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1.
Wiad Lek ; 73(9 cz. 2): 1968-1972, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33148842

RESUMO

OBJECTIVE: The aim: Is to increase effectiveness and assess safety of the antiviral therapy in complex treatment of patients with psoriasis with activated chronic herpes virus infection of types 1 and 2. PATIENTS AND METHODS: Matherials and methods: 120 patients and 25 practically healthy persons were examined. RESULTS: Results: It has been studied an effect of antiviral therapy on the background of basic therapy in patients with P+HSV 1,2: the percentage of HSV 1,2 DNA detection after the use of acyclovir and/or inosine pranobex was decreased in saliva from 22.0±3.43 % to 6.7±1.32 % (р<0.01) and in epithelium - from 33.3±4.23 % to 6.7±1.8 % (р<0.01); The use of antiviral therapy has showed a decrease in the expression of miR 155 molecules from 126.3 ±10.5 U/6 to 62.4±5.48 U/6 (р<0.05), an increase in the number of T-regulatory lymphocytes from 6.8±1.25% to 9.1±1.41% (p=0.0503); a decrease of IFN-α level in saliva from10.1±1.84 ng/ml to 8.2±1.27 ng/ml (р1=0.0398); in the serum IL-23 level was significantly decreased from14.9±2.11 pg/ml to 8.8±2.03 pg/ml (р<0.05) and TGF-ß synthesis was increased from 3.9±1.23 pg/ml to 9.3±2.21 pg/ml (р<0.01). CONCLUSION: Conclusions: An improved method of treatment and evaluation of its clinical and immunological effectiveness based on an integral criterion was suggested as a result of conducted antiviral therapy amid basic therapy in patients with psoriasis with activated HSV-1 and HSV-2.


Assuntos
Antivirais , Herpesvirus Humano 1 , Psoríase , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Herpesvirus Humano 2 , Humanos , Psoríase/complicações , Psoríase/tratamento farmacológico
2.
BMC Infect Dis ; 20(1): 832, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176697

RESUMO

BACKGROUND: Carvacrol, as the major components of aromatic plants used for treating human skin diseases including origanum, Satureja, thymus, and coridothymus species, presented a kind of antiviral activity. To explore the mechanisms of carvacrol against herpes simplex virus (HSV) in vitro. METHOD: The BSC-1 cells model of HSV infection was established, and from the two aspects of viral replication level and cell death pathway, the antiviral effects of carvacrol on HSV infected cells were also evaluated by plaque assay under the three modes including prevention, treatment, and direct inactivation. RESULTS: In the three ways, the half-maximal effective concentration (EC50) of 2% true carvacrol solution on HSV-2 infected cells were severally 0.43, 0.19 and 0.51 mmol/L, and the corresponding therapeutic index (TI) were 4.02, 9.11 and 3.39, respectively. It's the opposite of the increased levels caused by HSV-2 infection, that both the expressions at the transcription genes and protein levels of virus own replication key factors (including ICP4, ICP27, VP16, gB, and UL30) and cytokines (including RIP3, TNF-α, and MLKL) of infected cells treated with carvacrol were dose-dependently inhibited. Besides, HSV-2 infection can cause the decrease of intracellular protein ubiquitination level, and carvacrol can reverse the ubiquitination decrease level caused by HSV-2 infection. CONCLUSION: Carvacrol exhibits significant antiviral activity by inhibiting the HSV-2 proliferation process and HSV-2-induced TNF-α increasing levels, decreasing RIP3 and MLKL protein expressions through the intracellular RIP3-mediated programmed cell necrosis pathway. In addition, carvacrol also may exhibit anti-HSV-2 activity by reversing the ubiquitination decrease level caused by HSV-2 infection on the ubiquitin-proteasome system, which provides insights into the molecular mechanism.


Assuntos
Antivirais/farmacologia , Apoptose/efeitos dos fármacos , Cimenos/farmacologia , Células Epiteliais/virologia , Herpes Simples/metabolismo , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Ubiquitina/metabolismo , Animais , Chlorocebus aethiops , Citocinas/metabolismo , Herpes Simples/virologia , Transdução de Sinais/efeitos dos fármacos , Células Vero , Replicação Viral/efeitos dos fármacos
3.
PLoS Pathog ; 16(7): e1008795, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32716975

RESUMO

HSV-1 causes 50% of first-time genital herpes infections in resource-rich countries and affects 190 million people worldwide. A prophylactic herpes vaccine is needed to protect against genital infections by both HSV-1 and HSV-2. Previously our laboratory developed a trivalent vaccine that targets glycoproteins C, D, and E present on the HSV-2 virion. We reported that this vaccine protects animals from genital disease and recurrent virus shedding following lethal HSV-2 challenge. Importantly the vaccine also generates cross-reactive antibodies that neutralize HSV-1, suggesting it may provide protection against HSV-1 infection. Here we compared the efficacy of this vaccine delivered as protein or nucleoside-modified mRNA immunogens against vaginal HSV-1 infection in mice. Both the protein and mRNA vaccines protected mice from HSV-1 disease; however, the mRNA vaccine provided better protection as measured by lower vaginal virus titers post-infection. In a second experiment, we compared protection provided by the mRNA vaccine against intravaginal challenge with HSV-1 or HSV-2. Vaccinated mice were totally protected against death, genital disease and infection of dorsal root ganglia caused by both viruses, but somewhat better protected against vaginal titers after HSV-2 infection. Overall, in the two experiments, the mRNA vaccine prevented death and genital disease in 54/54 (100%) mice infected with HSV-1 and 20/20 (100%) with HSV-2, and prevented HSV DNA from reaching the dorsal root ganglia, the site of virus latency, in 29/30 (97%) mice infected with HSV-1 and 10/10 (100%) with HSV-2. We consider the HSV-2 trivalent mRNA vaccine to be a promising candidate for clinical trials for prevention of both HSV-1 and HSV-2 genital herpes.


Assuntos
Proteção Cruzada/imunologia , Herpes Genital , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 2/imunologia , Vacinas contra Herpesvirus/imunologia , Latência Viral/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Feminino , Herpes Genital/virologia , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro , Proteínas do Envelope Viral/imunologia
4.
Arch Microbiol ; 202(9): 2569-2578, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32671418

RESUMO

This study screened mastic gum (Pistacia lentiscus L.) for antiviral activity against herpes simplex virus type 2 (HSV-2), coxsackievirus type B3, and adenovirus type 5. The organs of this plant (leaves, stem, and seed) were macerated sequentially using solvents of increasing polarity (hexane, dichloromethane, ethyl acetate, and methanol). Only the methanol extract of stem exhibited significant activity against HSV-2. This extract showed anti-HSV-2 activity with a selectivity index of 51 (50% cytotoxic concentration = 186 µg/mL; 50% inhibitory concentration = 3.63 µg/mL), and demonstrated direct inhibition against this virus with a virucidal selectivity index of 620 (50% virucidal concentration = 0.30 µg/mL). A bio-guided assay involving thin-layer chromatography led to the isolation of two active compounds, which have been identified as dammaradienone and dammaradienol using high-performance liquid chromatography-diode array detection coupled with electrospray ionization mass spectrometry. P. lentiscus has been widely studied for other biological activities. However, to our knowledge, this is the first report of P. lentiscus L. exhibiting antiviral activity.


Assuntos
Pistacia/química , Extratos Vegetais/farmacologia , Vírus/efeitos dos fármacos , Adenoviridae/efeitos dos fármacos , Antivirais/química , Antivirais/farmacologia , Cromatografia Líquida de Alta Pressão , Enterovirus/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Folhas de Planta/química , Sementes/química , Solventes/química
6.
Planta Med ; 86(7): 505-515, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32247285

RESUMO

Spondias mobin leaves have been traditionally used for treating cold sores. The study investigated the mechanism of antiherpes action of S. mombin extract, fractions, and geraniin. Different concentrations of samples were used to evaluate the in vitro antiherpes activity (anti-HSV-1) in virucidal, post-infection, attachment, and penetration assays. The mechanism of action of geraniin was investigated considering the glycoproteins gB and gD of HSV-1 surface as potential molecular targets. Molecular docking simulations were carried out for both in order to determine the possible binding mode position of geraniin at the activity sites. The binding mode position was posteriorly optimized considering the flexibility of the glycoproteins. The chemical analysis of samples was performed by LC-MS and revealed the presence of 22 substances, which are hydrolysable tannins, O-glycosylated flavonoids, phenolic acids, and a carbohydrate. The extract, tannin-rich fraction and geraniin showed important in vitro virucidal activity through blocking viral attachment but showed no relevant inhibition of viral penetration. The in silico approaches demonstrated a high number of potential strong intermolecular interactions as hydrogen bonds between geraniin and the activity site of the glycoproteins, particularly the glycoprotein gB. In silico experiments indicated that geraniin is at least partially responsible for the anti-herpes activity through interaction with the viral surface glycoprotein gB, which is responsible for viral adsorption. These results highlight the therapeutic potential of S. mombin anti-herpes treatment and provides support for its traditional purposes. However, further studies are required to validate the antiviral activities in vivo, as well as efficacy in humans.


Assuntos
Anacardiaceae , Antivirais , Herpes Simples , Herpesvirus Humano 1 , Herpesvirus Humano 2 , Humanos , Simulação de Acoplamento Molecular , Extratos Vegetais , Folhas de Planta , Células Vero , Replicação Viral
7.
Arch Virol ; 165(6): 1385-1396, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32346764

RESUMO

Human herpesviruses are among the most prevalent pathogens worldwide and have become an important public health issue. Recurrent infections and the emergence of resistant viral strains reinforce the need of searching new drugs to treat herpes virus infections. Cardiac glycosides are used clinically to treat cardiovascular disturbances, such as congestive heart failure and atrial arrhythmias. In recent years, they have sparked new interest in their potential anti-herpes action. It has been previously reported by our research group that two new semisynthetic cardenolides, namely C10 (3ß-[(N-(2-hydroxyethyl)aminoacetyl]amino-3-deoxydigitoxigenin) and C11 (3ß-(hydroxyacetyl)amino-3-deoxydigitoxigenin), exhibited potential anti-HSV-1 and anti-HSV-2 with selectivity index values > 1,000, comparable with those of acyclovir. This work reports the mechanism investigation of anti-herpes action of these derivatives. The results demonstrated that C10 and C11 interfere with the intermediate and final steps of HSV replication, but not with the early stages, since they completely abolished the expression of the UL42 (ß) and gD (γ) proteins and partially reduced that of ICP27 (α). Additionally, they were not virucidal and had no prophylactic effects. Both compounds inhibited HSV replication at nanomolar concentrations, but cardenolide C10 was more active than C11 and can be considered as an anti-herpes drug candidate including against acyclovir-resistant HSV-1 strains.


Assuntos
Antivirais/farmacologia , Cardenolídeos/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Aciclovir/farmacologia , Animais , Antivirais/síntese química , Cardenolídeos/síntese química , Chlorocebus aethiops , Avaliação Pré-Clínica de Medicamentos , Farmacorresistência Viral , Infecções por Herpesviridae/tratamento farmacológico , Humanos , Células Vero
8.
BMC Infect Dis ; 20(1): 234, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32192456

RESUMO

BACKGROUND: Herpes simplex virus (HSV) typically infects oral or anogenital squamous epithelium and causes blisters and ulcerations. Here we reported an unusual case of HSV induced exuberant rectal inflammatory pseudotumor with vascular endothelial involvement. CASE PRESENTATIONS: A 52-year old man with HIV presented with abdominal pain, rectal drainage and constipation. Proctoscopy and CT scans revealed an 8 × 5 × 4 cm circumferential, mid-lower rectal mass that was concerning for malignancy. PET-CT showed mild to moderate FDG uptake of the rectal mass. Repeated biopsies showed exuberant lymphoplasmacytic inflammation with rich eosinophils and necrosis in the submucosa and scattered single or multi-nucleated viral inclusions in vascular endothelial cells that were positive for HSV by immunostains. There was no evidence of malignancy on histology or by immunostains. The patient started valacyclovir for three weeks and symptoms resolved after the antiviral therapy. Follow-up CT and sigmoidoscopy with biopsy revealed no rectal mass or drainable collection. CONCLUSIONS: HSV may present as proctitis with exuberant inflammatory response and mass-like lesion, and damages vascular endothelial cells in patients with HIV. The HSV-associated mass-like lesion can be effectively treated by 3-week valacyclovir.


Assuntos
Endotélio Vascular/virologia , Granuloma de Células Plasmáticas/complicações , Infecções por HIV/complicações , Herpes Simples/complicações , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 2/imunologia , Proctite/complicações , Reto/virologia , Antivirais/uso terapêutico , Células Endoteliais/virologia , Endotélio Vascular/patologia , Seguimentos , Granuloma de Células Plasmáticas/diagnóstico , Infecções por HIV/tratamento farmacológico , Herpes Simples/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Proctite/tratamento farmacológico , Proctite/virologia , Reto/patologia , Resultado do Tratamento , Valaciclovir/uso terapêutico
9.
BMC Infect Dis ; 20(1): 204, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143643

RESUMO

BACKGROUND: Bolivia has the highest prevalence of cervical cancer in South America and the prevalence of viral sexually transmitted infections (STIs) among people in urban cities is increasing. Little is known about the prevalence of viral STIs in rural communities, which generally have limited access to health care. In order to study the prevalence of viral STIs in rural Bolivia, we recruited women from villages and towns in the Department of La Paz in Bolivia. METHODS: Three hundred ninety-four female participants were assessed for IgG-antibodies to herpes simplex virus type 2 (HSV-2), human immunodeficiency virus (HIV) and hepatitis B virus (HBV, anti-HBc), as well as for the presence of HBV surface antigen (HBsAg) in dried blood spots. The prevalence of 12 high-risk types of human papillomavirus (HPV) was assessed by qPCR in dried cervicovaginal cell spots from 376 of these women. χ2 test was used to compare variables between the populations and binary logistic regression was used to identify risk factors associated with the positivity of the tests. RESULTS: The seroprevalence of HSV-2 was 53% and of HBV 10.3%. HBAg was detected in 15.8% of women with anti-HBV antibodies indicating chronic infection. The frequency of high-risk HPV infection was 27%, with the most prevalent high-risk HPV types being HPV 56, 39 and 31 followed by HPV 16 and 18. Finally, none of the 394 women were seropositive for HIV, and about 64% of the studied population was positive for at least one of the viral infections. CONCLUSIONS: Women in Bolivian rural communities in La Paz show a high prevalence of HBV, HPV and, in particular, HSV-2. In contrast, none of the women were HIV positive, suggesting that the HIV prevalence in this population is low. The pattern of high-risk HPV types differed from many other countries with a predominance of HPV-types not included in the Gardasil vaccine which was officially introduced in Bolivia in April 2017.


Assuntos
Herpesvirus Humano 2/genética , Infecções por Papillomavirus/diagnóstico , Doenças Virais Sexualmente Transmissíveis/diagnóstico , Adulto , Anticorpos Antivirais/sangue , Bolívia/epidemiologia , Feminino , Genótipo , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Herpesvirus Humano 2/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Prevalência , Risco , População Rural , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Adulto Jovem
10.
Lancet Psychiatry ; 7(5): 399-410, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32220288

RESUMO

BACKGROUND: Prenatal and perinatal insults are implicated in the aetiopathogenesis of psychotic disorders but the consistency and magnitude of their associations with psychosis have not been updated for nearly two decades. The aim of this systematic review and meta-analysis was to provide a comprehensive and up-to-date synthesis of the evidence on the association between prenatal or perinatal risk and protective factors and psychotic disorders. METHODS: In this systematic review and meta-analysis, we searched the Web of Science database for articles published up to July 20, 2019. We identified cohort and case-control studies examining the association (odds ratio [OR]) between prenatal and perinatal factors and any International Classification of Diseases (ICD) or Diagnostic and Statistical Manual of Mental Disorders (DSM) non-organic psychotic disorder with a healthy comparison group. Other inclusion criteria were enough data available to do the analyses, and non-overlapping datasets. We excluded reviews, meta-analyses, abstracts or conference proceedings, and articles with overlapping datasets. Data were extracted according to EQUATOR and PRISMA guidelines. Extracted variables included first author, publication year, study type, sample size, type of psychotic diagnosis (non-affective psychoses or schizophrenia-spectrum disorders, affective psychoses) and diagnostic instrument (DSM or ICD and version), the risk or protective factor, and measure of association (primary outcome). We did random-effects pairwise meta-analyses, Q statistics, I2 index, sensitivity analyses, meta-regressions, and assessed study quality and publication bias. The study protocol was registered at PROSPERO, CRD42017079261. FINDINGS: 152 studies relating to 98 risk or protective factors were eligible for analysis. Significant risk factors were: maternal age younger than 20 years (OR 1·17) and 30-34 years (OR 1·05); paternal age younger than 20 years (OR 1·31) and older than 35 years (OR 1·28); any maternal (OR 4·60) or paternal (OR 2·73) psychopathology; maternal psychosis (OR 7·61) and affective disorder (OR 2·26); three or more pregnancies (OR 1·30); herpes simplex 2 (OR 1·35); maternal infections not otherwise specified (NOS; OR 1·27); suboptimal number of antenatal visits (OR 1·83); winter (OR 1·05) and winter to spring (OR 1·05) season of birth in the northern hemisphere; maternal stress NOS (OR 2·40); famine (OR 1·61); any famine or nutritional deficits in pregnancy (OR 1·40); maternal hypertension (OR 1·40); hypoxia (OR 1·63); ruptured (OR 1·86) and premature rupture (OR 2·29) of membranes; polyhydramnios (OR 3·05); definite obstetric complications NOS (OR 1·83); birthweights of less than 2000 g (OR 1·84), less than 2500 g (OR 1·53), or 2500-2999 g (OR 1·23); birth length less than 49 cm (OR 1·17); small for gestational age (OR 1·40); premature birth (OR 1·35), and congenital malformations (OR 2·35). Significant protective factors were maternal ages 20-24 years (OR 0·93) and 25-29 years (OR 0·92), nulliparity (OR 0·91), and birthweights 3500-3999 g (OR 0·90) or more than 4000 g (OR 0·86). The results were corrected for publication biases; sensitivity and meta-regression analyses confirmed the robustness of these findings for most factors. INTERPRETATION: Several prenatal and perinatal factors are associated with the later onset of psychosis. The updated knowledge emerging from this study could refine understanding of psychosis pathogenesis, enhance multivariable risk prediction, and inform preventive strategies. FUNDING: None.


Assuntos
Peso ao Nascer , Anormalidades Congênitas/epidemiologia , Complicações na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Transtornos Psicóticos/epidemiologia , Adulto , Fome Epidêmica , Feminino , Macrossomia Fetal/epidemiologia , Ruptura Prematura de Membranas Fetais/epidemiologia , Herpes Simples/epidemiologia , Herpesvirus Humano 2 , Humanos , Hipertensão/epidemiologia , Hipóxia/epidemiologia , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Masculino , Desnutrição/epidemiologia , Idade Materna , Transtornos do Humor/epidemiologia , Paridade , Idade Paterna , Poli-Hidrâmnios/epidemiologia , Gravidez , Complicações na Gravidez/psicologia , Complicações Infecciosas na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Cuidado Pré-Natal/estatística & dados numéricos , Fatores de Proteção , Fatores de Risco , Estações do Ano , Estresse Psicológico/epidemiologia , Adulto Jovem
12.
Actas dermo-sifiliogr. (Ed. impr.) ; 111(1): 53-58, ene.-feb. 2020. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-191485

RESUMO

INTRODUCCIÓN Y OBJETIVO: Se ha constatado un cambio en la epidemiología del herpes genital en los últimos años con un aumento de la incidencia del virus herpes (VHS) tipo 1. El objetivo de nuestro estudio es analizar las características clínico-epidemiológicas de los pacientes diagnosticados de un herpes genital. MATERIAL Y MÉTODOS: Se diseñó un estudio observacional retrospectivo donde se incluyeron todos los pacientes diagnosticados de herpes genital entre enero de 2016 y enero de 2019 en una Unidad de Infecciones de Transmisión Sexual (ITS) en Valencia, España. RESULTADOS: Se diagnosticaron 895 ITS, de las cuales 126 fueron un herpes genital (14%), 68 (54%) en mujeres y 58 (46%) en hombres. En 110 de ellos (87,3%) se confirmó el herpes genital por la detección de ADN viral por técnicas moleculares. Se diagnosticaron 52 casos de VHS tipo 1 (47,3%) y 58 casos de VHS tipo 2 (52,7%). En el 69,5% de los hombres se detectó el VHS tipo 2, mientras que en el 59,3% de las mujeres se detectó el VHS tipo 1. La edad media de las mujeres diagnosticadas de VHS tipo 1 fue de 26 años, mientras que la de las mujeres diagnosticadas de VHS tipo 2 fue de 34 años (p = 0,015). Las recurrencias de las lesiones en los pacientes con VHS tipo 1 y VHS tipo 2 fue del 13% y del 40%, respectivamente. CONCLUSIÓN: Destacamos un aumento de la prevalencia del VHS tipo 1 en nuestro medio como agente causante de herpes genital, especialmente en mujeres jóvenes. Esto tiene un valor pronóstico importante dado el menor riesgo de recurrencias que tiene


INTRODUCTION AND OBJECTIVE: The epidemiology of genital herpes has changed in recent years with an increase in the incidence of herpes simplex virus type 1 (HSV-1) infection. The aim of this study was to analyze the clinical and epidemiological characteristics of patients diagnosed with genital herpes. MATERIAL AND METHODS: A retrospective observational study was designed. All patients diagnosed with genital herpes between January 2016 and January 2019 in a Sexually Transmitted Infections Unit (ITS) in Valencia, Spain, were included. RESULTS: We identified 895 STI diagnoses. Of these, 126 (14%) were genital herpes; 68 (54%) of these cases were in women and 58 (46%) in men. Diagnosis was confirmed by molecular detection of HSV DNA in 110 cases (87.3%). Of these, 52 were cases of HSV-1 infection (47.3%) and 58 were HSV-2 infection (52.7%). HSV-2 was more common in men (69.5%), while HSV-1 was more common in women (59.3%). In the subgroup of women, mean age at diagnosis was 26 years for HSV-1 and 34 years for HSV-2 (P = .015). Recurrent genital herpes rates were 13% for HSV-1 and 40% for HSV-2. CONCLUSIONS: There has been an increase in the number of cases of genital herpes caused by HSV-1 in our setting, with young women in particular being affected. This has important prognostic implications because genital herpes caused by HSV-1 is less likely to recur


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Herpes Genital/epidemiologia , Herpes Genital/diagnóstico , Herpesvirus Humano 2/isolamento & purificação , Herpesvirus Humano 1/isolamento & purificação , Estudos Retrospectivos , Espanha/epidemiologia , Herpes Genital/microbiologia , DNA Viral/análise , Homossexualidade Masculina/estatística & dados numéricos , Reação em Cadeia da Polimerase/métodos
13.
BMC Infect Dis ; 20(1): 150, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070282

RESUMO

BACKGROUND: Human encephalitis can originate from a variety of different aetiologies, of which infection is the most common one. The diagnostic work-up is specifically challenging in patients with travel history since a broader spectrum of unfamiliar additional infectious agents, e. g. tropical disease pathogens, needs to be considered. Here we present a case of encephalitis of unclear aetiology in a female traveller returning from Africa, who in addition developed an atypical herpes simplex virus (HSV) encephalitis in close temporal relation with high-dose steroid treatment. CASE PRESENTATION: A previously healthy 48-year-old female presented with confusion syndrome and impaired vigilance which had developed during a six-day trip to The Gambia. The condition rapidly worsened to a comatose state. Extensive search for infectious agents including a variety of tropical disease pathogens was unsuccessful. As encephalitic signs persisted despite of calculated antimicrobial and antiviral therapy, high-dose corticosteroids were applied intravenously based on the working diagnosis of an autoimmune encephalitis. The treatment did, however, not improve the patient's condition. Four days later, bihemispheric signal amplification in the insular and frontobasal cortex was observed on magnetic resonance imaging (MRI). The intracranial pressure rapidly increased and could not be controlled by conservative treatment. The patient died due to tonsillar herniation 21 days after onset of symptoms. Histological examination of postmortem brain tissue demonstrated a generalized lymphocytic meningoencephalitis. Immunohistochemical reactions against HSV-1/2 indicated an atypical manifestation of herpesviral encephalitis in brain tissue. Moreover, HSV-1 DNA was detected by a next-generation sequencing (NGS) metagenomics approach. Retrospective analysis of cerebrospinal fluid (CSF) and serum samples revealed HSV-1 DNA only in specimens one day ante mortem. CONCLUSIONS: This case shows that standard high-dose steroid therapy can contribute to or possibly even trigger fulminant cerebral HSV reactivation in a critically ill patient. Thus, even if extensive laboratory diagnostics including wide-ranging search for infectious pathogens has been performed before and remained without results, continuous re-evaluation of potential differential diagnoses especially regarding opportunistic infections or reactivation of latent infections is of utmost importance, particularly if new symptoms occur.


Assuntos
Encefalite por Herpes Simples/diagnóstico , Encefalite por Herpes Simples/tratamento farmacológico , Encefalite por Herpes Simples/etiologia , Herpes Simples/diagnóstico , Herpesvirus Humano 1/isolamento & purificação , Esteroides/efeitos adversos , Autopsia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , DNA Viral/sangue , DNA Viral/líquido cefalorraquidiano , Encefalite/diagnóstico , Feminino , Gâmbia , Doença de Hashimoto/diagnóstico , Herpes Simples/diagnóstico por imagem , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/patogenicidade , Herpesvirus Humano 2/patogenicidade , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Estudos Retrospectivos , Esteroides/uso terapêutico , Viagem
14.
Immunohorizons ; 4(2): 72-81, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-32047094

RESUMO

Norethisterone enanthate (NET-EN) and depot-medroxyprogesterone acetate (DMPA) are two forms of injectable progestin used for contraception. Whereas clinical research indicates that women using DMPA are more susceptible to HIV and other genital pathogens, causal relationships have not been determined. Providing an underlying mechanism for this connection, however, is recent work that showed DMPA weakens genital mucosal barrier function in mice and humans and respectively promotes susceptibility of wild-type and humanized mice to genital infection with HSV type 2 and HIV type 1. However, analogous effects of NET-EN treatment on antivirus immunity and host susceptibility to genital infection are much less explored. In this study, we show that compared with mice in estrus, treatment of mice with DMPA or NET-EN significantly decreased genital levels of the cell-cell adhesion molecule desmoglein-1 and increased genital mucosal permeability. These effects, however, were more pronounced in DMPA- versus NET-EN-treated mice. Likewise, we detected comparable mortality rates in DMPA- and NET-EN-treated wild-type and humanized mice after intravaginal infection with HSV type 2 or cell-associated HIV type 1, respectively, but NET-EN treatment was associated with slower onset of HSV-induced genital pathology and lower burden of systemic HIV disease. These findings reveal DMPA and NET-EN treatment of mice significantly reduces genital desmoglein-1 levels and increases genital mucosal permeability and susceptibility to genital pathogens while also implying that NET-EN generates less compromise of genital mucosal barrier function than DMPA.


Assuntos
Anticoncepcionais Femininos/efeitos adversos , HIV-1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Noretindrona/análogos & derivados , Vagina/virologia , Animais , Desmogleína 1/metabolismo , Suscetibilidade a Doenças/virologia , Feminino , Infecções por HIV/virologia , HIV-1/patogenicidade , Herpes Genital/virologia , Herpesvirus Humano 2/patogenicidade , Acetato de Medroxiprogesterona/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos SCID , Membrana Mucosa/efeitos dos fármacos , Membrana Mucosa/metabolismo , Membrana Mucosa/virologia , Noretindrona/efeitos adversos , Permeabilidade , Vagina/efeitos dos fármacos , Vagina/metabolismo
15.
BMC Res Notes ; 13(1): 52, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005126

RESUMO

OBJECTIVE: Herpes simplex virus-2 (HSV-2) infections are almost exclusively sexually transmitted. The presence of vaginal gels during sexual activity may have a significant positive or negative impact on viral transmission. Therefore we investigated three off-the-shelf vaginal lubricants and one pH restoring gel to evaluate their impact on HSV-2 replication. RESULTS: HeLa cells were infected with untreated virions and virions incubated with the particular gels. The accumulation of viral genomes was monitored by quantitative PCR (qPCR) method at 24 h post infection. Two of the tested gels had no significant effect on HSV-2 replication at the maximum applied concentration, while two had a strong inhibitory effect (~ 98% reduction of replication). The replication inhibitory effect was observed at various multiplicity of infection (MOI 0.4-6.4) and the two inhibitory gels were also capable of inhibiting the HSV-2 induced cytopathic effect on HeLa cells. The surface tension decreasing activity-an indication of detergent activity-was strongly correlated with the anti-HSV-2 activity of the gels (R2: 0.88). Our results indicate that off-the-shelf vaginal gels have a markedly different anti-HSV-2 activity that may influence HSV-2 transmission.


Assuntos
Antivirais/farmacologia , Detergentes/farmacologia , Herpesvirus Humano 2/efeitos dos fármacos , Cremes, Espumas e Géis Vaginais/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células HeLa , Humanos , Tensão Superficial , Replicação Viral/efeitos dos fármacos
16.
PLoS One ; 15(1): e0226237, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31914165

RESUMO

INTRODUCTION: Approximately two-thirds of HIV-infected individuals reside in sub-Saharan Africa. The region accounts for 68% of the new HIV infections occurring worldwide with almost one-half of these infections being among young adults aged 12-24 years. Cowan and colleagues conducted a community-based, multi-component HIV intervention aimed at youth in rural Zimbabwe. Despite some changes in knowledge and attitudes, the community-based intervention did not affect the prevalence of HIV or HSV-2. We selected this frequently cited study for replication since it incorporates individual-, community-, and structural- level intervention components that are often considered in global HIV/AIDS prevention programs. Additionally, the intervention could be easily scaled-up, which is especially important in the context of limited resources. Although this study indicated no intervention effects in reducing HIV, the authors acknowledged some key methodological challenges. Our replication analysis provided important insights regarding the impact of these challenges to the interpretation of the results of this study. METHODS: Our replication study focused on replicating Cowan's findings and assessing the robustness of Cowan's results to alternative analytical models based on their study design. We determined how out-migration occurring during Cowan's study may have affected the population characteristics, the intervention exposure level, and the study findings. While the original intervention targeted knowledge and attitudes as a mechanism to decrease HIV/HSV-2, the Cowan study evaluated the intervention effects on knowledge, attitudes, and prevalence of HIV or HSV-2 separately. To better identify the pathway describing the interrelationship among the intervention and knowledge, attitudes, and prevalence of HIV or HSV-2, we assessed whether increases in knowledge or attitudes were associated with decreased HIV or HSV-2 prevalence. RESULTS: We replicated the original findings with minor discrepancies during the pure replication. Our additional analyses revealed that the study population characteristics changed over time in ways that may have affected outcomes. These changes also affected the levels of intervention exposure, with 48.7% males and 75.5% females of the intervention group receiving low-level exposure. Both genders with higher level intervention exposure experienced higher increments in multiple knowledge, attitude, and sexual risk behavior outcomes. Unfortunately, these did not translate to a significant reduction in HIV or HSV-2 regardless of the level and combination of knowledge and attitude domains. However, males receiving high-level intervention exposure compared to control indicated significantly lower odds of having HIV or HSV-2 under a Bayesian modeling paradigm. CONCLUSIONS: Our findings suggest a more robust conclusion on the study intervention effects. Further study based on a design that more consistently maximizes the exposure level of the intervention is necessary and should ideally be an evaluated goal in similar studies. Evaluation of the intervention impact for key subgroups of the target population is important and would better advise the use and scale-up of the evaluated interventions in various contexts. Our observation of a consistent lack of relationship between knowledge/attitudes and HIV/HSV-2 suggests a need to explore and include relevant additional and or complementary interventions, e.g., promoting effective skills in reducing risky sexual behaviors and addressing cultural and structural bottlenecks that may reduce HIV/HSV-2 risk among youth.


Assuntos
Serviços de Saúde Comunitária/métodos , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde , Herpes Genital/prevenção & controle , Educação de Pacientes como Assunto , Adolescente , Adulto , Teorema de Bayes , Feminino , HIV/isolamento & purificação , Infecções por HIV/transmissão , Infecções por HIV/virologia , Herpes Genital/transmissão , Herpes Genital/virologia , Herpesvirus Humano 2/isolamento & purificação , Humanos , Masculino , Comportamento de Redução do Risco , Adulto Jovem , Zimbábue
17.
Int J Mol Sci ; 21(1)2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31947962

RESUMO

Herpes Simplex Virus Type 2 (HSV-2) is one of the most prevalent sexually transmitted viruses and is a known risk factor for HIV acquisition in the Female Genital Tract (FGT). Previously, we found that curcumin can block HSV-2 infection and abrogate the production of inflammatory cytokines and chemokines by genital epithelial cells in vitro. In this study, we investigated whether curcumin, encapsulated in nanoparticles and delivered by various in vivo routes, could minimize inflammation and prevent or reduce HSV-2 infection in the FGT. Female mice were pre-treated with curcumin nanoparticles through oral, intraperitoneal and intravaginal routes, and then exposed intravaginally to the tissue inflammation stimulant CpG-oligodeoxynucleotide (ODN). Local intravaginal delivery of curcumin nanoparticles, but not intraperitoneal or oral delivery, reduced CpG-mediated inflammatory histopathology and decreased production of pro-inflammatory cytokines Interleukin (IL)-6, Tumor Necrosis Factor Alpha (TNF-α) and Monocyte Chemoattractant Protein-1 (MCP-1) in the FGT. However, curcumin nanoparticles did not demonstrate anti-viral activity nor reduce tissue pathology when administered prior to intravaginal HSV-2 infection. In an alternative approach, intravaginal pre-treatment with crude curcumin or solid dispersion formulations of curcumin demonstrated increased survival and delayed pathology following HSV-2 infection. Our results suggest that curcumin nanoparticle delivery in the vaginal tract could reduce local tissue inflammation. The anti-inflammatory properties of curcumin delivered to the vaginal tract could potentially reduce the severity of HSV-2 infection and decrease the risk of HIV acquisition in the FGT of women.


Assuntos
Curcumina/farmacologia , Herpes Simples/patologia , Inflamação/patologia , Administração Intravaginal , Animais , Quimiocina CCL2/metabolismo , Curcumina/química , Curcumina/uso terapêutico , Portadores de Fármacos/química , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Feminino , Genitália Feminina/citologia , Genitália Feminina/metabolismo , Herpes Simples/veterinária , Herpes Simples/virologia , Herpesvirus Humano 2/fisiologia , Humanos , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Oligodesoxirribonucleotídeos/toxicidade , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismo , Vagina/metabolismo , Vagina/patologia
18.
Hautarzt ; 71(4): 293-297, 2020 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-31965208

RESUMO

BACKGROUND: Herpes simplex virus (HSV) type 1 and type 2 may infect the anal region and induce aphthous ulcers. HSV-induced proctitis may be severe with fever, anal pain, anal bleeding, and diarrhea. OBJECTIVES: The pathogenic agents and treatment are reviewed. MATERIALS AND METHODS: A review of the current literature was performed. RESULTS: The shift to later primary infections with HSV1 and changes towards more frequent oro-genital and oro-anal sex has increased the incidence of HSV1-induced primary anal infections. Due to frequent recurrences, HSV2 remains the most common cause of anal HSV infection. Anal and genital HSV infections are a risk factor for subsequent HIV infection. In case of suspicion, pathogen detection by polymerase chain reaction (PCR) should be performed and other sexually transmitted diseases should be excluded. HSV proctitis may mimic inflammatory bowel disease. Treatment should include antiviral medication as in genital herpes simplex. CONCLUSIONS: HSV may induce perianal infections, anal infections and HSV proctitis. Diagnosis of HSV1 and HSV2 using PCR is recommended. Anal and genital HSV infections are a risk factor for subsequent HIV infection. The risk is higher for HSV2 infection due to more frequent recurrences.


Assuntos
Doenças do Ânus/virologia , Herpes Genital/diagnóstico , Herpes Simples/diagnóstico , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 2/isolamento & purificação , Proctite/diagnóstico , Comportamento Sexual , Infecções por HIV , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , Humanos , Reação em Cadeia da Polimerase , Proctite/virologia , Doenças Sexualmente Transmissíveis
19.
Planta Med ; 86(4): 267-275, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31968380

RESUMO

Infections caused by HSV-2 are a public health concern worldwide, and there is still a great demand for the discovery of novel anti-herpes virus agents effective against strains resistant to current antiviral agents. In this context, medicinal plants represent an alternative source of active compounds for developing efficient antiviral therapies. The aim of this study was to evaluate the antiviral activity of Arisaema tortuosum, a plant used in the traditional medicine of India. A chloroform soluble fraction of the leaves exhibited anti-HSV-2 activity with a selectivity index of 758. The extract was also active against acyclovir-resistant HSV-2 and HSV-1. The mechanism of action of the extract was investigated evidencing inhibition of both early and late events of the HSV-2 replicative cycle. A HPLC-PDA-MS/MS analysis showed the presence of flavonoids including apigenin and luteolin in the chloroform extract (CE). Apigenin and luteolin showed a high inhibitory activity with EC50 values of 0.05 and 0.41 µg/mL, respectively. Both compounds exhibited antiviral activity when added up to 6 h post infection and were able to reduce the viral progeny production. In addition, apigenin interfered with cell-to-cell virus spread.


Assuntos
Antivirais , Arisaema , Herpes Simples , Herpesvirus Humano 2 , Índia , Extratos Vegetais , Espectrometria de Massas em Tandem , Células Vero
20.
Carbohydr Polym ; 229: 115487, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31826428

RESUMO

Purified fucoidans SHAP-1 and SHAP-2 with apparent molecular weights of 6.55 × 105 and 5.89 × 105, respectively, were isolated from Sargassum henslowianum by ion-exchange and gel-filtration column chromatography. They are both composed of fucose and galactose at a ratio of around 3:1 and 31.9% sulfate. The backbone of two fucoidans consists of α-(1→3)-linked L-Fucp residues which are mainly sulfated on the C-2 and C-4 positions. Side chains composed of terminally linked α-L-Fucp and α-D-Galp residues, and (1→2)-, (1→6)-, and (1→2,6)-linked ß-D-Galp residues attach mainly at O-4 position of backbone residues. Antiviral test showed that the IC50 values of SHAP-1 and SHAP-2 against HSV-1 were estimated to be 0.89 and 0.82 µg/mL by plaque reduction assay, respectively, whereas both as low as 0.48 µg/mL against HSV-2. The antiviral mechanism of the fucoidans might be at least through blocking HSV-2 virion adsorption to host cells. These results suggest that the fucoidans have potential clinical applications.


Assuntos
Antivirais/química , Antivirais/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Sargassum/química , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos
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