ABSTRACT
En el Instituto Finlay de Vacunas se desarrolló el candidato vacunal SOBERANA 01 (FINLAY-FR-01) contra el coronavirus de tipo 2 causante del síndrome respiratorio agudo severo. Este trabajo tuvo como objetivo evaluar la inmunogenicidad y posibles efectos toxicológicos del candidato vacunal SOBERANA 01 (FINLAY-FR-01 en Cercopithecus aethiops. Se utilizaron cinco primates no humanos (hembras), de 1-3 años de edad y 1-4 kg de peso corporal, distribuidos en dos grupos experimentales: Control (Solución Salina Fisiológica) y Tratado SOBERANA 01 (FINLAY-FR-01). El estudio se extendió por 84 días, en un esquema a dosis repetida de cuatro inmunizaciones los días 0, 28, 56 y 70. Se realizaron observaciones clínicas diarias, peso corporal, signos vitales (temperatura rectal, frecuencia respiratoria, y frecuencia cardíaca), exámenes electrocardiográficos, toma de la temperatura del sitio de inyección, musculometría e irritabilidad dérmica. Fueron realizados exámenes de hematología, bioquímica sanguínea, así como estudios inmunológicos. El ensayo concluyó con una supervivencia del 100por ciento, no se manifestaron signos de toxicidad, no hubo variaciones hematológicas, ni de la bioquímica sanguínea asociadas a la sustancia de ensayo. Además, no se observaron efectos locales en el sitio de administración. Por último, el candidato vacunal resultó inmunogénico, ya que se indujeron títulos altos de IgG anti-RBD, así como de la inhibición de la unión de RBD a ACE2(AU)
At Finlay Vaccine Institute has been developed the vaccine candidate SOBERANA 01 (FINLAY-FR-01) against SARS-CoV-2 virus, causing COVID-19. This work aims to evaluate the immunogenicity and possible toxicological effects of the SOBERANA 01 (FINLAY-FR-01) vaccine candidate in Cercopithecus aethiops. Five non-human primates (females) from 1-3 years old and 1-4 kg of body weight were distributed in two experimental groups: Control (Physiological Saline Solution) and Treated (SOBERANA 01 FINLAY-FR-01). The study extended through 84 days, in a repeated dose schedule of four immunizations on days 0, 28, 56, and 70. Daily clinical observations, body weight, vital signs (rectal temperature, respiratory rate, and heart rate), electrocardiographic examinations, temperature of the injection site, musculometry and dermic irritability, were performed. Hematological and blood biochemistry tests, as well as immunological studies were assessed. At the end of the assay 100percent survival was obtained, there were no signs of toxicity neither hematological or blood biochemistry variations associated with the test substance. In addition, no local effects were observed at the administration site. Finally, the vaccine candidate was immunogenic, since high titers of anti-RBD IgG, as well as inhibition of the RBD to ACE2 binding were induced(AU)
Subject(s)
Animals , Haplorhini , Immunogenicity, Vaccine , COVID-19 Vaccines/therapeutic use , VaccinesABSTRACT
Despite recent advances in the treatment of some forms of leishmaniasis, the available drugs are still far from ideal due to inefficacy, parasite resistance, toxicity and cost. The wide-spectrum antimicrobial activity of 2-nitrovinylfuran compounds has been described, as has their activity against Trichomonas vaginalis and other protozoa. Thus, the aim of this study was to test the antileishmanial activities of six 2-nitrovinylfurans in vitro and in a murine model of leishmaniasis. Minimum parasiticide concentration (MPC) and 50% inhibitory concentration (IC50) values for these compounds against the promastigotes of Leishmania amazonensis, Leishmania infantum and Leishmania braziliensis were determined, as were the efficacies of two selected compounds in an experimental model of cutaneous leishmaniasis (CL) caused by L. amazonensis in BALB/c mice. All of the compounds were active against the promastigotes of the three Leishmania species tested. IC50 and MPC values were in the ranges of 0.8-4.7 µM and 1.7-32 µM, respectively. The compounds 2-bromo-5-(2-bromo-2-nitrovinyl)-furan (furvina) and 2-bromo-5-(2-methyl-2-nitrovinyl)-furan (UC245) also reduced lesion growth in vivo at a magnitude comparable to or higher than that achieved by amphotericin B treatment. The results demonstrate the potential of this class of compounds as antileishmanial agents and support the clinical testing of Dermofural(r) (a furvina-containing antifungal ointment) for the treatment of CL.
Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/drug therapy , Hodgkin Disease/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bleomycin/adverse effects , Bleomycin/therapeutic use , Combined Modality Therapy , Decision Making , Dacarbazine/adverse effects , Dacarbazine/therapeutic use , Doxorubicin/adverse effects , Doxorubicin/therapeutic use , Hodgkin Disease/mortality , Neoplasm Staging , Practice Guidelines as Topic , Risk Assessment , Treatment Outcome , Vinblastine/adverse effects , Vinblastine/therapeutic useABSTRACT
Introducción: el extracto oleoso de la semilla de Carapa guianensis Aublet ha tenido diversos usos biomédicos. Recientemente fue evaluado este extracto, el cual manifestó grandes potencialidades como antioxidante en ensayos in vivo; pero poco se conoce de su efecto sobre el ADN en biomodelos experimentales. Objetivo: evaluar el potencial genotóxico del extracto oleoso de la semilla de Carapa guianensis en el ensayo de aberraciones cromosómicas de células de la médula ósea de ratones Balb/c. Métodos: se formaron cinco grupos experimentales: un grupo placebo (Tween 65 al 2 por ciento), tres tratados con niveles de dosis del extracto (400, 1 000 y 2 000 mg/kg), administrados por vía oral durante 14 días; por último, un grupo control positivo tratado con ciclofosfamida, en dosis de 50 mg/kg por vía intraperitoneal 48 y 24 h antes de la eutanasia. Se administraron cinco animales/sexo/grupo. Después de los 14 días de administración se les efectuó la eutanasia por dislocación cervical y se les extrajo la médula ósea del fémur para proceder a realizar la técnica citogenética de aberraciones cromosómicas. Resultados: los resultados entre controles y tratados con el extracto no difirieron para los dos sexos en las variables índice mitótico, Gaps, células con poliploidías, número de células con aberraciones cromosómicas y cromatídicas y el porcentaje de células con aberraciones. Sin embargo, sí difirieron controles y tratados contra el grupo tratado con ciclofosfamida, lo que valida nuestros resultados. Conclusiones: el extracto oleoso de la semilla de la Carapa guianensis no posee potencialidades genotóxicas en la formación de aberraciones cromosómicas, sobre todo estructurales en células de la médula ósea de ratones Balb/c de ambos sexos(AU)
Introduction: the oil extract from Carapa guianensis seed has various biomedical applications. It was recently evaluated and revealed great potentialities as antioxidant in in vivo assays, but little is known about its effect on DNA in experimental biomodels. Objective: to evaluate the genotoxic potential of the oil extract from Carapa guianensis seed in the chromosomal aberration of the bone marrow cells test performed in Balb/c mice. Methods: five experimental groups were created: one placebo group (Tween 65, 2 percent), three treated with different extract doses (400, 1000 and 2000 mg/kg) orally administered for 14 days and one positive control group treated with cyclophosphamide at a dose of 50 mg/kg intraperitoneally at 48 and 24 h before euthanasia. Five animals per sex from each group were administered the set dose. After 14 days of treatment, the animals were euthanized through cervical dislocation and their femoral bone marrow was taken out to perform the cytogenetic chromosomal aberration technique. Results: the results between the control group and the groups treated with the extract did not differ between the two sexes in terms of the mitotic index variables, Gaps, polyploidy cells, number of cells with chromosome and chromatic aberrations and the percentage of aberration cells. However, the results of controls and of treated groups were different from those of the group treated with cyclophosphamide, which proved the validation of our results. Conclusions: the oil extract from Carapa guianensis seeds does not have genotoxic potential for the formation of chromosome aberrations, mainly structural, in Balb/c mice bone marrow of both sexes(AU)
Subject(s)
Animals , Mice , Chromosome Aberrations , Genotoxicity/methodsABSTRACT
Se realizó la prueba toxicológica de dosis única para la vacuna antileptospirósica vax-SPIRAL en ratones. No se encontraron síntomas clínicos de toxicidad y las diferencias entre las variables evaluadas no fueron importantes desde el punto de vista biológico