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1.
Pediatr Dermatol ; 40(3): 440-445, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36716766

RESUMO

BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a locally aggressive and potentially lethal vascular tumor of infancy. Current consensus recommendations include the use of vincristine and/or systemic steroids as first-line treatment. Mammalian target of rapamycin (mTOR) inhibitors represent a promising therapy for patients with KHE. The goal of our study is to critically assess the existing literature on outcomes of patients with KHE treated with mTOR inhibitors. METHODS: We conducted a literature search from 1 January 2000, to 30 April 2022. Articles reporting outcomes of patients treated with mTOR inhibitors for KHE were included. Descriptive statistics were used to describe and summarize the outcomes of the treatment. RESULTS: We included 327 patients with a mean age at diagnosis of 9.1 months (SD ± 9). Patients were treated with an mTOR inhibitor for a mean of 15.2 months (SD ± 4.1). A total of 315 (96.3%) patients had positive outcomes including improvement of the tumor size, symptoms and/or laboratory parameters in 227 (85%) and complete remission in 38 (12%). Seven (2%) patients did not respond to treatment and seven (2%) died of sepsis (4), Kasabach-Merritt phenomenon complications (1), cardiac and liver failure due to ductus arteriosus (1), or metastatic disease (1). CONCLUSION: This systematic review supports the efficacy and safety of mTOR inhibitors for KHE. Their use resulted in positive outcomes in terms of decreased symptoms, reduction in tumor size and improvement in biochemical parameters with a mortality rate of 2%. According to these findings, we suggest revised consensus treatment guidelines for KHE with mTOR inhibitors potentially considered first-line therapy.


Assuntos
Hemangioendotelioma , Síndrome de Kasabach-Merritt , Sarcoma de Kaposi , Humanos , Lactente , Síndrome de Kasabach-Merritt/diagnóstico , Sirolimo/uso terapêutico , Inibidores de MTOR , Hemangioendotelioma/diagnóstico , Sarcoma de Kaposi/complicações , Serina-Treonina Quinases TOR/uso terapêutico
2.
Psychol Health Med ; 28(4): 938-945, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35722993

RESUMO

Self-concept has been associated with health-related behaviors and emotional self-regulation, which can improve sleep. However, its involvement in sleep quality in a healthy adolescent population has been little studied. This study evaluated the association between self-concept and sleep quality in adolescents adjusting for sleep/wake habits. The cross-sectional study included 1,751 adolescents, 54% females, with an age of M = 16.76 ± 1.04 years. The information was collected through an electronic survey that contained the Patient Health Questionnaire, Sleep Habits Questionnaire, Pittsburgh Sleep Quality Index, and Self-Concept Scale. A significant association between self-concept, adjustment for adolescents´ characteristics and sleep/wake habits was observed (R2 = .17, F = 26.61, p < .001). That is, in addition to the adolescent habits, self-concept also contributed to the explanation of sleep/wake habits. These results reinforce the idea that the self-concept can be an essential factor that contributes to better sleep quality, despite the habits of adolescents.


Assuntos
Qualidade do Sono , Transtornos do Sono-Vigília , Feminino , Humanos , Adolescente , Masculino , Estudos Transversais , Sono/fisiologia , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/psicologia , Inquéritos e Questionários
3.
Immunol Cell Biol ; 101(2): 97-103, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36006827

RESUMO

Kindness in Science is a grassroots initiative to establish a scientific community built on diversity, respect and well-being, which would ultimately lead to happier scientists and better scientific outcomes. We believe that the key areas that we can become kinder as scientists include yourself, each other, the environment and the wider community. Here, we discuss the key barriers to kindness in each of these areas, and ways we can overcome these issues to create kinder, more sustainable and harmonious research teams.

6.
Stem Cell Res ; 53: 102319, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33894548

RESUMO

The advent of cellular reprogramming technology converting somatic cells into induced pluripotent stem cells (iPSCs) has revolutionized our understandings of neurodegenerative diseases that are otherwise hard to access and model. Multiple Sclerosis (MS) is a chronic demyelinating, inflammatory disease of central nervous system eventually causing neuronal death and accompanied disabilities. Here, we report the generation of several relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) iPSC lines from MS patients along with their age matched healthy controls from peripheral blood mononuclear cells (PBMC). These patient specific iPSC lines displayed characteristic embryonic stem cell (ESC) morphology and exhibited pluripotency marker expression. Moreover, these MS iPSC lines were successfully differentiated into neural progenitor cells (NPC) after subjecting to neural induction. Furthermore, we identified the elevated expression of cellular senescence hallmarks in RRMS and PPMS neural progenitors unveiling a novel drug target avenue of MS pathophysiology. Thus, our study altogether offers both RRMS and PPMS iPSC cellular models as a good tool for better understanding of MS pathologies and drug testing.


Assuntos
Células-Tronco Pluripotentes Induzidas , Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Leucócitos Mononucleares
7.
World J Stem Cells ; 11(2): 84-99, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30842807

RESUMO

BACKGROUND: An in vitro injury model mimicking a corneal surface injury was optimised using human corneal epithelial cells (hCEC). AIM: To investigate whether corneal-stroma derived stem cells (CSSC) seeded on an amniotic membrane (AM) construct manifests an anti-inflammatory, healing response. METHODS: Treatment of hCEC with ethanol and pro-inflammatory cytokines were compared in terms of viability loss, cytotoxicity, and pro-inflammatory cytokine release, in order to generate the in vitro injury. This resulted in an optimal injury of 20% (v/v) ethanol for 30 s with 1 ng/mL interleukin-1 (IL-1) beta. Co-culture experiments were performed with CSSC alone and with CSSC-AM constructs. The effect of injury and co-culture on viability, cytotoxicity, IL-6 and IL-8 production, and IL1B, TNF, IL6, and CXCL8 mRNA expression were assessed. RESULTS: Co-culture with CSSC inhibited loss of hCEC viability caused by injury. Enzyme linked immunosorbent assay and polymerase chain reaction showed a significant reduction in the production of IL-6 and IL-8 pro-inflammatory cytokines, and reduction in pro-inflammatory cytokine mRNA expression during co-culture with CSSC alone and with the AM construct. These results confirmed the therapeutic potential of the CSSC and the possible use of AM as a cell carrier for application to the ocular surface. CONCLUSION: CSSC were shown to have a potentially therapeutic anti-inflammatory effect when treating injured hCEC, demonstrating an important role in corneal regeneration and wound healing, leading to an improved knowledge of their potential use for research and therapeutic purposes.

8.
Arq Neuropsiquiatr ; 75(3): 160-166, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28355323

RESUMO

We aimed to investigate whether infants with myelomeningocele would improve their motor ability and functional independence after ten sessions of physical therapy and compare the outcomes of conventional physical therapy (CPT) to a physical therapy program based on reflex stimulation (RPT). Twelve children were allocated to CPT (n = 6, age 18.3 months) or RPT (n = 6, age 18.2 months). The RPT involved proprioceptive neuromuscular facilitation. Children were assessed with the Gross Motor Function Measure and the Pediatric Evaluation of Disability Inventory before and after treatment. Mann-Whitney tests compared the improvement on the two scales of CPT versus RPT and the Wilcoxon test compared CPT to RPT (before vs. after treatment). Possible correlations between the two scales were tested with Spearman correlation coefficients. Both groups showed improvement on self-care and mobility domains of both scales. There were no differences between the groups, before, or after intervention. The CPT and RPT showed similar results after ten weeks of treatment.


Assuntos
Meningomielocele/reabilitação , Modalidades de Fisioterapia , Atividades Cotidianas , Feminino , Humanos , Lactente , Masculino , Distribuição Aleatória , Recuperação de Função Fisiológica , Reflexo , Índice de Gravidade de Doença , Resultado do Tratamento
9.
Arq. neuropsiquiatr ; 75(3): 160-166, Mar. 2017. tab
Artigo em Inglês | LILACS | ID: biblio-838876

RESUMO

ABSTRACT We aimed to investigate whether infants with myelomeningocele would improve their motor ability and functional independence after ten sessions of physical therapy and compare the outcomes of conventional physical therapy (CPT) to a physical therapy program based on reflex stimulation (RPT). Twelve children were allocated to CPT (n = 6, age 18.3 months) or RPT (n = 6, age 18.2 months). The RPT involved proprioceptive neuromuscular facilitation. Children were assessed with the Gross Motor Function Measure and the Pediatric Evaluation of Disability Inventory before and after treatment. Mann-Whitney tests compared the improvement on the two scales of CPT versus RPT and the Wilcoxon test compared CPT to RPT (before vs. after treatment). Possible correlations between the two scales were tested with Spearman correlation coefficients. Both groups showed improvement on self-care and mobility domains of both scales. There were no differences between the groups, before, or after intervention. The CPT and RPT showed similar results after ten weeks of treatment.


RESUMO O estudo investigou se crianças com mielomeningocele melhorariam sua habilidade motora/funcional após dez sessões de fisioterapia e comparou o quadro motor de um grupo submetido à fisioterapia convencional (FC) com outro tratado com fisioterapia com estimulação reflexa (RF). Doze crianças foram alocadas em FC (n=6, 18,3 meses de idade) ou FR (n=6, 18,2 meses de idade). FR envolveu facilitação neuromuscular proprioceptiva. As crianças foram avaliadas com a Medida de Função Motora Grossa (GMFM) e o Inventário de Avaliação Pediátrica de Incapacidade (PEDI) antes e depois do tratamento. Testes de Mann-Whitney compararam a melhora na GMFM e PEDI (FC versus FR) e testes de Wilcoxon compararam FC e FR (antes versus depois). Possíveis correlações entre GMFM e PEDI foram testadas por coeficientes de Spearman. Ambos os grupos melhoraram na GMFM e PEDI (domínios autocuidado e mobilidade). Não houve diferença entre os grupos antes e após a intervenção. FC e FR apresentaram efeitos semelhantes depois de dez semanas de tratamento.


Assuntos
Humanos , Masculino , Feminino , Lactente , Meningomielocele/reabilitação , Modalidades de Fisioterapia , Reflexo , Índice de Gravidade de Doença , Atividades Cotidianas , Distribuição Aleatória , Resultado do Tratamento , Recuperação de Função Fisiológica
10.
Toxicol In Vitro ; 36: 89-96, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27448499

RESUMO

Reconstructed human epidermis (RhE) models have been used for in vitro testing of the potential harmful effects of exposure to chemical compounds on health. In the past, skin irritation and corrosion were evaluated in animal models; however, in recent years, due to the bioethics implications of the method and, to minimize the use of experimental animals, alternative procedures have been proposed. The Organisation for Economic Co-operation and Development (OECD) in its test guidelines (TG) 431 and 439 indicates the requirements for validating new methods for the evaluation of skin corrosion and irritation, respectively. Here, we present an in-house human dermal-epidermal model, useful for the performance of these tests. Using the methods described in this work, it was possible to obtain human fibrin-based dermal-epidermal organotypic skin cultures (ORGs) displaying similar histological characteristics to native skin and expressing specific differentiation epithelial proteins. The end points to classify a substance as irritant or corrosive were cell viability evaluated by MTT assay, and cytokine release measured by BD CBA for human inflammatory cytokines. According to the MTT test, the ORGs correctly classified irritating and corrosive substances. Moreover, the cytokine release assay was difficult to interpret in the context of testing chemical hazard classification. Further experiments are needed to validate this new model for the evaluation of surfactants because the fibrin matrix was affected in the presence of these substances.


Assuntos
Cáusticos/toxicidade , Fibrina , Irritantes/toxicidade , Testes de Irritação da Pele/métodos , Pele/efeitos dos fármacos , Alternativas aos Testes com Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Fibroblastos , Humanos , Queratinócitos , Organização para a Cooperação e Desenvolvimento Econômico , Pele/metabolismo , Técnicas de Cultura de Tecidos
11.
Ann Med Surg (Lond) ; 5: 81-5, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26900456

RESUMO

BACKGROUND: Choledochal cyst (CC) is a rare congenital anomaly of the bile duct that approximately 75% of the patients are diagnosed in childhood. Without a standardized surgical procedure for the biliary reconstruction, we present our experience over the last 15 years and show the differences between the biliary reconstructions techniques in our population. METHODS: We did a retrospective hospital archive search for patients admitted to the pediatric surgery department with the diagnosis of a choledochal cyst from January 2000 to June 2015. RESULTS: We found 15 patients, of which, 1 was excluded because of missing data from the hospital record. Of the remaining 14, eight had hepaticojejunal (HY) anastomosis in Roux-en-Y, with a 25% rate of complications; six had hepatoduodenal (HD) anastomosis with a rate of complications of 16.6%. The average hospital length of stay in the group of HD vs. HY was 14 ± 1.6-days vs. 19 ± 8.2-days respectively. DISCUSSION: There are no standardized surgical reconstruction techniques of the biliary tract after the CC excision, there is literature that supports the biliary reconstruction with an HY and an HD without a distinct advantage over one or the other. CONCLUSION: In our series HD anastomosis represents a safe procedure with fewer complications than HY.

12.
Int J Surg Case Rep ; 12: 143-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26073917

RESUMO

INTRODUCTION: Gallstone ileus can be a lethal disease, rarely suspected in the clinical scenario. It represents about 25% of all bowel obstruction cases in patients older than 65. There is a classification of gallstone ileus based on the onset time: acute, subacute and chronic (Karewsky syndrome). We describe the first reported case of chronic gallstone ileus. CASE PRESENTATION: A 78-year-old female was admitted to the ER with a 15-day case of consistent bowel obstruction. The subject reported a five-year history of recurrent hospital admissions that resolved spontaneously after non-surgical management. Karewsky syndrome was diagnosed and managed with enterolithotomy. After five days of postoperative evolution the patient was discharged, and at six months follow up, no other hospital admission or relapse has been registered. DISCUSSION: The gallstone ileus diagnosis demands a higher clinical suspicion, there is no biochemical marker, and an abdominal CT is ideal for imaging-based diagnosis. There is no consensus on the optimal surgical approach. CONCLUSION: We describe the first case of Karewsky syndrome and a gastro-jejune and gastric-choledochus double fistula. We emphasize the importance of higher clinical suspicion for patients with bowel obstruction older than 65 years old and make evident that although there are not evidence-based guidelines for this treatment, enterolithotomy is a recommended approach.

13.
Metallomics ; 7(7): 1173-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25966022

RESUMO

Streptococcus pneumoniae is a human pathogen whose principal virulence factor is its capsule. This structure allows the bacterium to evade the human immune system. Treatment of infections caused by this bacterium is based on antibiotics; however, the emergence of antibiotic-resistant strains makes this task increasingly difficult. Therefore, it is necessary to investigate new therapies, such as those based on gold nanoparticles, for which unfortunately the mechanisms involved have not yet been investigated. As far as we know, this study is the first that attempts to explain how gold nanoparticles destroy the bacterium Streptococcus pneumoniae. We found that the mean particle size was an important issue, and that the effect on the bacterium was dose-dependent. Cellular growth was inhibited by the presence of the nanoparticles, as was cell viability. The pH of the bacterial growth media was acidified, but interestingly the reactive species were not affected. A transmission electron microscopy analysis revealed the presence of inclusion bodies of gold nanoparticles within the bacterium. We present the first findings that attempt to explain how gold nanoparticles lyse Gram-positive bacteria.


Assuntos
Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas/química , Streptococcus pneumoniae/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Nanopartículas Metálicas/ultraestrutura , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/citologia , Streptococcus pneumoniae/crescimento & desenvolvimento
14.
J Biomed Mater Res A ; 103(11): 3449-62, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25904210

RESUMO

Gold nanoparticles are materials with unique optical properties that have made them very attractive for numerous biomedical applications. With the increasing discovery of techniques to synthesize novel nanoparticles such as star-shaped gold nanoparticles for biomedical applications, the safety and performance of these new nanomaterials must be systematically assessed before use. In this study, gold nanostars (AuNSTs) with multibranched surface structures were synthesized, and their influence on the cytotoxicity of human skin fibroblasts and rat fat pad endothelial cells (RFPECs) were assessed and compared with that of gold nanospheres (AuNSPs) with unbranched surfaces. Results showed that the AuNSPs with diameters of approximately 61.46 nm showed greater toxicity with fibroblast cells and RFPECs compared with the synthesized AuNSTs with diameters of approximately 33.69 nm. The AuNSPs were lethal at concentrations of 40 µg/mL for both cell lines, whereas the AuNSTs were less toxic at higher concentrations (400 µg/mL). The calculated IC50 (50% inhibitory concentration) values of the AuNSPs exposed to fibroblast cells were greater at 1 and 4 days of culture (26.4 and 27.7 µg/mL, respectively) compared with the RFPECs (13.6 and 13.8 µg/mL, respectively), indicating that the AuNSPs have a greater toxicity to endothelial cells. It was proposed that possible factors that could be promoting the reduced toxicity effects of the AuNSTs to fibroblast cells and RFPECs, compared with the AuNSPs may be size, surface chemistry, and shape of the gold nanoparticles. The reduced cell toxicity observed with the AuNSTs suggests that AuNSTs may be a promising material for use in biomedical applications.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Nanosferas/química , Tecido Adiposo/citologia , Animais , Morte Celular , Proliferação de Células , Forma Celular , Células Cultivadas , Células Endoteliais/citologia , Humanos , Hidrodinâmica , Nanopartículas Metálicas/ultraestrutura , Nanosferas/ultraestrutura , Fenômenos Ópticos , Tamanho da Partícula , Ratos , Propriedades de Superfície
15.
Invest Clin ; 55(2): 133-41, 2014 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-24974629

RESUMO

The increase in lipid plasma values is an important cardiovascular risk factor. Lipoprotein lipase (LPL) plays an important role in the lipoprotein metabolism and metabolic and genetic factors may influence its levels and functions. The S447X variant of the lipoprotein lipase gene is associated with changes in plasma lipids in different populations. The objective of this research was to analyze the S447X variant of the LPL gene and its relation with plasma lipids of individuals in Zulia state, Venezuela. With this purpose, we studied 75 individuals (34 men and 41 women) between 20 and 60 years of age. Each subject had a medical history which included family history, anthropometric characteristics, nutritional status evaluation and biochemical tests. Genomic DNA was extracted for the molecular study and the polymerase chain reaction was used, followed by enzyme digestion, for restriction fragments length polymorphisms using the Hinf I enzyme. The individuals studied had normal levels of blood glucose, triglycerides, total cholesterol and low density lipoproteins (LDL-C) and slightly decreased levels of high density lipoproteins (HDL-C). The genotypic distribution of the LPL gene S447X variant in the studied population was 90.6% for the homozygous genotype SS447 and 9.4% for the heterozygote SX447. The genotype 447XX was not identified. The population was found in Hardy Weinberg genetic equilibrium. No association between the S447X polymorphism of lipoprotein lipase gene and plasma lipids was observed.


Assuntos
Lipídeos/sangue , Lipase Lipoproteica/genética , Polimorfismo de Nucleotídeo Único , Adulto , Glicemia/análise , Índice de Massa Corporal , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Insulina/análise , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Venezuela , Adulto Jovem
16.
Invest. clín ; 55(2): 133-141, jun. 2014. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-749971

RESUMO

El aumento en los valores de los lípidos sanguíneos, constituye un importante factor de riesgo cardiovascular. La lipoproteína lipasa (LPL) juega un papel importante en el metabolismo lipoproteico. Factores metabólicos y genéticos pueden influir en la función de la LPL. La variante S447X de la LPL se ha asociado con cambios en el perfil lipídico en diferentes poblaciones. El objetivo de esta investigación fue analizar la relación entre la variante S447X del gen de la LPL y lípidos plasmáticos de individuos del Estado Zulia, Venezuela. Se estudiaron 75 individuos entre 20 y 60 años, 34 hombres y 41 mujeres. A cada individuo se le realizó una historia clínica con antecedentes familiares, características antropométricas, estado nutricional y pruebas bioquímicas. Para el estudio molecular, se extrajo el ADN genómico, se utilizó la reacción en cadena de la polimerasa (RCP) seguida de digestión enzimática para polimorfismos de longitud de fragmentos de restricción utilizando la enzima Hinf I. Los individuos estudiados presentaron niveles normales de glicemia, triglicéridos, colesterol total, lipoproteínas de baja densidad (C-LDL) y niveles ligeramente disminuidos de las lipoproteínas de alta densidad (C-HDL). La distribución genotípica dela variante S447X del gen LPL fue 90,6% para el genotipo homocigoto 447SS y 9,4% para el genotipo heterocigoto 447SX; no se identificó el genotipo 447XX. La población se ajustó al equilibrio genético de Hardy Weinberg. No se encontró relación entre el polimorfismo S447X del gen LPL y los valores lipídicos plasmáticos.


The increase in lipid plasma values is an important cardiovascular risk factor. Lipoprotein lipase (LPL) plays an important role in the lipoprotein metabolism and metabolic and genetic factors may influence its levels and functions. The S447X variant of the lipoprotein lipase gene is associated with changes in plasma lipids in different populations. The objective of this research was to analyze the S447X variant of the LPL gene and its relation with plasma lipids of individuals in Zulia state, Venezuela. With this purpose, we studied 75 individuals (34 men and 41 women) between 20 and 60 years of age. Each subject had a medical history which included family history, anthropometric characteristics, nutritional status evaluation and biochemical tests. Genomic DNA was extracted for the molecular study and the polymerase chain reaction was used, followed by enzyme digestion, for restriction fragments length polymorphisms using the Hinf I enzyme. The individuals studied had normal levels of blood glucose, triglycerides, total cholesterol and low density lipoproteins (LDL-C) and slightly decreased levels of high density lipoproteins (HDL-C). The genotypic distribution of the LPL gene S447X variant in the studied population was 90.6% for the homozygous genotype SS447 and 9.4% for the heterozygote SX447. The genotype 447XX was not identified. The population was found in Hardy Weinberg genetic equilibrium. No association between the S447X polymorphism of lipoprotein lipase gene and plasma lipids was observed.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Lipídeos/sangue , Lipase Lipoproteica/genética , Polimorfismo de Nucleotídeo Único , Índice de Massa Corporal , Glicemia/análise , Análise Mutacional de DNA , Genótipo , Insulina/análise , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Venezuela
17.
Basic Clin Pharmacol Toxicol ; 112(5): 314-8, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23057752

RESUMO

Immunisation with neural-derived peptides is a promising strategy in models of spinal cord (SC) injury. Recent studies have also demonstrated that the addition of glutathione monoethyl ester (GHSE) to this strategy further improves motor recovery, tissue protection and neuronal survival after SC injury. As it is realistic to envision that this combination therapy could be tested in clinical trials, the therapeutic window should be experimentally explored before implementing its use in SC-injured human beings. For this purpose, 50 rats (10 per group) were subjected to a moderate SC contusion. The combined therapy was initiated at 10 min., 24, 72 or 120 hr after injury. Motor recovery and the survival of rubrospinal (RS) and ventral horn (VH) neurones were evaluated 60 days after injury. Results showed a significant motor improvement even if the combined therapy was initiated up to 72 hr after injury. BBB scores were as follows: 10 min.: 10.5 ± 0.7, 24 hr: 10.7 ± 0.5, 72 hr: 11.0 ± 1.3 and PBS: 6.7 ± 1 (mean ± S.D.). Initiation of combined therapy 120 hr after injury had no beneficial effect on motor recovery. Survival of RS and VH neurones was significantly higher in animals treated during the first 72 hr than those treated only with PBS. In this case again, animals treated with combined therapy 120 hr after injury did not present significant survival of neurones. Treatment with this combined strategy has a clinically feasible therapeutic window. This therapy provides enough time to transport and diagnose the patient and allows the concomitant use of other neuroprotective therapies.


Assuntos
Glutationa/análogos & derivados , Atividade Motora/efeitos dos fármacos , Proteína Básica da Mielina/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Traumatismos da Medula Espinal/terapia , Tempo para o Tratamento , Animais , Células do Corno Anterior/efeitos dos fármacos , Células do Corno Anterior/patologia , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Esquema de Medicação , Quimioterapia Combinada , Feminino , Glutationa/administração & dosagem , Glutationa/imunologia , Atividade Motora/fisiologia , Proteína Básica da Mielina/imunologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/imunologia , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/imunologia , Traumatismos da Medula Espinal/fisiopatologia , Fatores de Tempo
18.
Environ Res ; 110(5): 428-34, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20138265

RESUMO

Human exposure to inorganic arsenic (iAs) has been associated with cancer and serious injury to various internal organs, as well as peripheral neuropathy, endocrine disruption and diverse effects in the central nervous system (CNS). Using rodent models, it is possible to demonstrate As accumulation in the brain that leads to defects in operant learning, behavioral changes, and affect pituitary gonadotrophins. iAs biomethylation in the CNS is a significant process, yielding products that are more reactive and toxic than the parent compound. Mice received 2.5, 5, and 10 mg/kg/day sodium arsenite orally for 9 days. We investigated the distribution of iAs and its metabolites as well as the mRNA and protein expression of arsenic (III) methyltransferase (AS3MT), which encodes the key enzyme in iAs metabolism, in the cerebral cortex, hippocampus, striatum, mesencephalon, thalamus, cerebellum, hypothalamus, pons, medulla oblongata, and pituitary of mouse brain. Our findings show that methylated As metabolites are present in all brain regions studied suggesting that AS3MT is ubiquitously expressed in the brain and it is not inducible by dose of arsenite. There is also a dose-related accumulation of As species in all brain regions, with the highest accumulation observed in the pituitary. The higher distribution of arsenicals in pituitary can help to explain the neuroendocrine effects associated with iAs exposure.


Assuntos
Arsênio/toxicidade , Encéfalo/efeitos dos fármacos , Metiltransferases/metabolismo , Animais , Arsênio/farmacocinética , Arsenitos/farmacocinética , Arsenitos/toxicidade , Encéfalo/metabolismo , Expressão Gênica/efeitos dos fármacos , Masculino , Metiltransferases/genética , Camundongos , Compostos de Sódio/farmacocinética , Compostos de Sódio/toxicidade
19.
Invest Clin ; 49(1): 29-38, 2008 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-18524329

RESUMO

Osteoporosis (OP) is an important public issue affecting more than 150 millions all over the world, mainly post-menopausic women. Epidemiological studies have shown that the genetic factors could be involved in 80-90% of the bone mineral density variabiblity and therefore, related to the risk of OP manifestations. The vitamin D receptor (VRD) gene has been extensively studied, but its relationship with OP has been controversial. The aim of this investigation was to study the association of Bsm I, Apa I and Taq I VDR gene polymorphism with OP in 147 post-menopausic women; 71 with OP and 76 without the disease (control). The molecular gene analysis was performed using the polymerase chain reaction (PCR). The genotypes BB, AA, and tt were found in 56.33, 50.70 and 25.35% and in 21.05, 28.95 and 10.53% of OP patients and controls respectively. The haplotype BBAAtt was observed in 23.94% of OP patients and 5.26% of the controls. This haplotype was a risk factor for OP, since a odds ratio (OR) of 5.66 was found, while, haplotype BbaaTT was a protection factor (OR: 0.10). These findings support the association of the vitamin D receptor gene BBAAtt haplotype with OP.


Assuntos
Desoxirribonucleases de Sítio Específico do Tipo II/genética , Osteoporose/genética , Polimorfismo Genético , Pós-Menopausa/genética , Receptores de Calcitriol/genética , Feminino , Humanos
20.
Invest. clín ; 49(1): 29-38, Mar. 2008. tab
Artigo em Espanhol | LILACS | ID: lil-486598

RESUMO

La Osteoporosis (OP) es un problema de salud pública, que afecta a más de 150 millones de personas en el mundo, mayoritariamente mujeres posmenopáusicas. Estudios epidemiológicos demuestran que los factores genéticos podrían representar el 80-90 por ciento de la variabilidad en la densidad mineral ósea y en consecuencia relacionarse con el riesgo a sufrir OP. El gen del receptor de la vitamina D (RVD) se ha estudiado ampliamente en este campo y su relación con la osteoporosis ha sido controversial. El objetivo de esta investigación fue estudiar la asociación de los polimorfismos Bsm I, Apa I y Taq I del gen del RVD con la OP en 147 mujeres posmenopáusicas, 71 con OP y 76 sin la enfermedad (control). El análisis molecular se realizó utilizando la reacción en cadena de la polimerasa (RCP). Los genotipos BB, AA y tt se encontraron en 56,33, 50,70 y 25,35 por ciento y en 21,05, 28,95 y 10,53 por ciento, en el grupo con OP y control, respectivamente. El haplotipo BBAAtt se observó en un 23,94 por ciento en el grupo con OP y en 5,26 por ciento en el grupo control. Este haplotipo resultó ser factor de riesgo para la OP con Razón de disparidad (RD) de 5,66, mientras que el haplotipo BbaaTT, factor de protección (RD: 0,10). Estos hallazgos apoyan la asociación del haplotipo BBAAtt del gen del receptor de la vitamina D con la OP.


Assuntos
Humanos , Feminino , Genes , Haplótipos , Osteoporose , Pós-Menopausa , Vitamina D , Medicina , Saúde Pública , Venezuela
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