RESUMEN
The efficacy of the selective cyclooxygenase-2 (COX-2) inhibitor meloxicam for treatment of postoperative oral surgical pain was assessed in a randomized controlled trial. Patients undergoing unilateral mandibular 3rd molar extraction surgery were allocated to 3 groups, A, B and C. After oral premedication of meloxicam 10 mg in group A, ampiroxicam 27 mg in group B and placebo in group C, surgery was completed within 30 min under local anaesthesia using 2% lidocaine. For postoperative pain relief the patients were allowed to take oral loxoprofen (60 mg per tablet). Postoperative pain was evaluated at the clinic on the 1st, 7th and 14th postoperative day (POD) using a visual analogue scale (VAS), as was the number of loxoprofen tablets consumed, and the results were compared among the 3 groups with statistical significance of P<0.05. VAS scores on 1 POD were significantly lower in group A than in group C. Loxoprofen consumption on the day of surgery and 1 POD was significantly lower in group A than in group C (P<0.01). Total analgesic consumption was significantly lower in groups A and B than in group C (P<0.02). The COX-2 inhibitor, meloxicam 10 mg used for premedication reduced postoperative pain compared with control in oral surgery.
Asunto(s)
Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Dolor Postoperatorio/prevención & control , Tiazinas/administración & dosificación , Tiazoles/administración & dosificación , Extracción Dental , Administración Oral , Adulto , Análisis de Varianza , Anestesia Local , Antiinflamatorios no Esteroideos/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Masculino , Meloxicam , Tercer Molar/cirugía , Dimensión del Dolor , Fenilpropionatos/uso terapéutico , Premedicación , Estudios ProspectivosRESUMEN
We have reported previously that Lactobacillus casei ssp. casei, together with specific substrate dextran, exhibited an adjuvant effect of stimulating humoral immune responses against bovine serum albumin (BSA) as a model antigen in BALB/c mice. In the present study, among the Lactobacillus species tested, L. casei ssp. casei with dextran significantly elevated the natural killer (NK) cell activities in spleen mononuclear cells from BALB/c mice in comparison to L. casei ssp. casei alone or other Lactobacillus species with or without dextran. Oral administration of L. casei ssp. casei together with dextran also resulted in a significant increase of NK cell activities in healthy human volunteers. Further, L. casei ssp. casei induced significant production of interleukin (IL)-12 in human peripheral blood mononuclear cells and IL-15 mRNA expression in the human intestinal epithelial cell line Caco-2. L. casei ssp. casei with dextran in food also significantly elevated the survival rate of BALB/c mice bearing Meth-A cells. Taken together, these results demonstrate that dietary synbiotic supplementation which is a combination of the L. casei ssp. casei used as a probiotic together with the dextran, a specific substrate as a prebiotic, efficiently elicits murine and human NK cell activities.
Asunto(s)
Dextranos/administración & dosificación , Células Asesinas Naturales/inmunología , Lacticaseibacillus casei/inmunología , Probióticos , Adulto , Animales , Formación de Anticuerpos , Línea Celular , Suplementos Dietéticos , Femenino , Humanos , Interleucina-12/análisis , Interleucina-15/genética , Lacticaseibacillus casei/fisiología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/microbiología , Activación de Linfocitos , Masculino , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , ARN Mensajero , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Albúmina Sérica Bovina/administración & dosificaciónRESUMEN
OBJECTIVE: It has been proposed that low density lipoprotein (LDL) plays a role in the self-limiting nature of pseudogout inflammation. We investigated changes of LDL concentration in rat air pouch fluid during periods of acute and subsiding inflammation to evaluate whether LDL contributes to inhibiting inflammation of pseudogout. We examined whether LDL binds to calcium pyrophosphate dihydrate (CPPD) crystals as a possible mechanism for reduction of inflammation. METHODS: In this in vivo study, 5 mg suspensions of CPPD crystals and saline were injected into the rat air pouch. Fluid samples were taken from rat air pouch at 0, 3, 6, 12, 24, and 48 h after injection. White blood cells in the samples were counted; the remaining fluid was centrifuged and concentrations of beta-glucuronidase and PGE2 in the supernatant were measured as inflammatory markers. LDL in the supernatant was immunochemically identified by Western blotting, then pellets containing crystals were examined by the same technique. RESULTS: LDL was identified in the air pouch 3 h after CPPD crystal injection, and its concentration increased and reached a peak level after 24 h. Inflammatory markers reached maximal level from 6 to 12 h, then decreased after 24 h. In the pellets containing crystals, LDL could not be identified in every specimen. CONCLUSION: LDL in the rat air pouch increased during the inflammatory course induced by CPPD crystal and the inflammation subsided as the LDL increased. Since some reports indicate LDL was related to reduction of crystal induced inflammation such as gout or pseudogout, we concluded that LDL could contribute to the resolution of acute pseudogout arthritis in vivo with or without binding to CPPD crystals.
Asunto(s)
Artritis Experimental/metabolismo , Artritis Gotosa/metabolismo , Pirofosfato de Calcio/metabolismo , Condrocalcinosis/metabolismo , Lipoproteínas LDL/metabolismo , Animales , Artritis Experimental/inducido químicamente , Artritis Gotosa/etiología , Western Blotting , Líquidos Corporales/efectos de los fármacos , Líquidos Corporales/metabolismo , Pirofosfato de Calcio/toxicidad , Condrocalcinosis/inducido químicamente , Cristalización , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Electroforesis en Gel de Poliacrilamida , Glucuronidasa/metabolismo , Recuento de Leucocitos , Leucocitos/efectos de los fármacos , Leucocitos/patología , Masculino , Ratas , Ratas WistarRESUMEN
OBJECTIVES: To investigate the allergen-induced messenger RNA (mRNA) expression of interleukin (IL) 4, IL-5 and interferon gamma (IFN-gamma) in peripheral blood mononuclear cells from individuals sensitized by Japanese cedar (Cryptomeria japonica) pollens, and to elucidate the clinical role of IL-4, IL-5, and IFN-gamma in the allergen sensitization and clinical manifestation of allergic disorders. DESIGN: This study included 30 patients sensitized to the pollen and 14 nonatopic healthy volunteers. Peripheral blood mononuclear cells (1.0 x 10(6) cells/mL) of each individual were cultured at 37 degrees C for 24 hours in the presence of 10 microg/mL of Cry j 1, a major allergen of the pollens. Total cellular RNA was extracted from the peripheral blood mononuclear cells, and IL-4, IL-5, and IFN-gamma mRNA expression was determined with a reverse transcriptase polymerase chain reaction. RESULTS: From the results of a survey of symptom diary cards and interviews regarding nasal symptoms during the pollen season in 1998, we found that 20 patients (symptomatic group), but not 10 patients (asymptomatic group), had typical symptoms of seasonal allergic rhinitis. Interleukin 4 mRNA was not expressed in the nonatopic subjects but was expressed in 9 asymptomatic patients and in 17 symptomatic patients. Interleukin 5 mRNA was exclusively expressed in the symptomatic patients. Interferon gamma mRNA expression did not differ significantly among the nonatopic subjects, asymptomatic patients, and symptomatic patients. CONCLUSIONS: This study has clearly highlighted an interesting and new concept that IL-4 is implicated in allergen sensitization but not in clinical manifestation, and that IL-5 may not be a feature of atopy in itself but seems to be a hallmark of clinical manifestation of ongoing atopic diseases.
Asunto(s)
Alérgenos/efectos adversos , Expresión Génica/genética , Interferón gamma/genética , Interleucina-4/genética , Interleucina-5/genética , Rinitis Alérgica Estacional/inmunología , Adolescente , Adulto , Cromatografía de Afinidad/métodos , Femenino , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Polen/genética , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Rinitis Alérgica Estacional/genéticaRESUMEN
ClC-4 gene was isolated as a putative Cl(-) channel. Due to a lack of functional expression of ClC-4, its physiological role remains unknown. We isolated a human ClC-4 clone (hClC-4sk) from human skeletal muscles and stably transfected it to Chinese hamster ovary cells. Whole cell patch-clamp studies showed that the hClC-4sk channel was activated by external acidic pH and inhibited by DIDS. It passed a strong outward Cl(-) current with a permeability sequence of I(-) > Cl(-) > F(-). The hClC-4sk has consensus sites for phosphorylation by protein kinase A (PKA); however, stimulation of PKA had no effect on the currents. hClC-4sk mRNA was expressed in excitable tissues, such as heart, brain, and skeletal muscle. These functional characteristics of hClC-4sk provide a clue to its physiological role in excitable cells.
Asunto(s)
Ácidos/farmacología , Canales de Cloruro/genética , Activación del Canal Iónico/efectos de los fármacos , Músculo Esquelético/química , Ácido 4,4'-Diisotiocianostilbeno-2,2'-Disulfónico/farmacología , Secuencia de Aminoácidos , Animales , Células CHO , Canales de Cloruro/metabolismo , Cloruros/metabolismo , Clonación Molecular , Colforsina/farmacología , Cricetinae , ADN Complementario/aislamiento & purificación , Espacio Extracelular/metabolismo , Expresión Génica/fisiología , Humanos , Concentración de Iones de Hidrógeno , Mesocricetus , Datos de Secuencia Molecular , Músculo Esquelético/fisiología , Técnicas de Placa-Clamp , TransfecciónRESUMEN
A 66-year-old woman had been treated for 3 years by her local physician with Sho-saiko-to for chronic hepatitis C virus (HCV) infection and liver cirrhosis. She was admitted to our hospital because of cough, fever, and infiltrative shadows on chest x-ray films. Sho-saiko-to-induced pneumonitis was diagnosed and steroid therapy started. Though a temporary improvement was observed, interstitial pneumonitis relapsed and the patient died of respiratory failure and liver dysfunction. Autopsy findings showed diffuse alveolar damage and honeycombing. Furthermore, reverse-transcriptase polymerase chain reaction techniques detected HCV-RNA in specimens of fibrotic lung tissue. For comparison, HCV-RNA was not histologically detected in lung tissue specimens from 4 control subjects who were positive for HCV antibodies but who did not have interstitial lung disease. It was speculated that the progression of interstitial pneumonia in the present case may have been caused by HCV in combination with Sho-saiko-to-induced lung injury.
Asunto(s)
Medicamentos Herbarios Chinos/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Anciano , Enfermedad Crónica , Resultado Fatal , Femenino , Hepatitis C/complicaciones , Humanos , Cirrosis Hepática/complicaciones , Pulmón/patología , Enfermedades Pulmonares Intersticiales/patologíaRESUMEN
Epidemiological studies have suggested a protective effect of lycopene and lycopene-rich tomatoes against various cancers. Here, the inhibition of colon carcinogenesis by lycopene and tomato juice was investigated. Seven-week-old female F344/NSlc rats received an intrarectal dose of 2 mg (experiment I) or 4 mg (experiment II) of N-methylnitrosourea 3 times a week for 3 weeks, and had free access to one of 4 drinking fluids: plain water (control group), 17 ppm lycopene water solution (Ly group), and diluted tomato juice containing 17 ppm (Tj group) or 3.4 ppm (tj group) lycopene, throughout the experiments. The colon cancer incidence at week 35 was significantly lower in the Tj group, but not in the Ly group, than in the control group: 21% and 33% vs. 54%, in experiment I (24 rats in each group). It was significantly lower in the Tj group than in the tj and control groups, 40% vs. 72% and 84%, in experiment II (25 rats in each group). An appreciable amount of lycopene (0.02 microgram/g) was detected in the colon mucosa of rats in the Tj group, but not in the tj group. The results suggest that tomato juice rich in lycopene may have a protective effect against colon carcinogenesis.
Asunto(s)
Anticarcinógenos/uso terapéutico , Bebidas , Carotenoides/uso terapéutico , Neoplasias del Colon/prevención & control , Metilnitrosourea/toxicidad , Solanum lycopersicum , Animales , Bebidas/análisis , Carcinógenos/toxicidad , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/patología , Femenino , Licopeno , Solanum lycopersicum/química , Valor Nutritivo , Ratas , Ratas Endogámicas F344RESUMEN
This study was undertaken to reveal whether integration of the peripheral signals, leptin and estradiol, that convey information on the metabolic state and gonadal function, respectively, might occur in the same hypothalamic neuronal perikarya. Light and electron microscopic immunolabeling for leptin receptors (LRs) and estrogen receptors (ERs) was carried out on hypothalamic sections of female rats. In the medial preoptic area, periventricular regions, including the parvicellular paraventricular nucleus, the arcuate nucleus and the ventromedial hypothalamic nucleus, all of the cells that expressed immunoreactivity for ERs were also immunopositive for LR. On the other hand, only a subpopulation of LR-containing cells was found to express ERs. The extensive colocalization of receptors for leptin and estrogen in neuronal perikarya of all parts of the hypothalamus suggests a closely coupled interaction between these peripheral signals in the regulation of a variety of behavioral and neuroendocrine mechanisms.
Asunto(s)
Proteínas Portadoras/análisis , Hipotálamo/química , Neuronas/química , Obesidad , Receptores de Superficie Celular , Receptores de Estrógenos/análisis , Animales , Femenino , Hipotálamo/citología , Ratas , Ratas Sprague-Dawley , Receptores de LeptinaRESUMEN
Since IL-4 plays a key role in inducing and increasing the generation of not only primary polyclonal but also secondary specific IgE responses by B lymphocytes, a seasonal increase in IL-4 is likely to be involved in such seasonal rises in specific IgE in seasonal allergic rhinitis. The first aim of this study was to investigate the possible seasonal increase in serum IL-4 in patients with seasonal allergic rhinitis due to Japanese cedar pollens. If serum IL-4 increases in response to seasonal pollen exposure and is responsible for the seasonal increase in pollen-specific IgE in sera, this increase in IL-4 might theoretically affect specific IgE synthesis for other allergens. The second aim was to investigate the effect of natural pollen exposure on serum concentrations of house dust mite-specific IgE in patients who have seasonal allergic rhinitis and concurrent perennial allergic rhinitis due to house dust mites. This study included 55 adult patients with seasonal and perennial allergic rhinitis due to Japanese cedar pollens and Dermatophagoides farinae (D. farinae). Venous blood was collected twice from each patient, before and during the cedar pollen season 1996, to determine IL-4, cedar pollen-specific IgE and D. farinae-specific IgE in sera. Both IL-4 and pollen-specific IgE in sera were significantly increased during the pollen season, and the seasonal increase rate in pollen-specific IgE was significantly correlated with the seasonal increase rate in IL-4. By contrast, D. farinae-specific IgE was not changed during the pollen season in these patients. In conclusion, an elevation of IL-4 in sera during the pollen season may play an important part in the seasonal rise in pollen-specific IgE, and enhancement of specific IgE synthesis is likely to need not only an increase in IL-4 but also an increase in the number and/or capacity of specific IgE-secreting B cells.
Asunto(s)
Inmunoglobulina E/sangre , Interleucina-4/sangre , Ácaros/inmunología , Polen/inmunología , Rinitis/inmunología , Estaciones del Año , Adolescente , Adulto , Animales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rinitis Alérgica Perenne/inmunologíaRESUMEN
This study was designed to investigate the clinical role of specific IgG4 and IgE responses in patients during immunotherapy for seasonal allergy. The study included 109 patients with seasonal allergic rhinitis due to Japanese cedar pollens. They were divided into the control group and the immunotherapy group. Serum samples were obtained at the start of immunotherapy, before the pollen season and during the season, to determine serum specific IgE and IgG4. In the control group specific IgE was significantly increased, but specific IgG4 was not changed during the pollen season. In the immunotherapy group specific IgE was not significantly increased, but specific IgG4 was significantly increased during the season. In the patients having immunotherapy for 2 years or less, the seasonal increase in specific IgG4 related to the magnitude of the clinical effect. In the patients having immunotherapy for 3 years or more, the seasonal increase in specific IgE related to the magnitude of the clinical effect. In conclusion, the specific IgG4 response and specific IgE response during the pollen season make a significant contribution to the clinical effect of immunotherapy. However, modulation of specific IgE and IgG4 responses out of the pollen season was unlikely to be an important phenomenon related to the clinical effect of immunotherapy.
Asunto(s)
Anticuerpos/inmunología , Inmunoglobulina E/inmunología , Inmunoglobulina G/inmunología , Inmunoterapia , Rinitis Alérgica Estacional/terapia , Adolescente , Adulto , Alérgenos/inmunología , Anticuerpos/sangre , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Polen/inmunología , Rinitis Alérgica Estacional/inmunología , Estaciones del Año , Factores de Tiempo , Resultado del Tratamiento , ÁrbolesRESUMEN
Serum specific IgE and IgG4 in 70 patients with seasonal rhinitis caused by Japanese cedar pollens were determined before and during the pollen season. Seasonal increase rate in specific IgE was significantly smaller in the immunotherapy patients than the pharmacotherapy patients, and seasonal increase in specific IgG4 was significant in the immunotherapy patients only. Seasonal increase rate in specific IgE was not significantly different between the patients who responded markedly to short-term immunotherapy and those who did not. On the other hand, seasonal increase rate in specific IgG4 was significantly different between them. In contrast, seasonal increase rate in specific IgE was significantly smaller in the patients who showed marked response to the long-term immunotherapy than those who did not show marked response to the long-term immunotherapy, but seasonal increase rate in specific IgG4 was not significantly different between them. In conclusion, our results suggest that modulation of specific IgG4 response and specific IgE response might be involved in the early and late symptom relief during immunotherapy, respectively. However, further studies might be necessary to definitively establish the clinical roles of specific IgE and specific IgG4 in immunotherapy.
Asunto(s)
Desensibilización Inmunológica , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Rinitis Alérgica Estacional/terapia , Adolescente , Adulto , Alérgenos/inmunología , Antígenos/administración & dosificación , Antígenos/uso terapéutico , Femenino , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Humanos , Inmunoglobulina E/inmunología , Inmunoglobulina G/inmunología , Inyecciones Subcutáneas , Japón , Masculino , Persona de Mediana Edad , Polen/inmunología , Inducción de Remisión , Rinitis Alérgica Estacional/tratamiento farmacológico , Rinitis Alérgica Estacional/inmunología , Estaciones del Año , Factores de Tiempo , Resultado del Tratamiento , ÁrbolesRESUMEN
BACKGROUND: There is increasing evidence that soluble interleukin-2 receptor (sIL-2R) might reflect T cell activation in vivo and soluble intercellular adhesion molecule-1 (sICAM-1) might reflect the ongoing inflammatory response in the inflamed site. OBJECTIVE: The aim of this study was to determine the effect of antihistamine tablets and allergen-specific immunotherapy on the seasonal changes in specific IgE, sIL-2R, and sICAM-1 in the serum of patients with seasonal allergic rhinitis. METHODS: This prospective study included 99 patients with seasonal allergic rhinitis due to Japanese cedar pollens and 27 nonatopic healthy volunteers. The patients were divided into an antihistamine-treated group and an immunotherapy group. Serum samples were collected before and during the pollen season from each patient to determine specific IgE, sIL-2R, and sICAM-1. RESULTS: Levels of sIL-2R before the pollen season did not differ significantly among the nonatopic group, the antihistamine-treated group, and the immunotherapy group. The levels of sICAM-1 before the pollen season were significantly higher in the antihistamine-treated group and in the immunotherapy group than in the nonatopic group. Seasonal increase in specific IgE was significant in the antihistamine-treated group regardless of their clinical outcomes. In contrast, significant increase in specific IgE was observed during the pollen season in poor responders but not in good responders to immunotherapy. Serum levels of sIL-2R and sICAM-1 were significantly increased during the pollen season in poor responders of the antihistamine-treated group and the immunotherapy group. On the other hand, neither seasonal increase in sIL-2R nor sICAM-1 was significant in good responders of the antihistamine-treated group and the immunotherapy group. CONCLUSIONS: Serum levels of sICAM-1 are higher in patients with seasonal allergic rhinitis, even outside of the pollen season when the allergen does not naturally exist. Seasonal changes in serum sICAM-1 as well as sIL-2R and specific IgE are probably objective markers to indicate the clinical efficacy of antihistamines and immunotherapy on seasonal allergic rhinitis.
Asunto(s)
Inmunoglobulina E/sangre , Molécula 1 de Adhesión Intercelular/sangre , Receptores de Interleucina-2/sangre , Rinitis Alérgica Estacional/sangre , Adulto , Especificidad de Anticuerpos , Epítopos/inmunología , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Humanos , Inmunoglobulina E/inmunología , Inmunoterapia , Japón/epidemiología , Persona de Mediana Edad , Polen/inmunología , Rinitis Alérgica Estacional/epidemiología , SolubilidadRESUMEN
The pharmacokinetics of dietary capsanthin was measured in four male volunteers to assess the bioavailability of oxygenated carotenoids (xanthophylls). Capsanthin was used because this carotenoid was not detected in the men's plasma before ingestion of paprika juice. Supplementing capsanthin-rich paprika juice for 1 wk (equivalent to three doses of 5.4 micromol capsanthin/d; 16.2 micromol/d), the level of capsanthin reached a plateau (0.10-0.12 micromol/L) between d 2 and 7 and was not detectable by d 16. Capsanthin was distributed in the plasma lipoproteins (VLDL, 13 +/- 3%; LDL , 44 +/- 3%; HDL, 43 +/- 3%) at the end of the experiment. In a separate experiment involving the single ingestion of paprika juice (equivalent to 34.2 micromol capsanthin) in the same men, the plasma concentration of capsanthin ranged from 0.10 to 0.29 micromol/L at 8 h after ingestion. In contrast, the elevation of the plasma concentration of an acyclic hydrocarbon carotenoid, lycopene, by a single ingestion of tomato soup (equivalent to 186.3 micromol lycopene) in the same subjects was minimal (0.02-0.06 micromol/L). The areas under the curves (AUC) for capsanthin between 0 and 74 h and for lycopene between 0 and 72 h were 4.68 +/- 1.22 and 0.81 +/- 0.17(micromol.h)/L, respectively. The half-lives (t1/2) were calculated to be 20.1 +/- 1.3 and 222 +/- 15 h for capsanthin and lycopene, respectively. We conclude that the clearance of capsanthin is much faster than that of lycopene, although capsanthin is transported into plasma lipoproteins in larger amounts. This polar carotenoid may be metabolized in the human body more rapidly than lycopene. These data justify further research on the physiological functions of capsanthin and other xanthophylls.
Asunto(s)
Capsicum , Carotenoides/análogos & derivados , Plantas Medicinales , Adulto , Anticarcinógenos/administración & dosificación , Anticarcinógenos/sangre , Área Bajo la Curva , Disponibilidad Biológica , Carotenoides/administración & dosificación , Carotenoides/sangre , Carotenoides/farmacocinética , Cromatografía Líquida de Alta Presión , Dieta , Humanos , Absorción Intestinal , Lipoproteínas/sangre , Licopeno , Solanum lycopersicum , Masculino , Tasa de Depuración Metabólica , XantófilasRESUMEN
This study was designed to determine seasonal changes in cytokines, soluble CD23 and specific IgE in the serum of patients with seasonal allergic rhinitis, and the effect of immunotherapy on these seasonal changes. Fifty-four patients with seasonal allergic rhinitis caused by Japanese ceder pollens were divided into a medication group and an immunotherapy group. The patients of the medication group were treated with non-sedating antihistamines alone during the pollen season. The patients of the immunotherapy group had been treated for variable periods (mean, 5.0 +/- 3.2 years) with immunotherapy using japanese cedar pollen antigens. Serum samples were collected before and during the pollen season from each patient, to determine specific IgE, interleukin-4 (IL-4), interferon-gamma (IFN-gamma) and soluble CD23 levels in serum. A significant increase in specific IgE and IL-4 and a significant decrease in IFN-gamma were observed during the pollen season in the medication group. In contrast, in the immunotherapy group, none of specific IgE, IL-4 and IFN-gamma was significantly changed following natural exposure to pollens. However, these effects were not significant in patients undergoing immunotherapy for 3 or fewer years. Seasonal rates of increase in specific IgE and IL-4 differed significantly between good responders and poor responders to immunotherapy, but seasonal rates of decrease in IFN-gamma did not. A seasonal rate of increase in soluble CD23 was significantly correlated with a seasonal rate of increase in specific IgE, in both the medication and the immunotherapy groups. The seasonal rate of increase in soluble CD23 was significantly smaller in the good responders than in the poor responders to immunotherapy. In conclusion, pollen immunotherapy reduces the seasonal increase in specific IgE, IL-4 and soluble CD23 in serum, and in addition switches the seasonal preferential activation of Th-2 cells to reciprocal activation of Th-1 cells with treatment over several years. It is likely that the mechanisms responsible for the clinically beneficial effects of immunotherapy principally involve the modulation of Th-2 rather than Th-1 cytokines.
Asunto(s)
Inmunoglobulina E/sangre , Interleucina-4/sangre , Rinitis Alérgica Estacional/inmunología , Adulto , Femenino , Humanos , Inmunoterapia , Interferón gamma/sangre , Masculino , Persona de Mediana Edad , Polen/inmunología , Receptores de IgE/inmunología , Rinitis Alérgica Estacional/terapia , Estaciones del Año , Factores de Tiempo , ÁrbolesRESUMEN
The role of serum eosinophil cationic protein levels in allergic rhinitis is controversial. It is also unclear whether with immunotherapy it is possible to reduce these serum levels in allergic diseases. We studied serum eosinophil cationic protein levels in patients with cedar-induced allergic rhinitis and compared them with non-atopic controls. The second aim of this study was to elucidate whether immunotherapy is capable of decreasing the seasonal elevation in serum eosinophil cationic protein levels in seasonal allergic rhinitis. The serum eosinophil cationic protein levels of the untreated patient group were significantly higher than those of the non-atopic controls. The levels in patients who received immunotherapy for 2 yr were also significantly higher than those of the non-atopic controls. However, the levels were not different between the patients undergoing immunotherapy for over 3 yr and the non-atopic controls. The serum levels of the 31 patients treated with immunotherapy correlated with the duration of immunotherapy. In conclusion, the serum eosinophil cationic protein levels are higher in untreated patients with seasonal allergic rhinitis and this seasonal activation in circulating eosiohophils decreases gradually during immunotherapy, but this inhibitory effect becomes apparent only after a number of years of immunotherapy. This prevention of seasonal eosinophil activation is one of the mechanisms responsible for the clinical effect of immunotherapy.
Asunto(s)
Proteínas Sanguíneas/análisis , Eosinófilos/inmunología , Inmunoterapia , Mediadores de Inflamación/sangre , Rinitis Alérgica Estacional/terapia , Ribonucleasas , Adolescente , Adulto , Alérgenos , Estudios de Casos y Controles , Proteínas en los Gránulos del Eosinófilo , Femenino , Humanos , Inmunoglobulina E/sangre , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Extractos Vegetales/inmunología , Extractos Vegetales/uso terapéutico , Polen , Rinitis Alérgica Estacional/sangre , Rinitis Alérgica Estacional/inmunología , Factores de Tiempo , ÁrbolesRESUMEN
To determine bioavailability, expressed as the protein efficiency ratio (PER) and biological value (BV) in rats, of the epsilon-(gamma-glutamyl)lysine [epsilon-(gamma-Glu)Lys] moiety in crosslinked proteins, we prepared heavily crosslinked [21.5 /micromol epsilon-(gamma-Glu)Lys/g casein] and intermediately crosslinked [13.6 micromol epsilon-(gamma-Glu)Lys/g casein] casein, using microbial transglutaminase. In Experiment 1, rats were assigned to one of four diets (heavily or intermediately crosslinked caseins, intact casein or non-protein diet) for 4 wk to evaluate the bioavailability of the epsilon-(gamma-Glu)Lys moiety in crosslinked casein as the sole source of dietary protein. Rats that were fed intact casein and the two crosslinked caseins had similar growth rates, PER, and BV, indicating that crosslinked caseins supported the growth of rats similarly to the intact casein. In Experiment 2, heavily crosslinked casein was added to wheat gluten-based diets in concentrations of 20 and 40 g/kg diet to evaluate the bioavailability of lysine in the epsilon-(gamma-Glu)Lys moiety of the casein as a lysine supplement for lysine-poor gluten. One of six diets (heavily crosslinked or intact casein diets in the two concentrations, gluten diet, or non-protein diet) was fed to rats for 4 wk. No significant differences in food intake, body weight gain, PER or BV were observed among rats fed the intact or crosslinked casein diets at either 2 or 4 g/100 g casein. These results suggest that the epsilon-(gamma-Glu)Lys moiety in crosslinked caseins are absorbed and therefore supplement the gluten. HPLC analysis of urine and feces of rats fed the crosslinked caseins actually confirmed that approximately 99% of the epsilon-(gamma-Glu)Lys moiety was absorbed in the body.
Asunto(s)
Caseínas/química , Dipéptidos/análisis , Lisina/análisis , Lisina/farmacocinética , Animales , Disponibilidad Biológica , Caseínas/análisis , Caseínas/metabolismo , Cromatografía Líquida de Alta Presión , Proteínas en la Dieta/análisis , Dipéptidos/metabolismo , Ingestión de Alimentos/fisiología , Glútenes/química , Lisina/metabolismo , Masculino , Ratas , Ratas Wistar , Transglutaminasas/análisis , Transglutaminasas/fisiología , Aumento de Peso/fisiología , gamma-Glutamiltransferasa/análisis , gamma-Glutamiltransferasa/metabolismoRESUMEN
A novel pyradine-derivative was isolated from the mushroom Albatrellus confluens. This compound promoted melanin synthesis by B16 melanoma cells.
Asunto(s)
Basidiomycota , Melaninas/biosíntesis , Melanoma Experimental/metabolismo , Pirazinas/aislamiento & purificación , Animales , Cristalografía por Rayos X , Espectroscopía de Resonancia Magnética , Ratones , Extractos Vegetales , Pirazinas/química , Pirazinas/farmacologíaRESUMEN
FK037 has potent therapeutic activity against lethal systemic infections and experimental local infections due to a wide variety of Gram-positive and Gram-negative bacteria such as staphylococci, Streptococcus pneumoniae, Enterobacteriaceae and Pseudomonas aeruginosa in mice. In murine systemic infections, FK037 was the most effective of the cephalosporins and imipenem tested against highly methicillin-resistant Staphylococcus aureus (H-MRSA). It was more effective than ceftazidime against selected strains of S. aureus and Enterobacteriaceae, except Serratia marcescens and P. aeruginosa against which FK037 was as effective as ceftazidime and was as effective as cefpirome against all organisms tested, except MRSA and P. aeruginosa against which FK037 was more effective than cefpirome. These results correlated well with its in vitro activity. In murine local infections, with few exceptions, FK037 was more effective than ceftazidime and cefpirome against Klebsiella pneumonia in ED50 values and against methicillin-sensitive S. aureus (MSSA) subcutaneous abscess, pyelonephritis with Staphylococcus epidermidis, E. coli and P. aeruginosa, intrauterine infections with S. aureus and E. coli in reducing the number of viable bacteria in the abscess, kidneys and uterus. It is noteworthy that the therapeutic effects of FK037 were more potent than had been anticipated from its in vitro activity against local infections with staphylococci and P. aeruginosa when compared with ceftazidime or cefpirome. In addition, the therapeutic effects of FK037 were equipotent or superior to those of cefpirome and ceftazidime against pneumonia due to MSSA, K. pneumoniae and P. aeruginosa in reducing the number of viable bacteria in the lungs in mice using an in vivo pharmacokinetic model simulating human plasma concentrations after drip infusion of usual clinical doses (0.25 to 1.0 g for MSSA, 0.063 to 0.125 g for K. pneumoniae and 1.0 to 2.0 g for P. aeruginosa). FK037 induced an in vivo post-antibiotic effect (PAE) of 3.4 hours against a thigh infection with MSSA in neutropenic mice. These results strongly suggest that it has potential for clinical use against various infections due to bacteria which include staphylococci and P. aeruginosa.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Ceftizoxima/análogos & derivados , Absceso/tratamiento farmacológico , Animales , Bacterias/efectos de los fármacos , Ceftizoxima/uso terapéutico , Permeabilidad de la Membrana Celular/efectos de los fármacos , Femenino , Infusiones Parenterales , Masculino , Ratones , Ratones Endogámicos ICR , Pruebas de Sensibilidad Microbiana , Neumonía/tratamiento farmacológico , Pielonefritis/tratamiento farmacológico , Enfermedades Uterinas/tratamiento farmacológicoRESUMEN
FK037 exhibits potent in vitro and in vivo antibacterial activity against methicillin-resistant staphylococci. In in vitro studies, FK037 was the most active of the cephalosporins and imipenem tested against the highly methicillin-resistant staphylococci (MIC > 100 micrograms/ml). Only 2 of 57 strains of highly methicillin-resistant Staphylococcus aureus (H-MRSA) had a FK037 MIC value of 50 micrograms/ml. On the other hand, 55, 40 and 19 strains had MICs of 50 or > or = 100 micrograms/ml to cefpirome, flomoxef and imipenem, respectively. Against 13 strains of highly methicillin-resistant coagulase-negative staphylococci (H-MRCNS), FK037 inhibited all the strains at < or = 50 micrograms/ml, but there were many strains highly resistant to the reference drugs with MICs of > or = 100 micrograms/ml. The influence of culture conditions such as low temperature, high inoculum and supplementation with 4% NaCl on the anti-MRSA activity of FK037 was less than those with cefpirome, flomoxef and imipenem. The in vitro frequency of spontaneous mutant cells highly resistant to FK037 in MRSA was lower than that to cefpirome and flomoxef. These findings were supported by lack of colonies inside the inhibition zone demarcated by FK037 in a disk sensitivity test, although many colonies proliferated inside the inhibition zone demarcated by flomoxef and imipenem. The increase in MIC of FK037 against a MRSA strain during subculture in the presence of the drug was smaller than that noted with the reference drugs. FK037 had higher affinity and faster binding for the PBP 2a of MRSA than that of the reference drugs. Moreover, the capacity to induce PBP 2a was lower for FK037 than that of cefpirome but higher than that of flomoxef. In an in vitro pharmacokinetic model simulating human plasma concentrations, FK037 showed potent bactericidal activity against H-MRSA in the plasma concentrations after intravenous infusion dosing with 1.0 g. FK037 was synergistically active against H-MRSA in combination with either imipenem of fosfomycin. The in vitro post-antibiotic effect (PAE) of FK037 against H-MRSA ranged from 1.2 to 1.7 hours at one to four times the MIC. FK037 had potent therapeutic effects against lethal systemic infections and experimental local infections in mice such as pneumonia, endocarditis, subcutaneous abscess, intrauterine infection and granuloma pouch infection due to MRSA or methicillin-resistant Staphylococcus epidermidis (MRSE). FK037 was about 4, 8 and 1.5 times more effective than cefpirome, flomoxef and imipenem, respectively, against lethal systemic infections with H-MRSA.(ABSTRACT TRUNCATED AT 400 WORDS)