RESUMEN
BACKGROUND AND OBJECTIVE: Green tea extract exerts a variety of biological effects, including anti-inflammatory activities. However, there has been no report on the effect of green tea extract on loss of attachment, which is an important characteristic of periodontitis. Here, we examined the inhibitory effects of green tea extract on the onset of periodontitis in a rat model. MATERIAL AND METHODS: Rats were immunized intraperitoneally with Escherichia coli lipopolysaccharide (LPS). The LPS group (n = 12) received a topical application of LPS onto the palatal gingival sulcus every 24 h. The green tea extract group (n = 12) received a topical application of LPS mixed with green tea extract, sunphenon BG, every 24 h. The phosphate-buffered saline (PBS) group (n = 6) received a topical application of PBS every 24 h. The levels of anti-LPS immunoglobulin G (IgG) in serum were determined using ELISA. Rats in the LPS and green tea extract groups were killed after the 10th and 20th applications. Rats in the PBS group were killed after the 20th application. Loss of attachment, level of alveolar bone and inflammatory cell infiltration were investigated histopathologically and histometrically. RANKL-positive cells and the formation of immune complexes were evaluated immunohistologically. RESULTS: There was no significant difference in the serum levels of anti-LPS IgG between the LPS group and the green tea extract group. In contrast, loss of attachment, level of alveolar bone, inflammatory cell infiltration and RANKL expression in the green tea extract group were significantly decreased compared with those in the LPS group. CONCLUSION: These findings demonstrate that green tea extract suppresses the onset of loss of attachment and alveolar bone resorption in a rat model of experimental periodontitis.
Asunto(s)
Antiinflamatorios/uso terapéutico , Camellia sinensis , Periodontitis/prevención & control , Fenoles/uso terapéutico , Extractos Vegetales/uso terapéutico , Pérdida de Hueso Alveolar/patología , Pérdida de Hueso Alveolar/prevención & control , Animales , Anticuerpos Antibacterianos/sangre , Complejo Antígeno-Anticuerpo/análisis , Tejido Conectivo/patología , Modelos Animales de Enfermedad , Inserción Epitelial/patología , Escherichia coli/inmunología , Inmunización , Inmunoglobulina G/sangre , Lipopolisacáridos/inmunología , Masculino , Osteoclastos/patología , Pérdida de la Inserción Periodontal/patología , Pérdida de la Inserción Periodontal/prevención & control , Periodontitis/patología , Fitoterapia , Ligando RANK/análisis , Ratas , Ratas Endogámicas LewRESUMEN
Antimutagenicity of the water extracts prepared from the storage roots of four varieties of sweetpotato with different flesh colors was investigated using Salmonella typhimurium TA 98. The extract from the whole roots of the purple-colored Ayamurasaki variety effectively decreased the reverse mutation induced not only by Trp-P-1, Trp-P-2, IQ, B[a]P, and 4-NQO but also by dimethyl sulfoxide extracts of grilled beef. Comparison of the inhibitory activity of the extracts from the normal Ayamurasaki and its anthocyanin-deficient mutant one suggested that the anthocyanin pigment in the flesh decreases the mutagenic activity of the mutagens as heterocyclic amines. Two anthocyanin pigments purified from purple-colored sweet-potato, 3-(6,6'-caffeylferulylsophoroside)-5-glucoside of cyanidin (YGM-3) and peonidin (YGM-6) effectively inhibited the reverse mutation induced by heterocyclic amines, Trp-P-1, Trp-P-2, and IQ in the presence of rat liver microsomal activation systems.
Asunto(s)
Antimutagênicos/farmacología , Solanaceae/química , Animales , Antocianinas/aislamiento & purificación , Antocianinas/farmacología , Antimutagênicos/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Técnicas In Vitro , Pruebas de Mutagenicidad , Fenoles/aislamiento & purificación , Fenoles/farmacología , Pigmentos Biológicos/aislamiento & purificación , Pigmentos Biológicos/farmacología , Extractos Vegetales/farmacología , Raíces de Plantas/química , Ratas , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genéticaRESUMEN
We investigated the functional role of a CXC chemokine, growth-related protein (GRO), in the recruitment of neutrophils in lipopolysaccharide (LPS)-induced rabbit arthritis. The amounts of GRO in the synovial fluids (SF) reached the first peak (major) at 2 hours and the second peak (minor) at 9 hours after injection of LPS into the knee joints. Administration of anti-GRO mouse monoclonal antibody inhibited 54% of the peak leukocyte accumulation at 9 hours (neutrophils greater than 95%), which was similar to the inhibition by anti-IL-8 IgG (48%). Co-administration of these inhibitors increased the inhibition up to 70% at 9 hours and also inhibited 65% of the initial phase of leukocyte infiltration at 2 hours (neutrophils greater than 99%), which was not affected by a single administration of each inhibitor. The amounts of GRO in SF at 2 hours were not altered by either anti-TNFalpha mAb or anti-IL-8 IgG, but reduced by rabbit recombinant IL-1 receptor antagonist (rrlL-1Ra) by 39%. The inhibition by rrlL-1 Ra was augmented further to 59% with coadministered anti-TNFalpha mAb. In contrast, the amounts of GRO at 9 hours were reduced by rrlL-1Ra by 67%. There was no additional reduction in the amounts of GRO at 9 hours by either combination of rrlL-1Ra with anti-TNFalpha mAb or anti-IL-8 IgG. Administration of anti-GRO mAb did not alter TNFalpha or IL-8 contents in SF at their peak (2 hours), but reduced the amounts of IL-1beta at 6 hours and IL-1Ra at 9 hours by 42% and 49%, respectively. These results provide evidence for the following: (a) GRO as well as IL-8 are important mediators involved in the recruitment of neutrophils both in the early and the late phase of LPS-induced arthritis, (b) IL-1 produced in the early phase stimulates GRO production, (c) GRO plays a role in the later induction of IL-1beta and IL-1Ra, and (d) induction of GRO is not regulated by IL-8.
Asunto(s)
Artritis/metabolismo , Quimiocinas CXC/fisiología , Sustancias de Crecimiento/fisiología , Lipopolisacáridos/farmacología , Animales , Anticuerpos Monoclonales/biosíntesis , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Artritis/inducido químicamente , Línea Celular , Quimiocinas CXC/genética , Quimiocinas CXC/inmunología , Fluoroinmunoensayo , Sustancias de Crecimiento/genética , Sustancias de Crecimiento/inmunología , Inmunoglobulina G/inmunología , Inmunohistoquímica , Proteína Antagonista del Receptor de Interleucina 1 , Interleucina-1/metabolismo , Interleucina-8/inmunología , Interleucina-8/metabolismo , Recuento de Leucocitos , Ratones , Ratones Endogámicos BALB C , Neutrófilos/citología , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Conejos , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Sialoglicoproteínas/inmunología , Sialoglicoproteínas/metabolismo , Líquido Sinovial/química , Líquido Sinovial/efectos de los fármacos , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Cases of hyperfractionated radiotherapy and adjuvant chemotherapy for nasopharyngeal cancer are reported. Seven patients received hyperfractionated radiotherapy (76.8-81.6 Gy/64-68 fractions to primary tumor) and two cycles of cisplatin (80 mg/m2 i.v. on day 1) plus 5-FU (800 mg/m2 continuous infusion on days 2-6). Mucositis was the most frequent side effect in hyperfractionated radiotherapy. Moderate leukopenia was the major side effect of adjuvant chemotherapy. With a mean follow-up time of 34 months (range 25-48 months), five of the seven patients were locoregionally controlled. Two developed distant metastases. Two patients suffered late complications (posterior nasopharyngeal wall necrosis and brain necrosis). These results suggested that our regimen was almost well tolerated and might be of use in locoregional control of nasopharyngeal cancer. However, it carries some risk of late complications and might be inadequate for preventing distant metastases. A three-dimensional conformal boost irradiation technique and adequate dose intensity chemotherapy might be encouraged.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Adulto , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Terapia Combinada , Fraccionamiento de la Dosis de Radiación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Radioterapia/efectos adversos , Resultado del TratamientoRESUMEN
Studies have suggested the role of cytokines in inflammation, as determined by results obtained in vitro, or with assessments of clinical samples. However, extrapolation of in vitro results to an in vivo situation must be made with caution, and findings obtained from clinical samples tend to lack a causal relation between cytokines and inflammatory responses. Animal models of inflammation can be useful in understanding roles of cytokines at sites of inflammation. We examined the production kinetics and cellular sources of tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, IL-8, and IL-1 receptor antagonist (IL-1Ra), and obtained evidence for the involvement of these cytokines in a rabbit model of arthritis induced by lipopolysaccharide (LPS). We also attempted to analyze the inflammatory cytokine network among TNFalpha, IL-1beta, IL-8, and IL-1Ra. Understanding the role of cytokines in animal models paves the way to a better understanding of disease in humans.
Asunto(s)
Citocinas/metabolismo , Inflamación/metabolismo , Neutrófilos/metabolismo , Animales , Artritis/metabolismo , Modelos Animales de Enfermedad , Femenino , Proteína Antagonista del Receptor de Interleucina 1 , Interleucina-1/metabolismo , Interleucina-8/metabolismo , Conejos , Sialoglicoproteínas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The production of monocyte chemoattractant protein-1 (MCP-1) and its regulation by TNFalpha, IL-1, and IL-8 were investigated in two rabbit models of arthritis induced by intra-articular injection of lipopolysaccharide (LPS) or monosodium urate (MSU) crystals. We first prepared recombinant rabbit MCP-1 and antibodies and then developed an immunoassay. The immunoassay detected 3 pg/ml rabbit MCP-1 and did not cross-react with other rabbit chemokines such as IL-8 or GRO. MCP-1 was first detected in synovial fluid (SF) at 1 hour, and peaked at 4 or 2 hours after the injection of LPS or MSU crystals, respectively. Immunohistochemically, MCP-1 was detected in synovial lining cells and infiltrating neutrophils. The amounts of MCP-1 detected in SF from neutrophil-depleted rabbits were similar to those in normal rabbits, suggesting that synovial lining cells were the main source of MCP-1 detected in SF. The peak level of MCP-1 in SF after LPS-injection was inhibited by 57% with anti-TNFalpha mAb and by 41% with IL-1 receptor antagonist (IL-1Ra). Coadministration of anti-TNFalpha mAb and IL-1Ra inhibited 90% of MCP-1 production. In contrast, the peak level of MCP-1 in SF after MSU crystal-injection was not affected by any cytokine inhibitor, but was reduced by 52% with coadministration of anti-TNFalpha mAb and IL-1Ra. Anti-IL-8 IgG had no effect on the production of MCP-1 in either model. Thus, the production of MCP-1 in LPS-induced arthritis was mostly regulated by TNFalpha and IL-1, whereas half the extent of MCP-1 production in MSU crystal-induced arthritis was independent of TNFalpha or IL-1. IL-8 does not seem to regulate the production of MCP-1 in SF either directly or indirectly. Finally, administration of neutralizing anti-MCP-1 antibody inhibited LPS- and MSU crystal-induced monocyte infiltration by 58.4% and 44.9%, respectively, suggesting that synovial production of MCP-1 plays an important role in the recruitment of monocytes in these arthritis models.
Asunto(s)
Artritis/metabolismo , Quimiocina CCL2/biosíntesis , Interleucina-1/fisiología , Interleucina-8/fisiología , Lipopolisacáridos/toxicidad , Factor de Necrosis Tumoral alfa/fisiología , Ácido Úrico/toxicidad , Animales , Anticuerpos Monoclonales/biosíntesis , Artritis/inducido químicamente , Artritis/patología , Células COS , Movimiento Celular/inmunología , Quimiocina CCL2/análisis , Quimiocina CCL2/genética , Quimiocina CCL2/inmunología , Cristalización , Femenino , Fluoroinmunoensayo , Sueros Inmunes/administración & dosificación , Sueros Inmunes/biosíntesis , Inyecciones Intraarticulares , Inyecciones Intravenosas , Articulación de la Rodilla/patología , Monocitos/patología , Conejos , Proteínas Recombinantes/análisis , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/inmunología , Líquido Sinovial/químicaRESUMEN
In the present study, we analyzed the cytokine network among TNFalpha, IL-1beta, IL-8, and IL-1 receptor antagonist (IL-1Ra) in a rabbit experimental model of acute gout. The production of TNFalpha in synovial fluids reached the peak at 2 hours after the intra-articular injection of monosodium urate (MSU) crystals. The production of IL-1beta and IL-8 reached the first peak at 2 hours and the second peak at 9 and 12 hours, respectively. The production of endogenous IL-1Ra reached the peak at 9 hours. The source of TNFalpha and the first phase of IL-8 was synovial cells, whereas infiltrating leukocytes were the source of the second phase of IL-8 and also of IL-1beta and IL-1Ra. The production of TNFalpha was not altered by either anti-lL-8 IgG or IL-1Ra. The first IL-1beta peak was reduced only with a combination of anti-TNFalpha mAb and anti-lL-8 IgG, whereas the second peak was significantly reduced by either inhibitor. The first IL-8 peak was not altered with anti-TNFalpha mAb or IL-1 Ra, whereas the second IL-8 peak was reduced with IL-1Ra. Anti-TNFalpha mAb or anti-lL-8 IgG significantly reduced the peak level of endogenous IL-1Ra. These cytokine inhibitors also attenuated the maximal leukocyte accumulation at 9 hours, but not the initial phase, which occurred within 2 hours. These results provide evidence that IL-8 and TNFalpha were responsible for the production of IL-1beta and IL-1Ra, and that IL-1beta was responsible for the second phase of IL-1beta and IL-8 production. Our data also suggest that the initial and the maximal phases of leukocyte influx are differently regulated. Finally, the intravenous injection of colchicine inhibited neutrophil infiltration without affecting the production of TNFalpha or the first peak of IL-8, suggesting that colchicine inhibits MSU crystal-induced arthritis by directly inhibiting the migration of neutrophils.
Asunto(s)
Artritis/metabolismo , Citocinas/metabolismo , Interleucina-1/metabolismo , Interleucina-8/metabolismo , Receptores de Interleucina-1/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Anticuerpos Monoclonales/inmunología , Artritis/inducido químicamente , Movimiento Celular/fisiología , Colchicina/farmacología , Cristalización , Citocinas/inmunología , Femenino , Supresores de la Gota/farmacología , Inmunoglobulina G/inmunología , Inmunohistoquímica , Recuento de Leucocitos , Leucocitos/efectos de los fármacos , Leucocitos/fisiología , Neutrófilos/patología , Conejos , Proteínas Recombinantes , Ácido Úrico/farmacologíaRESUMEN
BACKGROUND: Viridans group streptococci, especially penicillin-resistant strains, have been emerging as pathogens of bacteremia in neutropenic patients with hematologic malignancies. OBJECTIVES: To survey the penicillin susceptibilities of viridans group streptococci in Japanese children with and without oncohematologic diseases and to evaluate the effect of the short term administration of beta-lactam agents on the antibiotic susceptibility. METHODS: We tested 113 isolates of viridans group streptococci by the microdilution method for the minimal inhibitory concentrations (MICs) to 10 antibiotics. We isolated 40 isolates from the throats of children with an upper respiratory infection (URI) before beta-lactam antibiotic treatment, 32 isolates after the treatment, 33 isolates in hospitalized children with oncohematologic diseases and 8 isolates from blood. RESULTS: Twenty-five isolates (62.5%) from the children with URI before treatment were penicillin-intermediate or -high level resistant (MIC > or = 0.25 microg/ml). The prevalence of those isolates after antibiotic treatment (87.5%) was significantly increased compared with that before treatment (P = 0.03). The prevalences of the penicillin-high level resistant isolates (MIC > or = 4 microg/ml) in the children with oncohematologic diseases (39.4%) and in the isolates from blood (62.5%) were significantly higher than that in the children with URI before treatment (12.5%) (P < 0.01). Decreased susceptibilities to other beta-lactam agents were observed in the penicillin-high level resistant strains. CONCLUSIONS: The high prevalence of penicillin-intermediate or -high level resistant viridans group streptococci in healthy Japanese children was documented. The administration of beta-lactam agents decreased the prevalence of penicillin-susceptible isolates in the children with URI. High prevalences of penicillin-high level resistant isolates were observed in the oncohematologic patients and in the isolates from blood.
Asunto(s)
Antibacterianos/uso terapéutico , Neoplasias Hematológicas/complicaciones , Resistencia a las Penicilinas , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Niño , Preescolar , Humanos , Pruebas de Sensibilidad Microbiana , Streptococcus/efectos de los fármacos , beta-LactamasRESUMEN
A novel neutrophil elastase inhibitor, ONO-5046, was administered to BB/DR rats and DBA/1 mice immunized with type II collagen to study its effect on the development of collagen-induced arthritis (CA), an experimental model of human rheumatoid arthritis. ONO-5046 reduced the incidence as well as the severity of CA in both rats and mice. This suppressive effect on severity was correlated with improvement of the histological findings, particularly with reduced destruction of the articular cartilage. These results indicate that neutrophil elastase may play an important role in the pathogenesis of CA.
Asunto(s)
Artritis Experimental/prevención & control , Glicina/análogos & derivados , Inhibidores de Serina Proteinasa/farmacología , Sulfonamidas/farmacología , Animales , Formación de Anticuerpos , Artritis Experimental/inducido químicamente , Artritis Experimental/patología , Colágeno/inmunología , Femenino , Glicina/farmacología , Inmunidad Celular , Masculino , Ratones , Ratones Endogámicos DBA , Ratas , Ratas Endogámicas BBRESUMEN
Injection of lipopolysaccharide (LPS) into rabbit knee joints provoked leucocyte infiltration and loss of proteoglycan (PG) from the cartilage. We investigated the role of IL-1 and IL-1 receptor antagonist (IL-1Ra) and its significance in the pathogenesis of LPS-arthritis. Production of IL-1 beta peaked at 6 h (196.7 +/- 89.4 pg/joint) after injection of 10 ng of LPS, while IL-1Ra peaked at 9 h (34.5 +/- 13.4 ng/joint). The amount of IL-1Ra was 180-200-fold molar excess of IL-1, and a large amount of IL-1Ra was sustained for 1 week. Both IL-1 beta and IL-1Ra were mainly produced by synovial exudate cells. Arthritis was reproduced by rabbit IL-1 beta. LPS-induced leucocyte infiltration was inhibited 70-75% by rabbit IL-1Ra. Loss of PG in LPS-arthritis was prevented by IL-1Ra and also by neutrophil elastase inhibitor, and superoxide dismutase. In leucopenic rabbits, injection of LPS induced neither production of IL-1 beta nor loss of PG. Direct injection of inflammatory exudated cells in leucopenic rabbits reproduced loss of PG, and there was only a partial recovery by IL-1Ra. These results suggest that LPS-initiated IL-1 acts as a key mediator in LPS-arthritis and that endogenous IL-1Ra may suppress a part of IL-1 activity at the site, but its amount was too low for suppression of the produced IL-1. Loss of PG is a sequela of infiltrated leucocytes and leucocyte-derived elastase, and superoxide anion may play a pivotal role in the destruction of cartilage.
Asunto(s)
Artritis/metabolismo , Interleucina-1/biosíntesis , Lipopolisacáridos/toxicidad , Sialoglicoproteínas/biosíntesis , Animales , Femenino , Glicina/análogos & derivados , Glicina/farmacología , Proteína Antagonista del Receptor de Interleucina 1 , Interleucina-1/antagonistas & inhibidores , Elastasa de Leucocito , Leucopenia/metabolismo , Elastasa Pancreática/fisiología , Proteoglicanos/metabolismo , Conejos , Sulfonamidas/farmacologíaRESUMEN
Cernitin pollen extract (CN-009), extract from several pollen species, has been used for urinary dysfunction. As its mode of action has not been clarified, we investigated the action of CN-009 on the isolated bladder smooth muscles of rats, guinea pigs and cats and the intravesical pressure in female rats. CN-009 contracted isolated detrusor muscles of rats, guinea pigs and cats in a concentration-dependent manner. In the guinea pig detrusor muscle, the contractile effect of CN-009 was depressed by atropine, diphenhydramine and increased by cimetidine. In the rat detrusor muscle, the CN-009-induced contraction was depressed by atropine. In adult rats (11-23 weeks old) and aged rats (2 years old), CN-009 showed a dose-dependent increase of intravesical pressure to the same extent in spite of the fact that the aged rats had a lower responsiveness to acetylcholine. In adult rats, the CN-009-induced increase of intravesical pressure was reduced completely by atropine and partly reduced by phentolamine and guanethidine. Three weeks consecutive oral administration of CN-009 tended to increase the basal intravesical pressure and tended to elevate the isoproterenol-induced decrease and serotonin-induced increase in the intravesical pressure. These results suggest that CN-009 contracts the detrusor muscle, a process that is mainly mediated by muscarinic receptor activation. The contraction induced by CN-009 of detrusor muscle causes the increase of intravesical pressure.
Asunto(s)
Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Extractos Vegetales , Polen , Vejiga Urinaria/efectos de los fármacos , Envejecimiento , Animales , Atropina/farmacología , Gatos , Cimetidina/farmacología , Difenhidramina/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Femenino , Cobayas , Técnicas In Vitro , Isoproterenol/farmacología , Masculino , Presión , Ratas , Receptores Muscarínicos/metabolismo , Secale , Serotonina/farmacología , Especificidad de la EspecieRESUMEN
In order to evaluate the effect of vitamin K prophylaxis on the incidence of intracranial hemorrhage (ICH) in infants aged from 1 week to 12 months, a prospective surveillance study, from 1974 to 1988, was performed on the well-defined population of Nagasaki Prefecture, Japan. The incidence of ICH in infancy markedly decreased, from 34.3/100,000 to 10.1/100,000 live births, with the oral administration of vitamin K2 at both birth and 1 week, or with additional supplementation at 1 month of age. The diminished incidence was attributed to the decreased occurrence of acute ICH due to late hemorrhagic disease (LHD), a late onset form of vitamin K deficiency, and chronic subdural hematoma. On comparing the possible etiological factors, and clinical and laboratory findings between these 2 groups, it became apparent that chronic subdural hematoma shared some etiological factors (such as breast-feeding, liver dysfunction and no supplementation of vitamin K) with LHD. Furthermore, chronic subdural hematoma developed in some patients who had previously had acute ICH due to LHD. These findings suggest that coagulopathy due to vitamin K deficiency, including LHD, is causally related in the majority of, if not all, cases of chronic subdural hematoma without any history of trauma or central nervous system infections.