in the NOD mouse, and antigen-presenting cells like DC and macrophages are expected to be involved in the processes from their role in generating regulatory or effector T cells. The present study shows that transfer of IFN-gamma-stimulated DC of the NOD or ICR mouse into the NOD mouse did not accelerate IDDM onset but afforded long-lasting protection against clinical and histological signs of IDDM in the recipient mice. The anti-diabetogenic ability was unique to IFN-gamma-stimulated DC when compared with unstimulated DC. A considerable proportion of the injected IFN-gamma-stimulated DC was demonstrated to migrate into the pancreas and its associated lymphoid tissues, suggesting the DC exert their anti-diabetogenic effects there. These findings suggest that development of autoimmune diabetes in the NOD mouse is under the control of DC, and that IDDM onset could be controlled by appropriately manipulating DC systems in vivo, which may open the gate for the therapeutic application of ex vivo-conditioned DC to human IDDM.

Asunto(s)

Células Presentadoras de Antígenos/inmunología , Enfermedades Autoinmunes/inmunología , Células Dendríticas/inmunología , Diabetes Mellitus Tipo 1/inmunología , Interferón gamma/farmacología , Traslado Adoptivo , Animales , Enfermedades Autoinmunes/patología , Células Dendríticas/patología , Diabetes Mellitus Tipo 1/patología , Femenino , Humanos , Islotes Pancreáticos/inmunología , Islotes Pancreáticos/patología , Masculino , Ratones , Ratones Endogámicos ICR , Ratones Endogámicos NOD

RESUMEN

On polyacrylamide gel (PAG) disc electrophoresis of serum lipoproteins, the band(s) which migrates between pre beta- and beta-lipoproteins was more frequently observed in hyperlipidemics with diabetes mellitus (73%), than in those without diabetes mellitus (37%) (P < 0.01). Those bands were seen at three positions between pre beta- and beta-lipoproteins. A higher incidence of coronary artery disease (CAD) was observed in patients with midband as a shoulder of beta-lipoproteins (44%), than in those without midband (11%) (P < 0.05) after the matching of other risk factors. These results suggest that midband as a shoulder of beta-lipoproteins may be a risk factor for CAD in diabetes mellitus with hyperlipidemia.

Asunto(s)

Enfermedad Coronaria/complicaciones , Complicaciones de la Diabetes , Hiperlipidemias/complicaciones , Lipoproteínas LDL/sangre , Enfermedad Coronaria/sangre , Diabetes Mellitus/sangre , Electroforesis Discontinua , Hemoglobina Glucada/análisis , Lipoproteínas de Alta Densidad Pre-beta , Humanos , Hiperlipidemias/sangre , Lipoproteínas HDL/sangre , Factores de Riesgo

RESUMEN

BACKGROUND: In mutations of the low-density lipoprotein (LDL) receptor gene, the defect of internalization is caused by a mutation in the cytoplasmic domain of the receptor linked with exons 17 and 18, and the O-linked sugar domain linked with exon 15 has been speculated not to affect the function of the receptor. Here, we describe a novel mutation of the O-linked sugar domain of the LDL receptor gene, designated familial hypercholesterolaemia (FH)-Mishima with Japanese pedigree, which resembles but still differs from classical defective internalization cases. METHODS: LDL metabolism was examined in cultured skin fibroblasts from patients. Immunoprecipitation and immunohistochemical techniques were applied for the detection of the receptor protein size and distribution. Screening of the mutant exon(s) of the LDL receptor gene was performed using the polymerase chain reaction-single-strand conformation polymorphism technique (PCR-SSCP), and sequencing of the mutated alleles was carried out using the dideoxy chain termination method. RESULTS: LDL-binding activity at 4 degrees C in skin fibroblasts from patients was similar to normal, but that at 37 degrees C with the ligand decreased time dependently and was lost at 6 h, resulting in the defect of internalization and degradation of LDL. The receptor protein on the cell surface was detected at 4 degrees C by IgG-C7, an anti-LDL receptor antibody, but was not detected after incubation with LDL at 37 degrees C. The size of the receptor was 112 kD as determined by immunoprecipitation analysis. A deletion of two nucleotides in exon 15 was detected in the DNA sequence of the LDL receptor gene. The deletion results in a shift of the reading frame after Thr-713 of the mutant and makes a stop codon at amino acid 759. CONCLUSION: Deletion of the two nucleotides caused novel amino acid sequences after the O-linked sugar domain, which has the ability of sorting on the cell membrane at 4 degrees C, but not at 37 degrees C in vivo, resulting in the complete cessation of activity of the LDL receptor.

Asunto(s)

Hiperlipoproteinemia Tipo II/genética , Receptores de LDL/genética , Eliminación de Secuencia , Secuencia de Aminoácidos , Secuencia de Bases , Membrana Celular/metabolismo , Células Cultivadas , Niño , ADN/genética , Exones , Femenino , Fibroblastos/metabolismo , Humanos , Hiperlipoproteinemia Tipo II/metabolismo , Japón , Lipoproteínas LDL/metabolismo , Lipoproteínas VLDL/metabolismo , Masculino , Datos de Secuencia Molecular , Peso Molecular , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Receptores de LDL/química , Receptores de LDL/metabolismo , Temperatura

RESUMEN

Effects of fatty acids on intimal thickening induced by a balloon catheter injury model were investigated by feeding rabbits a small amount of either lard [L] or fish oil [F]. Serum lipids of these groups were not different from those of basal diet-fed rabbits [controls] after 4 weeks of feeding. Serum saturated fatty acids such as 14:0, 16:0, and 18.0 were significantly greater in the L-fed rabbits compared with controls, but those of the aorta were not significantly different. Fatty acid composition of the F-fed rabbits was only different from that of the controls in that n-3 fatty acids slightly increased. The mean and maximum intimal thickening 2 weeks after ballooning, carried out 2 weeks after feeding, were significantly higher in the carotid arteries of the L-fed rabbits than in the controls. The intimal thickening of the F-fed rabbits did not significantly differ from that of the controls. These results suggest that lard promotes the formation of the smooth muscle cell dominant type of arteriosclerosis without affecting serum lipid levels.

Asunto(s)

Cateterismo , Grasas de la Dieta/administración & dosificación , Lípidos/sangre , Túnica Íntima/patología , Alimentación Animal , Animales , Peso Corporal , Colesterol/sangre , HDL-Colesterol/sangre , Grasas de la Dieta/efectos adversos , Modelos Animales de Enfermedad , Ácidos Grasos/sangre , Aceites de Pescado/administración & dosificación , Masculino , Conejos , Trombosis/sangre , Trombosis/etiología , Trombosis/patología , Triglicéridos/sangre

RESUMEN

The binding characteristic of PHB depolymerase has been studied by using glutathione S-transferase (GST) fusion proteins with substrate-binding domain of three bacterial PHB depolymerases, Alcaligenes faecalis, Comamonas acidovorans and Comamonas testosteroni. Analysis using immuno-gold labeling technique and transmission electron microscopy indicated that a novel GST fusion protein derived from A. Faecalis enzyme adsorbed to the surface of poly(3-hydroxybutyric acid) (P(3HB)) single crystals like other fusion proteins. Comparison of inhibiting degree of P(3HB) powder hydrolysis activity of PHB depolymerase by fusion proteins indicated that three fusion proteins bind to P(3HB) powder in the same degree. The measurement of the surface hydrophobicity of proteins suggests that the interaction of the substrate-binding domain with insoluble P(3HB) may include not only a hydrophobic effect but also molecule-specific contacts.

Asunto(s)

Aciltransferasas/farmacocinética , Hidroxibutiratos/farmacocinética , Poliésteres/farmacocinética , Aciltransferasas/genética , Adsorción , Alcaligenes/enzimología , Secuencia de Aminoácidos , Glutatión Transferasa/genética , Glutatión Transferasa/farmacocinética , Bacilos y Cocos Aerobios Gramnegativos , Datos de Secuencia Molecular , Proteínas Recombinantes de Fusión/farmacocinética , Alineación de Secuencia , Propiedades de Superficie

Asunto(s)

Trastorno Autístico/diagnóstico , Electroencefalografía , Epilepsia del Lóbulo Frontal/diagnóstico , Epilepsia/diagnóstico , Adolescente , Adulto , Factores de Edad , Edad de Inicio , Trastorno Autístico/epidemiología , Trastorno Autístico/fisiopatología , Niño , Preescolar , Comorbilidad , Epilepsia/epidemiología , Epilepsia/fisiopatología , Epilepsia del Lóbulo Frontal/fisiopatología , Estudios de Seguimiento , Lóbulo Frontal/fisiopatología , Humanos , Discapacidad Intelectual/epidemiología , Discapacidad Intelectual/fisiopatología

RESUMEN

A poly(3-hydroxybutyric acid) (PHB) depolymerase gene of Comamonas testosteroni YM1004 was cloned on Sau3AI fragment from genomic DNA into Escherichia coli DH5. Nucleotide sequence analysis dedicated a 1539 bp open reading frame encoding a protein 513 amino acid with a putative 25 residue signal peptide for secretion. The deduced amino acid sequence was very similar to that of PHB depolymerase of Comamonas sp. In order to understand the characteristics of substrate-binding domain of the depolymerase, we constructed its glutathione S-transferase (GST) fusion protein and investigated the ability of adsorption on PHB single crystals by using gold-conjugated antibody and transmission electron microscopy. The fusion protein adsorbed on PHB single crystals tightly and homogeneously, suggesting that binding domain contributes to the adsorption of enzyme on solid PHB without site specificity.

Asunto(s)

Hidrolasas de Éster Carboxílico/química , Hidrolasas de Éster Carboxílico/genética , Bacilos y Cocos Aerobios Gramnegativos/enzimología , Bacilos y Cocos Aerobios Gramnegativos/genética , Secuencia de Aminoácidos , Hidrolasas de Éster Carboxílico/metabolismo , Clonación Molecular , ADN Bacteriano/análisis , Glutatión Transferasa/genética , Inmunohistoquímica , Microscopía Electrónica , Datos de Secuencia Molecular , Unión Proteica/fisiología , Estructura Terciaria de Proteína , Proteínas Recombinantes de Fusión/metabolismo , Análisis de Secuencia de ADN

RESUMEN

S-1 is a newly developed antineoplastic agent consisting of the mixture of tegafur (FT), 5-chloro-2, 4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1. As part of a reproductive and developmental toxicity study of S-1, a fertility study was carried out in Sprague-Dawley rats. Twenty-four male rats were administered S-1 orally starting at 64 days before mating and 24 female rats were administered S-1 orally from 15 days before mating to day 7 of pregnancy at doses of 0, 1, 4, or 7 mg/kg/day (as a dose of FT) in order to investigate the effect of S-1 on the reproductive ability and development of embryos and fetuses. There were no dose-related changes in clinical signs. Body weight gains and food consumption were decreased and were associated with the decreased weights of thymus, testis and epididymis in male rats receiving S-1 at the 7 mg/kg/day group. In females, the only organ affected was the kidney at 7 mg/kg/day. There were no dose-related changes in copulation, fertility, pre-implantation loss and implantation. Decreases in live fetal body weight and retardation of fetal ossification were observed in the 7 mg/kg/day group. There were no dose-related changes in post-implantation loss, and no fetal malformations were observed. The results suggest that the non-observed effects dose level of S-1 for general toxicity in male and female rats in 4 mg/kg/day, for reproductive toxicity in adults is more than 7 mg/kg/day, and for developmental toxicity in utero is 4 mg/kg/day.

Asunto(s)

Antimetabolitos Antineoplásicos/toxicidad , Desarrollo Embrionario y Fetal/efectos de los fármacos , Fertilidad/efectos de los fármacos , Ácido Oxónico/toxicidad , Piridinas/toxicidad , Tegafur/toxicidad , Anomalías Inducidas por Medicamentos , Administración Oral , Animales , Antimetabolitos Antineoplásicos/administración & dosificación , Peso Corporal/efectos de los fármacos , Huesos/anomalías , Huesos/efectos de los fármacos , Combinación de Medicamentos , Ingestión de Alimentos/efectos de los fármacos , Femenino , Masculino , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Ácido Oxónico/administración & dosificación , Ácido Oxónico/química , Embarazo , Piridinas/administración & dosificación , Piridinas/química , Ratas , Tegafur/administración & dosificación , Tegafur/química

RESUMEN

S-1 is a newly developed antineoplastic agent consisting of the mixture of tegafur (FT), 5-chloro-2, 4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1. The teratogenic potential of S-1 was studied in rats given S-1 at the daily oral doses of 0, 1, 3, 5 and 7 mg/kg/day (as a dose of FT). S-1 was given from day 7 to day 17 of pregnancy. The study included postnatal evaluation of the growth, development, and reproductive performance of the F1 generation. In rats receiving 7 mg/kg of S-1, maternal body weight gain and food consumptions were reduced, stillbirths increased, livebirths decreased slightly and F1 viability decreased. Fetal body weights decreased significantly in rats receiving 5 mg/kg or more of S-1. External and skeletal anomalies did not increase, but hydrocephaly increased slightly and total number of visceral anomalies increased significantly in the fetuses of rats receiving 7 mg/kg of S-1. Hydrocephaly was observed also in F1 offspring from the rats receiving 7 mg/kg of S-1 during lactation period. Body weight gains of F1 offspring from the rats receiving 7 mg/kg of S-1 during lactation period was reduced. Functional development, emotional tests, learning tests, reproductive performance of the F1 generation and development of the F2 generation were not effected by the S-1 administration. In conclusion, under the condition of this study, the non-observed effect dose levels (NOELs) of S-1 for general toxicity for dams was 5 mg/kg/day, however, NOELs of S-1 was determined to be 7 mg/kg/day or more for reproductive ability. The NOELs of S-1 for the offspring was established to be 3 mg/kg/day.

Asunto(s)

Anomalías Inducidas por Medicamentos , Antimetabolitos Antineoplásicos/toxicidad , Desarrollo Embrionario y Fetal/efectos de los fármacos , Ácido Oxónico/toxicidad , Preñez/efectos de los fármacos , Piridinas/toxicidad , Tegafur/toxicidad , Administración Oral , Animales , Animales Recién Nacidos/crecimiento & desarrollo , Animales Recién Nacidos/psicología , Antimetabolitos Antineoplásicos/administración & dosificación , Peso Corporal/efectos de los fármacos , Huesos/anomalías , Huesos/efectos de los fármacos , Combinación de Medicamentos , Ingestión de Alimentos/efectos de los fármacos , Femenino , Fertilidad/efectos de los fármacos , Masculino , Nivel sin Efectos Adversos Observados , Ácido Oxónico/administración & dosificación , Embarazo , Piridinas/administración & dosificación , Ratas , Reproducción/efectos de los fármacos , Tegafur/administración & dosificación

RESUMEN

S-1 is a newly developed antineoplastic agent consisting of the mixture of tegafur (FT), 5-chloro-2, 4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1. As part of a reproductive and developmental toxicity study of S-1, a teratogenicity study was carried out in rabbits administered daily oral doses of S-1 0, 0.5, 1, or 1.5 mg/kg/day (as a dose of FT). S-1 was administered from day 6 to day 18 of pregnancy. Two additional studies were conducted in order to evaluate the effect on embryos or fetuses at higher S-1 dosage. One study (additional study I) tested during organogenesis dividing it into 3 periods (Day 6-10, Day 10-14, and Day 14-18) at doses of 2, 4 or 6 mg/kg/day. Another study (additional study II) tested during organogenesis dividing it into 4 periods (Day 8 x 9, Day 10 x 11, Day 12 x 13, and Day 14 x 15) at doses of 3 or 6 mg/kg/day due to many embryo deaths at high dose level in the additional study I. The results were as follows. 1. Teratogenicity study One dam died on day 16 of pregnancy and there was a weak teratogenic potential in the 1.5 mg/kg/day group. There were no remarkable other changes in dams and fetuses. The non-observed effects dose level of S-1 for general toxicity in dams was 1 mg/kg/day, for pregnancy in dams was 1.5 mg/kg/day, and for development of fetuses was 1 mg/kg/day under the conditions of this study. 2. Additional study I Abortion was observed at 6 mg/kg/day in the day 14-18 administration group. General toxicity in dams were observed in all administration groups. Fetal lethality was observed at 4 mg/kg/day or more in the day 6-10 and day 10-14 groups, and at 6 mg/kg/day in the day 14-18 administration group. Inhibition of fetal growth was observed at 2 mg/kg/day in the day 10-14 group and at 2 mg/kg/day or more in the day 14-18 administration group. There was a week teratogenic potential at 2 mg/kg/day or more in the day 10-14 groups and at 4 mg/kg/day in the day 14-18 administration group. 3. Additional study II Abortion was observed at 6 mg/kg/day in the day 8-9, day 10-11, and day 12-13 administration groups. General toxicity in dams were observed in all administration groups. Fetal lethality was observed at 3 mg/kg/day in the day 8-9 group and at 6 mg/kg/day in all administration groups. Inhibition of fetal growth and teratogenic potential were clearly observed at 3 mg/kg/day in the day 8-9 and day 10-11 groups, and at 6 mg/kg/day in the day 12-13 and day 14-15 administration groups. 4. In conclusion, when S-1 was administered at a low dose (< = or 1.5 mg/kg/day) during organogenesis effects were not detected clearly. When higher doses were administered (2-6 mg/kg/day), fetal lethality, inhibition of fetal growth, and teratogenicity were observed.

Asunto(s)

Anomalías Inducidas por Medicamentos , Antimetabolitos Antineoplásicos/toxicidad , Desarrollo Embrionario y Fetal/efectos de los fármacos , Ácido Oxónico/toxicidad , Preñez/efectos de los fármacos , Piridinas/toxicidad , Tegafur/toxicidad , Administración Oral , Animales , Antimetabolitos Antineoplásicos/administración & dosificación , Peso Corporal/efectos de los fármacos , Huesos/anomalías , Huesos/efectos de los fármacos , Combinación de Medicamentos , Ingestión de Alimentos/efectos de los fármacos , Femenino , Masculino , Nivel sin Efectos Adversos Observados , Osteogénesis/efectos de los fármacos , Ácido Oxónico/administración & dosificación , Embarazo , Piridinas/administración & dosificación , Conejos , Reproducción/efectos de los fármacos , Tegafur/administración & dosificación , Factores de Tiempo

RESUMEN

OBJECTIVE: To clarify the possibility that midband Lp in LDL fractions might act as an atherogenic lipoprotein in their interaction with macrophages. DESIGN AND METHODS: Low density lipoproteins (LDL) isolated by zonal ultracentrifugation from midband lipoprotein-positive serum in type lib hyperlipidemics were subjected to polyacrylamide gel disc electrophoresis. RESULTS: A part of midband lipoprotein was observed between pre beta-and beta-band, in addition to the main beta-band. We named this midband lipoprotein "slow beta-migrating Lp (slow beta-Lp)." The larger LDL subfraction from midband-lipoprotein positive serum on Sepharose 2B column chromatography contained much slow beta-Lp, named slow beta-Lp-rich LDL. The smaller LDL subfraction contained a little slow beta-Lp, named slow beta-Lp-poor LDL. Slow beta-Lp-rich LDL had similar composition to the control LDL except for apolipoprotein E. The uptake of [3H]cholesteryl linoleate-labeled slow beta-Lp-rich LDL by J774 macrophages was higher than that of control LDL. The cholesterol ester content of J774 macrophages incubated with slow beta-Lp-rich LDL increased significantly compared with slow beta-Lp-poor LDL, beta-VLDL, and control LDL. CONCLUSION: These results suggest that slow beta-Lp in type llb might generate foam cells from macrophages in atherosclerotic lesions.

Asunto(s)

Lipoproteínas LDL/química , Lipoproteínas LDL/metabolismo , Macrófagos/metabolismo , Animales , Apolipoproteínas/análisis , Apolipoproteínas/química , Fraccionamiento Químico , Colesterol/análisis , Ésteres del Colesterol/metabolismo , Ésteres del Colesterol/farmacocinética , Femenino , Humanos , Hiperlipidemias/metabolismo , Incidencia , Lípidos/análisis , Lípidos/química , Lipoproteínas LDL/sangre , Macrófagos/química , Masculino , Ratones , Tritio

RESUMEN

A previous study showed a lower incidence of ischemic stroke in patients with Parkinson's disease (PD) than in controls. It has been speculated that this may be related to less severe atherosclerosis in PD. In this study we examined the magnetic resonance imaging (MRI) and blood chemistry in 106 parkinsonian patients and compared the data with those from control cases. Abnormal MRI findings (état criblé, lacunar infarctions or periventricular hyperintensity) were found in 55.7% of cases. No case of cortical artery infarction was found. In comparison with a control population, the PD group showed a lower frequency of hypercholesterolemia, a higher frequency of low HDL cholesterol and a lower frequency of obesity. These results suggest that patients with PD have a reduction in risk factors for cortical artery infarction.

RESUMEN

A comparative assessment has been made regarding efficacy and safety of the double filtration plasmapheresis (DFPP), thermofiltration (TFPP), and low-density lipoprotein (LDL) adsorptive (PA) methods by making a crossover test on heterozygous familial hypercholesterolemia patients. Treatments by DFPP, TFPP (secondary membrane Evalux 5A), and PA (Liposorber LA-40) were carried out 5 times each, with a 2-week interval, in 5 patients with heterozygous familial hypercholesterolemia. The same plasma separator (Plasmacure PS-60, polysulfone) was used in all cases, and the volume of plasma processed was set at 4 L. High removal rates were obtained of total cholesterol, LDL cholesterol, triglycerides TG, and apolipoprotein B (apoB) by all three methods, and no differences were observed. Lipoprotein (a), apoA-2, apoC-3, fibrinogen, and immunoglobulin M (IgM) showed significantly high removal rates by the DFPP and TFPP methods compared with the PA method. The sieving coefficient of albumin and high-density lipoprotein (HDL) cholesterol at 2 and 4 L of plasma processed exhibited high permeabilities using all three methods. Supplementing albumin was not necessary. An increase of the transmembrane pressure was observed in 1 case treated by DFPP but was not observed when using the TFPP or PA method. No changes were observed in serum interleukin 1beta (IL-1beta) or tumor necrosis factor-alpha (TNF-alpha) before and after treatment by any of the three methods. No remarkable side effects were observed using either the DFPP or TFPP method. The DFPP and TFPP methods showed efficacy and safety that was not inferior to the PA method in conventional LDL apheresis, and the dead-end method of the filter operation without the discarding of plasma was shown to be possible.

Asunto(s)

Hiperlipoproteinemia Tipo II/terapia , Plasmaféresis/normas , Adsorción , Adulto , Apolipoproteína A-II/sangre , Apolipoproteína A-II/aislamiento & purificación , Apolipoproteínas B/sangre , Apolipoproteínas B/aislamiento & purificación , Apolipoproteínas C/sangre , Apolipoproteínas C/aislamiento & purificación , Análisis Químico de la Sangre , Proteínas Sanguíneas/metabolismo , Estudios Cruzados , Femenino , Fibrinógeno/aislamiento & purificación , Filtración , Calor , Humanos , Inmunoglobulina M/aislamiento & purificación , Interleucina-1/metabolismo , Lipoproteína(a)/aislamiento & purificación , Lipoproteínas LDL/sangre , Lipoproteínas LDL/aislamiento & purificación , Lipoproteínas VLDL/sangre , Lipoproteínas VLDL/aislamiento & purificación , Masculino , Persona de Mediana Edad , Triglicéridos/sangre , Triglicéridos/aislamiento & purificación , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

We studied the relationship between automatic processing and controlled processing in schizophrenic disorder and examined the changes of the relationship through various clinical courses of the illness using event related potentials (ERPs). Thirty schizophrenic patients were classified into two groups according to ERP variations; group-A consisted of schizophrenics who showed higher mismatch negativity (MMN) amplitudes and lower P300 amplitudes than group-B patients. After pharmacological treatment, MMN amplitudes decreased and P300 increased in group-A patients. On the other hand, MMN amplitudes increased, but no significant changes in P300 amplitudes were recognized in group-B patients. MMN amplitudes had a negative correlation with the extent of dilatation of the left Sylvian fissure and the bilateral lateral ventricles on CT scans. From these results, it is suggested that automatic processing and controlled processing complement each other in information processing of schizophrenics. In group-A, higher MMN amplitudes suggested plasticity of processing dysfunction, which showed good social adjustment after pharmacological treatment. In group-B, more severe vulnerability to the disorder was suggested from lower MMN amplitudes, which showed poor social adjustment after the treatment.

Asunto(s)

Potenciales Relacionados con Evento P300 , Procesos Mentales , Psicología del Esquizofrénico , Adulto , Femenino , Humanos , Masculino