RESUMEN
The present work aimed to evaluate the immunogenicity of Leishmania amazonensis iron superoxide dismutase (SOD)-encoding DNA experimental vaccine and the protective properties of this DNA vaccine during infection. The SOD gene was subcloned into the pVAX1 plasmid, and it was used to immunize BALB/c mice. Twenty-one days after the last immunization, mice were sacrificed (immunogenicity studies) or subcutaneously challenged with L. amazonensis (studies of protection), and alterations in cellular and humoral immune responses were evaluated, as well as the course of infection. Mice only immunized with pVAX1-SOD presented increased frequencies of CD4(+) IFN-γ(+), CD8(+)IFN-γ(+) and CD8(+)IL-4(+) lymphocytes; moreover, high levels of IgG2a were detected. After challenge, mice that were immunized with pVAX1-SOD had increased frequencies of the CD4(+)IL-4(+), CD8(+)IFN-γ(+) and CD8(+)IL-4(+) T lymphocytes. In addition, the lymph node cells produced high amounts of IFN-γ and IL-4 cytokines. Increased IgG2a was also detected. The pattern of immunity induced by pVAX1-SOD partially protected the BALB/c mice from a challenge with L. amazonensis, as the animals presented reduced parasitism and lesion size when compared to controls. Taken together, these results indicate that leishmanial SOD modulates the lymphocyte response, and that the elevation in IFN-γ possibly accounted for the decreased skin parasitism observed in immunized animals.
Asunto(s)
Leishmania mexicana/inmunología , Vacunas contra la Leishmaniasis/inmunología , Leishmaniasis/inmunología , Vacunas de ADN/inmunología , Animales , Citocinas/inmunología , Inmunización , Inmunoglobulina G/inmunología , Interferón gamma/inmunología , Interleucina-4/inmunología , Leishmaniasis/prevención & control , Masculino , Ratones , Ratones Endogámicos BALB C , Superóxido Dismutasa/genética , Subgrupos de Linfocitos T/inmunologíaRESUMEN
The host immune response, including innate and adaptive immunity, plays a critical role in determining the outcome of viral infection. Nevertheless, little is known about the exact reasons for the failure of the host immune system in controlling hepatitis C virus (HCV) infection. Impairment of dendritic cells (DCs) function is probably one of the mechanisms responsible for immune evasion of HCV. In this study, the frequency and phenotype of DCs subsets were analyzed in three groups: HCV-infected individuals who developed viral persistence (1), HCV-infected individuals who spontaneously cleared the virus (2) and HCV-seronegative uninfected subjects (3). The results showed that the frequency of DCs subsets was not statistically significant between groups. Plasmacytoid DCs circulating exhibited an immature phenotype characterized by low expression of CD86. On the other hand, CD86 expression in myeloid DCs was significantly higher in chronic infected individuals compared to healthy controls (P=0.037). A positive correlation was observed between CD86(+) myeloid DC (mDC) and HCV viral load (r=0.4121, P=0.0263). These results suggest that HCV did not have an inhibitory effect on mDC maturation and the HCV viremia drives the increase of CD86 expression in mDC. The regulation of DCs maturation and migration lies at the level of intracellular signaling. HCV can activate or block intracellular signaling pathways and alter DC function. In conclusion, the present study suggests that imbalance of DC maturation by the virus represents a mechanism of evasion of the immune system despite the fact that HCV viremia appears to exert a "stimulatory" effect on cell-surface immune phenotype.
Asunto(s)
Antígeno B7-2/biosíntesis , Células Dendríticas/inmunología , Hepacivirus/inmunología , Hepatitis C/inmunología , Viremia/inmunología , Adulto , Femenino , Voluntarios Sanos , Hepatitis C/virología , Humanos , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Carga ViralRESUMEN
Endometriosis is a chronic benign disease that affects women of reproductive age causing abdominal pain and infertility. Its pathogenesis remains obscure despite all the research conducted over the past 100 years. However, there is a consensus among the specialists that the basis of its pathophysiology would be multifactorial. Many publications have demonstrated that chemokines are somehow associated with the development of endometriosis and infertility. In this study, we reviewed all PubMed literature using MeSH terms "chemokines" and "endometriosis" as well as "chemokines" and "female infertility" to establish what we know and what we do not yet know about this relationship.
Asunto(s)
Quimiocinas/inmunología , Endometriosis/inmunología , Infertilidad Femenina/inmunología , Animales , Femenino , HumanosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The stem barks of Zanthoxylum rhoifolium Lam. (Rutaceae), locally known as "mamica de cadela", are popularly used in dyspepsies, stomachic, tonic, antitumoral, antipyretic and are used in treating flatulence and colic. The objective of this study was to evaluate the gastroprotective effect of the ethanolic extract of Zanthoxylum rhoifolium (EEZR) stem barks in acute gastric lesion models, investigating their possible mechanisms. MATERIALS AND METHODS: Mice were used for the evaluation of the acute toxicity, and mice and rats to study the gastroprotective activity. The gastroprotective action of EEZR was analyzed in the absolute ethanol, HCl/ethanol and indomethacin-induced gastric lesion models in mice, hypothermic-restraint stress, and ischemia/reperfusion in rats. In the investigation of the gastroprotective mechanisms of EEZR, the participation of the NO-synthase pathway, ATP-sensitive potassium channels (K(ATP)), the levels of the non-protein sulfhydril groups (NP-SH) and the catalase activity using the ethanol-induced gastric mucosa lesion model and the quantification of the gastric mucus and the antisecretory activity through pylorus ligature model in rats were analyzed. RESULTS: The animals did not present any signs of acute toxicity for the EEZR (up to the 4 g/kg dose, po), and it was not possible to calculate the DL(50). EEZR (125-500 mg/kg) exhibited a significant gastroprotective effect in absolute ethanol, HCl/ethanol, hypothermic-restraint stress, and ischemia/reperfusion-induced gastric lesion models. EEZR (250 and 500 mg/kg) exhibited still a gastroprotective activity in the indomethacin-induced ulcer model. Gastroprotection of EEZR was significantly decreased in pre-treated mice with l-NAME or glibenclamide, the respective nitric oxide synthase and K(ATP) channels inhibitors. Our studies revealed that EEZR (500 mg/kg) prevented the decrease of the non-protein sulfhydril groups (NP-SH) and increased the catalase levels in ethanol-treated animals. Furthermore, the extract (500 mg/kg) significantly increased the mucus production, however, the gastric secretion parameters (volume, [H(+)], pH) did not show any alteration. CONCLUSIONS: Our results indicate that the ethanolic extract of Zanthoxylum rhoifolium exhibits a significant gastroprotection, because it inhibits the formation of gastric lesions using different models. The release of the nitric oxide, the opening of the K(ATP) channels, the participation of the non-protein sulfhydril groups (NP-SH), catalase and the increase of mucous secretion seem to be involved in the gastroprotection activity of the EEZR. Nevertheless, this activity does not seem to be related to antisecretory mechanisms.
Asunto(s)
Antiulcerosos/farmacología , Mucosa Gástrica/efectos de los fármacos , Extractos Vegetales/farmacología , Daño por Reperfusión/prevención & control , Úlcera Gástrica/prevención & control , Zanthoxylum , Animales , Antiulcerosos/química , Antiulcerosos/aislamiento & purificación , Antiulcerosos/toxicidad , Catalasa/metabolismo , Citoprotección , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Etanol , Femenino , Jugo Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Ácido Clorhídrico , Concentración de Iones de Hidrógeno , Indometacina , Canales KATP/antagonistas & inhibidores , Canales KATP/metabolismo , Masculino , Ratones , Moco/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Corteza de la Planta , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Bloqueadores de los Canales de Potasio/farmacología , Ratas , Ratas Wistar , Daño por Reperfusión/etiología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Úlcera Gástrica/etiología , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Estrés Fisiológico , Zanthoxylum/químicaRESUMEN
The frequencies of human platelet-specific alloantigens (HPAs) vary between different ethnic groups, and genotyping using DNA techniques has been preferred over immunophenotyping methods for population studies. Using a polymerase chain reaction with allele-specific primers (PCR-ASP) method, we determined the allelic polymorphisms of five HPA systems among 174 unrelated individuals of two different Brazilian ethnic groups including Amazon Indians (n = 95) and blood donors (n = 79). Comparison of the calculated gene frequencies of the two alleles of HPA-1, -2, -3, -4 and -5 systems for Amazon Indians and Brazilian blood donors showed that gene frequencies obtained for the two alleles of HPA-1 (P<0.001), HPA-2 (P = 0.001) and HPA-5 (P<0.001) were significantly different between the two groups of individuals. All natives tested carried the HPA-2a and the HPA-5a alleles, but the HPA-1b and HPA-4b alleles are absent from the Indian population. It was also observed that all blood donors carried the HPA-1a, HPA-4a and HPA-5a alleles. In conclusion, the present data indicate differences in the frequency of the HPA systems between Amazon Indians and Brazilian subjects who present a high rate of racial admixture. While the frequencies of the HPA-1 and HPA-5 genes seen in Amazon Indians are similar to those reported for Oriental populations, the frequencies of the HPAs alleles in Brazilian blood donors are comparable to those reported for populations in North America and Europe.
Asunto(s)
Antígenos de Plaqueta Humana/genética , Donantes de Sangre , Alelos , Antígenos de Plaqueta Humana/sangre , Brasil/epidemiología , Etnicidad/genética , Frecuencia de los Genes , Genotipo , Humanos , Indígenas Sudamericanos/genética , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo GenéticoRESUMEN
BACKGROUND: The immunomodulatory effects of allogeneic blood transfusions have been attributed to the white cells (WBCs) present in the cellular blood components transfused to patients. STUDY DESIGN AND METHODS: The effect of the transfusion of allogeneic red cells (RBCs) or allogeneic prestorage WBC-reduced RBCs (WBC-reduced RBCs) on host immune responsiveness was evaluated by measuring the lymphocyte subsets and the in-vitro cytokine production in response to phytohemagglutinin stimulation of WBCs of orthopedic surgery patients. Forty-seven patients undergoing hip replacement surgery were randomly assigned to receive allogeneic RBCs (n = 17) or WBC-reduced RBCs (n = 14; 99.95% WBC removal). Sixteen patients were not transfused. Patient blood samples taken before surgery and on Days 1 and 4 after surgery were tested for complete blood count, lymphocyte subset analysis, and measurement of cytokine levels. RESULTS: After surgery, the lymphocyte count was significantly decreased in patients transfused with > or = 3 units of allogeneic RBCs (2.0 +/- 0.5 vs. 1.3 +/- 0.3 x 10(9)/L; p = 0.017), but not in patients transfused with > or = 3 units of WBC-reduced RBCs (2.0 +/- 0.9 vs. 1.7 +/- 0.8 x 10(9)/L). Compared with preoperative levels, on Day 4 after surgery, patients transfused with > or = 3 units of allogeneic RBCs also had a decrease in the number of natural killer cells (0.07 +/- 0.05 vs. 0.04 +/- 0.03 x 10(9)/L; p = 0.018). Postoperatively, interleukin-2 was decreased in one patient who received WBC-reduced RBCs compared with that in four patients transfused with allogeneic RBCs (p = 0.32), and eight untransfused patients (p = 0.01). On Day 4, about 70 percent of patients transfused with allogeneic RBCs showed a 20-percent decrease in the interferon gamma level. CONCLUSION: Taken together, these data support the hypothesis that transfusion of > or = 3 units of allogeneic RBCs is associated with early postoperative lymphopenia in otherwise healthy individuals undergoing surgery. These findings were not observed in those individuals transfused with RBCs that had undergone prestorage WBC reduction.