RESUMEN
This study aimed to evaluate the ability of chewing gum containing sodium metaphosphate (SMP) to remove coffee stains from enamel in situ. This was a double-blind (subjects, evaluators), parallel-group, crossover, randomized clinical trial with 30 healthy adult volunteers. Each participant held an appliance with a hydroxyapatite (HA) pellet on the lower lingual side of his or her mouth for two hours to allow pellicle formation. The appliances were subsequently immersed in coffee solution at 37°C for 48 hours. The color of the HA pellet before and after coffee immersion was measured using a spectrophotometer. The participant set the appliance and chewed two pieces of test gum, which contained 7.5 mg of SMP per piece, or control gum without SMP. Each cycle included five minutes of exposure to chewing gum, after which the appliances were placed in 100% relative humidity at room temperature for a 30-minute incubation. This cycle was repeated five times for each gum type. The color of the HA pellet was measured after each chewing cycle using the spectrophotometer. In addition, ΔE* values, which indicate the change in pellet color after each chewing cycle compared with after coffee immersion, were calculated. Data were analyzed using the paired t-test with Bonferroni adjustment to compare ΔE* values of control and test gum after each chewing cycle. The ΔE* values of test gum were significantly higher than those of control gum after all chewing cycles, excluding the first cycle (p<0.05). This finding indicates that test gum containing SMP was more effective at removing coffee stains from the HA pellet than control gum. We conclude that chewing gum containing SMP can effectively remove coffee stains from HA pellets. Thus, SMP is a promising agent to be further explored in tooth-cleaning studies.
Asunto(s)
Goma de Mascar , Decoloración de Dientes , Adulto , Café , Colorantes , Método Doble Ciego , Femenino , Humanos , SodioRESUMEN
Propolis, a resinous substance produced by bees, is used as a folk medicine for treatment of periodontal diseases. However, its mode of the action and the compounds responsible for its activities remain obscure. In the present study, we comprehensively investigated the antibacterial activities of ethanol-extracted propolis (EEP) and EEP-derived compounds toward Porphyromonas gingivalis, a keystone pathogen for periodontal diseases. Broth microdilution and agar dilution assays were used to determine the minimum inhibitory concentrations of EEP against a range of oral bacterial species, of which P. gingivalis showed a higher level of sensitivity than oral commensals such as streptococci. Its antibacterial activity toward P. gingivalis was maintained even after extensive heat treatment, demonstrating a high level of thermostability. EEP also induced death of P. gingivalis cells by increasing membrane permeability within 30 min. Spatiotemporal analysis based on high-speed atomic force microscopy revealed that EEP immediately triggered development of aberrant membrane blebs, followed by bleb fusion events on the bacterial surface. Furthermore, we isolated artepillin C, baccharin, and ursolic acid from EEP as antibacterial compounds against P. gingivalis. Of those, artepillin C and baccharin showed bacteriostatic activities with membrane blebbing, while ursolic acid showed bactericidal activity with membrane rupture. In particular, ursolic acid demonstrated a greater ability to affect bacterial membrane potential with increased membrane permeability, probably because of its highly lipophilic nature as compared with other compounds. Taken together, these findings provide mechanistic insight into the antibacterial activities of EEP and its exquisite membrane-targeting antibacterial compounds and imply the applicability of narrow-spectrum therapeutics with EEP for treatment of periodontitis. In addition, the advanced technology utilized in the present study to visualize the nanometer-scale dynamics of microorganisms will contribute to expanding our understanding of the activities of antimicrobials and the mechanism of drug resistance in bacteria.
Asunto(s)
Antibacterianos/farmacología , Porphyromonas gingivalis/efectos de los fármacos , Própolis/farmacología , Biopelículas/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Potenciales de la Membrana/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Microscopía de Fuerza Atómica , Microscopía Electrónica , Periodontitis/tratamiento farmacológico , Periodontitis/microbiologíaRESUMEN
PURPOSE: To investigate changes in optic nerve head (ONH) circulation, visual evoked potentials (VEPs), and ONH cupping after stimulation of the optic nerve. METHODS: Electrodes were fixed above the optic chiasma in rabbits under general anesthesia. Screw-type electrodes for VEP recording were fixed on the dura. ONH circulation, intraocular pressure (IOP), and blood pressure (BP) were measured after the passage of a current of 0.1 mA for 0.1 second (weak stimulation), 1 mA for 1 second (moderate), 5 mA for 10 seconds (strong), or 25 mA for 10 seconds (severe). Normalized blur (NB), indicative of tissue blood flow and velocity, was measured in the ONH after each stimulation, by using a laser speckle circulation analyzer. Changes in VEP and ocular fundus were also recorded. The ratio of cup area (CA) to disc area (DA) was measured before and 4 weeks after stimulation. After all experiments, the ONH was histologically examined. RESULTS: Weak stimulation increased NB in ONH for 10 minutes, whereas strong or severe stimulation significantly decreased NB for a longer time, in a dose-dependent manner. BP showed no significant change, except with severe stimulation. IOP was not significantly changed. VEP amplitude was reduced 30 minutes after strong stimulation. The CA-to-DA ratio was significantly increased 4 weeks after strong stimulation. In some rabbits, disc hemorrhage occurred, followed by enlargement of disc cupping, with slight gliosis. CONCLUSIONS: Electrical stimulation of the optic nerve changed ONH circulation and VEPs and increased disc cupping. This technique warrants further investigation as an experimental model for normal-tension glaucoma.
Asunto(s)
Glaucoma de Ángulo Abierto/diagnóstico , Disco Óptico/irrigación sanguínea , Disco Óptico/patología , Nervio Óptico/fisiología , Animales , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Estimulación Eléctrica , Potenciales Evocados Visuales , Glaucoma de Ángulo Abierto/fisiopatología , Hipertrofia , Presión Intraocular , Flujometría por Láser-Doppler , Masculino , Microelectrodos , Modelos Animales , Conejos , Flujo Sanguíneo RegionalRESUMEN
Four novel withanolide-type steroids named cilistols p, pm, p1 and u (1-4, respectively), were isolated from the leaves of Solanum cilistum. The respective structures were characterized by spectroscopic means as follows: cilistol p (1) was (22R,24R,25R,26S)-1-oxo-22,26-epoxy-3alpha,5alpha-cycloergostane-6beta,17alpha, 24,25,26-pentaol 26-O-beta-D-glucopyranoside, cilistol pm (2) corresponded to the 6-O-methyl ether derivative of 1; cilistol p1 (3) was represented as the 24-O-methyl ether of 1, and cilistol u (4) was shown to be the epoxide between C-24 and -25, presumably bearing cilistols p, pm and p1 by ring-opening.
Asunto(s)
Disacáridos/química , Glicósidos/química , Lactonas/química , Alcaloides Solanáceos/química , Trisacáridos/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Disacáridos/aislamiento & purificación , Glicósidos/aislamiento & purificación , Lactonas/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Alcaloides Solanáceos/aislamiento & purificación , Esteroides/química , Esteroides/aislamiento & purificación , Trisacáridos/aislamiento & purificaciónRESUMEN
Noninvasive markers reflecting repolarization inhomogeneity have been proposed to be useful indices for identifying patients at risk of ventricular arrhythmias based on organic heart disease. In this study, we clarify whether or not repolarization inhomogeneity markers are useful in patients with idiopathic ventricular tachycardia (VT). We investigated T-wave alternans (TWA) and corrected QT-interval dispersion (QTD) in 84 consecutive patients with idiopathic VT, 90 patients with VT associated with organic heart disease (organic VT), and 87 normal individuals. VT was defined as tachycardia lasting > or =5 consecutive ventricular ectopic beats at a rate of > or =120 beats/min. TWA was positive in 20 of 84 patients (24%) with idiopathic VT, 59 of 90 patients (66%) with organic VT, and 16 of 87 normal individuals (18%). The alternans voltage was 2.6 +/- 3.1 micro V in idiopathic VT patients, 5.6 +/- 6.4 micro V in organic VT patients, and 2.9 +/- 5.7 micro V in normal individuals. QTD were 53 +/- 20 ms in idiopathic VT patients, 92 +/- 20 ms in organic VT patients, 46 +/- 18 ms in normal individuals, respectively. A positive TWA test result was seen more (P <.01) frequently, and QTD was longer (P <.01) in organic VT patients compared to normal individuals, whereas there was no difference between idiopathic VT patients and normal individuals. In addition, in patients with idiopathic VT, neither did any of these measurements differ between patients with sustained VT (lasting for > or =30 s) and those with nonsustained VT. Noninvasive markers of repolarization inhomogeneity, such as TWA and QTD, are not useful for identifying patients with idiopathic VT. Repolarization inhomogeneity may not affect to the pathogenesis of idiopathic VT.
Asunto(s)
Electrocardiografía , Sistema de Conducción Cardíaco/fisiopatología , Taquicardia Ventricular/diagnóstico , Adulto , Técnicas Electrofisiológicas Cardíacas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Taquicardia Ventricular/fisiopatologíaRESUMEN
Resting energy expenditure (REE) values after consuming chicken essence tablets were significantly higher than those observed after consuming skim milk protein tablets (control trial). The increased thermogenic effects continued at least for a period of one hour and gradually decreased towards the baseline. The REE values during control treatment did not show such an augmented response.
Asunto(s)
Metabolismo Basal , Medicina Tradicional China , Administración Oral , Adulto , Animales , Alimentos , Humanos , Masculino , Comprimidos/administración & dosificación , TermogénesisRESUMEN
OBJECTIVE: The purpose of this study was to evaluate the potential utility of implantation of a nickel-titanium alloy (nitinol) stent for the treatment of malignant or benign tracheobronchial stenosis. METHODS: We evaluated 18 patients (14 men and 4 women) who received 24 nitinol stents, between November 1997 and May 2000. All 18 patients had severe dyspnea caused by tracheobronchial stenosis. The underlying condition was malignant disease in 15 patients, and benign tracheal collapse in the other 3 patients. RESULTS: Implantation of the stent was successfully performed in all patients. Seventeen patients experienced immediate clinical improvement in respiratory symptoms. The remaining 1 patient with a bronchial fistule after lobectomy did not benefit, and died of pneumonia at 16 days after the implantation. In 15 patients, the procedure was performed using a flexible bronchoscope under local anesthesia alone, while the remaining 3 patients needed intravenous sedation. There was no complication resulting from the stent implantation. Among the 3 patients with benign tracheal collapse, 2 patients were alive at 746 and at 401 days after the stent implantation, at the time of this report. One patient with cicatricial stenosis after intubation died of heart failure due to previous myocardial infarction. Among the 15 patients with malignant disease, 4 patients have survived for 177 to 305 days to date, while the other 11 patients have died of primary malignancy with a mean survival duration of 60.2 days. CONCLUSION: The nitinol stent was effective in treating malignant or benign tracheobronchial stenosis, and had some remarkable advantages compared with other tracheobronchial stents. In stenting, most procedures can be performed using flexible bronchoscope under local anesthesia.
Asunto(s)
Aleaciones/uso terapéutico , Enfermedades Bronquiales/terapia , Stents , Estenosis Traqueal/terapia , Adulto , Anciano , Anciano de 80 o más Años , Anestesia Local , Broncoscopía , Constricción Patológica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Tráquea/complicacionesRESUMEN
The specificity and dose dependence of the synergistic effects of soybean intake with iodine deficiency on the induction of thyroid proliferation were investigated in female F344 rats. In the first experiment, rats were divided into 6 groups, each consisting of 5 animals, and fed a basal diet containing 20% gluten, an iodine-deficient basal diet alone or an iodine-deficient diet containing 0.2%, 1.0%, 5.0% or 25% defatted soybean for 5 weeks. Soybean feeding synergistically induced thyroid hyperplasias with iodine deficiency only at the 25% dose. In the second experiment, rats were also divided into 6 groups, each consisting of 5 animals, and fed a basal diet, a diet containing 20% defatted soybean, 0.025% sulfadimethoxine (SDM), 20% defatted soybean + 0.025% SDM, 0.05% phenobarbital (PB) or 20% defatted soybean + 0.05% PB for 5 weeks. The SDM treatments significantly (P < 0.05 - 0.01) increased the thyroid weights, but this increase rate was less prominent in the SDM + soybean group than in the SDM alone group. The PB treatment was also associated with a tendency for increase in thyroid weight, but again this was smaller in the PB + soybean group than in the PB alone group. Although the SDM or PB treatments reduced the serum triiodothyronine and thyroxine levels and consequently increased the serum thyroid-stimulating hormone (TSH) levels, the soybean feeding did not affect or rather attenuated these changes. Our results clearly indicate that soybean feeding does not synergistically enhance the effects of SDM or PB on the rat thyroid. Thus it can be concluded that soybean intake specifically interacts with iodine deficiency in induction of thyroid proliferative lesions in rats, only at high doses.
Asunto(s)
Glycine max/toxicidad , Yodo/deficiencia , Fenobarbital/toxicidad , Sulfadimetoxina/toxicidad , Glándula Tiroides/efectos de los fármacos , Animales , División Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Femenino , Hiperplasia/inducido químicamente , Ratas , Ratas Endogámicas F344 , Glándula Tiroides/metabolismo , Glándula Tiroides/patología , Neoplasias de la Tiroides/inducido químicamente , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangreRESUMEN
More than 20 different partner genes with MLL have been cloned from leukemia cells with translocations involving chromosome 11 band q23 (11q23). All reported partner genes fused in-frame to MLL and the fusion cDNA encode chimeric MLL proteins with a significant portion derived from the partner genes. We analyzed one patient with de novo acute monoblastic leukemia with t(11;14)(q23;q24) and identified that a human homologue of gephyrin (human gephyrin) fused with MLL. Gephyrin is a rat glycine receptor-associated protein, which forms submembranous complexes and anchor glycine or gamma-aminobutyric acidA receptors to microtubules. Alternative splicing of human gephyrin gene created two different forms of fusion cDNA. In one form, human gephyrin gene fused in-frame to MLL exon 9, and the chimeric product had COOH terminus of human gephyrin protein, including the tubulin binding site. In the other, the reading frame terminated shortly after the fusion point. As a result, only seven amino acids with no known function were attached to the NH2 terminus of MLL protein. The functional significance of this de facto truncated MLL gene product is not clear.
Asunto(s)
Proteínas Portadoras/genética , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 14 , Proteínas de Unión al ADN/genética , Leucemia Monocítica Aguda/genética , Proteínas de la Membrana/genética , Proteínas de Fusión Oncogénica/genética , Proto-Oncogenes , Factores de Transcripción , Translocación Genética , Anciano , Animales , Fusión Artificial Génica , Secuencia de Bases , Southern Blotting , Clonación Molecular , ADN Complementario/genética , ADN de Neoplasias/genética , Proteínas de Unión al ADN/metabolismo , Femenino , N-Metiltransferasa de Histona-Lisina , Humanos , Leucemia Monocítica Aguda/metabolismo , Datos de Secuencia Molecular , Proteína de la Leucemia Mieloide-Linfoide , Proteínas de Fusión Oncogénica/metabolismo , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Ácido NucleicoRESUMEN
We examined the effect of berberine, a major component with anti-fungal properties contained in Coptidis Rhizoma and Phellodendri Cortex, on the lymph node metastasis of murine lung cancer. Oral administration of berberine for 14 days significantly inhibited the spontaneous mediastinal lymph node metastasis produced by orthotopic implantation of Lewis lung carcinoma (LLC) into the lung parenchyma in a dose-dependent manner, but did not affect the tumor growth at the implantation site of the lung. Combined treatment with berberine and an anti-cancer drug, CPT-11, resulted in a marked inhibition of tumor growth at the implantation site and of lymphatic metastasis, as compared with either treatment alone. Anti-activator protein-1 (anti-AP-1) transcriptional activity of non-cytotoxic concentrations of berberine caused the inhibition of the invasiveness of LLC cells through the repression of expression of urokinase-type plasminogen activator (u-PA).
Asunto(s)
Berberina/uso terapéutico , Camptotecina/análogos & derivados , Carcinoma Pulmonar de Lewis/secundario , Neoplasias Pulmonares/patología , Neoplasias del Mediastino/prevención & control , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/uso terapéutico , Carcinoma Pulmonar de Lewis/prevención & control , Modelos Animales de Enfermedad , Femenino , Irinotecán , Neoplasias Pulmonares/prevención & control , Metástasis Linfática , Ratones , Ratones Endogámicos C57BL , Invasividad Neoplásica/prevención & control , Trasplante de Neoplasias , Factor de Transcripción AP-1/antagonistas & inhibidoresAsunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Tamoxifeno/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Hormona Liberadora de Gonadotropina/agonistas , Humanos , PremedicaciónRESUMEN
The anticomplementary properties of kaikasaponin III (4) and soyasaponin I (8) from Pueraria lobata and their hydrolytic analogs were investigated in vitro. Diglycosidic saponins [kaikasaponin I (3), soyasaponin III (7)] showed most potent anticomplementary activities, followed by monoglycosidic saponins [soyasapogenol B monoglucuronide (6), sophoradiol monoglucuronide (2)] and triglycosidic saponins [soyasaponin I (8), kaikasaponin III (4)], whereas sophoradiol (1) and soyasapogenol B (5) showed enhancement of hemolysis under the presence of serum on the classical pathway of complement system. But all of them showed very weak or no anticomplementary activities on the alternative pathway of complement system. The anticomplementary activity of the saponins was influenced by the nature of glucuronic acid, where the free acid forms (-COOH) showed much more potent activity than the sodium salt forms (-COO-Na+) or methyl ester forms (-COOCH3), and the reduced forms (-CH2OH) decreased the activity significantly.
Asunto(s)
Proteínas Inactivadoras de Complemento/farmacología , Fabaceae/química , Ácido Glucurónico/farmacología , Hemólisis/efectos de los fármacos , Plantas Medicinales , Triterpenos/farmacología , Hemólisis/inmunología , Triterpenos/química , Triterpenos/aislamiento & purificaciónRESUMEN
This prospective randomized study aimed at establishing the optimal postoperative adjuvant chemotherapy regimen for premenopausal n+ breast cancer patients. The treatments were Regimen A, comprising 6 courses of CMF (cyclophosphamide, 100 mg/body on days 1-14; methotrexate, 40 mg/m2 on days 1 and 8; and 5-fluorouracil, 500 mg/m2 on days 1 and 8), and Regimen B, consisting of UFT (300 mg/day) and tamoxifen (30 mg/day) administered orally each day for 2 years. Telephone registration allocated the patients to the treatment groups by the minimization method in relation to the T category, number of n+ lesions and estrogen receptor status. Forty-five patients were registered, and 44 of them were eligible (22 cases each to Regimen A and Regimen B). The principal background factors showed no biases between the groups. The adverse reaction incidence was significantly higher with Regimen A (90.9% vs 22.7%). The 5-year survival rate was 89.8% with Regimen A and 100% with Regimen B, while the 5-year disease-free rates were 64.5% and 76.3%, showing no statistical significance. Regimen B showed a better QOL rating after 6 months of therapy in relation to nausea-vomiting and hair loss, and after 24 months in relation to appetite, sleep, performance status, happiness, anorexia and hair loss.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Metástasis Linfática , Metotrexato/administración & dosificación , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Tasa de Supervivencia , Tamoxifeno/administración & dosificación , Tegafur/administración & dosificación , Uracilo/administración & dosificaciónRESUMEN
KKIAMRE is a serine/threonine protein kinase whose transcripts increase in the deep cerebellar nuclei of the rabbit after eyeblink conditioning, a model of associative learning and memory. We here characterized the expression, isoforms, and promoters of murine KKIAMRE gene. The expression of KKIAMRE was detected, by in situ hybridization and immunohistochemistry, in neurons in various brain regions including deep cerebellar nuclei. The gene spans approximately 40 kb and consists of 15 exons. Analysis of cDNA clones revealed multiple variants, having diversity in the putative carboxy-terminal regulatory domain, generated by alternative splicing and intraexonal termination. Furthermore, they had alternative 5' noncoding sequences. Primer extension, RNase protection, and transient expression assays revealed that two alternative promoters linked to distinct noncoding exons direct the expression of KKIAMRE. The gene was mapped on chromosomes 5 and 4 in mouse and human, respectively.
Asunto(s)
Proteínas Quinasas Dependientes de Calcio-Calmodulina/genética , Variación Genética , Regiones Promotoras Genéticas , Secuencia de Aminoácidos/genética , Animales , Secuencia de Bases/genética , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Mapeo Cromosómico , Quinasas Ciclina-Dependientes , ADN Complementario/genética , Genoma , Humanos , Luciferasas/genética , Ratones , Datos de Secuencia Molecular , Fosfopiruvato Hidratasa/metabolismo , Regiones Promotoras Genéticas/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Serina-Treonina Quinasas , Conejos , Distribución Tisular , TransfecciónRESUMEN
OBJECTIVE: We investigated the effect of hyperthermic pretreatment 24 hours before hypoxic-ischemic exposure on neuronal cell damage in 7-day-old rats. METHODS: Newborn rats were separated on postnatal day 7 into two groups: 1) preheated (those exposed to 2 hours of hyperthermic pretreatment at 42-43C) (n = 29), and 2) nonheated (n = 20). At 24 hours after the hyperthermic stress, rats from both groups were subjected to left carotid artery ligation followed by 2 hours of hypoxia (8% oxygen/92% nitrogen) at 33C. All rats were killed 1 week after hypoxia-ischemia, and brains were extracted for histologic study. A different group of 7-day-old rats (n = 8) was placed in the same hyperthermic environment as mentioned above for 2 hours, and 24 hours after heat exposure brains were extracted for immunohistochemistry of heat-shock protein 70. RESULTS: The total incidence of hypoxic-ischemic brain damage significantly decreased in the preheated group (12 of 25 [48%]) compared with the nonheated group (17 of 20 [85%]; P < .03). The induction of immunoreactive heat-shock protein 70 was observed mainly in glial and vascular endothelial cells and, in a lesser amount, in neuronal cells of the cerebral cortex and hippocampus. CONCLUSION: Incidence of hypoxic-ischemic brain damage is consistently reduced by 2 hours of hyperthermic pretreatment in 7-day-old rats.
Asunto(s)
Hipertermia Inducida , Hipoxia-Isquemia Encefálica/patología , Neuronas/patología , Animales , Animales Recién Nacidos , Encéfalo/patología , Proteínas HSP70 de Choque Térmico/análisis , Inmunohistoquímica , RatasRESUMEN
OBJECTIVE: Intraarticular administration of hyaluronic acid (HA) has been widely used for the treatment of osteoarthritis (OA). Fibrinolysis is closely related to the pericellular proteolysis involved in inflammation. However, the role of HA in the regulation of fibrinolytic factors is not yet known. We investigated the effect of HA on the pericellular fibrinolytic system of human synovial fibroblasts derived from OA and rheumatoid arthritis (RA). METHODS: Human synovial fibroblasts obtained from OA and RA were cultured in the presence and absence of HA. The antigen of urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured by ELISA, and u-PA activity was evaluated by electrophoretic enzymography. The binding assay of u-PA and the immunohistochemical analysis of u-PA were employed to detect u-PA receptor (u-PAR). RESULTS: HA suppressed the secretion of both u-PA and PAI-1 antigens from the synovial fibroblasts of OA to their conditioned medium. Suppression of u-PA activity in OA synovial fibroblasts was more marked than in those of RA. The u-PA binding assay of OA and RA synovial fibroblasts revealed a single class of binding site: dissociation constant (Kd) 23.7 nM, maximal number of binding sites (Bmax) 3.11x10(4) binding sites/cell; Kd 16.5 nM, Bmax of 9.88x10(4) binding sites/cell, respectively. HA decreased Bmax in fibroblasts of both OA and RA. Immunohistochemical analysis showed that u-PAR was constitutively expressed in both synovial fibroblasts, but if these cells were treated with HA, the decrease of the staining of u-PAR was more pronounced in the cells of RA than in OA. CONCLUSION: Pericellular fibrinolytic activity mediated by the u-PA/u-PAR system and PAI-1 was attenuated by HA in synovial fibroblasts derived from OA and RA. Thus, HA may be a useful agent to inhibit the inflammation of arthritis.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Artritis Reumatoide/metabolismo , Ácido Hialurónico/farmacología , Osteoartritis/metabolismo , Inhibidor 1 de Activador Plasminogénico/metabolismo , Receptores de Superficie Celular/metabolismo , Membrana Sinovial/enzimología , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Unión Competitiva/efectos de los fármacos , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Activación Enzimática/efectos de los fármacos , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/enzimología , Humanos , Radioisótopos de Yodo , Osteoartritis/tratamiento farmacológico , Receptores de Superficie Celular/análisis , Receptores del Activador de Plasminógeno Tipo Uroquinasa , Membrana Sinovial/química , Membrana Sinovial/citologíaRESUMEN
Since some Solanum-genus plants have traditionally been used for anti-cancer and anti-herpes agents from olden times, we examined anti-herpes simplex virus type 1 (HSV-1) activity of typical steroidal glycosides with the frameworks of spirostane (including nuatigenin glycoside), furostane, solasodane, tomatidane and ergostane (including dimer) obtained from Solanum plants. Among these steroidal glycosides, the spirostanol glycosides were most effective. An inclination was observed for the potency of activity to decrease in the order of spirostane, tomatidane, ergostane, solasodane, nuatigenin type, dimer of ergostane and furostane. It was also suggested that the activity depends on the kind of oligosacchride moiety.
Asunto(s)
Antivirales/farmacología , Glicósidos/farmacología , Herpesvirus Humano 1/efectos de los fármacos , Plantas Medicinales/química , Esteroides/química , Animales , Antivirales/química , Conformación de Carbohidratos , Secuencia de Carbohidratos , Línea Celular , Glicósidos/química , Pruebas de Sensibilidad Microbiana , Relación Estructura-ActividadRESUMEN
The carcinogenicity of gardenia blue colour was examined in Fischer 344 (F344) rats. Groups of 50 males and 50 females were given the material at dietary doses of 0 (control), 2.5 or 5% for 104 weeks and then sacrificed. The doses were selected on the basis of results from a 13-week subchronic toxicity study. A slight increase in relative organ weights of the left lung was observed in male rats of the 5% group. However, no significant differences between the control and treated groups were noted with regard to clinical signs, mortality and haematological findings. A variety of tumours developed in all groups, including the controls, but all were histologically similar to those known to occur spontaneously in F344 rats, and no statistically significant increase in the incidence of any type of neoplastic lesion was found for either sex in the treated groups. Thus, it was concluded that, under the present experimental conditions, gardenia blue colour is not carcinogenic in F344 rats.
Asunto(s)
Glucósidos/toxicidad , Piranos/toxicidad , Administración Oral , Animales , Sangre/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Pruebas de Carcinogenicidad , Relación Dosis-Respuesta a Droga , Femenino , Glucósidos/administración & dosificación , Glucósidos/química , Iridoides , Masculino , Neoplasias Experimentales/inducido químicamente , Tamaño de los Órganos/efectos de los fármacos , Extractos Vegetales , Piranos/administración & dosificación , Piranos/química , Ratas , Ratas Endogámicas F344 , Tasa de SupervivenciaRESUMEN
OBJECTIVES: Hypoxic-ischemic tolerance can be induced in neonatal rats through hyperthermic preconditioning. The purposes of this study were to determine the interval between hyperthermic preconditioning and a subsequent hypoxic-ischemic insult that would provide optimal neuroprotection against the insult and to examine the relationship between tolerance induction and heat shock protein expression. STUDY DESIGN: On postnatal day 7 Wistar rat pups were separated into the following 2 groups: a heated group (those exposed to 15 minutes of hyperthermic pretreatment at a brain temperature of 41.5 degrees C-42.0 degrees C) and an unheated control group. At 6, 12, 24, 48, and 72 hours after the hyperthermic stress, rats from both groups were exposed to left carotid artery ligation followed by 2 hours of hypoxia (8% oxygen and 92% nitrogen) at 33 degrees C. Twenty animals from each group were used at each time point. All rats were killed at 1 week after hypoxia-ischemia, at which time the brains were processed and neuronal damage in the cortex and hippocampus was assessed histologically. Another set of 7-day-old rats (n = 30) was studied immunohistochemically at 6, 12, 24, 48, and 72 hours after the same hyperthermic treatment. Expression of 72-kd heat shock protein was measured in neuronal, glial, and vascular endothelial cells. RESULTS: Hyperthermia-induced hypoxic-ischemic tolerance was observed at 6, 12, and 24 hours but not at 48 and 72 hours after hyperthermic preconditioning. Heat shock protein 72 expression in the vascular endothelial cells, rather than in the glial or neuronal cells, was most strongly associated with hypoxic-ischemic tolerance. CONCLUSION: These findings suggest that heat shock protein 72 in endothelial cells plays an important role in the acquisition of hypoxic-ischemic tolerance at postnatal day 7, a time when maximal angiogenesis occurs and the blood-brain barrier is still immature.
Asunto(s)
Endotelio Vascular/metabolismo , Regulación del Desarrollo de la Expresión Génica , Proteínas de Choque Térmico/biosíntesis , Hipoxia-Isquemia Encefálica/prevención & control , Animales , Animales Recién Nacidos , Anticuerpos Monoclonales , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Endotelio Vascular/patología , Femenino , Proteínas del Choque Térmico HSP72 , Proteínas de Choque Térmico/análisis , Hipocampo/metabolismo , Hipocampo/patología , Hipertermia Inducida , Hipoxia-Isquemia Encefálica/etiología , Inmunohistoquímica , Neuroglía/metabolismo , Neuroglía/patología , Neuronas/metabolismo , Neuronas/patología , Ratas , Ratas WistarRESUMEN
The mutant catalase purified previously from acatalasemic dog liver was heat-labile but possessed normal activity, suggesting a mutation within the coding region distal from the catalytic site. The nucleotide and deduced amino acid sequences of acatalasemic beagle dog catalase were determined by analysis of cDNA obtained by 5'- and 3'-RACE and reverse transcriptase-polymerase chain reaction (RT-PCR) methods. Comparative analysis of cDNA sequences of normal and acatalasemic dog catalases indicated a single nucleotide difference where alanine(327) (G macro CT) was substituted with threonine (ACT). The mutant catalase, which was overexpressed in COS-1 cells, was heat-labile as previously observed with the purified enzyme from acatalasemic dog liver, indicating that this amino acid substitution can lead to structural instability. No catalase protein and activity were detected by immunoblotting and spectrophotomeric assay in acatalasemic dog reticulocytes although almost the same level of mRNA expression as that in the normal reticulocytes was observed. Pulse-labeling and immunoprecipitation examination indicated that the level of catalase synthesis in the acatalasemic dog reticulocytes was almost the same (approximately 80%) as that in the normal reticulocytes. On the other hand, the synthesized mutant catalase in reticulocytes was rapidly degraded (t(1/2): 1.8 h) compared with the normal catalase (t(1/2): 14.0 h) and this degradation was almost completely inhibited by lactacystin (LC). These results suggested that the proteolytic degradation mediated most likely by proteasome might be involved in disposing of the mutant catalase in acatalasemic erythroid cells.