RESUMO
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multifunctional neuropeptide belonging to the glucagon/secretin superfamily. In teleost fish, PACAP has been demonstrated to have an immunomodulatory role. Although previous studies have shown that viral/bacterial infections can influence the transcription of PACAP splicing variants and associated receptors in salmonids, the antiviral activity of PACAP has never been studied in teleost. Thus, in the present work, we investigated in vitro the influence of synthetic Clarias gariepinus PACAP-38 on the transcription of genes related to viral immunity using the rainbow trout monocyte/macrophage-like cell line RTS11 as a model. Positive transcriptional modulation of interferon gamma (IFNγ), interferon alpha (FNα1,2), interleukin 8 (IL-8), Mx and Toll-like receptor 3 (TLR3) genes was found in a dose and time dependent manner. We also explored how a pre-treatment with PACAP could enhance antiviral immune response using poly (I:C) as viral mimic. Interferons and IL-8 transcription levels were enhanced when PACAP was added 24 h previous to poly (I:C) exposure. With these evidences, we tested in vivo how PACAP administration by immersion bath affected the survival of rainbow trout fry to a challenge with viral hemorrhagic septicemia virus (VHSV). After challenge, PACAP-treated fish had increased survival compared to non-treated/challenge fish. Furthermore, PACAP was able to decrease the viral load in spleen/kidney and stimulate the transcription of IFNs and Mx when compared to untreated infected fish. Altogether, the results of this work provide valuable insights regarding the role of teleost PACAP in antiviral immunity and point to a potential application of this peptide to reduce the impact of viral infections in aquaculture.
Assuntos
Antivirais/imunologia , Peixes-Gato/imunologia , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Imunidade Inata , Oncorhynchus mykiss , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Animais , Proteínas de Peixes/imunologia , Novirhabdovirus/fisiologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/imunologia , Poli I-C/farmacologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/veterináriaRESUMO
Tuberculosis (TB) is one of the deadliest infectious diseases in humankind history. Although, drug sensible TB is slowly decreasing, at present the rise of TB cases produced by multidrug-resistant (MDR) and extensively drug-resistant strains is a big challenge. Thus, looking for new therapeutic options against these MDR strains is mandatory. In the present work, we studied, in BALB/c mice infected with MDR strain, the therapeutic effect of supra-pharmacological doses of the conventional primary antibiotics rifampicin and isoniazid (administrated by gavage or intratracheal routes), in combination with recombinant human hepatocyte growth factor (HGF). This high dose of antibiotics administered for 3 months, overcome the resistant threshold of the MDR strain producing a significant reduction of pulmonary bacillary loads but induced liver damage, which was totally prevented by the administration of HGF. To address the long-term efficiency of this combined treatment, groups of animals after 1 month of treatment termination were immunosuppressed by glucocorticoid administration and, after 1 month, mice were euthanized, and the bacillary load was determined in lungs. In comparison with animals treated only with a high dose of antibiotics, animals that received the combined treatment showed significantly lower bacterial burdens. Thus, treatment of MDR-TB with very high doses of primary antibiotics particularly administrated by aerial route can produce a very good therapeutic effect, and its hepatic toxicity can be prevented by the administration of HGF, becoming in a new treatment modality for MDR-TB.
Assuntos
Antibióticos Antituberculose/toxicidade , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fator de Crescimento de Hepatócito/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos , Animais , Quimioterapia Combinada , Humanos , Isoniazida/toxicidade , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis , Rifampina/toxicidadeRESUMO
The family Picornaviridae is a large and diverse group of viruses that infect humans and animals. Picornaviruses are among the most common infections of humans and cause a wide spectrum of acute human disease. This study began as an investigation of acute flaccid paralysis (AFP) in a small area of eastern Bolivia, where surveillance had identified a persistently high AFP rate in children. Stools were collected and diagnostic studies ruled out poliovirus. We tested stool specimens from 51 AFP cases and 34 healthy household or community contacts collected during 2002-2003 using real-time and semi-nested reverse transcription polymerase chain reaction assays for enterovirus, parechovirus, cardiovirus, kobuvirus, salivirus and cosavirus. Anecdotal reports suggested a temporal association with neurological disease in domestic pigs, so six porcine stools were also collected and tested with the same set of assays, with the addition of an assay for porcine teschovirus. A total of 126 picornaviruses were detected in 73 of 85 human individuals, consisting of 53 different picornavirus types encompassing five genera (all except Kobuvirus). All six porcine stools contained porcine and/or human picornaviruses. No single virus, or combination of viruses, specifically correlated with AFP; however, the study revealed a surprising complexity of enteric picornaviruses in a single community.
Assuntos
Infecções por Picornaviridae/epidemiologia , Infecções por Picornaviridae/virologia , Picornaviridae/classificação , Picornaviridae/genética , Adolescente , Animais , Bolívia/epidemiologia , Criança , Pré-Escolar , Fezes/virologia , Feminino , Humanos , Lactente , Masculino , Epidemiologia Molecular , Dados de Sequência Molecular , Paraplegia/epidemiologia , Paraplegia/virologia , Picornaviridae/isolamento & purificação , Infecções por Picornaviridae/veterinária , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , População Rural , Análise de Sequência de DNA , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/virologia , Adulto JovemRESUMO
OBJECTIVE: To determine genetic relatedness of clone Colombia(5) ST289 with invasive Streptococcus pneumoniae serotype 5 isolates recovered in nine Latin American countries. METHODS: Forty-four invasive S. pneumoniae serotype 5 isolates recovered from children under 5 years of age in Bolivia, Chile, Dominican Republic, Ecuador, Nicaragua, Panama, Paraguay, Peru, and Venezuela were studied. Pulsed-field gel electrophoresis patterns of DNA treated with SmaI restriction enzyme were classified using Tenover's criteria and analyzed with the Fingerprinting II program to determine their genetic relatedness with the Colombian clone. RESULTS: All isolates had a genetic similarity of 78.5% or more with the Colombian clone. Thirteen electrophoretic subtypes derived of pattern A were identified, and five of them (A5, A6, A8, A13, A27) comprised 61.4% of the isolates. CONCLUSIONS: Clone Colombia(5) ST289 is disseminated in Latin America. This is important because S. pneumoniae serotype 5 frequently causes invasive disease in the region and is associated with trimethoprim-sulfamethoxazole resistance.
Assuntos
Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação , Colômbia , Humanos , América LatinaRESUMO
OBJECTIVE: To determine genetic relatedness of clone Colombia5 ST289 with invasive Streptococcus pneumoniae serotype 5 isolates recovered in nine Latin American countries. METHODS: Forty-four invasive S. pneumoniae serotype 5 isolates recovered from children under 5 years of age in Bolivia, Chile, Dominican Republic, Ecuador, Nicaragua, Panama, Paraguay, Peru, and Venezuela were studied. Pulsed-field gel electrophoresis patterns of DNA treated with SmaI restriction enzyme were classified using Tenover's criteria and analyzed with the Fingerprinting II program to determine their genetic relatedness with the Colombian clone. RESULTS: All isolates had a genetic similarity of 78.5 percent or more with the Colombian clone. Thirteen electrophoretic subtypes derived of pattern A were identified, and five of them (A5, A6, A8, A13, A27) comprised 61.4 percent of the isolates. CONCLUSIONS: Clone Colombia5 ST289 is disseminated in Latin America. This is important because S. pneumoniae serotype 5 frequently causes invasive disease in the region and is associated with trimethoprim-sulfamethoxazole resistance.
OBJETIVO: Determinar la relación genética del clon Colombia5 ST289 con los aislamientos invasores de Streptococcus pneumoniae serotipo 5 provenientes de nueve países latinoamericanos. MÉTODOS: Se estudiaron 45 aislamientos invasores de Streptococcus pneumoniae serotipo 5 procedentes de niños menores de 5 años de Bolivia, Chile, Ecuador, Nicaragua, Panamá, Paraguay, Perú, República Dominicana y Venezuela. Los patrones en electroforesis en gel de campo pulsante del ADN tratado con la enzima de restricción SmaI se clasificaron mediante el criterio de Tenover y se analizaron con el programa Fingerprinting II para determinar su relación genética con el clon colombiano. RESULTADOS: Todos los aislamientos tuvieron una similitud genética de 78,5 por ciento o mayor con el clon colombiano. Se identificaron 13 subtipos electroforéticos derivados del patrón A y cinco de ellos (A5, A6, A8, A13 y A27) constituyeron 61,4 por ciento de los aislamientos. CONCLUSIONES: El clon Colombia5 ST289 está diseminado por América Latina. Esto es importante ya que S. pneumoniae serotipo 5 es causa frecuente de enfermedades invasoras en la Región y está asociado con la resistencia a trimetoprim-sulfametoxazol.
Assuntos
Humanos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação , Colômbia , América LatinaRESUMO
Streptococcus pneumoniae es uno de los principales patógenos causantes de infecciones respiratorias e invasivas, por lo que es importante identificar rápidamente este microorganismo y determinar la susceptibilidad a los antibióticos frecuentemente utilizados, para la realización de terapias adecuadas. Con este fin se realizó la identificación de 32 aislamientos de Streptococcus pneumoniae, a partir de pacientes con infecciones respiratorias e invasivas; para su identificación se utilizaron métodos microbiológicos convencionales y como pruebas confirmatorias, métodos moleculares por reacción en cadena de la polimerasa (PCR), amplificando regiones de los genes lyt A y ply y métodos serológicos para la determinación del antígeno capsular. Se realizaron antibiogramas para determinar la susceptibilidad a Penicilina y Eritromicina. Los resultados revelaron, un mayor número de aislamientos en menores de 10 años y en mayores de 49 años y en relación a épocas estacionales, de aislamientos un mayor número durante los meses de invierno. En las pruebas de susceptibilidad a los antibióticos se encontró una sensibilidad disminuida a Penicilina (SDP) de 46.88 %; resistencia a eritromicina de 6.25 % y resistencia intermedia de 15,63%. Realizando un análisis estadístico de los tres métodos como pruebas de reconfirmación, se observó una correlación baja, por lo que la prueba de la optoquina con fines de reconfirmación para Streptococcus pneumoniae, es inferior a las pruebas serológica y molecular.
Streptococcus pneumoniae is one of the main pathogens that cause breathing and invasive infections, that is why is important a quick identification of this microorganism and determine the sensitivity of the frequently used antibiotics, to execute appropriate therapies. With this purpose the identification of 32 isolates of Streptococcus pneumoniae from patients with breathing and invasive infections were carried out, conventional microbiological tests were applied for identification and for confirmation were used molecular techniques based on the chain reaction of polymerase (PCR), amplifying the regions of lyt A and ply genes and serological methods for the determination of the capsular antigen. Antibiograms were carried out in order to determinate the sensitivity to penicillin and erythromycin. The results showed a higher amount of isolates in children under 10 and adults over 49, and according to seasons, more isolates on winter months. Regarding sensitivity to antibiotics, we found a drop of 46.88% to penicillin, a drop of 6.25 to erythromycin and an intermediate drop of 15.63%. The statistical analysis among the three techniques used for reconfirmation revealed there is a low correlation among them. Therefore, optochin, used as a re-confirmation method, is lower than serological and molecular tests.
Assuntos
Fagos de StreptococcusRESUMO
Este registro pretende ser una ayuda en el trabajo que desarrollan los laboratorios de bacteriología del país de manera que la información pueda ser almacenada más allá de contar probablemente con sistemas electrónicos-para luego ser aprovechada en todos aquellos aspectos que fueran pertinentes, por ejemplo en la análisis retrospectivo de lo hecho, en brindar información sistemátizada para fines de vigilancia epidemiológica, en la proyeccción del trabajo futuro, etc. En todo caso esta herramienta, por su carácter dinámico buscará su continua actualización y adaptación a las necesidades de la Red nacional de Bacteriología del país