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1.
Horiz. sanitario (en linea) ; 22(3): 607-613, Sep.-Dec. 2023. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1557965

ABSTRACT

Resumen Objetivo: Evaluar el impacto de una intervención educativa individualizada en los conocimientos, autocuidado de los pies, control glucémico, riesgo de ulceración e incidencia de úlceras en pacientes con diabetes tipo 2. Material y Métodos: Estudio de intervención realizado en 65 pacientes ambulatorios, mayores de 35 años, con diabetes tipo 2, distribuidos aleatoriamente en dos grupos: grupo control (35) quien recibió un manual de cuidado de los pies, y grupo intervención (30) quien recibió la intervención, un kit de cuidado de los pies y un manual. El seguimiento se realizó a los tres y seis meses después de la intervención. El análisis estadístico incluyó la prueba de Chi-cuadrado, prueba de Wilcoxon y prueba ANOVA de mediciones repetidas. Resultados: La intervención mejoró los conocimientos y el autocuidado de pies en el grupo de intervención, con diferencias significativas entre grupos (p=.001), pero no mejoró el control glucémico ni el riesgo de ulceración. Conclusiones: El programa "tus pies te llaman" fue efectivo parcialmente, este estudio puede ser replicado en instituciones de primer nivel de forma ordinaria para mejorar el autocuidado y prevenir la ulceración del pie a mediano plazo.


Abstract Objective: To evaluate the impact of an individualized educational intervention on knowledge, self-care of the feet, glycemic control, risk of ulceration and incidence of ulcers in patients with type 2 diabetes. Material and Methods: The intervention study, was carried out on 65 outpatients, over 35 years of age, with type 2 diabetes, patients were randomly distributed into two groups: the control group (35), who received a manual on foot care, and the intervention group (30), who received the intervention, a foot care kit, and manual. Follow-up was done at three and six months after the intervention. Statistical analysis included the Chi-square test, Wilcoxon test and the ANOVA test of repeated measures. Results: The intervention improved knowledge and foot self-care in the intervention group with significant differences between groups (p=.001), but not the glycemic control or the ulceration risk. Conclusions: The program "Your Feet Call You" was partially effective, and this study can be ordinarily replicated in first-level institutions to improve self-care and prevent foot ulceration in the medium term.

2.
Article in English | MEDLINE | ID: mdl-37770135

ABSTRACT

Duplex sequencing (DS) is an error-corrected next-generation sequencing method in which molecular barcodes informatically link PCR-copies back to their source DNA strands, enabling computational removal of errors in consensus sequences. The resulting background of less than one artifactual mutation per 107 nucleotides allows for direct detection of somatic mutations. TwinStrand Biosciences, Inc. has developed a DS-based mutagenesis assay to sample the rat genome, which can be applied to genetic toxicity testing. To evaluate this assay for early detection of mutagenesis, a time-course study was conducted using male Hsd:Sprague Dawley SD rats (3 per group) administered a single dose of 40 mg/kg N-ethyl-N-nitrosourea (ENU) via gavage, with mutation frequency (MF) and spectrum analyzed in stomach, bone marrow, blood, and liver tissues at 3 h, 24 h, 7 d, and 28 d post-exposure. Significant increases in MF were observed in ENU-exposed rats as early as 24 h for stomach (site of contact) and bone marrow (a highly proliferative tissue) and at 7 d for liver and blood. The canonical, mutational signature of ENU was established by 7 d post-exposure in all four tissues. Interlaboratory analysis of a subset of samples from different tissues and time points demonstrated remarkable reproducibility for both MF and spectrum. These results demonstrate that MF and spectrum can be evaluated successfully by directly sequencing targeted regions of DNA obtained from various tissues⁠, a considerable advancement compared to currently used in vivo gene mutation assays.


Subject(s)
Ethylnitrosourea , Nitrosourea Compounds , Rats , Male , Animals , Ethylnitrosourea/toxicity , Reproducibility of Results , Rats, Sprague-Dawley , Mutagenesis , Mutation , Mutagens/toxicity
3.
Article in English | MEDLINE | ID: mdl-37491114

ABSTRACT

Error-corrected duplex sequencing (DS) enables direct quantification of low-frequency mutations and offers tremendous potential for chemical mutagenicity assessment. We investigated the utility of DS to quantify induced mutation frequency (MF) and spectrum in human lymphoblastoid TK6 cells exposed to a prototypical DNA alkylating agent, N-ethyl-N-nitrosourea (ENU). Furthermore, we explored appropriate experimental parameters for this application, and assessed inter-laboratory reproducibility. In two independent experiments in two laboratories, TK6 cells were exposed to ENU (25-200 µM) and DNA was sequenced 48, 72, and 96 h post-exposure. A DS mutagenicity panel targeting twenty 2.4-kb regions distributed across the genome was used to sample diverse, genome-representative sequence contexts. A significant increase in MF that was unaffected by time was observed in both laboratories. Concentration-response in the MF from the two laboratories was strongly positively correlated (r = 0.97). C:G>T:A, T:A>C:G, T:A>A:T, and T:A>G:C mutations increased in consistent, concentration-dependent manners in both laboratories, with high proportions of C:G>T:A at all time points. The consistent results across the three time points suggest that 48 h may be sufficient for mutation analysis post-exposure. The target sites responded similarly between the two laboratories and revealed a higher average MF in intergenic regions. These results, demonstrating remarkable reproducibility across time and laboratory for both MF and spectrum, support the high value of DS for characterizing chemical mutagenicity in both research and regulatory evaluation.


Subject(s)
DNA , Mutagens , Humans , Reproducibility of Results , Mutation , Mutagens/toxicity , Mutagenesis , Ethylnitrosourea
4.
bioRxiv ; 2023 May 09.
Article in English | MEDLINE | ID: mdl-37214853

ABSTRACT

Duplex sequencing (DuplexSeq) is an error-corrected next-generation sequencing (ecNGS) method in which molecular barcodes informatically link PCR-copies back to their source DNA strands, enabling computational removal of errors by comparing grouped strand sequencing reads. The resulting background of less than one artifactual mutation per 10 7 nucleotides allows for direct detection of somatic mutations. TwinStrand Biosciences, Inc. has developed a DuplexSeq-based mutagenesis assay to sample the rat genome, which can be applied to genetic toxicity testing. To evaluate this assay for early detection of mutagenesis, a time-course study was conducted using male Hsd:Sprague Dawley SD rats (3 per group) administered a single dose of 40 mg/kg N-ethyl-N-nitrosourea (ENU) via gavage, with mutation frequency (MF) and spectrum analyzed in stomach, bone marrow, blood, and liver tissues at 3 h, 24 h, 7 d, and 28 d post-exposure. Significant increases in MF were observed in ENU-exposed rats as early as 24 h for stomach (site of contact) and bone marrow (a highly proliferative tissue) and at 7 d for liver and blood. The canonical, mutational signature of ENU was established by 7 d post-exposure in all four tissues. Interlaboratory analysis of a subset of samples from different tissues and time points demonstrated remarkable reproducibility for both MF and spectrum. These results demonstrate that MF and spectrum can be evaluated successfully by directly sequencing targeted regions of DNA obtained from various tissues, a considerable advancement compared to currently used in vivo gene mutation assays. HIGHLIGHTS: DuplexSeq is an ultra-accurate NGS technology that directly quantifies mutationsENU-dependent mutagenesis was detected 24 h post-exposure in proliferative tissuesMultiple tissues exhibited the canonical ENU mutation spectrum 7 d after exposureResults obtained with DuplexSeq were highly concordant between laboratoriesThe Rat-50 Mutagenesis Assay is promising for applications in genetic toxicology.

5.
Int J Oncol ; 52(1): 47-54, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29115565

ABSTRACT

Glioblastoma multiforme (GBM) is one of the most common primary malignant brain tumors. Unraveling the molecular and genetic complexity that determines GBM's pronounced migratory property could provide new options for therapeutic targeting that may significantly complement current surgical and chemoradiation therapy and alter the current poor outcome. In this study, we establish stable AJAP1 overexpressing glioma cells in order to examine in vivo tumor growth. We examine AJAP1 localization by confocal microscopy and AJAP1's functional effect on migration and invasion across surfaces coated with laminin. Finally, analysis of AJAP1 expression in murine xenografts and GBM primary tumors revealed its association with tumor growth and survival. Stable overexpression of AJAP1 promotes adherence, decreases invasion of glioma cells through an extracellular-like matrix, and slows migration in the presence of laminin. These observations are reversed by gene knockdown using multiple siRNAs. Additionally, overexpression of AJAP1 decreases colony formation in glioma cells, and leads to smaller tumor growth with increased survival in glioma xenograft mice. Loss of AJAP1 protein expression predicts worse survival in GBM patients. AJAP1 overexpression decreases cell motility in the presence of laminin and decreases tumor growth in xenografts. Its loss of expression predicts worse survival in patients. This study extends our prior observations and implicates AJAP1 as a potential prognostic marker and a viable target for therapeutic intervention in GBM.


Subject(s)
Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cell Adhesion Molecules/biosynthesis , Cell Movement/physiology , Glioblastoma/metabolism , Glioblastoma/pathology , Animals , Apoptosis/physiology , Brain Neoplasms/genetics , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/metabolism , Cell Growth Processes/physiology , Cell Membrane/metabolism , Gene Knockdown Techniques , Glioblastoma/genetics , Heterografts , Humans , Mice , Neoplasm Invasiveness , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/genetics
6.
Cad. Ter. Ocup. UFSCar (Impr.) ; 24(3): [639-650], jul.-set. 2016.
Article in English, Spanish | LILACS | ID: biblio-827491

ABSTRACT

Introducción: Este artículo versa sobre la experiencia de un taller de teatro realizado durante el año 2011 en una Escuela Hospitalaria, para niños y niñas con diversas condiciones de salud. El trabajo se convirtió en una posibilidad de difusión del arte como herramienta terapéutica y una invitación para reflexionar sobre la discapacidad y sus limitaciones reales y/o construidas simbólicamente. La problemática central se focalizó en la identificación de presencia de Factores de Riesgo Ocupacional y Apartheid Ocupacional, en el desempeño escolar de niños y niñas de la escuela Hospitalaria y de la autora. Se plantea que algunos de estos, eran provocados por elementos ambientales como también por construcciones simbólico-sociales generadas en torno a la idea de discapacidad. Objetivo: Describir el impacto que genera el uso de un taller de teatro como medio terapéutico en una escuela hospitalaria. Método: La metodología idónea fue autoetnográfica, que valida la experiencia de la investigadora como fuente de información. Desarrollo: Se analizan teóricamente las ideas sobre los Factores de Riesgo Ocupacional y Apartheid Ocupacional, además de los conceptos desarrollados a través del taller y utilizados para el combate de las condiciones adversas. Conclusion: Es necesario que todos experimentemos en nuestros diferentes contextos espacios de "no evaluación" y libertad para el uso, disfrute y despliegue de todas nuestras habilidades. Tener certeza que el cuerpo guarda las vivencias lo que potenciará esa alma resiliente que todos merecemos tener y abrirá camino a la posibilidad de destruir nuestras condiciones determinantes.


Introdução: Este artigo versa sobre a experiência de uma oficina de teatro realizada durante o ano de 2011, em um Hospital Escola, para crianças em diferentes condições de saúde. O trabalho converteu-se numa possibilidade de difusão da arte como ferramenta terapêutica e um convite para refletir sobre as pessoas em situação de deficiência e suas limitações reais e/ou construídas simbolicamente. A problemática central focaliza a identificação de Fatores de Risco Ocupacional e o Apartheid Ocupacional no desempenho escolar de crianças em um Hospital Escola e da autora. Observaram-se problemas provocados por elementos ambientais e também por construções simbólico-sociais geradas em torno da ideia de "deficientes". Objetivo: Descrever o impacto de uma oficina de teatro como meio terapêutico, em um Hospital Escola. Método: A metodologia aplicada foi a autoetnografia, que valida a experiência da pesquisadora como fonte de informação. Resultados: Analisaram-se teoricamente as ideias sobre os Fatores de Risco Ocupacional e o Apartheid Ocupacional, além dos conceitos desenvolvidos através da oficina e utilizados para o combate das condições adversas. Conclusão: É necessário que experimentemos, em nossos diferentes contextos, espaços que propiciem o "não avaliar" e a liberdade para o uso, o prazer e a manifestação de todas as nossas habilidades. Ter a certeza de que o corpo guarda as vivências que potenciarão a alma resiliente, que todos merecemos ter, e de que tais vivências abrirão caminho para a possibilidade de destruir nossas condições determinantes.


Introduction: This article recounts the experience of a theater workshop conducted in a hospital school with children under diverse health conditions in 2011. The work became a possibility of art diffusion as a therapeutic tool and an invitation to reflect on disability and its real and/or symbolically constructed limitations. The central problem focused on identifying the presence of Occupational Risk Factors and Occupational Apartheid in the school achievement of the hospital school children and the author. Problems caused by environmental elements as well as by symbolic-social constructions generated by the idea of disability were observed. Objective: To describe the impact generated by a theater workshop as a therapeutic means in a children's hospital school environment. Method: The autoethnographic methodology was chosen to validate the experience of the investigator as a source of information. Results: The ideas on Occupational Risk Factors, Occupational Apartheid, as well as the concepts developed in the workshop and those used to combat adverse conditions were theoretically analyzed. Conclusion: It is necessary that we experiment contexts that enable spaces free of evaluation and the freedom to use, enjoy and express all our abilities. We must be certain that the body keeps track of past experiences that potentialize the resilience of the soul, which we all deserve to have and which opens the path to the possibility of destroying our predetermined conditions.

7.
J Comp Neurol ; 523(6): 892-906, 2015 Apr 15.
Article in English | MEDLINE | ID: mdl-25424606

ABSTRACT

Only a few distantly related mammals and birds have the trait of complex vocal learning, which is the ability to imitate novel sounds. This ability is critical for speech acquisition and production in humans, and is attributed to specialized forebrain vocal control circuits that have several unique connections relative to adjacent brain circuits. As a result, it has been hypothesized that there could exist convergent changes in genes involved in neural connectivity of vocal learning circuits. In support of this hypothesis, expanding on our related study (Pfenning et al. [2014] Science 346: 1256846), here we show that the forebrain part of this circuit that makes a relatively rare direct connection to brainstem vocal motor neurons in independent lineages of vocal learning birds (songbird, parrot, and hummingbird) has specialized regulation of axon guidance genes from the SLIT-ROBO molecular pathway. The SLIT1 ligand was differentially downregulated in the motor song output nucleus that makes the direct projection, whereas its receptor ROBO1 was developmentally upregulated during critical periods for vocal learning. Vocal nonlearning bird species and male mice, which have much more limited vocal plasticity and associated circuits, did not show comparable specialized regulation of SLIT-ROBO genes in their nonvocal motor cortical regions. These findings are consistent with SLIT and ROBO gene dysfunctions associated with autism, dyslexia, and speech sound language disorders and suggest that convergent evolution of vocal learning was associated with convergent changes in the SLIT-ROBO axon guidance pathway.


Subject(s)
Axons/physiology , Brain/anatomy & histology , Gene Expression Regulation/physiology , Glycoproteins/metabolism , Learning/physiology , Nerve Tissue Proteins/metabolism , Receptors, Immunologic/metabolism , Vocalization, Animal/physiology , Age Factors , Animals , Birds/physiology , Female , Glycoproteins/genetics , Male , Mice , Mice, Inbred C57BL , Nerve Tissue Proteins/genetics , Neurons/cytology , RNA, Messenger/metabolism , Receptors, Immunologic/genetics , Roundabout Proteins
8.
Science ; 346(6215): 1256846, 2014 Dec 12.
Article in English | MEDLINE | ID: mdl-25504733

ABSTRACT

Song-learning birds and humans share independently evolved similarities in brain pathways for vocal learning that are essential for song and speech and are not found in most other species. Comparisons of brain transcriptomes of song-learning birds and humans relative to vocal nonlearners identified convergent gene expression specializations in specific song and speech brain regions of avian vocal learners and humans. The strongest shared profiles relate bird motor and striatal song-learning nuclei, respectively, with human laryngeal motor cortex and parts of the striatum that control speech production and learning. Most of the associated genes function in motor control and brain connectivity. Thus, convergent behavior and neural connectivity for a complex trait are associated with convergent specialized expression of multiple genes.


Subject(s)
Brain/physiology , Finches/genetics , Finches/physiology , Gene Expression Regulation , Learning , Speech , Transcriptome , Vocalization, Animal , Adult , Animals , Birds/genetics , Birds/physiology , Brain/anatomy & histology , Brain Mapping , Corpus Striatum/anatomy & histology , Corpus Striatum/physiology , Evolution, Molecular , Humans , Male , Motor Cortex/anatomy & histology , Motor Cortex/physiology , Neural Pathways , Species Specificity , Transcription, Genetic
9.
Enferm. clín. (Ed. impr.) ; 24(6): 339-344, nov.-dic. 2014. tab
Article in Spanish | IBECS | ID: ibc-131187

ABSTRACT

OBJETIVO: Los pacientes ostomizados enfrentan una serie de problemas que impactan negativamente en su bienestar personal. El objetivo de este trabajo es determinar la naturaleza e intensidad de la relación entre el nivel de adaptación del modo autoconcepto y la capacidad de uso consistente de estrategias de afrontamiento de los adultos mayores ostomizados. Metodología Cuantitativo, correlacional y transversal. Se aplicaron los instrumentos VIVEROS 03 y CAPS en 3 hospitales de la Ciudad de Durango, México. El estudio incluyó a 90 adultos mayores con un estoma de eliminación intestinal con complicaciones. Se utilizó el estadístico no paramétrico Tau-b de Kendall para medir esta asociación. RESULTADOS: La mayoría de los adultos estudiados (61,3 < % < 79,9) no se encuentran completamente adaptados a la condición de vivir con un estoma intestinal. Asimismo, existe una correlación positiva moderada (0,569) entre el nivel de adaptación en el modo de autoconcepto de los adultos mayores con estoma y el uso consistente de estrategias de afrontamiento. CONCLUSIONES: La presencia de un estoma intestinal representa un problema de salud físico y emocional que se refleja en el nivel de adaptación de la autoimagen. Los adultos mayores ostomizados emplean solo una pequeña parte de sus mecanismos de defensa como parte del proceso de afrontamiento. Lo anterior limita su capacidad para encarar las adversidades relacionadas con su condición, generando potencialmente mayores complicaciones a su salud


OBJECTIVE: Ostomy patients face a number of problems that impact negatively on their personal welfare. The aim of this research is determine the nature and intensity of the relationship between the level of self-concept adaptive mode and the consistent use of coping strategies of older adults with a stoma. Methodology Quantitative, correlational and transversal. VIVEROS 03 and CAPS surveys were applied in 3 hospitals in the City of Durango, México. The study included 90 older adults with an intestinal elimination stoma with complications. Kendall's Tau-b coefficient was the non-parametric test used to measure this association. RESULTS: Most older adults analyzed (61.3 < % < 79.9) are not completely adapted to the condition of living with an intestinal stoma. There is also a moderate positive correlation (0,569) between the level of adaptation of the older adults with a stoma and the conscious use of coping strategies. CONCLUSIONS: The presence of an intestinal stoma represents a physical and psychological health problem that is reflected in the level of adaptation of the self-image. Elderly people with a stoma use only a small part of defense mechanisms as part of coping process. This limits their ability to face the adversities related to their condition, potentially causing major health complications


Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Self Concept , Surgical Stomas/adverse effects , Adaptation, Psychological , Aging , Risk Factors , Depression/epidemiology
10.
Enferm Clin ; 24(6): 339-44, 2014.
Article in Spanish | MEDLINE | ID: mdl-25240989

ABSTRACT

OBJECTIVE: Ostomy patients face a number of problems that impact negatively on their personal welfare. The aim of this research is determine the nature and intensity of the relationship between the level of self-concept adaptive mode and the consistent use of coping strategies of older adults with a stoma. METHODOLOGY: Quantitative, correlational and transversal. VIVEROS 03 and CAPS surveys were applied in 3 hospitals in the City of Durango, México. The study included 90 older adults with an intestinal elimination stoma with complications. Kendall's Tau-b coefficient was the non-parametric test used to measure this association. RESULTS: Most older adults analyzed (61.3 < % < 79.9) are not completely adapted to the condition of living with an intestinal stoma. There is also a moderate positive correlation (0,569) between the level of adaptation of the older adults with a stoma and the conscious use of coping strategies. CONCLUSIONS: The presence of an intestinal stoma represents a physical and psychological health problem that is reflected in the level of adaptation of the self-image. Elderly people with a stoma use only a small part of defense mechanisms as part of coping process. This limits their ability to face the adversities related to their condition, potentially causing major health complications.


Subject(s)
Adaptation, Psychological , Defense Mechanisms , Enterostomy/psychology , Self Concept , Aged , Cross-Sectional Studies , Enterostomy/adverse effects , Female , Humans , Male
11.
Int J Oncol ; 45(1): 13-7, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24807315

ABSTRACT

In a broad range of human cancers 1p36 has been a mutational hotspot which strongly suggests that the loss of tumor suppressor activity maps to this genomic region during tumorigenesis. Adherens junctional associated protein-1 (AJAP1; also known as Shrew1) was initially discovered as a novel transmembrane protein of adherent junctions in epithelial cells. Gene profiling showed AJAP1 on 1p36 is frequently lost or epigenetically silenced. AJAP1 may affect cell motility, migration, invasion and proliferation by unclear mechanisms. AJAP1 may be translocated to the nucleus, via its interaction with ß-catenin complexes, where it can regulate gene transcription, then possibly have a potent impact on cell cycling and apoptosis. Significantly, loss of AJAP1 expression predicts poor clinical outcome of patients with malignant gliomas such as GBM and it may serve as a promising tumor suppressor-related target. In this review, we summarize and discuss current knowledge that may identify AJAP1 as a tumor suppressor in gliomas.


Subject(s)
Cell Adhesion Molecules/genetics , Glioma/genetics , Glioma/pathology , Cell Adhesion Molecules/metabolism , Chromosomes, Human, Pair 1/metabolism , Epigenesis, Genetic , Gene Deletion , Gene Silencing , Humans , Mutation , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism
12.
CNS Neurosci Ther ; 20(5): 429-37, 2014 May.
Article in English | MEDLINE | ID: mdl-24483339

ABSTRACT

AIMS: Down-regulation of AJAP1 in glioblastoma multiforme (GBM) has been reported. However, the expression profiles of AJAP1 in gliomas and the underlying mechanisms of AJAP1 function on invasion are still poorly understood. METHODS: The gene profiles of AJAP1 in glioma patients were studied among four independent cohorts. Confocal imaging was used to analyze the AJAP1 localization. After AJAP1 overexpression in GBM cell lines, cellular polarity, cytoskeleton distribution, and antitumor effect were investigated in vitro and in vivo. RESULTS: AJAP1 expression was significantly decreased in gliomas compared with normal brain in REMBRANDT and CGCA cohorts. Additionally, low AJAP1 expression was associated with worse survival in GBMs in REMBRANDT and TCGA U133A cohorts and was significantly associated with classical and mesenchymal subtypes of GBMs among four cohorts. Confocal imaging indicated AJAP1 localized in cell membranes in low-grade gliomas and AJAP1-overexpressing GBM cells, but difficult to assess in high-grade gliomas due to its absence. AJAP1 overexpression altered the cytoskeleton and cellular polarity in vitro and inhibited the tumor growth in vivo. CONCLUSIONS: AJAP1 is dysregulated at an early stage of gliomagenesis and may suppress glioma cell invasion and proliferation, which suggests that AJAP1 may be a potential diagnostic and prognostic marker for gliomas.


Subject(s)
Brain Neoplasms/metabolism , Brain/metabolism , Cell Adhesion Molecules/metabolism , Cytoskeleton/metabolism , Glioma/metabolism , Animals , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Membrane/metabolism , Cell Membrane/ultrastructure , Cohort Studies , Cytoskeleton/ultrastructure , Disease Progression , Down-Regulation , Gene Expression Regulation, Neoplastic , Glioma/genetics , Glioma/pathology , Humans , Kaplan-Meier Estimate , Mice, Nude , Microscopy, Confocal , Neoplasm Staging , Neoplasm Transplantation
13.
Int J Oncol ; 44(4): 1243-51, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24481586

ABSTRACT

Previous studies identified the frequent loss of adherens junction-associated protein 1 (AJAP1) expression in glioblastoma (GBM) and its correlation with worse survival. AJAP1 may suppress glioma cell migration, which plays an important role in tumor progression in malignant gliomas such as GBM. However, the role of AJAP1 in cell cycle arrest or apoptosis and resistance to chemotherapy remains unclear. Based on microarray screening results, quantitative PCR and luciferase plasmid reporter constructs were used to evaluate the possible regulatory role of AJAP1 on MAGEA2 expression and function. Cell death assays, TUNEL and other markers of apoptosis were utilized to detect cell apoptosis. Restoration of AJAP1 expression in glioma cells was analyzed after temozolomide exposure. AJAP1 suppressed the expression of MAGEA2 and inhibited the transcriptional activity of MAGEA2 in glioma cells. As AJAP1 expression decreased MAGEA2 protein expression apoptosis increased moderately. Consistent with increased cell death, the induced loss of MAGEA2 expression correlated with increased caspase 3/7 activity, BCL2/BAX ratio and TUNEL signal. AJAP1 expression enhanced cell death in the presence of temozolomide. This study suggests AJAP1 may also function as a pro-apoptotic factor and potentiate cell death by temozolomide in glioma cells. This effect may be partially explained by AJAP1-mediated gene regulation of MAGEA2.


Subject(s)
Apoptosis/genetics , Brain Neoplasms/pathology , Cell Adhesion Molecules/genetics , Glioblastoma/pathology , Melanoma-Specific Antigens/biosynthesis , Neoplasm Proteins/biosynthesis , Adherens Junctions , Antineoplastic Agents, Alkylating/pharmacology , Apoptosis/drug effects , Brain Neoplasms/drug therapy , Caspase 3/metabolism , Caspase 7/metabolism , Cell Cycle Checkpoints , Cell Line, Tumor , Cell Movement , Dacarbazine/analogs & derivatives , Dacarbazine/pharmacology , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Glioblastoma/drug therapy , HEK293 Cells , Histone Deacetylases/metabolism , Humans , In Situ Nick-End Labeling , Temozolomide , Transcription, Genetic , Tumor Suppressor Protein p53/biosynthesis , bcl-2-Associated X Protein/biosynthesis
14.
J Comp Neurol ; 521(16): 3614-65, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23818122

ABSTRACT

Based on quantitative cluster analyses of 52 constitutively expressed or behaviorally regulated genes in 23 brain regions, we present a global view of telencephalic organization of birds. The patterns of constitutively expressed genes revealed a partial mirror image organization of three major cell populations that wrap above, around, and below the ventricle and adjacent lamina through the mesopallium. The patterns of behaviorally regulated genes revealed functional columns of activation across boundaries of these cell populations, reminiscent of columns through layers of the mammalian cortex. The avian functionally regulated columns were of two types: those above the ventricle and associated mesopallial lamina, formed by our revised dorsal mesopallium, hyperpallium, and intercalated hyperpallium; and those below the ventricle, formed by our revised ventral mesopallium, nidopallium, and intercalated nidopallium. Based on these findings and known connectivity, we propose that the avian pallium has four major cell populations similar to those in mammalian cortex and some parts of the amygdala: 1) a primary sensory input population (intercalated pallium); 2) a secondary intrapallial population (nidopallium/hyperpallium); 3) a tertiary intrapallial population (mesopallium); and 4) a quaternary output population (the arcopallium). Each population contributes portions to columns that control different sensory or motor systems. We suggest that this organization of cell groups forms by expansion of contiguous developmental cell domains that wrap around the lateral ventricle and its extension through the middle of the mesopallium. We believe that the position of the lateral ventricle and its associated mesopallium lamina has resulted in a conceptual barrier to recognizing related cell groups across its border, thereby confounding our understanding of homologies with mammals.


Subject(s)
Birds/anatomy & histology , Cerebrum/anatomy & histology , Cerebrum/metabolism , Nerve Tissue Proteins/metabolism , Animals , Cell Count , Gene Expression , Imaging, Three-Dimensional , Nerve Tissue Proteins/genetics , Neuroimaging , Neurons/metabolism , Species Specificity
15.
PLoS One ; 7(1): e29457, 2012.
Article in English | MEDLINE | ID: mdl-22238614

ABSTRACT

Spoken language and learned song are complex communication behaviors found in only a few species, including humans and three groups of distantly related birds--songbirds, parrots, and hummingbirds. Despite their large phylogenetic distances, these vocal learners show convergent behaviors and associated brain pathways for vocal communication. However, it is not clear whether this behavioral and anatomical convergence is associated with molecular convergence. Here we used oligo microarrays to screen for genes differentially regulated in brain nuclei necessary for producing learned vocalizations relative to adjacent brain areas that control other behaviors in avian vocal learners versus vocal non-learners. A top candidate gene in our screen was a calcium-binding protein, parvalbumin (PV). In situ hybridization verification revealed that PV was expressed significantly higher throughout the song motor pathway, including brainstem vocal motor neurons relative to the surrounding brain regions of all distantly related avian vocal learners. This differential expression was specific to PV and vocal learners, as it was not found in avian vocal non-learners nor for control genes in learners and non-learners. Similar to the vocal learning birds, higher PV up-regulation was found in the brainstem tongue motor neurons used for speech production in humans relative to a non-human primate, macaques. These results suggest repeated convergent evolution of differential PV up-regulation in the brains of vocal learners separated by more than 65-300 million years from a common ancestor and that the specialized behaviors of learned song and speech may require extra calcium buffering and signaling.


Subject(s)
Birds/genetics , Brain/metabolism , Learning/physiology , Parvalbumins/genetics , Vocalization, Animal/physiology , Animals , Birds/anatomy & histology , Birds/metabolism , Birds/physiology , Brain/anatomy & histology , Brain/physiology , Brain Mapping/veterinary , Gene Expression Regulation , Humans , Macaca/anatomy & histology , Macaca/genetics , Macaca/metabolism , Microarray Analysis , Models, Biological , Parrots/anatomy & histology , Parrots/genetics , Parrots/metabolism , Parvalbumins/metabolism , Phylogeny , Quail/anatomy & histology , Quail/genetics , Quail/metabolism , Songbirds/anatomy & histology , Songbirds/genetics , Songbirds/metabolism
16.
rev. cuid. (Bucaramanga. 2010) ; 3(1): 287-292, ene.-dic. 2012. tab, graf
Article in Spanish | LILACS, BDENF - Nursing | ID: biblio-870018

ABSTRACT

Introducción: El dolor es definido como una experiencia sensorial o emocional desagradable, asociada a daño real o potencial, es la experiencia humana más compleja y pese a la importancia de este síntoma es frecuentemente infravalorado. Objetivo: Describir como es el manejo del dolor que ofrece el personal de enfermería al paciente pediátrico postquirúrgico de apendicetomía Materiales y Métodos: Estudio descriptivo-transversal, exploratorio, con metodología cuantitativo, se utilizó un Instrumento semi-estructurado que se aplicó al personal de enfermeras que laboran en el área de pediatría en un hospital de segundo nivel en la ciudad de Durango, dicho instrumento consta de siete reactivos. Resultados: El 55% de la muestra solo utiliza la ministración de analgésicos como acción dependiente para manejar el dolor, mientras que el (45%) además realiza otras intervenciones independientes como parte del cuidado de enfermería. Del 45% de las enfermeras que realizan otras intervenciones se obtuvieron los siguientes resultados: apoyo emocional (56%), cambio de posición (22%), manejo ambiental (11%) y escala analgésica de la Organización Mundial de la Salud (11%). Discusión: En los resultados obtenidos no se reflejó de manera clara que entre mayor nivel académico más intervenciones propias de enfermería se realizarían para proporcionar alivio al dolor, para que este manejo sea más efectivo, algunos autores coinciden con nuestros resultados ya que a pesar de que se siguen algunas pautas para el manejo del dolor posquirúrgico, es necesario también cambiar de conductas. Conclusiones: Expuesto lo anterior se adjudica la necesidad de elaborar un modelo innovador en el cual las enfermeras en el servicio de pediatría apliquen intervenciones independientes propias de enfermería, con el objetivo de mejorar la calidad en la atención en el manejo del dolor en pacientes postquirúrgicos de apendicectomía.


Introduction: Pain is defined as an unpleasant sensory or emotional experience associated with actual or potential harm is more complex human experience, and despite the importance of this symptom is often underestimated. Objective: Describe how pain management is offered by the nursing staff of the pediatric patient after surgery appendectomy. Materials and Methods: Descriptive, no experimental, exploratory, quantitative approach, we used a semi-structured instrument that was applied to staff nurses working in the area of pediatrics at a second level hospital in the city of Durango, this instrument consists of seven items. Results: 55% of the sample only uses the ministry as dependent action of analgesics to manage pain, while (45%) also performed other independent operations as part of nursing care. 45% of nurses engaged in other interventions yielded the following results: emotional support (56%), position change (22%), environmental management (11%) and the OMS analgesic ladder (11%). Discussion: The results obtained are not clearly reflect that the higher academic level more typical of nursing interventions would be made to provide pain relief, so that more effective management, some authors are agree with our results because, although they are some guidelines for postoperative pain management is also necessary to change behavior. Conclusions: Exposed above the need to develop an innovative model in which nurses in the pediatric ward apply its own independent nursing interventions, in order to improve the quality of care in the management of postoperative pain in patient’s appendectomy.


Subject(s)
Humans , Appendectomy , Nursing Care , Pain, Postoperative , Pediatrics
17.
Invest Clin ; 52(3): 239-51, 2011 Sep.
Article in Spanish | MEDLINE | ID: mdl-21950195

ABSTRACT

Systemic diseases affect skeletal muscle, and inflammation and oxidative stress are some of the involved mechanisms. There is scarce information about the effects of essential hypertension on skeletal muscle. The soleus and extensor digitorum longus (EDL) muscles of spontaneously hypertensive rats (SHR) were studied compared to control Wistar Kyoto (WKY) rats. The levels of nitrite and nitrate in micromol/mg-protein; endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) nitric oxide synthases, nitrotyrosine and tumour necrosis factor alpha (TNF-alpha) in ng/mg-protein were determined. Compared with controls, the SHR showed increased levels of nitrotyrosine (soleus 24.4 +/- 5.0 vs. 3.3 +/- 0.3, p<0.001; EDL 20.2 +/- 4.3 vs. 4.5 +/- 0.4, p<0.0037), iNOS (soleus 26.6 +/- 3.7 vs. 8.3 +/- 0.9; EDL 21.3 +/- 3.7 vs. 11.0 +/- 0.8, both p<0.0001) and TNF-alpha (soleus 2.2 +/- 0.5 vs. 0.6 +/- 0.1, p<0.05; EDL 1.9 +/- 0.2 vs. 0.6 +/- 0.1, p<0.02). A decrease of eNOS was found in soleus muscle (20.6 +/- 1.4 vs. 30.3 +/- 1.2, p<0.00001); of nNOS (soleus 16.8 +/- 1.4 vs. 20.7 +/- 1.8, p< 0.05; EDL 13.6 +/- 1.3 vs. 21.9 +/- 1.8, p<.005) and nitrite in EDL (5.8 +/- 0.3 vs. 7.1 +/- 0.5, p<0.026).There was a positive correlation between TNF-alpha vs. nitrotyrosine in soleus (r=0.798; p<0.031) and a tendency in EDL (r=0.739; p=0.059); iNOS vs. nitrotyrosine (soleus: r=0.908; p<0.0001; EDL: r=0.707; p<0.01), a tendency between TNF-alpha and iNOS (EDL: r=0.736; p<0.059); and a negative correlation between eNOS vs. nitrotyrosine in soleus muscle (r=-0.816; p<0.0012). In conclusion, in skeletal muscles of SHR an inflammatory process was found evidenced by the increase in TNF-alpha, nitrotyrosine and iNOS. The decreased levels of constitutive synthases, together with the higher level of iNOS, are indicative of endothelial dysfunction.


Subject(s)
Hypertension/metabolism , Muscle, Skeletal/metabolism , Oxidative Stress , Animals , Endothelium, Vascular/physiopathology , Male , Muscle, Skeletal/chemistry , Myositis/metabolism , Nitric Oxide Synthase Type I/analysis , Nitric Oxide Synthase Type II/analysis , Nitric Oxide Synthase Type III/analysis , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Tumor Necrosis Factor-alpha/analysis , Tyrosine/analogs & derivatives , Tyrosine/analysis
18.
Invest. clín ; 52(3): 239-251, sep. 2011. ilus, tab
Article in Spanish | LILACS | ID: lil-659214

ABSTRACT

Las enfermedades sistémicas crónicas afectan el músculo esquelético, siendo la inflamación y el estrés oxidativo algunos de los mecanismos involucrados. El efecto de la hipertensión arterial esencial sobre el músculo esquelético no es bien conocido. Se estudiaron los músculos soleo y extensor digitorum longus (EDL) de ratas espontáneamente hipertensas (SHR), comparadas con las controles normotensas Wistar Kyoto (WKY). Se determinaron los niveles de nitritos y nitratos en µmoles/mg-proteína; las sintasas del óxido nítrico: endotelial (eNOS); neuronal (nNOS); e inducible (iNOS), nitrotirosina y el factor de necrosis tumoral-alfa (TNF-α) en ng/mg-proteína. En las SHR, en el soleo y el EDL respectivamente, se incrementó la nitrotirosina (24,4 ± 5,0 vs. 3,3 ± 0,3, p<0,001; 20,2 ± 4,3 vs. 4,5 ± 0,4, p<0,0037), iNOS (26,6 ± 3,7 vs. 8,3 ± 0,9; 21,3 ± 3,7 vs. 11,0 ± 0,8 ambos p<0,0001), y TNF-α (2,2 ± 0,5 vs. 0,6 ± 0,1, p<0,05; 1,9 ± 0,2 vs. 0,6 ± 0,1, p<0,02); hubo disminución de eNOS en el soleo (20,6 ± 1,4 vs. 30,3 ± 1,2, p<0,00001); de nNOS (soleo 16,8 ± 1,4 vs. 20,7 ± 1,8, p< 0,05; EDL 13,6 ± 1,3 vs. 21,9 ± 1,8, p<0,005) y de nitrito en el EDL (5,8 ± 0,3 vs. 7,1 ± 0,5, p<0,026). En las SHR se observó correlación positiva entre TNF-α vs. nitrotirosina: soleo (r=0,798; p<0,031) y tendencia en EDL (r=0,739; p<0,057); iNOS vs. nitrotirosina (soleo: r=0,908 p<0,0001; EDL: r=0,707; p=0,01), tendencia entre TNF-α vs. iNOS en EDL (r=0,736; p=0,059); y correlación negativa entre eNOS vs. nitrotirosina en soleo (r=-0,816; p=0,0012). En conclusión, las SHR presentan un proceso inflamatorio muscular, evidenciado por el incremento de TNF-α, nitrotirosina, e iNOS. La disminución de las sintasas constitutivas, con incremento de la iNOS es evidencia de la disfunción endotelial.


Systemic diseases affect skeletal muscle, and inflammation and oxidative stress are some of the involved mechanisms. There is scarce information about the effects of essential hypertension on skeletal muscle. The soleus and extensor digitorum longus (EDL) muscles of spontaneously hypertensive rats (SHR) were studied compared to control Wistar Kyoto (WKY) rats. The levels of nitrite and nitrate in µmol/mg-protein; endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) nitric oxide synthases, nitrotyrosine and tumour necrosis factor alpha (TNF-α) in ng/mg-protein were determined. Compared with controls, the SHR showed increased levels of nitrotyrosine (soleus 24.4 ± 5.0 vs. 3.3±0.3, p<0.001; EDL 20.2 ± 4.3 vs. 4.5 ± 0.4, p<0.0037), iNOS (soleus 26.6 ± 3.7 vs. 8.3 ± 0.9; EDL 21.3 ± 3.7 vs. 11.0 ± 0.8, both p<0.0001) and TNF-α (soleus 2.2 ± 0.5 vs. 0.6 ± 0.1, p<0.05; EDL 1.9 ± 0.2 vs. 0.6 ± 0.1, p<0.02). A decrease of eNOS was found in soleus muscle (20.6 ± 1.4 vs. 30.3 ± 1.2, p<0.00001); of nNOS (soleus 16.8 ± 1.4 vs. 20.7 ± 1.8, p< 0.05; EDL 13.6 ± 1.3 vs. 21.9 ± 1.8, p<0.005) and nitrite in EDL (5.8 ± 0.3 vs. 7.1 ± 0.5, p<0.026).There was a positive correlation between TNF-α vs. nitrotyrosine in soleus (r=0.798; p<0.031) and a tendency in EDL (r=0.739; p=0.059); iNOS vs. nitrotyrosine (soleus: r=0.908; p<0.0001; EDL: r=0.707; p<0.01), a tendency between TNF-α and iNOS (EDL: r=0.736; p<0.059); and a negative correlation between eNOS vs. nitrotyrosine in soleus muscle (r=-0.816; p<0.0012). In conclusion, in skeletal muscles of SHR an inflammatory process was found evidenced by the increase in TNF-α, nitrotyrosine and iNOS. The decreased levels of constitutive synthases, together with the higher level of iNOS, are indicative of endothelial dysfunction.


Subject(s)
Animals , Male , Rats , Hypertension/metabolism , Muscle, Skeletal/metabolism , Oxidative Stress , Endothelium, Vascular/physiopathology , Muscle, Skeletal/chemistry , Myositis/metabolism , Nitric Oxide Synthase Type I/analysis , Nitric Oxide Synthase Type II/analysis , Nitric Oxide Synthase Type III/analysis , Rats, Inbred SHR , Rats, Inbred WKY , Tumor Necrosis Factor-alpha/analysis , Tyrosine/analysis , Tyrosine/analogs & derivatives
19.
J Comp Neurol ; 518(14): 2873-901, 2010 Jul 15.
Article in English | MEDLINE | ID: mdl-20506480

ABSTRACT

Many immediate early genes (IEGs) have activity-dependent induction in a subset of brain subdivisions or neuron types. However, none have been reported yet with regulation specific to thalamic-recipient sensory neurons of the telencephalon or in the thalamic sensory input neurons themselves. Here, we report the first such gene, dual specificity phosphatase 1 (dusp1). Dusp1 is an inactivator of mitogen-activated protein kinase (MAPK), and MAPK activates expression of egr1, one of the most commonly studied IEGs, as determined in cultured cells. We found that in the brain of naturally behaving songbirds and other avian species, hearing song, seeing visual stimuli, or performing motor behavior caused high dusp1 upregulation, respectively, in auditory, visual, and somatosensory input cell populations of the thalamus and thalamic-recipient sensory neurons of the telencephalic pallium, whereas high egr1 upregulation occurred only in subsequently connected secondary and tertiary sensory neuronal populations of these same pathways. Motor behavior did not induce high levels of dusp1 expression in the motor-associated areas adjacent to song nuclei, where egr1 is upregulated in response to movement. Our analysis of dusp1 expression in mouse brain suggests similar regulation in the sensory input neurons of the thalamus and thalamic-recipient layer IV and VI neurons of the cortex. These findings suggest that dusp1 has specialized regulation to sensory input neurons of the thalamus and telencephalon; they further suggest that this regulation may serve to attenuate stimulus-induced expression of egr1 and other IEGs, leading to unique molecular properties of forebrain sensory input neurons.


Subject(s)
Auditory Perception/physiology , Avian Proteins/metabolism , Dual Specificity Phosphatase 1/metabolism , Motor Activity/physiology , Neurons, Afferent/metabolism , Visual Perception/physiology , Animals , Avian Proteins/genetics , Brain/metabolism , Columbidae , Dual Specificity Phosphatase 1/genetics , Early Growth Response Protein 1/genetics , Early Growth Response Protein 1/metabolism , Gene Expression Regulation , Male , Melopsittacus , Mice , Songbirds , Species Specificity , Telencephalon/metabolism , Thalamus/metabolism
20.
PLoS One ; 3(3): e1768, 2008 Mar 12.
Article in English | MEDLINE | ID: mdl-18335043

ABSTRACT

Vocal learning is a critical behavioral substrate for spoken human language. It is a rare trait found in three distantly related groups of birds-songbirds, hummingbirds, and parrots. These avian groups have remarkably similar systems of cerebral vocal nuclei for the control of learned vocalizations that are not found in their more closely related vocal non-learning relatives. These findings led to the hypothesis that brain pathways for vocal learning in different groups evolved independently from a common ancestor but under pre-existing constraints. Here, we suggest one constraint, a pre-existing system for movement control. Using behavioral molecular mapping, we discovered that in songbirds, parrots, and hummingbirds, all cerebral vocal learning nuclei are adjacent to discrete brain areas active during limb and body movements. Similar to the relationships between vocal nuclei activation and singing, activation in the adjacent areas correlated with the amount of movement performed and was independent of auditory and visual input. These same movement-associated brain areas were also present in female songbirds that do not learn vocalizations and have atrophied cerebral vocal nuclei, and in ring doves that are vocal non-learners and do not have cerebral vocal nuclei. A compilation of previous neural tracing experiments in songbirds suggests that the movement-associated areas are connected in a network that is in parallel with the adjacent vocal learning system. This study is the first global mapping that we are aware for movement-associated areas of the avian cerebrum and it indicates that brain systems that control vocal learning in distantly related birds are directly adjacent to brain systems involved in movement control. Based upon these findings, we propose a motor theory for the origin of vocal learning, this being that the brain areas specialized for vocal learning in vocal learners evolved as a specialization of a pre-existing motor pathway that controls movement.


Subject(s)
Animal Communication , Birds/physiology , Learning , Models, Theoretical , Movement , Animals , Female , Male , Species Specificity
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