RESUMEN
Efforts are underway for the development of an effective vaccine against Helicobacter pylori infection. We prepared recombinant full-length (568 aa) H. pylori recombinant urease B (rUreB) protein and tested it for immunogenicity and protection. BALB/c mice received either rUreB (40 µg) plus CpG (10 µg) intranasally, rUreB (50 µg) plus 3% aluminum hydroxide (50 µL) intramuscularly or rUreB (25 µg) plus Freund's adjuvant (25 µL) subcutaneously, three times (weeks 0, 2 and 6). Intranasal rUreB plus CpG was neither immunogenic nor protective; intramuscular rUreB plus aluminum hydroxide was immunogenic and modestly protective, and subcutaneous rUreB plus Freund's adjuvant was immunogenic and highly protective. The fact that protection was improved with Freund's adjuvant indicates that rUreB is a good antigen for a vaccine but that it needs a stronger adjuvant than aluminum hydroxide.
Asunto(s)
Adyuvantes Inmunológicos , Hidróxido de Aluminio/inmunología , Anticuerpos Antibacterianos/sangre , Vacunas Bacterianas/inmunología , Infecciones por Helicobacter/prevención & control , Helicobacter pylori/inmunología , Ureasa/inmunología , Animales , Vacunas Bacterianas/administración & dosificación , ADN/inmunología , Modelos Animales de Enfermedad , Adyuvante de Freund , Infecciones por Helicobacter/inmunología , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inyecciones Intramusculares , Inyecciones Subcutáneas , Ratones , Ratones Endogámicos BALB C , Oligodesoxirribonucleótidos , Reacción en Cadena de la Polimerasa , Proteínas Recombinantes/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/inmunologíaRESUMEN
BACKGROUND: Disseminated intravascular coagulation (DIC) is a pathological disturbance of the complex balance between coagulation and anticoagulation that is precipitated by vascular injury, acidosis, endotoxin release and/or sepsis and characterized by severe bleeding and excessive clotting. The innately low levels of coagulation factors found in newborn infants place them at extremely high risk for DIC. Anecdotal reports suggest that either anticoagulant or fibrinolytic therapy may alleviate some of the manifestations of DIC. To test the hypothesis that replacement of both anticoagulants and fibrinolytics may improve survival and outcome better than either single agent or supportive care alone, we utilized a neonatal piglet model of endotoxin-induced DIC. METHODS: DIC was induced in twenty-seven neonatal pigs (7 to 14 days of age) by intravenous administration of E. coli endotoxin (800 microg/kg over 30 min). The piglets were divided into 4 groups on the basis of treatment protocol [A: supportive care alone; B: Antithrombin III (AT, 50 microg/kg bolus, 25 microg/kg per hr continuous infusion) and supportive care; C: Recombinant Tissue Plasminogen Activator (R-TPA, 25 microg/kg per hr continuous infusion) and supportive care; D: AT, R-TPA and supportive care] and monitored for 3 primary outcome parameters (survival time, macroscopic and microscopic organ involvement) and 4 secondary outcome parameters (hematocrit; platelet count; fibrinogen level; and antithrombin III level). RESULTS: Compared with supportive care alone, combination therapy with AT and R-TPA resulted in a significant improvement of survival time, hematocrit, AT level, macroscopic and microscopic organ involvement, p < 0.05. Compared with supportive care alone, R-TPA alone significantly reduced macroscopic organ involvement and AT alone increased AT levels. CONCLUSION: The findings suggest that combining AT, R-TPA and supportive care may prove more advantageous in treating the clinical manifestations of DIC in this neonatal pig model than either single modality or supportive care alone.
RESUMEN
noni, the juice of the fruit from the Morinda citrifolia plant, has been used for centuries as a medicinal agent. We tested the effects of noni juice in a three-dimensional fibrin clot matrix model using human placental vein and human breast tumor explants as sources for angiogenic vessel development. Noni in concentrations of 5% (vol/vol) or greater was highly effective in inhibiting the initiation of new vessel sprouts from placental vein explants, compared with initiation in control explants in media supplemented with an equivalent amount of saline. These concentrations of noni were also effective in reducing the growth rate and proliferation of newly developing capillary sprouts. When used at a concentration of 10% in growth media, noni was able to induce vessel degeneration and apoptosis in wells with established capillary networks within a few days of its application. We also found that 10% noni juice in media was an effective inhibitor of capillary initiation in explants from human breast tumors. In tumor explants which did show capillary sprouting, the vessels rapidly degenerated (2-3 days) in those exposed to media supplemented with 10% noni.