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1.
Clin Exp Rheumatol ; 42(5): 1035-1042, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38372719

RESUMO

OBJECTIVES: Rheumatic and musculoskeletal diseases (RMD) may exhibit different immune responses to novel coronavirus (COVID-19) infection compared to healthy individuals. While previous studies have primarily investigated changes in COVID-19-related antibodies post-vaccination for RMD patients, this study sought to explore the dynamics of SARS-CoV-2 IgG antibodies and neutralising antibodies (NAb) in RMD patients after COVID-19 infection. METHODS: In this longitudinal study, we monitored the SARS-CoV-2 IgG antibodies and NAb levels in RMD patients and healthy controls (HC) at 60 and 90 days post-COVID-19 infection. Chemiluminescent immunoassay was used to detect the levels of novel coronavirus-specific IgG (anti-S1/S2 IgG) antibodies and NAb. RESULTS: A total of 292 RMD patients and 104 HC were enrolled in the study. At both the 60-day and 90-day post-COVID-19 infection, RMD patients exhibited significantly lower levels of anti-S1/S2 IgG and NAb than those in the HC group (p<0.001). The anti-S1/S2 IgG antibody levels remained relatively stable, while the NAb levels in RMD patients could vary greatly between the 60th and 90th days. A logistic regression analysis revealed that the prior administration of glucocorticoids (GC), immunosuppressants, and b/tsDMARDs stood out as independent risk factors associated with reduced anti-S1/S2 IgG and NAb levels, irrespective of the specific RMD subtypes. CONCLUSIONS: GC and anti-rheumatic medications can potentially alter the production of specific antibodies, especially NAb, in RMD patients post-COVID-19 infection. These findings emphasise the importance of continuous monitoring for NAb fluctuations in RMD patients following a COVID-19 infection.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Imunoglobulina G , Doenças Musculoesqueléticas , Doenças Reumáticas , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/sangue , Doenças Reumáticas/imunologia , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Estudos Longitudinais , Adulto , Doenças Musculoesqueléticas/imunologia , Doenças Musculoesqueléticas/sangue , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Idoso , Estudos de Casos e Controles
2.
Ann Rheum Dis ; 81(12): 1712-1721, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35977808

RESUMO

OBJECTIVES: Families that contain multiple siblings affected with childhood onset of systemic lupus erythematosus (SLE) likely have strong genetic predispositions. We performed whole exome sequencing (WES) to identify familial rare risk variants and to assess their effects in lupus. METHODS: Sanger sequencing validated the two ultra-rare, predicted pathogenic risk variants discovered by WES and identified additional variants in 562 additional patients with SLE. Effects of a splice site variant and a frameshift variant were assessed using a Minigene assay and CRISPR/Cas9-mediated knock-in (KI) mice, respectively. RESULTS: The two familial ultra-rare, predicted loss-of-function (LOF) SAT1 variants exhibited X-linked recessive Mendelian inheritance in two unrelated African-American families. Each LOF variant was transmitted from the heterozygous unaffected mother to her two sons with childhood-onset SLE. The p.Asp40Tyr variant affected a splice donor site causing deleterious transcripts. The young hemizygous male and homozygous female Sat1 p.Glu92Leufs*6 KI mice spontaneously developed splenomegaly, enlarged glomeruli with leucocyte infiltration, proteinuria and elevated expression of type I interferon-inducible genes. SAT1 is highly expressed in neutrophils and encodes spermidine/spermine-N1-acetyltransferase 1 (SSAT1), a rate-limiting enzyme in polyamine catabolism. Young male KI mice exhibited neutrophil defects and decreased proportions of Foxp3 +CD4+ T-cell subsets. Circulating neutrophil counts and proportions of Foxp3 +CD4+ T cells correlated with decreased plasma levels of spermine in treatment-naive, incipient SLE patients. CONCLUSIONS: We identified two novel SAT1 LOF variants, showed the ability of the frameshift variant to confer murine lupus, highlighted the pathogenic role of dysregulated polyamine catabolism and identified SAT1 LOF variants as new monogenic causes for SLE.


Assuntos
Doenças Genéticas Ligadas ao Cromossomo X , Lúpus Eritematoso Sistêmico , Animais , Criança , Feminino , Humanos , Masculino , Camundongos , Predisposição Genética para Doença , Homozigoto , Lúpus Eritematoso Sistêmico/genética , Espermina/sangue , Doenças Genéticas Ligadas ao Cromossomo X/genética , Acetiltransferases/genética
3.
Int J Gen Med ; 13: 1661-1667, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33408503

RESUMO

PURPOSE: This study was to investigate the clinical characteristics and laboratory parameters of severe fever with thrombocytopenia syndrome (SFTS). PATIENTS AND METHODS: A detailed retrospective analysis of clinical records for SFTS patients was conducted. Fifty-one cases confirmed SFTS virus infected were enrolled. The clinical characteristics and laboratory parameters between survivors and non-survivors were analyzed. RESULTS: All patients aged between 30 and 80 years were farmers or residing in wooded and hilly areas. All patients occurred between April and October. The major clinical manifestations were fever, fatigue, diarrhea, myalgia, nausea and vomiting. Conscious disturbance, lymph node enlargement and hemorrhage were common. Fatal outcome occurred in 31.4% (16/51) of patients. Compared with survivors group, in non-survivors group, the proportion of consciousness disturbance, age, the levels of AST, LDH, Bun, Cr, PT and APTT were significantly increased, and PLT was significantly decreased. The age, PLT, AST, LDH, Cr, PT and APTT were the risk factors for fatal outcomes. Moreover, the age (OR, 1.245; 95% CI, 1.052-1.474) and APTT (OR, 1.095; 95% CI, 1.005-1.192) were the independent risk factors for fatal outcomes. Heteromorphic lymphocyte and hemophagocytosis could be found in SFTS patients, especially the proportion of finding hemophagocytosis was significantly higher in non-survivors group compared with survivors group. CONCLUSION: These results suggest SFTS is a systemic infection, the age and APTT can be used as potential predictors referring to severe SFTS cases.

4.
Planta Med ; 72(5): 398-404, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16557452

RESUMO

This research attempts to clarify the cause for poor oral absorption of ginsenoside Rb1 (Rb1), one main ingredient of the well known Panax notoginseng saponins (PNS) for curing hemorrhage. Caco-2 cell monolayers were used as an in vitro model to reveal the transport mechanism of Rb1 across the intestinal mucosa. Moreover, the serum concentration-time profiles of Rb1 after tail venous (IV), portal venous (PV), intraduodenal (ID) and peroral (PO) administration to rats were compared to evaluate the first-pass effects of stomach, intestine and liver. In vitro experiments showed that uptake by Caco-2 cell monolayers was temperature dependent, but was not influenced by cyclosporine A and ketoconazole. The change in the apical pH showed no obvious effects on the uptake of Rb1. The uptake and transport were non-saturable, and flux from the apical compartment to the basolateral compartment (A-B) increased linearly with increasing concentration, which indicated a passive transport. Meanwhile, an apparent permeability coefficient of (5.90 +/- 1.02) x 10(-8) cm/s (C0 = 1 mg/mL) predicted an incomplete absorption. The investigation on the pharmacokinetic behavior of Rb1 after different routes of administration to rats showed a significant difference between PO (F(PO) was 0.64%), ID (F(ID) was 2.46%) and PV (F(PV) was 59.49%) administration, and the first-pass effect of the intestine is more significant than that of the stomach and liver in the absorption process. In summary, elimination in the stomach, large intestine and liver contributed to the poor absorption of Rb1, but the low membrane permeability might be a more important factor dominating the extent of absorption.


Assuntos
Ginsenosídeos/farmacologia , Hemostáticos/farmacocinética , Panax , Fitoterapia , Administração Oral , Animais , Células CACO-2 , Ginsenosídeos/administração & dosagem , Hemostáticos/administração & dosagem , Humanos , Absorção Intestinal , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacocinética , Raízes de Plantas , Ratos , Ratos Sprague-Dawley
5.
Yao Xue Xue Bao ; 40(4): 377-81, 2005 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-16011272

RESUMO

AIM: To investigate the pharmacokinetic course of intranasal powders of Panax notoginseng Saponins (PNS) in a rat model and its protective effects against cardio-cerebrovascular diseases administrated in the form of its suspension. METHODS: After administration, Rgl concentration in the serum was analyzed by HPLC and the absolute bioavailability was calculated. The protective effects against cardia-cerebrovascular diseases were studied on actue myocardial infarction model in rats built by occlusion of left coronary artery and cerebral ischemia-reperfusion model in gerbils built by occlusion of bilateral common carotid artery (CCA). RESULTS: The in vivo course of Rgl in rats conformed to two-compartment model after intranasal administration of PNS suspension and the absolute bioavailability was 103.56%. The suspension significantly reduced myocardial infarct size induced by occlusion of the left coronary artery, alleviated cerebral edema and the stroke symptoms induced by occlusion of bilateral common carotid artery (CCA). And the effects were dose-dependent, the higher dose, the better effects. CONCLUSION: The results of pharmacokinetics and pharmacodynamics demonstrated that PNS intranasal preparation has a pretty prospect to develop.


Assuntos
Ginsenosídeos/farmacologia , Ginsenosídeos/farmacocinética , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão/patologia , Administração Intranasal , Animais , Disponibilidade Biológica , Isquemia Encefálica/complicações , Relação Dose-Resposta a Droga , Feminino , Gerbillinae , Ginsenosídeos/administração & dosagem , Ginsenosídeos/sangue , Masculino , Miocárdio/patologia , Panax/química , Plantas Medicinais/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia
6.
Eur J Pharm Sci ; 24(5): 477-86, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15784337

RESUMO

The aim of this study was to investigate the effect of two novel self-microemulsifying drug delivery systems (SMEDDS) containing Labrasol with different dilutions on tight junctions. Changes in barrier properties of Caco-2 cell monolayers, including transepithelial electrical resistance (TEER) and permeability to the paracellular marker, i.e., mannitol, were assessed in response to dilutions and surfactants contents within formulations. The cytotoxicity of SMEDDS and the effect of surfactants on Caco-2 cells were evaluated by the MTT. Changes in subcellular localization of the tight junction proteins, ZO-1 and F-actin, were examined by confocal laser scanning microscopy. Results demonstrated that negatively charged SMEDDS with different dilutions had no effect on the TEER, but significantly increased the permeability of mannitol. In contrast, the positively charged formulation showed a dilution-dependent reduction in TEER. A corresponding increase in mannitol permeability of up to 29.4-fold to 64.7-fold greater than the control was also observed across the monolayer. Labrasol with the concentration of 0.1 and 1% was shown to increase the permeability of mannitol by 4.6-fold and 33.8-fold, respectively. The mechanism of opening of tight junctions was found to involve F-actin-related changes and redistribution of ZO-1.


Assuntos
Sistemas de Liberação de Medicamentos , Emulsões/administração & dosagem , Junções Íntimas/efeitos dos fármacos , Actinas/análise , Células CACO-2 , Impedância Elétrica , Glicerídeos , Humanos , Manitol/metabolismo , Proteínas de Membrana/análise , Compostos Orgânicos , Fosfoproteínas/análise , Junções Íntimas/metabolismo , Proteína da Zônula de Oclusão-1
7.
Yao Xue Xue Bao ; 39(10): 839-43, 2004 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-15700828

RESUMO

AIM: To study the kinetics of uptake, transepithelial transport and efflux of 9-nitrocamptothecin (9-NC). METHODS: A human intestinal epithelial cell model Caco-2 cell in vitro cultured had been applied to study the kinetics of uptake, transport and efflux kinetics of 9-NC at small intestine. The effects of time, pH, temperature and P-glycoprotein inhibitors on the uptake of 9-NC were investigated. The determination of 9-NC was performed by HPLC. RESULTS: The uptake and absorption of 9-NC were passive diffusion as the dominating process. The uptake of 9-NC is positively correlated to uptake time, and negatively correlated to pH and temperature. The inhibitors, cyclosporine A and verapamil, significantly enhanced the uptake amount of 9-NC (P < 0.05). P(app) of Basolateral to Apical was much more than that of Apical to Basolateral (2.6-6.9 fold). The efflux of 9-NC was fitted to apparent two-order process. The m0 [(148.0 +/- 2.2) pmol x cm(-2)] and the efflux rate (41.1 pmol x cm2 min(-1)) on Apical side were higher than the m0 [(121 +/- 7) pmol x cm(-2)] (P < 0.05) and the efflux rate (29.2 pmol x cm2 x min(-1)) on Basolateral side (P < 0.01). CONCLUSION: The uptake and absorption of 9-NC were passive diffusion as the dominating process. P-glycoprotein had strong efflux effects on the uptake and transepithelial transport of 9-NC.


Assuntos
Antineoplásicos/farmacocinética , Camptotecina/análogos & derivados , Camptotecina/farmacocinética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Transporte Biológico , Células CACO-2/metabolismo , Camptotecina/antagonistas & inibidores , Ciclosporina/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Temperatura , Verapamil/farmacologia
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