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1.
Aesthet Surg J ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38366902

RESUMO

Liposuction is considered one of the most common procedures in plastic surgery. However, major postoperative complications such as visceral injury, fluid overload, and necrotizing fasciitis still occur. Likewise, minor complications such as ecchymosis, seromas, infections, and contour irregularities that do not threaten the life of the patient do generate significant dissatisfaction. Current evidence regarding the management of fibrosis after previous liposuction remains limited. The objective of this article is to standardize a management algorithm based on the extensive experience and successful results of the primary author. Patients who underwent secondary liposculpture between August 2022 and May 2023 were evaluated prospectively. Inclusion criteria: Women between 18 and 60 years, non-smokers, with a body mass index (BMI) <35 kg/m2, history of previous body contouring surgeries. Identification of the patient's skin condition and subcutaneous lesions in the adipose tissue were obtained in detail. Statistical analysis of preoperative and postoperative medical photographs was also performed with Fiji Biological image analyzer. Photographic analysis showed a statistically significant difference between the areas affected by fibrosis from the preoperative photos compared to that from the postoperative ones (p<.001). The most frequent clinical findings were depressions in 99% of the women (74), followed by soft nodules in 95% (70), hard nodules in 81% (61), adherences in 47% (35), and finally, cutaneous bursas in 4%. Our classification system and management algorithm for fibrosis and contour irregularities is a safe and reliable tool and results were objectively verified, yielding statistically significant outcomes.

2.
EMBO Rep ; 24(10): e56380, 2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-37548091

RESUMO

Oxidative phosphorylation and glycolysis are the dominant ATP-generating pathways in mammalian metabolism. The balance between these two pathways is often shifted to execute cell-specific functions in response to stimuli that promote activation, proliferation, or differentiation. However, measurement of these metabolic switches has remained mostly qualitative, making it difficult to discriminate between healthy, physiological changes in energy transduction or compensatory responses due to metabolic dysfunction. We therefore present a broadly applicable method to calculate ATP production rates from oxidative phosphorylation and glycolysis using Seahorse XF Analyzer data and empirical conversion factors. We quantify the bioenergetic changes observed during macrophage polarization as well as cancer cell adaptation to in vitro culture conditions. Additionally, we detect substantive changes in ATP utilization upon neuronal depolarization and T cell receptor activation that are not evident from steady-state ATP measurements. This method generates a single readout that allows the direct comparison of ATP produced from oxidative phosphorylation and glycolysis in live cells. Additionally, the manuscript provides a framework for tailoring the calculations to specific cell systems or experimental conditions.


Assuntos
Smegmamorpha , Animais , Smegmamorpha/metabolismo , Mitocôndrias/metabolismo , Metabolismo Energético , Glicólise , Fosforilação Oxidativa , Trifosfato de Adenosina/metabolismo , Mamíferos/metabolismo
4.
Rev Assoc Med Bras (1992) ; 68(9): 1172-1177, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36228248

RESUMO

OBJECTIVE: This study aimed to characterize hand hygiene behavioural intention by hospital services clusters in a medium-sized hospital in an Ecuadorian city. METHODS: This is a cross-sectional study based on the World Health Organization Hand Hygiene Knowledge Questionnaire for Health-Care Workers. The responses on hand hygiene behavioural intention for the Five Moments for hand hygiene according to the World Health Organization were recorded in three categories: before patient contact, before and after sterile technique and management of body fluids, and after contact with the environment of the patient. The variables were the knowledge regarding the source of germs causing nosocomial infections, the optimal time to achieve disinfection with alcohol, hospital services clusters (clinical medicine, surgery, and therapeutic services), and history of previous formal hand hygiene training. The variables in each moment were analysed using a saturated log-linear model. RESULTS: The average age of participants was 34 years (Q1 32.1-Q3 36.4). Of them, 62% belonged to the clinic cluster and 87.6% had previous formal hand hygiene training. The incorrect response rates for before and after sterile technique and management of body fluids, before patient contact, and after contact with the environment of the patient were 30.2, 88.4, and 99.2%, respectively. In before patient contact, the incorrect responses for optimal time depended on the department (worse surgery cluster situation), and in before and after sterile technique and management of body fluids and after contact with the environment of the patient, the incorrect responses for source of germs depended on the previous formal hand hygiene training and the department (worse surgery and clinic clusters). CONCLUSION: The incorrect answer related to hand hygiene behavioural intention was high compared to other reports, and the worse situation was found in after contact with the environment of the patient and before patient contact. These data suggest the need of strengthening permanently the hand hygiene programme.


Assuntos
Infecção Hospitalar , Higiene das Mãos , Adulto , Estudos Transversais , Equador , Fidelidade a Diretrizes , Desinfecção das Mãos/métodos , Pessoal de Saúde/educação , Hospitais , Humanos , Intenção
5.
Rev. Assoc. Med. Bras. (1992, Impr.) ; 68(9): 1172-1177, Sept. 2022. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1406645

RESUMO

SUMMARY OBJECTIVE: This study aimed to characterize hand hygiene behavioural intention by hospital services clusters in a medium-sized hospital in an Ecuadorian city. METHODS: This is a cross-sectional study based on the World Health Organization Hand Hygiene Knowledge Questionnaire for Health-Care Workers. The responses on hand hygiene behavioural intention for the Five Moments for hand hygiene according to the World Health Organization were recorded in three categories: before patient contact, before and after sterile technique and management of body fluids, and after contact with the environment of the patient. The variables were the knowledge regarding the source of germs causing nosocomial infections, the optimal time to achieve disinfection with alcohol, hospital services clusters (clinical medicine, surgery, and therapeutic services), and history of previous formal hand hygiene training. The variables in each moment were analysed using a saturated log-linear model. RESULTS: The average age of participants was 34 years (Q1 32.1-Q3 36.4). Of them, 62% belonged to the clinic cluster and 87.6% had previous formal hand hygiene training. The incorrect response rates for before and after sterile technique and management of body fluids, before patient contact, and after contact with the environment of the patient were 30.2, 88.4, and 99.2%, respectively. In before patient contact, the incorrect responses for optimal time depended on the department (worse surgery cluster situation), and in before and after sterile technique and management of body fluids and after contact with the environment of the patient, the incorrect responses for source of germs depended on the previous formal hand hygiene training and the department (worse surgery and clinic clusters). CONCLUSION: The incorrect answer related to hand hygiene behavioural intention was high compared to other reports, and the worse situation was found in after contact with the environment of the patient and before patient contact. These data suggest the need of strengthening permanently the hand hygiene programme.

6.
Rev. chil. enferm. respir ; 38(3): 184-193, sept. 2022. tab
Artigo em Espanhol | LILACS | ID: biblio-1423700

RESUMO

Introducción: La pandemia por COVID-19 obligó a los gobiernos a implementar medidas de restricción social para proteger la salud de la población, afectando la calidad de vida de las personas, especialmente en grupos vulnerables como los niños, niñas y adolescentes (NNA). El objetivo de esta revisión sistemática (RS) fue evaluar el efecto de las medidas de restricción sobre la actividad física (AF) y conducta sedentaria (CS) de los NNA. Adicionalmente, se exploraron posibles factores determinantes de estos cambios. Métodos: Se realizó una RS, utilizando tres bases de datos. Se incluyeron estudios observacionales en donde se hubiera analizado la AF y CS de los participantes, utilizando cualquier método de evaluación. Dos investigadores analizaron los estudios, extrajeron los datos y evaluaron la calidad metodológica de los artículos primarios. El metaanálisis se realizó utilizando el modelo de efectos aleatorios, considerando un valor p < 0,05 como estadísticamente significativo. Resultados: Se incluyeron 19 artículos, con una muestra total de 15.095 NNA. La mayoría de los estudios reveló una reducción de la AF y un incremento de la CS en los sujetos, durante los confinamientos por COVID-19. El metaanálisis mostró una caída en la AF total, la AF moderada a vigorosa y un incremento del tiempo de sedentarismo. Diversos factores biodemográficos, familiares y ambientales exacerbaron las variaciones en la AF y la CS de los NNA. Conclusión: Las medidas de restricción aplicadas durante pandemia por COVID-19 redujo la AF e incrementó la CS de los NNA. Factores biodemográficos, familiares y ambientales determinaron estas variaciones.


Introduction: The COVID-19 pandemic forced governments to implement social restriction measures to protect the health of the population, affecting the quality of life of people, especially in vulnerable groups, such as children and adolescents (CA). The objective of this systematic review (SR) was to evaluate the effect of restriction measures on physical activity (PA) and sedentary behavior (SB) of CA. Additionally, possible determining factors of these changes were explored. Methods: An SR was carried out, using three databases. Observational studies were included in which the PA and SB of the participants were analyzed, using any evaluation method. Two investigators analyzed the studies, extracted data, and assessed the methodological quality of the primary articles. The meta-analysis was performed using the random effects model, considering a value of p < 0.05 as statistically significant. Results: 19 articles were included, with a total sample of 15,095 subjects. Most studies revealed a reduction in PA and an increase in SB in subjects during COVID-19 lockdowns. The meta-analysis showed a drop in total PA, moderate to vigorous PA, and an increase in sedentary time. Various biodemographic, family and environmental factors exacerbated the variations in the PA and SB of the CA. Conclusion: The restriction measures applied during the COVID-19 pandemic reduced the PA and increased the SB of the CA. Biodemographic, family and environmental factors determined these variations.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Exercício Físico , Comportamento Sedentário , COVID-19 , Qualidade de Vida , Quarentena , Aptidão Física , Pandemias
7.
Nat Biomed Eng ; 5(10): 1115-1130, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34155355

RESUMO

Silicone is widely used in chronic implants and is generally perceived to be safe. However, textured breast implants have been associated with immune-related complications, including malignancies. Here, by examining for up to one year the foreign body response and capsular fibrosis triggered by miniaturized or full-scale clinically approved breast implants with different surface topography (average roughness, 0-90 µm) placed in the mammary fat pads of mice or rabbits, respectively, we show that surface topography mediates immune responses to the implants. We also show that the surface surrounding human breast implants collected during revision surgeries also differentially alters the individual's immune responses to the implant. Moreover, miniaturized implants with an average roughness of 4 µm can largely suppress the foreign body response and fibrosis (but not in T-cell-deficient mice), and that tissue surrounding these implants displayed higher levels of immunosuppressive FOXP3+ regulatory T cells. Our findings suggest that, amongst the topographies investigated, implants with an average roughness of 4 µm provoke the least amount of inflammation and foreign body response.


Assuntos
Implante Mamário , Implantes de Mama , Corpos Estranhos , Animais , Implante Mamário/efeitos adversos , Implantes de Mama/efeitos adversos , Reação a Corpo Estranho/etiologia , Humanos , Camundongos , Coelhos , Silicones/efeitos adversos
8.
Nat Commun ; 12(1): 2804, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33990571

RESUMO

Chemotherapy remains the standard of care for most cancers worldwide, however development of chemoresistance due to the presence of the drug-effluxing ATP binding cassette (ABC) transporters remains a significant problem. The development of safe and effective means to overcome chemoresistance is critical for achieving durable remissions in many cancer patients. We have investigated the energetic demands of ABC transporters in the context of the metabolic adaptations of chemoresistant cancer cells. Here we show that ABC transporters use mitochondrial-derived ATP as a source of energy to efflux drugs out of cancer cells. We further demonstrate that the loss of methylation-controlled J protein (MCJ) (also named DnaJC15), an endogenous negative regulator of mitochondrial respiration, in chemoresistant cancer cells boosts their ability to produce ATP from mitochondria and fuel ABC transporters. We have developed MCJ mimetics that can attenuate mitochondrial respiration and safely overcome chemoresistance in vitro and in vivo. Administration of MCJ mimetics in combination with standard chemotherapeutic drugs could therefore become an alternative strategy for treatment of multiple cancers.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Trifosfato de Adenosina/metabolismo , Resistencia a Medicamentos Antineoplásicos/fisiologia , Mitocôndrias/metabolismo , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Linhagem Celular Tumoral , Respiração Celular/efeitos dos fármacos , Respiração Celular/fisiologia , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos/fisiologia , Feminino , Proteínas de Choque Térmico HSP40/deficiência , Proteínas de Choque Térmico HSP40/metabolismo , Humanos , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Mitocôndrias/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Consumo de Oxigênio/efeitos dos fármacos
9.
Int J Artif Organs ; 43(1): 45-57, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31385550

RESUMO

The main physiological functions of renal proximal tubule cells in vivo are reabsorption of essential nutrients from the glomerular filtrate and secretion of waste products and xenobiotics into urine. Currently, there are several established cell lines of human origin available as in vitro models of proximal tubule. However, these cells appeared to be limited in their biological relevance, because essential characteristics of the original tissue are lost once the cells are cultured. As a consequence of these limitations, primary human proximal tubule cells constitute a suitable and a biologically more relevant in vitro model to study this specific segment of the nephron and therefore, these cells can play an important role in renal regenerative medicine applications. Here, we describe a protocol to isolate proximal tubule cells from human nephrectomies. We explain the steps performed for an in-depth characterization of the cells, including the study of markers from others segments of the nephron, with the goal to determine the purity of the culture and the stability of proteins, enzymes, and transporters along time. The human proximal tubule cells isolated and used throughout this study showed many proximal tubule characteristics, including monolayer organization, cell polarization with the expression of tight junctions and primary cilia, expression of proximal tubule-specific proteins, such as megalin and sodium/glucose cotransporter 2, among others. The cells also expressed enzymatic activity for dipeptidyl peptidase IV, as well as for gamma glutamyl transferase 1, and expressed transporter activity for organic anion transporter 1, P-glycoprotein, multidrug resistance proteins, and breast cancer resistance protein. In conclusion, characterization of our cells confirmed presence of putative proximal tubule markers and the functional expression of multiple endogenous organic ion transporters mimicking renal reabsorption and excretion. These findings can constitute a valuable tool in the development of bioartificial kidney devices.


Assuntos
Técnicas de Cultura de Células/métodos , Túbulos Renais Proximais/citologia , Terapia de Substituição Renal , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Dipeptidil Peptidase 4/metabolismo , Humanos , Proteínas de Neoplasias/metabolismo , Nefrectomia , Transportadores de Ânions Orgânicos/metabolismo , gama-Glutamiltransferase/metabolismo
10.
Hepatology ; 72(1): 257-270, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31715015

RESUMO

BACKGROUND AND AIMS: The gap between patients on transplant waiting lists and available donor organs is steadily increasing. Human organoids derived from leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5)-positive adult stem cells represent an exciting new cell source for liver regeneration; however, culturing large numbers of organoids with current protocols is tedious and the level of hepatic differentiation is limited. APPROACH AND RESULTS: Here, we established a method for the expansion of large quantities of human liver organoids in spinner flasks. Due to improved oxygenation in the spinner flasks, organoids rapidly proliferated and reached an average 40-fold cell expansion after 2 weeks, compared with 6-fold expansion in static cultures. The organoids repopulated decellularized liver discs and formed liver-like tissue. After differentiation in spinner flasks, mature hepatocyte markers were highly up-regulated compared with static organoid cultures, and cytochrome p450 activity reached levels equivalent to hepatocytes. CONCLUSIONS: We established a highly efficient method for culturing large numbers of LGR5-positive stem cells in the form of organoids, which paves the way for the application of organoids for tissue engineering and liver transplantation.


Assuntos
Técnicas de Cultura de Células , Proliferação de Células , Hepatócitos/citologia , Regeneração Hepática , Transplante de Fígado , Organoides/citologia , Receptores Acoplados a Proteínas G/biossíntese , Células-Tronco/metabolismo , Engenharia Tecidual , Diferenciação Celular , Células Cultivadas , Humanos
11.
Rev. chil. nutr ; 46(2): 181-189, abr. 2019. tab
Artigo em Espanhol | LILACS | ID: biblio-1003692

RESUMO

RESUMEN Las algas marinas constituyen un valioso recurso para el desarrollo de productos alimenticios gracias a su composición nutricional, contienen alta concentración de proteínas, vitaminas, minerales y fibra dietética, que en el caso de las algas es particularmente rica en fracción soluble. Las algas además contienen componentes beneficiosos para la salud, como ácidos grasos ω-3 y moléculas bioactivas, con actividad antioxidante, antiinflamatoria, anticancerígena y antidiabética. Además, poseen propiedades tecnológicas, por lo que su incorporación en alimentos procesados y especialmente productos cárnicos como salchichas, hamburguesas, emulsiones cárnicas y otras, resulta beneficioso desde el punto de vista tecnológico y sensorial, siempre que se incorpore en una concentración adecuada.


ABSTRACT Seaweed is a valuable resource for food development due to its nutritional composition. It is high in protein, vitamins, minerals and dietary fiber, and particularly rich in soluble fiber. Seaweed also contains components beneficial to health such as ω-3 PUFAs, bioactive molecules with antioxidants, and anti-inflammatory, anticancer, and antidiabetic activity. It also has technological properties, so its incorporation in processed foods and especially meat products such as sausages, hamburgers, meat emulsions and others would be beneficial from the technological and sensorial point of view, if it is incorporated in an adequate concentration.


Assuntos
Alga Marinha , Ingredientes de Alimentos , Produtos da Carne , Valor Nutritivo
12.
Colomb. med ; 49(4): 261-264, Oct.-Dec. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-984306

RESUMO

Abstract Introduction: There is a high rate of deliveries in adolescents in Mexico. This age group is vulnerable to obstetric complications, including lacerations of the anal sphincter. Objective: To determine the prevalence of third and fourth degree perineal tears in adolescents during childbirth, and to evaluate risk factors in comparison with deliveries with lacerations of adult women. Methods: All obstetric care episodes were reviewed from a public tertiary hospital data in Monterrey, Mexico in 2014. Age, primiparity, delivery instrumentation, episiotomy, body mass index, product weight and tear´s degree were documented at the deliveries with tears of third and fourth degree. Results: The prevalence of third and fourth degree tears of 2.0% was found in the general population, being adolescents the most affected with 2.5%. The unadjusted odds ratio of high-grade tears in adolescent females at delivery, compared to adult females, was 1.36 (95% CI = 0.99-1.86, p= 0.05). No difference was found when comparing risk factors among high-grade tear deliveries in adolescents versus adults. Conclusions: A higher prevalence than previous reported for high grade tears during delivery was found. The data suggest adolescence as a risk factor for high-grade tears during delivery.


Resumen Introducción: En México hay una elevada tasa de partos en adolescentes. Este grupo es vulnerable para complicaciones obstétricas, entre ellas laceración del esfínter anal. Objetivo: Conocer la prevalencia de desgarros perineales de tercer y cuarto grado en adolescentes durante el parto y evaluar factores de riesgo en comparación con partos con laceración de mujeres adultas. Métodos: Se revisaron todas las atenciones obstétricas en un hospital publico de tercer nivel en Monterrey, Nuevo León, México en el año 2014. Se documentó edad, primiparidad, instrumentación del parto, realización de episiotomía, índice de masa corporal, peso del producto y grado del desgarro en los partos que presentaron desgarros de tercer y cuarto grado Resultados: Se encontró una prevalencia general de 2.0% de desgarros de tercer y cuarto grado y en adolescentes de 2.5%. La razón de momios sin ajustar de desgarros de alto grado en mujeres adolescentes en comparación con mujeres adultas fue de 1.36 (IC 95%= 0.99-1.86, p= 0.05). No se encontró diferencia al comparar factores de riesgo entre los partos con desgarro de alto grado en adolescentes contra adultas. Conclusiones: Se encontró una prevalencia mayor a lo reportado de desgarros de alto grado durante el parto. Los datos sugieren a la adolescencia como factor de riesgo para desgarros de alto grado.


Assuntos
Adolescente , Adulto , Feminino , Humanos , Gravidez , Adulto Jovem , Canal Anal/lesões , Períneo/lesões , Lacerações/epidemiologia , Complicações do Trabalho de Parto/epidemiologia , Gravidez na Adolescência , Trabalho de Parto , Prevalência , Fatores de Risco , Lacerações/etiologia , Episiotomia/estatística & dados numéricos , México/epidemiologia
13.
Nursing (Ed. bras., Impr.) ; 21(246): 2435-2438, nov.2018. tab
Artigo em Português | BDENF - Enfermagem, LILACS | ID: biblio-969216

RESUMO

O objetivo desta pesquisa foi conhecer a concepção das mulheres sobre o exame Papanicolau, e os fatores relacionados a não adesão ao exame preventivo de Papanicolau. Método: Método: Trata-se de um estudo transversal quantitativo, retrospectivo onde foram aplicados questionários com mulheres que procuraram a Unidade Saúde da Família para prevenção câncer colo útero, no período de junho a agosto/2016. Resultados: Foi evidenciado que a maioria 46% tem 40 ou mais anos de idade, quando analisado a variável realizam o exame anualmente 88% responderam sim. Considerações: Foi observado que a maioria das mulheres entenderam a importância da promoção e prevenção do câncer colo de útero.


The objective of this research was to know the conception of women on the Pap smear, and the factors related to non adherence to the preventive examination of Papanicolau. Method: This is a cross-sectional, quantitative, retrospective study in which questionnaires were applied to women who sought the Family Health Unit for cervical cancer prevention in the period from June to August / 2016. Results: It was evidenced that most 46% are 40 or more years of age, when analyzed the variable they perform the exam annually 88% answered yes. Considerations: It was observed that most women understood the importance of promoting and preventing cervical cancer.The objective of this research was to know the conception of women on the Pap smear, and the factors related to non adherence to the preventive examination of Papanicolau. Method: This is a cross-sectional, quantitative, retrospective study in which questionnaires were applied to women who sought the Family Health Unit for cervical cancer prevention in the period from June to August / 2016. Results: It was evidenced that most 46% are 40 or more years of age, when analyzed the variable they perform the exam annually 88% answered yes. Considerations: It was observed that most women understood the importance of promoting and preventing cervical cancer.


Assuntos
Humanos , Feminino , Adulto , Neoplasias Uterinas , Esfregaço Vaginal , Teste de Papanicolaou , Promoção da Saúde , Serviços de Saúde da Mulher , Saúde da Mulher
14.
Drug Metab Dispos ; 46(9): 1338-1350, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29980578

RESUMO

Drug-induced kidney injury in medicinal compound development accounts for over 20% of clinical trial failures and involves damage to different nephron segments, mostly the proximal tubule. Yet, currently applied cell models fail to reliably predict nephrotoxicity; neither are such models easy to establish. Here, we developed a novel three-dimensional (3D) nephrotoxicity platform on the basis of decellularized rat kidney scaffolds (DS) recellularized with conditionally immortalized human renal proximal tubule epithelial cells overexpressing the organic anion transporter 1 (ciPTEC-OAT1). A 5-day SDS-based decellularization protocol was used to generate DS, of which 100-µm slices were cut and used for cell seeding. After 8 days of culturing, recellularized scaffolds (RS) demonstrated 3D-tubule formation along with tubular epithelial characteristics, including drug transporter function. Exposure of RS to cisplatin (CDDP), tenofovir (TFV), or cyclosporin A (CsA) as prototypical nephrotoxic drugs revealed concentration-dependent reduction in cell viability, as assessed by PrestoBlue and Live/Dead staining assays. This was most probably attributable to specific uptake of CDDP by the organic cation transporter 2 (OCT2), TFV through organic anion transporter 1 (OAT1), and CsA competing for P-glycoprotein-mediated efflux. Compared with 2D cultures, RS showed an increased sensitivity to cisplatin and tenofovir toxicity after 24-hour exposure (9 and 2.2 fold, respectively). In conclusion, we developed a physiologically relevant 3D nephrotoxicity screening platform that could be a novel tool in drug development.


Assuntos
Cisplatino/toxicidade , Rim/citologia , Rim/efeitos dos fármacos , Tenofovir/toxicidade , Alicerces Teciduais , Animais , Antineoplásicos/toxicidade , Antivirais/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos/métodos , Rim/metabolismo , Masculino , Ratos , Ratos Wistar
15.
Free Radic Biol Med ; 113: 16-25, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28917508

RESUMO

RATIONALE: Hydrogen peroxide (H2O2) is a stable reactive oxygen species (ROS) that has long been implicated in insulin signal transduction in adipocytes. However, H2O2's role in mediating insulin's effects on the heart are unknown. OBJECTIVE: We investigated the role of H2O2 in activating insulin-dependent changes in cardiac myocyte metabolic and inotropic pathways. The sources of insulin-dependent H2O2 generation were also studied. METHODS AND RESULTS: In addition to the canonical role of insulin in modulating cardiac metabolic pathways, we found that insulin also inhibited beta adrenergic-induced increases in cardiac contractility. Catalase and NADPH oxidase (NOX) inhibitors blunted activation of insulin-responsive kinases Akt and mTOR and attenuated beta adrenergic receptor-mediated responses. These insulin responses were lost in a mouse model of type 2 diabetes, suggesting a role for these H2O2-dependent pathways in the diabetic heart. The H2O2-sensitive fluorescent biosensor HyPer revealed rapid increases in cytosolic and caveolar H2O2 concentrations in response to insulin treatment, which were blocked by NOX inhibitors and attenuated in NOX2 KO and NOX4 KO mice. In NOX2 KO cardiac myocytes, insulin-mediated phosphorylation of Akt and mTOR was blocked, while these responses were unaffected in cardiac myocytes from NOX4 KO mice. In contrast, insulin's effects on contractility were lost in cardiac myocytes from NOX4 KO animals but were retained in NOX2 KO mice. CONCLUSIONS: These studies identify a proximal point of bifurcation in cardiac insulin signaling through the simultaneous activation of both NOX2 and NOX4. Each NOX isoform generates H2O2 in cardiac myocytes with distinct time courses, with H2O2 derived from NOX2 augmenting Akt-dependent metabolic effects of insulin, while H2O2 from NOX4 blocks beta adrenergic increases in inotropy. These findings suggest that insulin resistance in the diabetic heart may lead to potentially deleterious potentiation of beta adrenergic responses.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Insulina/metabolismo , Miócitos Cardíacos/metabolismo , NADPH Oxidase 2/metabolismo , NADPH Oxidase 4/metabolismo , Transdução de Sinais , Animais , Diabetes Mellitus Tipo 2/enzimologia , Modelos Animais de Doenças , Peróxido de Hidrogênio/metabolismo , Camundongos , Miócitos Cardíacos/enzimologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo
16.
Mol Pharm ; 14(6): 2147-2157, 2017 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-28493713

RESUMO

The combination of methotrexate with epidermal growth factor receptor (EGFR) recombinant antibody, cetuximab, is currently being investigated in treatment of head and neck carcinoma. As methotrexate is cleared by renal excretion, we studied the effect of cetuximab on renal methotrexate handling. We used human conditionally immortalized proximal tubule epithelial cells overexpressing either organic anion transporter 1 or 3 (ciPTEC-OAT1/ciPTEC-OAT3) to examine OAT1 and OAT3, and the efflux pumps breast cancer resistance protein (BCRP), multidrug resistance protein 4 (MRP4), and P-glycoprotein (P-gp) in methotrexate handling upon EGF or cetuximab treatment. Protein kinase microarrays and knowledge-based pathway analysis were used to predict EGFR-mediated transporter regulation. Cytotoxic effects of methotrexate were evaluated using the dimethylthiazol bromide (MTT) viability assay. Methotrexate inhibited OAT-mediated fluorescein uptake and decreased efflux of Hoechst33342 and glutathione-methylfluorescein (GS-MF), which suggested involvement of OAT1/3, BCRP, and MRP4 in transepithelial transport, respectively. Cetuximab reversed the EGF-increased expression of OAT1 and BCRP as well as their membrane expressions and transport activities, while MRP4 and P-gp were increased. Pathway analysis predicted cetuximab-induced modulation of PKC and PI3K pathways downstream EGFR/ERBB2/PLCg. Pharmacological inhibition of ERK decreased expression of OAT1 and BCRP, while P-gp and MRP4 were increased. AKT inhibition reduced all transporters. Exposure to methotrexate for 24 h led to a decreased viability, an effect that was reversed by cetuximab. In conclusion, cetuximab downregulates OAT1 and BCRP while upregulating P-gp and MRP4 through an EGFR-mediated regulation of PI3K-AKT and MAPKK-ERK pathways. Consequently, cetuximab attenuates methotrexate-induced cytotoxicity, which opens possibilities for further research into nephroprotective comedication therapies.


Assuntos
Cetuximab/farmacologia , Fator de Crescimento Epidérmico/metabolismo , Metotrexato/farmacologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Benzimidazóis/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Glutationa/análogos & derivados , Glutationa/metabolismo , Células HEK293 , Humanos , Compostos de Metilmercúrio/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Proteínas de Neoplasias/metabolismo , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo
17.
Arch Esp Urol ; 70(4): 385-399, 2017 May.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-28530618

RESUMO

OBJECTIVES: To review the role of robot- assisted laparoscopic colposacropexy (RALCS) as a treatment for pelvic organ prolapse (POP) accordingly with the available literature and our own experience. METHODS: We have analyzed the studies with the results of robot-assisted colposacropexy (RALCS) and others in which this technique is compared with the abdominal (ACS) and/or the laparoscopic approach (LCS), including our own series. The main data collected are surgical time, blood loss, complications, clinical outcomes, quality of life and the different costs of LCS versus RALCS. We have reviewed the last systematic reviews and meta-analysis. RESULTS: Clinical outcomes were similar within both RALCS and LCS, surgical time was a bit longer for the robot-assisted compared with laparoscopy, blood loss was similar, as complications. The costs of RALCS were significantly higher than those of LCS, although we must conseconsider that the different studies used different variables to measure them. CONCLUSIONS: Considering that comparative studies are necessary, it is reasonable to assume that RALCS is a feasible and secure technique for the treatment of POP.


Assuntos
Prolapso de Órgão Pélvico/cirurgia , Procedimentos Cirúrgicos Robóticos , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Complicações Pós-Operatórias/etiologia , Sacro , Procedimentos Cirúrgicos Urológicos/métodos , Vagina
18.
Scand J Urol ; 51(1): 81-84, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27905212

RESUMO

The association of ipsilateral renal agenesis and cystic seminal vesicle is a rare congenital syndrome described by Zinner in 1914. The cases of two patients with this syndrome are presented, one of them associated with infertility, the other with cryptorchidism and testicular pain. A brief review of the literature is undertaken, regarding the main clinical and imaging implications, and the developmental anomalies that are involved in this unusual congenital anomaly are analyzed.


Assuntos
Anormalidades Congênitas/diagnóstico por imagem , Ductos Ejaculatórios/diagnóstico por imagem , Nefropatias/congênito , Rim/anormalidades , Glândulas Seminais/diagnóstico por imagem , Anormalidades Urogenitais/diagnóstico por imagem , Adulto , Criptorquidismo/complicações , Criptorquidismo/cirurgia , Ductos Ejaculatórios/anormalidades , Humanos , Infertilidade Masculina/etiologia , Rim/diagnóstico por imagem , Nefropatias/complicações , Nefropatias/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Glândulas Seminais/anormalidades , Síndrome , Tomografia Computadorizada por Raios X , Ultrassonografia , Anormalidades Urogenitais/complicações
19.
Hig. aliment ; 30(256/257): 148-151, maio/junho 2016. tab
Artigo em Português | LILACS | ID: biblio-1711

RESUMO

Avaliou-se a qualidade microbiológica da carne bovina moída comercializada em 15 diferentes pontos de comercialização no norte do Mato Grosso, pelo método do número mais provável (NMP) para coliformes totais, coliformes a 45°C e Escherichia coli e pesquisa de Salmonella spp. Os resultados mostram que 100% das amostras analisadas apresentam contaminação por coliformes totais, 33,3% por coliformes a 45°C, 13,3% por Escherichia coli e ausência de Salmonella. De acordo com a legislação vigente, RDC N° 12/2001 (ANVISA), não há especificação dos limites permitidos em relação à presença de coliformes totais, coliformes a 45°C e Escherichia coli, no entanto a presença desses micro-organismos em alimentos é considerada uma indicação útil de contaminação por deterioradores e patogênicos. Quanto à presença de Salmonella, a legislação especifica ausência em 25g.


This study aimed to analyse the microbiological quality of ground beef sold in 15 differents commercial establishments in northern Mato Grosso, through the research of total coliforms, coliforms at 45°C, Escherichia coli and Salmonella spp. The results showed that 100% of the samples were contaminated with total coliforms, 33.3% with coliforms at 45°C, 13.3% with Escherichia coli and absence of Salmonella spp. The current legislation, RDC N° 12/2001 (ANVISA), does not specifies limits for the presence of total coliform, coliform at 45°C and Escherichia coli in ground beef, however the presence of these microorganisms in food is considered a useful indication of contamination. For the presence of Salmonella, the legislation specifies absence in 25g.


Assuntos
Animais , Bovinos , Contaminação de Alimentos/análise , Microbiologia de Alimentos , Carne/microbiologia , Salmonella/isolamento & purificação , Amostras de Alimentos , Escherichia coli/isolamento & purificação , Fiscalização Sanitária , Coliformes , Método de Tubulação Múltiplo
20.
Rev Esp Enferm Dig ; 108(3): 156-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26949147

RESUMO

A 35-year-old man, with a history of rhinitis, eczema and a dubious achalasia was admitted due to chest pain and sialorrhea. Upper endoscopy showed a little hole and a narrowing of the distal esophagus. A CT-scan with oral contrast exposed a discontinuity of the lumen of the middle third of the esophagus and a dissection of submucosal space 16 cm long. The patient recovered after parenteral nutrition. After four months, an esophageal endoscopic showed transient whitish exudates, longitudinal furrows and esophageal lacerations. The biopsies illustrated significant eosinophilic inflammation, eosinophilic microabscesses and basal cell hyperplasia.


Assuntos
Esofagite Eosinofílica/diagnóstico por imagem , Esofagite Eosinofílica/terapia , Esôfago/diagnóstico por imagem , Adulto , Antibacterianos/uso terapêutico , Endoscopia Gastrointestinal , Humanos , Masculino , Inibidores da Bomba de Prótons/uso terapêutico , Tomografia Computadorizada por Raios X
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