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1.
Eur J Immunol ; 50(1): 130-137, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31434164

RESUMO

Inosine pranobex (IP) is a synthetic immunomodulating compound, indicated for use in the treatment of human papillomavirus-associated warts and subacute sclerosing panencephalitis. Previous studies demonstrate that the immunomodulatory activity of IP is characterized by enhanced lymphocyte proliferation, cytokine production, and NK cell cytotoxicity. The activation of NKG2D signaling on NK cells, CD8+ T cells, and γδ T cells also produces these outcomes. We hypothesized that IP alters cellular immunity through the induction of NKG2D ligand expression on target cells, thereby enhancing immune cell activation through the NKG2D receptor. We tested this hypothesis and show that exposure of target cells to IP leads to increased expression of multiple NKG2D ligands. Using both targeted metabolic interventions and unbiased metabolomic studies, we found that IP causes an increase in intracellular concentration of purine nucleotides and tricarboxylic acid (TCA) cycle intermediates and NKG2D ligand induction. The degree of NKG2D ligand induction was functionally significant, leading to increased NKG2D-dependent target cell immunogenicity. These findings demonstrate that the immunomodulatory properties of IP are due to metabolic activation with NKG2D ligand induction.


Assuntos
Adjuvantes Imunológicos/farmacologia , Citotoxicidade Imunológica/efeitos dos fármacos , Inosina Pranobex/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Subfamília K de Receptores Semelhantes a Lectina de Células NK/imunologia , Ativação Metabólica/efeitos dos fármacos , Citotoxicidade Imunológica/imunologia , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Ligantes , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo
2.
Molecules ; 26(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34361591

RESUMO

Each drug has pharmacokinetics that must be defined for the substance to be used in humans and animals. Currently, one of the basic analytical tools for pharmacokinetics studies is high-performance liquid chromatography coupled with mass spectrometry. For this analytical method to be fully reliable, it must be properly validated. Therefore, the aims of this study were to develop and validate a novel analytical method for 4-acetamidobenzoic acid, a component of the antiviral and immunostimulatory drug Inosine Pranobex, and to apply the method in the first pharmacokinetics study of 4-acetamidobenzoic acid in pigs after oral administration. Inosine Pranobex was administered under farm conditions to pigs via drinking water 2 h after morning feeding at doses of 20, 40, and 80 mg/kg. For sample preparation, we used liquid-liquid extraction with only one step-protein precipitation with 1 mL of acetonitrile. As an internal standard, we used deuterium labeled 4-acetamidobenzoic acid. The results indicate that the described method is replicable, linear (r2 ≥ 0.99), precise (2.11% to 13.81%), accurate (89% to 98.57%), selective, and sensitive (limit of quantitation = 10 ng/mL). As sample preparation requires only one step, the method is simple, effective, cheap, and rapid. The results of the pilot pharmacokinetics study indicate that the compound is quickly eliminated (elimination half-life from 0.85 to 1.42 h) and rapidly absorbed (absorption half-life from 0.36 to 2.57 h), and that its absorption increases exponentially as the dose is increased.


Assuntos
Adjuvantes Imunológicos/farmacocinética , Antivirais/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Inosina Pranobex/farmacocinética , Espectrometria de Massas em Tandem/métodos , para-Aminobenzoatos/farmacocinética , Adjuvantes Imunológicos/administração & dosagem , Animais , Antivirais/administração & dosagem , Inosina Pranobex/administração & dosagem , Projetos Piloto , Suínos
3.
Acta Med Indones ; 53(3): 308-314, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34611070

RESUMO

COVID-19 became a widespread infectious disease in late 2019. Indonesia currently has the highest COVID-19 mortality rate in Asia, between 4-5 percent. Interestingly, COVID-19-associated coagulopathy characterized by an increase of several procoagulant factor levels, including fibrinogen and D-dimer, that has been associated with higher mortality and unfavorable outcomes. We report a case of a 30-year-old male admitted to the hospital with a profuse vomiting and worsening fever, cough and shortness of breath, and was diagnosed with COVID-19-associated coagulopathy. Seven days after admission, he became deteriorated with significant reduction of oxygen saturation and his coagulation parameter levels were increased with highly suspicion of pulmonary embolism. He was treated with azithromycin, isoprinosine, lopinavir, and fondaparinux with thromboprophylaxis dosage since admission. The role of increased fondaparinux dosage at the time of clinical deterioration was then followed by clinical improvement and reduced D-dimer level. Anticoagulant therapy, mainly with fondaparinux, showed a better prognosis in patients with markedly elevated D-Dimer. Fondaparinux needs to be monitored appropriately to prevent bleeding and adverse. The patient was discharged from the hospital in an improved condition and normal D-Dimer levels. There was no bleeding event nor other major side effects had been found in this case. The decision for increasing dose of anticoagulant may be determined on individual basis, considering risks, benefits, and also the most important is clinical findings.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Fondaparinux , Hemorragia/prevenção & controle , Embolia Pulmonar , SARS-CoV-2/isolamento & purificação , Trombofilia , Adulto , Antivirais , Azitromicina/administração & dosagem , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/fisiopatologia , Deterioração Clínica , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fondaparinux/administração & dosagem , Fondaparinux/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Inosina Pranobex/administração & dosagem , Lopinavir/administração & dosagem , Masculino , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/etiologia , Trombofilia/complicações , Trombofilia/diagnóstico , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Resultado do Tratamento
4.
Arch Virol ; 164(11): 2691-2698, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31428916

RESUMO

Aleutian mink disease virus is one of the greatest threats to modern mink farming. The disease reduces fecundity and causes high mortality among kits. The aim of this study was to evaluate the effectiveness of methisoprinol in counteracting the effects of Aleutian disease, both by inhibiting replication of the virus and by mitigating the harmful effects of the disease on the fecundity and weight of infected animals. The study included 300 individuals with confirmed infection, divided according to antibody titres into three experimental groups, which received a 20% methisoprinol solution, and three control groups, which did not receive the immunostimulant. In the mink from the experimental groups, the number of copies of the genetic material of the virus in the spleens and lymph nodes was one order of magnitude lower than in the case of the control groups. Mink receiving the supplement also showed higher fecundity (on average 5.83 in the experimental groups and 4.83 in the control groups), and the weight of their offspring before slaughter was over 200 g higher. Given the lack of effective methods for immunoprophylaxis and treatment, methisoprinol supplementation can be an effective means of counteracting the effects of AMDV on persistently infected farms.


Assuntos
Vírus da Doença Aleutiana do Vison/efeitos dos fármacos , Doença Aleutiana do Vison/tratamento farmacológico , Doença Aleutiana do Vison/prevenção & controle , Antivirais/farmacologia , Inosina Pranobex/farmacologia , Doença Aleutiana do Vison/mortalidade , Vírus da Doença Aleutiana do Vison/genética , Animais , Fazendas , Feminino , Linfonodos/virologia , Vison/virologia , Baço/virologia , Replicação Viral/efeitos dos fármacos
5.
Australas J Dermatol ; 60(1): e1-e13, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30191561

RESUMO

A range of systemic treatments are used for alopecia areata with variable evidence supporting efficacy. In this systematic review, we evaluated the evidence surrounding systemic treatments for alopecia areata, alopecia totalis and alopecia universalis. A systematic search was conducted of the peer-reviewed literature published between 1946 and March 2018 via Medline, Embase, Amed, the Cochrane Central Register of Controlled Trials, PsychINFO and Lilacs. All randomised controlled trials (RCTs) that evaluated the effectiveness of systemic treatments for individuals with alopecia areata, totalis or universalis were included. Sixteen studies were included with a total of 768 participants. We found eight placebo-controlled RCTs, three RCTs comparing two systemic treatments and five RCTs comparing three treatments. A total of 15 different systemic therapies were investigated. The most frequently investigated therapy was oral prednisolone pulse therapy and oral inosiplex. There was significant variability in the definition of treatment success. No study evaluated the impact of pharmacotherapy on quality of life using complete quantitative quality of life instruments. Adverse events were reported in 13 studies and were corticosteroid related or otherwise well tolerated. Relapse rates were considerable in the four studies that reported this outcome. There is currently no specific systemic therapy that is supported by robust body of evidence from RCTs. The current evidence suggests efficacy of oral prednisolone pulse therapy and oral inosiplex. Evidence does not support the use of oral zinc sulphate, alefacept and efalizumab. Future RCTs should be adequately powered and employ clearly defined clinical response endpoints to allow future meta-analyses.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Alopecia em Áreas/tratamento farmacológico , Alopecia/tratamento farmacológico , Glucocorticoides/uso terapêutico , Administração Intravenosa , Administração Oral , Antidepressivos/uso terapêutico , Produtos Biológicos/uso terapêutico , Terapias Complementares , Humanos , Inosina Pranobex/uso terapêutico , Prednisolona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Acta Virol ; 61(1): 32-38, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28105852

RESUMO

We demonstrated the positive effect of Isoprinosine treatment on persistent infection of Balb/c mice with murine gammaherpesvirus 68 (MHV-68). Increased number of leukocytes, increased percentage of neutrophils, elevated levels of virus-neutralizing (VN) antibodies, reduced number of atypical lymphocytes and reduced virus titers were detected in the examined organs after a 14-day treatment. The positive effect of Isoprinosine therapy vanished after 120-150 days. After this interval, we demonstrated lower numbers of leukocytes, lower levels of VN antibodies and an increased number of atypical lymphoid monocytes in the Isoprinosine-treated group. Immunological parameters correlated with increased titers of virus in all investigated organs. Evidence of immunostimulation was demonstrated by lower incidence of tumor formation (7.5%) in the group of MHV-infected and Isoprinosine-treated mice in comparison to group without Isoprinosine treatment (17.5%). The presented results showed that Isoprinosine therapy had a positive impact on persistent infection of mice with MHV-68, but this effect was time-limited. The improvement of the investigated parameters lasted for five months only. Our presented results confirmed that each treatment with Isoprinosine should be repeated and must be long-term in some chronic infections.


Assuntos
Antivirais/uso terapêutico , Gammaherpesvirinae , Infecções por Herpesviridae/tratamento farmacológico , Inosina Pranobex/uso terapêutico , Animais , Chlorocebus aethiops , Macrófagos Peritoneais/virologia , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Células Vero
7.
BMC Infect Dis ; 16(1): 648, 2016 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-27821093

RESUMO

BACKGROUND: Inosine pranobex (Isoprinosine®) is an immunomodulatory drug approved in several countries for the treatment of viral infections. This study compared the efficacy and safety of inosine pranobex versus placebo in subjects with clinically diagnosed influenza-like illness, including subjects with laboratory-confirmed acute respiratory viral infections. Subgroup analyses evaluated the efficacy of inosine pranobex compared to placebo in otherwise healthy (without related ongoing disease) subjects that were less than 50 years of age and healthy subjects that were at least 50 years of age. The effect of body mass index (BMI) was evaluated in subjects less than 50 years of age. METHODS: A total of 463 subjects were randomly assigned to receive inosine pranobex (n = 231) or placebo (n = 232) in this Phase 4, randomised, double-blind, multicentre study. The primary efficacy endpoint was time to resolution of all influenza-like symptoms present at baseline to none. Safety was evaluated through analysis of adverse events, vital signs, and physical examinations. RESULTS: The difference in time to resolution of all influenza-like symptoms between treatment groups was not statistically significant but showed a faster improvement in subjects in the inosine pranobex group versus those in the placebo group - Hazard Ratio = 1.175; (95 % CI: 0.806-1.714). P-value = 0.324. In the subgroup analysis for subjects less than 50 years of age, statistically significant differences in time to resolution of influenza-like symptoms that favoured the inosine pranobex group over the placebo group were observed in those without related ongoing disease and those who were non-obese (BMI <30 kg/m2). The differences between the inosine pranobex and placebo groups in subjects at least 50 years of age without related ongoing disease and in subjects less than 50 years of age who were obese (BMI ≥30 kg/m2) were not statistically significant. Inosine pranobex was generally well tolerated, and no deaths were reported. CONCLUSIONS: The study results indicate the safety of inosine pranobex for the treatment of subjects with confirmed acute respiratory viral infections and confirm the efficacy of inosine pranobex versus placebo in healthy non-obese subjects less than 50 years of age with clinically diagnosed influenza-like illnesses. TRIAL REGISTRATION: EWO-ISO-2014/1, EudraCT 2014-001863-11 ; Date of registration: 29 APR 2014; Detail information web link: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001863-11/results.


Assuntos
Antivirais/uso terapêutico , Influenza Humana/tratamento farmacológico , Inosina Pranobex/uso terapêutico , Doença Aguda , Adulto , Antivirais/toxicidade , Método Duplo-Cego , Feminino , Humanos , Inosina Pranobex/toxicidade , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
8.
Dig Dis Sci ; 61(8): 2344-2350, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27344315

RESUMO

BACKGROUND: Gastroparesis (GP) is a disabling chronic gastroenterologic disorder with high morbidity that severely impacts patients' quality of life. GP can present acutely after a viral-like gastrointestinal illness resulting in speculation that in some patients, neurologic damage caused by the infection might underlie the pathogenesis of idiopathic gastroparesis (IGP). AIMS: The aim of this study is to document case reports of Enterovirus (EV) infection as a possible cause of IGP. METHODS: Eleven patients referred with a diagnosis of GP underwent workup to exclude known causes of GP. Those with a history of flu-like symptoms or gastroenteritis prior to onset of GP symptoms had gastric biopsies taken during upper endoscopy to assess for the presence of gastric mucosal EV infection. Data on presenting symptoms, extra-intestinal symptoms and conditions, prior nutritional support requirements, upper endoscopy findings, and response to therapy were cataloged. RESULTS: Eleven patients were diagnosed as IGP. Nine had active EV infection on gastric biopsies and were included (7/9 female, mean age 43 years). Eight out of nine received EV treatment with antivirals and/or immune therapies, with a wide degree of variability in treatment regimens. Four out of eight who received EV treatment had symptomatic improvement. One patient had stable symptoms. Three patients are currently undergoing therapy. CONCLUSIONS: Gastric EV infection was frequently detected (82 %) in patients undergoing investigation for IGP. Antiviral and/or immune therapies against EV seem to be favorable, as most of our patients had resolution of their GP symptoms after treatment. This is the first study to identify EV as a possible infectious etiology of IGP.


Assuntos
Infecções por Enterovirus/epidemiologia , Gastrite/epidemiologia , Gastroparesia/epidemiologia , 2-Aminopurina/análogos & derivados , 2-Aminopurina/uso terapêutico , Adulto , Idoso , Antivirais/uso terapêutico , Biópsia , Infecções por Enterovirus/patologia , Infecções por Enterovirus/terapia , Famciclovir , Feminino , Gastrite/patologia , Gastrite/terapia , Refluxo Gastroesofágico/epidemiologia , Gastroparesia/terapia , Gastroparesia/virologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Inosina Pranobex/uso terapêutico , Masculino , Pessoa de Meia-Idade , Síndrome da Taquicardia Postural Ortostática/epidemiologia , Ribavirina/uso terapêutico , Estômago/patologia , Adulto Jovem
9.
Acta Pol Pharm ; 73(3): 637-44, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27476281

RESUMO

Key issues in the development of novel antivirals are the emergence of resistant strains. The development of new drugs effective against herpes diseases has proven to be both difficult and time-consuming. Some alternative may be to optimize the efficacy and selectivity of existing antiviral drugs or combining them with other well known agents. Inosine pranobex exerts a direct antiviral effect as well as secondary effect to its immunomodulatory activity. We found that increasing concentrations of inosine pranobex (50-400 µg/mL) produced progressively growing inhibitory effect on HHV-1 replication, following infection of different cell lines. The combination of 1000 IU/mL IFN-α and inosine pranobex also resulted in enhanced anti-HHV activity. Immunotherapy may be beneficial for patients from whom strains resistant to currently known antiviral drugs have been isolated.


Assuntos
Antivirais/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Inosina Pranobex/farmacologia , Interferon-alfa/farmacologia , Replicação Viral/efeitos dos fármacos , Aciclovir/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos
10.
Med Dosw Mikrobiol ; 68(1): 64-71, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28146624

RESUMO

INTRODUCTION: Interferon- a (IFN-a), produced by immune cells, exhibits pleiotropic anti- viral activity. Inosine pranobex (PI), a synthetic derivative of a purine, shows direct anti- viral activity, and also acts indirectly, by activation of immune cells. The aim of this study was to evaluate an in vitro inhibition of Coxackievirus A16 (CAI6), enterovirus 71 (EV71) and human parainfluenza virus 4 (HPIV-4) replication by PI in combination with IFN-a. MATERIALS AND METHODS: In the present study we evaluated an in vitro effect of interferon-a and inosine pranobex on replication ofRNAviruses: CA-16, EV71, HPIV-4. Antiviral effects of IFN-a and IPwere assessed by phenotypic assays. The yield reduction assay (YRA), which evaluates the ability of the compounds to inhibit virus multiplication in cell cultures, was ap- plied. The Reed-Muench statistical method was used to determine the 50% end point (IC51). RESULTS: Our studies have shown that combination of IFN-a and inosine pranobex dis- play higher efficacy than treatment with either compound alone, and suggest syn- ergy that may increase therapeutic effectiveness. The reduction of the average viral ti- ters of EV71, CA-16 and HPIV-4 in A549 cell culture after applying 400 Ig/mL Ip and IFN-a (1000 IU/mL), in comparison to the viral titer in the control was reduced by 1,76 log,, TCID,,/ml, o 3,00 log, TCID50/ml , and 1,60 log,( TCID50/ml respec- tively. The antiviral activity of the tested compounds was also analyzed on the basis of IC., values. Application of 1000 IU/ml IFN-a, with PI after infection of A549 cells with mention above viruses reduced the IC,, by 3,5%, 41,3% and 29% respectively. CONCLUSIONS: Our study demonstrated that enhanced antiviral activity was observed when cells infected with RNA viruses were treated with combination of IFN-a and IP. The ef- fectiveness of IFN-a and IP under these conditions has not been previously reported. CA16 virus turned out to be the most sensitive to the action of used inhibitors.


Assuntos
Antivirais/farmacologia , Inosina Pranobex/farmacologia , Interferon-alfa/farmacologia , Vírus de RNA/fisiologia , Replicação Viral/efeitos dos fármacos , Humanos , Vírus de RNA/efeitos dos fármacos
11.
Neuropediatrics ; 46(6): 377-84, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26479761

RESUMO

Subacute sclerosing panencephalitis (SSPE) is a chronic infection of the central nervous system caused by the measles virus (MV). Its prevalence remains high in resource poor countries and is likely to increase in the Northern Europe as vaccination rates decrease. Clinical knowledge of this devastating condition, however, is limited. We therefore conducted this multinational survey summarizing experience obtained from more than 500 patients treated by 24 physicians in seven countries. SSPE should be considered in all patients presenting with otherwise unexplained acquired neurological symptoms. In most patients, the diagnosis will be established by the combination of typical clinical symptoms (characteristic repetitive myoclonic jerks), a strong intrathecal synthesis of antibodies to MV and typical electroencephalogram findings (Radermecker complexes). Whereas the therapeutic use of different antiviral (amantadine, ribavirin) and immunomodulatory drugs (isoprinosine, interferons) and of immunoglobulins has been reported repeatedly, optimum application regimen of these drugs has not been established. This is partly due to the absence of common diagnostic and clinical standards focusing on neurological and psychosocial aspects. Carbamazepine, levetiracetam, and clobazam are the drugs most frequently used to control myoclonic jerks. We have established a consensus on essential laboratory and clinical parameters that should facilitate collaborative studies. Those are urgently needed to improve outcome.


Assuntos
Antivirais/uso terapêutico , Inosina Pranobex/uso terapêutico , Interferons/uso terapêutico , Panencefalite Esclerosante Subaguda/diagnóstico , Anticonvulsivantes/uso terapêutico , Ásia , Carbamazepina/uso terapêutico , Eletroencefalografia , Europa (Continente) , Humanos , Vírus do Sarampo/isolamento & purificação , Mioclonia/tratamento farmacológico , Mioclonia/etiologia , Panencefalite Esclerosante Subaguda/complicações , Panencefalite Esclerosante Subaguda/tratamento farmacológico , Inquéritos e Questionários
12.
Med Dosw Mikrobiol ; 67(2): 107-13, 2015.
Artigo em Polonês | MEDLINE | ID: mdl-26591662

RESUMO

INTRODUCTION: There are no specific antivirals designed for many viral infections. Inosine pranobex (PI) is a purine nucleoside that is involved in a wide variety of intracellular biochemical processes. The mechanism of action in human body is still unclear but numerous studies have demonstrated that this drug inhibits viral replication and exhibit pleiotropic effect. We evaluated in vitro effect of inosine pranobex (PI) on replication of human viruses: parainfluenza viruses (HPIV-2, HPIV-4), entroviruses A (CA16, EV71) and adenoviruses C (HAdV-2, HAdV-5). MATERIALS AND METHODS: In the present study, cytotoxic effect of inosine pranobex was assessed using A549 cell line exposed to different concentrations of compound (PI: 50-800 ig/mL) for 48 hours. Cytotoxic effect of inosine pranobex was assessed visually using light, inverted microscopy Olympus CK2 under 400x magnification and by the MTT colorimetric assay. Antiviral effect was estimated according to the reduction of virus titer. The yield reduction assay (YRA), which evaluates the ability of the PI (50-800 µg/mL) to inhibit virus multiplication in cell cultures, was applied. The cytopathic effect of the virus was evaluated 48 h after infection ofA549 cell cultures with viruses by means of light, inverted microscopy. The Reed-Muench statistical method was used to determine the 50% end point (IC50) (yield reduction assay, YRA) in the presence of inosine pranobex with the controlled one. RESULTS: There were no morphological changes, as assessed visually, in cell cultures treated with PI. MTT cytotoxicity assay confirmed microscopic observations. The viability of cells in the presence of the tested compounds was average 98, 36 %. After conducting the experiments and analyzing the results we noticed that higher concentrations of PI strongly inhibited multiplication of all viruses. PI weakly reduced the titer of infectious enteroviruses and HPIV-4 as compared with the control. Adenoviruses showed the highest sensitivity to the antiviral activity of PI, however, increasing concentrations of PI up to 800 µg /ml slightly enhanced the antiviral activity of 400 µg/ml PI. CONCLUSIONS: Our study demonstrated that inosine pranobex shows no cytotoxic activity on the A549 cell line. In conducted study was observed that adenoviruses (HAdV-2 and HAdV-5) and HPIV-2 have the highest sensitivity to the antiviral activity of inosine pranobex from all tested viral strains.


Assuntos
Adenoviridae/efeitos dos fármacos , Antivirais/farmacologia , Enterovirus/efeitos dos fármacos , Inosina Pranobex/farmacologia , Vírus da Parainfluenza 2 Humana/efeitos dos fármacos , Vírus da Parainfluenza 4 Humana/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Adenoviridae/crescimento & desenvolvimento , Técnicas de Cultura de Células , Linhagem Celular , Humanos , Carga Viral/efeitos dos fármacos
13.
Vopr Onkol ; 61(2): 205-7, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26087599

RESUMO

Secondary prevention of cervical cancer is the identification and treatment of preinvasive forms of the disease, which include dysplasia or cervical intraepithelial neoplasia. Traditional surgical treatment of preinvasive neoplasia does not always result in elimination of the virus that, in its turn, cannot completely exclude the possibility of recurrence. The article presents references and own observations on possibilities of drug therapy in complex treatment for cervical neoplasia.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Anticarcinógenos/uso terapêutico , Antivirais/uso terapêutico , Inosina Pranobex/uso terapêutico , Displasia do Colo do Útero/tratamento farmacológico , Displasia do Colo do Útero/imunologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/imunologia , Adulto , Idoso , Alphapapillomavirus , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Resultado do Tratamento , Displasia do Colo do Útero/virologia
14.
Urologiia ; (5): 118-20, 122-3, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26859953

RESUMO

The review analyzed 59 sources of domestic and foreign literature on the use of immunomodulator izoprinozin in treating patients infected with human papilloma virus, and the results of their own experience. The high prevalence of HPV and its role in the development of cervical cancer are shown, the mechanisms of HPV development and the host protection from this infection are described. The authors present approaches to the treatment of HPV-infected patients with particular attention to izoprinozin. Isoprinosine belongs to immunomodulators with antiviral activity. It inhibits the replication of viral DNA and RNA by binding to cell ribosomes and changing their stereochemical structure. HPV infection, especially in the early stages, may be successfully cured till the complete elimination of the virus. Inosine Pranobex (izoprinozin) having dual action and the most abundant evidence base, may be recognized as the optimal treatment option.


Assuntos
Antivirais/uso terapêutico , Condiloma Acuminado/terapia , Inosina Pranobex/uso terapêutico , Papillomaviridae , Terapia Combinada , Condiloma Acuminado/patologia , Feminino , Humanos
15.
Urologiia ; (2): 39-40, 42, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26237804

RESUMO

This study evaluates the effectiveness of immunomodulating drug isoprinosine in a comprehensive treatment of genital warts in men. Most of the patients were aged 20-30 years. The combination therapy was found to have long term effectiveness. In the group of patients undergoing only destructive methods of treatment relapse after 8 month follow-up was diagnosed in 32% and in patients of the combination therapy group (destruction plus isoprinosine) - in 7% of patients. The pharmacological action of the drug (immunostimulating, antiviral) and the effectiveness of its combination with destructive therapies justify the use of inosine pranobex (isoprinosine) both in the complex therapy of genital warts and for the prevention of the disease recurrence.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Antivirais/uso terapêutico , Condiloma Acuminado/tratamento farmacológico , Doenças dos Genitais Masculinos/tratamento farmacológico , Inosina Pranobex/uso terapêutico , Infecções por Papillomavirus/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Adulto , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Terapia Combinada , Condiloma Acuminado/imunologia , Condiloma Acuminado/cirurgia , Condiloma Acuminado/virologia , Quimioterapia Combinada , Doenças dos Genitais Masculinos/imunologia , Doenças dos Genitais Masculinos/cirurgia , Doenças dos Genitais Masculinos/virologia , Humanos , Inosina Pranobex/administração & dosagem , Inosina Pranobex/efeitos adversos , Masculino , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/cirurgia , Infecções por Papillomavirus/virologia , Resultado do Tratamento , Adulto Jovem
16.
Stomatologiia (Mosk) ; 94(6): 19-21, 2015.
Artigo em Russo | MEDLINE | ID: mdl-27002696

RESUMO

The aim of the study was to prove the rationale for antiviral therapy combined with surgical procedures for treatment of severe oral leukoplakia. Complex clinical and laboratory evaluation and treatment was performed in 56 patients divided in 2 groups. Control group was presented by 13 patients receiving dental treatment, local and systemic keratoplastic formulations. Main group involved 43 patients in which conventional treatment protocol was completed by antiviral therapy and surgical procedures. Leukoplakia diagnosis was based on clinical findings, histological and immunohistochemical studies as well as optic coherent tomography data. The obtained results evidently prove the necessity for including antiviral therapy and surgical procedures in treatment scheme of severe oral leukoplakia.


Assuntos
Antivirais/uso terapêutico , Inosina Pranobex/uso terapêutico , Leucoplasia Oral/terapia , Peptídeos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Imuno-Histoquímica , Leucoplasia Oral/tratamento farmacológico , Leucoplasia Oral/patologia , Leucoplasia Oral/cirurgia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Tomografia de Coerência Óptica
17.
Front Cell Infect Microbiol ; 14: 1331779, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510965

RESUMO

Background: Commercial foot-and-mouth disease (FMD) vaccines have limitations, such as local side effects, periodic vaccinations, and weak host defenses. To overcome these limitations, we developed a novel FMD vaccine by combining an inactivated FMD viral antigen with the small molecule isoprinosine, which served as an adjuvant (immunomodulator). Method: We evaluated the innate and adaptive immune responses elicited by the novel FMD vaccine involved both in vitro and in vivo using mice and pigs. Results: We demonstrated isoprinosine-mediated early, mid-term, and long-term immunity through in vitro and in vivo studies and complete host defense against FMD virus (FMDV) infection through challenge experiments in mice and pigs. We also elucidated that isoprinosine induces innate and adaptive (cellular and humoral) immunity via promoting the expression of immunoregulatory gene such as pattern recognition receptors [PRRs; retinoic acid-inducible gene (RIG)-I and toll like receptor (TLR)9], transcription factors [T-box transcription factor (TBX)21, eomesodermin (EOMES), and nuclear factor kappa B (NF-kB)], cytokines [interleukin (IL)-12p40, IL-23p19, IL-23R, and IL-17A)], and immune cell core receptors [cluster of differentiation (CD)80, CD86, CD28, CD19, CD21, and CD81] in pigs. Conclusion: These findings present an attractive strategy for constructing novel FMD vaccines and other difficult-to-control livestock virus vaccine formulations based on isoprinosine induced immunomodulatory functions.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Inosina Pranobex , Vacinas Virais , Animais , Camundongos , Suínos , Adjuvantes de Vacinas , Anticorpos Antivirais , Adjuvantes Imunológicos , Interleucinas , Imunidade
18.
Artigo em Inglês | MEDLINE | ID: mdl-38050692

RESUMO

INTRODUCTION: SARS-CoV-2 respiratory infection is associated with significant morbidity and mortality, especially in hospitalized high-risk patients. We aimed to evaluate the effects of treatment options (vitamin D, anticoagulation, isoprinosine, ivermectin) on hospital mortality in non-vaccinated patients during the 2021 spring wave in the Czech Republic. METHODS: Initially, 991 patients hospitalized in the period January 1, 2021, to March 31, 2021, with PCR-confirmed SARS-CoV-2 acute respiratory infection in two university and five rural hospitals were included in the study. After exclusion of patients with an unknown outcome, a total of 790 patients entered the final analysis. The effects of different treatments were assessed in this cohort by means of propensity score matching. RESULTS: Of the 790 patients, 282 patients died in the hospital; 37.7% were male and 33.3% were female. Age, sex, state of the disease, pneumonia, therapy, and several comorbidities were matched to simulate a case-control study. For anticoagulation treatment, 233 cases (full-dose) vs. 233 controls (prophylactic dose) were matched. The difference in mortality was significant in 16 of the 50 runs. For the treatment with isoprinosine, ivermectin, and vitamin D, none of the 50 runs led to a significant difference in hospital mortality. CONCLUSION: Prophylactic-dose anticoagulation treatment in our study was found to be beneficial in comparison with the full dose. Supplementation with vitamin D did not show any meaningful benefit in terms of lowering the hospital mortality. Neither ivermectin nor, isoprinosine was found to significantly decrease hospital mortality.


Assuntos
COVID-19 , Inosina Pranobex , Humanos , Masculino , Feminino , SARS-CoV-2 , Ivermectina/uso terapêutico , Estudos Retrospectivos , Estudos de Casos e Controles , Vitamina D/uso terapêutico , Pontuação de Propensão , Vitaminas , Anticoagulantes/uso terapêutico
19.
Pediatr Infect Dis J ; 43(6): 582-586, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38380931

RESUMO

BACKGROUND: Immunocompromised individuals are at increased risk for severe disease and complications from viral infections, highlighting the importance of vaccination. However, in extremely rare situations, vaccine associated viral infections can be associated with disseminated disease and complications in immunocompromised hosts. CASE: Herein, we present a case of a 1-year-old child diagnosed with acute myeloid leukemia less than 2 weeks after receiving live viral vaccines who developed acute vaccine-strain measles virus disease, later complicated by central nervous system involvement following hematopoietic stem cell transplantation. A brain biopsy specimen was positive for vaccine-strain measles virus detected by reverse transcriptase polymerase chain reaction. MANAGEMENT AND OUTCOME: She was treated with intravenous ribavirin, inosine pranobex, intrathecal interferon-alpha and donor lymphocyte infusion following measles-mumps-rubella vaccine boost. Despite these measures, the patient suffered neurologic decline and dysautonomia, expiring after compassionate extubation. Management and ideal risk mitigation strategies are discussed within the context of existing literature for this rare complication.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Sarampo , Humanos , Sarampo/complicações , Feminino , Lactente , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Vírus do Sarampo/genética , Hospedeiro Imunocomprometido , Antivirais/uso terapêutico , Vacina contra Sarampo-Caxumba-Rubéola/efeitos adversos , Ribavirina/uso terapêutico , Encefalite Viral/etiologia , Encefalite Viral/tratamento farmacológico , Corpos de Inclusão Viral , Inosina Pranobex/uso terapêutico , Vacina contra Sarampo/efeitos adversos , Vacina contra Sarampo/administração & dosagem
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