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2.
Dermatol Online J ; 26(3)2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32609439

RESUMO

BACKGROUND: New treatment options for warts include intralesional wart injection with agents such as vitamin D, measles, mumps, and rubella (MMR) vaccine antigen, Bacillus Calmette-Guerin (BCG) antigen, and candida antigen but there have been limited studies to compare their efficacies. OBJECTIVE: The purpose of this systematic review is to compare the efficacy and safety of injectable agents used for the treatment of warts. METHODS: A PubMed search included terms "intralesional wart therapy," "wart injection" and "verruca injection." Articles reviewed were published over 10 years. RESULTS: A total of 43 articles were reviewed; 30 covered studies with more than 10 participants and 13 were case reports, case series, and reviews. In comparison studies intralesional agents have equal or superior efficacy (66%-94.9%) compared to first-line salicylic acid or cryotherapy (65.5-76.5%). One advantage of intralesional injections is the rate of complete resolution of distant warts. LIMITATIONS: Each study varied in their agents, treatment interval, and treatment dose, making comparisons difficult. CONCLUSIONS: Intralesional wart injections are safe, affordable, and efficacious treatments for warts. Physicians should consider intralesional injections for patients with refractory warts, multiple warts, or warts in sensitive areas.


Assuntos
Injeções Intralesionais , Verrugas/tratamento farmacológico , Ácido Aminolevulínico/administração & dosagem , Antibacterianos/administração & dosagem , Antivirais/administração & dosagem , Vacina BCG/administração & dosagem , Vacinas Bacterianas/administração & dosagem , Humanos , Interferon-alfa/administração & dosagem , Mycobacterium , Tuberculina/administração & dosagem , Vitamina D/administração & dosagem
3.
Int J Nanomedicine ; 15: 3669-3680, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547021

RESUMO

Introduction: The exhaustion and poor homing of activated lymphocytes are critical obstacles in adoptive cell immunotherapy for solid tumors. In order to effectively deliver immune cells into tumors, we encapsulated interferon-α2b (IFN-α2b) into macroporous hydrogels as an enhancement factor and utilized low-dose irradiation (LDI) as a tumoral attractor of T cells. Methods: Hydroxypropyl cellulose hydrogels were prepared by irradiation techniques, and the cross-sectional microstructure was characterized by scanning electron microscopy. The synergistic antitumor mechanism of combination of IFN-α2b and CIK cells was evaluated by detecting the expression of activation marker CD69 on CIK cell surface and IFN-γ production by CIK cells. The in vivo antitumor activity of IFN-α2b-incorporated hydroxypropyl cellulose hydrogels combined with CIK and radiation was evaluated in an MKN-45 xenografted nude mice model. Results: The bioactivity of IFN-α2b was well maintained in ultraviolet-reactive, rapidly cross-linkable hydroxypropyl cellulose hydrogels. In vitro studies demonstrated IFN-α2b-activated T cells, as evidenced by upregulating early activation marker CD69 and secretion inflammatory cytokine IFN-γ. In vivo real-time image showed our hydrogels kept a higher amount of drug delivery at the tumor site for a long time compared with free drug injection. Low-dose irradiation promoted T cell accumulation and infiltration in subcutaneous tumors. Combination of IFN-α2b-loaded hydrogels (Gel-IFN) with T cells and LDI exhibited higher efficacy to eradicate human gastric cancer xenograted tumors with less proliferating cells and more necrotic regions compared with IFN-α2b or T cells alone. Discussion: HPC hydrogels kept the activity of IFN-α2b and stably release of IFN-α2b to stimulate T cells for a long time. At the same time, low-dose radiation recruits T cells into tumors. This innovative integration mode of IFN-α2b-loaded hydrogels and radiotherapy offers a potent strategy to improve the therapeutic outcome of T cell therapy.


Assuntos
Antineoplásicos/uso terapêutico , Reagentes para Ligações Cruzadas/química , Hidrogéis/química , Interferon-alfa/uso terapêutico , Luz , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/radioterapia , Linfócitos T/imunologia , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Celulose/análogos & derivados , Celulose/química , Relação Dose-Resposta à Radiação , Elétrons , Humanos , Interferon-alfa/farmacologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Linfócitos T/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Front Immunol ; 11: 1061, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574262

RESUMO

The global pandemic of COVID-19 cases caused by infection with SARS-CoV-2 is ongoing, with no approved antiviral intervention. We describe here the effects of treatment with interferon (IFN)-α2b in a cohort of confirmed COVID-19 cases in Wuhan, China. In this uncontrolled, exploratory study, 77 adults hospitalized with confirmed COVID-19 were treated with either nebulized IFN-α2b (5 mU b.i.d.), arbidol (200 mg t.i.d.) or a combination of IFN-α2b plus arbidol. Serial SARS-CoV-2 testing along with hematological measurements, including cell counts, blood biochemistry and serum cytokine levels, and temperature and blood oxygen saturation levels, were recorded for each patient during their hospital stay. Treatment with IFN-α2b with or without arbidol significantly reduced the duration of detectable virus in the upper respiratory tract and in parallel reduced duration of elevated blood levels for the inflammatory markers IL-6 and CRP. These findings suggest that IFN-α2b should be further investigated as a therapy in COVID-19 cases.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Interferon-alfa/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , China , Estudos de Coortes , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Citocinas/sangue , Quimioterapia Combinada , Feminino , Humanos , Indóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Fatores Sexuais
5.
Pol Merkur Lekarski ; 48(285): 147-151, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32564036

RESUMO

Every year, 3-4 million people become infected with HCV, most of them are asymptomatic. In more than 20-30 years from infection, it leads to 10-20% of patients with cirrhosis, followed by hepatocellular carcinoma. Cardiological complications of the antiviral treatment are relatively rare, but force us to take additional diagnostic or discontinuation of therapy. AIM: The aim of study was to assess the cardiovascular safety of chronic hepatitis C treatment of genotype 1 in a triple regimen containing pegylated interferon-α in combination with ribavirin and boceprevir based on analysis of 24-hour ECG Holer monitoring, as well as changes in the concentration of cardiac fraction of fatty acid binding proteins (h-FABP). MATERIALS AND METHODS: 14 hepatitis C patients and 15 healthy people were included. The participants had an ambulatory 24-hour ECG-Holter recording at home condition and the determined level of h-FABP at baseline, after 4 and 12-16 weeks of treatment and 2 weeks after the end of therapy. The HRV parameters, AC/DC and QTc was calculated. RESULTS: At baseline there were no statistically significant differences in the HRV parameters, DC/AC, and QTc-interval. Absolute DC/AC values, HRV parameters: SDNN-ix, rMSDD, TP, HF, VLF and ULF were significantly lower in the treated group. LF/HF ratio was higher in this group (p=0.047). These changes persisted during the follow-up and disappeared after treatment. QTc was the shortest in the 4th week and withdrew during further follow-up. H-FABP levels did not differ statistically significantly between any subsequent determinations. CONCLUSIONS: At baseline there were no statistically significant differences in the HRV parameters, DC/AC, and QTc-interval. Absolute DC/AC values, HRV parameters: SDNN-ix, rMSDD, TP, HF, VLF and ULF were significantly lower in the treated group. LF/HF ratio was higher in this group (p=0.047). These changes persisted during the follow-up and disappeared after treatment. QTc was the shortest in the 4th week and withdrew during further follow-up. H-FABP levels did not differ statistically significantly between any subsequent determinations.


Assuntos
Eletrocardiografia Ambulatorial , Hepatite C Crônica , Interferon-alfa , Polietilenoglicóis , Antivirais/uso terapêutico , Biomarcadores/análise , Proteína 3 Ligante de Ácido Graxo/análise , Frequência Cardíaca , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico
6.
Medicine (Baltimore) ; 99(25): e20820, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569231

RESUMO

INTRODUCTION: Interferon alpha (IFNα) has been used for a long time in patients with functionally active neuroendocrine tumors (NET). However, due to the unfavorable toxicity profile of interferon, the perceived limited efficacy as well as the development of novel substances, IFNα is only used sparingly in the treatment of NET to date. PATIENTS CONCERNS AND DIAGNOSIS: We describe the case of a 63-year-old male patient with highly differentiated, functional NET of the ileum and synchronous liver metastasis. INTERVENTIONS: After failure of classical therapies including dose-intensified somatostatin analog treatment and palliative primary tumor resection, a therapy with pegylated IFNα2a (135 µg/wk) was initiated. Following this treatment, the patient fully recovered from signs of hypersecretion and demonstrated an impressive tumor response. OUTCOMES: Thirty months after initiating IFNα, the patient is still free of clinical symptoms and shows a sustained tumor response. Notably, no relevant side effects were observed. CONCLUSION: Our case report supports the use of IFNα in patients with functional NET refractory to classical treatments.


Assuntos
Neoplasias do Íleo/tratamento farmacológico , Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Tumores Neuroendócrinos/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Humanos , Neoplasias do Íleo/patologia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Proteínas Recombinantes/uso terapêutico , Falha de Tratamento , Resultado do Tratamento
7.
Brasília; s.n; 8 jun. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1100298

RESUMO

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.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Acetilcisteína/uso terapêutico , Avaliação da Tecnologia Biomédica , gama-Globulinas/uso terapêutico , Imunoglobulinas/uso terapêutico , Metilprednisolona/uso terapêutico , Vacina BCG , Vacinas contra Influenza , Famotidina/uso terapêutico , Auto-Hemoterapia , Cloroquina/uso terapêutico , Colchicina/uso terapêutico , Interferon-alfa/uso terapêutico , Ritonavir/uso terapêutico , Vacinas Pneumocócicas , Lopinavir/uso terapêutico , Estudo Observacional , Óxido Nítrico/uso terapêutico
8.
Brasília; s.n; 11 jun. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1100320

RESUMO

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.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Avaliação da Tecnologia Biomédica , Imunoglobulinas/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Heparina/uso terapêutico , Interferon-alfa/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Células-Tronco Mesenquimais , Hidroxicloroquina/uso terapêutico , Antibacterianos/uso terapêutico
9.
Antiviral Res ; 179: 104811, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32360182

RESUMO

There is an urgent need to identify antivirals to curtail the COVID-19 pandemic. Herein, we report the sensitivity of SARS-CoV-2 to recombinant human interferons α and ß (IFNα/ß). Treatment with IFN-α or IFN-ß at a concentration of 50 international units (IU) per milliliter reduces viral titers by 3.4 log or over 4 log, respectively, in Vero cells. The EC50 of IFN-α and IFN-ß treatment is 1.35 IU/ml and 0.76 IU/ml, respectively, in Vero cells. These results suggest that SARS-CoV-2 is more sensitive than many other human pathogenic viruses, including SARS-CoV. Overall, our results demonstrate the potential efficacy of human Type I IFN in suppressing SARS-CoV-2 infection, a finding which could inform future treatment options for COVID-19.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Interferon Tipo I/farmacologia , Pneumonia Viral/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Animais , Chlorocebus aethiops , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Humanos , Imunidade Inata , Interferon-alfa/farmacologia , Interferon beta/farmacologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Proteínas Recombinantes/farmacologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Células Vero , Carga Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
10.
Cytokine Growth Factor Rev ; 53: 38-42, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32360420

RESUMO

Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/patologia , Citocinas/sangue , Insuficiência de Múltiplos Órgãos/mortalidade , Pneumonia Viral/patologia , Corticosteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Terapia de Substituição Renal Contínua/métodos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Citocinas/biossíntese , Feminino , Humanos , Interferon-alfa/uso terapêutico , Masculino , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/patologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos
11.
mSphere ; 5(3)2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404512

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2, or SARS-CoV-2) is the cause of the respiratory infection known as COVID-19. From an immunopathological standpoint, coronaviruses such as SARS-CoV-2 induce increased levels of a variety of T-helper 1 (Th1) and inflammatory cytokines and chemokines, including interleukin-1 (IL-1), IL-6, CCL2 protein, and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti-inflammatory and/or Th2 immune response to counteract COVID-19 symptoms and severity. This report briefly describes the following four unconventional but commercially accessible immunomodulatory agents that can be employed in clinical trials to evaluate their effectiveness at alleviating disease symptoms and severity: low-dose oral interferon alpha, microdose DNA, low-dose thimerosal, and phytocannabinoids.


Assuntos
Canabinoides/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , DNA/uso terapêutico , Imunomodulação , Interferon-alfa/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Timerosal/uso terapêutico , Betacoronavirus , Citocinas/imunologia , Humanos , Pandemias , Compostos Fitoquímicos/uso terapêutico
12.
J Clin Virol ; 128: 104425, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32446167

RESUMO

BACKGROUND: At present, coronavirus disease 2019 (COVID-19) has spread in many countries. We conducted this study to help pediatricians understand the conditions of COVID-19 in children. METHODS: We retrospectively summarized the characteristics, treatment and outcomes of pediatric cases in Wuhan Children's Hospital which was the only designated hospital for children with COVID-19 in Hubei Province. A Cox proportional hazards regression analysis was used to evaluate factors associated with clinical outcomes. RESULTS: As of February 29, 75 children had been discharged, of which only one was has severe pneumonia and one was critical cases. Children younger than 2 years were more susceptible to COVID-19. All patients have received interferon-α nebulization, and eight cases including the severe and critical cases were co-administrated ribavirin. Five patients with mild pneumonia were given arbidol. Twenty-three patients were given traditional Chinese medicine (TCM). The average length of stay (LOS) and the time of SARS-CoV-2 clearance were 10.57 and 6.39 days, respectively. None of the factors was associated with LOS or time of SARS-CoV-2 clearance. CONCLUSIONS: The severity of COVID-19 in pediatric cases were milder than adults. The efficacy of the antiviral therapy in children with COVID-19 remains to be evaluated.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Suscetibilidade a Doenças , Pneumonia Viral/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , China , Infecções por Coronavirus/virologia , Feminino , Hospitais Pediátricos , Humanos , Lactente , Interferon-alfa/administração & dosagem , Tempo de Internação , Masculino , Pandemias , Pediatras , Pneumonia Viral/virologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Ribavirina/administração & dosagem , Índice de Gravidade de Doença
14.
Expert Rev Anti Infect Ther ; 18(7): 617-624, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32362193

RESUMO

INTRODUCTION: The novel coronavirus (COVID-19) is currently in epidemic stage. After large-scale interpersonal infection, asymptomatic patients appear. Whether asymptomatic patients are contagious or not and whether they need medication are the arguments among clinical experts. AREAS COVERED: This paper reports a special asymptomatic couple with COVID-19, of which the male patient is an intercity bus driver but has not induced confirmed infection of his 188 passengers. The patients were treated with four combinations of lopinavir/ritonavir tablets, arbidol tablets, Lianhuaqingwen granules, and recombinant human interferon-α2b (IFN-α2b) injection via aerosol. Their clinical characteristics and medication were summarized and analyzed. EXPERT OPINION: The two asymptomatic patients far away from Wuhan did not seem to be highly contagious. They improved obviously, after treatment with the quadruple therapy, but the effective drug is still unknown. It should be noted that lopinavir/ritonavir tablets have many drug interactions and are the most likely drugs to cause hyperlipidemia and hyperglycemia in these two patients. IFN-α2b is more effective in the early stage of virus infection. Arbidol instruction dose may not be sufficient to inhibit the novel coronavirus in vivo. The evidence-based medicine of Lianhuaqingwen granules for treating various viral infections is just based on Chinese patients.


Assuntos
Infecções Assintomáticas , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Indóis/administração & dosagem , Interferon-alfa/administração & dosagem , Lopinavir/administração & dosagem , Masculino , Pessoa de Meia-Idade , Pandemias , Ritonavir/administração & dosagem
15.
Isr Med Assoc J ; 22(5): 320-325, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32378826

RESUMO

BACKGROUND: Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Several viral and host factors related to viral response have been reported in the era of treatment with pegylated (PEG)-interferon and ribavirin. OBJECTIVES: To quantify histological findings from patients with chronic HCV using computerized morphometry and to investigate whether the results can predict response to medical treatment with peg-interferon and ribavirin. METHODS: We followed 58 patients with chronic HCV infection with METAVIR score F1 and F2 in our liver unit who were grouped according to treatment response sustained viral response (SVR) and non-SVR. Liver needle biopsies from these patients were evaluated and histological variables, such as inflammatory cells, collagen fibers and liver architecture, were quantified using computerized morphometrics. The pathologist who performed the histomorphometric analysis was blinded to previous patient clinical and histological information. RESULTS: Histomorphometric variables including the density of collagen fibers were collected. The number of inflammatory cells in the portal space and textural variable were found to be statistically significant and could be used together in a formula to predict response to treatment, with a sensitivity of 93% and a 100% specificity. CONCLUSIONS: Histomorphometry may help to predict a patient's response to treatment at an early stage.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/patologia , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento
16.
Drugs Today (Barc) ; 56(3): 195-202, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32282866

RESUMO

Ropeginterferon alfa-2b is a novel mono-PEGylated alfa interferon. It is the first interferon approved for the treatment of patients with polycythemia vera (PV) and the first and only approved treatment for PV independent of previous hydroxyurea exposure. In contrast to other interferons, the drug has to be subcutaneously injected every 2 weeks only, with intervals of 4 weeks being possible after prolonged use. It is generally well tolerated and can lead to deep molecular responses. In this article, we provide a review of available preclinical and clinical data of ropeginterferon alfa-2b leading to its E.U. approval and give an outlook on future clinical trials involving this drug.


Assuntos
Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Policitemia Vera/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Humanos , Hidroxiureia , Interferon alfa-2/administração & dosagem , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico
17.
Parasitol Res ; 119(5): 1641-1652, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32285266

RESUMO

Clonorchis sinensis (C. sinensis) can induce a food-borne parasitic disease (clonorchiasis). Numerous studies have analyzed functional proteins, immunologic factors, pro-inflammatory cytokines, and cell signaling transduction that promote the development of clonorchiasis. In a previous study, it was shown that C. sinensis adult-derived total protein (CsTP) might be involved in the pathogenesis and development of liver fibrosis via bringing about Th2 immune response. In the present study, further investigation of CsTP on cellular function and inflammatory effect in vitro and in vivo has been elicited. CsTP induced inflammation and autophagy as evidenced by upregulation of TNF-α, IFN-γ, and autophagic markers LC3B and P62. Exposed to CsTP upregulated the antiapoptotic gene Bcl-2 expression, diminished the apoptosis induced by H2O2, but promoted the proliferation and migration of LX-2 cells in proper concentration range. Additionally, the protein levels of p-AKT and p-mTOR were repressed in response to CsTP, suggesting a correlation of blocking the activation of mTOR/AKT signaling pathway. These results revealed that CsTP might exacerbate hepatic pathological changes by regulating cell proliferation, apoptosis, autophagy, and inflammation in the liver and LX-2 cells. Some effects might be partially involved in the mTOR and AKT pathways.


Assuntos
Apoptose/fisiologia , Clonorquíase/patologia , Clonorchis sinensis/patogenicidade , Cirrose Hepática/patologia , Proteínas de Protozoários/metabolismo , Animais , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Clonorquíase/parasitologia , Clonorchis sinensis/genética , Citocinas/metabolismo , Doenças Transmitidas por Alimentos/parasitologia , Humanos , Peróxido de Hidrogênio/metabolismo , Inflamação/patologia , Interferon-alfa/metabolismo , Cirrose Hepática/parasitologia , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
18.
PLoS One ; 15(4): e0230893, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32275726

RESUMO

BACKGROUND AND AIMS: Sustained off-treatment immune control is achievable in a proportion of patients with chronic hepatitis B treated with peginterferon alfa-2a. We evaluated on-treatment predictors of hepatitis B surface antigen (HBsAg) clearance 3 years after peginterferon alfa-2a treatment and determined the incidence of hepatocellular carcinoma. METHODS: A prospective, international, multicenter, observational study in patients with chronic hepatitis B who have been prescribed peginterferon alfa-2a (40KD) in a real-world setting. The primary endpoint was HBsAg clearance after 3 years' follow-up. RESULTS: The modified intention-to-treat population comprised 844 hepatitis B e antigen (HBeAg)-positive patients (540 [64%] completed 3 years' follow-up), and 872 HBeAg-negative patients (614 [70%] completed 3 years' follow-up). At 3 years' follow-up, HBsAg clearance rates in HBeAg-positive and HBeAg-negative populations, respectively, were 2% (16/844) and 5% (41/872) in the modified intention-to-treat population and 5% [16/328] and 10% [41/394] in those with available data. In HBeAg-positive patients with data, Week 12 HBsAg levels <1500, 1500-20,000, and >20,000 IU/mL were associated with HBsAg clearance rates at 3 years' follow-up of 11%, 1%, and 5%, respectively (Week 24 predictability was similar). In HBeAg-negative patients with available data, a ≥10% decline vs a <10% decline in HBsAg at Week 12 was associated with HBsAg clearance rates of 16% vs 4%. Hepatocellular carcinoma incidence was lower than REACH-B (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B) model predictions. CONCLUSIONS: Sustained off-treatment immune control is achieved with peginterferon alfa-2a in a real-world setting. HBsAg clearance 3 years after completion of peginterferon alfa-2a can be predicted on the basis of on-treatment HBsAg kinetics.


Assuntos
Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Internacionalidade , Polietilenoglicóis/uso terapêutico , Adulto , Feminino , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos E da Hepatite B/metabolismo , Hepatite B Crônica/metabolismo , Humanos , Interferon-alfa/efeitos adversos , Masculino , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Segurança , Resultado do Tratamento
19.
Pharmacotherapy ; 40(5): 416-437, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32259313

RESUMO

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID-19) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacologic management of patients with COVID-19. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immunomodulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS-CoV-2. Critically ill patients with COVID-19 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID-19, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic.


Assuntos
Antivirais/administração & dosagem , Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Imunomodulação , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Corticosteroides , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/análogos & derivados , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Azetidinas/administração & dosagem , Azetidinas/efeitos adversos , Betacoronavirus , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Infecções por Coronavirus/terapia , Combinação de Medicamentos , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Imunização Passiva , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Nelfinavir/administração & dosagem , Nelfinavir/efeitos adversos , Pandemias , Ribavirina/administração & dosagem , Ribavirina/efeitos adversos , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos
20.
J Chin Med Assoc ; 83(6): 534-536, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32243270

RESUMO

The emerging outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 continues to spread all over the world. Agents or vaccines of proven efficacy to treat or prevent human coronavirus infection are in urgent need and are being investigated vigorously worldwide. This review summarizes the current evidence of potential therapeutic agents, such as lopinavir/ritonavir, remdesivir, favipiravir, chloroquine, hydroxychloroquine, interferon, ribavirin, tocilizumab, and sarilumab. More clinical trials are being conducted for further confirmation of the efficacy and safety of these agents in treating COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Humanos , Hidroxicloroquina/uso terapêutico , Interferon-alfa/uso terapêutico , Lopinavir/uso terapêutico , Pandemias , Ritonavir/uso terapêutico
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