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1.
Acta Neurochir (Wien) ; 166(1): 207, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38719997

RESUMO

PURPOSE: While hearing loss is a well-known condition following microvascular decompression (MVD) for hemifacial spasm (HFS), tinnitus is an underreported one. This study aims to identify prevalence, characteristics, severity, and predictors of tinnitus following MVD for HFS. METHODS: A single-center cohort of 55 HFS patients completed a questionnaire approximately 5 years following MVD. Data encompassed tinnitus presence, side, type, onset, and severity measured by a 10-point Visual Analogue Scale (VAS). Descriptive, correlation, and logistic regression analyses were conducted. RESULTS  : At surgery, participants' median age was 58 years (IQR 52-65). The median duration of HFS symptoms before surgery was 5 years (IQR 3-8), slightly predominant on the left (60%). Postoperative tinnitus was reported by 20 patients (36%), versus nine (16%) that reported preoperative tinnitus. Postoperative tinnitus was ipsilateral on the surgical side in 13 patients (65%), bilateral in six (30%), and contralateral in one (5%). Among patients with bilateral postoperative tinnitus, 33% did not have this preoperatively. Tinnitus was continuous in 70% of cases and pulsatile in 30%. Onset of new tinnitus was in 58% immediately or within days, in 25% within three months, and in 17% between three months and one year after surgery. The mean severity of postoperative tinnitus was 5.1 points on the VAS. Preoperative tinnitus and presence of arachnoid adhesions had suggestive associations with postoperative tinnitus in initial analyses (p = 0.005 and p = 0.065). However, preoperative tinnitus was the only significant predictor of postoperative tinnitus (p = 0.011). CONCLUSION: Tinnitus is a common condition following MVD for HFS, with a moderate overall severity. Causes behind postoperative tinnitus remain obscure but could be related to those of postoperative hearing loss in this patient population. Clinicians should be aware of tinnitus following MVD and vigilantly monitor its occurrence, to facilitate prevention efforts and optimize outcome for HFS patients undergoing MVD.


Assuntos
Espasmo Hemifacial , Cirurgia de Descompressão Microvascular , Complicações Pós-Operatórias , Zumbido , Humanos , Zumbido/etiologia , Zumbido/epidemiologia , Espasmo Hemifacial/cirurgia , Pessoa de Meia-Idade , Cirurgia de Descompressão Microvascular/efeitos adversos , Cirurgia de Descompressão Microvascular/métodos , Feminino , Masculino , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos de Coortes
3.
J Pediatr Gastroenterol Nutr ; 77(6): 748-752, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37229767

RESUMO

NOD2/CARD15 was the first susceptibility gene recognized for adult-onset Crohn's (or Crohn) disease (CD). Recessive inheritance of NOD2 polymorphisms has been implicated as a mechanistic driver of pediatric-onset CD. In patients with very early-onset inflammatory bowel disease (VEO-IBD), however, the clinical relevance of NOD2 polymorphisms has not been fully established. Ten VEO-IBD patients with NOD2 polymorphisms ( NOD2 +) were compared to 16 VEO-IBD patients without genetic variants in NOD2 or any other VEO-IBD susceptibility genes ( NOD2 -). The majority of NOD2 + patients exhibited a CD-like phenotype (90%), linear growth impairment (90%), and arthropathy (60%), all of which were significantly more common than in the NOD2 - group ( P = 0.037, P = 0.004, P = 0.026, respectively). We propose that the presence of NOD2 polymorphisms in patients with VEO-IBD might confer a CD-like phenotype, linear growth impairment, and arthropathy. These findings should be validated in larger cohorts and may guide precision medicine for patients with VEO-IBD in the future.


Assuntos
Colite Ulcerativa , Doença de Crohn , Artropatias , Adulto , Criança , Humanos , Doença de Crohn/genética , Colite Ulcerativa/genética , Predisposição Genética para Doença , Proteína Adaptadora de Sinalização NOD2/genética , Idade de Início , Fenótipo , Mutação
4.
Sci Rep ; 13(1): 3936, 2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36894606

RESUMO

Strategic, sustainable, and ecofriendly alternatives to chemical pesticides are needed to effectively control mosquitoes and reduce the incidence of their vectored diseases. We evaluated several Brassicaceae (mustard family) seed meals as sources of plant derived isothiocyanates produced from the enzymatic hydrolysis of biologically inactive glucosinolates for the control of Aedes aegypti (L., 1762). Five defatted seed meals (Brassica juncea (L) Czern., 1859, Lepidium sativum L., 1753, Sinapis alba L., 1753, Thlaspi arvense L., 1753, and Thlaspi arvense-heat inactivated and three major chemical products of enzymatic degradation (allyl isothiocyanate, benzyl isothiocyanate and 4-hydroxybenzyl isothiocyanate) were assayed to determine toxicity (LC50) to Ae. aegypti larvae. All seed meals except the heat inactivated T. arvense were toxic to mosquito larvae. L. sativum seed meal was the most toxic treatment to larvae (LC50 = 0.04 g/120 mL dH2O) at the 24-h exposure. At the 72-h evaluation, the LC50 values for B. juncea, S. alba and T. arvense seed meals were 0.05, 0.08 and 0.1 g/120 mL dH2O, respectively. Synthetic benzyl isothiocyanate was more toxic to larvae 24-h post treatment (LC50 = 5.29 ppm) compared with allyl isothiocyanate (LC50 = 19.35 ppm) and 4-hydroxybenzyl isothiocyanate (LC50 = 55.41 ppm). These results were consistent with the higher performance of the benzyl isothiocyanate producing L. sativum seed meal. Isothiocyanates produced from seed meals were more effective than the pure chemical compounds, based on calculated LC50 rates. Using seed meal may provide an effective method of delivery for mosquito control. This is the first report evaluating the efficacy of five Brassicaceae seed meals and their major chemical constituent against mosquito larvae and demonstrates how natural compounds from Brassicaceae seed meals can serve as a promising ecofriendly larvicides to control mosquitoes.


Assuntos
Aedes , Culicidae , Inseticidas , Animais , Larva , Mostardeira , Isotiocianatos/farmacologia , Sementes/química , Inseticidas/química , Extratos Vegetais/farmacologia
5.
Exp Parasitol ; 244: 108440, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36495953

RESUMO

A general method to spin-label a fatty acid was demonstrated as well as an assay of the effectiveness of methyl 10-undecenoate and the spin-labeled version, against the larvae of Aedes aegypti. The LC50s were 66 and 58 µL/120 mL (55 and 48 ppm) respectively, and the LC90s were 108 and 90 µL/120 mL (113 and 90) ppm. This shows that the spin-label has very little effect on the larvicidal activity of the compound. This opens the possibility of the use of spin-labeling as a tool to determine mechanisms of larvicidal effectiveness, as it can be employed without altering the system under study.


Assuntos
Aedes , Inseticidas , Animais , Extratos Vegetais , Larva , Ácidos Graxos
6.
Exp Appl Acarol ; 86(2): 299-312, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35076809

RESUMO

The repellency and toxicity of a CO2-derived cedarwood oil (CWO) was evaluated against actively questing unfed nymphs of four species of hard ticks: Amblyomma americanum (L.), Dermacentor variabilis (Say), Ixodes scapularis Say, and Rhipicephalus sanguineus (Latreille). Using a vertical climb bioassay for repellency, nymphs of these species avoided a CWO-treated filter paper in proportional responses to treatment concentrations. At 60 min of exposure, I. scapularis nymphs were most sensitive with 50% repellency concentration (RC50) of 19.8 µg cm-2, compared with RC50 of 30.8, 83.8 and 89.6 µg cm-2 for R. sanguineus, D. variabilis and A. americanum, respectively. Bioassays determined the lethal concentration for 50% (LC50) and 90% (LC90) mortality of nymphs exposed to CWO in treated vials after 24- and 48-h exposure. After 24 h exposure, the LC50 values were 1.25, 3.45 and 1.42 µg cm-2 and LC90 values were 2.39, 7.59 and 4.14 µg cm-2 for D. variabilis, I. scapularis and R. sanguineus, respectively, but had minimal effect on A. americanum. After 48 h exposure, the LC50 values were 4.14, 0.78, 0.79 and 0.52 µg cm-2, and LC90 values were 8.06, 1.48, 1.54 and 1.22 µg cm-2 for A. americanum, D. variabilis, I. scapularis and R. sanguineus, respectively. The repellency of CWO on tick species decreased with time. The repellency and toxicity bioassays demonstrated concentration-dependent responses of tick nymphs to the oil, indicating the potential of the CO2-derived cedarwood oil be developed as an eco-friendly repellent and/or acaricide.


Assuntos
Ixodes , Ixodidae , Óleos Voláteis , Animais , Dióxido de Carbono , Ixodidae/fisiologia
7.
Hum Mutat ; 42(5): 592-599, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33600035

RESUMO

BAP1 germline pathogenic sequence variants (PSVs) underlie a unique tumor predisposition syndrome (BAP1-TPDS) associated with an increased lifetime risk for developing primarily pleural and peritoneal mesothelioma and uveal and cutaneous melanoma. Overwhelmingly, BAP1 PSVs are unique, family-specific inactivating variants. We identified seven families, six of Jewish Iraqi origin, harboring an identical BAP1 splice variant (c.783+2T>C), currently assigned a "likely pathogenic" status. Given a nonclassical BAP1-TPDS tumor type clustering and low penetrance in these families, the pathogenicity of this variant was re-evaluated by a combined approach including literature analysis, revised bioinformatics analysis, allelic loss, effect on the transcript, and tumor protein expression patterns. None of the three available tumors showed an allelic loss, there was no discernable effect on alternative splicing based on reverse-transcription polymerase chain reaction, and there was no decrease or loss of somatic protein expression in 2/3 analyzed tumors. This led to assigning a Benign Strong (BS) criteria, BS4, supporting BS3 criteria, and weakening the Pathogenic Supporting (PP) criteria PP5. Combined, these data suggest that this sequence variant should be reclassified as a variant of unknown significance by American College of Medical Genetics (ACMG) criteria.


Assuntos
Melanoma , Neoplasias Cutâneas , Neoplasias Uveais , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Melanoma/genética , Melanoma/patologia , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Neoplasias Uveais/patologia
8.
Clin Microbiol Infect ; 27(1): 127.e1-127.e6, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32283266

RESUMO

OBJECTIVES: To describe the prevalence, clinical features and complications of human metapneumovirus (hMPV) infections in a population of adults hospitalized with influenza-like illness (ILI). METHODS: This was a retrospective, observational, multicenter cohort study using prospectively collected data from adult patients hospitalized during influenza virus circulation, for at least 24 h, for community-acquired ILI (with symptom onset <7 days). Data were collected from five French teaching hospitals over six consecutive winters (2012-2018). Respiratory viruses were identified by multiplex reverse transcription polymerase chain reaction (RT-PCR) on nasopharyngeal specimens. hMPV + patients were compared with hMPV- patients, influenza+ and respiratory syncytial virus (RSV)+ patients using multivariate logistic regressions. Primary outcome was the prevalence of hMPV in patients hospitalized for ILI. RESULTS: Among the 3148 patients included (1449 (46%) women, 1988 (63%) aged 65 and over; 2508 (80%) with chronic disease), at least one respiratory virus was detected in 1604 (51%, 95% confidence interval (CI) 49-53), including 100 cases of hMPV (100/3148, 3% 95% CI 3-4), of which 10 (10%) were viral co-infection. In the hMPV + patients, mean length of stay was 7 days, 62% (56/90) developed a complication, 21% (14/68) were admitted to intensive care unit and 4% (4/90) died during hospitalization. In comparison with influenza + patients, hMPV + patients were more frequently >65 years old (adjusted odds ratio (aOR) = 3.3, 95% CI 1.9-6.3) and presented more acute heart failure during hospitalization (aOR = 1.8, 95% CI 1.0-2.9). Compared with RSV + patients, hMPV + patients had less cancer (aOR = 0.4, 95% CI 0.2-0.9) and were less likely to smoke (aOR = 0.5, 95% CI 0.2-0.9) but had similar outcomes, especially high rates of respiratory and cardiovascular complications. CONCLUSIONS: Adult hMPV infections mainly affect the elderly and patients with chronic conditions and are responsible for frequent cardiac and pulmonary complications similar to those of RSV infections. At-risk populations would benefit from the development of antivirals and vaccines targeting hMPV.


Assuntos
Influenza Humana/diagnóstico , Metapneumovirus/isolamento & purificação , Infecções por Paramyxoviridae/diagnóstico , Infecções por Vírus Respiratório Sincicial/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/virologia , Feminino , França/epidemiologia , Hospitalização , Humanos , Influenza Humana/epidemiologia , Influenza Humana/virologia , Masculino , Metapneumovirus/genética , Pessoa de Meia-Idade , Nasofaringe/virologia , Orthomyxoviridae/genética , Orthomyxoviridae/isolamento & purificação , Infecções por Paramyxoviridae/epidemiologia , Infecções por Paramyxoviridae/virologia , Prevalência , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Estudos Retrospectivos , Fatores de Risco , Estações do Ano
9.
Pest Manag Sci ; 75(7): 2043-2048, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30632272

RESUMO

BACKGROUND: Some plant essential oils have insecticidal properties against mosquitoes and can be harnessed as ecofriendly tools for mosquito control. We conducted bioassays to determine the toxicity of Italian honeysuckle (Lonicera caprifolium) essential oil and its fractions against larvae of the yellow fever mosquito, Aedes aegypti. RESULTS: Sixteen constituents were identified in honeysuckle essential oil compared to 15, 15, 15, and 11 constituents in fractions A, B, C, and E, respectively. The chemical constituents for fraction D were not determined due to lack of enough fraction sample. The two major constituents identified were patchouli alcohol (29.3%) and 6-acetyl-1,1,2,4,4,7-hexamethyltetralin (20.6%) in whole essential oil, alpha-bulnesene (27.6%) and 6-acetyl-1,1,2,4,4,7-hexamethyltetralin (23.2%) in fraction A, unknown chemical (47.3%) and diethyl phthalate (19.5%) in fraction B, unknown chemical (38.3%) and diethyl phthalate (23.2%) in fraction C, and patchouli alcohol (58.7%) and diethyl phthalate (20.5%) in fraction E. The LC50 for whole essential oil was 34.4 ppm and significantly higher than 20.6, 19.7, 18.6, and 17.7 ppm for fractions B, C, D, and E, respectively. In contrast, fraction A was inactive. At 50 ppm, all individual constituents tested were less toxic than the whole essential oil with exception of patchouli alcohol, which caused 100% mortality. CONCLUSION: These findings suggest that patchouli alcohol is one of the chemical constituents responsible for bioactivity of honeysuckle essential oil and some of its fractions. The findings also demonstrate that honey suckle essential oil and its fractions can be exploited as a source of ecofriendly larvicides for mosquito control. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.


Assuntos
Aedes/efeitos dos fármacos , Lonicera/química , Óleos Voláteis/farmacologia , Animais , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Controle de Mosquitos , Óleos Voláteis/química , Sesquiterpenos/farmacologia
10.
Clin Microbiol Infect ; 24(4): 431.e5-431.e12, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28899840

RESUMO

OBJECTIVES: We discussed which method between the test-negative design (TND) and the screening method (SM) could provide more robust real-time and end-of-season vaccine effectiveness (VE) estimates using data collected from routine influenza surveillance in primary care. METHODS: We used data collected during two influenza seasons, 2014-15 and 2015-16. Using the SM, we estimated end-of-season VE in preventing medically attended influenza-like illness and laboratory-confirmed influenza among the population at risk. Using the TND, we estimated end-of-season VE in preventing influenza among both the general and the at-risk population. We estimated real-time VE using both methods. RESULTS: For the SM, the overall adjusted end-of-season VE was 24% (95% confidence interval (CI), 16 to 32) and 12% (95% CI, -16 to 33) during season 2014-15, and 53% (95% CI, 44 to 60) and 47% (95% CI, 23 to 64) during season 2015-16, in preventing influenza-like illness and laboratory-confirmed influenza, respectively. For the TND, the overall adjusted end-of-season VE was -17% (95% CI, -79 to 24) and -38% (95% CI, -199 to 13) in 2014-15, and 10% (95% CI, -31 to 39) and 18% (95% CI, -33 to 50) in 2015-16, among the general and at-risk population, respectively. Real-time VE estimates obtained through the TND showed more variability across each season and lower precision than those estimated with the SM. CONCLUSIONS: Although the worldwide use of the TND allows for comparison of overall VE estimates among countries, the SM performs better in providing robust real-time VE estimates among the population at risk.


Assuntos
Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Monitoramento Epidemiológico , Feminino , França/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Atenção Primária à Saúde , Resultado do Tratamento , Adulto Jovem
11.
Clin Microbiol Infect ; 23(4): 253-259, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27903461

RESUMO

OBJECTIVES: The aim of this study was to analyse characteristics and outcome of respiratory syncytial virus (RSV) infection in adults hospitalized with influenza-like illness (ILI). METHODS: Patients hospitalized with ILI were included in this prospective, multicentre study carried out in six French hospitals during three consecutive influenza seasons (2012-2015). RSV and other respiratory viruses were detected by multiplex PCR in nasopharyngeal swabs. Risk factors for RSV infection were identified by backward stepwise logistic regression analysis. RESULTS: A total of 1452 patients hospitalized with ILI were included, of whom 59% (861/1452) were >65 years and 83% (1211/1452) had underlying chronic illnesses. RSV was detected in 4% (59/1452), and influenza virus in 39% (566/1452). Risk factors for RSV infection were cancer (adjusted OR 2.1, 95% CI 1.1-4.1, p 0.04), and immunosuppressive treatment (adjusted OR 2.0, 95% CI 1.1-3.8, p 0.03). Patients with RSV had a median length of stay of 9 days (6-25), and 57% of them (30/53) had complications, including pneumonia (23/53, 44%) and respiratory failure (15/53, 28%). Fifteen per cent (8/53) were admitted to an intensive care unit, and the in-hospital mortality rate was 8% (4/53). Pneumonia was more likely to occur in patients with RSV than in patients with RSV-negative ILI (44% (23/53) versus 26% (362/1393), p 0.006) or with influenza virus infection (44% versus 28% (157/560), p 0.02). CONCLUSION: RSV is an infrequent cause of ILI during periods of influenza virus circulation but can cause severe complications in hospitalized adults. Risk factors for RSV detection in adults hospitalized with ILI include cancer and immunosuppressive treatment. Specific immunization and antiviral therapy might benefit patients at risk.


Assuntos
Hospitalização , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sincicial Respiratório Humano , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Comorbidade , Diagnóstico Diferencial , Feminino , França/epidemiologia , Mortalidade Hospitalar , Humanos , Lactente , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Razão de Chances , Avaliação de Resultados da Assistência ao Paciente , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/virologia , Fatores de Risco , Estações do Ano , Adulto Jovem
12.
Blood ; 125(4): 591-9, 2015 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-25359994

RESUMO

Germline loss-of-function mutations in the transcription factor signal transducer and activator of transcription 3 (STAT3) cause immunodeficiency, whereas somatic gain-of-function mutations in STAT3 are associated with large granular lymphocytic leukemic, myelodysplastic syndrome, and aplastic anemia. Recently, germline mutations in STAT3 have also been associated with autoimmune disease. Here, we report on 13 individuals from 10 families with lymphoproliferation and early-onset solid-organ autoimmunity associated with 9 different germline heterozygous mutations in STAT3. Patients exhibited a variety of clinical features, with most having lymphadenopathy, autoimmune cytopenias, multiorgan autoimmunity (lung, gastrointestinal, hepatic, and/or endocrine dysfunction), infections, and short stature. Functional analyses demonstrate that these mutations confer a gain-of-function in STAT3 leading to secondary defects in STAT5 and STAT1 phosphorylation and the regulatory T-cell compartment. Treatment targeting a cytokine pathway that signals through STAT3 led to clinical improvement in 1 patient, suggesting a potential therapeutic option for such patients. These results suggest that there is a broad range of autoimmunity caused by germline STAT3 gain-of-function mutations, and that hematologic autoimmunity is a major component of this newly described disorder. Some patients for this study were enrolled in a trial registered at www.clinicaltrials.gov as #NCT00001350.


Assuntos
Doenças Autoimunes/genética , Doenças Genéticas Inatas/genética , Transtornos Linfoproliferativos/genética , Fator de Transcrição STAT3/genética , Adolescente , Adulto , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Criança , Pré-Escolar , Feminino , Doenças Genéticas Inatas/imunologia , Doenças Genéticas Inatas/patologia , Humanos , Lactente , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/patologia , Masculino , Mutação , Fosforilação/genética , Fosforilação/imunologia , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/imunologia , Fator de Transcrição STAT3/imunologia , Fator de Transcrição STAT5/genética , Fator de Transcrição STAT5/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia
13.
Med Mal Infect ; 43(2): 81-4, 2013 Feb.
Artigo em Francês | MEDLINE | ID: mdl-23453670

RESUMO

OBJECTIVE: The authors had for objective to describe patients with confirmed influenza A(H1N1)pdm09 admitted to an intensive care unit (ICU) in a university hospital and to identify risk factors correlated with the severity of the disease. DESIGN: A prospective study was conducted in an university hospital during the A(H1N1)pdm09 influenza pandemic. Severe laboratory confirmed cases (admitted to an ICU) were described and compared with non-severe confirmed cases (not admitted to an ICU). RESULTS: Sixty-nine patients were included; 36 (52%) were 15 to 44 years of age. Sixteen (23%) cases were defined as severe, ten of these (63%) concerned patients 45 to 64 years of age. The independent factors associated with severity were: a history of heart disease, obesity, and tobacco abuse. CONCLUSIONS: This work reinforces the need to identify and protect groups at risk of severe outcomes.


Assuntos
Surtos de Doenças , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/epidemiologia , Unidades de Terapia Intensiva , Adolescente , Adulto , Comorbidade , Feminino , França/epidemiologia , Cardiopatias/epidemiologia , Hospitais Universitários/estatística & dados numéricos , Humanos , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Estudos Prospectivos , Fatores de Risco , Fumar/epidemiologia , Adulto Jovem
14.
Food Chem Toxicol ; 50(8): 2845-53, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22609490

RESUMO

The safety of the apple polyphenol extract EvesseEPC, which is rich in flavan-3-ols, particularly epicatechin, was evaluated. Both in a bacterial reverse mutation test and a mouse lymphoma assay, EvesseEPC showed a positive response in vitro. In vivo studies (UDS test in hepatocytes, bone marrow micronucleus test and comet assay in intestinal cells) were all negative and hence Evesse EPC is considered not to have genotoxic properties in vivo. In a 90-day study in rats, EvesseEPC was administered at dietary levels of 0%, 1.25%, 2% and 3.25%. Body weights were decreased in the high-dose group in both sexes without effects on feed or water intake. In the high-dose group, thrombocytes (males) and creatinine (both sexes) were decreased, prothrombin time (males) was increased, and liver, kidneys and spleen weights were increased (males), without histological correlates. Diffuse acinar cell hypertrophy, observed in the parotid salivary glands in all treatment groups, was not considered as adverse and presumably reflected a local, reversible and adaptive response to direct contact with EvesseEPC. The NOAEL for EvesseEPC in rats was 2% in the diet, equivalent to an overall average intake of 1.3 and 1.5 g/kg body weight/day for males and females, respectively.


Assuntos
Flavonoides/farmacologia , Malus/química , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Animais , Feminino , Flavonoides/efeitos adversos , Masculino , Camundongos , Testes para Micronúcleos , Extratos Vegetais/efeitos adversos , Polifenóis/efeitos adversos , Ratos , Ratos Wistar
15.
Cancer Gene Ther ; 19(1): 58-68, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22015640

RESUMO

Oncolytic adenoviruses are promising anticancer agents. To study and optimize their tumor-killing potency, genuine tumor models are required. Here we describe the use of the chicken chorioallantoic membrane (CAM) tumor model in studies on oncolytic adenoviral vectors. Suspensions of human melanoma, colorectal carcinoma and glioblastoma multiforme cell lines were grafted on the CAM of embryonated chicken eggs. All cell lines tested formed 5-10 mm size tumors, which recapitulated hallmarks of corresponding human specimens. Furthermore, melanoma tumors were injected with adenoviral vector-carrying gene encoding the fusion protein of parainfluenza virus type 5. This led to the induction of cell fusion and syncytia formation in the infected cells. At 6 days post-injection, histological and immunohistochemical analyses of tumor sections confirmed adenovirus replication and syncytia formation. These results demonstrate that the CAM model allows rapid assessment of oncolytic viruses in three-dimensional tumors. Hence, this model constitutes an easy and affordable system for preclinical characterization of viral oncolytic agents that may precede the mandatory process of animal testing. Application of this model will help reducing the use of human xenografts in mice for preclinical evaluation of oncolytic viruses and other anticancer agents.


Assuntos
Membrana Corioalantoide/virologia , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/genética , Adenoviridae/genética , Animais , Linhagem Celular Tumoral , Galinhas , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Neoplasias Colorretais/virologia , Vetores Genéticos/genética , Glioblastoma/genética , Glioblastoma/patologia , Glioblastoma/terapia , Glioblastoma/virologia , Humanos , Imuno-Histoquímica , Melanoma/genética , Melanoma/patologia , Melanoma/terapia , Melanoma/virologia
16.
J Med Entomol ; 48(2): 322-6, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21485368

RESUMO

Toxicity of nootkatone was determined in laboratory assays against unfed nymphs of Amblyomma americanum L., Dermacentor variabilis (Say), Ixodes scapularis Say, and Rhipicephalus sanguineus Latreille. We determined the 50% lethal concentration (LC50) and 90% lethal concentration (LC90) of nootkatone by recording tick mortality 24 h after exposure in treated glass vials. Nymphs were susceptible to nootkatone with LC50 values of 0.352, 0.233, 0.169, and 0.197 microg/cm2, and LC90 values of 1.001, 0.644, 0.549, and 0.485 microg/cm2 for A. americanum, D. variabilis, I. scapularis, and R. sanguineus, respectively. The LC50 value for R. sanquineus was not significantly different from D. variabilis or I. scapularis. Other LC50 comparisons were significantly different. The LC90 for A. americanum was higher when compared with the three other tick species, which were not significantly different. Because nootkatone is volatile, we measured the amount of nootkatone recovered from duplicate-treated vials before tick exposure and from vials after tick exposure. Nootkatone recovered from vials before exposure ranged from 82 to 112% of the expected amounts. The nootkatone recovered after the 24-h exposure period ranged from 89% from vials coated with higher concentrations of nootkatone, down to 29% from vials coated with low nootkatone concentrations. Determination of the nootkatone residue after vial coating demonstrated loss of the active compound while verifying the levels of tick exposure. Toxicity of low concentrations of nootkatone to the active questing stage of ticks reported in this study provides a reference point for future formulation research to exploit nootkatone as a safe and environment-friendly tick control.


Assuntos
Citrus paradisi/química , Ixodidae/efeitos dos fármacos , Óleos Voláteis/química , Óleos de Plantas/química , Sesquiterpenos/farmacologia , Acaricidas/química , Acaricidas/farmacologia , Animais , Sesquiterpenos Policíclicos
17.
Virus Res ; 146(1-2): 115-24, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19770012

RESUMO

The entry of enveloped viruses into host cells is accomplished by fusion of the viral envelope with the target cell membrane. For the paramyxovirus parainfluenza virus type 5 (PIV-5), this fusion involves an attachment protein (HN) and a class I viral fusion protein (F). We investigated the effect of 20 different combinations of 12 amino-acid substitutions within functional domains of the PIV-5 F glycoprotein, by performing cell surface expression measurements, quantitative fusion and syncytia assays. We found that combinations of mutations conferring an autonomous phenotype with mutations leading to an increased fusion activity were compatible and generated functional PIV-5 F proteins. The addition of mutations in the heptad-repeat domains led to both autonomous and hyperfusogenic phenotypes, despite the low cell surface expression of the corresponding mutants. Such engineering approach may prove useful not only for deciphering the fundamental mechanism behind viral-mediated membrane fusion but also in the development of potential therapeutic applications.


Assuntos
Evolução Molecular Direcionada , Respirovirus/fisiologia , Proteínas Virais de Fusão/fisiologia , Internalização do Vírus , Substituição de Aminoácidos/genética , Animais , Linhagem Celular , Células Gigantes/virologia , Haplorrinos , Humanos , Mutagênese , Respirovirus/genética , Proteínas Virais de Fusão/genética
18.
Food Chem Toxicol ; 47(10): 2407-18, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19576260

RESUMO

The safety of a refined arachidonic acid-rich oil (RAO) was evaluated for reverse mutation, chromosome aberration and gene mutation, and in a 90-day Wistar rat feeding study with in utero exposure. The results of the genotoxicity assays were all negative. The in utero phase of the 90-day study involved dietary exposure to 0.5%, 1.5% and 5% RAO and two controls diets, a standard feed low-fat diet and a high-fat diet supplemented with 5% corn oil. This exposure covered four-weeks prior to mating, through mating, gestation and lactation until offspring (F(1)) weaning. A subsequent 90-day feeding study in the F(1) rats evaluated the same test and control diets. Statistically significant effects were seen for selected histopathology, clinical chemistry and organ weight endpoints; however, other than increased absolute and relative monocytes seen in both sexes of high-dose rats, the observations were not attributed to treatment for one or more reasons. Based on these findings, no adverse treatment-related effects for RAO were seen at up to 5% in the diet, equivalent to an overall average RAO intake of 3170 mg/kg bwt/day. These and similar findings for other refined ARA-rich oils establish a strong body of evidence for the safety of this RAO.


Assuntos
Ácido Araquidônico/toxicidade , Gorduras Insaturadas na Dieta/toxicidade , Exposição Materna/efeitos adversos , Monócitos/efeitos dos fármacos , Mutagênicos/toxicidade , Reprodução/efeitos dos fármacos , Animais , Ácido Araquidônico/classificação , Ácido Araquidônico/metabolismo , Células CHO , Linhagem Celular Tumoral , Aberrações Cromossômicas/induzido quimicamente , Cricetinae , Cricetulus , Gorduras Insaturadas na Dieta/classificação , Gorduras Insaturadas na Dieta/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Feminino , Leucemia L5178/tratamento farmacológico , Leucemia L5178/enzimologia , Leucemia L5178/genética , Masculino , Monócitos/patologia , Testes de Mutagenicidade , Mutagênicos/classificação , Mutagênicos/metabolismo , Nível de Efeito Adverso não Observado , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Wistar , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Timidina Quinase/genética , Timidina Quinase/metabolismo
19.
Pathol Biol (Paris) ; 57(1): 86-9, 2009 Feb.
Artigo em Francês | MEDLINE | ID: mdl-18838230

RESUMO

The performances of two diagnostic tests for rotavirus infection in stool samples were evaluated during a prospective study in children of less than 36 months in child-care centers of Lyon from November 2004 to May 2005. The VIKIA Rota-Adeno immuno-chromatographic test (bioMérieux) and the ELISA IDEIA Rotavirus kit (Dako) were compared with a referral method, the genotyping. Fifty-seven stool samples were collected and analyzed by RT-PCR. The virus genome was detected in 29 samples. The most frequent genotypic combinations were G9P[8] with a prevalence of 75.9%. Sensitivity and specificity of the VIKIA Rota-Adeno test and the ELISA IDEIA Rotavirus kit were strictly comparable and very good: 96.6% (83.0; 99.9) and 96.4% (81.6; 99.9), respectively. The immuno-chromatographic technique were in concordance with the ELISA tests in 93.6% of cases. Thus, the VIKIA Rota-Adeno test is a good alternative for the occasional analysis of stool samples in ambulatory practice.


Assuntos
Infecções por Adenoviridae/diagnóstico , Cromatografia de Afinidade , Ensaio de Imunoadsorção Enzimática , Gastroenterite/virologia , Imunoensaio , Infecções por Rotavirus/diagnóstico , Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/virologia , Anticorpos Antivirais/imunologia , Antígenos Virais/análise , Creches , Pré-Escolar , Cromatografia de Afinidade/métodos , Colorimetria , Diarreia Infantil/epidemiologia , Diarreia Infantil/virologia , Diagnóstico Precoce , Fezes/virologia , Feminino , França/epidemiologia , Gastroenterite/epidemiologia , Genótipo , Humanos , Imunoensaio/métodos , Lactente , Masculino , Mastadenovirus/genética , Mastadenovirus/imunologia , Estudos Prospectivos , Rotavirus/genética , Rotavirus/imunologia , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/virologia , Sensibilidade e Especificidade
20.
Ann Biol Clin (Paris) ; 66(4): 433-6, 2008.
Artigo em Francês | MEDLINE | ID: mdl-18725345

RESUMO

We report a case of enterovirus related pericarditis associated to mediastinitis in a hospitalised 53-year-old male after heart surgery. Mediastinitis caused by enterovirus has not previously been described.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Infecções por Enterovirus , Mediastinite/virologia , Pericardite/virologia , Humanos , Masculino , Pessoa de Meia-Idade
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