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1.
IJID Reg ; 10: 146-149, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38304758

RESUMO

Objectives: Human T-lymphotropic virus (HTLV) antenatal screening is not mandatory in Spain. Surveys conducted decades ago reported HTLV-1 seroprevalence rates of 0.2% among foreign pregnant women in Spain. The migrant flow to Spain from HTLV-1 endemic regions in Latin America and sub-Saharan Africa has increased during the last decade. Currently, 25% of pregnant women in Spain are foreigners. Methods: From January 2021 to October 2023 a cross-sectional study was carried out in all consecutive pregnant women attended at eleven Spanish clinics. A commercial enzyme immunoassay (EIA) was used for screening of serum HTLV-1/2 antibodies. Reactive samples were confirmed by immunoblot. Results: A total of 9813 pregnant women with a median age of 34 years-old were examined. Native Spaniards were 6977 (76.5%). Of 2147 foreigners (23.5%), 903566 (9.9%) were Latin Americans, 416 (4.5%) North Africans, 293 (3.2%) from Romania, and 196 (2.1%) from sub-Saharan Africa. A total of 47 samples were EIA reactive but only five were confirmed as HTLV-1 positive using immunoblot. Infected women came from Paraguay, Colombia, the Dominican Republic, Venezuela and Peru. All but one were primigravida, with ages ranging from 20 to 33 years-old. One was HIV-1 positive, and another was infected with Chlamydia trachomatis. Conclusion: The overall seroprevalence for HTLV-1 among pregnant women in Spain is 0.05% but rises ten-fold (0.55%) among Latin Americans. This rate is higher than in surveys conducted decades ago. Our results support that anti-HTLV testing should be part of antenatal screening in Spain in pregnant women coming from Latin America, as it is already done with Chagas disease.

2.
Int J Mol Sci ; 24(17)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37686257

RESUMO

We aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS-COV cohort (73 IS-COV cases vs. 701 population controls) and different aetiological subtypes. Polygenic risk scores (PRSs) for each subtype were generated and tested in the IS-COV cohort using PRSice-2 and PLINK to find genetic associations. Both analyses used the IS-COV cohort and GWAS from MEGASTROKE (67,162 stroke patients vs. 454,450 population controls), GIGASTROKE (110,182 vs. 1,503,898), and the NINDS Stroke Genetics Network (16,851 vs. 32,473). Three genomic regions were associated (p-value < 0.05) with large artery atherosclerosis (LAA) and cardioembolic stroke (CES). We found four loci targeting the genes PITX2 (rs10033464, IS-COV beta = 0.04, p-value = 2.3 × 10-2, se = 0.02), previously associated with CES, HS6ST1 (rs4662630, IS-COV beta = -0.04, p-value = 1.3 × 10-3, se = 0.01), TMEM132E (rs12941838 IS-COV beta = 0.05, p-value = 3.6 × 10-4, se = 0.01), and RFFL (rs797989 IS-COV beta = 0.03, p-value = 1.0 × 10-2, se = 0.01). A statistically significant PRS was observed for LAA. Our results suggest that IS-COV cases are genetically similar to LAA and CES subtypes. Larger cohorts are needed to assess if the genetic factors in IS-COV cases are shared with the general population or specific to viral infection.


Assuntos
Aterosclerose , Isquemia Encefálica , COVID-19 , AVC Embólico , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética , Isquemia Encefálica/complicações , Isquemia Encefálica/genética , COVID-19/complicações , COVID-19/genética , AVC Isquêmico/genética , Artérias
3.
J Med Virol ; 95(5): e28779, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37212269

RESUMO

The 2022 annual meeting of the HTLV & HIV-2 Spanish Network was held in Madrid on December 14. We summarize here the main information presented and discussed at the workshop and review time trends for human retroviral infections in Spain. As transmissible agents, infections by human retroviruses are of obligatory declaration. Until the end of 2022, the Spanish national registry had recorded 451 cases of HTLV-1, 821 of HTLV-2, and 416 of HIV-2. For HIV-1, estimates are of 150 000 people currently living with HIV-1 and 60 000 cumulative deaths due to AIDS. During year 2022, new diagnoses in Spain were of 22 for HTLV-1, 6 for HTLV-2, and 7 for HIV-2. The last updated figures for HIV-1 are from 2021 and counted 2786 new diagnoses. The slowdown in yearly infections for HIV-1 in Spain points out that new strategies are needed to achieve the United Nations 95-95-95 targets by 2025. For the remaining neglected human retroviral infections, their control might be pushed throughout four interventions: (1) expanding testing; (2) improving education and interventions aimed to reduce risk behaviors; (3) facilitating access to antiretrovirals as treatment and prevention, including further development of long-acting formulations; and (4) increasing vaccine research efforts. Spain is a 47 million population country in South Europe with strong migration flows from HTLV-1 endemic regions in Latin America and Sub-Saharan Africa. At this time universal HTLV screening has been implemented only in the transplantation setting, following the report of 5 cases of HTLV-associated myelopathy shortly after transplantation of organs from HTLV-1 positive donors. There are four target populations for expanding testing and unveiling asymptomatic carriers responsible for silent HTLV-1 transmissions: (1) migrants; (2) individuals with sexually transmitted infections; (3) pregnant women; and (4) blood donors.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Feminino , Gravidez , Espanha/epidemiologia , Vírus Linfotrópico T Tipo 2 Humano , HIV-2 , Infecções por HTLV-I/epidemiologia
4.
Int J Infect Dis ; 122: 970-975, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35902023

RESUMO

OBJECTIVES: Although only 10% of persons infected with human T-lymphotropic virus type 1 (HTLV-1) may develop virus-associated illnesses over their lifetime, missing the earlier diagnosis of asymptomatic carriers frequently leads to late presentation. METHODS: A nationwide HTLV-1 register was created in Spain in 1989. We examined the main demographics and clinical features at the time of the first diagnosis for more than three decades. RESULTS: A total of 428 individuals infected with HTLV-1 had been reported in Spain until the end of 2021. Up to 96 (22%) individuals presented clinically with HTLV-1-associated conditions, including subacute myelopathy (57%), T-cell lymphoma (34%), or Strongyloides stercoralis infestation (8%). Since 2008, HTLV-1 diagnosis has been made at blood banks (44%) or clinics (56%). Native Spaniards and Sub-Saharan Africans are overrepresented among patients presenting with HTLV-1-associated illnesses suggesting that poor epidemiological and/or clinical suspicion, which led to the late presentation are more frequent in them than carriers from Latin America (LATAM) (31.7% vs 20.4%, respectively; P = 0.015). CONCLUSION: HTLV-1 infection in Spain is frequently diagnosed in patients presenting with characteristic illnesses. Although screening in blood banks mostly identifies asymptomatic carriers from LATAM, a disproportionately high number of Spaniards and Africans are diagnosed too late at the time of clinical manifestations. Expanding testing to all pregnant women and clinics for sexually transmitted infections could help to unveil HTLV-1 asymptomatic carriers.


Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Strongyloides stercoralis , Animais , Feminino , Infecções por HTLV-I/complicações , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/epidemiologia , Humanos , América Latina , Gravidez , Espanha/epidemiologia
5.
An Pediatr (Engl Ed) ; 96(4): 334-341, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35609953

RESUMO

INTRODUCTION: Coinfections of influenza and other respiratory viruses (ORVs) are frequent in the epidemic season. The aim of this study was to examine the demographic and virological variables associated with coinfections by influenza and ORVs. MATERIALS AND METHODS: We analysed respiratory samples of patients with laboratory-confirmed influenza using molecular diagnostic methods obtained in 8 consecutive influenza seasons (2011-2012 to 2018-2019). We analysed data focusing on different variables: age, sex, type of patient (hospitalized/sentinel) and detected type/subtype of influenza. RESULTS: Coinfections of influenza and ORVs were detected in 17.8% of influenza-positive samples. The probability of detecting coinfection was significantly higher in young children (0-4 years; OR: 2.7; 95% CI: 2.2-3.4), children (5-14 years; OR: 1.6; 95% CI: 1.2-2.1) and patients infected with the A(H3N2) subtype (OR: 1.4; 95% CI: 1.14-1.79). Also, we found a significantly higher frequency of coinfections involving influenza and 2 or more other respiratory viruses in young children (0-4 years; OR: 0.5; 95% CI: 0.32-0.8), adults (40-64 years; OR: 0.5; 95% CI: 0.3-0.9) and women (OR: 0.7; 95% CI: 0.5-0.9). DISCUSSION: These results show that coinfections of influenza and ORVs are more frequent in young children and children, and in cases involving the A(H3N2) influenza subtype. Our findings can be useful to guide the use of multiplex diagnostic methods in laboratories with limited resources.


Assuntos
Coinfecção , Epidemias , Influenza Humana , Adulto , Criança , Pré-Escolar , Coinfecção/diagnóstico , Coinfecção/epidemiologia , Feminino , Humanos , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/complicações , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Estações do Ano
6.
An. pediatr. (2003. Ed. impr.) ; 96(4): 334-341, abril 2022. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-205459

RESUMO

Introducción: Las coinfecciones por gripe y otros virus respiratorios (OVR) durante las epidemias gripales son frecuentes. El objetivo de este estudio es examinar las variables demográficas y virológicas relacionadas con las coinfecciones entre la gripe y OVR. Materiales y métodos: En este estudio se analizaron muestras respiratorias de 8 epidemias gripales consecutivas (desde la temporada 2011-2012 hasta la temporada 2018-2019), en las que se había detectado un resultado positivo de gripe mediante test en laboratorio. Analizamos los datos objetivándolos frente a diferentes variables: edad, sexo, tipo de paciente (hospitalizado/centinela) y tipo/subtipo de gripe detectada. Resultados: Las coinfecciones entre gripe y OVR se detectaron en el 17,8% de los casos positivos de gripe. En los niños de entre 0-4 años (OR: 2,7; IC 95%: 2,2-3,4), los niños de entre 5-14 años (OR: 1,6; IC 95%: 1,2-2,1) y los pacientes infectados por el subtipo A(H3N2) (OR: 1,4; IC 95%: 1,14-1,79), se detectó una probabilidad significativamente mayor de detectar estas coinfecciones. Además, observamos que las coinfecciones entre gripe y 2 o más OVR fueron llamativamente más frecuentes en niños de 0-4 años (OR: 0,5; IC 95%: 0,32-0,8), en adultos de entre 40-64 años (OR: 0,5; IC 95%: 0,3-0,9) y en mujeres (OR: 0,7; IC 95%: 0,5-0,9). Discusión: Estos resultados muestran que las coinfecciones entre gripe y OVR son más frecuentes en niños de 0-4 años y de 5-14 años, y en los casos en los que el subtipo A(H3N2) está implicado. Estos datos pueden ser útiles para enfocar el diagnóstico mediante métodos multiplex en aquellos laboratorios que posean pocos recursos económicos y humanos. (AU)


Introduction: Coinfections of influenza and other respiratory viruses (ORVs) are frequent in the epidemic season. The aim of this study was to examine the demographic and virological variables associated with coinfections by influenza and ORVs. Materials and methods: We analysed respiratory samples of patients with laboratory-confirmed influenza using molecular diagnostic methods obtained in 8 consecutive influenza seasons (2011-2012 to 2018-2019). We analysed data focusing on different variables: age, sex, type of patient (hospitalized/sentinel) and detected type/subtype of influenza. Results: Coinfections of influenza and ORVs were detected in 17.8% of influenza-positive samples. The probability of detecting coinfection was significantly higher in young children (0-4 years; OR: 2.7; 95% CI: 2.2-3.4), children (5-14 years; OR: 1.6; 95% CI: 1.2-2.1) and patients infected with the A(H3N2) subtype (OR: 1.4; 95% CI: 1.14-1.79). Also, we found a significantly higher frequency of coinfections involving influenza and 2 or more other respiratory viruses in young children (0-4 years; OR: 0.5; 95% CI: 0.32-0.8), adults (40-64 years; OR: 0.5; 95% CI: 0.3-0.9) and women (OR: 0.7; 95% CI: 0.5-0.9). Discussion: These results show that coinfections of influenza and ORVs are more frequent in young children and children, and in cases involving the A(H3N2) influenza subtype. Our findings can be useful to guide the use of multiplex diagnostic methods in laboratories with limited resources. (AU)


Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Orthomyxoviridae , Infecções Respiratórias , Influenza Humana/epidemiologia , Estudos Retrospectivos , Coinfecção
9.
AIDS Res Hum Retroviruses ; 37(8): 610-612, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34078135

RESUMO

The medical demand imposed by COVID-19 has distracted proper care of other illnesses. Herein, we report the impact on new diagnoses of HTLV-1, HTLV-2, and HIV-2 in Spain, where these infections are mostly driven by immigration flows from endemic regions. As expected, case reporting declined for all three retroviral infections with respect to prior years. Furthermore, late presentations were more common. The two major reasons for these observations were significant declines in the arrival of foreigners from endemic regions and a shift in medical resources to prioritize COVID-19.


Assuntos
COVID-19/epidemiologia , Infecções por Deltaretrovirus/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-2/isolamento & purificação , Infecções por Deltaretrovirus/diagnóstico , Emigração e Imigração/legislação & jurisprudência , Infecções por HIV/diagnóstico , Humanos , Incidência , SARS-CoV-2 , Espanha/epidemiologia
10.
An Pediatr (Engl Ed) ; 2021 Mar 18.
Artigo em Espanhol | MEDLINE | ID: mdl-33745837

RESUMO

INTRODUCTION: Coinfections of influenza and other respiratory viruses (ORVs) are frequent in the epidemic season. The aim of this study was to examine the demographic and virological variables associated with coinfections by influenza and ORVs. MATERIALS AND METHODS: We analysed respiratory samples of patients with laboratory-confirmed influenza using molecular diagnostic methods obtained in 8 consecutive influenza seasons (2011-2012 to 2018-2019). We analysed data focusing on different variables: age, sex, type of patient (hospitalized/sentinel) and detected type/subtype of influenza. RESULTS: Coinfections of influenza and ORVs were detected in 17.8% of influenza-positive samples. The probability of detecting coinfection was significantly higher in young children (0-4 years; OR: 2.7; 95% CI: 2.2-3.4), children (5-14 years; OR: 1.6; 95% CI: 1.2-2.1) and patients infected with the A(H3N2) subtype (OR: 1.4; 95% CI: 1.14-1.79). Also, we found a significantly higher frequency of coinfections involving influenza and 2 or more other respiratory viruses in young children (0-4 years; OR: 0.5; 95% CI: 0.32-0.8), adults (40-64 years; OR: 0.5; 95% CI: 0.3-0.9) and women (OR: 0.7; 95% CI: 0.5-0.9). DISCUSSION: These results show that coinfections of influenza and ORVs are more frequent in young children and children, and in cases involving the A(H3N2) influenza subtype. Our findings can be useful to guide the use of multiplex diagnostic methods in laboratories with limited resources.

12.
Asian J Androl ; 22(4): 401-408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31210149

RESUMO

The sperm nucleus is prone to sustain DNA damage before and after ejaculation. Distribution of the damage is not homogeneous, and the factors determining differential sensitivity among nuclear regions have not yet been characterized. Human sperm chromatin contains three structural domains, two of which are considered the most susceptible to DNA damage: the histone bound domain, harboring developmental related genes, and the domain associated with nuclear matrix proteins. Using a quantitative polymerase chain reaction (qPCR) approach, we analyzed the number of lesions in genes homeobox A3 (HOXA3), homeobox B5 (HOXB 5), sex-determining region Y (SRY)-box 2 (SOX2), ß-GLOBIN, rDNA 18S, and rDNA 28S in human sperm after ultraviolet irradiation (400 µW cm-2, 10 min), H2O2treatment (250 mmol l-1, 20 min), and cryopreservation, which showed differential susceptibility to genetic damage. Differential vulnerability is dependent on the genotoxic agent and independent of the sperm nuclear proteins to which the chromatin is bound and of accessibility to the transcription machinery. Immunodetection of 8-hydroxy-2'-deoxyguanosine (8-OHdG) showed that the highest level of oxidation was observed after H2O2treatment. The distribution of oxidative lesions also differed depending on the genotoxic agent. 8-OHdG did not colocalize either with histone 3 (H3) or with type IIα + ß topoisomerase (TOPO IIα + ß) after H2O2treatment but matched perfectly with peroxiredoxin 6 (PRDX6), which is involved in H2O2metabolism. Our study reveals that the characteristics of the sperm head domains are responsible for access of the genotoxicants and cause differential degree of damage to nuclear areas, whereas chromatin packaging has a very limited relevance. The histone-enriched genes analyzed cannot be used as biomarkers of oxidative DNA damage.


Assuntos
Cromatina/efeitos dos fármacos , Cromatina/efeitos da radiação , Criopreservação , Dano ao DNA , Oxidantes/farmacologia , Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos da radiação , Raios Ultravioleta/efeitos adversos , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Adulto , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Núcleo Celular/efeitos da radiação , Cromatina/metabolismo , DNA Ribossômico/genética , Voluntários Saudáveis , Proteínas de Homeodomínio/genética , Humanos , Peróxido de Hidrogênio/farmacologia , Masculino , Reação em Cadeia da Polimerase , RNA Ribossômico 18S/genética , RNA Ribossômico 28S/genética , Fatores de Transcrição SOXB1/genética , Preservação do Sêmen , Cabeça do Espermatozoide/efeitos dos fármacos , Cabeça do Espermatozoide/metabolismo , Cabeça do Espermatozoide/efeitos da radiação , Espermatozoides/metabolismo , Globinas beta/genética
13.
Sci Rep ; 9(1): 18029, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792261

RESUMO

Exposure to bisphenol A (BPA) has been related to male reproductive disorders. Since this endocrine disruptor also displays genotoxic and epigenotoxic effects, it likely alters the spermatogenesis, a process in which both hormones and chromatin remodeling play crucial roles. The hypothesis of this work is that BPA impairs early embryo development by modifying the spermatic genetic and epigenetic information. Zebrafish males were exposed to 100 and 2000 µg/L BPA during early spermatogenesis and during the whole process. Genotoxic and epigenotoxic effects on spermatozoa (comet assay and immunocytochemistry) as well as progeny development (mortality, DNA repairing activity, apoptosis and epigenetic profile) were evaluated. Exposure to 100 µg/L BPA during mitosis slightly increased sperm chromatin fragmentation, enhancing DNA repairing activity in embryos. The rest of treatments promoted high levels of sperm DNA damage, triggering apoptosis in early embryo and severely impairing survival. Regarding epigenetics, histone acetylation (H3K9Ac and H3K27Ac) was similarly enhanced in spermatozoa and embryos from males exposed to all the treatments. Therefore, BPA male exposure jeopardizes embryonic survival and development due to the transmission of a paternal damaged genome and of a hyper-acetylated histone profile, both alterations depending on the dose of the toxicant and the temporal window of exposure.


Assuntos
Compostos Benzidrílicos/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Epigênese Genética/efeitos dos fármacos , Fenóis/toxicidade , Espermatogênese/efeitos dos fármacos , Acetilação/efeitos dos fármacos , Animais , Cromatina/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Embrião não Mamífero , Histonas/metabolismo , Masculino , Modelos Animais , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia , Fatores de Tempo , Peixe-Zebra
14.
AIDS ; 33(14): 2167-2172, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31373918

RESUMO

BACKGROUND: Whereas HIV-1 has spread globally, HIV-2 is mainly found in West Africa where dual HIV-1/HIV-2 coinfection is nowadays uncommon. Herein, we report the rate, main characteristics, and treatment outcomes of all dually infected patients living in Spain. METHODS: We identified retrospectively all persons coinfected with HIV-1 recorded at the Spanish HIV-2 registry. Dual infection had been confirmed using PCR in plasma and/or cells, and/or using discriminatory serological tests. RESULTS: From a total of 373 individuals with HIV-2 recorded at the Spanish registry, 34 (9.1%) were coinfected with HIV-1. Compared with HIV-2 monoinfected persons, dually infected patients were more often male (67.6%), presented with lower median CD4 cell counts (204 cells/µl), and had developed more frequently AIDS events (26.5%). Although 61.7% came from West Africa, 6 (17.6%) were native Spaniards. HIV-1 non-B subtypes were recognized in 75% of coinfected patients, being the most prevalent CRF02_AG. At baseline, 45% of dually infected patients had undetectable plasma HIV-2 RNA. After a median follow-up of 32 (13-48) months on antiretroviral therapy, dually infected patients achieved undetectable viremia in 85% for HIV-1, in 80% for HIV-2; and in 70% for both viruses. Median CD4 cell counts reached up to 418 cells/µl. CONCLUSION: Roughly 9% of individuals with HIV-2 infection living in Spain are coinfected with HIV-1. Overall, 70% of dually infected patients achieved viral suppression for both viruses under antiretroviral therapy. Given the relatively large population of West Africans living in Spain and the continuous migration flow from HIV-2 endemic areas, HIV-1/HIV-2 coinfection should always be excluded at first diagnosis in all HIV-seroreactive persons.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , HIV-2/isolamento & purificação , Adulto , Contagem de Linfócito CD4 , Coinfecção/virologia , Feminino , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Resultado do Tratamento , Carga Viral , Viremia/tratamento farmacológico
15.
Environ Pollut ; 246: 1008-1019, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31126002

RESUMO

Exposure to the emerging contaminant bisphenol A (BPA) is ubiquitous and associated with cardiovascular disorders. BPA effect as endocrine disruptor is widely known but other mechanisms underlying heart disease, such as epigenetic modifications, remain still unclear. A compound of green tea, epigallocatechin gallate (EGCG), may act both as anti-estrogen and as inhibitor of some epigenetic enzymes. The aims of this study were to analyze the molecular processes related to BPA impairment of heart development and to prove the potential ability of EGCG to neutralize the toxic effects caused by BPA on cardiac health. Zebrafish embryos were exposed to 2000 and 4000 µg/L BPA and treated with 50 and 100 µM EGCG. Heart malformations were assessed at histological level and by confocal imaging. Expression of genes involved in cardiac development, estrogen receptors and epigenetic enzymes was analyzed by qPCR whereas epigenetic modifications were evaluated by whole mount immunostaining. BPA embryonic exposure led to changes in cardiac phenotype, induced an overexpression of hand2, a crucial factor for cardiomyocyte differentiation, increased the expression of estrogen receptor (esr2b), promoted an overexpression of a histone acetyltransferase (kat6a) and also caused an increase in histone acetylation, both mechanisms being able to act in sinergy. EGCG treatment neutralized all the molecular alterations caused by BPA, allowing the embryos to go on with a proper heart development. Both molecular mechanisms of BPA action (estrogenic and epigenetic) likely lying behind cardiogenesis impairment were successfully counteracted by EGCG treatment.


Assuntos
Compostos Benzidrílicos/toxicidade , Catequina/análogos & derivados , Disruptores Endócrinos/toxicidade , Organogênese/efeitos dos fármacos , Fenóis/toxicidade , Acetilação/efeitos dos fármacos , Animais , Catequina/farmacologia , Epigênese Genética , Estrogênios/metabolismo , Histonas/metabolismo , Receptores de Estrogênio/metabolismo , Peixe-Zebra/embriologia
16.
Biol Open ; 7(5)2018 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-29712649

RESUMO

Spermatozoa carry DNA damage that must be repaired by the oocyte machinery upon fertilization. Different strategies could be adopted by different vertebrates to face the paternal genotoxic damage. Mammals have strong sperm selection mechanisms and activate a zygotic DNA damage response (DDR) (including cell cycle arrest, DNA repair and alternative apoptosis) in order to guarantee the genomic conformity of the reduced progeny. However, external fertilizers, with different reproductive strategies, seem to proceed distinctively. Previous results from our group showed a downregulation of apoptotic activity in trout embryos with a defective DNA repairing ability, suggesting that mechanisms of tolerance to damaged DNA could be activated in fish to maintain cell survival and to progress with development. In this work, zebrafish embryos were obtained from control or UV-irradiated sperm (carrying more than 10% of fragmented DNA but still preserving fertilization ability). DNA repair (γH2AX and 53BP1 foci), apoptotic activity, expression of genes related to DDR and malformation rates were analyzed throughout development. Results showed in the progeny from damaged sperm, an enhanced repairing activity at the mid-blastula transition stage that returned to its basal level at later stages, rendering at hatching a very high rate of multimalformed larvae. The study of transcriptional and post-translational activity of tp53 (ZDF-GENE-990415-270) revealed the activation of an intense DDR in those progenies. However, the downstream pro-apoptotic factor noxa (ZDF-GENE-070119-3) showed a significant downregulation, whereas the anti-apoptotic gene bcl2 (ZDF-GENE-051015-1) was upregulated, triggering a repressive apoptotic scenario in spite of a clear genomic instability. This repression can be explained by the observed upregulation of p53 isoform Δ113p53, which is known to inhibit bcl2 transcription. Our results showed that tp53 is involved in DNA damage tolerance (DDT) pathways, allowing the embryo survival regardless of the paternal DNA damage. DDT could be an evolutionary mechanism in fish: tolerance to unrepaired sperm DNA could introduce new mutations, some of them potentially advantageous to face a changing environment.

17.
Vaccines (Basel) ; 5(3)2017 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-28714923

RESUMO

Avian influenza viruses are currently one of the main threats to human health in the world. Although there are some screening reports of antibodies against these viruses in humans from Western countries, most of these types of studies are conducted in poultry and market workers of Asian populations. The presence of antibodies against avian influenza viruses was evaluated in an elderly European population. An experimental study was conducted, including pre- and post-vaccine serum samples obtained from 174 elderly people vaccinated with seasonal influenza vaccines of 2006-2007, 2008-2009, 2009-2010, and 2010-2011 Northern Hemisphere vaccine campaigns. The presence of antibodies against A/H5N1, A/H7N3, and A/H9N2 avian influenza viruses were tested by using haemaglutination inhibition assays. Globally, heterotypic antibodies were found before vaccination in 2.9% of individuals against A/H5N1, 1.2% against A/H7N3, and 25.9% against A/H9N2. These pre-vaccination antibodies were present at titers ≥1/40 in 1.1% of individuals against A/H5N1, in 1.1% against H7N3, and in 0.6% against the A/H9N2 subtype. One 76 year-old male showed pre-vaccine antibodies (Abs) against those three avian influenza viruses, and another three individuals presented Abs against two different viruses. Seasonal influenza vaccination induced a significant number of heterotypic seroconversions against A/H5N1 (14.4%) and A/H9N2 (10.9%) viruses, but only one seroconversion was observed against the A/H7N3 subtype. After vaccination, four individuals showed Abs titers ≥1/40 against those three avian viruses, and 55 individuals against both A/H5N1 and A/H9N2. Seasonal vaccination is able to induce some weak heterotypic responses to viruses of avian origin in elderly individuals with no previous exposure to them. However, this response did not accomplish the European Medicament Agency criteria for influenza vaccine efficacy. The results of this study show that seasonal vaccines induce a broad response of heterotypic antibodies against avian influenza viruses, albeit at a low level.

18.
Rev. esp. quimioter ; 30(3): 177-182, jun. 2017. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-163229

RESUMO

Introducción. El virus del papiloma humano (VPH), es causa necesaria para el desarrollo de cáncer de cuello uterino. El objetivo del estudio fue estimar la prevalencia de mujeres con infección por VPH, adheridas al Programa de Prevención y Detección precoz de Cáncer de cuello de útero de Castilla y León (España). Material y métodos. Se han evaluado los resultados del análisis de VPH en las muestras de las mujeres incluidas en el programa de cribado poblacional. El estudio incluye un total de 120.326 muestras de frotis de cérvix, recogidas en el periodo comprendido entre enero de 2012 y diciembre de 2014. Resultados. Se obtuvieron 12.183 muestras con detección positiva de ADN de VPH, correspondiendo a una prevalencia de 9,6‰ (IC 95% 9,5%-9,8%), en la población femenina. Los VPH asociados a un alto riesgo de transformación celular se encuentran en mayor proporción que los de bajo riesgo (5,9% vs 2,23%). La prevalencia está inversamente relacionada con la edad de las mujeres del cribado. La presencia de infecciones múltiples de VPH se demuestra en un tercio de las mujeres analizadas. Conclusiones. Estos resultados son los primeros y más amplios de un programa de cribado poblacional estructurado en España y deben servir como referencia para futuros estudios y medir el impacto futuro de la vacunación (AU)


Introduction. The human papillomavirus (HPV), is necessary to cause a woman developing cervical cancer. The aim of the study was to estimate the prevalence of women with HPV infection, covered by the program of prevention and early detection of cervical cancer of Castile and León (Spain). Material and methods. Samples of women included in the screening program were analyzed. Including a total of 120,326 cervical swab samples, collected in the period from January 2012 to December 2014. Results. 12,183 HPV positive samples were detected, representing a prevalence of 9.6 ‰, (IC 95% 9.5%-9.8%) in the female population. High-risk HPV were found in higher proportion that HPV low-risk genotypes. HPV prevalence correlates inversely with women age. Coinfections of multiple genotypes were found in one third of screened women population. Conclusions. Data showed in this study are the first and wider Spanish results from a cervical cancer screening program population non opportunistic based on HPV detection. These results would serve as a reference for future prevalence studies and to evaluate the future impact of HPV vaccination campaigns (AU)


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Diagnóstico Precoce , Neoplasias Uterinas/diagnóstico , Programas de Rastreamento/métodos , Esfregaço Vaginal/estatística & dados numéricos , Esfregaço Vaginal , Colo do Útero/citologia , Colo do Útero/patologia , Técnicas de Genotipagem/métodos
20.
Environ Pollut ; 206: 667-78, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26322593

RESUMO

Bisphenol A (BPA) is an endocrine disruptor used in manufacturing of plastic devices, resulting in an ubiquitous presence in the environment linked to human infertility, obesity or cardiovascular diseases. Both transcriptome and epigenome modifications lie behind these disorders that might be inherited transgenerationally when affecting germline. To assess potential effects of paternal exposure on offspring development, adult zebrafish males were exposed to BPA during spermatogenesis and mated with non-treated females. Results showed an increase in the rate of heart failures of progeny up to the F2, as well as downregulation of 5 genes involved in cardiac development in F1 embryos. Moreover, BPA causes a decrease in F0 and F1 sperm remnant mRNAs related to early development. Results reveal a paternal inheritance of changes in the insulin signaling pathway due to downregulation of insulin receptor ß mRNAs, suggesting a link between BPA male exposure and disruption of cardiogenesis in forthcoming generations.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Cardiopatias Congênitas/induzido quimicamente , Exposição Paterna/efeitos adversos , Fenóis/toxicidade , Espermatozoides/efeitos dos fármacos , Peixe-Zebra/crescimento & desenvolvimento , Animais , Metilação de DNA/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Cardiopatias Congênitas/embriologia , Cardiopatias Congênitas/genética , Humanos , Masculino , Organogênese/efeitos dos fármacos , Organogênese/genética , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra/genética
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