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3.
Cardiovasc Pathol ; 44: 107155, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31760237

RESUMO

"Since the pathological conditions take place at the cellular level, viral myocarditis and postinfectious autoimmunity can be suggested but not diagnosed clinically. All clinical methods including imaging techniques are misleading if infectious agents are involved. Accurate diagnosis demands simultaneous histologic, immunohistochemical, and molecular biological workup of the tissue. If the primary infectious or immune-mediated causes of the disease are carefully defined by clinical and biopsy-based tools, specific antiviral treatment options in addition to basic symptomatic therapy are available under certain conditions. These may allow a tailored cause-specific treatment that improves symptoms and prognosis of patients with acute and chronic disease." Uwe Kühl; Heinz-Peter SchultheissViral myocarditis.Swiss Medical Weekly. 144():w14010, JAN 2014 DOI:10.4414/smw.2014.14010.


Assuntos
Doenças Autoimunes/patologia , Cardiomiopatias/patologia , Miocardite/patologia , Miocárdio/patologia , Viroses/patologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Autoimunidade , Biópsia , Cardiomiopatias/imunologia , Cardiomiopatias/terapia , Cardiomiopatias/virologia , Interações Hospedeiro-Patógeno , Humanos , Miocardite/epidemiologia , Miocardite/terapia , Miocardite/virologia , Miocárdio/imunologia , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Viroses/imunologia , Viroses/terapia , Viroses/virologia
4.
Fertil Steril ; 112(6): 1129-1135, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843089

RESUMO

OBJECTIVE: To study the association between mode of conception and offspring infectious morbidity risk. DESIGN: Population-based cohort study. SETTING: Regional university medical center. PATIENT(S): All singleton infants born between the years 1991 and 2014 and discharged alive from the hospital. INTERVENTION(S): Follow-up time in the study was calculated from birth to an event, defined as the first offspring hospitalization with any infectious morbidity. All infectious diagnoses were compared between the study groups, and a multivariable survival model was created to study the association between mode of conception and offspring pediatric hospitalization with infectious morbidity, and adjusting for confounding or clinically significant variables. MAIN OUTCOME MEASURE(S): First offspring pediatric hospitalization with infectious morbidity. RESULT(S): During the study period, 242,187 newborns met the inclusion criteria: 2,603 (1.1%) of which were conceived after undergoing IVF, 1,172 (0.7%) after ovulation induction (OI), and 237,863 (98.3%) were conceived spontaneously. Mothers receiving fertility treatments were older and with higher rates of preterm births and low birthweights. The hospitalizations rates per 1,000 person years of follow-up were 16.34/1,000 person years, 11.61/1,000 person years, and 10.19/1,000 person years, among the IVF, OI, and spontaneously conceived offspring, respectively. The adjusted hazard ratios were 1.26 (95% confidence interval 1.13-1.42) and 1.14 (95% confidence interval 1.00-1.38), for the IVF and OI compared with the spontaneously conceived offspring, respectively. The model adjusted for preterm delivery, birthweight, maternal age, hypertension, diabetes, and cesarean section. CONCLUSION(S): Higher risk for infectious morbidity was found among offspring conceived after fertility treatments compared with spontaneously conceived offspring.


Assuntos
Infecções Bacterianas/epidemiologia , Infertilidade/terapia , Técnicas de Reprodução Assistida/efeitos adversos , Viroses/epidemiologia , Adolescente , Adulto , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Infecções Bacterianas/terapia , Criança , Pré-Escolar , Feminino , Seguimentos , Hospitalização , Humanos , Lactente , Recém-Nascido , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Israel/epidemiologia , Masculino , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Viroses/mortalidade , Viroses/terapia , Viroses/virologia , Adulto Jovem
7.
Med Sci (Paris) ; 35(8-9): 667-673, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31532379

RESUMO

Viruses are obligatory intracellular parasites that rely on a wide range of cellular factors to successfully accomplish their infectious cycle. Among those, micro (mi)RNAs have recently emerged as important modulators of viral infections. These small regulatory molecules act as repressors of gene expression. During infection, miRNAs can function by targeting either cellular or viral RNAs. In this review, we will recapitulate what has been reported to date on this interplay between cellular miRNAs and viruses and the effect on the infection. Furthermore, we will briefly discuss the possibilities of interfering with the infection through the modulation of this pathway to develop novel antiviral therapies.


Assuntos
Interações Hospedeiro-Patógeno/genética , MicroRNAs/fisiologia , Viroses/genética , Viroses/imunologia , Animais , Antivirais/uso terapêutico , Interações Hospedeiro-Patógeno/imunologia , Humanos , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Viroses/terapia , Replicação Viral/genética , Vírus/genética , Vírus/imunologia
8.
Clin Microbiol Rev ; 32(4)2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31511250

RESUMO

Patients undergoing solid-organ transplantation (SOT) or allogeneic hematopoietic cell transplantation (HCT) are at increased risk for infectious complications. Community-acquired respiratory viruses (CARVs) pose a particular challenge due to the frequent exposure pre-, peri-, and posttransplantation. Although influenza A and B viruses have a top priority regarding prevention and treatment, recent molecular diagnostic tests detecting an array of other CARVs in real time have dramatically expanded our knowledge about the epidemiology, diversity, and impact of CARV infections in the general population and in allogeneic HCT and SOT patients. These data have demonstrated that non-influenza CARVs independently contribute to morbidity and mortality of transplant patients. However, effective vaccination and antiviral treatment is only emerging for non-influenza CARVs, placing emphasis on infection control and supportive measures. Here, we review the current knowledge about CARVs in SOT and allogeneic HCT patients to better define the magnitude of this unmet clinical need and to discuss some of the lessons learned from human influenza virus, respiratory syncytial virus, parainfluenzavirus, rhinovirus, coronavirus, adenovirus, and bocavirus regarding diagnosis, prevention, and treatment.


Assuntos
Biodiversidade , Infecções Comunitárias Adquiridas/virologia , Infecções Respiratórias/virologia , Transplantados , Viroses/virologia , Vírus/classificação , Humanos , Infecções Respiratórias/terapia , Viroses/terapia , Fenômenos Fisiológicos Virais
9.
Photochem Photobiol Sci ; 18(11): 2565-2612, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31397467

RESUMO

Photodynamic therapy (PDT) is a well-established treatment option in the treatment of certain cancerous and pre-cancerous lesions. Though best-known for its application in tumor therapy, historically the photodynamic effect was first demonstrated against bacteria at the beginning of the 20th century. Today, in light of spreading antibiotic resistance and the rise of new infections, this photodynamic inactivation (PDI) of microbes, such as bacteria, fungi, and viruses, is gaining considerable attention. This review focuses on the PDI of viruses as an alternative treatment in antiviral therapy, but also as a means of viral decontamination, covering mainly the literature of the last decade. The PDI of viruses shares the general action mechanism of photodynamic applications: the irradiation of a dye with light and the subsequent generation of reactive oxygen species (ROS) which are the effective phototoxic agents damaging virus targets by reacting with viral nucleic acids, lipids and proteins. Interestingly, a light-independent antiviral activity has also been found for some of these dyes. This review covers the compound classes employed in the PDI of viruses and their various areas of use. In the medical area, currently two fields stand out in which the PDI of viruses has found broader application: the purification of blood products and the treatment of human papilloma virus manifestations. However, the PDI of viruses has also found interest in such diverse areas as water and surface decontamination, and biosafety.


Assuntos
Luz , Fotoquimioterapia/tendências , Viroses/terapia , Vírus/efeitos da radiação , Humanos , Papillomaviridae/efeitos dos fármacos , Papillomaviridae/efeitos da radiação , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Viroses/tratamento farmacológico , Viroses/metabolismo , Vírus/efeitos dos fármacos , Vírus/metabolismo
12.
Biometals ; 32(3): 545-561, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31209680

RESUMO

Oncolytic viruses rewire the immune system and can lead to long-lasting antitumor defenses against primary and metastatic tumors. However, results from clinical studies have shown heterogeneity in responses suggesting that multiplexed approaches may be necessary to consistently generate positive outcomes in patients. To this end, we explored the combination of oncolytic rhabdovirus VSV∆51 with vanadium(V) dipicolinate derivatives, which have already been explored for their antidiabetic properties in animal models. The combination of vanadium-based dipicolinate compounds with VSV∆51 significantly increased viral replication and cytotoxicity in the human renal cell carcinoma cell line 786-0. The effects of three vanadium(V)-dipicolinate coordination complexes ([VO2dipic]-, [VO2dipic-OH]- and [VO2dipic-Cl]- with -OH or -Cl in the para position) were compared to that of the simple salts using spectroscopy and speciation profiles. Like the vanadate salts and the vanadyl cation, all dioxovanadium(V) dipicolinate complexes tested were found to increase viral infection and cytotoxicity when used in combination with VSV∆51. Viral sensitization is dependent on the vanadium since free dipicolinate ligands exerted no effect on viral infection and viability. The ability of these complexes to interact with interfaces and the stability of the complexes were evaluated under physiological conditions. Results indicate that these complexes undergo hydrolysis in cell culture media thereby generating vanadate. The vanadium dipicolinate derivatives in the context of immunovirotherapy shares similarities with previous studies exploring the antidiabetic properties of the compounds. The synergy between vanadium compounds and the oncolytic virus suggests that these compounds may be valuable in the development of novel and effective pharmaco-viral therapies.


Assuntos
Antivirais/farmacologia , Complexos de Coordenação/farmacologia , Terapia Viral Oncolítica , Vírus Oncolíticos/efeitos dos fármacos , Ácidos Picolínicos/farmacologia , Compostos de Vanádio/farmacologia , Viroses/terapia , Antivirais/síntese química , Antivirais/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Humanos , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ácidos Picolínicos/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Compostos de Vanádio/química , Viroses/tratamento farmacológico
15.
Paediatr Respir Rev ; 30: 58-64, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30962153

RESUMO

Cough is a forced expulsive manoeuvre, usually against a closed glottis and is associated with a characteristic sound that is easily recognised. It is a protective reflex against aspiration and to clear airway secretions. In children cough is extremely common and when prolonged it is often a cause for concern for parents, resulting in a high proportion of attendances to primary and secondary care. There are many causes of cough which may be divided into productive or non-productive in character. As there are many guidelines for the management of productive or 'wet' cough the focus of this paper will be to discuss some of the main causes, investigations and management options for 'dry' cough. Dry coughing suggests airway irritation and or inflammation (without excessive extra secretion formation) and is predominantly the result of an acute viral respiratory infection that may last up to 3-4 weeks.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Tosse/terapia , Refluxo Gastroesofágico/tratamento farmacológico , Infecções Respiratórias/terapia , Rinite Alérgica/tratamento farmacológico , Viroses/terapia , Coqueluche/terapia , Asma/complicações , Criança , Tosse/etiologia , Progressão da Doença , Refluxo Gastroesofágico/complicações , Humanos , Infecções Respiratórias/complicações , Rinite Alérgica/complicações , Poluição por Fumaça de Tabaco/efeitos adversos , Viroses/complicações , Coqueluche/complicações
16.
Molecules ; 24(7)2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30959782

RESUMO

From its unexpected discovery as a bacterial adaptive immune system to its countless applications as one of the most versatile gene-editing tools, the CRISPR/Cas9 system has revolutionized every field of life science. Virology is no exception to this ever-growing list of CRISPR/Cas9-based applications. Direct manipulation of a virus genome by CRISPR/Cas9 has enabled a systematic study of cis-elements and trans-elements encoded in a virus genome. In addition, this virus genome-specific mutagenesis by CRISPR/Cas9 was further funneled into the development of a novel class of antiviral therapy targeting many incurable chronic viral infections. In this review, a general concept on the CRISPR/Cas9-based antiviral strategy will be described first. To understand the current status of the CRISPR/Cas9-based antiviral approach, a series of recently published antiviral studies involving CRISPR/Cas9-mediated control of several clinically-relevant viruses including human immunodeficiency virus, hepatitis B virus, herpesviruses, human papillomavirus, and other viruses will be presented. Lastly, the potential challenge and future prospect for successful clinical translation of this CRISPR/Cas9-based antiviral method will be discussed.


Assuntos
Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Viroses/genética , Vírus/genética , Genoma Viral/genética , Humanos , Viroses/terapia , Viroses/virologia , Vírus/patogenicidade
17.
Math Biosci Eng ; 16(3): 1709-1717, 2019 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-30947439

RESUMO

The interaction between viral proteins and small molecule compounds is the basis of drug design. Therefore, it is a fundamental challenge to identify viral proteins according to their amino acid sequences in the field of biopharmaceuticals. The traditional prediction methods su er from the data imbalance problem and take too long computation time. To this end, this paper proposes a deep learning framework for virus protein identifying. In the framework, we employ Temporal Convolutional Network(TCN) instead of Recurrent Neural Network(RNN) for feature extraction to improve computation e ciency. We also customize the cost-sensitive loss function of TCN and introduce the misclassification cost of training samples into the weight update of Gradient Boosting Decision Tree(GBDT) to address data imbalance problem. Experiment results show that our framework not only outperforms traditional data imbalance methods but also greatly reduces the computation time with slight performance enhancement.


Assuntos
Produtos Biológicos , Biologia Computacional/métodos , Proteínas Virais/química , Algoritmos , Antivirais/farmacologia , Simulação por Computador , Bases de Dados Factuais , Aprendizado Profundo , Humanos , Internet , Aprendizado de Máquina , Fatores de Tempo , Viroses/terapia
18.
Front Immunol ; 10: 169, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30814995

RESUMO

The long-term persistence of viral antigens drives virus-specific CD8 T cell exhaustion during chronic viral infection. Yet exhausted, CD8 T cells are still endowed with certain levels of effector function, by which they can keep viral replication in check in chronic infection. However, the regulatory factors involved in regulating the effector function of exhausted CD8 T cell are largely unknown. Using mouse model of chronic LCMV infection, we found that the deletion of transcription factor TCF-1 in LCMV-specific exhausted CD8 T cells led to the profound reduction in cytokine production and degranulation. Conversely, ectopic expression of TCF-1 or using agonist to activate TCF-1 activities promotes the effector function of exhausted CD8 T cells. Mechanistically, TCF-1 fuels the functionalities of exhausted CD8 T cells by promoting the expression of an array of key effector function-associated transcription regulators, including Foxo1, Zeb2, Id3, and Eomes. These results collectively indicate that targeting TCF-1 mediated transcriptional pathway may represent a promising immunotherapy strategy against chronic viral infections by reinvigorating the effector function of exhausted virus-specific CD8 T cells.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Fator 1 de Transcrição de Linfócitos T/metabolismo , Viroses/etiologia , Viroses/metabolismo , Transferência Adotiva , Animais , Sobrevivência Celular , Doença Crônica , Citocinas/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Coriomeningite Linfocítica/imunologia , Coriomeningite Linfocítica/metabolismo , Coriomeningite Linfocítica/terapia , Coriomeningite Linfocítica/virologia , Vírus da Coriomeningite Linfocítica/imunologia , Camundongos , Camundongos Transgênicos , Fator 1 de Transcrição de Linfócitos T/genética , Quimeras de Transplante , Carga Viral , Viroses/terapia
19.
Am J Med Sci ; 357(4): 348-351, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30638600

RESUMO

Allopurinol is a first line agent in treating gout, but it also carries the risk of severe side effects. Stevens-Johnson syndrome (SJS) is one of the life threatening severe cutaneous adverse reactions caused by allopurinol. The severity of the severe cutaneous adverse reactions can be categorized based upon the area of skin involvement: (1) erythema multiforme major limited to 1-2 % of the body surface area (BSA); (2) SJS involving <10% of the BSA, (3) SJS and toxic epidermal necrolysis overlap involving 10-30% of the BSA and (4) toxic epidermal necrolysis syndrome involving >30% of the BSA. SJS can be caused by drugs and viruses, the former being more frequent. We report a case of an 85-year-old Han-Chinese female who developed SJS after ingestion of allopurinol 8 days prior to the hospitalization. The patient also had concomitant acute viral illness, which complicated the clinical scenario causing acute renal failure and hemodynamic compromise.


Assuntos
Alopurinol/efeitos adversos , Supressores da Gota/efeitos adversos , Síndrome de Stevens-Johnson/terapia , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/terapia , Lesão Renal Aguda/virologia , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Síndrome de Stevens-Johnson/etiologia , Resultado do Tratamento , Viroses/complicações , Viroses/fisiopatologia , Viroses/terapia
20.
Cells ; 8(1)2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30646564

RESUMO

Adverse outcomes following virus-associated disease in patients receiving allogeneic haematopoietic stem cell transplantation (HSCT) have encouraged strategies to control viral reactivation in immunosuppressed patients. However, despite timely treatment with antiviral medication, some viral infections remain refractory to treatment, which hampers outcomes after HSCT, and are responsible for a high proportion of transplant-related morbidity and mortality. Adoptive transfer of donor-derived lymphocytes aims to improve cellular immunity and to prevent or treat viral diseases after HSCT. Early reports described the feasibility of transferring nonspecific lymphocytes from donors, which led to the development of cell therapy approaches based on virus-specific T cells, allowing a targeted treatment of infections, while limiting adverse events such as graft versus host disease (GvHD). Both expansion and direct selection techniques have yielded comparable results in terms of efficacy (around 70⁻80%), but efficacy is difficult to predict for individual cases. Generating bespoke products for each donor⁻recipient pair can be expensive, and there remains the major obstacle of generating products from seronegative or poorly responsive donors. More recent studies have focused on the feasibility of collecting and infusing partially matched third-party virus-specific T cells, reporting response rates of 60⁻70%. Future development of this approach will involve the broadening of applicability to multiple viruses, the optimization and cost-control of manufacturing, larger multicentred efficacy trials, and finally the creation of cell banks that can provide prompt access to virus-specific cellular product. The aim of this review is to summarise present knowledge on adoptive T cell manufacturing, efficacy and potential future developments.


Assuntos
Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunoterapia Adotiva/métodos , Linfócitos T/transplante , Viroses/terapia , Adulto , Criança , Doação Dirigida de Tecido , Doença Enxerto-Hospedeiro/etiologia , Humanos , Viroses/etiologia
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