RESUMEN
Nasal administration of Ags using a novel hybrid Ag delivery vehicle composed of envelope glycoproteins of Sendai virus on the surface of liposome membranes (fusogenic liposome) efficiently delivered Ags to Ag-sampling M cells in nasopharyngeal-associated lymphoreticular tissue. Additionally, fusogenic liposomes also effectively delivered the Ags into epithelial cells and macrophages in nasopharyngeal-associated lymphoreticular tissue and nasal passages. In vitro Ag presentation assays clearly showed that fusogenic liposomes effectively presented encapsulated Ags via the MHC class II-dependent pathway of epithelial cells as well as macrophages. Fusogenic liposomes also have an adjuvant activity against mucosal epithelial cells to enhance MHC class II expression. According to these high delivery and adjuvant activities of fusogenic liposomes, nasal immunization with OVA-encapsulated fusogenic liposomes induced high levels of OVA-specific CD4(+) Th1 and Th2 cell responses. Furthermore, Ag-specific CTL responses and Ab productions were also elicited at both mucosal and systemic sites by nasal immunization with Ag-encapsulated fusogenic liposomes. These results indicate that fusogenic liposome is a versatile and effective system for the stimulation of Ag-specific immune responses at both mucosal and systemic compartments.
Asunto(s)
Antígenos de Histocompatibilidad Clase II/fisiología , Antígenos de Histocompatibilidad Clase I/fisiología , Tejido Linfoide/inmunología , Sistema Mononuclear Fagocítico/inmunología , Mucosa Nasal/inmunología , Nasofaringe/inmunología , Respirovirus/inmunología , Proteínas Virales de Fusión/inmunología , Administración Intranasal , Animales , Presentación de Antígeno/inmunología , Línea Celular , Femenino , Antígenos de Histocompatibilidad Clase II/biosíntesis , Inmunoglobulina A/biosíntesis , Inmunoglobulina G/biosíntesis , Liposomas/administración & dosificación , Liposomas/inmunología , Tejido Linfoide/virología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Sistema Mononuclear Fagocítico/virología , Mucosa Nasal/virología , Nasofaringe/virología , Células TH1/inmunología , Células TH1/metabolismo , Células Th2/inmunología , Células Th2/metabolismo , Células Tumorales Cultivadas , Proteínas Virales de Fusión/administración & dosificaciónRESUMEN
In the present study, mucoadhesive polymer-dispersed microspheres (MS) were examined as a potential mucosal vaccine carrier. A major focus of the study was aimed at directly assessing the influence of antigen release and persistence in the mouse small intestine for the induction of mucosal and systemic immune responses. BALB/c mice were immunized with various forms of MS containing chicken egg ovalbumin (OVA) by administration into the duodenum. No detectable anti-OVA immune responses were observed following the administration of OVA alone or that of MS without mucoadhesive polymer (MS-0). MS-10 containing 10% mucoadhesive polymer rapidly released OVA and hardly induced anti-OVA antibody responses in either serum or fecal extracts. In contrast, MS-8 and MS-6 (with 8 and 6% mucoadhesive polymer) showed controlled release of OVA, which elicited strong OVA-specific IgG and IgA responses in serum and fecal extracts, respectively. Additionally, the strongest immune responses were induced in mice immunized with MS-8, which had both the optimal release-profile of OVA and the longest persistence in the small intestine. These findings indicate that antigen movement in the small intestine is an important factor and that appropriate microsphere forms with mucoadhesive polymers might be useful candidates as mucosal vaccine carriers.
Asunto(s)
Sistemas de Liberación de Medicamentos , Inmunidad Mucosa , Microesferas , Vacunas/administración & dosificación , Adhesivos , Animales , Formación de Anticuerpos , Pollos , Portadores de Fármacos , Estabilidad de Medicamentos , Femenino , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/administración & dosificación , Ovalbúmina/inmunología , PolímerosRESUMEN
It has been demonstrated that PCB metabolism is mainly catalyzed by 1A and 2B subfamily cytochrome P450s, CYP1A1/2 and CYP2B1/2. These studies were conducted mostly with hepatic enzymes in rodents. The 1A and 2B subfamily P450 s are constitutively expressed little, but markedly induced by xenobiotics such as 3-methylcholanthrene and phenobarbital in rodents. On the other hand, the recent studies showed that cytochrome P450s in human liver are remarkably different from isoform of rodents in constitution and enzyme activities. In the present study, we first tried to metabolize some PCBs with 2C subfamily cytochrome P450 (CYP2C) purified from dog liver microsomes. The data suggested that CYP2C may not be involved in PCB metabolism. Since CYP2C is the same most abundant enzyme as 3A subfamily P450 in human liver and plays a major role for metabolism of many drugs used clinically, and may also play an important role for metabolism of some steroid hormones, we further studied the inhibition of CYP2C-catalyzed steroid metabolism by typical PCB congeners. CYP2C-mediated steroid metabolism is greatly inhibited by 2, 4, 5, 2', 4', 5'-hexachlorbiphenyl, but not by 3, 4, 5, 3', 4'-pentachlorobiphenyl. On the contrary, 3, 4, 5, 3', 4'-pentachlorobiphenyl markedly suppressed CYP2C expression in the dog liver. These results suggest that residual PCBs may affect the current situation of steroid hormones in Yusho patients, and may cause PCB drug interactions.
Asunto(s)
Sistema Enzimático del Citocromo P-450/fisiología , Bifenilos Policlorados/toxicidad , Secuencia de Aminoácidos , Animales , Sistema Enzimático del Citocromo P-450/metabolismo , Perros , Femenino , Humanos , Masculino , Microsomas Hepáticos/enzimología , Datos de Secuencia Molecular , Bifenilos Policlorados/metabolismo , Roedores , Testosterona/metabolismoRESUMEN
OBJECTIVES: Retrospective and prospective studies examined the surgical effects in lowering intraocular pressure levels of trabeculotomy ab externo in adult eyes with either primary open angle glaucoma or pseudoexfoliation syndrome. We report the results of primary trabeculotomy as an intervention for glaucoma. PATIENTS: Included in the retrospective study were 357 eyes of 227 patients with primary open angle glaucoma and 82 eyes of 65 patients with pseudoexfoliation syndrome, each of which underwent trabeculotomy ab externo alone and none of which had a history of laser or surgical treatment for ocular disease. Included in the prospective study were 33 eyes of 22 patients with primary open angle glaucoma and 17 eyes of 15 patients (older than 40 years) with pseudoexfoliation syndrome. RESULTS: A life-table analysis for the retrospective study showed that the final success probability (mean +/- SE) at 5 years after surgery was 73.5% +/- 6.3% in eyes with pseudoexfoliation syndrome, which is significantly better than 58.0% +/- 3.1% in eyes with primary open angle glaucoma (P < .05). Also, the higher the preoperative intraocular pressure levels are, the less likely that the postoperative intraocular pressure levels will be brought under control (P < .01). Surgical outcome in the prospective study demonstrated success in 27 (79%) of 34 eyes after 3 years and in 16 (64%) of 25 eyes after 5 years, with medication. Complications included Descemet's membrane detachment (one eye), cyclodialysis (one eye), and decreased visual acuity due to progression of cataract (four eyes). CONCLUSION: The surgical results of trabeculotomy ab externo remain effective in controlling intraocular pressure levels for a long time in selected patients. It thus appears that trabeculotomy ab externo can be considered as an alternative choice of surgical treatment in some cases of glaucoma.
Asunto(s)
Síndrome de Exfoliación/cirugía , Glaucoma de Ángulo Abierto/cirugía , Trabeculectomía/métodos , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Presión Intraocular , Tablas de Vida , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Probabilidad , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Agudeza VisualRESUMEN
A 62-year-old woman, who frequently had numbness seizures in the right half of her body, is reported. Weakness and consciousness disturbance did not occur during the seizure, and an abnormal electroencephalogram was not observed during the seizure or between seizures. The seizure was completely inhibited by a single-blind administration of phenytoin. It also disappeared on administration of carbamazepine, suggesting that the numbness seizures in this patient were of an epileptic nature.