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1.
Vaccine ; 42(9): 2429-2437, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38458875

RESUMO

Louping ill virus (LIV) is a tick-borne flavivirus that predominantly causes disease in livestock, especially sheep in the British Isles. A preventive vaccine, previously approved for veterinary use but now discontinued, was based on an inactivated whole virion that likely provided protection by induction of neutralizing antibodies recognizing the viral envelope (E) protein. A major disadvantage of the inactivated vaccine was the need for high containment facilities for the propagation of infectious virus, as mandated by the hazard group 3 status of the virus. This study aimed to develop high-efficacy non-infectious protein-based vaccine candidates. Specifically, soluble envelope protein (sE), and virus-like particles (VLPs), comprised of the precursor of membrane and envelope proteins, were generated, characterized, and studied for their immunogenicity in mice. Results showed that the VLPs induced more potent virus neutralizing response compared to sE, even though the total anti-envelope IgG content induced by the two antigens was similar. Depletion of anti-monomeric E protein antibodies from mouse immune sera suggested that the neutralizing antibodies elicited by the VLPs targeted epitopes spanning the highly organized structure of multimer of the E protein, whereas the antibody response induced by sE focused on E monomers. Thus, our results indicate that VLPs represent a promising LIV vaccine candidate.


Assuntos
Vírus da Encefalite Transmitidos por Carrapatos , Vacinas de Partículas Semelhantes a Vírus , Vacinas , Animais , Camundongos , Ovinos , Anticorpos Neutralizantes , Anticorpos Antivirais , Proteínas do Envelope Viral
2.
Cell ; 187(6): 1363-1373.e12, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38366591

RESUMO

In response to the 2022 outbreak of mpox driven by unprecedented human-to-human monkeypox virus (MPXV) transmission, we designed BNT166, aiming to create a highly immunogenic, safe, accessible, and scalable next-generation vaccine against MPXV and related orthopoxviruses. To address the multiple viral forms and increase the breadth of immune response, two candidate multivalent mRNA vaccines were evaluated pre-clinically: a quadrivalent vaccine (BNT166a; encoding the MPXV antigens A35, B6, M1, H3) and a trivalent vaccine (BNT166c; without H3). Both candidates induced robust T cell responses and IgG antibodies in mice, including neutralizing antibodies to both MPXV and vaccinia virus. In challenge studies, BNT166a and BNT166c provided complete protection from vaccinia, clade I, and clade IIb MPXV. Furthermore, immunization with BNT166a was 100% effective at preventing death and at suppressing lesions in a lethal clade I MPXV challenge in cynomolgus macaques. These findings support the clinical evaluation of BNT166, now underway (NCT05988203).


Assuntos
Monkeypox virus , Mpox , Vacina Antivariólica , Animais , Humanos , Camundongos , Macaca fascicularis , Monkeypox virus/genética , Mpox/imunologia , Mpox/prevenção & controle , Vacinas Combinadas , Vaccinia virus/genética
3.
Molecules ; 28(13)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37446546

RESUMO

Re-emerging arboviruses represent a serious health problem due to their rapid vector-mediated spread, mainly in urban tropical areas. The 2013-2015 Zika virus (ZIKV) outbreak in South and Central America has been associated with cases of microcephaly in newborns and Guillain-Barret syndrome. We previously showed that the conjugate gallic acid-Hecate (GA-FALALKALKKALKKLKKALKKAL-CONH2)-is an efficient inhibitor of the hepatitis C virus. Here, we show that the Hecate peptide is degraded in human blood serum into three major metabolites. These metabolites conjugated with gallic acid were synthesized and their effect on ZIKV replication in cultured cells was evaluated. The GA-metabolite 5 (GA-FALALKALKKALKKL-COOH) was the most efficient in inhibiting two ZIKV strains of African and Asian lineage at the stage of both virus entry (virucidal and protective) and replication (post-entry). We also demonstrate that GA-metabolite 5 does not affect cell growth after 7 days of continuous treatment. Thus, this study identifies a new synthetic antiviral compound targeting different steps of ZIKV replication in vitro and with the potential for broad reactivity against other flaviviruses. Our work highlights a promising strategy for the development of new antivirals based on peptide metabolism and bioconjugation.


Assuntos
Fármacos Dermatológicos , Infecção por Zika virus , Zika virus , Recém-Nascido , Humanos , Antivirais/química , Replicação Viral , Fármacos Dermatológicos/farmacologia , Ácido Gálico/farmacologia
4.
PeerJ ; 11: e14738, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36778155

RESUMO

Background: Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2) are chronic degenerative diseases with complex molecular processes that are potentially interconnected. The aim of this work was to predict the potential molecular links between AD and DM2 from different sources of biological information. Materials and Methods: In this work, data mining of nine databases (DisGeNET, Ensembl, OMIM, Protein Data Bank, The Human Protein Atlas, UniProt, Gene Expression Omnibus, Human Cell Atlas, and PubMed) was performed to identify gene and protein information that was shared in AD and DM2. Next, the information was mapped to human protein-protein interaction (PPI) networks based on experimental data using the STRING web platform. Then, gene ontology biological process (GOBP) and pathway analyses with EnrichR showed its specific and shared biological process and pathway deregulations. Finally, potential biomarkers and drug targets were predicted with the Metascape platform. Results: A total of 1,551 genes shared in AD and DM2 were identified. The highest average degree of nodes within the PPI was for DM2 (average = 2.97), followed by AD (average degree = 2.35). GOBP for AD was related to specific transcriptional and translation genetic terms occurring in neurons cells. The GOBP and pathway information for the association AD-DM2 were linked mainly to bioenergetics and cytokine signaling. Within the AD-DM2 association, 10 hub proteins were identified, seven of which were predicted to be present in plasma and exhibit pharmacological interaction with monoclonal antibodies in use, anticancer drugs, and flavonoid derivatives. Conclusion: Our data mining and analysis strategy showed that there are a plenty of biological information based on experiments that links AD and DM2, which could provide a rational guide to design further diagnosis and treatment for AD and DM2.


Assuntos
Doença de Alzheimer , Diabetes Mellitus Tipo 2 , Humanos , Doença de Alzheimer/genética , Diabetes Mellitus Tipo 2/genética , Mapas de Interação de Proteínas/genética , Biologia Computacional , Bases de Dados Factuais
5.
Urologia ; 90(1): 180-184, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35796543

RESUMO

INTRODUCTION: Urethral Pressure Profilometry (UPP) assesses the urethral closing function. The literature is scarce regarding the change in the Maximum Urethral Closure Pressure (MUCP) values during Pelvic Floor Muscle Contraction (PFMC). The objective was to evaluate the change in the urethral closure pressure (UCP) at rest and during a PFMC in patients with Stress Urinary Incontinence. MATERIALS AND METHODS: This was a descriptive, comparative, and observational study. The study comprised female patients with either Pure Stress Urinary Incontinence (PSUI) or Complicated Stress Urinary Incontinence (CSUI). The urethral closure pressure was measured at rest and during PFMC using urethral profilometry. The effect of the pelvic musculature contraction was evaluated by comparing the changes in the indicated values. RESULTS: Patients with pure stress urinary incontinence had a mean age of 57.18 ± 10.74 years (p = 0.12), while those with complicated stress urinary incontinence had a mean age of 58.26 ± 14.39 years (p = 0.12). UCP in PSUI was 58.58 ± 26.96 cmH2O at rest compared to 61.26 ± 34.17 cmH2O in CSUI (p = 0.59), with MUCP increasing to 73.93 ± 31.51 and 79.71 ± 36.26 cmH2O during PFMC (p = 0.001). Between the two measurements, there was an average rise of 26.2% (range 26.2%-32.59%) (p = 0.001). MUCP during PFM contractions was found to be inversely associated to age (r = -0.28, p = 0.007). CONCLUSION: The urethral pressure profile is the same for all types of urinary stress incontinence, whether simple or complicated. When comparing UCP at rest to MUCP during PFMC, there is at least a functional 25% increase.


Assuntos
Incontinência Urinária por Estresse , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Uretra , Procedimentos Cirúrgicos Urológicos , Pelve , Músculos Abdominais , Urodinâmica
6.
BMC Infect Dis ; 22(1): 917, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36482326

RESUMO

BACKGROUND: Despite the development and application of vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) around the world, the scientific community is still trying to find some therapies to avoid or ameliorate the fatal evolution of the Coronavirus disease 2019 (COVID-19). Since the publication of the potential use of ivermectin as a treatment against the disease, a pleiad of information about it has been published. However, the evidence is not strong or weak enough to conclude its usefulness in the clinical evolution of patients infected with SARS-CoV-2. We evaluate the efficacy and safety of ivermectin in the treatment of Mexican patients with asymptomatic and mild COVID-19 in a three-day administration in comparison to placebo. METHODS: A randomized, double-blind, placebo-controlled trial was carried out in 66 adults with asymptomatic and mild COVID-19. Patients were randomly assigned 1:1 ratio to ivermectin plus acetaminophen or placebo plus acetaminophen. The primary endpoint was the proportion of subjects without a disease progression to severity according to COVID-19 guidelines by the National Institutes of Health (NIH) since randomization to 14 days. RESULTS: None of the participants presented progression to a severe state in either group. Viral load was measured on Days 1, 5, and 14. No significant differences were observed in baseline or 14-day between groups (p = 0.720 and 0.362, respectively). However, on Day 5, a significant difference in viral load was observed between groups (p = 0.039). The frequency of symptoms was similar between groups, and no significant differences were observed. The most frequent symptom was cough. One severe adverse event associated with SARS-CoV-2 infection was observed in the ivermectin group. CONCLUSIONS: At standard doses, ivermectin is not effective to prevent progression to a severe state or reducing symptoms in adults with asymptomatic and mild COVID-19. Trial registration The study was registered with ClinicalTrial.gov (NCT04407507) on May 29, 2020.


Assuntos
COVID-19 , Ivermectina , Humanos , Progressão da Doença , Ivermectina/uso terapêutico , SARS-CoV-2 , Estados Unidos
7.
Viruses ; 14(8)2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-36016278

RESUMO

Natural hepatitis C virus (HCV) infection is restricted to humans, whereas other primates such as rhesus macaques are non-permissive for infection. To identify human and rhesus macaque genes that differ or share the ability to inhibit HCV replication, we conducted a medium-throughput screen of lentivirus-expressed host genes that disrupt replication of HCV subgenomic replicon RNA expressing secreted Gaussia luciferase. A combined total of >800 interferon-stimulated genes (ISGs) were screened. Our findings confirmed established anti-HCV ISGs, such as IRF1, PKR and DDX60. Novel species−specific inhibitors were also identified and independently validated. Using a cell-based system that recapitulates productive HCV infection, we identified that over-expression of the 'Rho Guanine Nucleotide Exchange Factor 3' gene (ARHGEF3) from both species inhibits full-length virus replication. Additionally, replication of two mosquito-borne flaviviruses, yellow fever virus (YFV) and Zika virus (ZIKV), were also reduced in cell lines over-expressing ARHGEF3 compared to controls. In conclusion, we ascribe novel antiviral activity to the cellular gene ARHGEF3 that inhibits replication of HCV and other important human viral pathogens belonging to the Flaviviridae, and which is conserved between humans and rhesus macaques.


Assuntos
Hepatite C , Infecção por Zika virus , Zika virus , Animais , Antivirais/farmacologia , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Humanos , Interferons/farmacologia , Macaca mulatta , Fatores de Troca de Nucleotídeo Guanina Rho , Replicação Viral , Infecção por Zika virus/tratamento farmacológico
8.
urol. colomb. (Bogotá. En línea) ; 31(2): 68-72, 2022. ilus
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1411985

RESUMO

Introducción y Objetivo El reflejo bulbocavernoso (RBCV) se ha observado ausente incluso en pacientes neurológicamente sanos. Los trastornos funcionales del piso pélvico deben incluir su evaluación. Nuestro objetivo primario fue evaluar la prevalencia de ausencia de RBCV en pacientes sanos. El objetivo secundario fue observar la afectación del RBCV en presencia de otras comorbilidades cómo enfermedad neurológica y diabetes mellitus tipo 2. Métodos Estudio descriptivo y retrospectivo, en el que se revisaron mil expedientes clínicos de pacientes sometidos a estudio urodinámico a quienes se les realizó exploración mecánica del RBCV como parte de una exploración rutinaria. Se realizó estadística descriptiva para las variables cuantitativas y cualitativas utilizando la prueba tde Student y la de chi cuadrado, respectivamente. Se consideraron estadísticamente significativos valores de p < 0,05. Resultados La muestra tenía una media de edad de 59,84 años (desviación estándar [DE]: ± 14,13 años), y contenía 36,19% de mujeres y 21,13% de hombres sin enfermedad neurológica y RBCV ausente. Se observó mayor ausencia de RBCV en pacientes con presencia de enfermedad neurológica en comparación con pacientes neurológicamente sanos: 21,6% versus 10,6%, respectivamente (p < 0,0001); además, se observó una ausencia importante de RBCV en presencia de diabetes mellitus en comparación con pacientes no diabéticos: 30.8% versus 18.8%, respectivamente (p < 0,0001). No se observaron diferencias al comparar grupos con respecto a disfunción vesical. Conclusión La ausencia de RBCV no es exclusiva de una enfermedad neurológica con repercusión de síntomas del tracto urinario inferior, y la proporción de pacientes neurológicamente sanos con ausencia de RBCV no es despreciable. No se encontró una diferencia significativa en los grupos con ausencia de RBCV con respecto a disfunción vesical.


Introduction and Objective Absence of the bulbocavernosus reflex (BCVR) has been observed even in neurologically-healthy subjects. Functional disorders of the pelvic floor should include its assessment. The primary objective of the present study was to evaluate the absence of BCVR in healthy subjects. The secondary objective was to evaluate the BCVR with regards to the presence of other comorbidities, such as neurogenic bladder and type-2 diabetes mellitus. Methods A descriptive and retrospective study in which we reviewed the clinical files of one thousand subjects who underwent a urodynamic study and were submitted to a mechanical exploration of the BCVR as part of a routine evaluation. Descriptive statistics were performed for the quantitative and qualitative variables using the Student t and the Chi-squared tests accordingly. Values of p < 0.05 was considered statistically significant. Results The sample had a mean age of 59.84 years (standard deviation [SD] ± 14.13 years), and it contained 36.19% of women and 21.13% of men without neurological disease and absent BCVR. A higher proportion of BCVR absence was observed in patients with neurological disease compared to their healthy counterparts: 21.6% and 10.6% respectively (p ≤ 0.0001); furthermore, an important absence of the BCVR was observed in patients with type-2 diabetes mellitus compared to non-diabetic patients: 30.8% and 18.8% respectively (p ≤ 0.0001). No statistically significant differences were observed in the group comparison regarding bladder dysfunction. Conclusion The absence of the RBCV is not exclusive to a neurological disease with repercussions in terms of lower urinary tract symptoms, and the proportion of neurologically healthy subjects with absence of the BCVR is not negligible. No significant difference was found in groups with absence of the BCVR with regards to bladder dysfunction


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Bexiga Urinaria Neurogênica , Reflexo Anormal , Diafragma da Pelve , Sintomas do Trato Urinário Inferior , Urodinâmica , Bexiga Urinária , Diclorodifenildicloroetano , Diabetes Mellitus
9.
Rev. Fac. Odontol. (Córdoba) ; 31(2): 3-6, ago. 2021.
Artigo em Espanhol | UNISALUD | ID: biblio-1359567

RESUMO

En los últimos años, las células madres mesenquimales (CMM) se han convertido en la piedra angular de la ingeniería tisular y medicina regenerativa. Las CMM se pueden obtener fácilmente de los tejidos adultos, es en este ámbito que la obtención y utilización de las CMM orales, se han convertido en una buena fuente de experimentación. No es desconocido que las CMM tienen gran poder regenerativo, alta capacidad proliferativa, de diferenciación y alto potencial osteogénico. Sin embargo, pueden ser afectados por múltiples factores externos. El objetivo de este artículo es describir el efecto del tabaco sobre las CMM orales. El cigarrillo y sus componentes son un factor de riesgo para varias enfermedades a nivel de cavidad oral, tienen muchos efectos adversos en la biología celular de la boca, por eso, no se hace extraño pensar en la afectación que estos componentes pueden teneren las CMM de origen oral. Los últimos estudios realizados demuestran que la nicotina y el humo condensado del cigarrillo tiene efectos biológicos negativos sobre las CMM, en particular de las orales. A pesar de la literatura existente, no está del todo claro cuáles son los mecanismos involucrados en los efectos negativos del tabaco sobre las CMM orales y cómo podrían ser revertidos


Assuntos
Humanos , Masculino , Feminino , Adulto , Células-Tronco , Nicotiana , Nicotina , Boca
10.
J Virol ; 95(1)2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33028720

RESUMO

Zika virus (ZIKV) envelope (E) protein is the major target of neutralizing antibodies in infected hosts and thus represents a candidate of interest for vaccine design. However, a major concern in the development of vaccines against ZIKV and the related dengue virus is the induction of cross-reactive poorly neutralizing antibodies that can cause antibody-dependent enhancement (ADE) of infection. This risk necessitates particular care in vaccine design. Specifically, the engineered immunogens should have their cross-reactive epitopes masked, and they should be optimized for eliciting virus-specific strongly neutralizing antibodies upon vaccination. Here, we developed ZIKV subunit- and virus-like particle (VLP)-based vaccines displaying E in its wild-type form or E locked in a covalently linked dimeric (cvD) conformation to enhance the exposure of E dimers to the immune system. Compared with their wild-type derivatives, cvD immunogens elicited antibodies with a higher capacity to neutralize virus infection in cultured cells. More importantly, these immunogens protected animals from lethal challenge with both the African and Asian lineages of ZIKV, impairing virus dissemination to brain and sexual organs. Moreover, the locked conformation of E reduced the exposure of epitopes recognized by cross-reactive antibodies and therefore showed a lower potential to induce ADE in vitro Our data demonstrated a higher efficacy of the VLPs in comparison with that of the soluble dimer and support VLP-cvD as a promising ZIKV vaccine.IMPORTANCE Infection with Zika virus (ZIKV) leads to the production by the host of antibodies that target the viral surface envelope (E) protein. A subset of these antibodies can inhibit virus infection, thus making E a suitable candidate for the development of vaccine against the virus. However, the anti-ZIKV E antibodies can cross-react with the E protein of the related dengue virus on account of the high level of similarity exhibited by the two viral proteins. Such a scenario may lead to severe dengue disease. Therefore, the design of a ZIKV vaccine requires particular care. Here, we tested two candidate vaccines containing a recombinant form of the ZIKV E protein that is forced in a covalently stable dimeric conformation (cvD). They were generated with an explicit aim to reduce the exposure of the cross-reactive epitopes. One vaccine is composed of a soluble form of the E protein (sE-cvD), the other is a more complex virus-like particle (VLP-cvD). We used the two candidate vaccines to immunize mice and later infected them with ZIKV. The animals produced a high level of inhibitory antibodies and were protected from the infection. The VLP-cvD was the most effective, and we believe it represents a promising ZIKV vaccine candidate.


Assuntos
Vacinas de Partículas Semelhantes a Vírus/imunologia , Proteínas do Envelope Viral/imunologia , Vacinas Virais/imunologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Facilitadores , Proteção Cruzada , Camundongos , Conformação Proteica , Multimerização Proteica , Vacinação , Proteínas do Envelope Viral/química , Zika virus/classificação
11.
Antiviral Res ; 183: 104939, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32980446

RESUMO

Yellow fever virus (YFV), a member of the Flaviviridae family, is an arthropod-borne virus that can cause severe disease in humans with a lethality rate of up to 60%. Since 2017, increases in YFV activity in areas of South America and Africa have been described. Although a vaccine is available, named strain 17D (Theiler and Smith, 1937), it is contraindicated for use in the elderly, expectant mothers, immunocompromised people, among others. To this day there is no antiviral treatment against YFV to reduce the severity of viral infection. Here, we used a circular polymerase extension reaction (CPER)-based reverse genetics approach to generate a full-length reporter virus (YFVhb) by introducing a small HiBit tag in the NS1 protein. The reporter virus replicates at a similar rate to the parental YFV in HuH-7 cells. Using YFVhb, we designed a high throughput antiviral screening luciferase-based assay to identify inhibitors that target any step of the viral replication cycle. We validated our assay by using a range of inhibitors including drugs, immune sera and neutralizing single chain variable fragments (scFv). In light of the recent upsurge in YFV and a potential spread of the virus, this assay is a further tool in the development of antiviral therapy against YFV.


Assuntos
Antivirais/farmacologia , Ensaios de Triagem em Larga Escala/métodos , Genética Reversa/métodos , Vírus da Febre Amarela/efeitos dos fármacos , Vírus da Febre Amarela/genética , Animais , Linhagem Celular , Descoberta de Drogas/métodos , Genes Reporter , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Replicação Viral/efeitos dos fármacos , Vírus da Febre Amarela/isolamento & purificação , Vírus da Febre Amarela/fisiologia
12.
Rev. sanid. mil ; 72(5/6): 339-343, sep.-dic. 2018. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1020884

RESUMO

Resumen Introducción La coriorretinopatía esclopetaria es una rara entidad resultante de un trauma por proyectil de alta velocidad que haya pasado adyacente o a través de la órbita, sin penetrar el globo ocular. Provoca daño coriorretiniano de espesor completo y pérdida visual. Objetivo Presentar un caso clínico de esta rara entidad, tratada de manera poco habitual, dados los hallazgos clínicos iniciales y con buen resultado final. Reporte de un caso Masculino de 42 años de edad, que refirió una fuerte detonación de arma de fuego cerca del globo ocular. Presentó baja visual los días posteriores y se diagnosticó hemovítreo; se realizó un ultrasonido ocular, el cual reportó desgarro retiniano, por lo que se realizó vitrectomía pars plana. Al final del seguimiento, se encontró con capacidad visual de cuenta dedos a 30 cm. Se realizaron estudios complementarios para documentar los hallazgos clínicos, presentando fractura coroidea con involucro macular. Se describe su seguimiento por cuatro semanas; se mantiene con estabilidad visual, sin complicaciones posteriores. Conclusiones Presentamos el caso de una coriorretinopatía esclopetaria, la cual está escasamente reportada. Hasta el momento, es el primer caso tratado con vitrectomía temprana sin complicaciones posteriores y estabilidad visual posterior.


Abstract Introduction Chorioretinitis sclopetaria is a rare entity resulting from trauma by a high-velocity projectile that passed adjacent or through the orbit without penetrating the eyeball. It causes full-thickness chorioretinal damage and visual loss. Objective To present a clinical case of the entity treated in an unusual way, with a good result. Case report 42 year-old male who mentioned a strong firearm detonation near the eyeball. Days later, he presented with visual loss, and hemovitreous was diagnosed. An ocular ultrasound was done, which reported retinal tear, so a pars plana vitrectomy was performed. At the end of the follow up, there was a visual ability to count fingers at 30 cm. Complementary studies were carried out to document the clinical findings, showing a choroidal fracture with macular involvement. Follow-up was carried up to four weeks after the intervention, without complications and with visual stability. Conclusions We present a case of chorioretinitis sclopetaria, which is scarcely reported; so far, this is the first case treated with early vitrectomy without later complications.

13.
Nat Commun ; 9(1): 2441, 2018 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-29934593

RESUMO

Zika virus (ZIKV) emerged on a global scale and no licensed vaccine ensures long-lasting anti-ZIKV immunity. Here we report the design and comparative evaluation of four replication-deficient chimpanzee adenoviral (ChAdOx1) ZIKV vaccine candidates comprising the addition or deletion of precursor membrane (prM) and envelope, with or without its transmembrane domain (TM). A single, non-adjuvanted vaccination of ChAdOx1 ZIKV vaccines elicits suitable levels of protective responses in mice challenged with ZIKV. ChAdOx1 prME ∆TM encoding prM and envelope without TM provides 100% protection, as well as long-lasting anti-envelope immune responses and no evidence of in vitro antibody-dependent enhancement to dengue virus. Deletion of prM and addition of TM reduces protective efficacy and yields lower anti-envelope responses. Our finding that immunity against ZIKV can be enhanced by modulating antigen membrane anchoring highlights important parameters in the design of viral vectored ZIKV vaccines to support further clinical assessments.


Assuntos
Antígenos Virais/genética , Desenho de Fármacos , Vacinas Virais/imunologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Adenoviridae/genética , Animais , Anticorpos Facilitadores/imunologia , Antígenos Virais/imunologia , Vírus da Dengue/imunologia , Modelos Animais de Doenças , Feminino , Vetores Genéticos/genética , Humanos , Imunogenicidade da Vacina , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Pan troglodytes/virologia , Domínios Proteicos/genética , Domínios Proteicos/imunologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética , Zika virus/genética , Infecção por Zika virus/imunologia , Infecção por Zika virus/virologia
14.
J Funct Biomater ; 8(3)2017 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-28753925

RESUMO

Periodontitis is an infectious and inflammatory disease associated with significant loss of alveolar crest and soft tissue attached to the teeth. Chitosan and hydroxyapatite are biomaterials used for bone tissue repair because of their biodegradability and biocompatibility in nature. The present study evaluated the effects of chitosan (CH) in combination with hydroxyapatite (HAP) to promote alveolar bone growth. A chitosan implant mixed with hydroxyapatite was implanted into the affected area of 9 patients suffering chronic periodontitis. Patients were evaluated through X-ray images and a millimetric slide over a one year period. The application of CH/HAP produced an average alveolar bone growth of 5.77 mm (±1.87 mm). At the onset of the study, the dental pocket exhibited a depth level (DPDL) of 8.66 mm and decreased to 3.55 mm one year after the implant. Tooth mobility grade was 2.44 mm at the onset and 0.8 mm at the end of the study with a significant difference of p < 0.001. Moreover, the bone density in the affected areas was similar to the density of the bone adjacent to it. This result was confirmed with the software implant viewer from Anne Solutions Company. In conclusion, the CH/HAP implant promoted alveolar bone growth in periodontitis patients.

15.
Org Biomol Chem ; 8(21): 4940-8, 2010 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-20820651

RESUMO

A facile and mild macrolactonization reaction of ω-hydroxy acids was developed based on the transesterification of benzotriazole esters. Treatment of ω-hydroxy acids with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and 1-hydroxy benzotriazole (HOBT) in chloroform provided macrolactones in excellent yields. The reactions were performed under basic, neutral and acidic conditions using N,N-dimethylaminopyridine (DMAP), tetrabutylammonium tetrafluoroborate (TBABF(4)) and BF(3)·Et(2)O, respectively. A calcined hydrotalcite was also used instead of DMAP. Finally, to test the scope of the protocol in the synthesis of biologically relevant macrolactones, the total synthesis of Sansalvamide A was carried out.


Assuntos
Depsipeptídeos/síntese química , Hidroxiácidos/química , Triazóis/química , Depsipeptídeos/química , Ésteres/síntese química , Ésteres/química , Hidroxiácidos/síntese química , Triazóis/síntese química
16.
Rev Med Inst Mex Seguro Soc ; 47(4): 405-12, 2009.
Artigo em Espanhol | MEDLINE | ID: mdl-20553646

RESUMO

OBJECTIVE: To value the psychiatric clinical aptitude (CA) in physical medicine and rehabilitation residents (PMR). METHODS: An instrument of evaluation of the psychiatric clinical aptitude was built, with five summarized real clinical cases, with 120 items to respond, 60 with true answer and 60 with false. The instrument was validated by experts, three psychiatrists and two specialists in physical medicine and rehabilitation that coincided completely in 44 % of the answers and in 56 % four of the five experts. It was applied to all medical residents of this specialty (n = 16), the internal consistency of the instrument was measured by the test of Kuder-Richardson (formula 20) showing a coefficient of 0.85, the random response was calculated by the Pérez Padilla-Viniegra test, being of 20 (17 %). Comparisons among the groups with U of Mann-Whitney and Kruskal-Wallis were made. RESULTS: Degrade of CA in the whole sample was low and there were differences statistically significant in favor of the third year residents. CONCLUSIONS: The educational strategies in the psychiatry area do not enhance the development of the CA in this specialty.


Assuntos
Competência Clínica , Internato e Residência , Medicina Física e Reabilitação/educação , Reabilitação/educação , Inquéritos e Questionários
17.
In. Instituto Superior de Ciencias Médicas. Facultad de Medicina No. 1. Infosalud 2006: II Congreso de Informática de Salud en Santiago de Cuba. Santiago de Cuba, CDS Ediciones Digitales- CDIMED, 6-8 dic. 2006. , CD-ROM.
Monografia em Espanhol | CUMED | ID: cum-46223

RESUMO

Se presenta un compendio de los principales términos que se emplean en el proceso de enseñanze–aprendizaje de la Informática Médica II para la carrera de Medicina. Elaborado en HTML con un diseño de navegación amigable, GlosIMed ofrece facilidades al estudiante para acceder a los términos por temas y por orden alfabético. Este software constituye una herramienta de consulta en manos del estudiante que lo ayudará a consolidar los conocimientos teóricos fundamentales asociados a la Metodología de la Investigación y la Bioestadística correspondientes al programa de la asignatura Informática Médica II en la carrera de Medicina(AU)


Assuntos
Humanos , Software , Dicionários como Assunto , Educação Médica/métodos , Informática Médica/métodos
18.
Ginecol. obstet. Méx ; 54(6): 148-51, jun. 1986. tab, ilus
Artigo em Espanhol | LILACS | ID: lil-77413

RESUMO

Se analizan los resultados de esterilización portparto de 147 pacientes atendidas en el Hospital Universitario "Dr J. E. González" en el periodo comprendido entre febrero y agosto de 1984. Se analizan los siguientes factores: edad, escolaridad, estado civil, lugar de procedencia y de residencia; anticoncepción previa, paridad, tipo de parto y anestesia durante el mismo; tiempo previo de rupturas de membranas y control prenatal; antecedentes de cirugía previa, indicación del procedimiento quirúrgico, técnica del mismo y complicaciones. El tipo de anestesia durante la salpingoclasia y sus complicaciones, así como el intervalo entre parto y salpingoclasia y entre ésta y el alta


Assuntos
Adulto , Humanos , Feminino , Esterilização Tubária/métodos , Internato e Residência , Obstetrícia/educação , Paridade
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