RESUMO
Arterial stiffness is an index of vascular health; normal pregnancy is associated with reduced arterial stiffness. This cross sectional study compared arterial stiffness in older (≥35 years) and the younger (≤34 years) age groups of pregnant women. Arterial stiffness was assessed noninvasively in 66 pregnant women between 23 - 32 weeks gestation (41 women ≤ 34 years, 25 women ≥ 35 years) using the parameters pulse wave analysis and pulse wave velocity. Blood pressure (BP), body mass index (BMI), serum total cholesterol (TC) and fasting blood glucose (FBS) were also recorded. Mean ages of the younger and older age groups were 27.6±0.62 and 39.3±0.58 years; no significant difference was seen between the groups in their BMI, TC, FBS, SBP, DBP and gestational age. The older age group of women have increased arterial stiffness (augmentation index 19.4±1.9% vs 13.2±1.6%, p=0.015) and aortic stiffness (pulse wave velocity 8.7±0.3 vs 7.7±0.2 m/s, p=0.004) compared to the younger women. Linear regression analysis showed a positive significant correlation between age and augmentation index (R=0.278, p=0.026), and pulse wave velocity (R=0.350, p=0.004). We conclude that older pregnant women has increased arterial stiffness compared to a younger age group of pregnant women suggesting that vascular changes due to ageing occurs in pregnancy despite cardiovascular adaptations occurring in pregnancy.
Assuntos
Análise de Onda de Pulso , Rigidez Vascular , Pressão Sanguínea , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , GravidezRESUMO
OBJECTIVES: Myxovirus resistance protein A (MxA) can be used as a marker of the bioactivity of interferon-beta (IFN-beta) therapy. Two to forty per cent of IFN-beta-treated multiple sclerosis (MS) patients develop IFN-beta-neutralizing antibodies (NAb) with subsequent attenuation of MxA protein induction. The aim of this study was to set up a simple MxA enzyme immunoassay (EIA) for the measurement of MxA protein and to evaluate the EIA test by comparing the results with flow cytometric analysis and the measurement of NAb. METHODS: total of 51 IFN-beta-treated relapsing-remitting MS (RRMS) patients were tested for MxA protein expression by using both MxA EIA assay and flow cytometric analysis. Thirteen patients were confirmed to be NAb-positive. RESULTS: The correlation between EIA and flow cytometric analysis was significant with a wider range of measured levels in the EIA. Patients with NAb had low MxA levels, but in some patients, remaining MxA induction could be detected despite NAb. CONCLUSIONS: The MxA EIA assay seems to be a practical method for large-scale analysis of the bioactivity of IFN-beta treatment.
Assuntos
Adjuvantes Imunológicos/farmacocinética , Proteínas de Ligação ao GTP/sangue , Técnicas Imunoenzimáticas/métodos , Interferon beta/farmacocinética , Esclerose Múltipla Recidivante-Remitente/sangue , Adjuvantes Imunológicos/uso terapêutico , Disponibilidade Biológica , Humanos , Interferon beta-1a , Interferon beta-1b , Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Proteínas de Resistência a Myxovirus , Valor Preditivo dos Testes , Fatores de TempoRESUMO
Duchenne Muscular Dystrophy (DMD) is an X-linked recessive genetic disorder characterized by rapidly progressive muscle weakness. The disease is caused by deletion, duplication or point mutation of the dystrophin gene, located on the X chromosome (Xp21). Deletion accounts for 60% of the mutations within the 79 exons of the dystrophin gene. Seven exons (43, 44, 45, 46, 49, 50, and 51) were found to be most commonly deleted among the Asian patients. To detect the frequency of deletion of these 7 exons in Malaysian DMD patients, we carried out a molecular genetic analysis in 20 Malaysian DMD patients. The mean age of initial presentation was 60 months (SD 32 months, range 5-120 months). Fourteen patients were found to have deletion of at least one of the seven exons. The remaining six patients did not show any deletion on the tested exons. Deletions of exons 49, 50 and 51 were the most frequent (71.43%) and appear to be the hot spots in our cohort of patients.
Assuntos
Deleção Cromossômica , Distrofina/genética , Distrofia Muscular de Duchenne/genética , Adolescente , Criança , Pré-Escolar , Éxons , Humanos , Lactente , Malásia , MasculinoRESUMO
Affinity of viral antibodies matures slowly after primary virus infections. Recent investigations with human sera and mouse monoclonal antibodies have provided the first evidence for a role of antibody affinity in the pathogenesis of chronic virus infections. More detailed studies are necessary before the rules and exceptions of this phenomenon are revealed.
Assuntos
Anticorpos Antivirais/imunologia , Afinidade de Anticorpos , Viroses/imunologia , Animais , Humanos , Tolerância Imunológica , CamundongosRESUMO
A novel form of adjuvant-neuroantigen formulation was established which was highly encephalitogenic in previously resistant BALB/c mice. The antigen formulation contained mouse whole spinal cord homogenate (MSCH), mycobacteria, and mineral oil, identically to the conventional preparation, but emulsification was completed by sonication instead of extrusion. Sonication of MSCH alone did not render a conventionally prepared emulsion encephalitogenic. The novel adjuvant formulation showed reduced water-oil droplet size, and the neuroantigen was located on the surface of the droplets as well as in the intermicellar space, while in the extruded formulation the material was buried in the droplet interior. Mice inoculated with the sonicated emulsion showed strong brain and spinal cord infiltration of lymphoid cells. The sonicated emulsion was highly encephalitogenic in all six BALB/c substrains tested. The results suggest that availability of the neuroantigen is of critical importance for the development of clinical EAE in the BALB/c mouse.
Assuntos
Encefalomielite Autoimune Experimental/imunologia , Camundongos Endogâmicos BALB C/imunologia , Proteínas do Tecido Nervoso/imunologia , Adjuvantes Imunológicos/química , Animais , Emulsões , Feminino , Camundongos , Microscopia Eletrônica , Proteínas do Tecido Nervoso/química , Sonicação , Medula Espinal/imunologiaRESUMO
Linomide (quinoline-3-carboxamide) is an immunomodulator with diverse effects on the immune system. Its beneficial effects on experimental autoimmune disease models have been linked to downregulation of Th1 cytokines and altered macrophage functions. We studied this effect of downregulation of Th1-type of immune response on Semliki Forest A7 virus infection in experimental autoimmune encephalomyelitis (EAE) susceptible Th1-prone SJL mice and in EAE-resistant Th2-prone BALB/c mice. We aimed at addressing the target-cell population of Linomide responsible for this Th1 downregulation. Treatment with Linomide led to increased virus infection in brain and this effect coincided with decreased production of IL-12 and IFN-gamma from stimulated spleen cells in SJL mice. In contrast, IL-12 and IFN-gamma expression were increased in Linomide-treated BALB/c mice. Treatment of infected SJL mice resulted in decreased percentage of CD11b+ and CD11c+ cells. Thus, the target cell population of Linomide may be antigen-presenting cells (APC) which are considered as candidates for regulatory cells of Th1/Th2 balance.
Assuntos
Adjuvantes Imunológicos/farmacologia , Infecções por Alphavirus/imunologia , Hidroxiquinolinas/farmacologia , Células Th1/imunologia , Células Th2/imunologia , Animais , Células Apresentadoras de Antígenos/efeitos dos fármacos , Encéfalo/virologia , Antígeno CD11b/análise , Encefalomielite Autoimune Experimental/imunologia , Interferon gama/biossíntese , Interleucina-12/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , RNA Viral/análise , Vírus da Floresta de Semliki , Baço/citologia , Carga ViralRESUMO
This report describes two mechanisms by which virus infection can facilitate demyelinating autoimmune inflammation in the murine CNS. In the BALB/c mouse model of experimental allergic encephalomyelitis (EAE), peripheral infection with an avirulent strain (A7) of Semliki Forest virus (SFV) increased the morbidity to EAE by infecting endothelial cells and damaging the blood-brain barrier (BBB). An influx of hematogenous CD18+ (LFA-1+ and MAC-1+) cells into the CNS compartment was followed by a local increase in intercellular adhesion molecule 1 (ICAM-1) expression on the vascular endothelium. Although SFV A7 infection without EAE induction caused multifocal cerebral vascular endothelial cell infection and BBB damage followed by cellular infiltration and transient increase of ICAM-1, inflammation and demyelination of CNS white matter with classical clinical signs of EAE was observed only in EAE-induced BALB/c mice, whereas the control mice remained neurologically healthy. The upregulation of ICAM-1 after virus infection was detected after the CD18+ (LFA-1+ and MAC-1+) cells had infiltrated the CNS both after EAE induction and also in nonsensitized control mice. The observed increase in ICAM-1 expression was transient in nonsensitized SFV A7 infected mice just as in the cellular infiltrates in the CNS, but EAE induction resulted in prolongation in both the cellular infiltrates and upregulation of ICAM-1. Thus, SFV A7 infection causes BBB damage and prolongs increased ICAM-1 expression on brain endothelium. This results in increased and more rapid morbidity to EAE in mice which have been sensitized with neuroantigen. However, SFV A7-infected mice without neuroantigen sensitization remain neurologically healthy.
Assuntos
Infecções por Alphavirus , Barreira Hematoencefálica , Encefalomielite Autoimune Experimental/fisiopatologia , Encefalomielite Autoimune Experimental/virologia , Molécula 1 de Adesão Intercelular/metabolismo , Vírus da Floresta de Semliki , Animais , Antígenos Virais/análise , Antígenos CD18/análise , Permeabilidade Capilar , Encefalomielite Autoimune Experimental/imunologia , Feminino , Fibrinogênio/análise , Imuno-Histoquímica , Hibridização In Situ , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Susceptibility to autoimmunity has been associated with polarization of Th1/Th2 balance in immune system towards the Th1-type of reactivity. We report here that orally administered quinoline-3-carboxamide (Linomide) selectively downregulates Th1 response in BALB/c and SJL mice, leading to reduction of autoimmunity in the BALB/c and SJL models of experimental allergic encephalomyelitis (EAE). This was shown by prevention of EAE in Th1 responding SJL mice and partial downregulation of EAE in Th2-prone BALB/c mice. In a BALB/c model of EAE, in which infection with Semliki Forest A7 virus (SFV-A7) is used for enhancement of autoimmunity, clinical signs of EAE were reduced while mortality due to viral infection in the CNS was enhanced. Selective downregulation of the Th1 response by Linomide also rendered initially resistant SJL mice susceptible to SFV-A7 CNS infection. This was shown by immunohistochemical detection of extensive deposits of viral antigen in numerous perivascular foci within the CNS and abolished virus antigen-specific lymphocyte reactivity in Linomide-treated SJL mice. In addition, analysis of spleen cell cytokine mRNA production profile revealed decreased number of IFN-gamma producing cells in both SJL and BALB/c mice, reduced number of IL-12p40 producing cells in SJL and increased number of 12p40 producing cells in BALB/c mice along with slightly increased IL-4 production in both strains of mice. These results indicate that oral treatment with Linomide induces selective downregulation of Th1 reactivity causing reduction of autoimmunity and increased susceptibility to SFV-A7 CNS infection. Selective downregulation of Th1 response is a desired effect in the treatment of autoimmune diseases but our results suggest that the benefits have to be balanced against the possible loss in immunoprotection against pathogens.
Assuntos
Adjuvantes Imunológicos/farmacologia , Infecções por Alphavirus/imunologia , Autoimunidade/efeitos dos fármacos , Hidroxiquinolinas/farmacologia , Vírus da Floresta de Semliki , Células Th1/efeitos dos fármacos , Animais , Formação de Anticorpos/efeitos dos fármacos , Antígenos Virais/imunologia , Sistema Nervoso Central/virologia , Citocinas/genética , Suscetibilidade a Doenças/imunologia , Encefalomielite Autoimune Experimental/imunologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos , RNA Mensageiro/metabolismo , Vírus da Floresta de Semliki/imunologia , Vírus da Floresta de Semliki/isolamento & purificação , Baço/metabolismo , Baço/patologia , Células Th1/imunologia , Células Th1/fisiologiaRESUMO
Experimental autoimmune encephalomyelitis (EAE) can be induced in resistant BALB/c mice by ultrasound-formed adjuvant emulsion. In contrast to susceptible mouse strains large numbers of neutrophils secreting TNF-alpha occupied the central nervous system (CNS) of BALB/c mice with severe EAE, whereas only small numbers of macrophages and CD4+ T-cells could be detected. CNS infiltration was preceded with activation of microglial cells. Ultrasound formed adjuvant induced early IFN-gamma expression in popliteal lymph nodes of BALB/c mice, whereas conventional adjuvant induced delayed IFN-gamma production. Although the clinical outcome of EAE was similar to that seen in susceptible mice, the pathogenesis was distinct having possible implications on the different forms seen in multiple sclerosis.
Assuntos
Encéfalo/imunologia , Encefalomielite Autoimune Experimental/imunologia , Neutrófilos/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Feminino , Interferon-alfa/fisiologia , Interleucina-12/fisiologia , Interleucina-18/fisiologia , Interleucina-4/genética , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/análiseRESUMO
Antigenicity of rubella virus E1 polypeptide was analyzed using synthetic peptides with predicted amino acid sequences. Overlapping solid-phase bound peptides were used to define antibody binding domains and a panel of free peptides to study T-cell responsiveness. Several antibody-binding areas including those earlier described to contain major neutralizing epitopes were recognized by human sera positive for rubella antibodies. T-cell lines specific for rubella virus were established from 14 rubella immune subjects. All cell lines responded to rubella virion-derived antigen but only eight (57%) responded to one or more of the synthetic peptides. Individual patterns of peptide recognition were found but peptide 8 representing amino acids 402-422 was most often stimulatory to T-cells lines, either alone (3 subjects) or in combination with peptide 3 (amino acids 245-269) or 3 and 4 (amino acids 269-287). The response was HLA restricted but no single DR specificity for this restriction was identified.
Assuntos
Anticorpos Antivirais/imunologia , Peptídeos/imunologia , Vírus da Rubéola/imunologia , Linfócitos T/imunologia , Proteínas do Envelope Viral/imunologia , Antígenos Virais/imunologia , Sítios de Ligação de Anticorpos/imunologia , Linhagem Celular , Células Cultivadas , Epitopos/imunologia , Antígenos HLA-DR/imunologia , Humanos , Técnicas Imunoenzimáticas , Ativação Linfocitária/imunologia , Peptídeos/síntese químicaRESUMO
Guinea pig and rabbit antisera from animals immunized with purified measles virus hemagglutinin (G) protein were used to establish a solid-phase four-layer radioimmunoassay for quantitative measurement of the G protein. The sensitive of the assay was 2 ng of purified G protein, and 200 micrograms of protein from uninfected Vero cells neither decreased the sensitivity nor reacted non-specifically in the assay. Radioimmunoassay standard dose-response curves were established and unknown values interpolated from these using the logit program of a desktop computer. Using this procedure, a measles virus growth curve in infected Vero cells was determined by measurement of G protein production. Under these same conditions, hemagglutination was not sensitive enough to detect early hemagglutinin production. Viral antigens in canine distemper virus, Newcastle disease virus, parainfluenza viruses 1-4, simian virus 5, and respiratory syncytial virus-infected cell lysates did not cross-react in the radioimmunoassay. A small degree of cross-reactivity was detected with mumps viral antigens, both with Vero cell-derived (wild-type strain) and egg-derived (Enders strain) purified virus preparations and with a cell lysate antigen prepared from wild-type mumps virus-infected Vero cells.
Assuntos
Hemaglutininas Virais/análise , Vírus do Sarampo/imunologia , Animais , Linhagem Celular , Chlorocebus aethiops , Reações Cruzadas , Testes de Hemaglutinação , Vírus do Sarampo/crescimento & desenvolvimento , Vírus da Caxumba/imunologia , Radioimunoensaio , Especificidade da EspécieRESUMO
Cerebrospinal fluid (CSF) cells from 4 mumps meningitis and 11 multiple sclerosis (MS) patients were cultured in vitro for 7 days with and without pokeweed mitogen (PWM) stimulation. The cells produced varying amounts of IgG without stimulation and no significant increase of IgG synthesis was observed after PWM stimulation. Antibodies against mumps, measles, rubella, herpes simplex, and adeno viruses were measured in the supernatants of the cultures by a sensitive enzyme immunoassay. In the mumps meningitis patients, the largest amount of antibody was against mumps virus but low amounts of antibodies with other specificities were also synthesized by CSF cells of one patient. The most commonly detected specificities in MS patients were against measles and rubella viruses, whereas antibodies against adeno and mumps viruses were detected in only one CSF cell supernatant. No antibodies produced against herpes simplex virus in vitro were detected in any of the supernatants. The amounts of viral antibodies produced in vitro and intrathecally were only partially correlated.
Assuntos
Anticorpos Antivirais/metabolismo , Líquido Cefalorraquidiano , Meningite/imunologia , Esclerose Múltipla/imunologia , Caxumba/complicações , Células Cultivadas , Humanos , Técnicas In Vitro , Meningite/líquido cefalorraquidiano , Meningite/etiologia , Esclerose Múltipla/líquido cefalorraquidianoRESUMO
Two hundred and twenty-eight paired serum and CSF samples collected from 31 patients with MS during a 2-3-year follow-up were analyzed for the presence of immune complexes (IC) by C1q RIA and PIPA (platelet [125I]protein A) techniques. One hundred and forty-four sera from 11 healthy individuals were analyzed as controls. In almost all patients (29/31) IC were detectable during some period of the disease, as tested by either of the techniques. The results obtained by C1q RIA and PIPA correlated positively with each other in MS when mean serum values of each patient were compared. The mean CSF IC levels detected by C1q RIA appeared to correlate to the mean IgG indexes, an indicator of the intrathecal rate of IgG synthesis. The amount of IC in serum and CSF fluctuated independently in MS. The results of the PIPA test for MS serum IC correlated significantly to the duration of the disease. The PIPA test results also showed that patients in stable or chronic phases of MS displayed IC in serum and CSF more often than patients with a relapsing/remitting course of disease but there was no clear correlation between fluctuations in IC levels in individual patients measured by C1q RIA or PIPA techniques and the disease course. Because of the lack of a clear correlation between the presence, quantity and fluctuation of IC and the clinical picture we suggest that those IC detected in the present study are probably not a precipitating factor in the pathogenesis of multiple sclerosis.