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1.
Sci Rep ; 12(1): 18929, 2022 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-36344597

RESUMEN

To reveal waning humoral immunity after second dose BNT162b2 vaccinations in a rural Japanese community and determine factors affecting antibody titers. We aimed to report Immunoglobulin G (IgG) antibody against the SARS-CoV-2 spike (S1) protein levels and neutralizing activity in a large scale community based cohort. METHODS: Participants in the observational cross-sectional study received a second dose of vaccination with BNT162b2 (Pfizer/BioNTech) and were not previously infected with COVID-19. Questionnaire-collected data on sex, age, adverse vaccine reactions, and medical history was obtained. RESULTS: Data from 2496 participants revealed that older age groups reached a low antibody titer 90-120 days after the second vaccination. Neutralizing activity decreased with age; 35 (13.3%) of those aged ≥ 80 years had neutralizing activity under the cut-off value. Neutralizing activity > 179 days from the second vaccination was 11.6% compared to that at < 60 days from the second vaccination. Significantly lower IgG antibody titers and neutralizing activity were associated with age, male sex, increased time from second vaccination, smoking, steroids, immunosuppression, and comorbidities. CONCLUSIONS: Antibody titer decreased substantially over time. Susceptible populations, older people, men, smokers, steroid users, immunosuppression users, and people with three or more comorbidities may require a special protection strategy.


Asunto(s)
COVID-19 , Vacunas , Masculino , Humanos , Anciano , Inmunidad Humoral , Estudios Transversales , Vacuna BNT162 , Anticuerpos Antivirales , Japón , SARS-CoV-2 , COVID-19/prevención & control , Vacunación , Encuestas y Cuestionarios , Anticuerpos Neutralizantes
2.
Biochim Biophys Acta ; 1590(1-3): 123-30, 2002 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-12063175

RESUMEN

Increased production of plasminogen activator inhibitor-1 (PAI-1) in plaques plays a role in the pathogenesis of atherosclerosis. This study was conducted to investigate the effect of blockade of Rho/Rho-kinase signaling on the synthesis of PAI-1 in cultured human peripheral blood monocytes. HMG-CoA reductase inhibitors (statins) and inhibitors of Rho and Rho-kinase were added to monocyte cultures. The levels of PAI antigen and mRNA were determined by Western blotting and RT-PCR, respectively, and PAI-1 expression was assessed by immunohistochemistry. We performed pull-down assays to determine the activity of Rho by measuring the GTP-bound form of Rho A. In unstimulated and lipopolysaccharide (LPS)-stimulated cultured monocytes, statins reduced the levels of PAI-1 antigen and mRNA. The suppressive effects of statins on PAI-1 synthesis were reversed by geranylgeranylpyrophosphate (GGPP) and were mimicked by C3 exoenzyme. Immunohistochemistry confirmed the role of lipid modification by GGPP in suppressive effect of statins in PAI-1 synthesis. Pull-down assays demonstrated that statins decreased the levels of the GTP-bound form of Rho A. Our findings suggest that statins decrease the activity of Rho by inhibiting geranylgeranylation. Moreover, Rho-kinase inhibitors, Y-27632 and fasudil, suppressed the synthesis of PAI-1 in this culture system. We show that inhibition of Rho/Rho-kinase signaling downregulates the synthesis of PAI-1 in human monocytes.


Asunto(s)
1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , Toxinas Botulínicas , Monocitos/metabolismo , Inhibidor 1 de Activador Plasminogénico/biosíntesis , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas de Unión al GTP rho/metabolismo , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , ADP Ribosa Transferasas/farmacología , Amidas/farmacología , Arteriosclerosis/etiología , Secuencia de Bases , Células Cultivadas , Inhibidores Enzimáticos/farmacología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Péptidos y Proteínas de Señalización Intracelular , Monocitos/efectos de los fármacos , Inhibidor 1 de Activador Plasminogénico/genética , Fosfatos de Poliisoprenilo/farmacología , Pravastatina/farmacología , Prenilación de Proteína/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Piridinas/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal/efectos de los fármacos , Quinasas Asociadas a rho
3.
Atherosclerosis ; 163(1): 39-47, 2002 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12048120

RESUMEN

Monocytes and macrophages synthesize tissue factor (TF) which plays a role in thrombogenicity in coronary artery disease. This study was conducted to investigate the effect of Rho/Rho-kinase inhibition on the synthesis of TF in cultured human monocytes. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), C3 exoenzyme and Rho-kinase inhibitors were added to isolated peripheral blood monocytes and the synthesis of TF was assessed by reverse transcriptase polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry. Rho activity was determined by measuring the GTP-bound form of Rho A. Cerivastatin and pravastatin reduced the levels of TF antigen and mRNA. The suppressive effect of statins on TF synthesis was reversed by geranylgeranylpyrophosphate (GGPP) and the restoring effect of GGPP was eliminated by C3 exoenzyme and Y-27632. Pravastatin decreased the activity of Rho A, suggesting that the suppression of TF synthesis by statins is mediated via inhibition of the geranylgeranylation of Rho. Moreover, inhibition of Rho and Rho-kinase downregulated the synthesis of TF. Our results suggest that Rho/Rho-kinase signaling is involved in the synthesis of TF in human monocytes and that inhibition of Rho/Rho-kinase may be useful for treating thrombogenicity in coronary artery disease.


Asunto(s)
Acilcoenzima A/farmacología , Pravastatina/farmacología , Proteínas Serina-Treonina Quinasas/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Piridinas/farmacología , Tromboplastina/efectos de los fármacos , Análisis de Varianza , Secuencia de Bases , Western Blotting , Células Cultivadas , Estenosis Coronaria/patología , Estenosis Coronaria/fisiopatología , Regulación hacia Abajo , Humanos , Inmunohistoquímica , Péptidos y Proteínas de Señalización Intracelular , Leucocitos Mononucleares , Datos de Secuencia Molecular , Probabilidad , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Tromboplastina/biosíntesis , Quinasas Asociadas a rho
4.
Circ J ; 66(10): 965-71, 2002 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12381094

RESUMEN

It remains to be clarified how angiotensin-converting enzyme inhibitor-induced function (ie, increased NO related action or the inhibition of angiotensin II AT1 receptor dependent action) affects apoptosis of smooth muscle cells in the neointima following arterial injury. Saline (control), enalapril, L-arginine, combined enalapril and L-arginine, or losartan was administered for 14 days to Sprague-Dawley rats after balloon carotid injury and the ratio of intima to media areas (I/M), inducible NO synthase (iNOS) concentrations and %TUNEL were measured. I/M decreased similarly in the enalapril, L-arginine and losartan groups, and the combination of enalapril and L-arginine resulted in the largest I/M decrease. TUNEL positivity was increased compared with controls in the following order: losartan, L-arginine, enalapril and combination of enalapril and L-arginine. The intensity of immunostaining for iNOS was increased approximately 1.9-fold compared with the control in the combined enarapril and L-arginine group as well as in the enalapril group. These data suggest that the apoptosis in the neointima is different for L-arginine, losartan and enalapril under similar conditions and was higher under treatment with enalapril, not only via the action of NO or blocking of the AT1, but also by upregulation of iNOS.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Apoptosis/efectos de los fármacos , Traumatismos de las Arterias Carótidas/tratamiento farmacológico , Oclusión de Injerto Vascular/tratamiento farmacológico , Animales , Arginina/farmacología , Traumatismos de las Arterias Carótidas/etiología , Cateterismo/efectos adversos , División Celular/efectos de los fármacos , Enalapril/farmacología , Losartán/farmacología , Masculino , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/enzimología , Músculo Liso Vascular/patología , Óxido Nítrico Sintasa/biosíntesis , Óxido Nítrico Sintasa/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II , Ratas , Ratas Sprague-Dawley , Regulación hacia Arriba/efectos de los fármacos
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