RESUMEN
AIMS: Evaluate the participation of IL-17 pathway in T1D pathogenesis. T helper 17 cells are potent, highly inflammatory cells that produce interleukin 17A (IL-17A), considered a mediator of various immune disorders. However, their role in Type 1 diabetes (T1D) pathogenesis in humans is not totally elucidated. METHODS: The expression of IL-17 Receptor A (IL-17RA) in peripheral T lymphocytes and IL-17A serum levels in recent-onset patients with T1D were compared with healthy controls. IL-17A gene variants were evaluated in a greater cohort. RESULTS: Patients with recent-onset T1D (less than 6â¯months of diagnosis) exhibited lower expression of IL-17RA in CD3+ T (% of cellsâ¯=â¯31.3%â¯×â¯43.6%; pâ¯=â¯.041) and CD4+ T cells (11.1%â¯×â¯25.2%; pâ¯=â¯.0019) and lower number of IL-17RA in CD4+ T cells (MFIâ¯=â¯1.16â¯×â¯4.56; pâ¯=â¯.03) than controls. IL-17RA expression in CD8+ T cells and IL-17A serum levels were similar in both groups. The coding regions and boundary intron sequences of IL17A were sequenced. Seventeen allelic variants, including three novel variants in exon 3 (3'UTR n) were identified, but no one was associated with T1D susceptibility, as well as the resulting haplotypes and diplotypes. The expression of IL-17RA was not correlated with metabolic variables (glucose and HbA1c levels) or pancreatic autoantibodies titers. CONCLUSIONS: The lower expression of IL-17RA in CD3+â¯and CD4+ T cells suggests a reduced effect of IL-17A in immune response of recent-onset T1D patients, at least at peripheral tissues. IL-17A allelic variants were not related with T1D susceptibility.
Asunto(s)
Diabetes Mellitus Tipo 1/metabolismo , Interleucina-17/metabolismo , Células Th17/metabolismo , Adolescente , Alelos , Brasil , Linfocitos T CD4-Positivos/metabolismo , Niño , Preescolar , Femenino , Frecuencia de los Genes/genética , Humanos , Lactante , Interleucina-17/análisis , Interleucina-17/sangre , Masculino , Receptores de Interleucina-17/análisis , Receptores de Interleucina-17/sangre , Receptores de Interleucina-17/genética , Transducción de Señal/inmunología , Transducción de Señal/fisiologíaRESUMEN
The Human T-cell Leukemia Virus-1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a devastating neurodegenerative disease with no effective treatment, which affects an increasing number of people in Brazil. Immune cells from the adaptive compartment are involved in disease manifestation but whether innate cell functions participate in disease occurrence has not been evaluated. In this study, we analyzed innate cell responses at steady state and after blood cell stimulation using an agonist of the toll-like receptor (TLR)7/8-signaling pathway in blood samples from HTLV-1-infected volunteers, including asymptomatic carriers and HAM/TSP patients. We observed a lower response of IFNα+ DCs and monocytes in HAM/TSP compared to asymptomatic carriers, as a potential consequence of corticosteroid treatments. In contrast, a higher frequency of monocytes producing MIP-1α and pDC producing IL-12 was detected in HAM/TSP blood samples, together with higher IFNγ responsiveness of NK cells, suggesting an increased sensitivity to inflammatory response in HAM/TSP patients compared to asymptomatic carriers. This sustained inflammatory responsiveness could be linked or be at the origin of the neuroinflammatory status in HAM/TSP patients. Therefore, the mechanism underlying this dysregulations could shed light onto the origins of HAM/TSP disease.
Asunto(s)
Inmunidad Innata , Paraparesia Espástica Tropical/inmunología , Adulto , Brasil , Estudios de Cohortes , Células Dendríticas/inmunología , Femenino , Virus Linfotrópico T Tipo 1 Humano/genética , Virus Linfotrópico T Tipo 1 Humano/fisiología , Humanos , Interleucina-12/genética , Interleucina-12/inmunología , Células Asesinas Naturales/inmunología , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Paraparesia Espástica Tropical/virologíaRESUMEN
Allergens can be maternally transferred to the fetus or neonate, though it is uncertain how this initial allergen exposure may impact the development of allergy responses. To evaluate the roles of timing and level of maternal allergen exposure in the early life sensitization of progeny, female BALB/c mice were given ovalbumin (OVA) orally during pregnancy, lactation or weekly at each stage to investigate the immunoglobulin E (IgE) antibody production and cellular responsiveness of their offspring. Exposure to OVA during pregnancy was also evaluated in OVA-specific T-cell receptor (TCR) transgenic (DO11.10) mice. The effect of prenatal antigen exposure on offspring sensitization was dependent on antigen intake, with low-dose OVA inducing tolerance followed by neonatal immunization that was sustained even when pups were immunized when 3 weeks old. These offspring received high levels of transforming growth factor-beta via breastfeeding. High-dose exposure during the first week of pregnancy or perinatal period induced transient inhibition of IgE production following neonatal immunization; although for later immunization IgE production was enhanced in these offspring. Postnatal maternal antigen exposure provided OVA transference via breastfeeding, which consequently induced increased offspring susceptibility to IgE antibody production according to week post-birth. The effect of low-dose maternal exposure during pregnancy was further evaluated using OVA transgenic TCR dams as a model. These progeny presented pronounced entry of CD4(+) T cells into the S phase of the cell cycle with a skewed T helper type 2 response early in life, revealing the occurrence of allergen priming in utero. The balance between tolerance and sensitization depended on the amount and timing of maternal allergen intake during pregnancy.
Asunto(s)
Alérgenos/inmunología , Citocinas/inmunología , Hipersensibilidad/inmunología , Tolerancia Inmunológica , Exposición Materna , Intercambio Materno-Fetal/inmunología , Administración Oral , Animales , Linfocitos T CD4-Positivos/inmunología , Citocinas/biosíntesis , Femenino , Inmunoglobulina E/sangre , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Transgénicos , Ovalbúmina/inmunología , Embarazo , Receptores de Antígenos de Linfocitos T/metabolismo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Cathorops spixii is one of the most abundant venomous fish of the southeastern coast of the State of São Paulo, and consequently causes a great part of the accidents seen there. The accidents affect mainly fishermen, swimmers and tourists and are characterized by punctiform or wide wounds, erythema, edema, pain, sudoresis, indisposition, fever, nausea, vomiting and secondary infection. The objective of this work was to characterize the inflammatory response induced in mice by both venoms (mucus and sting) of the catfish C. spixii. Our results demonstrated that both venoms induced a great number of rolling and adherent leukocytes in the post-capillary venules of cremaster muscle of mice, and an increase in the vascular permeability in peritoneal cavity. Mucus induced the recruitment of neutrophils immediately after injection followed later by macrophage infiltration. In contrast, the cellular infiltration elicited by sting venom was rapidly resolved. The peritonitis reaction provoked by venoms was characterized by cytokine (IL-6), chemokines (MCP-1 and KC) or lipid mediator (LTB4) production in the peritoneal cavity. The macrophages from 7-day mucus venom-induced exudates upon in vitro mucus venom stimulation, expressed CD11c x MHC class II and release bioactive IL-12p70. On the other hand, sting venom-elicited peritoneal macrophages lost the ability to differentiate into dendritic cells, following re-stimulation in vitro with sting venom, they do not express CD11c, nor do they exhibit sufficient levels of MHC class II. In conclusion, both types of venoms (mucus or sting) promote inflammatory reaction with different profiles, and the inflammatory reaction induced by the first was characterized by antigen persistence in peritoneal cavity that allowed the activation of phagocytic cells with capacity of antigenic presentation.
Asunto(s)
Bagres , Venenos de los Peces/toxicidad , Inflamación/inducido químicamente , Animales , Biomarcadores/análisis , Permeabilidad Capilar/efectos de los fármacos , Venenos de los Peces/química , Venenos de los Peces/inmunología , Inmunidad Celular/efectos de los fármacos , Inflamación/inmunología , Masculino , Ratones , Cavidad Peritoneal/irrigación sanguínea , Cavidad Peritoneal/citología , Pruebas de ToxicidadRESUMEN
A study with transmission electron microscopy of mycoplasma-contaminated HeLa cells using five cell donors referred to as donors A, B, C, D and E, observations are herein presented. Experiments performed with cells from donors B, C and D, revealed the presence of Mycoplasma hyorhinis after PCR and sequencing experiments. Bacteria probably originated from a cytoplasm with compacted tiny granular particles replacing the normal cytosol territories, or from the contact with the cytoplasm through a clear semi-solid material. The compact granularity (CG) of the cytoplasm was crossed by stripes of smooth and rough endoplasmic reticulum cisternae. Among apparently normal mitochondria, it was noted, in variable proportions, mitochondria with crista-delimited lucent central regions that expand to and occupied the interior of a crista-less organelle, which can undergo fission. Other components of the scenarios of mycoplasma-induced cell demolition are villus-like structures with associated 80-200 nm vesicles and a clear, flexible semi-solid, process-sensitive substance that we named jam-like material. This material coated the cytoplasmic surface, its recesses, irregular protrusions and detached cytoplasmic fragments. It also cushioned forming bacteria. Cyst-like structures were often present in the cytoplasm. Cells, mainly apoptotic, exhibiting ample cytoplasmic sectors with characteristic net-like profile due to adjoined vacuoles, as well as ovoid or elongated profiles, consistently appeared in all cells from the last four cell donors. These cells were named "modified host cells" because bacteria arose in the vacuoles. The possibility that, in some samples, there was infection and/or coinfection of the host cell by another organism(s) cannot be ruled out.
Asunto(s)
Citosol/microbiología , Retículo Endoplásmico/microbiología , Células HeLa/microbiología , Mitocondrias/microbiología , Mycoplasma hyorhinis/aislamiento & purificación , Vacuolas/microbiología , Células Cultivadas , Citosol/patología , ADN Bacteriano , Retículo Endoplásmico/patología , Células HeLa/patología , Humanos , Microscopía Electrónica de Transmisión , Mitocondrias/patología , Reacción en Cadena de la Polimerasa , Estaurosporina/farmacología , Vacuolas/patologíaRESUMEN
Infants born to HIV-infected mothers are at high risk of becoming infected during gestation or the breastfeeding period. A search is thus warranted for vaccine formulations that will prevent mother-to-child HIV transmission. The LAMP/gag DNA chimeric vaccine encodes the HIV-1 p55gag fused to the lysosome-associated membrane protein-1 (LAMP-1) and has been shown to enhance anti-Gag antibody (Ab) and cellular immune responses in adult and neonatal mice; such a vaccine represents a new concept in antigen presentation. In this study, we evaluated the effect of LAMP/gag DNA immunization on neonates either before conception or during pregnancy. LAMP/gag immunization of BALB/c mice before conception by the intradermal route led to the transfer of anti-Gag IgG1 Ab through the placenta and via breastfeeding. Furthermore, there were an increased percentage of CD4+CD25+Foxp3+T cells in the spleens of neonates. When offspring were immunized with LAMP/gag DNA, the anti-Gag Ab response and the Gag-specific IFN-γ-secreting cells were decreased. Inhibition of anti-Gag Ab production and cellular responses were not observed six months after immunization, indicating that maternal immunization did not interfere with the long-lasting memory response in offspring. Injection of purified IgG in conjunction with LAMP/gag DNA immunization decreased humoral and cytotoxic T-cell responses. LAMP/gag DNA immunization by intradermal injection prior to conception promoted the transfer of Ab, leading to a diminished response to Gag without interfering with the development of anti-Gag T- and B-cell memory. Finally, we assessed responses after one intravenous injection of LAMP/gag DNA during the last five days of pregnancy. The intravenous injection led to in utero immunization. In conclusion, DNA vaccine enconding LAMP-1 with Gag and other HIV-1 antigens should be considered in the development of a protective vaccine for the maternal/fetal and newborn periods.
Asunto(s)
Animales Recién Nacidos/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Inmunidad Celular/fisiología , Proteínas de Membrana de los Lisosomas/genética , Precursores de Proteínas/genética , Útero/inmunología , Vacunas de ADN/administración & dosificación , Líquido Amniótico/química , Animales , Anticuerpos Antivirales/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Feto/inmunología , Infecciones por VIH/genética , Infecciones por VIH/virología , Inmunización , Inmunofenotipificación , Ratones , Leche Humana/química , Embarazo , Complicaciones Infecciosas del Embarazo , Bazo/inmunología , Bazo/metabolismo , Útero/virologíaRESUMEN
BACKGROUND: Among the various occupations which necessarily require long-term and chronic sun exposure is that of a fisherman. However, clinical experience in dermatology earned over several years of medical practice does not seem to confirm this hypothesis. OBJECTIVE: To evaluate clinical, histological and immunological effects of long-term and chronic exposure to ultraviolet radiation in fishermen. METHODS: A prospective, cross-sectional and observational study characterized skin lesions, immunological markers and histological alterations in fishermen, as well as lymphocyte subpopulations compared to a control group. Mann-Whitney, Fisher's and Wilcoxon statistical tests were used at a significance level of 0.05. RESULTS: There were significant differences between the exposed group and the group protected due to elastosis (p = 0.03), ectasia of dermal vessels (p = 0.012) and number of cells in the epidermal layers between cones (p = 0.029). Most common among fishermen were CD45RO, CD68 + and mastocytes in the skin (p = 0.040, p <0.001, p = 0.001) and CD3CD8CD45RO in the blood (p = 0.016). CONCLUSION: The alterations suggest that long-term and chronic sun exposure promotes tolerance to ultraviolet radiation, which protects against immunosuppression.
Asunto(s)
Exposición a Riesgos Ambientales/efectos adversos , Explotaciones Pesqueras , Conocimientos, Actitudes y Práctica en Salud , Piel/efectos de la radiación , Luz Solar/efectos adversos , Rayos Ultravioleta/efectos adversos , Adulto , Brasil , Estudios de Casos y Controles , Estudios Transversales , Humanos , Linfocitos/citología , Linfocitos/efectos de la radiación , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/inmunología , Estudios Prospectivos , Tolerancia a Radiación/inmunología , Tolerancia a Radiación/efectos de la radiación , Piel/inmunologíaRESUMEN
Considerable efforts are currently focused on the biology of DC in view of their possible clinical use as adjuvant for the generation of antigen-specific immunity and lifelong immunologic memory or for the treatment of tumors. We assessed the role of Nattectin a C-type lectin identified in the Thalassophryne nattereri fish venom in DC maturation. Nattectin induced a significant neutrophilic recruitment into peritoneal cavity of mice, followed by macrophages, with lipidic mediators and IL-12 p70 synthesis. Macrophages derived from 7day-Nattectin mice were CD11c+CD11b(low)Ly6(high)F4/80R(high) and express high levels of MHC class II and CD80 molecules. Culture of peritoneal exudates derived macrophages from 7day Nattectin-mice and immature BMDCs with Nattectin markedly increased the surface expression of CD40, CD80, CD86, and MHC class II in a dose-dependent manner, and the production of MMP-2 and MMP-9 distributed in nucleus and cytoplasm of cells, that was associated with strong activity in the culture supernatant. Nattectin treated DCs secreted IL-12 p70 and IL-10. The Nattectin-treated BMDC or macrophage-derived DCs were highly efficient at Ag capture. The specific immune response elicited by Nattectin was characterized by the production of specific antibodies IgG1 and mainly IgG2a with IL-10 and IFN-γ synthesis by splenic cells. These results enable us to address that Nattectin induces the recruitment of Ly6C(high) monocytes into the peritoneum, which exhibit a pro-inflammatory profile, where they differentiate into proliferating F4/80R(high) macrophages. Macrophage-derived DCs mature in the presence of the cytokine milieu generated against Nattectin, exhibiting T cell co-stimulatory molecule expression and induced a Th1 polarized response.
Asunto(s)
Batrachoidiformes , Citocinas/metabolismo , Células Dendríticas/efectos de los fármacos , Lectinas Tipo C/administración & dosificación , Macrófagos/efectos de los fármacos , Animales , Presentación de Antígeno/efectos de los fármacos , Antígenos de Diferenciación/metabolismo , Batrachoidiformes/inmunología , Transdiferenciación Celular/efectos de los fármacos , Células Cultivadas , Microambiente Celular/efectos de los fármacos , Microambiente Celular/inmunología , Citocinas/genética , Citocinas/inmunología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Células Dendríticas/patología , Proteínas de Peces/administración & dosificación , Inmunidad Celular/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Células TH1/inmunología , Balance Th1 - Th2/efectos de los fármacosAsunto(s)
Retículo Endoplásmico/ultraestructura , Aparato de Golgi/microbiología , Mycoplasma/fisiología , Membrana Celular/microbiología , Membrana Celular/ultraestructura , Retículo Endoplásmico/microbiología , Aparato de Golgi/ultraestructura , Células HeLa/microbiología , Células HeLa/ultraestructura , Interacciones Huésped-Parásitos/fisiología , Humanos , Microscopía Electrónica de Transmisión , Mycoplasma/ultraestructuraRESUMEN
BACKGROUND: Some studies have suggested reduced activity of clopidogrel on platelet activation and adherence in patients using statins. OBJECTIVE: To assess whether platelet activation and aggregation decrease with clopidogrel, and whether there is a reduction of the action of clopidogrel when associated with atorvastatin or simvastatin. METHODS: This prospective study included 68 patients with stable angina with previous use of simvastatin, atorvastatin, or no statin (control group), with previous elective indication of percutaneous coronary intervention (PCI). Platelet activation was analyzed by means of platelet count, levels of P-selectin and glycoprotein IIb/IIIa (with and without ADP stimulation) by flow cytometry. The findings were analyzed before and after percutaneous coronary intervention and the administration of clopidogrel. RESULTS: We observed reduction in platelet activity with use of clopidogrel. Furthermore, no differences were found between the variables analyzed to prove reduced activity of clopidogrel when combined with statins. We observed levels of p-selectin (pre-angioplasty: 14.23 ± 7.52 x 8.83 x 11.45 ± 7.65 ± 7.09; after angioplasty: 21.49 ± 23.82 x 4 37 ± 2.71 x 4.82 ± 4.47, ρ < 0.01) and glycoprotein IIb/IIIa (pre-angioplasty: 98.97 ± 0.43 ± 1.25 x 98.79 x 99.21 ± 0.40 after angioplasty: 99.37 ± 0.29 ± 1.47 x 98.50 x 98.92 ± 0.88, ρ = 0.52), respectively, in the control, atorvastatin and simvastatin groups. CONCLUSION: We concluded that platelet activation decreases with administration of clopidogrel, and clopidogrel has no antiplatelet effect reduced in the presence of simvastatin or atorvastatin.
Asunto(s)
Angioplastia Coronaria con Balón , Ácidos Heptanoicos/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Agregación Plaquetaria/efectos de los fármacos , Pirroles/farmacología , Simvastatina/farmacología , Ticlopidina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Atorvastatina , Clopidogrel , Interacciones Farmacológicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/metabolismo , Inhibidores de Agregación Plaquetaria/farmacología , Estudios Prospectivos , Ticlopidina/farmacologíaRESUMEN
FUNDAMENTOS: Existe um consenso de que a exposição à radiação ultravioleta determina alterações n o sistema imunológico da pele, o que permite que se avente a hipótese de que a exposição prolongada e crônica ao Sol pode representar uma das maiores agressões ambientais à saúde humana. Entre as várias ocupações que requerem, necessariamente, exposição prolongada e crônica ao Sol está a de pescador. No entanto, a experiência clínica dermatológica, amealhada ao longo de vários anos de exercício da Medicina, não parece confirmar essa hipótese. OBJETIVO: Avaliar efeitos clínicos, histológicos e imunológicos da exposição crônica e prolongada à radiação ultravioleta em pescadores. MÉTODOS: Em estudo prospectivo, transversal, observacional, foram caracterizadas lesões dermatológicas, marcadores imunológicos e alterações histológicas de pescadores e subpopulações de linfócitos comparadas a grupo-controle. Empregaram-se testes de Mann-Whitney, exato de Fisher, Wilcoxon em nível de 0,05. RESULTADOS: Houve diferenças entre os grupos exposto e protegido em elastose (p = 0,03), ectasia de vasos dérmicos (p = 0,012) e número de células nas camadas epidérmicas entre os cones (p = 0,029). Foram mais comuns em pescadores CD45RO, CD68+ e mastócitos na pele (p = 0,040, p < 0,001 e p = 0,001); CD3CD8CD45RO no sangue (p = 0,016). CONCLUSÃO: As alterações sugerem que exposição crônica e prolongada ao sol promove tolerância à radiação ultravioleta, protetora da imunossupressão.
BACKGROUND: Among the various occupations which necessarily require long-term and chronic sun exposure is that of a fisherman. However, clinical experience in dermatology earned over several years of medical practice does not seem to confirm this hypothesis. OBJECTIVE: To evaluate clinical, histological and immunological effects of long-term and chronic exposure to ultraviolet radiation in fishermen. METHODS: A prospective, cross-sectional and observational study characterized skin lesions, immunological markers and histological alterations in fishermen, as well as lymphocyte subpopulations compared to a control group. Mann-Whitney, Fisher's and Wilcoxon statistical tests were used at a significance level of 0.05. RESULTS: There were significant differences between the exposed group and the group protected due to elastosis (p = 0.03), ectasia of dermal vessels (p = 0.012) and number of cells in the epidermal layers between cones (p = 0.029). Most common among fishermen were CD45RO, CD68 + and mastocytes in the skin (p = 0.040, p <0.001, p = 0.001) and CD3CD8CD45RO in the blood (p = 0.016). CONCLUSION: The alterations suggest that long-term and chronic sun exposure promotes tolerance to ultraviolet radiation, which protects against immunosuppression.
Asunto(s)
Adulto , Humanos , Masculino , Persona de Mediana Edad , Exposición a Riesgos Ambientales/efectos adversos , Explotaciones Pesqueras , Conocimientos, Actitudes y Práctica en Salud , Piel/efectos de la radiación , Luz Solar/efectos adversos , Rayos Ultravioleta/efectos adversos , Brasil , Estudios de Casos y Controles , Estudios Transversales , Linfocitos/citología , Linfocitos/efectos de la radiación , Enfermedades Profesionales/inmunología , Estudios Prospectivos , Tolerancia a Radiación/inmunología , Tolerancia a Radiación/efectos de la radiación , Piel/inmunologíaAsunto(s)
Humanos , Retículo Endoplásmico/ultraestructura , Aparato de Golgi/microbiología , Mycoplasma/fisiología , Membrana Celular/microbiología , Membrana Celular/ultraestructura , Retículo Endoplásmico/microbiología , Aparato de Golgi/ultraestructura , Células HeLa/microbiología , Células HeLa/ultraestructura , Interacciones Huésped-Parásitos/fisiología , Microscopía Electrónica de Transmisión , Mycoplasma/ultraestructuraRESUMEN
FUNDAMENTO: Alguns estudos têm sugerido redução da atividade do clopidogrel sobre a ativação e adesão plaquetárias em pacientes em uso de estatinas. OBJETIVO: Avaliar se a ativação e agregação plaquetárias diminuem com clopidogrel, e se ocorre redução da ação do clopidogrel quando associado à atorvastatina ou à sinvastatina. MÉTODOS: Estudo prospectivo que incluiu 68 pacientes com angina estável em uso prévio de sinvastatina, atorvastatina, ou nenhuma estatina (grupo controle), com indicação prévia eletiva de realização de intervenção coronária percutânea. Foi analisada a ativação plaquetária através do número de plaquetas, níveis de P-selectina e glucoproteína IIb/IIIa (com e sem estímulo de ADP) através de citometria de fluxo. Os resultados foram analisados antes e após a intervenção coronária percutânea e da administração de clopidogrel. RESULTADOS: Observamos redução da atividade plaquetária com uso de clopidogrel. Além disso, não houve diferenças entre as variáveis analisadas que comprovassem redução da atividade do clopidogrel quando associado à estatinas. Observou-se níveis de p-selectina (pré-angioplastia: 14,23±7,52 x 11,45±8,83 x 7,65±7,09; pós angioplastia: 21,49±23,82 x 4,37±2,71 x 4,82±4,47, ρ<0,01) e glicoproteína IIb/IIIa (pré-angioplastia: 98,97±0,43 x 98,79±1,25 x 99,21±0,40; pós angioplastia: 99,37±0,29 x 98,50±1,47 x 98,92±0,88, ρ=0,52), respectivamente nos grupos controle, atorvastatina e sinvastatina. CONCLUSÃO: Concluímos que a ativação plaquetária diminui com a administração de clopidogrel, e que o clopidogrel não tem seu efeito antiplaquetário reduzido na presença de sinvastatina ou atorvastatina.
BACKGROUND: Some studies have suggested reduced activity of clopidogrel on platelet activation and adherence in patients using statins. OBJECTIVE: To assess whether platelet activation and aggregation decrease with clopidogrel, and whether there is a reduction of the action of clopidogrel when associated with atorvastatin or simvastatin. METHODS: This prospective study included 68 patients with stable angina with previous use of simvastatin, atorvastatin, or no statin (control group), with previous elective indication of percutaneous coronary intervention (PCI). Platelet activation was analyzed by means of platelet count, levels of P-selectin and glycoprotein IIb/IIIa (with and without ADP stimulation) by flow cytometry. The findings were analyzed before and after percutaneous coronary intervention and the administration of clopidogrel. RESULTS: We observed reduction in platelet activity with use of clopidogrel. Furthermore, no differences were found between the variables analyzed to prove reduced activity of clopidogrel when combined with statins. We observed levels of p-selectin (pre-angioplasty: 14.23 ± 7.52 x 8.83 x 11.45 ± 7.65 ± 7.09; after angioplasty: 21.49 ± 23.82 x 4 37 ± 2.71 x 4.82 ± 4.47, ρ < 0.01) and glycoprotein IIb/IIIa (pre-angioplasty: 98.97 ± 0.43 ± 1.25 x 98.79 x 99.21 ± 0.40 after angioplasty: 99.37 ± 0.29 ± 1.47 x 98.50 x 98.92 ± 0.88, ρ = 0.52), respectively, in the control, atorvastatin and simvastatin groups. CONCLUSION: We concluded that platelet activation decreases with administration of clopidogrel, and clopidogrel has no antiplatelet effect reduced in the presence of simvastatin or atorvastatin.
FUNDAMENTO: Algunos estudios han sugerido reducción de la actividad del clopidogrel sobre la activación y adhesión plaquetarias en pacientes en uso de estatinas. OBJETIVO: Evaluar si la activación y agregación plaquetarias disminuyen con clopidogrel, y si ocurre reducción de la acción del clopidogrel cuando está asociado a la atorvastatina o a la sinvastatina. MÉTODOS: Estudio prospectivo que incluyó 68 pacientes con angina estable en uso previo de sinvastatina, atorvastatina, o ninguna estatina (grupo control), con indicación previa electiva de realización de intervención coronaria percutánea. Fue analizada la activación plaquetaria a través del número de plaquetas, niveles de P-selectina y glucoproteína IIb/IIIa (con y sin estímulo de ADP) a través de citometría de flujo. Los resultados fueron analizados antes y después de la intervención coronaria percutánea y de la administración de clopidogrel. RESULTADOS: Observamos reducción de la actividad plaquetaria con uso de clopidogrel. Además de eso, no hubo diferencias entre las variables analizadas que comprobasen reducción de la actividad del clopidogrel cuando está asociado a las estatinas. Se observaron niveles de p-selectina (pre-angioplastia: 14,23±7,52 x 11,45±8,83 x 7,65±7,09; post angioplastia: 21,49±23,82 x 4,37±2,71 x 4,82±4,47, ρ<0,01) y glicoproteína IIb/IIIa (pre-angioplastia: 98,97±0,43 x 98,79±1,25 x 99,21±0,40; post angioplastia: 99,37±0,29 x 98,50±1,47 x 98,92±0,88, ρ=0,52), respectivamente en los grupos control, atorvastatina y sinvastatina. CONCLUSIÓN: Concluimos que la activación plaquetaria disminuye con la administración de clopidogrel, y que el clopidogrel no tiene su efecto antiplaquetario reducido en la presencia de sinvastatina o atorvastatina.
Asunto(s)
Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Angioplastia Coronaria con Balón , Ácidos Heptanoicos/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Agregación Plaquetaria/efectos de los fármacos , Pirroles/farmacología , Simvastatina/farmacología , Ticlopidina/análogos & derivados , Interacciones Farmacológicas , Estudios Prospectivos , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/metabolismo , Inhibidores de Agregación Plaquetaria/farmacología , Ticlopidina/farmacologíaRESUMEN
Kabuki syndrome is a genetic disorder of unknown etiology associated with characteristic features (long palpebral fissures, everted lower lids, and arched eyebrows), mental retardation, congenital malformations and increased susceptibility to infections, cancer and autoimmune diseases. However, few studies concerning the immunological aspects of the disease have been performed, and no clear cause of immunodeficiency has been established. Methods: Basic immunological evaluation of nine Brazilian children and adolescents with Kabuki syndrome was performed. Results: Clinical findings include recurrent respiratory infections (mainly otitis media and pneumonia) in 8 patients and allergic respiratory and/ or cutaneous diseases in 5 children. Laboratory findings include selective IgA deficiency, mildly decreased total IgG levels, decreased IgG2 and lack of an adequate response to delayed skin hypersensitivity testing. All of the patients seroconverted after vaccination with heptavalent conjugate pneumococcal vaccine. In two children, clinical and cytogenetic diagnosis of Turner syndrome was also established, while one of them also presented selective IgA deficiency. Conclusion: Due to these findings, we believe that further research is needed for a better understanding of the underlying causes of immunodeficiency in Kabuki syndrome...
A síndrome de Kabuki é uma condição genética de etiologia desconhecida caracterizada por retardo mental, baixa estatura, malformações congênitas, fáscies característico (fissuras palpebrais longas, eversão das pálpebras inferiores e supercílios arqueados) e uma susceptibilidade aumentada a infecções, doenças autoimunes e neoplasias. No entanto, há poucos estudos disponíveis sobre os aspectos imunológicos desta síndrome e até o momento não se estabeleceu causa para essa imunodeficiência. Método: Foi realizada uma avaliação imunológica básica de nove crianças e adolescentes brasileiros com síndrome de Kabuki. Resultados: Os achados clínicos incluíram infecções respiratórias recorrentes (principalmente otite média e pneumonia) em 8 dos pacientes e atopia (dermatite, rinite ou asma) em 5 crianças. Dentre os achados laboratoriais, pode-se citar deficiência seletiva de IgA, níveis reduzidos de IgG, redução de IgG2 e ausência de resposta aos testes cutâneos de hipersensibilidade tardia. Todos os pacientes soroconverteram após imunização com vacina pneumocócica conjugada heptavalente. Dois dos pacientes tiveram ainda o diagnóstico clínico e citogenético de síndrome de Turner, sendo que um deles também apresentava deficiência seletiva de IgA. Conclusão: Devido a estes achados, acreditamos que mais estudos devem ser realizados para que se tenha uma melhor compreensão das causas de imunodeficiência na síndrome de Kabuki...
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Anticuerpos , Hipersensibilidad/inmunología , Síndromes de Inmunodeficiencia , Factores Inmunológicos , Inmunocompetencia/genética , Inmunoglobulinas/deficiencia , Adolescente , NiñoRESUMEN
Objetivos: Caracterizar a Síndrome de Deficiência de Anticorpos anti Polissacarídeos com Níveis Séricos Normais de Imunoglobulinas (SAD) pelo estudo da resposta imunológica sob os seguintes aspectos: estudo das sub-populações. de linfócitos B e células T duplo negativas no sangue periférico e a capacidade linfoproliferativa frente a antígeno (toxóide tetânico) e mitógeno (PHA) em pacientes com SAD Casuística fi Métodos: Foram avaliados 13 pacientes maiores de quatro anos de idade que tiveram os seguintes critérios: a) níveis séricos normais de imunoglobulinas e subclasses de IgG para a idade b) níveis normais pós-vacinais de antic9rpos específicos para antígenosprotéicos c) níveis de anticorpos anti-pneumococo inferiores aos da normalidade para a idade e para cada sorotipo em estudo Foram incluídos como controles adultos saudáveis (n= 18) e um grupo de pacientes com Imunodeficiência Comum Variável (ICY). Resultados: Exceto em um paciente, os ensaios linfoproliferativos foram normais quando comparados aos controles. Os linfócitos B CD 19+ foram semelhantes ao grupo controle com exceção de um paciente. A porcentagem de células CD 19+CDS+ foi normal de acordo aos' valores obtidos do grupo controle. A porcentagem de linfócitos CD 19+CD21 +, exceto em uma paciente de seis anos de idade, foi semelhante ao grupo controle