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1.
Viruses ; 15(4)2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-37112864

RESUMO

Dengue virus (DENV) infection is a serious global health issue as it causes severe dengue hemorrhagic fever and dengue shock syndrome. Since no approved therapies are available to treat DENV infection, it is necessary to develop new agents or supplements that can do this. In this study, grape seed proanthocyanidins extract (GSPE), which is widely consumed as a dietary supplement, dose-dependently suppressed the replication of four DENV serotypes. The inhibitory mechanism demonstrated that GSPE downregulated DENV-induced aberrant cyclooxygenase-2 (COX-2) expression, revealing that the inhibitory effect of the GSPE on DENV replication involved targeting DENV-induced COX-2 expression. Mechanistic studies on signaling regulation have demonstrated that GSPE significantly reduced COX-2 expression by inactivating NF-κB and ERK/P38 MAPK signaling activities. Administrating GSPE to DENV-infected suckling mice reduced virus replication, mortality, and monocyte infiltration of the brain. In addition, GSPE substantially reduced the expression of DENV-induced inflammatory cytokines associated with severe dengue disease, including tumor necrosis factor-α, nitric oxide synthase, interleukin (IL)-1, IL-6, and IL-8, suggesting that GSPE has potential as a dietary supplement to attenuate DENV infection and severe dengue.


Assuntos
Vírus da Dengue , Dengue , Dengue Grave , Camundongos , Animais , NF-kappa B/metabolismo , Ciclo-Oxigenase 2/genética , Vírus da Dengue/fisiologia , Dengue Grave/tratamento farmacológico , Replicação Viral
2.
Homeopathy ; 111(3): 226-231, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749419

RESUMO

Dengue, with four viral serotypes, causes epidemics in tropical and sub-tropical regions. Allopathic antiviral therapies and a vaccine of general use are lacking. The homeopathic medicine Apis mellifica, advised in anaphylaxis from honeybee sting, is proposed to address the life-threatening dengue shock syndrome, which develops from dengue hemorrhagic fever and has features of anaphylaxis. In both dengue and anaphylaxis, immunoglobulin E activates, and released vasoactive mediators (importantly histamine, tryptase and platelet-activating factor) cause, a vascular permeability enabling shock. In dengue, another mechanism, namely antibody-dependent enhancement, due to secondary infection with a heterologous dengue serotype, is associated with release of vasoactive mediators. The homeopathic medicine Apis mellifica indicates plasma leak, shock, and the serous effusion that is noted in dengue patients, and is a suggested prophylactic and therapeutic medicine for dengue shock syndrome.


Assuntos
Anafilaxia , Vírus da Dengue , Dengue , Homeopatia , Mordeduras e Picadas de Insetos , Materia Medica , Dengue Grave , Anafilaxia/complicações , Anafilaxia/tratamento farmacológico , Animais , Abelhas , Humanos , Mordeduras e Picadas de Insetos/complicações , Dengue Grave/complicações , Dengue Grave/tratamento farmacológico
3.
BMC Infect Dis ; 21(1): 978, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544380

RESUMO

BACKGROUND: Dengue fever is a common mosquito borne viral infection. Severe dengue fever associated severe hepatitis carries high mortality. Based on the beneficial effect of N-acetylcysteine (NAC) in paracetamol poisoning and non-acetaminophen induced liver failure, it is used in dengue fever associated hepatitis in clinical practice. We aim to study the reversal of liver enzymes with NAC in the setting of severe hepatitis due to severe dengue infection. METHODS: A retrospective analysis was conducted on hospitalized 30 adults with severe dengue fever with severe hepatitis. These 30 patients had aspartate transaminase (AST) and alanine transaminases (ALT) more than 500 U/L and/or PT INR (prothrombin time and international normalized ratio) more than 1.5. They were treated with NAC infusion of 100 mg/h for 3 to 5 days. RESULTS: The mean age of the group was 49.9 ± 11.46 years and 18 (60%) patients were males. Nineteen patients (63%) developed dengue shock. Of them 12 patients (40%) developed hepatic encephalopathy. Median AST on the day of administration of NAC was 1125 U/L interquartile range (IQR) 1653.25 while median ALT was 752 (IQR 459.25). There was a statistically significant reduction of both ALT (p = 0.034) and AST (p = 0.049) from day 1 to 4 after NAC infusion. Rise of platelet count between day 1 and day 4 also showed statistically significant difference (p = 0.011) but the reduction of prothrombin time and international normalized ratio (PT/INR) from 1 to day 4 did not show statistical significance difference. Mean duration of treatment with NAC was 3.61 ± 0.75 days while mean length of hospital stay was 6.2 ± 1.27 days. Only one patient died (3.3%). None of the patients reported adverse drug reaction due to NAC. CONCLUSION: Majority of patients demonstrated marked clinical and biochemical improvements and they recovered fully. We observed faster and significant recovery of liver enzymes following administration of NAC. Based on the above findings, this study provides preliminary evidence for the beneficial effect of NAC in severe hepatitis in dengue infection with greater survival benefits.


Assuntos
Hepatite , Dengue Grave , Acetaminofen , Acetilcisteína/uso terapêutico , Adulto , Animais , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos , Dengue Grave/tratamento farmacológico
4.
Viruses ; 13(8)2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34452405

RESUMO

Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico-informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, "Adrenergic receptor antagonist", "ATPase inhibitor", "NF-kB pathway inhibitor" and "Serotonin receptor antagonist", were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.


Assuntos
Antivirais/uso terapêutico , Dengue/tratamento farmacológico , Transcriptoma , Adenosina Trifosfatases/antagonistas & inibidores , Antagonistas Adrenérgicos/farmacologia , Antagonistas Adrenérgicos/uso terapêutico , Antivirais/farmacologia , Encéfalo/metabolismo , Simulação por Computador , Dengue/sangue , Dengue/genética , Dengue/metabolismo , Descoberta de Drogas , Avaliação Pré-Clínica de Medicamentos , Reposicionamento de Medicamentos , Humanos , Fígado/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , NF-kappa B/metabolismo , Antagonistas da Serotonina/farmacologia , Antagonistas da Serotonina/uso terapêutico , Dengue Grave/sangue , Dengue Grave/tratamento farmacológico , Dengue Grave/genética , Dengue Grave/metabolismo , Baço/metabolismo
5.
Rev Med Virol ; 31(6): e2228, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33694220

RESUMO

Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used as antiviral agents for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. We performed a systematic review to examine whether prior clinical studies that compared the effects of CQ and HCQ to a control for the treatment of non-SARS-CoV2 infection supported the use of these agents in the present SARS-CoV2 outbreak. PubMed, EMBASE, Scopus and Web of Science (PROSPERO CRD42020183429) were searched from inception through 2 April 2020 without language restrictions. Of 1766 retrieved reports, 18 studies met our inclusion criteria, including 17 prospective controlled studies and one retrospective study. CQ or HCQ were compared to control for the treatment of infectious mononucleosis (EBV, n = 4), warts (human papillomavirus, n = 2), chronic HIV infection (n = 6), acute chikungunya infection (n = 1), acute dengue virus infection (n = 2), chronic HCV (n = 2), and as preventive measures for influenza infection (n = 1). Survival was not evaluated in any study. For HIV, the virus that was most investigated, while two early studies suggested HCQ reduced viral levels, four subsequent ones did not, and in two of these CQ or HCQ increased viral levels and reduced CD4 counts. Overall, three studies concluded CQ or HCQ were effective; four concluded further research was needed to assess the treatments' effectiveness; and 11 concluded that treatment was ineffective or potentially harmful. Prior controlled clinical trials with CQ and HCQ for non-SARS-CoV2 viral infections do not support these agents' use for the SARS-CoV2 outbreak.


Assuntos
Febre de Chikungunya/tratamento farmacológico , Cloroquina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Mononucleose Infecciosa/tratamento farmacológico , Dengue Grave/tratamento farmacológico , Verrugas/tratamento farmacológico , Alphapapillomavirus/efeitos dos fármacos , Alphapapillomavirus/imunologia , Alphapapillomavirus/patogenicidade , Antivirais/uso terapêutico , COVID-19/virologia , Febre de Chikungunya/imunologia , Febre de Chikungunya/patologia , Febre de Chikungunya/virologia , Vírus Chikungunya/efeitos dos fármacos , Vírus Chikungunya/imunologia , Vírus Chikungunya/patogenicidade , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/imunologia , Vírus da Dengue/patogenicidade , HIV/efeitos dos fármacos , HIV/imunologia , HIV/patogenicidade , Infecções por HIV/imunologia , Infecções por HIV/patologia , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/imunologia , Hepacivirus/patogenicidade , Hepatite C Crônica/imunologia , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/patogenicidade , Humanos , Mononucleose Infecciosa/imunologia , Mononucleose Infecciosa/patologia , Mononucleose Infecciosa/virologia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Dengue Grave/imunologia , Dengue Grave/patologia , Dengue Grave/virologia , Resultado do Tratamento , Verrugas/imunologia , Verrugas/patologia , Verrugas/virologia , Tratamento Farmacológico da COVID-19
6.
Sci Rep ; 9(1): 523, 2019 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-30679503

RESUMO

To detect drug candidates for dengue haemorrhagic fever (DHF), we employed a computational drug repositioning method to perform an integrated multiple omics analysis based on transcriptomic, proteomic, and interactomic data. We identified 3,892 significant genes, 389 proteins, and 221 human proteins by transcriptomic analysis, proteomic analysis, and human-dengue virus protein-protein interactions, respectively. The drug candidates were selected using gene expression profiles for inverse drug-disease relationships compared with DHF patients and healthy controls as well as interactomic relationships between the signature proteins and chemical compounds. Integrating the results of the multiple omics analysis, we identified eight candidates for drug repositioning to treat DHF that targeted five proteins (ACTG1, CALR, ERC1, HSPA5, SYNE2) involved in human-dengue virus protein-protein interactions, and the signature proteins in the proteomic analysis mapped to significant pathways. Interestingly, five of these drug candidates, valparoic acid, sirolimus, resveratrol, vorinostat, and Y-27632, have been reported previously as effective treatments for flavivirus-induced diseases. The computational approach using multiple omics data for drug repositioning described in this study can be used effectively to identify novel drug candidates.


Assuntos
Biologia Computacional/métodos , Reposicionamento de Medicamentos/métodos , Dengue Grave/tratamento farmacológico , Chaperona BiP do Retículo Endoplasmático , Humanos , Terapia de Alvo Molecular/métodos , Mapas de Interação de Proteínas/efeitos dos fármacos , Dengue Grave/genética , Dengue Grave/metabolismo , Transcriptoma/efeitos dos fármacos
7.
BMJ Case Rep ; 20182018 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-29950498

RESUMO

A 30-year-old woman with severe dengue presented on the sixth day of her illness with life-threatening thrombocytopenia, refractory to multiple platelet transfusions. Dengue IgM antibody and the non-structural-1 antigen tests as of day 3 were negative. The IgG antibody against the same was positive, suggesting a past episode of dengue. Since she had a history of menorrhagia prior to the current illness, a working diagnosis of idiopathic thrombocytopenic purpura was made, for which intravenous immunoglobulin (IVIg) was administered that led to a rapid rise in the platelet count with no adverse events. Subsequently, dengue IgM antibody repeated on day 6 came back positive, confirming dengue. This case report re-emphasises the potential use of IVIg in patients with severe thrombocytopenia in dengue.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Dengue Grave/tratamento farmacológico , Adulto , Feminino , Humanos , Púrpura Trombocitopênica Idiopática/virologia , Dengue Grave/complicações
8.
Antiviral Res ; 154: 104-109, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29665374

RESUMO

Dengue is a mosquito-borne disease of global public health importance caused by four genetically and serologically related viruses (DENV-1 to DENV-4). Efforts to develop effective vaccines and therapeutics for dengue have been slowed by the paucity of preclinical models that mimic human disease. DENV-2 models in interferon receptor deficient AG129 mice were an important advance but only allowed testing against a single DENV serotype. We have developed complementary AG129 mouse models of severe disseminated dengue infection using strains of the other three DENV serotypes. Here we used the adenosine nucleoside inhibitor NITD-008 to show that these models provide the ability to perform comparative preclinical efficacy testing of candidate antivirals in vivo against the full-spectrum of DENV serotypes. Although NITD-008 was effective in modulating disease caused by all DENV serotypes, the variability in protection among DENV serotypes was greater than expected from differences in activity in in vitro testing studies emphasizing the need to undertake spectrum of activity testing to help in prioritization of candidate compounds for further development.


Assuntos
Antivirais/uso terapêutico , Vírus da Dengue/efeitos dos fármacos , Modelos Animais de Doenças , Inibidores da Síntese de Ácido Nucleico/uso terapêutico , Dengue Grave/tratamento farmacológico , Adenosina/química , Animais , Avaliação Pré-Clínica de Medicamentos , Camundongos , Inibidores da Síntese de Ácido Nucleico/farmacologia , Estudo de Prova de Conceito , Sorogrupo
9.
Arch Virol ; 163(7): 1717-1726, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29520688

RESUMO

Dengue is the most prevalent arboviral disease in humans and leads to significant morbidity and socioeconomic burden in tropical and subtropical areas. Dengue is caused by infection with any of the four closely related serotypes of dengue virus (DENV1-4) and usually manifests as a mild febrile illness, but may develop into fatal dengue hemorrhagic fever and shock syndrome. There are no specific antiviral therapies against dengue because understanding of DENV biology is limited. A tetravalent chimeric dengue vaccine, Dengvaxia, has finally been licensed for use, but its efficacy was significantly lower against DENV-2 infections and in dengue-naïve individuals. The identification of mechanisms underlying the interactions between DENV and immune responses will help to determine efficient therapeutic and preventive options. It has been well established how the innate immune system responds to DENV infection and how DENV overcomes innate antiviral defenses, however further progress in this field remains hampered by the absence of appropriate experimental dengue models. Herein, we review the available in vitro and in vivo approaches to study the innate immune responses to DENV.


Assuntos
Vírus da Dengue/imunologia , Dengue/imunologia , Imunidade Inata , Dengue Grave/imunologia , Animais , Antivirais/uso terapêutico , Dengue/tratamento farmacológico , Dengue/prevenção & controle , Dengue/virologia , Vacinas contra Dengue/administração & dosagem , Vacinas contra Dengue/imunologia , Vírus da Dengue/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Camundongos , Primatas , Dengue Grave/tratamento farmacológico , Dengue Grave/prevenção & controle , Dengue Grave/virologia
10.
Expert Rev Anti Infect Ther ; 15(6): 585-604, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28480779

RESUMO

INTRODUCTION: Pooled human immunoglobulins (IGs) are prepared from plasma obtained from healthy donors as a concentrated antibody-containing solution. In addition, high-titer IGs (hyperimmune) against a specific pathogen can be obtained from vaccinated or convalescing donors. Currently, IGs can be used for the treatment of a variety of infections for which no specific therapy exists or that remain difficult to treat. Moreover, the recent pathogen outbreaks for which there is no approved treatment have renewed attention to the role of convalescent plasma and IGs. Areas covered: In this review, a historical perspective of the use of sera and IGs in humans as anti-infective agents (any viral, bacterial, parasitic infection), excluding immunodeficient patients, is presented from early development to the latest clinical studies. A Medline search was conducted to examine the peer-reviewed literature, with no date limits. Expert commentary: Human pooled plasma-derived IG products benefit from the polyclonal response of every individual donor and from the interindividual variability in such response. The trend to increased availability of vaccines for infectious diseases also opens new potential applications of hyperimmune IGs for emerging or re-emerging infectious diseases (e.g.: Ebola, Zika, Dengue), for the prevention and treatment in the general population, healthcare personnel and caregivers.


Assuntos
Doenças Transmissíveis Emergentes/tratamento farmacológico , Doença pelo Vírus Ebola/tratamento farmacológico , Soros Imunes/administração & dosagem , Imunização Passiva/métodos , Imunoglobulinas/uso terapêutico , Dengue Grave/tratamento farmacológico , Infecção por Zika virus/tratamento farmacológico , Ensaios Clínicos como Assunto , Doenças Transmissíveis Emergentes/imunologia , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/virologia , Convalescença , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/imunologia , Vírus da Dengue/patogenicidade , Ebolavirus/efeitos dos fármacos , Ebolavirus/imunologia , Ebolavirus/patogenicidade , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Doença pelo Vírus Ebola/virologia , Humanos , Dengue Grave/imunologia , Dengue Grave/prevenção & controle , Dengue Grave/virologia , Vacinação , Vacinas Virais/administração & dosagem , Vacinas Virais/biossíntese , Zika virus/efeitos dos fármacos , Zika virus/imunologia , Zika virus/patogenicidade , Infecção por Zika virus/imunologia , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/virologia
11.
J Pak Med Assoc ; 67(3): 400-404, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28303989

RESUMO

OBJECTIVE: To determine the frequency of worsening liver function among hospital in-patients with severe dengue hepatitis receiving paracetamol. METHODS: This retrospective study was conducted at the Department of Medicine, Aga Khan University Hospital, Karachi, and comprised records of dengue patients with severe hepatitis who received paracetamol for control of fever between June 2007 and December 2014. Alanine aminotransferase at baseline and following paracetamol administration was noted, as well as dosage and duration of paracetamol, along with participants' demographic details. Frequency of patients who developed worsening or improvement of alanine aminotransferase was also noted. SPSS 19 was used for data analysis. RESULTS: Of the 113 subjects, 73(64.6%) were male and 40(35.4%) were female. Overall improvement was observed in subsequent alanine aminotransferase levels (491 units per litre, IQR 356.5 TO 775 vs 151 units per litre, IQR 49.5 to 299.5). Most commonly prescribed dose of paracetamol was 2g (IQR 1 to 5 grams), which was taken for a median duration of 1 day (IQR 1 to 3 days). Moreover, 100(88.5 %) patients showed improvement in alanine aminotransferase. Only 13(11.5 %) patients developed worsening of alanine aminotransferase. Of those with worsening liver function, 8(61.5 %) were discharged home with no clinical deterioration and 5(38.5 %) deaths were observed. However, causes of deaths were unrelated to liver dysfunction. CONCLUSIONS: The frequency of worsening liver function following paracetamol administration in patients with severe dengue hepatitis was relatively low.


Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Narcóticos/efeitos adversos , Hepatite , Fígado , Dengue Grave , Acetaminofen/uso terapêutico , Adolescente , Adulto , Analgésicos não Narcóticos/uso terapêutico , Feminino , Hepatite/epidemiologia , Hepatite/etiologia , Hepatite/fisiopatologia , Humanos , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Paquistão , Estudos Retrospectivos , Dengue Grave/tratamento farmacológico , Dengue Grave/epidemiologia , Adulto Jovem
12.
Medicine (Baltimore) ; 96(8): e6159, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28225498

RESUMO

BACKGROUND: Infection-associated hemophagocytic syndrome (IAHS) is potentially a fatal disease caused by systemic infection complicated by hemophagocyticlymphohistiocytosis (HLH). Here, we report a case of HLH associated with dengue hemorrhagic fever (DHF) after a trip to Thailand. CASE SUMMARY: A 33-year-old healthy female patient presented with 3 days of fever, myalgia, and skin rash. Serotype 3 dengue virus was isolated. Clinical and laboratory findings fulfilled the criteria of HLH. After the initiation of corticosteroid therapy, the patient recovered and laboratory findings were normalized. CONCLUSION: It would be important to differentially diagnose dengue-associated HLH from severe DHF. Early recognition and initiation of steroid treatment would be crucial for the successful treatment of dengue fever complicated by HLH.


Assuntos
Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/diagnóstico , Dengue Grave/complicações , Dengue Grave/diagnóstico , Corticosteroides/uso terapêutico , Adulto , Diagnóstico Diferencial , Diagnóstico Precoce , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/patologia , Dengue Grave/tratamento farmacológico , Dengue Grave/patologia
13.
Antiviral Res ; 141: 7-18, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28188818

RESUMO

High viral load with liver injury is exhibited in severe dengue virus (DENV) infection. Mitogen activated protein kinases (MAPKs) including ERK1/2 and p38 MAPK were previously found to be involved in the animal models of DENV-induced liver injury. However, the role of JNK1/2 signaling in DENV-induced liver injury has never been investigated. JNK1/2 inhibitor, SP600125, was used to investigate the role of JNK1/2 signaling in the BALB/c mouse model of DENV-induced liver injury. SP600125-treated DENV-infected mice ameliorated leucopenia, thrombocytopenia, hemoconcentration, liver transaminases and liver histopathology. DENV-induced liver injury exhibited induced phosphorylation of JNK1/2, whereas SP600125 reduced this phosphorylation. An apoptotic real-time PCR array profiler was used to screen how SP600125 affects the expression of 84 cell death-associated genes to minimize DENV-induced liver injury. Modulation of caspase-3, caspase-8 and caspase-9 expressions by SP600125 in DENV-infected mice suggests its efficiency in restricting apoptosis via both extrinsic and intrinsic pathways. Reduced expressions of TNF-α and TRAIL are suggestive to modulate the extrinsic apoptotic signals, where reduced p53 phosphorylation and induced anti-apoptotic Bcl-2 expression indicate the involvement of the intrinsic apoptotic pathway. This study thus demonstrates the pivotal role of JNK1/2 signaling in DENV-induced liver injury and how SP600125 modulates this pathogenesis.


Assuntos
Antracenos/farmacologia , Fígado/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína Quinase 8 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 9 Ativada por Mitógeno/antagonistas & inibidores , Dengue Grave/metabolismo , Dengue Grave/patologia , Animais , Antracenos/administração & dosagem , Antracenos/uso terapêutico , Apoptose/efeitos dos fármacos , Caspases/efeitos dos fármacos , Vírus da Dengue/efeitos dos fármacos , Modelos Animais de Doenças , Leucopenia/tratamento farmacológico , Fígado/efeitos dos fármacos , Fígado/virologia , Camundongos , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Proteína Quinase 9 Ativada por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Dengue Grave/tratamento farmacológico , Dengue Grave/virologia , Ligante Indutor de Apoptose Relacionado a TNF/genética , Fator de Necrose Tumoral alfa/genética , Carga Viral , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
14.
Clin Respir J ; 11(2): 248-253, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26072955

RESUMO

INTRODUCTION: Pulmonary infiltration and pleural effusion caused by permeability syndrome are the hallmark of pulmonary manifestation of dengue cases. OBJECTIVE AND METHODS: We report a 95-year-old chronic obstructive pulmonary disease case having dengue shock syndrome. Chest X-ray examination revealed diffuse lung infiltration. However, bilateral pneumotoceles were unexpectedly found in computed tomography (CT) images. Dengue virus type 2 infection was confirmed by virus culture, serology and reverse transcriptase-polymerase chain reaction. Profound shock with bilateral lung infiltration developed rapidly in 2 days with supportive care and empirical ampicillin/ sulbactam. Bronchoscopy revealed a whitish plaque over bilateral upper bronchi. Biopsy via bronchoscopy revealed moulds with vascular invasion. Culture of bronchial alveolar lavage yielded Aspergillus flavus. The patient died despite amphotericin B treatment, which was started since finding the whitish plaque with bronchoscopy examination. RESULTS AND CONCLUSION: Besides to considering capillary leakage syndrome, our case report and literature review alert clinicians that CT and bronchoscopy may help to identify the true pathogen though all cases with concurrent dengue and Aspergillus infections had fatal outcomes.


Assuntos
Coinfecção/diagnóstico por imagem , Aspergilose Pulmonar/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/microbiologia , Dengue Grave/diagnóstico , Idoso de 80 Anos ou mais , Broncoscopia/métodos , Coinfecção/microbiologia , Evolução Fatal , Humanos , Masculino , Aspergilose Pulmonar/microbiologia , Dengue Grave/tratamento farmacológico
15.
Expert Rev Anti Infect Ther ; 15(1): 67-78, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27786589

RESUMO

INTRODUCTION: Traditionally a disease mainly affecting the pediatric population, dengue burden has increased significantly in recent decades and adults with severe disease may become more common. There is currently no effective anti-viral agent available for the treatment of dengue and supportive care is the mainstay of management. Areas covered: We present a review of current literature on dengue severity classification systems and the management of severe dengue in adults. In particular, emphasis was placed on organ impairment in dengue and management of elderly individuals with multiple medical problems. Expert commentary: There is an urgent need to search for an effective anti-viral agent to treat infected individuals. The commercial availability of a dengue vaccine in older children has provided optimism in reducing the disease burden but long term efficacy and safety are unknown. The results from phase III trials of two new candidate vaccines are eagerly awaited.


Assuntos
Antivirais/uso terapêutico , Vacinas contra Dengue/administração & dosagem , Vírus da Dengue/isolamento & purificação , Dengue Grave/tratamento farmacológico , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Permeabilidade Capilar/efeitos dos fármacos , Ensaios Clínicos como Assunto , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/imunologia , Hidratação , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Plasma/metabolismo , Dengue Grave/complicações , Dengue Grave/fisiopatologia , Índice de Gravidade de Doença
16.
Haemophilia ; 22 Suppl 5: 90-5, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27405683

RESUMO

Haemorrhagic disorders like Postpartum haemorrhage and Dengue haemorrhagic fever are life threatening and requires an active and efficient transfusion service that could provide the most appropriate blood product which could be effective in managing them. This would essentially require prompt identification of the coagulopathy so that the best available product can be given to the bleeding patient to correct the identified haemostatic defect which will help control the bleeding. This would only be possible if the transfusion service has a laboratory to correctly detect the haemostatic defect and that too with an accuracy and precision which is ensured by a good laboratory quality assurance practices. These same processes are necessary for the transfusion services to ensure the quality of the blood products manufactured by them and that it contains adequate amounts of haemostasis factors which will be good to be effective in the management of haemorrhagic disorders. These issues are discussed in detail individually in the management of postpartum haemorrhage and Dengue haemorrhagic fever including when these can help in the use of rFVIIa in Dengue haemorrhagic fever. The requirements to ensure good-quality blood products are made available for the management of these disorders and the same have also been described.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos Hemorrágicos/diagnóstico , Laboratórios/normas , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Gerenciamento Clínico , Fator VIIa/uso terapêutico , Feminino , Transtornos Hemorrágicos/prevenção & controle , Humanos , Hemorragia Pós-Parto/prevenção & controle , Gravidez , Proteínas Recombinantes/uso terapêutico , Dengue Grave/tratamento farmacológico
17.
Antiviral Res ; 129: 93-98, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26946111

RESUMO

The antiviral activity of UV-4 was previously demonstrated against dengue virus serotype 2 (DENV2) in multiple mouse models. Herein, step-wise minimal effective dose and therapeutic window of efficacy studies of UV-4B (UV-4 hydrochloride salt) were conducted in an antibody-dependent enhancement (ADE) mouse model of severe DENV2 infection in AG129 mice lacking types I and II interferon receptors. Significant survival benefit was demonstrated with 10-20 mg/kg of UV-4B administered thrice daily (TID) for seven days with initiation of treatment up to 48 h after infection. UV-4B also reduced infectious virus production in in vitro antiviral activity assays against all four DENV serotypes, including clinical isolates. A set of purified enzyme, in vitro, and in vivo studies demonstrated that inhibition of endoplasmic reticulum (ER) α-glucosidases and not the glycosphingolipid pathway appears to be responsible for the antiviral activity of UV-4B against DENV. Along with a comprehensive safety package, these and previously published data provided support for an Investigational New Drug (IND) filing and Phases 1 and 2 clinical trials for UV-4B with an indication of acute dengue disease.


Assuntos
1-Desoxinojirimicina/análogos & derivados , Antivirais/farmacologia , Vírus da Dengue/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases/farmacologia , Dengue Grave/tratamento farmacológico , alfa-Glucosidases/metabolismo , 1-Desoxinojirimicina/administração & dosagem , 1-Desoxinojirimicina/farmacologia , 1-Desoxinojirimicina/uso terapêutico , Animais , Anticorpos Antivirais/sangue , Anticorpos Facilitadores/efeitos dos fármacos , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Células Cultivadas , Chlorocebus aethiops , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Drogas em Investigação , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/enzimologia , Inibidores de Glicosídeo Hidrolases/administração & dosagem , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Humanos , Concentração Inibidora 50 , Camundongos , Monócitos/virologia , Receptores de Interferon/deficiência , Sorogrupo , Dengue Grave/virologia , Células Vero
20.
Pediatr Int ; 57(4): 763-5, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26011764

RESUMO

Infection-associated hemophagocytic syndrome (IAHS), a secondary form of hemophagocytic lymphohistiocytosis (HLH), has been found following several types of infections and can be fatal. We report herein a case of IAHS following dengue infection in a 14-year-old patient with underlying α-thalassemia syndrome (non-deletional Hb H/Hb Constant Spring disease). He developed prolonged fever, thrombocytopenia, and progressive splenomegaly. Further investigations indicated hyperferritinemia, and increased reactive histiocytes with hemophagocytic activity in the bone marrow. He responded promptly to dexamethasone and i.v. immune globulin. Physicians should be aware of this condition, especially in countries where both dengue hemorrhagic fever and thalassemia are prevalent. The fatal outcome of IAHS can be prevented with prompt appropriate treatment.


Assuntos
Hemoglobinas Anormais , Linfo-Histiocitose Hemofagocítica/etiologia , Dengue Grave/complicações , Adolescente , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Masculino , Dengue Grave/tratamento farmacológico , Talassemia alfa/complicações
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