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1.
Article in English | WPRIM | ID: wpr-927667

ABSTRACT

Objective@#This study aimed to investigate whether cytokine profiles and virological markers might add value in monitoring the effects of peginterferon (PEG-IFN) therapy for hepatitis B e-antigen (HBeAg) positive chronic hepatitis B (CHB).@*Methods@#HBeAg positive patients with CHB were treated with PEG-IFN for 48 weeks. Clinical biochemical, and HBV serological indexes, as well as cytokines, were detected at baseline and every 12 weeks.@*Results@#A total of 116 patients with CHB were enrolled in this study; 100 patients completed the 48-week treatment and follow-up, of whom 38 achieved serum HBeAg disappearance, 25 achieved HBeAg seroconversion, 37 showed HBsAg decreases ≥ 1 log 10 IU/mL, 9 showed HBsAg disappearance, and 8 became HBsAb positive. The cytokine levels at baseline and during treatment were similar between the HBeAg disappearance group and non-disappearance group. The disappearance of HBeAg was independently associated with HBeAg levels at weeks 12 and 24, and with the HBeAg decline at week 24 ( P < 0.05). The HBsAg response was independently associated with HBsAg, the HBsAg decline, HBeAg, the HBeAg decline at week 12, and HBsAg at week 24 ( P< 0.05).@*Conclusion@#There was no significant correlation between the response to interferon (IFN) and cytokines during PEG-IFN treatment. The changes in virological markers predicted the response to IFN after 48 weeks.


Subject(s)
Biomarkers , Cytokines , DNA, Viral , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B, Chronic/drug therapy , Humans , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use
2.
Rev. bras. ginecol. obstet ; 43(9): 682-689, Sept. 2021. graf
Article in English | LILACS | ID: biblio-1351778

ABSTRACT

Abstract Objective The aim of the present study was to compare the local and systemic expression of the factors linked to the interferon alpha (IFN-α) activation pathway in different degrees of cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods A total of 128 patients with CIN I, CIN II, CIN III and cervical cancer was evaluated. The real-time polymerase chain reaction (RT-PCR) technique was used to evaluate the gene expression of IFNR1, IFNR2, IFN-α, oligoadenylate synthase (2'5′OAS), cytokine signal suppressor 1 (SOCS) 1, SOCS3, signal transducer and transcription activator 1 (STAT1), and IRF9 from 128 biopsies. A total of 46 out of 128 samples were evaluated by flow cytometry for IFNAR1, IFNAR2, STAT1, IRF7 and IFN-α in peripheral blood cells. Results Patients with CIN II and III (63 samples) had a low local expression of IFNR1, but not IFNR2. Patients with some degree of injury showed high expression of SOCS1 and SOCS3. Systemically, patients with CIN II and III (20 samples) had a significant increase in IFNR1, IFNR2, STAT1, IRF7, and IFN-α in helper, cytotoxic T lymphocytes, and in monocytes. Conclusion Patients with high-grade lesions have increased systemic expression of IFN-α and its activation pathways in helper and cytotoxic T lymphocytes, as well as in monocytes due to an exacerbation of the immune response in these patients. This phenomenon is not accompanied by resolution of the lesion due to a defect in the IFN-α activation pathway that revealed by low local IFNAR1 expression and high local expression of SOCS1 and SOCS3.


Resumo Objetivo O objetivo do presente estudo foi comparar a expressão local e sistêmica dos fatores ligados à via de ativação do interferon alfa (IFN-α) em diferentes graus de neoplasia intraepitelial cervical (NIC) e câncer cervical (CA) Métodos Foram avaliados 128 pacientes com NIC I, NIC II, NIC III e CA. A técnica de reação de cadeia de polimerase em tempo real (RT-PCR, na sigla em inglês) foi realizada para avaliar a expressão gênica do receptor de interferon (IFNR) 1, IFNR2, IFN-α, 2′-5′- oligoadenilato sintetase (2′5′OAS), supressor de sinalização de citocina (SOCS)1, SOCS3, transdutor de sinal e ativador de transcrição 1 (STAT1) e fator regulador de interferon 9 (IRF9) das 128 biópsias. Das 128 amostras, 46 foram avaliadas por citometria de fluxo para IFNAR1, IFNAR2, STAT1, IRF7 e IFN-α em células de sangue periférico. Resultados Pacientes com NIC II e III (63 amostras) tiveram baixa expressão local de IFNR1 mas não de IFNR2. Pacientes com algum grau de lesão apresentaram alta expressão de SOCS1 e SOCS3. Sistemicamente, os pacientes com NIC II e III (20 amostras) tiveram um aumento significativo de IFNR1, IFNR2, STAT1, IRF7 e IFN-α em linfócitos T auxiliares, citotóxicos e monócitos. Conclusão Pacientes com lesões de alto grau apresentam expressão sistêmica aumentada de IFN-α e suas vias de ativação em linfócitos T auxiliares e citotóxicos, bem como em monócitos, devido à exacerbação da resposta imune nesses pacientes. Este fenômeno não é acompanhado pela resolução da lesão devido a um defeito na via de ativação do IFN-α que é revelado pela baixa expressão local de IFNR1 e alta expressão local de SOCS1 e SOCS3.


Subject(s)
Humans , Female , Uterine Cervical Neoplasms/genetics , Cervical Intraepithelial Neoplasia/genetics , Interferon-alpha , Suppressor of Cytokine Signaling Proteins/metabolism
3.
Braz. j. otorhinolaryngol. (Impr.) ; 87(3): 260-268, May-Jun. 2021. tab, graf
Article in English | LILACS | ID: biblio-1285685

ABSTRACT

Abstract Introduction Chronic rhinosinusitis is currently classified into two types: chronic rhinosinusitis without nasal polyps and chronic rhinosinusitis with nasal polyps. In the West, approximately 80% of chronic rhinosinusitis with nasal polyps cases are characterized by a predominantly eosinophilic cell infiltrate and a Th2 cytokine pattern. Objective To evaluate the effect of Interferon-α on cytokine levels of the eosinophilic nasal polyp cell culture supernatant. Methods Cell cultures were performed based on nasal polypoid tissue samples collected from 13 patients with eosinophilic chronic rhinosinusitis with nasal polyps. Polyps were considered eosinophilic according to the histopathological examination. Cell cultures were stimulated with 3000 IU of interferon-α. Before and after the stimulus, concentrations of Interferon-γ, tumor necrosis factor αand IL 2, 4, 6 and 10, using cytometric bead array, were assessed. Results Cell samples from eosinophilic nasal polyps from 13 patients were included in the study. Twenty-four hours after interferon-α stimulation, eosinophilic nasal polyp culture supernatants showed significantly decreased IL-4 concentrations and increase in interferon-γ, IL-10 and IL-6 concentrations compared to controls. There were no significant differences in tumor necrosis factor -α and IL-2 concentrations. Conclusion We demonstrated that interferon-α in vitro alters the pattern of cytokines in cell cultures of eosinophilic nasal polyps. Analysis of these alterations suggests that interferon-α promotes a rebalancing of inflammatory profiles in cell cultures, favoring the expression of Th1 and regulatory cytokines over Th2 cytokines.


Resumo Introdução A rinossinusite crônica, atualmente, é classificada em dois tipos: Rinossinusite Crônica sem Pólipos Nasais (RSCsPN) e Rinossinusite Crônica com Pólipos Nasais (RSCcPN). No Ocidente, cerca de 80% dos casos de RSCcPN caracterizam-se por um infiltrado celular predominantemente eosinofílico e um padrão de citocinas Th2. Objetivo Avaliar o efeito do Interferon-alpha nos níveis de citocinas do sobrenadante de culturas celulares de pólipos nasais eosinofílicos. Método Foram feitas culturas celulares a partir de amostras de tecido polipoide nasal coletadas de 13 pacientes com RSCcPN eosinofílica. Os pólipos eram considerados eosinofílicos segundo exame histopatológico. As culturas celulares foram estimuladas com 3000 UI de IFN-α. Antes e após tal estímulo, foram avaliadas, no sobrenadante das culturas celulares, as concentrações do Interferon-γ (IFN-γ), do Fator de Necrose Tumoral alfa (TNF-α) e das Interleucinas (IL) 2, 4, 6 e 10, usou-se o Cytometric Bead Array. Resultados Foram incluídas no estudo amostras celulares dos pólipos nasais eosinofílicos de 13 pacientes. Vinte e quatro horas após o estímulo com IFN-α, os sobrenadantes das culturas dos pólipos nasais eosinofílicos apresentaram, de forma significante, diminuição da concentração de IL-4 e aumento das concentrações de IFN-γ, IL-10 e IL-6, em relação ao controle. Não houve diferença significante nas concentrações de TNF-α e IL-2. Conclusão Demonstramos que o IFN-α, in vitro, altera o padrão de citocinas nas culturas celulares de pólipos nasais eosinofílicos. A análise do conjunto dessas alterações sugere que o IFN-α promove, nas culturas celulares, um rebalanceamento dos perfis inflamatórios, favorece a expressão de citocinas Th1 e regulatórias, em detrimento de citocinas do padrão Th2.


Subject(s)
Humans , Sinusitis/drug therapy , Rhinitis/drug therapy , Nasal Polyps , Chronic Disease , Cytokines , Interferon-alpha
4.
Article in English | WPRIM | ID: wpr-887715

ABSTRACT

Objective@#To investigate the changes in the cytokine profiles of chronic hepatitis B (CHB) patients undergoing antiviral treatment.@*Methods@#Hepatitis B e antigen (HBeAg)-positive patients were treated with Pegylated interferon (PEG-IFN) and entecavir (ETV). Clinical biochemistry and cytokines were detected at baseline and every 3 months.@*Results@#In all, 200 patients completed 48 weeks of treatment, 100 in the PEG-IFN group and 100 in the ETV group. During 3-6 months of treatment, compared with baseline, the PEG-IFN group showed a significant decrease in interferon-gamma (IFN-γ), interleukin-17A (IL-17A), interleukin-6(IL-6), interleukin-10(IL-10), and transforming growth factor beta (TGF-β) ( @*Conclusion@#During antiviral therapy, a change in the cytokine profile occurred; in the aspect of immune control and functional cure, PEG-IFN was significantly better than ETV.


Subject(s)
Adult , Antiviral Agents/therapeutic use , Cytokines/blood , Female , Guanine/therapeutic use , Hepatitis B, Chronic/drug therapy , Humans , Interferon-alpha/therapeutic use , Male , Polyethylene Glycols/therapeutic use , Prospective Studies , Recombinant Proteins/therapeutic use
5.
Article in Chinese | WPRIM | ID: wpr-880026

ABSTRACT

OBJECTIVE@#To explore the synergistic immunomodulatory mechanism of interferon alpha-1b, interleukin-2 and thalidomide (ITI) regimen on patients with acute myeloid leukemia (AML).@*METHODS@#Sixty eight untreated de novo or relapsed or refractory or maintenance therapy patients with AML admitted in the Affiliated Cancer Hospital of Zhengzhou University and the other 11 medical units from March 2016 to May 2019 were treated with ITI regimen. Peripheral blood specimen per patient was collected into EDTA-K3 anticoagulation vacuum tube before the administration of ITI and 3 months after the treatment; peripheral blood lymphocyte subsets and perforin and Granzyme B expression were analyzed by using flow cytometry; the levels of VEGF, IFN-γ, TNF-α and IL-6 in the plasma were detected by using a cytometric bead array. Thirty-five healthy subjects from the hospital physical examination centre were selected as normal controls.@*RESULTS@#The ratio of CD4@*CONCLUSION@#The ITI regimen can raise the ratio of CD4


Subject(s)
CD8-Positive T-Lymphocytes , Humans , Interferon-alpha , Interleukin-2 , Leukemia, Myeloid, Acute/drug therapy , Perforin , Thalidomide
6.
Brasília; s.n; 11 ago. 2020.
Non-conventional in Portuguese | LILACS, BRISA, PIE | ID: biblio-1117979

ABSTRACT

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 5 protocolos.


Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Betacoronavirus/drug effects , Ribavirin/therapeutic use , Technology Assessment, Biomedical , Ursodeoxycholic Acid/therapeutic use , Immunoglobulins/therapeutic use , Prednisolone/therapeutic use , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Chloroquine/therapeutic use , Cross-Sectional Studies , Cohort Studies , Interferon-alpha/therapeutic use , Tacrolimus/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Azithromycin/therapeutic use , Ritonavir/therapeutic use , Antibodies, Neutralizing/therapeutic use , Mesenchymal Stem Cells , Lopinavir/therapeutic use , Folic Acid/therapeutic use , Meropenem/therapeutic use , Hydroxychloroquine/therapeutic use , Antibodies, Monoclonal/therapeutic use , Mycophenolic Acid/therapeutic use
7.
Brasília; s.n; 8 jul. 2020.
Non-conventional in Portuguese | LILACS, BRISA, PIE | ID: biblio-1117634

ABSTRACT

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 16 artigos e 11 protocolos.


Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Betacoronavirus/drug effects , Antiviral Agents/therapeutic use , Technology Assessment, Biomedical , Immunoglobulins/therapeutic use , Vaccines/therapeutic use , Chloroquine/therapeutic use , Colchicine/therapeutic use , Cross-Sectional Studies/instrumentation , Cohort Studies , Interferon-alpha/therapeutic use , Tissue Plasminogen Activator/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Azithromycin/therapeutic use , Ritonavir/therapeutic use , Lopinavir/therapeutic use , Fibrinolytic Agents/therapeutic use , Hydroxychloroquine/therapeutic use , Anti-Bacterial Agents/therapeutic use
8.
Lima; Instituto Nacional de Salud; 27 jul. 2020.
Non-conventional in Spanish | LILACS, BRISA | ID: biblio-1104225

ABSTRACT

INTRODUCCIÓN: En diciembre del 2019 se identificó en Wuhan (China) una serie de pacientes con infecciones respiratorias que en algunos casos evolucionaban en una neumonía viral grave, entre el 1 al 5% de los casos requerían de cuidados intensivos. El 7 de enero del 2020, las autoridades chinas anunciaron a un "nuevo coronavirus" como el agente causante de estas infecciones. La OMS denomino a este virus Covid-19. Esta enfermedad se ha diseminado a todo el mundo, causando una gran repercusión social y económica. Actualmente no existe un tratamiento específico para la enfermedad, brindándose tratamiento de soporte para todos los casos. Se han administrado algunos fármacos específicos para tratar la enfermedad, pero no hay recomendaciones concluyentes. OBJETIVO: Revisar la literatura científica sobre las intervenciones farmacológicas para el tratamiento de la enfermedad por el coronavirus 2019 (COVID ­ 19). METODOLOGÍA: Se desarrolló una búsqueda electrónica en la base de datos Medline (a través de Pubmed). Para tal fin, se construyó una estrategia de búsqueda sistemática, utilizando términos del lenguaje natural y descriptores de lenguaje controlado, teniendo como fecha de búsqueda desde el 01 de diciembre de 2019 (mes donde se reportó los primeros casos de COVID-19 en China) hasta el 20 de marzo de 2020. Se incluyó únicamente estudios publicados en idioma español o inglés. RESULTADOS: Se identificaron 947 referencias potencialmente relevantes. Tras la remoción de duplicados, y lectura de títulos y resúmenes, se seleccionaron 43 referencias para lectura a texto completo. Finalmente, se seleccionaron 15 estudios que respondieron a la pregunta PICO de interés. CONCLUSIONES: No existe a la fecha, ninguna intervención farmacológica que haya demostrado ser efectivo y segura para tratamiento de COVID-19. La calidad de la evidencia para los desenlaces reportados por los ensayos clínicos donde se evaluó Favipiravir y Lopinavir/ritonavir fue calificada como baja (Es muy probable que nuevos estudios tengan un impacto importante en la confianza que se tiene en el resultado estimado y que estos puedan modificar el resultado. La calidad de la evidencia para los desenlaces reportados por el ensayos clínico donde se evaluó Hidroxicloroquina es Muy Baja (Cualquier resultado estimado es muy incierto). No se identificó evidencia concluyente respecto al uso de Lopinavir más interferón α2b, el único estudio encontrado correspondió a una serie de 10 pacientes. Asímismo, la evidencia encontrada respecto a la combinación de arbidol y lopinavir/ritonavir se basa en serie de casos, que son estudios con muchas limitaciones, por lo que sus resultados deben analizarse con cuidado. No se obtuvo evidencia concluyente sobre el uso de arbidol, esta se basa únicamente en series de casos, con un pequeño número de pacientes. No se obtuvo evidencia concluyente sobre el uso de interferón alfa, sólo se encontró un reporte de caso.(AU)


Subject(s)
Humans , Pneumonia, Viral/drug therapy , Interferons/therapeutic use , Interferon-alpha/therapeutic use , Coronavirus Infections/drug therapy , Ritonavir/therapeutic use , Lopinavir/therapeutic use , Hydroxychloroquine/therapeutic use , Technology Assessment, Biomedical , Health Evaluation
9.
Brasília; s.n; 11 jun. 2020.
Non-conventional in Portuguese | LILACS, BRISA, PIE | ID: biblio-1100320

ABSTRACT

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 15 artigos e 26 protocolos.


Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Betacoronavirus/drug effects , Technology Assessment, Biomedical , Immunoglobulins/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Heparin/therapeutic use , Interferon-alpha/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Mesenchymal Stem Cells , Hydroxychloroquine/therapeutic use , Anti-Bacterial Agents/therapeutic use
10.
Brasília; s.n; 8 jun. 2020.
Non-conventional in Portuguese | LILACS, BRISA, PIE | ID: biblio-1100298

ABSTRACT

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 13 artigos.


Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Betacoronavirus/drug effects , Acetylcysteine/therapeutic use , Technology Assessment, Biomedical , gamma-Globulins/therapeutic use , Immunoglobulins/therapeutic use , Methylprednisolone/therapeutic use , BCG Vaccine , Influenza Vaccines , Famotidine/therapeutic use , Autohemotherapy , Chloroquine/therapeutic use , Colchicine/therapeutic use , Interferon-alpha/therapeutic use , Ritonavir/therapeutic use , Pneumococcal Vaccines , Lopinavir/therapeutic use , Observational Study , Nitric Oxide/therapeutic use
12.
Article in English | WPRIM | ID: wpr-827441

ABSTRACT

OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).


Subject(s)
Administration, Inhalation , Adult , China , Coronavirus Infections , Diagnosis , Drug Therapy , Mortality , Dose-Response Relationship, Drug , Drug Administration Schedule , Drugs, Chinese Herbal , Female , Follow-Up Studies , Humans , Integrative Medicine , Interferon-alpha , Lopinavir , Male , Middle Aged , Pandemics , Pneumonia, Viral , Diagnosis , Drug Therapy , Mortality , Risk Assessment , Severe Acute Respiratory Syndrome , Diagnosis , Drug Therapy , Mortality , Severity of Illness Index , Survival Rate
13.
Article in English | WPRIM | ID: wpr-827079

ABSTRACT

OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).


Subject(s)
Administration, Inhalation , Adult , China , Coronavirus Infections , Diagnosis , Drug Therapy , Mortality , Dose-Response Relationship, Drug , Drug Administration Schedule , Drugs, Chinese Herbal , Female , Follow-Up Studies , Humans , Integrative Medicine , Interferon-alpha , Lopinavir , Male , Middle Aged , Pandemics , Pneumonia, Viral , Diagnosis , Drug Therapy , Mortality , Risk Assessment , Severe Acute Respiratory Syndrome , Diagnosis , Drug Therapy , Mortality , Severity of Illness Index , Survival Rate
14.
Chinese Journal of Biotechnology ; (12): 750-762, 2020.
Article in Chinese | WPRIM | ID: wpr-826901

ABSTRACT

PEGylation is considered one of the most successful techniques to improve the characteristics of protein drugs including to increase the circulating half-life of proteins in blood and to decrease their immunogenicity and antigenicity. One known PEG modification method is to attach PEG to the free amino group, typically at lysine residues or at the N-terminal amino acid with no selectivity, resulting in a heterogeneous product mixture. This lack of selectivity can present problems when a therapeutic PEGylated protein is being developed, because predictability of activity and manufacturing reproducibility are needed for regulatory approval. Enzymatic PEGylation of proteins is one route to overcome this limitation. Transglutaminases (TGase) are enzyme candidates for site-specific PEGylation. We use human interferon alpha 2a (IFN α2a) as a test case, and predict that the potential modification residues are Gln101 by computational approach as it contains 12 potential PEGylation sites. IFN α2a was PEGylated by Y shaped PEG40k-NH2 mediated by microbial transglutaminase. Our results show that the microbial transglutaminase mediated PEGylation of IFN α2a was site-specific only at the site of Gln101 in IFN α2a, yielding the single mono-conjugate PEG-Gln101-IFN α2a with a mass of 59 374.66 Da. Circular dichroism studies showed that PEG-Gln101-IFN α2a preserved the same secondary structures as native IFN α2a. As expected, the bioactivity and pharmacokinetic profile in rats of PEG-Gln101-IFN α2a revealed a significant improvement to unmodified IFN α2a, and better than PEGASYS.


Subject(s)
Animals , Antiviral Agents , Humans , Interferon alpha-2 , Metabolism , Interferon-alpha , Pharmacokinetics , Polyethylene Glycols , Pharmacokinetics , Protein Structure, Secondary , Rats , Recombinant Proteins , Pharmacokinetics , Pharmacology , Reproducibility of Results , Transglutaminases , Metabolism
15.
Cad. Saúde Pública (Online) ; 36(2): e00036619, 2020. graf
Article in English | LILACS | ID: biblio-1055632

ABSTRACT

Abstract: Cost-effectiveness analysis is essential in health decision making. Several countries use it as synthesis of evidence to incorporate health technologies. The protease inhibitors (PI) boceprevir (BOC) and telaprevir (TVR) are indicated for chronic hepatitis C treatment and were incorporated in guidelines worldwide. Pre-marketing clinical trials showed higher sustained virological response rates in relation to previous therapies, but the incorporation of PIs generated a significant financial impact. The aim of this study was to discuss the relevance of cost-effectiveness analysis through a study that involved the inclusion of PIs in a clinical protocol. The analysis was part of a real-life study that included patients infected with hepatitis C virus genotype 1 treated in a tertiary university hospital in Brazil. Triple therapies (TT) with ribavirin (RBV), peginterferon α-2a (Peg-INF α-2a) and BOC or TVR were compared to dual therapy with RBV and Peg-INF α-2a. Sensitivity analysis of the cost-effectiveness ratio indicated an 88.2% chance of TTs presenting a higher cost per cure. The incremental cost-effectiveness ratios (ICER) exceeded the Brazilian gross domestic product (GDP) per capita by three times in all proposed scenarios. The sensitivity of ICER showed an 88.4% chance of TT not being cost-effective. The impact of PI incorporation was negative and the conduct about this could have been different if a previous cost-effectiveness analysis had been conducted.


Resumo: A análise de custo-efetividade tem sido essencial para a tomada de decisões em saúde. Diversos países utilizam esse tipo de análise como síntese das evidências para incorporar as tecnologias em saúde. Os inibidores de protease (IPs) boceprevir (BOC) e telaprevir (TVR) são indicados para o tratamento da hepatite C crônica e foram incorporados nas diretrizes internacionais. Os ensaios clínicos pré-marketing demonstraram taxas mais altas de resposta virológica sustentada em relação às terapias anteriores, mas a incorporação dos IPs gerou um impacto financeiro significativo. O estudo teve como objetivo discutir a relevância da análise de custo-efetividade, através de um estudo que envolveu a inclusão de IPs em um protocolo clínico. A análise fez parte de um estudo de vida real que incluiu pacientes com infecção pelo vírus da hepatite C, genótipo 1, tratados em um hospital universitário terciário no Brasil. As terapias triplas (TTs) com ribavirina (RBV), peg-interferon α-2a (Peg-INF α-2a) e BOC ou TVR foram comparadas às terapias duplas com RBV e Peg-INF α-2a. A análise de sensibilidade da custo-efetividade indicou odds de 88,2% de TTs apresentarem custo mais elevado por paciente curado. Em todos os cenários propostos, as razões de custo-efetividade incremental (ICERs) superaram em três vezes o produto interno bruto (PIB) per capita brasileiro. A sensibilidade da ICER mostrou probabilidade de 88,4% das TTs não serem custo-efetivas. O impacto da incorporação dos IPs foi negativo, e a conduta teria sido diferente se tivesse sido realizada uma análise prévia de custo-efetividade.


Resumen: El análisis de coste-efectividad ha sido esencial para la toma de decisiones en salud. Diversos países utilizan este tipo de análisis como síntesis de evidencias para incorporar tecnologías en salud. Los inhibidores de proteasa (IPs) boceprevir (BOC) y telaprevir (TVR) se indican para el tratamiento de la hepatitis C crónica y fueron incorporados en directrices internacionales. Los ensayos clínicos pre-marketing demostraron tasas más altas de respuesta virológica sostenida, respecto a las terapias anteriores, pero la incorporación de los IPs generó un impacto financiero significativo. El objetivo del estudio fue discutir la relevancia del análisis de coste-efectividad, a través de un estudio que implicó la inclusión de IPs en un protocolo clínico. El análisis formó parte de un estudio de vida real que incluyó a pacientes con infección por el virus de la hepatitis C, genotipo 1, tratados en un hospital universitario terciario en Brasil. Las terapias triples (TTs) con ribavirina (RBV), peg-interferon α-2a (Peg-INF α-2a) y BOC o TVR se compararon con las terapias dobles con RBV y Peg-INF α-2a. El análisis de sensibilidad del coste-efectividad indicó odds de 88,2% de que las TTs presentaran un coste más elevado por paciente curado. En todos los escenarios propuestos, las razones de coste-efectividad incremental (ICERs) superaron tres veces el producto interno bruto (PIB) per cápita brasileño. La sensibilidad de la ICER mostró una probabilidad de que un 88,4% de las TTs no eran costo-efectivas. El impacto de la incorporación de los IPs fue negativo, y el resultado habría sido diferente si se hubiese realizado un análisis previo de coste-efectividad.


Subject(s)
Humans , Antiviral Agents/therapeutic use , Cost-Benefit Analysis , Hepatitis C, Chronic/drug therapy , Oligopeptides , Antiviral Agents/economics , Polyethylene Glycols , Ribavirin , Recombinant Proteins , Brazil , Proline/analogs & derivatives , Interferon-alpha , Hepacivirus , Quality-Adjusted Life Years , Hepatitis C, Chronic/economics , Drug Therapy, Combination , Interferon alpha-2 , Genotype
16.
Hematol., Transfus. Cell Ther. (Impr.) ; 41(2): 125-128, Apr.-June 2019. tab
Article in English | LILACS | ID: biblio-1012180

ABSTRACT

ABSTRACT We analyzed the management and outcomes of pregnancies of patients with chronic myeloid leukemia at a single center over fifteen years. Among the 203 CML female patients, there were ten pregnancies in seven women, all of them not planned. In three cases, the chronic myeloid leukemia diagnosis was made during pregnancy. Five patients received tyrosine kinase inhibitors in the first weeks of pregnancy and the drug was interrupted until delivery. One patient lost complete cytogenetic response, and two patients lost the hematological response. A patient with a stable major molecular response had two successful pregnancies without loss of response. There were four premature births. There were no maternal adverse events, fetal malformation or death. All patients received Interferon-alpha during gestation, and two received hydroxyurea for a short period. Leukapheresis was performed in two patients for hyperleukocytosis control. One patient with sickle cell disease died from disease progression six months after delivery. Conclusions: The tyrosine kinase inhibitors ministration should be interrupted during pregnancy. Patients should be advised to achieve a stable and deep molecular response if they plan to conceive, to avoid the risk of disease progression.


Subject(s)
Humans , Female , Pregnancy , Pregnancy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Interferon-alpha , Imatinib Mesylate , Dasatinib , Hydroxyurea
17.
Article in Chinese | WPRIM | ID: wpr-775079

ABSTRACT

OBJECTIVE@#To investigate the effect and molecular mechanism of interferon-α (INF-α) on the apoptosis of the mouse podocyte cell line MPC5 induced by hepatitis B virus X (HBx) protein.@*METHODS@#MPC5 cells were transfected with the pEX plasmid carrying the HBx gene. RT-PCR was used to measure the mRNA expression of HBx at different time points. MPC5 cells were divided into 4 groups: control group (MPC5 cells cultured under normal conditions), INF-α group (MPC5 cells cultured with INF-α), HBx group (MPC5 cells induced by HBx), and HBx+INF-α group (MPC5 cells induced by HBx and cultured with INF-α). After 48 hours of intervention under different experimental conditions, flow cytometry was used to measure the apoptosis of MPC5 cells, and quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression of slit diaphragm-related proteins (nephrin, CD2AP, and synaptopodin) and the cytoskeleton-related protein transient receptor potential cation channel 6 (TRPC6).@*RESULTS@#MPC5 cells transfected by pEX-HBx had the highest expression of HBx mRNA at 48 hours after transfection (P<0.05). Compared with the control, INF-α and HBx+INF-α groups, the HBx group had a significant increase in the apoptosis rate of MPC5 cells (P<0.05). Compared with the control and INF-α groups, the HBx group had significant reductions in the mRNA and protein expression of nephrin, synaptopodin, and CD2AP and significant increases in the mRNA and protein expression of TRPC6 (P<0.05). Compared with the HBx group, the HBx+INF-α group had significant increases in the mRNA and protein expression of nephrin, synaptopodin, and CD2AP and significant reductions in the mRNA and protein expression of TRPC6 (P<0.05).@*CONCLUSIONS@#INF-α can inhibit the apoptosis of podocytes induced by HBx, possibly through improving the abnormal expression of slit diaphragm-related proteins (CD2AP, nephrin, and synaptopodin) and cytoskeleton-related protein (TRPC6) induced by HBx.


Subject(s)
Animals , Apoptosis , Hepatitis B virus , Interferon-alpha , Mice , Podocytes , Trans-Activators
18.
Frontiers of Medicine ; (4): 238-249, 2019.
Article in English | WPRIM | ID: wpr-772707

ABSTRACT

The efficacy of salvage interferon-α (IFN-α) treatment was investigated in patients with unsatisfactory response to minimal residual disease (MRD)-directed donor lymphocyte infusion (DLI) (n = 24). Patients who did not become MRD-negative at 1 month after DLI were those with unsatisfactory response and were eligible to receive salvage IFN-α treatment within 3 months of DLI. Recombinant human IFN-α-2b injections were subcutaneously administered 2-3 times a week for 6 months. Nine (37.5%), 6 (25.0%), and 3 (12.5%) patients became MRD-negative at 1, 2, and > 2 months after the salvage IFN-α treatment, respectively. Two-year cumulative incidences of relapse and non-relapse mortality were 35.9% and 8.3%, respectively. Two-year probabilities of event-free survival, disease-free survival, and overall survival were 51.6%, 54.3%, and 68.0%, respectively. Outcomes of patients subjected to salvage IFN-α treatment after DLI were significantly better than those with persistent MRD without IFN-α treatment. Moreover, clinical outcomes were comparable between the salvage DLI and IFN-α treatment groups. Thus, salvage IFN-α treatment may help improve the outcome of patients with unsatisfactory responses to MRD-directed DLI and could be a potential salvage treatment for these patients after allogeneic hematopoietic stem cell transplantation.


Subject(s)
Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Beijing , Child , Child, Preschool , Female , Graft Survival , Graft vs Host Disease , Mortality , Hematopoietic Stem Cell Transplantation , Humans , Interferon-alpha , Therapeutic Uses , Leukemia, Myeloid, Acute , Mortality , Therapeutics , Lymphocyte Transfusion , Male , Middle Aged , Myelodysplastic Syndromes , Mortality , Therapeutics , Neoplasm, Residual , Recurrence , Salvage Therapy , Survival Analysis , Transplantation Conditioning , Transplantation, Homologous , Young Adult
19.
Article in Chinese | WPRIM | ID: wpr-772106

ABSTRACT

OBJECTIVE@#To evaluate the therapeutic effects of entecavir (ETV) and interferon- (IFN-) treatments for 48 weeks for chronic hepatitis B (CHB) in patients with different baseline alanine aminotransferase (ALT) levels.@*METHODS@#We retrospectively analyzed the data of 369 CHB patients receiving ETV and IFN- treatments for 48 weeks. We compared the virological response rates, HBsAg clearance, and HBsAg reduction between the patients receiving ETV and IFN- treatments with different baseline ALT levels[≤ 5×upper limits of normal (ULN) level (subgroup 1), 5-10×ULN (subgroup 2), and > 10× ULN (subgroup 3)].@*RESULTS@#In patients receiving ETV treatment, the virological response rate was 83.3% in subgroup 1, 91.4% in subgroup 2, and 95.5% in subgroup 3, as compared with 19.7%, 40%, and 42.9% in the 3 subgroups with IFN- treatment, respectively, showing significantly differences both among different subgroups with the same treatment and between the same subgroup with different treatments ( < 0.05). HBeAg clearance rates in the 3 subgroups were 8.3%, 16.7% and 35.5% in patients with ETV treatment and were 1.8%, 41.9%, and 38.1% in patients with IFN- treatment, respectively, showing significant differences among the 3 subgroups with the same treatment ( < 0.05); in the same subgroups with different treatments, the rates differed significantly only between subgroups 2 ( < 0.05). In ETV group, the rate of HBsAg reduction to below 200 IU/ml was 2.5% in subgroup 1 and 13.8% in subgroup 2, showing no significant difference between the two subgroups; in IFN- group, the rates were also similar between subgroups 1 and 2 (30.6% 33.3%, > 0.05); but the rates differed significantly between the same subgroups with different treatments ( < 0.05).@*CONCLUSIONS@#In all the subgroups with different baseline ALT levels, ETV treatment for 48 weeks results in significantly higher virological response rates than IFN- treatment in patients with CHB. In patients with a baseline ALT of 5-10 ×ULN, IFN- can result in a higher HBeAg clearance rate than ETV. In patients with comparable baseline ALT level, IFN- more effectively reduces HBsAg level than ETV. The patients with a relatively high baseline ALT level (> 5 × ULN) show better responses to both ETV and IFN- treatment than those with ALT level below 5×ULN. We thus recommend IFN- for patients with a baseline ALT of 5-10×ULN and ETV for patients with a baseline ALT either below 5 × ULN or beyond 10×ULN.


Subject(s)
Alanine Transaminase , Blood , Antiviral Agents , Therapeutic Uses , DNA, Viral , Guanine , Therapeutic Uses , Hepatitis B Surface Antigens , Blood , Hepatitis B e Antigens , Blood , Hepatitis B virus , Allergy and Immunology , Hepatitis B, Chronic , Drug Therapy , Allergy and Immunology , Virology , Humans , Interferon-alpha , Therapeutic Uses , Retrospective Studies , Time Factors , Treatment Outcome , Viral Load
20.
Chinese Journal of Biotechnology ; (12): 1029-1040, 2019.
Article in Chinese | WPRIM | ID: wpr-771825

ABSTRACT

To evaluate the optimal administration frequency for interferon-α (IFN-α) and the effect of its combined use with inactive virus on chicken flocks, the prokaryotic expression plasmid pET-22b-ChIFN-α was constructed and transferred into Escherichia coli BL21(DE3) host bacteria to induce the expression of chicken IFN-α and to harvest recombinant proteins inclusion bodies. The expression of recombinant chicken IFN-α was confirmed by SDS-PAGE, and the results demonstrated that the chicken IFN-α (20 kDa) was highly expressed using the prokaryotic expression vector with a concentration of 0.2 mg/mL in the medium. Chicken IFN-α was diluted to 2.5×10⁴ U/fowls and administered to immunized specific-pathogen-free chickens orally in combination with inactivated H9N2 subtype influenza virus. Chicken that received chicken IFN-α were safe after three repeated immunizations (96 h). In addition, chicken IFN-α could induce higher levels of antiviral-related inducible genes in peripheral blood, spleen, and thymus of chicken flocks. The results of a challenge assay revealed that the lowest detoxification rates of chicken IFN-α ranged from three to five days, suggesting a higher capacity to resist H9N2 subtype avian influenza virus. The present study obtained the optimal immune frequency and immunization period for chicken IFN-α to provide theoretical support for the optimal clinical application of IFN-α.


Subject(s)
Administration, Oral , Animals , Chickens , Humans , Influenza A Virus, H9N2 Subtype , Interferon-alpha , Virus Replication
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