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1.
Curr Microbiol ; 81(7): 197, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816607

RESUMO

Identifying and evaluating potential vaccine candidates has become one of the main objectives to combat tuberculosis. Among them, mannosylated Apa antigen from Mycobacterium tuberculosis and the non-mannosylated protein expressed in Escherichia coli, have been studied. Although both proteins can induce a protective response in mice, it has been considered that native protein can be dispensed. In this work, we study the protective response induced by Apa expressed in E. coli and in Streptomyces lividans. The latter, like native is secreted as a double band of 45/47 kDa, however, only its 47 kDa band is mannosylated. Both antigens and BCG were intranasal administrated in mice, and animals were then challenged by aerosol with M. tuberculosis H37Rv. The results showed that both, Apa from S. lividans and E. coli conferred statistically significantly protection to animals compared to controls. The cytokine immune response was studied by an immunoassay after animals' immunization, revealing that Apa from S. lividans induced a statistically significant proliferation of T cell, as well as the expression of IFN-γ, IL-1ß, IL-17 and IL-10. In contrast, non-proliferation was obtained with non-mannosylated protein, but induction of IL-12 and IL-17 was observed. Together, these results demonstrate that both proteins were able to modulate a specific immune response against M. tuberculosis, that could be driven by different mechanisms possibly associated with the presence or not of mannosylation. Furthermore, stimulation of cells from BCG-vaccinated animals with the proteins could be an important tool, to help define the use of a given subunit-vaccine after BCG vaccination.


Assuntos
Administração Intranasal , Citocinas , Mycobacterium tuberculosis , Streptomyces lividans , Tuberculose , Animais , Camundongos , Aerossóis , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/genética , Antígenos de Bactérias/administração & dosagem , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/administração & dosagem , Citocinas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/administração & dosagem , Streptomyces lividans/genética , Streptomyces lividans/imunologia , Tuberculose/prevenção & controle , Tuberculose/imunologia , Vacinas contra a Tuberculose/imunologia , Vacinas contra a Tuberculose/administração & dosagem , Vacinas contra a Tuberculose/genética
2.
J Surg Case Rep ; 2023(1): rjac626, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36636660

RESUMO

Obesity is a chronic disease with pandemic levels of prevalence worldwide. The most often performed bariatric procedure is sleeve gastrectomy. Although the patient's history may not indicate preoperative imaging studies, coincidental findings of unexpected pathology are not uncommon, such as leiomyoma. A 41-year-old female was scheduled to laparoscopic gastric sleeve with no contraindications for surgery. A tumor-like mass was identified on the left lateral face of the distal third of the esophagus. Trans-surgical endoscopy and pneumatic test were performed to rule out any type of communication. The surgeon managed to remove the tumor mass, that was sent to histopathological study, and concluded the procedure without complications. Benign tumors of the esophagus are rarely found lesions. Occasionally unexpected findings may occur during surgery, and they should be resolved intraoperatively when possible to allow the completion of the originally planned surgical procedure.

3.
J Surg Case Rep ; 2023(1): rjad009, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36685118

RESUMO

The one-anastomosis gastric bypass (OAGB) is one of the most popular performed bariatric surgeries and has good long-term success for treating obesity and metabolic diseases. However, some patients can develop severe complications such as malnutrition and hepatic steatosis, which can be corrected with a reversal procedure, as seen in this case. A 20-year-old woman underwent OAGB surgery, which was converted to Roux-en-Y gastric bypass 4 months after the initial procedure due to malnutrition, both surgeries were performed at a hospital in southern Mexico. After the second surgery, she presented to our hospital with intolerance to oral feeding, vomiting and loss of 44 kg in 4 months. The patient was stabilized and scheduled for reversion surgery to normal anatomy 5 months later. She had good short-term nutritional outcomes and at the 1-year follow-up her total weight gain was 14 kg.

4.
Rev Saude Publica ; 54: 80, 2020.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-32813868

RESUMO

OBJECTIVE To evaluate the effectiveness of adherence to a multidisciplinary renal health program in reducing mortality and progression to hemodialysis. METHODS We used a database that included patient monitoring (2013-2017), dialysis admissions and all cause of mortality in Peru. Adherence to the program was established by meeting minimum visits during the first year of monitoring. The outcome of interest was hemodialysis admissions or all cause-mortality. Kaplan-Meier curves, Log-Rank test and competing survival analysis methods were used to estimate the differential risk between adherent and non-adherent patients. RESULTS A total of 20,354 participants was evaluated; 54.1% were male, 72.1 years old in average, 2.2 years average follow-up, and 15,279 (75.1%) belonged to the early stages (1 to 3a) of Chronic Kidney Disease. Adherence decreased the risk of renal replacement therapy in 41.0% (HR = 0.59, 95%CI 0.41-0.85) in the low-risk group and mortality in the high-risk group was 31.0% (HR = 0.69, 95%CI 0.57-0.83). CONCLUSIONS The multidisciplinary care strategy with standardized assessments by stage is effective in reducing admission to .0when the patient is identified in early stages and in reducing mortality in advanced stages.


Assuntos
Fidelidade a Diretrizes , Falência Renal Crônica/terapia , Insuficiência Renal Crônica/terapia , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/epidemiologia , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Peru/epidemiologia , Avaliação de Programas e Projetos de Saúde , Diálise Renal , Terapia de Substituição Renal , Fatores de Risco , Análise de Sobrevida
5.
PLoS One ; 15(5): e0233651, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469980

RESUMO

Transference of RNAs and ribosomes from Schwann cell-to-axon was demonstrated in normal and regenerating peripheral nerves. Previously, we have shown that RNAs transfer is dependent on F-actin cytoskeleton and Myosin Va. Here, we explored the contribution of microtubules to newly synthesized RNAs transport from Schwann cell nuclei up to nodal microvilli in sciatic nerves. Results using immunohistochemistry and quantitative confocal FRET analysis indicate that Schwann cell-derived RNAs co-localize with microtubules in Schwann cell cytoplasm. Additionally, transport of Schwann cell-derived RNAs is nocodazole and colchicine sensitive demonstrating its dependence on microtubule network integrity. Moreover, mRNAs codifying neuron-specific proteins are among Schwann cell newly synthesized RNAs population, and some of them are associated with KIF1B and KIF5B microtubules-based motors.


Assuntos
Axônios/metabolismo , Microtúbulos/metabolismo , RNA/metabolismo , Células de Schwann/metabolismo , Nervo Isquiático/metabolismo , Animais , Masculino , Bainha de Mielina/metabolismo , Regeneração Nervosa , RNA/análise , Transporte de RNA , Ratos , Ratos Sprague-Dawley
6.
Bioinformatics ; 36(16): 4506-4507, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32470109

RESUMO

MOTIVATION: The amount of genomic data generated globally is seeing explosive growth, leading to increasing needs for processing, storage and transmission resources, which motivates the development of efficient compression tools for these data. Work so far has focused mainly on the compression of data generated by short-read technologies. However, nanopore sequencing technologies are rapidly gaining popularity due to the advantages offered by the large increase in the average size of the produced reads, the reduction in their cost and the portability of the sequencing technology. We present ENANO (Encoder for NANOpore), a novel lossless compression algorithm especially designed for nanopore sequencing FASTQ files. RESULTS: The main focus of ENANO is on the compression of the quality scores, as they dominate the size of the compressed file. ENANO offers two modes, Maximum Compression and Fast (default), which trade-off compression efficiency and speed. We tested ENANO, the current state-of-the-art compressor SPRING and the general compressor pigz on several publicly available nanopore datasets. The results show that the proposed algorithm consistently achieves the best compression performance (in both modes) on every considered nanopore dataset, with an average improvement over pigz and SPRING of >24.7% and 6.3%, respectively. In addition, in terms of encoding and decoding speeds, ENANO is 2.9× and 1.7× times faster than SPRING, respectively, with memory consumption up to 0.2 GB. AVAILABILITY AND IMPLEMENTATION: ENANO is freely available for download at: https://github.com/guilledufort/EnanoFASTQ. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Compressão de Dados , Nanoporos , Algoritmos , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência de DNA , Software
7.
RNA ; 26(5): 595-612, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32051223

RESUMO

Axonal protein synthesis has been shown to play a role in developmental and regenerative growth, as well as in the maintenance of the axoplasm in a steady state. Recent studies have begun to identify the mRNAs localized in axons, which could be translated locally under different conditions. Despite that by now hundreds or thousands of mRNAs have been shown to be localized into the axonal compartment of cultured neurons in vitro, knowledge of which mRNAs are localized in mature myelinated axons is quite limited. With the purpose of characterizing the transcriptome of mature myelinated motor axons of peripheral nervous systems, we modified the axon microdissection method devised by Koenig, enabling the isolation of the axoplasm RNA to perform RNA-seq analysis. The transcriptome analysis indicates that the number of RNAs detected in mature axons is lower in comparison with in vitro data, depleted of glial markers, and enriched in neuronal markers. The mature myelinated axons are enriched for mRNAs related to cytoskeleton, translation, and oxidative phosphorylation. Moreover, it was possible to define core genes present in axons when comparing our data with transcriptomic data of axons grown in different conditions. This work provides evidence that axon microdissection is a valuable method to obtain genome-wide data from mature and myelinated axons of the peripheral nervous system, and could be especially useful for the study of axonal involvement in neurodegenerative pathologies of motor neurons such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophies (SMA).


Assuntos
Esclerose Lateral Amiotrófica/genética , Neurônios Motores/metabolismo , Atrofia Muscular Espinal/genética , RNA/genética , Esclerose Lateral Amiotrófica/metabolismo , Animais , Axônios/metabolismo , Axônios/patologia , Diferenciação Celular/genética , Perfilação da Expressão Gênica , Humanos , Microdissecção , Atrofia Muscular Espinal/metabolismo , Atrofia Muscular Espinal/patologia , Sistema Nervoso Periférico/metabolismo , Sistema Nervoso Periférico/patologia , RNA Mensageiro/genética , RNA-Seq , Transcriptoma/genética
8.
PeerJ Comput Sci ; 6: e270, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33816921

RESUMO

Cancer classification is a topic of major interest in medicine since it allows accurate and efficient diagnosis and facilitates a successful outcome in medical treatments. Previous studies have classified human tumors using a large-scale RNA profiling and supervised Machine Learning (ML) algorithms to construct a molecular-based classification of carcinoma cells from breast, bladder, adenocarcinoma, colorectal, gastro esophagus, kidney, liver, lung, ovarian, pancreas, and prostate tumors. These datasets are collectively known as the 11_tumor database, although this database has been used in several works in the ML field, no comparative studies of different algorithms can be found in the literature. On the other hand, advances in both hardware and software technologies have fostered considerable improvements in the precision of solutions that use ML, such as Deep Learning (DL). In this study, we compare the most widely used algorithms in classical ML and DL to classify the tumors described in the 11_tumor database. We obtained tumor identification accuracies between 90.6% (Logistic Regression) and 94.43% (Convolutional Neural Networks) using k-fold cross-validation. Also, we show how a tuning process may or may not significantly improve algorithms' accuracies. Our results demonstrate an efficient and accurate classification method based on gene expression (microarray data) and ML/DL algorithms, which facilitates tumor type prediction in a multi-cancer-type scenario.

9.
Rev. saúde pública (Online) ; 54: 80, 2020. tab, graf
Artigo em Inglês | LILACS, BBO - Odontologia | ID: biblio-1127234

RESUMO

ABSTRACT OBJECTIVE To evaluate the effectiveness of adherence to a multidisciplinary renal health program in reducing mortality and progression to hemodialysis. METHODS We used a database that included patient monitoring (2013-2017), dialysis admissions and all cause of mortality in Peru. Adherence to the program was established by meeting minimum visits during the first year of monitoring. The outcome of interest was hemodialysis admissions or all cause-mortality. Kaplan-Meier curves, Log-Rank test and competing survival analysis methods were used to estimate the differential risk between adherent and non-adherent patients. RESULTS A total of 20,354 participants was evaluated; 54.1% were male, 72.1 years old in average, 2.2 years average follow-up, and 15,279 (75.1%) belonged to the early stages (1 to 3a) of Chronic Kidney Disease. Adherence decreased the risk of renal replacement therapy in 41.0% (HR = 0.59, 95%CI 0.41-0.85) in the low-risk group and mortality in the high-risk group was 31.0% (HR = 0.69, 95%CI 0.57-0.83). CONCLUSIONS The multidisciplinary care strategy with standardized assessments by stage is effective in reducing admission to .0when the patient is identified in early stages and in reducing mortality in advanced stages.


RESUMEN OBJETIVO Evaluar la efectividad de la adherencia a un programa de salud renal en la reducción de mortalidad y progresión a hemodiálisis. MÉTODOS Utilizamos una base de datos que condensaba el seguimiento de los pacientes (2013-2017), los ingresos a diálisis de los mismos y la mortalidad por todas las causas en Perú. La adherencia al programa se estableció con el cumplimiento de visitas mínimas durante su primer año de seguimiento. La efectividad de la adherencia al programa se midió en términos de debut a hemodiálisis o muerte por todas las causas. Se utilizaron curvas de Kaplan-Meier, test de diferencias en la distribución (Log-Rank test) y métodos de análisis de supervivencia. Los análisis se realizaron utilizando R estudio 3.5.0 RESULTADOS Fueron evaluados 20.354 participantes, 54,1% varones, edad media de 72,1 años, con un seguimiento medio de 2,2 años; 15.279 (75.1%) tuvieron ERC en estadios tempranos (estadio 1 al 3a). La adherencia disminuyó en un 41,0% el riesgo de terapia de reemplazo renal (HR = 0,59; IC95% 0,41-0,85) en el grupo de bajo riesgo y en un 31,0% (HR = 0,69; IC95% 0,57-0,83) la mortalidad en el grupo de alto riesgo. CONCLUSIONES La estrategia de cuidado multidisciplinario con evaluaciones estandarizadas según estadio es efectiva en reducir el ingreso a terapia de reemplazo renal cuando se identifica al paciente en estadios tempranos y en reducir la mortalidad en estadios avanzados.


Assuntos
Fidelidade a Diretrizes , Insuficiência Renal Crônica/terapia , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Falência Renal Crônica/terapia , Avaliação de Processos e Resultados em Cuidados de Saúde , Peru/epidemiologia , Avaliação de Programas e Projetos de Saúde , Análise de Sobrevida , Fatores de Risco , Diálise Renal , Terapia de Substituição Renal , Estimativa de Kaplan-Meier , Falência Renal Crônica/epidemiologia
10.
Proteomics ; 19(16): e1900054, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31131510

RESUMO

Neurons present a highly polarized morphology, often displaying a significantly imbalanced distribution of the cytoplasm between the somatic and axonal domains. This imbalance requires cell-specific mechanisms for the maintenance of the axoplasmic mass during development, neuronal homeostasis, and recovery after injury. Although it has been clearly demonstrated that axoplasmic transport contributes a large amount of proteins to the axons, local protein synthesis has been fully accepted as an important complementary source of proteins, which aids in the maintenance of the axoplasmic mass in both normal and regenerating conditions. This review analyzes and highlights the most important advances in the knowledge of the axonal transcriptome, translatome, and proteome at a genome-wide scale. It is discussed how this knowledge has provided researchers with new insights regarding the involvement of local protein synthesis in many key neuronal functions. In addition, challenges, open questions, and methods currently available to study axonal mRNA localization and protein synthesis are addressed.


Assuntos
Axônios/metabolismo , Perfilação da Expressão Gênica/métodos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Biossíntese de Proteínas , Proteoma/metabolismo , Proteômica/métodos , Animais , Homeostase/genética , Humanos , Biologia de Sistemas/métodos
11.
Ann Hepatobiliary Pancreat Surg ; 22(4): 412-415, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30588534

RESUMO

Different surgical procedures have been described for the treatment of colorectal liver metastases. The appropriate surgical approach depends, among many other factors, on the relationship between liver metastases and suprahepatic veins. If possible, the detachment of colorectal liver metastasis from suprahepatic veins is a good alternative liver parenchyma sparing technique. In this study, we describe a new two-step wedge liver resection technique for colorectal liver metastases located between suprahepatic veins. Prior to resection, intraoperative ultrasound is employed in order to plan and guide both steps. Initially, we place stitches and resect a cylindrical piece of normal liver parenchyma above the tumor and suprahepatic veins. Next, we place stitches on the future specimen located between suprahepatic veins, then resect it. The main advantages of this procedure are the good visualization and vascular control that may be achieved during the detachment of the tumor from suprahepatic veins. We call this procedure "zoom resection" because its dynamics are similar to the workings of a photograph camera's telescopic system. We present the case of a 55-year-old patient diagnosed with multiple colorectal liver metastases, one of which was resected through this technique.

13.
Rev Peru Med Exp Salud Publica ; 34(2): 209-217, 2017.
Artigo em Espanhol | MEDLINE | ID: mdl-29177378

RESUMO

OBJECTIVES.: To describe the characteristics of the population with chronic kidney disease (CKD) stage 3 and 4, to determine the factors associated with CKD progression and admission to renal replacement therapy (RRT), as well as renal survival. MATERIALS AND METHODS.: Longitudinal retrospective study of patients referred between January 2012 and December 2015 to the Renal Health Unit of the Hospital Nacional Edgardo Rebagliati Martins (HNERM), who were evaluated and followed by a multidisciplinary team. The clinical and laboratory data for each query were recorded in a software created specifically for the program. A multivariate logistic regression analysis was performed to assess the factors associated with the progression of CKD, a Cox regression model to predict the risk of entering RRT and the Kaplan-Meier method for renal survival analysis. RESULTS.: We assessed 1248 patients in stage 3A: 248 (20%), stage 3B: 548 (44%) and stage 4: 452 (36%). 352 (28%) progressed, being proteinuria the most important progression factor (OR: 3.2; CI 95%: 2,2-4.6). Proteinuria increases the risk of admission to RRT in four times and having a glomerular filtration rate < 30% in 3.6 times. Median follow-up was 12 months (RIC 5-27 months). 92 patients (7%) required to initiate RRT. Renal survival at 12 months of follow-up was 96% and at 24 months was 90%. CONCLUSIONS.: Our study shows that in a specialized center a significant proportion of patients with CKD does not progress in their disease and that the factor that is most associated with progression of disease and at the onset of RRT is proteinuria.


OBJETIVOS.: Describir las características de la población con enfermedad renal crónica (ERC) estadio 3 y 4, determinar los factores asociados a progresión de ERC y a ingreso a terapia de reemplazo renal (TRR), así como la sobrevida renal. MATERIALES Y MÉTODOS.: Estudio retrospectivo longitudinal de pacientes remitidos entre enero de 2012 y diciembre de 2015 a la Unidad de Salud Renal del Hospital Nacional de Edgardo Rebagliati Martins (HNERM), quienes fueron evaluados y seguidos por un equipo multidisciplinario. Los datos clínicos y de laboratorio de cada consulta se registraron en un software creado específicamente para el programa. Se realizó un análisis de regresión logística multivariado para evaluar los factores asociados con la progresión de la ERC, un modelo de regresión de Cox para predecir el riesgo de ingresar al TRR y el método de Kaplan-Meier para el análisis de supervivencia renal. RESULTADOS.: Se evaluó a 1248 pacientes en estadio 3A: 248 (20%), estadio 3b: 548 (44%) y estadio 4: 452 (36%). 352 (28%) progresaron, siendo la proteinuria el factor de progresión más importante (OR: 3,2; IC95%: 2,2-4,6). La proteinuria incrementa el riesgo de ingreso a la TRR en cuatro veces y el tener una tasa de filtración glomerular <30% en 3,6 veces. La mediana de seguimiento fue de 12 meses (RIC 5-27 meses). 92 pacientes (7%) requirieron iniciar TRR. La supervivencia renal a los 12 meses de seguimiento fue del 96% y a los 24 meses de 90%. CONCLUSIONES.: Nuestro estudio muestra que en un centro especializado una proporción significativa de pacientes con ERC no progresa en su enfermedad y que el factor que más se asocia a progresión de enfermedad y a inicio de TRR es la proteinuria.


Assuntos
Insuficiência Renal Crônica/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/terapia , Estudos Longitudinais , Masculino , Peru , Encaminhamento e Consulta , Terapia de Substituição Renal , Estudos Retrospectivos , Previdência Social , Fatores de Tempo
15.
Rev. peru. med. exp. salud publica ; 34(2): 209-217, abr.-jun. 2017. tab, graf
Artigo em Espanhol | LILACS, LIPECS | ID: biblio-902902

RESUMO

RESUMEN Objetivos. Describir las características de la población con enfermedad renal crónica (ERC) estadio 3 y 4, determinar los factores asociados a progresión de ERC y a ingreso a terapia de reemplazo renal (TRR), así como la sobrevida renal. Materiales y métodos. Estudio retrospectivo longitudinal de pacientes remitidos entre enero de 2012 y diciembre de 2015 a la Unidad de Salud Renal del Hospital Nacional de Edgardo Rebagliati Martins (HNERM), quienes fueron evaluados y seguidos por un equipo multidisciplinario. Los datos clínicos y de laboratorio de cada consulta se registraron en un software creado específicamente para el programa. Se realizó un análisis de regresión logística multivariado para evaluar los factores asociados con la progresión de la ERC, un modelo de regresión de Cox para predecir el riesgo de ingresar al TRR y el método de Kaplan-Meier para el análisis de supervivencia renal. Resultados. Se evaluó a 1248 pacientes en estadio 3A: 248 (20%), estadio 3b: 548 (44%) y estadio 4: 452 (36%). 352 (28%) progresaron, siendo la proteinuria el factor de progresión más importante (OR: 3,2; IC95%: 2,2-4,6). La proteinuria incrementa el riesgo de ingreso a la TRR en cuatro veces y el tener una tasa de filtración glomerular <30% en 3,6 veces. La mediana de seguimiento fue de 12 meses (RIC 5-27 meses). 92 pacientes (7%) requirieron iniciar TRR. La supervivencia renal a los 12 meses de seguimiento fue del 96% y a los 24 meses de 90%. Conclusiones. Nuestro estudio muestra que en un centro especializado una proporción significativa de pacientes con ERC no progresa en su enfermedad y que el factor que más se asocia a progresión de enfermedad y a inicio de TRR es la proteinuria.


ABSTRACT Objectives. To describe the characteristics of the population with chronic kidney disease (CKD) stage 3 and 4, to determine the factors associated with CKD progression and admission to renal replacement therapy (RRT), as well as renal survival. Materials and methods. Longitudinal retrospective study of patients referred between January 2012 and December 2015 to the Renal Health Unit of the Hospital Nacional Edgardo Rebagliati Martins (HNERM), who were evaluated and followed by a multidisciplinary team. The clinical and laboratory data for each query were recorded in a software created specifically for the program. A multivariate logistic regression analysis was performed to assess the factors associated with the progression of CKD, a Cox regression model to predict the risk of entering RRT and the Kaplan-Meier method for renal survival analysis. Results. We assessed 1248 patients in stage 3A: 248 (20%), stage 3B: 548 (44%) and stage 4: 452 (36%). 352 (28%) progressed, being proteinuria the most important progression factor (OR: 3.2; CI 95%: 2,2-4.6). Proteinuria increases the risk of admission to RRT in four times and having a glomerular filtration rate < 30% in 3.6 times. Median follow-up was 12 months (RIC 5-27 months). 92 patients (7%) required to initiate RRT. Renal survival at 12 months of follow-up was 96% and at 24 months was 90%. Conclusions. Our study shows that in a specialized center a significant proportion of patients with CKD does not progress in their disease and that the factor that is most associated with progression of disease and at the onset of RRT is proteinuria.


Assuntos
Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Insuficiência Renal Crônica/diagnóstico , Peru , Encaminhamento e Consulta , Previdência Social , Fatores de Tempo , Estudos Retrospectivos , Estudos Longitudinais , Terapia de Substituição Renal , Progressão da Doença , Falência Renal Crônica/terapia
17.
Dev Neurobiol ; 74(3): 292-302, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23997031

RESUMO

The existence of RNA in axons has been a matter of dispute for decades. Evidence for RNA and ribosomes has now accumulated to a point at which it is difficult to question, much of the disputes turned to the origin of these axonal RNAs. In this review, we focus on studies addressing the origin of axonal RNAs and ribosomes. The neuronal soma as the source of most axonal RNAs has been demonstrated and is indisputable. However, the surrounding glial cells may be a supplemental source of axonal RNAs, a matter scarcely investigated in the literature. Here, we review the few papers that have demonstrated that glial-to-axon RNA transfer is not only feasible, but likely. We describe this process in both invertebrate axons and vertebrate axons. Schwann cell to axon ribosomes transfer was conclusively demonstrated (Court et al. [2008]: J. Neurosci 28:11024-11029; Court et al. [2011]: Glia 59:1529-1539). However, mRNA transfer still remains to be demonstrated in a conclusive way. The intercellular transport of mRNA has interesting implications, particularly with respect to the integration of glial and axonal function. This evolving field is likely to impact our understanding of the cell biology of the axon in both normal and pathological conditions. Most importantly, if the synthesis of proteins in the axon can be controlled by interacting glia, the possibilities for clinical interventions in injury and neurodegeneration are greatly increased.


Assuntos
Axônios/metabolismo , Neuroglia/metabolismo , Transporte de RNA , RNA/metabolismo , Animais , Humanos , Miosina Tipo V/metabolismo , Regeneração Nervosa , Ribossomos/metabolismo
18.
Dev Neurobiol ; 74(3): 382-96, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24272908

RESUMO

Sorting of specific mRNAs to particular cellular locations and regulation of their translation is an essential mechanism underlying cell polarization. The transport of RNAs by kinesins and dyneins has been clearly established in several cell models, including neurons in culture. A similar role appears to exist in higher eukaryotes for the myosins. Myosin Va (Myo5a) has been described as a component of ribonucleoprotein particles (RNPs) in the adult rat nervous system and associated to ZBP1 and ribosomes in ribosomal periaxoplasmic plaques (PARPs), making it a likely candidate for mediating some aspects of RNA transport in neurons. To test this hypothesis, we have characterized RNPs containing Myo5a in adult brains of rats and mice. Microarray analysis of RNAs co-immunoprecipitated with Myo5a indicates that this motor may associate with a specific subpopulation of neuronal mRNAs. We found mRNAs encoding α-synuclein and several proteins with functions in translation in these RNPs. Immunofluorescence analyses of RNPs showed apparent co-localization of Myo5a with ribosomes, mRNA and RNA-binding proteins in discrete structures present both in axons of neurons in culture and in myelinated fibers of medullary roots. Our data suggest that PARPs include RNPs bearing the mRNA coding for Myo5a and are equipped with kinesin and Myo5a molecular motors. In conclusion, we suggest that Myo5a is involved in mRNA trafficking both in the central and peripheral nervous systems.


Assuntos
Axônios/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Miosina Tipo V/metabolismo , RNA Mensageiro/metabolismo , Ribonucleoproteínas/metabolismo , Actinas/metabolismo , Animais , Encéfalo/metabolismo , Células Cultivadas , Gânglios Espinais/metabolismo , Bulbo , Camundongos , Camundongos Endogâmicos C57BL , Fibras Nervosas Mielinizadas/metabolismo , Ratos , Ratos Sprague-Dawley , alfa-Sinucleína/metabolismo , Proteínas tau/metabolismo
19.
PLoS One ; 8(4): e61905, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23626749

RESUMO

To better understand the role of protein synthesis in axons, we have identified the source of a portion of axonal RNA. We show that proximal segments of transected sciatic nerves accumulate newly-synthesized RNA in axons. This RNA is synthesized in Schwann cells because the RNA was labeled in the complete absence of neuronal cell bodies both in vitro and in vivo. We also demonstrate that the transfer is prevented by disruption of actin and that it fails to occur in the absence of myosin-Va. Our results demonstrate cell-to-cell transfer of RNA and identify part of the mechanism required for transfer. The induction of cell-to-cell RNA transfer by injury suggests that interventions following injury or degeneration, particularly gene therapy, may be accomplished by applying them to nearby glial cells (or implanted stem cells) at the site of injury to promote regeneration.


Assuntos
Actinas/metabolismo , Axônios/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Miosina Tipo V/metabolismo , RNA/metabolismo , Células de Schwann/metabolismo , Nervo Isquiático/metabolismo , Actinas/antagonistas & inibidores , Actinas/genética , Animais , Transporte Biológico , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Comunicação Celular , Expressão Gênica , Cadeias Pesadas de Miosina/genética , Miosina Tipo V/genética , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Células de Schwann/citologia , Nervo Isquiático/citologia , Nervo Isquiático/lesões , Tiazolidinas/farmacologia
20.
World J Microbiol Biotechnol ; 29(8): 1421-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23475258

RESUMO

Culture conditions in shake flasks affect filamentous Streptomyces lividans morphology, as well the productivity and O-mannosylation of recombinant Ala-Pro-rich O-glycoprotein (known as the 45/47 kDa or APA antigen) from Mycobacterium tuberculosis. In order to scale up from previous reported shake flasks to bioreactor, data from the literature on the effect of agitation on morphology of Streptomyces strains were used to obtain gassed volumetric power input values that can be used to obtain a morphology of S. lividans in bioreactor similar to the morphology previously reported in coiled/baffled shake flasks by our group. Morphology of S. lividans was successfully scaled-up, obtaining similar mycelial sizes in both scales with diameters of 0.21 ± 0.09 mm in baffled and coiled shake flasks, and 0.15 ± 0.01 mm in the bioreactor. Moreover, the specific growth rate was successfully scaled up (0.09 ± 0.02 and 0.12 ± 0.01 h(-1), for bioreactors and flasks, respectively), and the recombinant protein productivity measured by densitometry, as well. More interestingly, the quality of the recombinant glycoprotein measured as the amount of mannoses attached to the C-terminal of APA was also scaled- up; with up to five mannose residues in cultures carried out in shake flasks; and six in the bioreactor. However, final biomass concentration was not similar, indicating that although the process can be scaled-up using the power input, others factors like oxygen transfer rate, tip speed or energy dissipation/circulation function can be an influence on bacterial metabolism.


Assuntos
Proteínas de Bactérias/biossíntese , Reatores Biológicos/microbiologia , Glicoproteínas/biossíntese , Microbiologia Industrial/métodos , Mycobacterium tuberculosis/genética , Streptomyces lividans/metabolismo , Proteínas de Bactérias/genética , Meios de Cultura/metabolismo , Glicoproteínas/genética , Microbiologia Industrial/instrumentação , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Streptomyces lividans/citologia , Streptomyces lividans/genética
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