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1.
Transfusion ; 64(3): 483-492, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38263774

RESUMO

BACKGROUND: Patients with hematologic malignancies (HM) often develop transfusion dependence. The patient and caregiver burdens associated with the need for frequent transfusions are high. Home blood transfusions has the potential to reduce these burdens, but is not widely practiced in the United States. We designed a qualitative study to evaluate the patient and caregiver perceptions of the potential for a home blood transfusion program. STUDY DESIGN AND METHODS: Eligible patients included Adult (≥18 years) patients who were English speaking and met the definition for transfusion dependence within 3 months of study enrollment. We identified and interviewed eligible participants (patients and caregivers), using a semi-structured interview guide to elicit patient perceptions of the acceptability, barriers, and benefits related to home blood product transfusions. Interviews were audio recorded and transcribed. Results were imported into NVivo 12 (version 12; QSR International, Burlington, VT) for coding and analysis. RESULTS: We recruited participants until we reached thematic saturation, which occurred at 29 participants (20 patients, 9 caregivers). Among the 20 patient participants, nine had MDS (45%) and 11 had acute leukemia (55%). Most of the patients (60%) reported getting one transfusion per week. Four themes emerged when the participants discussed their perception regarding the potential of a home blood transfusion program: (1) current in-person experience, (2) caregiver burden, (3) perceptions of home blood transfusions, and (4) interest in participating in a home blood transfusion program. CONCLUSION: The concept of home blood transfusions was well received and further research to study its implementation is warranted.


Assuntos
Neoplasias Hematológicas , Leucemia , Adulto , Humanos , Doença Aguda , Transfusão de Sangue/métodos , Cuidadores , Neoplasias Hematológicas/terapia , Pesquisa Qualitativa , Entrevistas como Assunto , Conhecimentos, Atitudes e Prática em Saúde
2.
Biosci Rep ; 42(7)2022 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-35674210

RESUMO

HDMX and its homologue HDM2 are two essential proteins for the cell; after genotoxic stress, both are phosphorylated near to their RING domain, specifically at serine 403 and 395, respectively. Once phosphorylated, both can bind the p53 mRNA and enhance its translation; however, both recognize p53 protein and provoke its degradation under normal conditions. HDM2 has been well-recognized as an E3 ubiquitin ligase, whereas it has been reported that even with the high similarity between the RING domains of the two homologs, HDMX does not have the E3 ligase activity. Despite this, HDMX is needed for the proper p53 poly-ubiquitination. Phosphorylation at serine 395 changes the conformation of HDM2, helping to explain the switch in its activity, but no information on HDMX has been published. Here, we study the conformation of HDMX and its phospho-mimetic mutant S403D, investigate its E3 ligase activity and dissect its binding with p53. We show that phospho-mutation does not change the conformation of the protein, but HDMX is indeed an E3 ubiquitin ligase in vitro; however, in vivo, no activity was found. We speculated that HDMX is regulated by induced fit, being able to switch activity accordingly to the specific partner as p53 protein, p53 mRNA or HDM2. Our results aim to contribute to the elucidation of the contribution of the HDMX to p53 regulation.


Assuntos
Proteínas Proto-Oncogênicas c-mdm2 , Proteína Supressora de Tumor p53 , Proteínas de Ciclo Celular/metabolismo , Proteínas Nucleares/genética , Ligação Proteica , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , RNA Mensageiro/metabolismo , Serina/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
3.
Int J Mol Sci ; 23(11)2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35682723

RESUMO

Angiotensin II (Ang II) is a critical regulator of insulin signaling in the cardiovascular system and metabolic tissues. However, in adipose cells, the regulatory role of Ang II on insulin actions remains to be elucidated. The effect of Ang II on insulin-induced insulin receptor (IR) phosphorylation, Akt activation, and glucose uptake was examined in 3T3-L1 adipocytes. In these cells, Ang II specifically inhibited insulin-stimulated IR and insulin receptor substrate-1 (IRS-1) tyrosine-phosphorylation, Akt activation, and glucose uptake in a time-dependent manner. These inhibitory actions were associated with increased phosphorylation of the IR at serine residues. Interestingly, Ang II-induced serine-phosphorylation of IRS was not detected, suggesting that Ang II-induced desensitization begins from IR regulation itself. PKC inhibition by BIM I restored the inhibitory effect of Ang II on insulin actions. We also found that Ang II promoted activation of several PKC isoforms, including PKCα/ßI/ßII/δ, and its association with the IR, particularly PKCßII, showed the highest interaction. Finally, we also found a similar regulatory effect of Ang II in isolated adipocytes, where insulin-induced Akt phosphorylation was inhibited by Ang II, an effect that was prevented by PKC inhibitors. These results suggest that Ang II may lead to insulin resistance through PKC activation in adipocytes.


Assuntos
Angiotensina II , Receptor de Insulina , Adipócitos/metabolismo , Angiotensina II/metabolismo , Angiotensina II/farmacologia , Glucose/metabolismo , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor de Insulina/metabolismo , Serina/metabolismo
4.
Rev. mex. ing. bioméd ; 43(1): 1214, Jan.-Apr. 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1389191

RESUMO

ABSTRACT In a sprint start, the athlete takes up a position with their hands just behind a line, arms vertical, feet generally placed about a shoe length apart, and the hips rising above the line of the head. Mistakes in this position influence the execution of the low-sprint start, and can drastically influence the initial running speed and acceleration achieved by the athlete. Common mistakes occur due to the misconception that athletes must also lean forward, bringing the shoulders ahead of their hands and putting pressure on them. A standard approach to identify sprint start mistakes is to use a stick or weighted string to drop down from the shoulders. The effective implementation of this approach depends on the coach's experience and remains a significant challenge. In this study, a three-dimensional motion capture system with the Vicon® Plug-in-Gait model was used to characterize the kinematic parameters that influence the execution of low-sprint start in six high-performance athletes. The main kinematic parameters are reaction time, stride length, and stride time. The obtained results demonstrate the potential utility of a three-dimensional motion capture system to assess the kinematic parameters of low-sprint start in high-performance athletes.

5.
Front Cell Dev Biol ; 9: 695723, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34957087

RESUMO

The p53 roles have been largely described; among them, cell proliferation and apoptosis control are some of the best studied and understood. Interestingly, the mutations on the six hotspot sites within the region that encodes the DNA-binding domain of p53 give rise to other very different variants. The particular behavior of these variants led to consider p53 mutants as separate oncogene entities; that is, they do not retain wild type functions but acquire new ones, namely Gain-of-function p53 mutants. Furthermore, recent studies have revealed how p53 mutants regulate gene expression and exert oncogenic effects by unbalancing specific microRNAs (miRNAs) levels that provoke epithelial-mesenchymal transition, chemoresistance, and cell survival, among others. In this review, we discuss recent evidence of the crosstalk between miRNAs and mutants of p53, as well as the consequent cellular processes dysregulated.

6.
Rev. cuba. enferm ; 37(4)dic. 2021.
Artigo em Espanhol | LILACS, BDENF - Enfermagem, CUMED | ID: biblio-1408304

RESUMO

Introducción: La violencia laboral entre el personal de enfermería en hospitales constituye un problema de salud pública, afectando de manera indirecta la calidad del cuidado. Objetivo: Determinar la relación de violencia laboral entre el personal de enfermería y la calidad del cuidado en hospitales públicos. Métodos: Estudio descriptivo correlacional y transversal, realizado en dos hospitales públicos de México durante agosto y septiembre de 2017. La muestra fue de 161 enfermeros y 117 pacientes. Se utilizaron el Barómetro Cisneros y el Caring Assessment Instrument para medir las variables de interés; se obtuvieron medias, desviación estándar y frecuencias para datos descriptivos, el coeficiente de correlación de Spearman y coeficientes de Contingencia y Chi cuadrada para determinar la relación. Resultados: Predominó el sexo femenino (85,70 por ciento), con una media de edad de 35,67 años, 45,90 por ciento), trabajaban en el turno nocturno, 79,40 por ciento), de los participantes refirió no haber experimentado violencia laboral, la evaluación inequitativa fue la estrategia de violencia laboral más frecuente. Respecto a los pacientes, más de la mitad reportó calidad en el cuidado. El Coeficiente de Correlación de Spearman no mostró significancia estadística (p > 0,05). Conclusión: El personal de enfermería no se encuentra familiarizado con la conceptualización de violencia laboral, por lo que es probable que la mayoría la haya experimentado y por temor a represalias, no la reportara(AU)


Introduction: Workplace violence among nursing personnel in hospitals constitutes a public health problem, indirectly affecting the quality of care. Objective: To determine the relationship of workplace violence among nursing staff and the quality of care in public hospitals. Methods: á Descriptive, correlational and cross-sectional study was carried out in two public hospitals in Mexico from August to September 2017. The sample consisted of 161 nurses and 117 patients. We used Cisneros Barometer and the Caring Assessment Instrument to measure the variables of interest; means, standard deviation and frequencies were obtained for descriptive data, Spearman's correlation coefficient and Contingency coefficients and Chi squared to determine the relationship. Results: Female predominated (85.70 percent)), with a mean age of 35.67 years, 45.90 percent worked the night shift, 79.40 percent),),of the participants referred not having experienced workplace violence, inequitable evaluation was the most frequent workplace violence strategy. Regarding patients, more than 50 percent), reported quality of care. The Spearman Correlation Coefficient did not show statistical significance (p> 0.05). Conclusion: Nursing staff are not familiar with the conceptualization of workplace violence, so it is likely that the majority have experienced it, but did not report it, for fear of reprisals(AU)


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Qualidade da Assistência à Saúde/normas , Gestão da Qualidade Total/métodos , Violência no Trabalho , Cuidados de Enfermagem/métodos , Epidemiologia Descritiva , Estudos Transversais , Empatia , Relatório de Pesquisa , Hospitais Públicos
7.
Enferm Clin (Engl Ed) ; 31(3): 148-155, 2021.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33589347

RESUMO

AIM: To determine the relationship between social support in social networks and risk factors of overweight and obesity including healthy lifestyles and perceived barriers in adolescents. METHOD: Descriptive and cross-sectional study with adolescents from a public high school in Nuevo León, Mexico. Anthropometric measurements were determined to obtain body mass index, behavioural measurements for perceived barriers to healthy eating and physical activity, as well as healthy lifestyles. RESULTS: A total of 188 adolescents participated, male sex predominated at 55.9%, mean age was 16.1 years. From them, 52.1% were overweight, less than half of the adolescents reported having friends on social networks (37.8%); 52% of overweight participants need changes in their diet and the majority reported low physical activity (82.7%). There is a correlation between social support in social networks and perceived barriers to physical activity in overweight adolescents (r2 0.144; p < 0.05). CONCLUSIONS: Most of the adolescents do not have an adequate diet or perform recommended physical activity, one of the main causes is lack of motivation as a perceived barrier. Social networks represent a tool for nursing staff to promote health and develop interventions aimed at preventing disease in a global context in digital transition.


Assuntos
Promoção da Saúde , Sobrepeso , Adolescente , Estudos Transversais , Humanos , Masculino , México/epidemiologia , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Fatores de Risco , Rede Social , Apoio Social
8.
Artigo em Espanhol | LILACS-Express | LILACS, BDENF - Enfermagem | ID: biblio-1384360

RESUMO

RESUMEN Objetivo: Describir el cuidado al personal de enfermería desde la perspectiva del supervisor en el contexto hospitalario. Material y Método: Estudio exploratorio con aproximación cualitativa en el que se empleó el diseño sistemático de la Teoría Fundamentada; la población se conformó por supervisores de enfermería en dos hospitales públicos de segundo nivel en la ciudad de Chihuahua, México; la recolección de datos se llevó a cabo durante agosto y septiembre de 2017 a través de un muestreo teórico, respetando los aspectos éticos de investigación. Resultados: Con diez participantes, hasta llegar a la saturación de datos, predominó el sexo femenino (7), en su mayoría casados (6) y con estudios de posgrado (6). Surgieron tres categorías: 1) Cuidado desde la perspectiva del supervisor de enfermería; 2) Interacción entre el supervisor de enfermería y sus compañeros de trabajo y 3) Desarrollo profesional como parte del cuidado al supervisor de enfermería. Conclusiones: La mayoría conceptualiza el cuidado como una actividad dirigida a otros pero no a sí mismos. La comunicación efectiva y estilo de liderazgo desempeñan una función importante para la interacción del supervisor de enfermería con el personal de enfermería operativo y sus directivos, pero estos atributos no se perciben de manera adecuada por ellos mismos.


ABSTRACT Objective: To describe nursing staff care from the supervisor's perspective in the hospital setting. Material and Methods: Exploratory study with a qualitative approach using the systematic design of the Grounded Theory. The population consisted of nursing supervisors in two secondary care public hospitals in the city of Chihuahua, Mexico; data collection was carried out during August and September 2017 through theoretical sampling, respecting ethical aspects of research. Results: With ten participants until reaching data saturation, female sex predominated (7), mostly married (6) and with postgraduate studies (6). Three categories emerged from this study: 1) Care from the nursing supervisor's perspective; 2) Interaction between the nursing supervisor and their coworkers and 3) Professional development as part of the nursing supervisor care. Conclusions: Most supervisors conceptualize care as an activity aimed at others, but not at themselves. Effective communication and leadership style play an important role in the interaction between nurse supervisors with operational nursing staff and their managers, but these attributes are not properly perceived by themselves.


RESUMO Objetivo: Descrever os cuidados do pessoal de enfermagem da perspectiva do supervisor no contexto hospitalar. Material e Método: Estudo exploratório com abordagem qualitativa usando o desenho sistemático da teoria fundamentada ou Grounded Theory. A população consistiu de gerentes de enfermagem em dois hospitais públicos de cuidados secundários na cidade de Chihuahua, México; a coleta de dados foi realizada nos meses de agosto e setembro de 2017 por amostragem teórica, respeitando os aspectos éticos da pesquisa. Resultados: com dez participantes até atingir a saturação de dados, predominando o sexo feminino (7), a maioria casada (6) e com estudos de pós-graduação (6). Três categorias emergiram deste estudo: 1) percepção do gerente de enfermagem sobre o cuidado; 2) interação entre o gerente de enfermagem e colegas de trabalho e 3) desenvolvimento profissional como parte do atendimento do gerente de enfermagem. Conclusões: A maioria dos enfermeiros gerentes conceitua o cuidado como uma atividade voltada para os outros, mas não para si mesmos. O estilo eficaz de comunicação e liderança desempenha um papel importante na interação do gerente de enfermagem com a equipe de enfermagem e seu diretor executivo, mas esses atributos não são percebidos adequadamente por eles mesmos.

9.
Rev Lat Am Enfermagem ; 27: e3195, 2019 Oct 14.
Artigo em Português, Inglês, Espanhol | MEDLINE | ID: mdl-31618388

RESUMO

OBJECTIVE: to identify the association between environmental risk factors and awareness of colorectal cancer in people at familial risk. METHOD: cross-sectional correlational study, with a sample consisted of people who met at least one of the Revised Bethesda criteria, and 80 participants were included in this study. A sociodemographic data record, the AUDIT Test for alcohol use, the Fagerström Test for tobacco smoking, the Estimation and Frequency of Food Intake scale, and the Cancer Awareness Measure questionnaire to assess the colorectal cancer awareness were used. Body mass index was calculated, and descriptive statistics and the Pearson's Correlation Coefficient were used to estimate the association. RESULTS: female sex predominated, with an average age of 37.8 years, almost half of the participants were overweight, 45% showed symptoms of alcohol dependence, half of the sample showed an association between hereditary factors and the development of colorectal cancer, and less than half of them were aware of cancer prevention programs. CONCLUSION: there is little information on the main environmental risk factors, signs and symptoms of colorectal cancer, and no significant association was found between these and colorectal cancer awareness.


Assuntos
Neoplasias Colorretais/etiologia , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Transtornos Induzidos por Álcool/complicações , Conscientização , Índice de Massa Corporal , Estudos Transversais , Dieta/efeitos adversos , Feminino , Predisposição Genética para Doença/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso , Medição de Risco , Fatores de Risco , Inquéritos e Questionários , Fumar Tabaco/efeitos adversos , Adulto Jovem
10.
Rev. latinoam. enferm. (Online) ; 27: e3195, 2019. tab
Artigo em Português | LILACS, BDENF - Enfermagem | ID: biblio-1043095

RESUMO

Objetivo identificar a associação entre os fatores de risco ambientais e a conscientização sobre o câncer colorretal em pessoas com risco familiar. Método estudo correlacional de corte transversal, cuja amostra foi constituída por pessoas que cumpriam pelo menos um dos critérios de Bethesda Revisados, sendo 80 participantes incluídos no estudo. Foram utilizados uma ficha com dados sociodemográficos, o Teste AUDIT para o consumo de álcool, o Teste de Fagerström para o tabagismo, a escala de Estimativa e Consumo de Alimentos, e o questionário Cancer Awareness Measure para avaliar a conscientização sobre o câncer colorretal. O índice de massa corporal foi calculado, e estatísticas descritivas e o Coeficiente de Correlação de Pearson foram usados para estimar a associação. Resultados o sexo feminino foi o mais prevalente, com média de idade de 37,8 anos, quase metade dos participantes apresentava sobrepeso, 45% apresentavam sintomas de dependência de álcool, metade da amostra teve o fator hereditário relacionado com o desenvolvimento de câncer colorretal, e menos da metade conhecia programas preventivos deste câncer. Conclusão há pouca informação sobre os principais fatores de risco ambientais, sinais e sintomas do câncer colorretal, e nenhuma associação significativa foi encontrada entre eles e conscientização sobre o câncer colorretal.


Objective to identify the association between environmental risk factors and awareness of colorectal cancer in people at familial risk. Method cross-sectional correlational study, with a sample consisted of people who met at least one of the Revised Bethesda criteria, and 80 participants were included in this study. A sociodemographic data record, the AUDIT Test for alcohol use, the Fagerström Test for tobacco smoking, the Estimation and Frequency of Food Intake scale, and the Cancer Awareness Measure questionnaire to assess the colorectal cancer awareness were used. Body mass index was calculated, and descriptive statistics and the Pearson's Correlation Coefficient were used to estimate the association. Results female sex predominated, with an average age of 37.8 years, almost half of the participants were overweight, 45% showed symptoms of alcohol dependence, half of the sample showed an association between hereditary factors and the development of colorectal cancer, and less than half of them were aware of cancer prevention programs. Conclusion there is little information on the main environmental risk factors, signs and symptoms of colorectal cancer, and no significant association was found between these and colorectal cancer awareness.


Objetivo identificar la asociación entre factores de riesgo ambientales y la conciencia sobre el cáncer colorrectal en personas con riesgo familiar. Método estudio transversal correlacional; la muestra estuvo constituida por personas que cumplieran al menos uno de los criterios de Bethesda Revisados; se incluyeron 80 participantes en el estudio; se empleó una cédula de datos sociodemográficos, el Test AUDIT para el consumo de alcohol, Test de Fagerström para el consumo de tabaco, escala Estimación y Consumo de Alimento y el cuestionario Cancer Awareness Measure para la conciencia sobre el cáncer colorrectal, además se calculó el índice de masa corporal; se obtuvo estadística descriptiva y el Coeficiente de Correlación de Pearson para la asociación. Resultados predominó el sexo femenino, con una media de edad de 37,8 años; casi la mitad de los participantes presentó sobrepeso, un 45% mostró síntomas de dependencia al alcohol, la mitad de la muestra relaciona el factor hereditario con el desarrollo de cáncer colorrectal y menos de la mitad conoce programas preventivos sobre el mismo. Conclusión existe poca información sobre los principales factores de riesgo ambientales, signos y síntomas del cáncer colorrectal; no se encontró una asociación significativa entre estos y la conciencia sobre el cáncer colorrectal.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Conscientização , Neoplasias Colorretais/etiologia , Fumar , Índice de Massa Corporal , Conhecimentos, Atitudes e Prática em Saúde , Indicadores Básicos de Saúde , Predisposição Genética para Doença , Transtornos Induzidos por Álcool , Dieta , Sobrepeso
11.
Mol Clin Oncol ; 9(6): 592-596, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30546886

RESUMO

Angiosarcoma is a rare soft tissue neoplasm, which accounts for <1% of all soft tissue tumours. It has been previously reported that the incidence rate of angiosarcomas increases following radiotherapy. The present study reports two cases of intra-abdominal angiosarcoma associated with previous radiotherapy treatment. To the best of our knowledge, these associations have not been previously described in English literature. The patients aged 71 and 83 years were admitted to the center for abdominal pain and diarrhea. Each patient had previously had treatment with radiotherapy for prostate adenocarcinoma. During their hospitalization, biopsies were obtained and the diagnosis of angiosarcoma was reached. In each patient the tumors had irregular proliferating vascular channels, lined by atypical endothelial cells, which varied from elongated and spindle-shaped to large and plump. Immunocytochemistry revealed that the tumor cells were positive for the cytoplasmic endothelial markers cluster of differentiation (CD)31 and CD34. The recognition of these associations is important and their occurrence in this rare type of neoplasm should not mislead the pathologist and cause a misdiagnosis of the sarcoma.

12.
J Pestic Sci ; 43(1): 1-9, 2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30363124

RESUMO

Millions of cases of pesticide intoxication occur yearly and represent a public health problem. In addition, pesticide poisoning is the preferred suicidal method in rural areas. The use of enzymes for the treatment of intoxication due to organophosphorus pesticides was proposed decades ago. Several enzymes are able to transform organophosphorus compounds such as pesticides and nerve agents. Some specific enzymatic treatments have been proposed, including direct enzyme injection, liposome and erythrocytes carriers, PEGylated preparations and extracorporeal enzymatic treatments. Nevertheless, no enzymatic treatments are currently available. In this work, the use of enzymes for treating of organophosphorus pesticide intoxication is critically reviewed and the remaining challenges are discussed.

13.
J Biol Chem ; 293(12): 4304-4323, 2018 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-29386353

RESUMO

Candida albicans is an opportunistic fungus that is part of the normal microflora commonly found in the human digestive tract and the normal mucosa or skin of healthy individuals. However, in immunocompromised individuals, it becomes a serious health concern and a threat to their lives and is ranked as the leading fungal infection in humans worldwide. As existing treatments for this infection are non-specific or under threat of developing resistance, there is a dire necessity to find new targets for designing specific drugs to defeat this fungus. Some authors reported the presence of the transglutaminase activity in Candida and Saccharomyces, but its identity remains unknown. We report here the phenotypic effects produced by the inhibition of transglutaminase enzymatic activity with cystamine, including growth inhibition of yeast cells, induction of autophagy in response to damage caused by cystamine, alteration of the normal yeast division pattern, changes in cell wall, and inhibition of the yeast-to-mycelium transition. The latter phenomenon was also observed in the C. albicans ATCC 26555 strain. Growth inhibition by cystamine was also determined in other Candida strains, demonstrating the importance of transglutaminase in these species. Finally, we identified enolase 1 as the cell wall protein responsible for TGase activity. After studying the inhibition of enzymatic activities with anti-CaEno1 antibodies and through bioinformatics studies, we suggest that the enolase and transglutaminase catalytic sites are localized in different domains of the protein. The aforementioned data indicate that TGase/Eno1 is a putative target for designing new drugs to control C. albicans infection.


Assuntos
Candida albicans/enzimologia , Divisão Celular , Proteínas Fúngicas/metabolismo , Morfogênese , Osmose , Fosfopiruvato Hidratase/metabolismo , Transglutaminases/metabolismo , Sequência de Aminoácidos , Candida albicans/crescimento & desenvolvimento , Candida albicans/metabolismo , Parede Celular/metabolismo , Proteínas Fúngicas/genética , Humanos , Fosfopiruvato Hidratase/genética , Transglutaminases/genética
14.
Nat Microbiol ; 2(11): 1462-1470, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28970482

RESUMO

The recent Zika pandemic in the Americas is linked to congenital birth defects and Guillain-Barré syndrome. White blood cells (WBCs) play an important role in host immune responses early in arboviral infection. Infected WBCs can also function as 'Trojan horses' and carry viruses into immune-sheltered spaces, including the placenta, testes and brain. Therefore, defining which WBCs are permissive to Zika virus (ZIKV) is critical. Here, we analyse ZIKV infectivity of peripheral blood mononuclear cells (PBMCs) in vitro and from Nicaraguan Zika patients and show CD14+CD16+ monocytes are the main target of infection, with ZIKV replication detected in some dendritic cells. The frequency of CD14+ monocytes was significantly decreased, while the CD14+CD16+ monocyte population was significantly expanded during ZIKV infection compared to uninfected controls. Viral RNA was detected in PBMCs from all patients, but in serum from only a subset, suggesting PBMCs may be a reservoir for ZIKV. In Zika patients, the frequency of infected cells was lower but the percentage of infected CD14+CD16+ monocytes was significantly higher compared to dengue cases. The gene expression profile in monocytes isolated from ZIKV- and dengue virus-infected patients was comparable, except for significant differences in interferon-γ, CXCL12, XCL1, interleukin-6 and interleukin-10 levels. Thus, our study provides a detailed picture of the innate immune profile of ZIKV infection and highlights the important role of monocytes, and CD14+CD16+ monocytes in particular.


Assuntos
Receptores de Lipopolissacarídeos/imunologia , Monócitos/imunologia , Monócitos/virologia , Receptores de IgG/imunologia , Infecção por Zika virus/imunologia , Infecção por Zika virus/virologia , Zika virus/fisiologia , Adolescente , Quimiocina CXCL12/genética , Quimiocinas C/genética , Criança , Pré-Escolar , Células Dendríticas/imunologia , Células Dendríticas/virologia , Dengue/imunologia , Dengue/virologia , Feminino , Proteínas Ligadas por GPI/imunologia , Humanos , Imunidade Inata/genética , Interferon gama/genética , Interleucina-10/genética , Interleucina-6/genética , Masculino , Monócitos/metabolismo , Nicarágua , RNA Viral/sangue , Transcriptoma , Carga Viral , Replicação Viral , Zika virus/imunologia
15.
Int J Biol Macromol ; 105(Pt 1): 163-170, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28690168

RESUMO

Pesticide intoxication is a major public health concern, and unfortunately there is not an effective treatment for severe organophosphorus pesticide intoxication. In this work, a non-immunogenic enzymatic bioconjugate based on cytochrome P450 was assayed for organophosphorus pesticide transformation. Enzyme therapy is an alternative approach to inactivate pesticides in the bloodstream, transforming them into less toxic metabolites. A variant of cytochrome P450 (CYPBM3 F87A) from Bacillus megaterium was chemically modified with polyethylene glycol. The PEGylated enzyme showed enhanced pesticide transformation activity when compared with the unmodified protein. The transformation rates were higher than those obtained with the unmodified enzyme for all six pesticides transformed. The specific activity of PEGylated preparation for parathion and dichlorophen was up to 9-times higher than these obtained with the unmodified enzyme. In addition, the modified CYP (CYP-PEG) remained active at extremely high pHs, maintaining 90% of its maximal activity at pH 11, as opposed to the unmodified CYP that retained less than 20% of its maximal activity at that pH. In addition, the bioconjugate showed good catalytic activity in blood serum and innocuousness on immune cells. The potential use of PEGylated CYP as a detoxification strategy for pesticide poisoning is demonstrated and discussed.


Assuntos
Biocatálise , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/metabolismo , Praguicidas/metabolismo , Polietilenoglicóis/química , Animais , Bacillus megaterium/enzimologia , Biotransformação , Concentração de Íons de Hidrogênio , Cinética , Macrófagos/metabolismo , Camundongos , Modelos Moleculares , Oxirredução , Conformação Proteica , Células RAW 264.7 , Especificidade por Substrato , Temperatura
18.
San Salvador; s.n; 2017. 53 p. graf.
Tese em Espanhol | LILACS, BISSAL | ID: biblio-1222766

RESUMO

En el Hospital Nacional Rosales se realizan cirugías cardíacas de las cuales no se dispone de registros de datos ni estudios en el seguimiento post quirúrgico de estos pacientes. La importancia de este estudio radica en determinar la evolución y la calidad de vida de los pacientes que se someten al manejo quirúrgico. La evolución post quirúrgica favorable inicia desde que el paciente consulta sintomático y se le realiza caracterización, se establece el tipo de cardiopatía (congénita o valvulopatía), se determinan comorbilidades y predictores de riesgo como enfermedades crónicas degenerativas, arritmiacardíaca, edad, estado nutricional; esto con el objetivo de estabilizar al paciente para el acto quirúrgico y para su adecuada recuperación post quirúrgica. Se realizó un estudio de tipo descriptivo observacional, en el que se dio seguimiento a dos cohortes de pacientes intervenidos quirúrgicamente de su patología cardiaca: valvulares aórtico-mitrales y congénitos en adultos, de quienes se describió la indicación quirúrgica, su estado clínico preoperatorio, su transquirurgico y postoperatorio. En el periodo de enero 2011 a junio 2013. Un estudio de fuentes documentales


Assuntos
Cardiopatias Congênitas , Cirurgia Torácica , Doenças das Valvas Cardíacas , Medicina Interna
19.
Rev. panam. salud pública ; 41: e56, 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-961706

RESUMO

ABSTRACT Objective To develop and evaluate serological methods for chikungunya diagnosis and research in Nicaragua. Methods Two IgM ELISA capture systems (MAC-ELISA) for diagnosis of acute chikungunya virus (CHIKV) infections, and two Inhibition ELISA Methods (IEM) to measure total antibodies against CHIKV were developed using monoclonal antibodies (mAbs) and hyperimmune serum at the National Virology Laboratory of Nicaragua in 2014-2015. The sensitivity, specificity, predictive values, and agreement of the MAC-ELISAs were obtained by comparing the results of 198 samples (116 positive; 82 negative) with the Centers for Disease Control and Prevention's IgM ELISA (Atlanta, Georgia, United States; CDC-MAC-ELISA). For clinical evaluation of the four serological techniques, 260 paired acute and convalescent phase serum samples of suspected chikungunya cases were used. Results All four assays were standardized by determining the optimal concentrations of the different reagents. Processing times were substantially reduced compared to the CDC-MAC-ELISA. For the MAC-ELISA systems, a sensitivity of 96.6% and 97.4%, and a specificity of 98.8% and 91.5% were obtained using mAb and hyperimmune serum, respectively, compared with the CDC method. Clinical evaluation of the four serological techniques versus the CDC real-time RT-PCR assay resulted in a sensitivity of 95.7% and a specificity of 88.8%-95.9%. Conclusion Two MAC-ELISA and two IEM systems were standardized, demonstrating very good quality for chikungunya diagnosis and research demands. This will achieve more efficient epidemiological surveillance in Nicaragua, the first country in Central America to produce its own reagents for serological diagnosis of CHIKV. The methods evaluated here can be applied in other countries and will contribute to sustainable diagnostic systems to combat the disease.


RESUMEN Objetivo Elaborar y evaluar métodos serológicos para el diagnóstico y la investigación del chikungunya. Métodos Se elaboraron dos sistemas de ELISA de captura de IgM (MAC-ELISA por sus siglas en inglés) para el diagnóstico de la infección aguda por el virus de (CHIKV) y dos métodos de ELISA de inhibición (MEI) para determinar el valor cuantitativo de los anticuerpos totales contra el CHIKV, en el Laboratorio Nacional de Virología de Nicaragua en 2014-2015, para lo cual se utilizaron anticuerpos monoclonales (AcMo) y sueros hiperinmunes. Se determinó la sensibilidad, la especificidad y los valores predictivos, así como la concordancia de los MAC-ELISA, comparando los resultados de 198 muestras (116 positivas y 82 negativas) con el ELISA de los Centros para el Control y la Prevención de Enfermedades de los Estados Unidos (Atlanta; MAC-ELISA-CDC). Para la evaluación clínica de las cuatro técnicas serológicas, se emplearon 260 muestras de suero obtenidas en la fase aguda y en la fase de convalecencia de presuntos casos de chikungunya. Resultados Se estandarizaron los cuatro métodos analíticos determinando las concentraciones óptimas de los diferentes reactivos. La duración del procesamiento se redujo sustancialmente en comparación con el MAC-ELISA-CDC. Con los sistemas de MAC-ELISA, se obtuvo una sensibilidad del 96,6% y del 97,4% y una especificidad del 98,8% y del 91,5% al utilizar AcMo y suero hiperinmune, respectivamente, en comparación con el método de los CDC. La evaluación clínica de las cuatro técnicas serológicas, en comparación con la PCR en tiempo real de los CDC, arrojó una sensibilidad del 95,7% y una especificidad del 88,8%-95,9%. Conclusiones Se estandarizaron dos sistemas de ELISA-MAC y dos de MEI y se comprobó que poseen la calidad adecuada para el diagnóstico y las investigaciones del chikungunya, con lo cual mejorará la eficiencia de la vigilancia epidemiológica en Nicaragua, el primer país centroamericano que produce sus propios reactivos para el diagnóstico serológico del CHIKV. Los métodos estudiados en este trabajo pueden aplicarse en otros países y contribuyen al desarrollo de sistemas de diagnóstico sostenibles para combatir la enfermedad.


Assuntos
Vírus Chikungunya/imunologia , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/epidemiologia , Anticorpos Antivirais/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Nicarágua/epidemiologia
20.
Caracas; s.n; 20160000. 73 p. Tablas, Gráficos.
Tese em Espanhol | LILACS, LIVECS | ID: biblio-1368536

RESUMO

Las micosis superficiales son infecciones causadas por hongos que afectan la parte más superficial de la piel, mucosa, pelos y uñas. En los últimos años no se han creado nuevas drogas para el tratamiento de estas micosis. Por lo que es necesario investigar y desarrollar nuevos compuestos con actividad antifúngica. El aceite de girasol ozonizado, que aún está en estudio, representa una posible alternativa. Se planteó el objetivo de evaluar actividad antifúngica in vitro del aceite de girasol ozonizado en aislados clínicos de micosis superficiales. Se recopilaron cultivos de Candida albicans, Microsporum canis, Trichophyton rubrum, Fusarium spp., los cuales fueron ensayados para determinar su sensibilidad frente al aceite de girasol ozonizado, que consta de una fase oleosa y otra acuosa, empleando el método de referencia por microdilución en caldo según el CLSI y el método de unidades formadoras de colonias. Los datos obtenidos fueron analizados en base a valores numéricos y medidas de tendencia central. Las comparaciones se llevaron a cabo por la prueba estadística U de Mann-Whitney para análisis de variables no paramétricas. Por el método de unidades formadoras de colonias empleando la cepa de C. albicans ATCC90028 se obtuvieron tiempos de letalidad entre 15 y 60 minutos de exposición a las muestras ozonizadas. Por el método de microdilución en caldo se obtuvieron CIM de 0,4% ­ 0,75% para C. albicans; entre 0,75% y 1,5% para Fusarium spp., frente al aceite de girasol ozonizado. Frente a la fracción acuosa ozonizada se obtuvieron CIM entre 1,5% y 6,25% para C. albicans, entre 0,4% y 1,5% para Fusarium spp. Para los dermatofitos, las CIM y CFM frente a la porción acuosa ozonizada fueron ≤ 0,2% y ≤ 0,75%. Se concluye que el aceite de girasol ozonizado, tanto en su fracción oleosa como acuosa, tiene mayor actividad antifúngica que el aceite de girasol virgen.


Superficial fungal infections are caused by fungus that affect the most superficial part of the skin, mucosa, hair and nails. In recent years there have not created new drugs to treat these fungal infections. So it is necessary to research and develop new compounds with antifungal activity. Ozonated sunflower oil, which is still under study, represents a possible alternative. In order to evaluate in vitro antifungal activity of ozonized sunflower oil in clinical isolates of superficial mycosis, it was raised cultures of Candida albicans, Microsporum canis, Trichophyton rubrum, Fusarium spp., which were tested for their sensitivity to ozonized sunflower oil, consisting of an oil phase and another aqueous was collected using the reference method microdilution CLSI broth according to the method and the colony forming units. The data obtained were analyzed based on numerical values and measures of central tendency. Comparisons were carried out by the statistical U Mann-Whitney test for nonparametric analysis variables. By the method of colony forming units using strain C. albicans ATCC90028 lethality times were obtained between 15 and 60 minutes of exposure to ozonized samples. By the method of microdilution, MICs there were obtained 0.4% - 0.75% for C. albicans; between 0.75% and 1.5% for Fusarium spp., against ozonized sunflower oil. Opposite the ozonized aqueous fraction was obtained MIC between 1.5% and 6.25% for C. albicans, from 0.4% to 1.5% for Fusarium spp. For dermatophytes, MIC and MFC against the ozonized aqueous portion were ≤0.2% and ≤0.75%. It is concluded that ozonized sunflower oil, both aqueous and oil fractions has antifungal activitygreater than virgin sunflower oil.


Assuntos
Humanos , Masculino , Feminino , Trichophyton , Candida albicans , Onicomicose , Dermatomicoses , Óleo de Girassol , Microsporum , Antifúngicos
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