RESUMO
OBJECTIVE: To identify condom use and drug consumption in migrants, as well as the association between these variables. METHOD: A systematic search was carried out for articles published in Spanish and English (2017-2022), in PubMed, EBSCO, WEB of SCIENCE, Elsevier, Scielo, Redalyc, with eligible studies reporting on condom use and drug consumption, and their association. RESULTS: The search strategy found 147 articles with the combination of terms and other sources. After excluding articles by title, abstract, and finding that they had the study variables, eight articles were included for qualitative analysis and only three met the criteria for quantitative analysis. CONCLUSION: Drug consumption favors inconsistent condom use, increasing the risk of acquiring an STI, and can lead to other mental health issues derived from the use of these substances.
Assuntos
Preservativos , Migrantes , HumanosRESUMO
ABSTRACT Objective: To identify condom use and drug consumption in migrants, as well as the association between these variables. Method: A systematic search was carried out for articles published in Spanish and English (2017-2022), in PubMed, EBSCO, WEB of SCIENCE, Elsevier, Scielo, Redalyc, with eligible studies reporting on condom use and drug consumption, and their association. Results: The search strategy found 147 articles with the combination of terms and other sources. After excluding articles by title, abstract, and finding that they had the study variables, eight articles were included for qualitative analysis and only three met the criteria for quantitative analysis. Conclusion: Drug consumption favors inconsistent condom use, increasing the risk of acquiring an STI, and can lead to other mental health issues derived from the use of these substances.
RESUMO Objetivo: Identificar o uso de preservativo e o consumo de drogas em migrantes, bem como a associação entre essas variáveis. Método: Foi realizada uma busca sistemática de artigos publicados em espanhol e inglês (2017-2022), em PubMed, EBSCO, WEB of SCIENCE, Elsevier, Scielo, Redalyc, com estudos elegíveis relatando o uso de preservativos e consumo de drogas, e sua associação. Resultados: Com a estratégia de busca foram identificados 147 artigos com a combinação de termos e outras fontes. Após eliminar os artigos por título, resumo e identificar que continham as variáveis do estudo, oito artigos foram incluídos para análise qualitativa e apenas três atenderam aos critérios para análise quantitativa. Conclusão: O consumo de drogas estimula o uso inconsistente do preservativo, o que aumenta o risco de aquisição de uma IST, além de outros problemas de saúde mental decorrentes do consumo dessas substâncias.
RESUMEN Objetivo: Identificar el uso del condón y el consumo de drogas en migrantes, así como la asociación entre estas variables. Método: Se realizó una búsqueda sistemática de artículos publicados en español e inglés (2017-2022), en PubMed, EBSCO, WEB of SCIENCE, Elsevier, Scielo, Redalyc, siendo que los estudios elegibles informaron sobre el uso del condón y el consumo de drogas, y su asociación Resultados: Con la estrategia de búsqueda se identificaron 147 artículos con la combinación de términos y de otras fuentes. Después de la eliminación de artículos por título, resumen, identificar que cuenten con las variables de estudio, se incluyeron ocho artículos para el análisis cualitativo y únicamente tres cumplieron con los criterios para el análisis cuantitativo. Conclusión: El consumo de drogas favorece el uso inconstante del condón, y esto incrementa el riesgo de adquirir alguna ITS, además de otras cuestiones de salud mental derivadas del consumo de estas sustancias.
Assuntos
Humanos , Transtornos Relacionados ao Uso de Substâncias , Emigrantes e Imigrantes , Drogas Ilícitas , PreservativosRESUMO
Hypoxic zones are spreading worldwide in marine environments affecting many organisms. Shrimp and other marine crustaceans can withstand environmental hypoxia using several strategies, including the regulation of energy producing metabolic pathways. Pyruvate carboxylase (PC) catalyzes the first reaction of gluconeogenesis to produce oxaloacetate from pyruvate. In mammals, PC also participates in lipogenesis, insulin secretion and other processes, but this enzyme has been scarcely studied in marine invertebrates. In this work, we characterized the gene encoding PC in the white shrimp Litopenaeus vannamei, modelled the protein structure and evaluated its gene expression in hepatopancreas during hypoxia, as well as glucose and lactate concentrations. The PC gene codes for a mitochondrial protein and has 21 coding exons and 4 non-coding exons that generate three transcript variants with differences only in the 5'-UTR. Total PC expression is more abundant in hepatopancreas compared to gills or muscle, indicating tissue-specific expression. Under hypoxic conditions of 1.53 mg/L dissolved oxygen, PC expression is maintained in hepatopancreas, indicating its key role even in energy-limited conditions. Finally, both glucose and lactate concentrations were maintained under hypoxia for 24-48 h in hepatopancreas.
Assuntos
Penaeidae , Piruvato Carboxilase , Sequência de Aminoácidos , Animais , Glucose/metabolismo , Hepatopâncreas/metabolismo , Hipóxia/metabolismo , Lactatos/metabolismo , Mamíferos/metabolismo , Estrutura Molecular , Penaeidae/metabolismo , Piruvato Carboxilase/genética , Piruvato Carboxilase/metabolismoRESUMO
Hypoxia (<2 mg O2/L) is one of the main environmental stressors that affects aquatic organisms, including the white shrimp (Litopenaeus vannamei). During hypoxia, reactive oxygen species (ROS) accumulation induces oxidative stress and damage to biomolecules. Redox state and ROS overproduction are modulated by the antioxidant system that is composed of several antioxidant enzymes, proteins, and other small compounds. Glutathione peroxidase 4 (GPx4) has emerged as an important antioxidant enzyme with cytoprotective roles. In vertebrates, antioxidant and pro-oxidant stress responses are regulated by several factors, including the p53 protein. However, little is known about GPx4 responses in crustaceans and the regulation by p53. Herein we analyzed and characterized the L. vannamei GPx4 and evaluated the responses to hypoxia and p53 knock-down. We found a unique GPx4 gene that produces five transcript variants (TVs) and only two protein isoforms with distinct cellular localization. GPx4 expression in hepatopancreas during hypoxia and p53 knock-down changed during short and long-term hypoxia, suggesting that GPx4 may be a sensitive indicator of antioxidant imbalance during stress. Knock-down of p53 induced a reduction in GPx4 expression, indicating that p53 modulates GPx4 responses during stress. This agrees with our findings of putative consensus sequences for p53 in the GPx4 gene promoter by in silico analysis. Also, the antioxidant response was effective in preventing major protein damage during hypoxia since no changes were detected in carbonylated proteins content in hepatopancreas during hypoxia. Conversely, p53 knock-down produced significant changes in carbonylated proteins.
Assuntos
Hepatopâncreas , Penaeidae , Animais , Antioxidantes/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Hepatopâncreas/metabolismo , Hipóxia/genética , Hipóxia/metabolismo , Penaeidae/genética , Penaeidae/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
The aim of this study was to describe clinical and survival characteristics of transplant-eligible multiple myeloma (MM) patients in Latin America (LA), with a special focus on differences between public and private healthcare facilities. We included 1293 patients diagnosed between 2010 and 2018. A great disparity in outcomes and survival between both groups was observed. Late diagnosis and low access to adequate frontline therapy and ASCT in public institutions probably explain these differences. Patients treated with novel drug induction protocols, followed by autologous stem cell transplantation (ASCT) and maintenance, have similar overall survival compared to that published internationally.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , América Latina/epidemiologia , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Transplante Autólogo , Resultado do TratamentoRESUMO
Lysozymes play a key role in innate immune response to bacterial pathogens, catalyzing the hydrolysis of the peptidoglycan layer of bacterial cell walls. In this study, the genes encoding the c-type (TmLyzc) and g-type (TmLyzg) lysozymes from Totoaba macdonaldi were cloned and characterized. The cDNA sequences of TmLyzg and TmLyzc were 582 and 432 bp, encoding polypeptides of 193 and 143 amino acids, respectively. Amino acid sequences of these lysozymes shared high identity (60-90%) with their counterparts of other teleosts and showed conserved functional-structural signatures of the lysozyme superfamily. Phylogenetic analysis indicated a close relationship with their vertebrate homologues but distinct evolutionary paths for each lysozyme. Expression analysis by qRT-PCR revealed that TmLyzc was expressed in stomach and pyloric caeca, while TmLyzg was highly expressed in stomach and heart. These results suggest that both lysozymes play important roles in defense of totoaba against bacterial infections or as digestive enzyme.
Assuntos
Antibacterianos/metabolismo , Proteínas de Peixes/genética , Peixes/imunologia , Mucosa Gástrica/metabolismo , Muramidase/genética , Miocárdio/metabolismo , Animais , Galinhas/genética , Clonagem Molecular , Digestão , Evolução Molecular , Proteínas de Peixes/metabolismo , Gansos/genética , Perfilação da Expressão Gênica , Imunidade Inata , Muramidase/metabolismo , Especificidade de Órgãos , Filogenia , Alinhamento de SequênciaRESUMO
Background The treatment of choice of newly diagnosed multiple myeloma (NDMM) is an induction with proteasome inhibitors followed autologous stem cell transplantation (HSCT). Since 2013, the treatment of these patients in the public system is based on CTD (cyclophosphamide, thalidomide, and dexamethasone). Aim To evaluate the response rates achieved with CTD, and the results of HSCT in patients with NDMM in the public setting. Material and Methods Data from patients considered as candidates for HSCT from different centers of the National Adult Antineoplastic Drug Program (PANDA, for its acronym in Spanish), diagnosed between 2013 and 2017, was analyzed. The response to treatment of first and second lines of treatment was evaluated, in addition to the results of HSCT. An optimal Response was defined as the sum of strict complete remission, complete remission and very good partial response (sCR, CR and VGPR). Results One hundred and seventy-seven patients were analyzed, 54% women, and 53% with IgG multiple myeloma. Information about the international staging system was retrieved in 127 patients (71%). Seventeen percent were ISS I, 22% in ISS II and 32% ISS III. CTD was used as first treatment in 106 patients (60%), and cyclophosphamide, bortezomib and dexamethasone (CyBorD) in 13 (7%). As first line, CTD had an overall response of 50.9%, and CyBorD of 76.9%. Thirty patients were treated with bortezomib as second line treatment. Forty patients (22%) underwent HSCT. The 5-year Overall Survival (OS) in transplanted patients and non-transplanted patients was 100 and 62% respectively (p < 0.01). Conclusions The response rate achieved by CTD in these patients is suboptimal. The response to CyBorD was better.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Fatores de Tempo , Transplante Autólogo , Dexametasona/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Estudos Retrospectivos , Terapia Combinada , Intervalo Livre de Doença , Ciclofosfamida/administração & dosagem , Estimativa de Kaplan-Meier , Bortezomib/administração & dosagem , Mieloma Múltiplo/mortalidadeRESUMO
ABSTRACT Background: Immunoglobulin light chain (AL) amyloidosis is a rare and underdiagnosed entity. Aim: To characterize patients with AL amyloidosis in Chilean public health centers. Material and Methods: We conducted a retrospective, multicenter study. Public centers of the Chilean Monoclonal Gammopathies Cooperative Group were asked to search for patients with AL amyloidosis in their databases. Epidemiological, clinical and laboratory characteristics were evaluated. Results: Forty-two patients aged 22 to 84 years were found. Twenty four percent had localized AL amyloidosis; 64% had a lambda light chain clone; 47% were associated with multiple myeloma and 9% with non-Hodgkin lymphoma. The most commonly involved organ was the kidney (76%). Serum free light chains were measured in 31% and an echocardiogram was performed in 74% of patients. Seventeen percent of patients received only palliative care, 17% were treated with bortezomib, 21% with thalidomide, and 40% with melphalan. No patient was transplanted. The mean overall survival (OS) of the group was 19 months. The 5-year OS was 28%. Conclusions: It is important to obtain these realistic, national data to initiate strategies to improve early diagnosis and proper management of this disease.
La amiloidosis AL es una entidad poco frecuente y subdiagnosticada. Mientras todo el mundo discute sobre las nuevas herramientas diagnósticas y terapéuticas, en Chile y en América Latina en general, estamos lejos de esa realidad. El objetivo del presente estudio fue caracterizar a los pacientes con amiloidosis AL en centros del sistema público de nuestro país. Se realizó un estudio retrospectivo, multicéntrico, descriptivo. Los centros públicos del grupo cooperativo hematológico chileno buscaron en sus bases de datos pacientes diagnosticados con amiloidosis AL. Se evaluaron las características epidemiológicas, clínicas y de laboratorio. La edad media fue de 65 años. A 24% de los pacientes se les diagnosticó amiloidosis AL localizada; 64% tuvo paraproteína con cadena ligera lambda; 47% se asoció con mieloma múltiple y 9% con linfoma no Hodgkin. El órgano afectado con mayor frecuencia fue el riñón (76%). Las cadenas ligeras libres de suero se realizaron en 31% y ecocardiograma en 74%. El 17% recibió solo cuidados paliativos, 17% recibió tratamiento con bortezomib, 21% con talidomida y 40% con melfalán. Ningún paciente fue trasplantado. La media de sobrevida global (SG) del grupo fue de 19 meses. La SG a 5 años fue de 28%. Es importante reportar estos resultados nacionales para iniciar estrategias que mejoren tanto el diagnóstico temprano como el tratamiento de esta patología. Por lo tanto, mejorar la sospecha diagnóstica es crucial.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Setor Público/estatística & dados numéricos , Amiloidose de Cadeia Leve de Imunoglobulina/epidemiologia , Serviços de Saúde/estatística & dados numéricos , Fatores de Tempo , Eletroforese das Proteínas Sanguíneas , Chile/epidemiologia , Estudos Retrospectivos , Cadeias lambda de Imunoglobulina , Estimativa de Kaplan-Meier , Amiloidose de Cadeia Leve de Imunoglobulina/fisiopatologiaRESUMO
El proceso de cuidar es un entendimiento propio de cada situación, la práctica en Enfermería es contextualizar un sinfín de tareas que el profesional debe llevar a cabo, lo cual se denomina como Práctica Avanzada. El cuidado humano se ha definido desde varias perspectivas filosóficas, para Heidegger el cuidado es la conciencia del desvelo por sí mismo, significando inquietud, preocupación y alarma por otros, implicando el quehacer expresado en la praxis mediante una clara manifestación del cuidado existencial. Las enfermeras de Práctica Avanzada son capaces de realizar cuidados a un elevado nivel de pericia, con un alto grado de complejidad basada en evidencia científica. Es claro que la filosofía del cuidado no es un mundo alejado de las competencias de la Enfermería, ya que descifrar esta, es comprender la esencia de la profesión y de la humanidad, llevarla a la Práctica Avanzada es fundamental para mantener la calidad integral del cuidado.
The process of caring is an understanding of each situation, the practice in nursing is to contextualize a myriad of tasks that the professional must carry out, which is called Advanced Practice. Human care has been defined from various philosophical perspectives, for Heidegger the care is the conscience of sleeplessness by itself, meaning restlessness, concern and alarm for others, implying the task expressed in praxis through a clear manifestation of existential care. The Advanced Practice Nurses are capable of performing care at an expert level, with a high degree of complexity based on scientific evidence. It is clear that the philosophy of care is not a world away from the competencies of nursing, because to decipher this, is to understand the essence of the profession and humanity, take it to Advanced Practice is essential to maintain comprehensive quality of care.
Assuntos
Humanos , Conhecimentos, Atitudes e Prática em Saúde , Enfermagem , Prática Avançada de Enfermagem , Prática Institucional , Cuidados de Enfermagem , MéxicoRESUMO
Mango (Mangifera indica L.) is an important commercial fruit that shows a noticeable loss of firmness during ripening. Polygalacturonase (PG, E.C. 3.2.1.15) is a crucial enzyme for cell wall loosening during fruit ripening since it solubilizes pectin and its activity correlates with fruit softening. Mango PGs were mapped to a genome draft using seventeen PGs found in mango transcriptomes and 48 bonafide PGs were identified. The phylogenetic analysis suggests that they are related to Citrus sinensis, which may indicate a recent evolutive divergence and related functions with orthologs in the tree. Gene expression analysis for nine PGs showed differential expression for them during post-harvest fruit ripening, MiPG21-1, MiPG14, MiPG69-1, MiPG17, MiPG49, MiPG23-3, MiPG22-7, and MiPG16 were highly up-regulated. PG enzymatic activity also increased during maturation and these results correlate with the loss of firmness observed in mango during post-harvest ripening, between the ethylene production burst and the climacteric peak. The analysis of PGs promoter regions identified regulatory sequences associated to ripening such as MADS-box, ethylene regulation like ethylene insensitive 3 (EIN3) factors, APETALA2-like and ethylene response element factors. During mango fruit ripening the action of at least these nine PGs contribute to softening, and their expression is regulated at the transcriptional level. The prediction of the tridimensional structure of some PGs showed a conserved parallel beta-helical fold related to polysaccharide hydrolysis and a modular architecture, where exons correspond to structural elements. Further biotechnological approaches could target specific softening-related PGs to extend mango post-harvest shelf life.
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Background The treatment of choice of newly diagnosed multiple myeloma (NDMM) is an induction with proteasome inhibitors followed autologous stem cell transplantation (HSCT). Since 2013, the treatment of these patients in the public system is based on CTD (cyclophosphamide, thalidomide, and dexamethasone). Aim To evaluate the response rates achieved with CTD, and the results of HSCT in patients with NDMM in the public setting. Material and Methods Data from patients considered as candidates for HSCT from different centers of the National Adult Antineoplastic Drug Program (PANDA, for its acronym in Spanish), diagnosed between 2013 and 2017, was analyzed. The response to treatment of first and second lines of treatment was evaluated, in addition to the results of HSCT. An optimal Response was defined as the sum of strict complete remission, complete remission and very good partial response (sCR, CR and VGPR). Results One hundred and seventy-seven patients were analyzed, 54% women, and 53% with IgG multiple myeloma. Information about the international staging system was retrieved in 127 patients (71%). Seventeen percent were ISS I, 22% in ISS II and 32% ISS III. CTD was used as first treatment in 106 patients (60%), and cyclophosphamide, bortezomib and dexamethasone (CyBorD) in 13 (7%). As first line, CTD had an overall response of 50.9%, and CyBorD of 76.9%. Thirty patients were treated with bortezomib as second line treatment. Forty patients (22%) underwent HSCT. The 5-year Overall Survival (OS) in transplanted patients and non-transplanted patients was 100 and 62% respectively (p < 0.01). Conclusions The response rate achieved by CTD in these patients is suboptimal. The response to CyBorD was better.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Estudos Retrospectivos , Fatores de Tempo , Transplante AutólogoRESUMO
BACKGROUND: Immunoglobulin light chain (AL) amyloidosis is a rare and underdiagnosed entity. AIM: To characterize patients with AL amyloidosis in Chilean public health centers. MATERIAL AND METHODS: We conducted a retrospective, multicenter study. Public centers of the Chilean Monoclonal Gammopathies Cooperative Group were asked to search for patients with AL amyloidosis in their databases. Epidemiological, clinical and laboratory characteristics were evaluated. RESULTS: Forty-two patients aged 22 to 84 years were found. Twenty four percent had localized AL amyloidosis; 64% had a lambda light chain clone; 47% were associated with multiple myeloma and 9% with non-Hodgkin lymphoma. The most commonly involved organ was the kidney (76%). Serum free light chains were measured in 31% and an echocardiogram was performed in 74% of patients. Seventeen percent of patients received only palliative care, 17% were treated with bortezomib, 21% with thalidomide, and 40% with melphalan. No patient was transplanted. The mean overall survival (OS) of the group was 19 months. The 5-year OS was 28%. CONCLUSIONS: It is important to obtain these realistic, national data to initiate strategies to improve early diagnosis and proper management of this disease.
Assuntos
Serviços de Saúde/estatística & dados numéricos , Amiloidose de Cadeia Leve de Imunoglobulina/epidemiologia , Setor Público/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletroforese das Proteínas Sanguíneas , Chile/epidemiologia , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/fisiopatologia , Cadeias lambda de Imunoglobulina , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
Thymidylate synthase (TS, E.C. 2.1.1.45) is a crucial enzyme for de novo deoxythymidine monophosphate (dTMP) biosynthesis. The gene for this enzyme is thyA, which encodes the folate-dependent TS that converts deoxyuridine monophosphate group (dUMP) into (dTMP) using the cofactor 5,10-methylenetetrahydrofolate (mTHF) as a carbon donor. We identified the thyA gene in the genome of the Vibrio parahaemolyticus strain FIM-S1708+ that is innocuous to humans but pathogenic to crustaceans. Surprisingly, we found changes in the residues that bind the substrate dUMP and mTHF, previously postulated as invariant among all TSs known (Finer-Moore, Santi & Stroud, 2003). Interestingly, those amino acid changes were also found in a clade of microorganisms that contains Vibrionales, Alteromonadales, Aeromonadales, and Pasteurellales (VAAP) from the Gammaproteobacteria class. In this work, we studied the biochemical properties of recombinant TS from V. parahemolyticus FIM-S1708+ (VpTS) to address the natural changes in the TS amino acid sequence of the VAAP clade. Interestingly, the Km for dUMP was 27.3 ± 4.3 µM, about one-fold larger compared to other TSs. The Km for mTHF was 96.3 ± 18 µM, about three- to five-fold larger compared to other species, suggesting also loss of affinity. Thus, the catalytic efficiency was between one or two orders of magnitude smaller for both substrates. We used trimethoprim, a common antibiotic that targets both TS and DHFR for inhibition studies. The IC50 values obtained were high compared to other results in the literature. Nonetheless, this molecule could be a lead for the design antibiotics towards pathogens from the VAAP clade. Overall, the experimental results also suggest that in the VAAP clade the nucleotide salvage pathway is important and should be investigated, since the de novo dTMP synthesis appears to be compromised by a less efficient thymidylate synthase.
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BACKGROUND: Patients with Glioblastoma multiforme (GBM) have a five years survival of less than 5%, but the response to chemotherapy with alkylating agents can vary depending on the methylation status of O6-methylguanine-DNA-methyltransferase (MGMT). Genetic testing has limitations for routine use, while immunohistochemistry (IHC) offers a fast and affordable technique but with heterogeneous results in the literature. AIM: To evaluate MGMT expression by IHC in tumor tissue of Chilean patients with GBM. MATERIAL AND METHODS: Tumor samples of 29 patients with a pathological diagnosis of GBM were studied. We performed IHC staining and manual analysis of positive and negative cells for MGMT expression. A cut-off of at least 10% of cells expressing MGMT was used. Demographic and clinical features of patients were obtained from clinical records. RESULTS: The median number of cells counted per case was 692 (interquartile range [IQR] 492-928). Fifteen cases (52%) were positive for MGMT expression. Median overall survival was 5.3 months (IQR 3.4-12-8). The effect of MGMT expression on the therapeutic response was not studied since only 3 patients received chemotherapy. CONCLUSIONS: Our results are similar to international reports, but we were not able to determine the association between MGMT expression and therapeutic response.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/enzimologia , Glioblastoma/enzimologia , O(6)-Metilguanina-DNA Metiltransferase/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Chile , Feminino , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , O(6)-Metilguanina-DNA Metiltransferase/genética , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Background: Patients with Glioblastoma multiforme (GBM) have a five years survival of less than 5%, but the response to chemotherapy with alkylating agents can vary depending on the methylation status of O6-methylguanine-DNA-methyltransferase (MGMT). Genetic testing has limitations for routine use, while immunohistochemistry (IHC) offers a fast and affordable technique but with heterogeneous results in the literature. Aim: To evaluate MGMT expression by IHC in tumor tissue of Chilean patients with GBM. Material and Methods: Tumor samples of 29 patients with a pathological diagnosis of GBM were studied. We performed IHC staining and manual analysis of positive and negative cells for MGMT expression. A cut-off of at least 10% of cells expressing MGMT was used. Demographic and clinical features of patients were obtained from clinical records. Results: The median number of cells counted per case was 692 (interquartile range [IQR] 492-928). Fifteen cases (52%) were positive for MGMT expression. Median overall survival was 5.3 months (IQR 3.4-12-8). The effect of MGMT expression on the therapeutic response was not studied since only 3 patients received chemotherapy. Conclusions: Our results are similar to international reports, but we were not able to determine the association between MGMT expression and therapeutic response.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Encefálicas/enzimologia , Biomarcadores Tumorais/metabolismo , Glioblastoma/enzimologia , O(6)-Metilguanina-DNA Metiltransferase/metabolismo , Prognóstico , Neoplasias Encefálicas/genética , Imuno-Histoquímica , Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Chile , Taxa de Sobrevida , Estudos Retrospectivos , Glioblastoma/genética , O(6)-Metilguanina-DNA Metiltransferase/genéticaRESUMO
We studied a mango glutathione S-transferase (GST) (Mangifera indica) bound to glutathione (GSH) and S-hexyl glutathione (GSX). This GST Tau class (MiGSTU) had a molecular mass of 25.5 kDa. MiGSTU Michaelis-Menten kinetic constants were determined for their substrates obtaining a Km, Vmax and kcat for CDNB of 0.792 mM, 80.58 mM min-1 and 68.49 s-1 respectively and 0.693 mM, 105.32 mM min-1 and 89.57 s-1, for reduced GSH respectively. MiGSTU had a micromolar affinity towards GSH (5.2 µM) or GSX (7.8 µM). The crystal structure of the MiGSTU in apo or bound to GSH or GSX generated a model that explains the thermodynamic signatures of binding and showed the importance of enthalpic-entropic compensation in ligand binding to Tau-class GST enzymes.
Assuntos
Glutationa Transferase/metabolismo , Mangifera/enzimologia , Glutationa/metabolismo , Glutationa Transferase/química , Cinética , Ligação ProteicaRESUMO
Although the accumulation of a misfolded and protease-resistant form of the prion protein (PrP) is a key event in prion pathogenesis, the cellular factors involved in its folding and quality control are poorly understood. PrP is a glycosylated and disulfide-bonded protein synthesized at the endoplasmic reticulum (ER). The ER foldase ERp57 (also known as Grp58) is highly expressed in the brain of sporadic and infectious forms of prion-related disorders. ERp57 is a disulfide isomerase involved in the folding of a subset of glycoproteins in the ER as part of the calnexin/calreticulin cycle. Here, we show that levels of ERp57 increase mainly in neurons of Creutzfeldt-Jacob patients. Using gain- and loss-of-function approaches in cell culture, we demonstrate that ERp57 expression controls the maturation and total levels of wild-type PrP and mutant forms associated with human disease. In addition, we found that PrP physically interacts with ERp57, and also with the closest family member PDIA1, but not ERp72. Furthermore, we generated a conditional knock-out mouse for ERp57 in the nervous system and detected a reduction in the steady-state levels of the mono- and nonglycosylated forms of PrP in the brain. In contrast, ERp57 transgenic mice showed increased levels of endogenous PrP. Unexpectedly, ERp57 expression did not affect the susceptibility of cells to ER stress in vitro and in vivo. This study identifies ERp57 as a new modulator of PrP levels and may help with understanding the consequences of ERp57 up-regulation observed in human disease.
Assuntos
Príons/metabolismo , Isomerases de Dissulfetos de Proteínas/metabolismo , Animais , Linhagem Celular , Síndrome de Creutzfeldt-Jakob/metabolismo , Humanos , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Dobramento de ProteínaRESUMO
Fruit ripening is a physiological and biochemical process genetically programmed to regulate fruit quality parameters like firmness, flavor, odor and color, as well as production of ethylene in climacteric fruit. In this study, a transcriptomic analysis of mango (Mangifera indica L.) mesocarp cv. "Kent" was done to identify key genes associated with fruit ripening. Using the Illumina sequencing platform, 67,682,269 clean reads were obtained and a transcriptome of 4.8 Gb. A total of 33,142 coding sequences were predicted and after functional annotation, 25,154 protein sequences were assigned with a product according to Swiss-Prot database and 32,560 according to non-redundant database. Differential expression analysis identified 2,306 genes with significant differences in expression between mature-green and ripe mango [1,178 up-regulated and 1,128 down-regulated (FDR ≤ 0.05)]. The expression of 10 genes evaluated by both qRT-PCR and RNA-seq data was highly correlated (R = 0.97), validating the differential expression data from RNA-seq alone. Gene Ontology enrichment analysis, showed significantly represented terms associated to fruit ripening like "cell wall," "carbohydrate catabolic process" and "starch and sucrose metabolic process" among others. Mango genes were assigned to 327 metabolic pathways according to Kyoto Encyclopedia of Genes and Genomes database, among them those involved in fruit ripening such as plant hormone signal transduction, starch and sucrose metabolism, galactose metabolism, terpenoid backbone, and carotenoid biosynthesis. This study provides a mango transcriptome that will be very helpful to identify genes for expression studies in early and late flowering mangos during fruit ripening.
RESUMO
BACKGROUND: Intensified treatment of Philadelphia chromosome negative acute lymphoblastic leukemia (Ph(-)ALL) in adolescents by pediatric teams, with fve years disease free survival (DFS) rate of 65%, encouraged the use of intensified protocols in patients between 15 and 30 years, improving the DFS from 45% to 60-80%. The protocol LLA 15-30 for patients between 15 and 30 years with Ph(-)ALL, based on the Children's Oncology Group (COG) protocol AALL0232 resulting in a five years DFS of 78%, was started in 2007 by the PANDA national program. AIM: To report the results of the prospective cohort study evaluating the results of this protocol four years after its implementation. PATIENTS AND METHODS: Between January 2007 and December 2010, 68 Ph(-) ALL patients, aged between 15-30 years (75% males) were incorporated. Survival was evaluated using Kaplan-Meier and log-rank tests. RESULTS: Fifty percent of patients were of high risk. A complete response was achieved in 91%, early death occurred in 6% and induction failure in 3%. Median follow-up was 23 months. Overall survival, disease free survival and relapse rates at 35 months were 61.8, 67.5% and 31% respectively. CONCLUSIONS: LLA 15-30 protocol significantly improved three-year overall survival from 31 to 62%. The 20% difference observed with AALL0232 protocol is explained by the high rate of relapse. Improving provider and patient compliance with protocols may eliminate this gap.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Asparaginase/administração & dosagem , Estudos de Coortes , Dexametasona/administração & dosagem , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Prognóstico , Estudos Prospectivos , Resultado do Tratamento , Vincristina/administração & dosagem , Adulto JovemRESUMO
Background: Intensified treatment of Philadelphia chromosome negative acute lymphoblastic leukemia (Ph(-)ALL) in adolescents by pediatric teams, with fve years disease free survival (DFS) rate of 65%, encouraged the use of intensified protocols in patients between 15 and 30 years, improving the DFS from 45% to 60-80%. The protocol LLA 15-30 for patients between 15 and 30 years with Ph(-)ALL, based on the Children’s Oncology Group (COG) protocol AALL0232 resulting in a five years DFS of 78%, was started in 2007 by the PANDA national program. Aim: To report the results of the prospective cohort study evaluating the results of this protocol four years after its implementation. Patients and Methods: Between January 2007 and December 2010, 68 Ph(-) ALL patients, aged between 15-30 years (75% males) were incorporated. Survival was evaluated using Kaplan-Meier and log-rank tests. Results: Fifty percent of patients were of high risk. A complete response was achieved in 91%, early death occurred in 6% and induction failure in 3%. Median follow-up was 23 months. Overall survival, disease free survival and relapse rates at 35 months were 61.8, 67.5% and 31% respectively. Conclusions: LLA 15-30 protocol significantly improved three-year overall survival from 31 to 62%. The 20% difference observed with AALL0232 protocol is explained by the high rate of relapse. Improving provider and patient compliance with protocols may eliminate this gap.