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1.
Immunopharmacol Immunotoxicol ; 43(6): 644-650, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34698601

RESUMO

BACKGROUND: The current outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread throughout the world. During treatment, we found that the majority of patients had a decrease in hemoglobin (Hb). Interferon-α2b (IFN-α2b) was the primary suspected drug that was related to Hb reduction. Thus, the study aimed to investigate whether IFN-α2b could induce Hb reduction in severe patients with COVID-19 and its potential mechanism. MATERIAL AND METHODS: A total of 50 patients who were admitted to the First Affiliated Hospital of Harbin Medical University with severe COVID-19 infection were enrolled from February 12th to 24th, 2020. The demographics, baseline characteristics, clinical data, and therapeutic regimen were collected retrospectively. The patients were divided into two groups according to the declined use of IFN-α2b on day 14. The Hb levels on admission, day 7, day14, and day 21 were collected and analyzed. The primary endpoint was the level of Hb on day 21. RESULTS: A total of 31 patients in the IFN-stop group and 19 patients in the non-IFN-stop group were reviewed. The age, gender, comorbidities, clinical symptoms, nutritional status, disease severity, complications, and other factors of the patients were compared, no difference was found between the IFN-stop group and the non-IFN-stop group. The Hb levels of all patients significantly decreased on day 7 compared with that on admission (p < .0001). In the IFN-stop group, the Hb level was increased in 7 days after IFN-α2b was stopped (p = .0008), whereas no difference was found between day 14 and day 21 in the non-IFN-stop group (p = .3152). CONCLUSIONS: IFN-α2b was associated with Hb reduction in the treatment of severe patients of COVID-19. Clinicians should be aware of the high incidence of Hb reduction for patients treated by IFN-α2b.


Assuntos
Anemia/induzido quimicamente , Antivirais/efeitos adversos , COVID-19/tratamento farmacológico , Interferon alfa-2/efeitos adversos , SARS-CoV-2/efeitos dos fármacos , Administração por Inalação , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/diagnóstico , Antivirais/administração & dosagem , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/virologia , China , Feminino , Hemoglobinas/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Interferon alfa-2/administração & dosagem , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Estudos Retrospectivos , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
2.
Biomacromolecules ; 22(11): 4521-4534, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34643378

RESUMO

Conjugation of biologics with polymers modulates their pharmacokinetics, with polyethylene glycol (PEG) as the gold standard. We compared alternative polymers and two types of cyclooctyne linkers (BCN/DBCO) for bioconjugation of interferon-α2a (IFN-α2a) using 10 kDa polymers including linear mPEG, poly(2-ethyl-2-oxazoline) (PEtOx), and linear polyglycerol (LPG). IFN-α2a was azide functionalized via amber codon expansion and bioorthogonally conjugated to all cyclooctyne linked polymers. Polymer conjugation did not impact IFN-α2a's secondary structure and only marginally reduced IFN-α2a's bioactivity. In comparison to PEtOx, the LPG polymer attached via the less rigid cyclooctyne linker BCN was found to stabilize IFN-α2a against thermal stress. These findings were further detailed by molecular modeling studies which showed a modulation of protein flexibility upon PEtOx conjugation and a reduced amount of protein native contacts as compared to PEG and LPG originated bioconjugates. Polymer interactions with IFN-α2a were further assessed via a limited proteolysis (LIP) assay, which resulted in comparable proteolytic cleavage patterns suggesting weak interactions with the protein's surface. In conclusion, both PEtOx and LPG bioconjugates resulted in a similar biological outcome and may become promising PEG alternatives for bioconjugation.


Assuntos
Polietilenoglicóis , Polímeros , Glicerol , Interferon alfa-2 , Proteínas Recombinantes/genética
3.
Int J Infect Dis ; 111: 281-287, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34428542

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of pegylated interferon alpha-2b (PEG IFN-α2b) administered in conjunction with the standard of care (SOC) in subjects with moderate coronavirus disease-19 (COVID-19). METHODS: In this study, adult subjects with confirmed moderate COVID-19 were randomized in a 1:1 ratio to receive either PEG IFN-α2b + SOC or SOC alone. The primary endpoint was a two-point improvement in clinical status on Day 11, measured by the World Health Organization's seven-point ordinal scale. RESULTS: Of 250 subjects, 120 were randomized to the PEG IFN-α2b + SOC arm and 130 were randomized to the SOC arm. The results for the PEG IFN + SOC arms vs the SOC arm for the proportion of subjects with a two-point improvement in the seven-point ordinal scale were 80.36% vs 68.18% (P=0.037) on Day 8, 91.60% vs 92.56% (P=0.781) on Day 11, and 94.12% vs 95.93% (P=0.515) on Day 15. There was a time-dependent decrease in the biomarkers in both arms, and no clinically significant changes in laboratory parameters. The safety profile was similar in both arms. CONCLUSION: PEG IFN-α2b induced early viral clearance, improved the clinical status, and decreased the duration of supplemental oxygen. It provides a viable treatment option and can limit the spread of severe acute respiratory syndrome coronavirus-2.


Assuntos
COVID-19 , Adulto , Antivirais/efeitos adversos , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes , SARS-CoV-2 , Resultado do Tratamento
4.
BMC Infect Dis ; 21(1): 885, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34461841

RESUMO

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) posed an enormous threat to public health. The use of antiviral drugs in patients with this disease have triggered people's attentions. Whether interferon alfa-2b or lopinavir/ritonavir (LPV/r) plus interferon alfa-2b treatment can against SARS-CoV-2 was unknown. The objectives of this study was to evaluate the efficacy and safety of interferon alfa-2b and LPV/r plus interferon alfa-2b for SARS-CoV-2 infection in adult patients hospitalized with COVID-19. METHODS: This is a retrospective cohort study of 123 patients confirmed SARS-CoV-2 infection by PCR on nasopharyngeal swab and symptoms between Jan. 13 and Apr. 23, 2020. All patients received standard supportive care and regular clinical monitoring. Patients were assigned to standard care group (n = 12), interferon alfa-2b group (n = 44), and combination LPV/r plus interferon alfa-2b group (n = 67). The primary endpoints were duration of required oxygen support and virus clearance time. Associations between therapies and these outcomes were assessed by Cox proportional hazards regression. RESULTS: Baseline clinical characteristics were not significantly different among the three groups (P > 0.05). No significant associations were observed between LPV/r/interferon alfa-2b and faster SARS-CoV-2 RNA clearance (HR, 0.85 [95% confidence interval (CI) 0.45-1.61]; P = 0.61 in interferon alfa-2b group vs HR, 0.59 [95% CI 0.32-1.11]; P = 0.10 in LPV/r plus interferon alfa-2b group). Individual therapy groups also showed no significant association with duration of required oxygen support. There were no significant differences among the three groups in the incidence of adverse events (P > 0.05). CONCLUSIONS: In patients with confirmed SARS-CoV-2 infection, no benefit was observed from interferon alfa-2b or LPV/r plus interferon alfa-2b treatment. The findings may provide references for treatment guidelines of patients with SARS-CoV-2 infection.


Assuntos
COVID-19 , Ritonavir , Adulto , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Combinação de Medicamentos , Humanos , Interferon alfa-2 , Lopinavir/uso terapêutico , RNA Viral , Estudos Retrospectivos , Ritonavir/uso terapêutico , SARS-CoV-2
5.
Artigo em Inglês | MEDLINE | ID: mdl-34438247

RESUMO

A sensitive method for determination of PEG-IFN-α-2b in human serum was developed using ultra performance liquid chromatography aligned with tandem mass spectrometric detection. A two-treatment, two-period, cross over study was conducted to establish bioequivalence between a test and reference formulation and the method was successfully applied to the quantification of PEG-IFN-α-2b in serum samples of this clinical study. The sample concentrations obtained from LC-MS/MS technique were compared with the concentrations obtained from ELISA technique. PEG-IFN-α-2b was isolated from serum using protein precipitation technique with isopropyl alcohol followed by overnight tryptic digestion. The signature peptide formed as result of tryptic digestion was separated on a chromatograph and detected using a mass detector. The mass transition ion-pair of m/z 741.3 → 1047.1 for PEG-IFN-α-2b and m/z 387.4 → 205.2 for internal standard were used for MS/MS detection. The sample extraction involves a simple protein precipitation method followed by tryptic digestion of the supernatant and further sample cleanup was not needed. The method has been validated over a linear range of 1.028-3200 ng/mL with a correlation coefficient ≥ 0.99. The precision (%RSD) was 5.52 to 7.90 and accuracy (%RE) was within -1.80 to 1.68. The total run time was 22.0 min. The sensitivity of LC-MS/MS method was 1.0 ng/ml which was found to be more sensitive than ELISA and resulted in improving the overall study data by being able to quantify all the samples without any below LOQ results helping to further improve the pharmacokinetic modeling. This improved method is a promising anti-body free LC-MS/MS based methodology for estimation of PEG-IFN-α-2b in human serum and may be applied for other such pegylated molecules.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Interferon alfa-2/sangue , Interferon-alfa/sangue , Fragmentos de Peptídeos/sangue , Espectrometria de Massas em Tandem/métodos , Estudos Cross-Over , Humanos , Interferon alfa-2/farmacocinética , Interferon-alfa/farmacocinética , Limite de Detecção , Modelos Lineares , Fragmentos de Peptídeos/metabolismo , Polietilenoglicóis/farmacocinética , Proteínas Recombinantes/sangue , Proteínas Recombinantes/farmacocinética , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray/métodos , Equivalência Terapêutica , Tripsina/metabolismo
6.
J Mol Biol ; 433(19): 167184, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34364876

RESUMO

Previously evidence was presented that the single-nucleotide polymorphism rs1344706 located in an intronic region of the ZNF804A gene is associated with reduced transcript levels in fetal brains. This genetic variation in the gene encoding the zinc-finger protein ZNF804A is associated with schizophrenia (SZ) and bipolar disorder. Currently, the molecular and cellular function of ZNF804A is unclear. Here, we generated a high-confidence protein-protein interaction (PPI) network for ZNF804A using a combination of yeast two-hybrid and bioluminescence-based PPI detection assays, directly linking 15 proteins to the disease-associated target protein. Among the top hits was the signal transducer and activator of transcription 2 (STAT2), an interferon-regulated transcription factor. Detailed mechanistic studies revealed that STAT2 binds to the unstructured N terminus of ZNF804A. This interaction is mediated by multiple short amino acid motifs in ZNF804A but not by the conserved C2H2 zinc-finger domain, which is also located at the N terminus. Interestingly, investigations in HEK293 cells demonstrated that ZNF804A and STAT2 both co-translocate from the cytoplasm into the nucleus upon interferon (IFN) treatment. Furthermore, a concentration-dependent effect of ZNF804A overproduction on STAT2-mediated gene expression was observed using a luciferase reporter, which is under the control of an IFN-stimulated response element (ISRE). Together these results indicate the formation of ZNF804A:STAT2 protein complex and its translocation from the cytoplasm into the nucleus upon IFN stimulation, suggesting that it may function as a signal transducer that activates IFN-mediated gene expression programs.


Assuntos
Interferon alfa-2/farmacologia , Fatores de Transcrição Kruppel-Like/metabolismo , Fator de Transcrição STAT2/metabolismo , Esquizofrenia/genética , Motivos de Aminoácidos , Sítios de Ligação , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Fatores de Transcrição Kruppel-Like/química , Fatores de Transcrição Kruppel-Like/genética , Polimorfismo de Nucleotídeo Único , Domínios Proteicos , Mapeamento de Interação de Proteínas , Técnicas do Sistema de Duplo-Híbrido
7.
Immunol Lett ; 237: 33-41, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34228987

RESUMO

OBJECTIVE: In this study, we focused on the interaction between SARS-CoV-2 and host Type I Interferon (IFN) response, so as to identify whether IFN effects could be influenced by the products of SARS-CoV-2. METHODS: All the structural and non-structural proteins of SARS-CoV-2 were transfected and overexpressed in the bronchial epithelial cell line BEAS-2B respectively, and typical antiviral IFN-stimulated gene (ISG) ISG15 expression was detected by qRT-PCR. RNA-seq based transcriptome analysis was performed between control and Spike (S) protein-overexpressed BEAS-2B cells. The expression of ACE2 and IFN effector JAK-STAT signaling activation were detected in control and S protein-overexpressed BEAS-2B cells by qRT-PCR or/and Western blot respectively. The interaction between S protein with STAT1 and STAT2, and the association between JAK1 with downstream STAT1 and STAT2 were measured in BEAS-2B cells by co-immunoprecipitation (co-IP). RESULTS: S protein could activate IFN effects and downstream ISGs expression. By transcriptome analysis, overexpression of S protein induced a set of genes expression, including series of ISGs and the SARS-CoV-2 receptor ACE2. Mechanistically, S protein enhanced the association between the upstream JAK1 and downstream STAT1 and STAT2, so as to promote STAT1 and STAT2 phosphorylation and ACE2 expression. CONCLUSION: SARS-CoV-2 S protein enhances ACE2 expression via facilitating IFN effects, which may help its infection.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Brônquios/efeitos dos fármacos , COVID-19/virologia , Células Epiteliais/efeitos dos fármacos , Interferon alfa-2/farmacologia , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Brônquios/enzimologia , Brônquios/virologia , COVID-19/enzimologia , Citocinas/genética , Citocinas/metabolismo , Células Epiteliais/enzimologia , Células Epiteliais/virologia , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Janus Quinase 1/metabolismo , Fosforilação , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT2/metabolismo , Transdução de Sinais , Glicoproteína da Espícula de Coronavírus/genética , Ubiquitinas/genética , Ubiquitinas/metabolismo , Regulação para Cima
8.
Int J Mol Sci ; 22(11)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071130

RESUMO

The diagnosis of autoimmune polyglandular syndrome (APS) types 1/2 is difficult due to their rarity and nonspecific clinical manifestations. APS-1 development can be identified with assays for autoantibodies against cytokines, and APS-2 development with organ-specific antibodies. In this study, a microarray-based multiplex assay was proposed for simultaneous detection of both organ-specific (anti-21-OH, anti-GAD-65, anti-IA2, anti-ICA, anti-TG, and anti-TPO) and APS-1-specific (anti-IFN-ω, anti-IFN-α-2a, and anti-IL-22) autoantibodies. Herein, 206 serum samples from adult patients with APS-1, APS-2, isolated autoimmune endocrine pathologies or non-autoimmune endocrine pathologies and from healthy donors were analyzed. The prevalence of autoantibodies differed among the groups of healthy donors and patients with non-, mono- and multi-endocrine diseases. APS-1 patients were characterized by the presence of at least two specific autoantibodies (specificity 99.5%, sensitivity 100%). Furthermore, in 16 of the 18 patients, the APS-1 assay revealed triple positivity for autoantibodies against IFN-ω, IFN-α-2a and IL-22 (specificity 100%, sensitivity 88.9%). No anti-cytokine autoantibodies were found in the group of patients with non-APS-1 polyendocrine autoimmunity. The accuracy of the microarray-based assay compared to ELISA for organ-specific autoantibodies was 88.8-97.6%. This multiplex assay can be part of the strategy for diagnosing and predicting the development of APS.


Assuntos
Autoanticorpos/sangue , Poliendocrinopatias Autoimunes/imunologia , Adolescente , Adulto , Autoantígenos/imunologia , Doenças do Sistema Endócrino/sangue , Doenças do Sistema Endócrino/imunologia , Feminino , Humanos , Proteínas Imobilizadas/imunologia , Interferon Tipo I/imunologia , Interferon alfa-2/imunologia , Interleucinas/imunologia , Masculino , Análise em Microsséries/métodos , Pessoa de Meia-Idade , Especificidade de Órgãos , Poliendocrinopatias Autoimunes/sangue , Poliendocrinopatias Autoimunes/diagnóstico , Sensibilidade e Especificidade , Adulto Jovem
9.
J Nutr Biochem ; 96: 108806, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34147603

RESUMO

Many cancer patients receive their classical therapies together with vitamin supplements. However, the effectiveness of these strategies is on debate. Here we aimed to evaluate how vitamin E supplementation affects the anticancer effects of interferon (IFN-α) using an early-model of liver cancer development (initiation-promotion, IP). Male Wistar rats subjected to this model were divided as follows: untreated (IP), IP treated with recombinant IFN-α-2b (6.5  ×  105 U/kg), IP treated with vitamin E (50 mg/kg), and IP treated with combination of vitamin E and IFN-α-2b. After treatments rats were fasted and euthanized and plasma and livers were collected. Combined administration of vitamin E and IFN-α-2b induced body weight drop, increased liver apoptosis, and low levels of hepatic lipids. Interestingly, vitamin E and IFN-α-2b combination also induced an increase in altered hepatic foci number, but not in size. It seems that vitamin E acts on its antioxidant capability in order to block the oxidative stress induced by IFN-α-2b, blocking in turn its beneficial effects on preneoplastic livers, leading to harmful final effects. In conclusion, this study shows that vitamin E supplementation in IFN-α-2b-treated rats exerts unwanted effects; and highlights that in spite of being natural, nutritional supplements may not always exert beneficial outcomes when used as complementary therapy for the treatment of cancer.


Assuntos
Anticarcinógenos/farmacologia , Interferon alfa-2/farmacologia , Neoplasias Hepáticas/prevenção & controle , Vitamina E/farmacologia , Vitaminas/farmacologia , Animais , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Interações Medicamentosas , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Ratos Wistar
11.
Vopr Virusol ; 66(2): 123-128, 2021 05 15.
Artigo em Russo | MEDLINE | ID: mdl-33993682

RESUMO

INTRODUCTION: The pandemic spread of a new coronavirus infection, COVID-19, has caused a global emergency and attracted the attention of public health professionals and the population of all countries. A significant increase in the number of new cases of SARS-CoV-2 infection demonstrates the urgency of finding drugs effective against this pathogen.The aim of this work was to evaluate the in vitro antiviral efficacy of human recombinant alpha-2b interferon (IFN-α2b) against SARS-CoV-2 virus. MATERIAL AND METHODS: The experiments had been carried out on Vero Cl008, the continuous line of African green monkey (Chlorocebus sabaeus) kidney cells. The effectiveness of the drugs was assessed by the suppression of viral reproduction in vitro. The biological activity was determined using titration of a virus-containing suspension in a Vero Cl008 cell culture by the formation of negative colonies. RESULTS: The antiviral efficacy of the IFN-α2b-based medications, which have a high safety profile and proven efficacy in the prevention and treatment of influenza and acute respiratory viral infections (ARVI), has been studied against the new pandemic SARS-CoV-2 virus in vitro experiments in Vero C1008 cell culture. IFN-α2b effectively inhibits the reproduction of the virus when applied both 24 hrs before and 2 hrs after infection. In the IFN-α2b concentration range 102-106 IU/ml a complete suppression of the reproduction of the SARS-CoV-2 virus had been demonstrated. DISCUSSION: IFN-α2b demonstrated in vitro high antiviral activity against SARS-CoV-2. In addition, the substance has a high chemotherapeutic index (>1000). CONCLUSION: Medications for intranasal use based on IFN-α2b have high antiviral activity and are promising drugs for in vivo study in terms of prevention and treatment of COVID-19.


Assuntos
COVID-19/tratamento farmacológico , COVID-19/imunologia , Interferon alfa-2/farmacologia , SARS-CoV-2/imunologia , Animais , COVID-19/patologia , Chlorocebus aethiops , Humanos , Células Vero
12.
AIDS ; 35(12): 2051-2054, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34049356

RESUMO

We report on the post-hoc analysis of three clinical studies (NCT01935089, NCT00594880 and NCT00051818) with chronically HIV-infected, immune-reconstituted individuals with similar entry criteria, and demographics interrupting antiretroviral therapy (ART) without or with 5 weeks of weekly pegylated (Peg)-IFN-α2b or Peg-IFN-α2a immunotherapy added onto ART. Results show similar rates of viral suppression between both immunotherapies when continued during a 4-week ART interruption, despite Peg-IFN-α2a maintaining significantly higher trough blood levels.


Assuntos
Antivirais , Infecções por HIV , Antivirais/uso terapêutico , Estudos Clínicos como Assunto , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico , Humanos , Interferon alfa-2/uso terapêutico , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes , Resultado do Tratamento
13.
Methods ; 195: 29-43, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33962011

RESUMO

Therapeutic approaches to COVID-19 treatment require appropriate inhibitors to target crucial proteins of SARS-CoV-2 replication machinery. It's been approximately 12 months since the pandemic started, yet no known specific drugs are available. However, research progresses with time in terms of high throughput virtual screening (HTVS) and rational design of repurposed, novel synthetic and natural products discovery by understanding the viral life cycle, immuno-pathological and clinical outcomes in patients based on host's nutritional, metabolic, and lifestyle status. Further, complementary and alternative medicine (CAM) approaches have also improved resiliency and immune responses. In this article, we summarize all the therapeutic antiviral strategies for COVID-19 drug discovery including computer aided virtual screening, repurposed drugs, immunomodulators, vaccines, plasma therapy, various adjunct therapies, and phage technology to unravel insightful mechanistic pathways of targeting SARS-CoV-2 and host's intrinsic, innate immunity at multiple checkpoints that aid in the containment of the disease.


Assuntos
Corticosteroides/administração & dosagem , Antivirais/administração & dosagem , Vacinas contra COVID-19/administração & dosagem , COVID-19/tratamento farmacológico , COVID-19/imunologia , Descoberta de Drogas/tendências , Animais , COVID-19/prevenção & controle , Descoberta de Drogas/métodos , Ensaios de Triagem em Larga Escala/métodos , Ensaios de Triagem em Larga Escala/tendências , Humanos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Interferon alfa-2/administração & dosagem , Interleucina-6/antagonistas & inibidores , Interleucina-6/imunologia
14.
Int J Infect Dis ; 107: 62-68, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33878461

RESUMO

OBJECTIVES: The treatment of acute herpangina is inconsistent. We aim to evaluate the effectiveness and safety of interferon α-2b spray versus Ribavirin for this disease. METHODS: A randomized, controlled trial was conducted in eight hospitals in China between 2016 and 2018. 668 patients (1-7 years old) were randomized into an experimental group (treated with Interferon α-2b spray) or control group (received Ribavirin Aerosol). Body temperature returning to normal within 72 h and remaining so for 24 h was the primary outcome; release of oral herpes and adverse events were the secondary outcomes. RESULTS: (1) The average age of onset was 2.5 years old. (2) After 72 h treatment, body temperature of 98.5% patients in experimental group and 94.3% in control group returned to normal and remained so for 24 h (P = 0.004). The differences were greater at 48 h treatment (95.2% vs. 85.9%, P < 0.001) and at 24 h (77.5% vs. 66.5%, P = 0.001). (3) The rate of improved oral herpes in the experimental group was higher than that in control group (46.7% vs.37.1%, P = 0.011). No adverse reaction occurred. CONCLUSIONS: Local application of recombinant interferon α-2b spray showed better efficacy for acute herpangina in children. It was safe for use.


Assuntos
Antivirais/administração & dosagem , Herpangina/tratamento farmacológico , Interferon alfa-2/administração & dosagem , Antivirais/efeitos adversos , Temperatura Corporal , Criança , Pré-Escolar , China , Método Duplo-Cego , Feminino , Febre/tratamento farmacológico , Humanos , Lactente , Interferon alfa-2/efeitos adversos , Masculino , Sprays Orais , Úlceras Orais/tratamento farmacológico , Ribavirina/administração & dosagem
15.
Int J Infect Dis ; 105: 516-521, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33713817

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of pegylated interferon alfa-2b (PEG IFN-α2b) along with the standard of care (SOC) in subjects with moderate COVID-19. METHODS: In this phase 2, randomized, open-label study, adult subjects aged ≥18 years with RT-PCR confirmed COVID-19 with moderate symptoms were randomized in a 1:1 to receive PEG IFN-α2b plus SOC, or SOC alone. The primary endpoint was improvement in clinical status on day 15, measured by the WHO 7-point ordinal scale. RESULTS: Forty subjects were randomized to PEG IFN-α2b plus SOC (n = 20) and SOC (n = 20). Overall, 19 (95.00%) subjects in PEG IFN-α2b plus SOC had achieved clinical improvement on day 15 compared to 13 (68.42%) subjects in SOC (p < 0.05). Overall, 80% and 95% of subjects in the PEG IFN-α2b plus SOC group had a negative RT-PCR result on day 7 and day 14, respectively, compared to 63% and 68% in the SOC group. Adverse events (AEs) were reported for eleven subjects in the PEG IFN-α2b plus SOC group and eight subjects in the SOC group. All reported AEs were mild. CONCLUSION: The significant improvement in clinical status on day 15 is likely due to faster viral reduction compared to SOC with the PEG IFN-α2b treated moderate COVID-19 subjects showing a difference as early as day seven and becoming significant by day 14.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , SARS-CoV-2 , Adulto , Idoso , Feminino , Humanos , Interferon alfa-2/efeitos adversos , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico
16.
Clin Drug Investig ; 41(4): 391-404, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33725322

RESUMO

BACKGROUND AND OBJECTIVES: Ropeginterferon alfa-2b is a novel monopegylated recombinant interferon alfa-2b for the treatment of patients with polycythemia vera. The objectives of this study were to evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of ropeginterferon alfa-2b in healthy Japanese subjects compared with Caucasian subjects. METHODS: In this multicenter, parallel-group phase I study, a cohort consisting of six Japanese and six Caucasian subjects was designated to receive a single subcutaneous dose of ropeginterferon alfa-2b (100, 200, 300, and 450 µg). Pharmacokinetic and pharmacodynamic parameters, and immunogenicity were evaluated. Safety was assessed throughout the study. RESULTS: Cohort 4 (450-µg dose) was not initiated because the primary objective of this study was achieved based on the three completed cohorts. A total of 36 enrolled subjects (18 Japanese and 18 Caucasian) in three cohorts were included in the safety, pharmacokinetic, and pharmacodynamic analysis sets. Ropeginterferon alfa-2b exposure in terms of the area under the serum concentration-time curve (AUC) from time zero extrapolated to infinity and the AUC from time zero to the time of the last quantifiable concentration was approximately 1.7-fold and two-fold higher in Japanese subjects than in Caucasian subjects, respectively. Across the same dose range, the maximum serum concentration was approximately 1.25-fold higher in Japanese subjects than in Caucasian subjects. The time to reach the median maximum serum concentration was similar between ethnicities (approximately 96-111 h). The terminal half-life was 48-57 h in Japanese subjects and 31-75 h in Caucasian subjects. The slope of the relationship between dose and drug exposure was greater than 1 in both ethnicities. The dose-dependent induction of beta-2 microglobulin and neopterin expression was observed in both ethnicities, and the two groups showed similar pharmacodynamic parameters. At the end of the study, 22.2% of Japanese subjects and 11.1% of Caucasian subjects developed anti-ropeginterferon alfa-2b-binding antibodies. The neutralizing capacity of these antibodies was not tested. Ropeginterferon alfa-2b up to 300 µg was safe and well tolerated, with no unexpected safety findings based on previous experiences with ropeginterferon alfa-2b and other forms of interferon. CONCLUSIONS: Ropeginterferon alfa-2b exposure was higher in Japanese subjects than in Caucasian subjects. The increase in ropeginterferon alfa-2b exposure was greater than the dose proportion in the dose range of 100-300 µg. Ropeginterferon alfa-2b was safe and well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03546465, registered on 6 June, 2018.


Assuntos
Antivirais/administração & dosagem , Interferon alfa-2/administração & dosagem , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Adulto , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , Grupo com Ancestrais do Continente Europeu , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Policitemia Vera/tratamento farmacológico , Proteínas Recombinantes/administração & dosagem , Adulto Jovem
18.
Vopr Virusol ; 66(1): 40-46, 2021 03 07.
Artigo em Russo | MEDLINE | ID: mdl-33683064

RESUMO

INTRODUCTION: Analysis of the pathogenesis of coronavirus infection caused SARS-CoV-2 indicates a significant impact of hemorheological disorders on its course and outcomes. It is known that chronic cardiovascular diseases are associated with the risk of severe course and lethal outcomes both in COVID-19 and other infectious diseases. Therefore, in each case it is necessary to study the interaction and mutual influence of different components of the treatment program prescribed to such patients.The purpose of this work was to evaluate the effect of coagulation activity on the course of a novel coronavirus infection (COVID-19) and to justify the management of comorbid patients having been received novel oral anticoagulants (NOACs) in previously selected doses according to indications in concomitant somatic diseases. MATERIAL AND METHODS: Total 76 cases of confirmed coronavirus infection in patients who had been received initial therapy on an outpatient basis were analyzed. 26 patients who received NOACs (rivaroxaban, apixaban, dabigatran) made up the main group and 50 - the comparison (control) group in which patients had not been administered any drugs that affect blood clotting until the episode of COVID-19. All patients have been prescribed therapy following the Provisional guidelines «Prevention, diagnosis and treatment of coronavirus infection (COVID-19)¼ (https://static-0.minzdrav.gov.ru/system/attachments/attaches/). RESULTS AND DISCUSSION: The number of hospitalizations was significantly fewer in the group of patients who had been received NOACs (19 vs. 66% in the control group). No deaths or cases of severe respiratory and/or renal failure were observed in the main group, while adverse outcomes were noted in 14% of patients who had not been administered these drugs. CONCLUSION: Taking NOACs reduces the probability of severe course and adverse outcomes in the development of coronavirus infection caused by SARS-CoV-2, which indicates a significant contribution of coagulation mechanisms to the pathogenesis in COVID-19. There were no indications for drug replacement and correction of anticoagulant therapy regimens in patients who received adequate therapy with oral anticoagulants for treating a non-severe form of coronavirus infection in ambulatory patient settings.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , COVID-19/tratamento farmacológico , Doença das Coronárias/tratamento farmacológico , Coagulação Intravascular Disseminada/tratamento farmacológico , Hipertensão/tratamento farmacológico , Arteriosclerose Intracraniana/tratamento farmacológico , Acetilcisteína/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/virologia , Azitromicina/uso terapêutico , COVID-19/mortalidade , COVID-19/patologia , COVID-19/virologia , Estudos de Coortes , Comorbidade , Doença das Coronárias/diagnóstico , Doença das Coronárias/mortalidade , Doença das Coronárias/virologia , Dabigatrana/uso terapêutico , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/mortalidade , Coagulação Intravascular Disseminada/virologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/mortalidade , Hipertensão/virologia , Indóis/uso terapêutico , Interferon alfa-2/uso terapêutico , Arteriosclerose Intracraniana/diagnóstico , Arteriosclerose Intracraniana/mortalidade , Arteriosclerose Intracraniana/virologia , Masculino , Pessoa de Meia-Idade , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Análise de Sobrevida
19.
BMJ Case Rep ; 14(3)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33766959

RESUMO

Double filtration plasmapheresis (DFPP) is an apheretic technique that selectively removes high molecular weight substances using a plasma component filter. DFPP has been used to treat positive-sense RNA virus infections, mainly chronic hepatitis C virus (HCV) infection, because of its ability to directly eliminate viral particles from blood plasma from 2008 to about 2015, before direct-acting antiviral agents was marketed. This effect has been termed virus removal and eradication by DFPP. HCV is a positive-sense RNA virus similar to West Nile virus, dengue virus and the SARS and Middle East respiratory syndrome coronaviruses. SARS-CoV-2 is classified same viral species. These viruses are all classified in Family Flaviviridae which are family of single-stranded plus-stranded RNA viruses. Viral particles are 40-60 nm in diameter, enveloped and spherical in shape. We present a rare case of HCV removal where an RNA virus infection that copresented with virus-associated autoimmune hepatitis was eliminated using DFPP. Our results indicate that DFPP may facilitate prompt viraemia reduction and may have novel treatment applications for SARS-CoV-2, that is, use of therapeutic plasma exchange for fulminant COVID-19.


Assuntos
Coinfecção/terapia , Coinfecção/virologia , Hepatite C Crônica/terapia , Hepatite Autoimune/terapia , Plasmaferese/métodos , Antivirais/uso terapêutico , COVID-19/complicações , COVID-19/terapia , Quimioterapia Combinada , Feminino , Hepatite C Crônica/complicações , Hepatite Autoimune/complicações , Humanos , Interferon alfa-2/uso terapêutico , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Vírus de RNA de Cadeia Positiva/isolamento & purificação , Ribavirina/uso terapêutico , SARS-CoV-2 , Resultado do Tratamento , Carga Viral
20.
BMJ Case Rep ; 14(2)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608345

RESUMO

A man with a history of blind eye due to trauma 22 years earlier consulted at 53 years of age with a large conjunctival neoplastic lesion, compromising almost the entire temporal limbus, and reaching a size of approximately 16 mm on its larger diameter, in the conjunctiva. Management was started with topical and subconjunctival chemotherapy (interferon alpha-2b) in order to perform immunoreduction, but a dramatic response with total disappearance of the lesion was observed. In the follow-up time period of more than 7 years, there were no signs of recurrence.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Oculares/tratamento farmacológico , Interferon alfa-2/uso terapêutico , Administração Tópica , Antineoplásicos/administração & dosagem , Seguimentos , Humanos , Interferon alfa-2/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
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