RESUMO
Escherichia coli bacterium is a rod-shaped organism composed of a complex double membrane structure. Knowledge of electric field driven ion transport through both membranes and the evolution of their induced permeabilization has important applications in biomedical engineering, delivery of genes and antibacterial agents. However, few studies have been conducted on Gram-negative bacteria in this regard considering the contribution of all ion types. To address this gap in knowledge, we have developed a deterministic and stochastic Brownian dynamics model to simulate in 3D space the motion of ions through pores formed in the plasma membranes of E. coli cells during electroporation. The diffusion coefficient, mobility, and translation time of Ca2+, Mg2+, Na+, K+, and Cl- ions within the pore region are estimated from the numerical model. Calculations of pore's conductance have been validated with experiments conducted at Gustave Roussy. From the simulations, it was found that the main driving force of ionic uptake during the pulse is the one due to the externally applied electric field. The results from this work provide a better understanding of ion transport during electroporation, aiding in the design of electrical pulses for maximizing ion throughput, primarily for application in cancer treatment.
Assuntos
Eletroporação , Escherichia coli , Transporte de Íons , Transporte Biológico , Eletroporação/métodos , ÍonsRESUMO
Low doses of mercury (Hg) promote deleterious effects on cardiovascular system, but the mechanisms implicated remain unclear. This study analyzed whether angiotensin II AT-1 receptors are involved in the vascular dysfunction caused by chronic exposure to low HgCl2 doses. For this, rats were divided into four groups and untreated (saline by im injections and tap water by gavage) or treated for 30 days as follows: Mercury (HgCl2im, first dose of 4.6⯵gâ¯kg-1 and subsequent doses of 0.07⯵gâ¯kg-1 day-1, and tap water by gavage); Losartan (saline im and losartan, 15â¯mgâ¯kg-1 day-1, by gavage); Losartan-Mercury (HgCl2im and Losartan by gavage). Systolic blood pressure was measured by tail plethysmography, vascular reactivity in aorta by isolated organ bath, oxidative stress by measuring the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and antioxidant capacity (FRAP) and protein expression of AT-1 receptors by Western Blot. As results, co-treatment with losartan prevented the increased aortic vasoconstrictor responses to phenylephrine (Phe), the involvement of ROS and prostanoids on the response to Phe and the reduced negative endothelial modulation by nitric oxide on these responses. Moreover, this co-treatment avoided the increase in plasmatic and vascular oxidative stress and AT-1 protein expression in aorta. In conclusion, these results suggest that AT-1 receptors upregulation might play a key role in the vascular damage induced by Hg exposure by increasing oxidative stress and probably by reducing NO bioavailability.
Assuntos
Angiotensina II , Mercúrio , Estresse Oxidativo , Receptor Tipo 1 de Angiotensina , Receptores de Angiotensina , Angiotensina II/efeitos dos fármacos , Angiotensina II/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Endotélio Vascular , Mercúrio/toxicidade , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/efeitos dos fármacos , Receptor Tipo 1 de Angiotensina/metabolismo , Receptores de Angiotensina/efeitos dos fármacos , Receptores de Angiotensina/metabolismo , Regulação para Cima , VasoconstriçãoRESUMO
Aluminum (Al) is a significant environmental contaminant. While a good deal of research has been conducted on the acute neurotoxic effects of Al, little is known about the effects of longer-term exposure at human dietary Al levels. Therefore, the purpose of this study was to investigate the effects of 60-day Al exposure at low doses for comparison with a model of exposure known to produce neurotoxicity in rats. Three-month-old male Wistar rats were divided into two major groups: (1) low aluminum levels, and (2) a high aluminum level. Group 1 rats were treated orally by drinking water for 60 days as follows: (a) control-received ultrapure drinking water; (b) aluminum at 1.5 mg/kg b.w., and (c) aluminum at 8.3 mg/kg b.w. Group 2 rats were treated through oral gavages for 42 days as follows: (a) control-received ultrapure water; (b) aluminum at 100 mg/kg b.w. We analyzed cognitive parameters, biomarkers of oxidative stress and acetylcholinesterase (AChE) activity in hippocampus and prefrontal cortex. Al treatment even at low doses promoted recognition memory impairment seen in object recognition memory testing. Moreover, Al increased hippocampal reactive oxygen species and lipid peroxidation, reduced antioxidant capacity, and decreased AChE activity. Our data demonstrate that 60-day subchronic exposure to low doses of Al from feed and added to the water, which reflect human dietary Al intake, reaches a threshold sufficient to promote memory impairment and neurotoxicity. The elevation of oxidative stress and cholinergic dysfunction highlight pathways of toxic actions for this metal.
Assuntos
Alumínio/toxicidade , Transtornos da Memória/induzido quimicamente , Acetilcolinesterase/metabolismo , Administração Oral , Animais , Antioxidantes/metabolismo , Dieta , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Água Potável , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/metabolismo , Atividade Motora/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Poluentes da Água/toxicidade , Poluição Química da ÁguaRESUMO
Mercury is a ubiquitous environmental pollutant and mercury contamination and toxicity are serious hazards to human health. Some studies have shown that mercury impairs male reproductive function, but less is known about its effects following exposure at low doses and the possible mechanisms underlying its toxicity. Herein we show that exposure of rats to mercury chloride for 30 days (first dose 4.6µgkg-1, subsequent doses 0.07µgkg-1day-1) resulted in mean (±s.e.m.) blood mercury concentrations of 6.8±0.3ngmL-1, similar to that found in human blood after occupational exposure or released from removal of amalgam fillings. Even at these low concentrations, mercury was deposited in reproductive organs (testis, epididymis and prostate), impaired sperm membrane integrity, reduced the number of mature spermatozoa and, in the testes, promoted disorganisation, empty spaces and loss of germinal epithelium. Mercury increased levels of reactive oxygen species and the expression of glutathione peroxidase (GPx) 1 and GPx4. These results suggest that the toxic effects of mercury on the male reproductive system are due to its accumulation in reproductive organs and that the glutathione system is its potential target. The data also suggest, for the first time, a possible role of the selenoproteins GPx1 and GPx4 in the reproductive toxicity of mercury chloride.
Assuntos
Glutationa Peroxidase/metabolismo , Mercúrio/farmacologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Epididimo/efeitos dos fármacos , Epididimo/metabolismo , Glutationa/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Espermatozoides/metabolismo , Testículo/metabolismoRESUMO
Mercury is a toxic and bio-accumulative heavy metal of global concern. While good deals of research have been conducted on the toxic effects of mercury, little is known about the mechanisms involved in the pathogenesis of male reproductive dysfunction induced by mercury. Therefore, the purpose of this study was to assess the effects and underlying mechanisms of chronic mercury exposure at low levels on male reproductive system of rats. Three-month-old male Wistar rats were divided into two groups and treated for 60 days with saline (i.m., Control) and HgCl2 (i.m. 1st dose: 4.6 µg/kg, subsequent doses 0.07 µg/kg/day). We analyzed sperm parameters, hormonal levels and biomarkers of oxidative stress in testis, epididymis, prostate and vas deferens. Mercury treatment decreased daily sperm production, count and motility and increased head and tail morphologic abnormalities. Moreover, mercury treatment decreased luteinizing hormone levels, increased lipid peroxidation on testis and decreased antioxidant enzymes activities (superoxide dismutase and catalase) on reproductive organs. Our data demonstrate that 60-day chronic exposure to low concentrations of HgCl2 impairs sperm quality and promotes hormonal imbalance. The raised oxidative stress seems to be a potential mechanism involved on male reproductive toxicity by mercury.
Assuntos
Cloreto de Mercúrio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Imunoensaio , Peroxidação de Lipídeos/efeitos dos fármacos , Hormônio Luteinizante/análise , Masculino , Ratos , Ratos Wistar , Contagem de Espermatozoides , Superóxido Dismutase/metabolismo , Testosterona/análise , Fatores de TempoRESUMO
Mercury (Hg) is a widespread environmental pollutant that adversely affects the male reproductive system. The precise mechanisms underlying mercuric chloride (HgCl2)-induced toxicity are not fully understood; however, evidence indicates that oxidative stress may be involved in this process. Although the adverse effects of high levels of inorganic Hg on the male reproductive system have been investigated, the effects of low levels of exposure are unknown. Therefore, the aim of this study was to investigate the effects of chronic exposure to low concentrations of HgCl2 on sperm parameters, lipid peroxidation, and antioxidant activity of male rats. Three-month-old male Wistar rats were treated for 30 d and divided into groups: control (saline, i.m.) and HgCl2 group (i.m., first dose 4.6 µg/kg, subsequent doses 0.07 µg/kg/d). Sperm parameters (count, motility and morphology) and biomarkers of oxidative stress in testis, epididymis, prostate, and vas deferens were analyzed. Mercury treatment produced a reduction in sperm quantity (testis and epididymis) and daily sperm production, following by decrease in sperm motility and increase on head and tail morphologic abnormalities. HgCl2 exposure was correlated with enhanced oxidative stress in reproductive organs, represented not only by augmented lipid peroxidation but also by changes in antioxidant enzymes activity superoxide dismutase (SOD) and catalase (CAT) and nonprotein thiol levels. In conclusion, chronic exposure to low doses of Hg impaired sperm quality and adversely affected male reproductive functions, which may be due, at least in part, to enhanced oxidative stress.
Assuntos
Poluentes Ambientais/toxicidade , Cloreto de Mercúrio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Espermatozoides/fisiologia , Testes de Toxicidade CrônicaRESUMO
UNLABELLED: Mercury increases the risk of cardiovascular disease and oxidative stress and alters vascular reactivity. This metal elicits endothelial dysfunction causing decreased NO bioavailability via increased oxidative stress and contractile prostanoid production. NADPH oxidase is the major source of reactive oxygen species (ROS) in the vasculature. Our aim was to investigate whether treatment with apocynin, an NADPH oxidase inhibitor, prevents the vascular effects caused by chronic intoxication with low concentrations of mercury. Three-month-old male Wistar rats were treated for 30 days with a) intramuscular injections (i.m.) of saline; b) HgCl(2) (i.m. 1(st) dose: 4.6 µg/kg, subsequent doses: 0.07 µg/kg/day); c) Apocynin (1.5 mM in drinking water plus saline i.m.); and d) Apocynin plus HgCl(2). The mercury treatment resulted in 1) an increased aortic vasoconstrictor response to phenylephrine and reduced endothelium-dependent responses to acetylcholine; 2) the increased involvement of ROS and vasoconstrictor prostanoids in response to phenylephrine, whereas the endothelial NO modulation of such responses was reduced; and 3) the reduced activity of aortic superoxide dismutase (SOD) and glutathione peroxidase (GPx) and increased plasma malondialdehyde (MDA) levels. Treatment with apocynin partially prevented the increased phenylephrine responses and reduced the endothelial dysfunction elicited by mercury treatment. In addition, apocynin treatment increased the NO modulation of vasoconstrictor responses and aortic SOD activity and reduced plasma MDA levels without affecting the increased participation of vasoconstrictor prostanoids observed in aortic segments from mercury-treated rats. CONCLUSIONS: Mercury increases the vasoconstrictor response to phenylephrine by reducing NO bioavailability and increasing the involvement of ROS and constrictor prostanoids. Apocynin protects the vessel from the deleterious effects caused by NADPH oxidase, but not from those caused by prostanoids, thus demonstrating a two-way action.
Assuntos
Acetofenonas/farmacologia , Aorta/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Cloreto de Mercúrio/toxicidade , Acetilcolina/farmacologia , Administração Oral , Animais , Aorta/metabolismo , Aorta/fisiopatologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Injeções Intramusculares , Masculino , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/metabolismo , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Estresse Oxidativo/efeitos dos fármacos , Fenilefrina/farmacologia , Prostaglandinas/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Técnicas de Cultura de Tecidos , Vasoconstritores/farmacologia , Vasodilatadores/farmacologiaAssuntos
Aterosclerose/imunologia , Autoanticorpos/imunologia , Imunoglobulina A/imunologia , beta 2-Glicoproteína I/imunologia , Síndrome Antifosfolipídica/complicações , Aterosclerose/sangue , Aterosclerose/complicações , Autoanticorpos/sangue , Feminino , Humanos , Imunoglobulina A/sangue , MasculinoRESUMO
A esclerose sistêmica progressiva (ESP) é uma doença crônica caracterizada por vasculopatia disseminada e fibrose tecidual. O envolvimento intersticial pulmonar constitui uma de suas principais causas de morbimortalidade. Foram estudados 22 pacientes (20 mulheres, 2 homens) com ESP (14 com forma limitada, 8 com forma difusa) quanto à presença de fibrose pulmonar através de tomografia computadorizada (TC). Em 13 pacientes (59 por cento), fibrose pulmonar foi documentada tomograficamente. O RX de tórax foi normal em 6 destes 13 pacientes; nos outros 7 casos, as alterações tomográficas foram mais precoces e definidas do que as encontradas no RX de tórax. Em dois terços dos pacientes com fibrose pulmonar o espirograma simples foi alterado. A presença de estertores crepitantes bibasais constitui-se na anormalidade respiratória mais frequente nos pacientes com fibrose pulmonar. Variáveis como sexo, raça, presença de fatores antinucleares (FAN), padrões de FAN, tosse e dispnéia não foram estatisticamente distintos nos pacientes com ou sem fibrose pulmonar. A frequência de fibrose pulmonar nessa casuística de ESP foi intermediária, considerando-se os contrastantes dados de literatura. A TC foi claramente mais sensível do que o RX de tórax no diagnóstico de alterações fibróticas
Assuntos
Humanos , Masculino , Feminino , Escleroderma Sistêmico/complicações , Fibrose Pulmonar , TomografiaRESUMO
Prefacio, Frank M. McCarthy. Valoración física previa al tratamiento en el consultorio dental. Diagnóstico de dolor maxilofacial agudo, Gustav O. Kruger, Donald C. Reynolds. Lesiones agudas de la cavidad bucal. Raymond F. Huesbsch. Complicaciones de la anestesia local, Niels Bjorn Jorgensen, Jess Hayden Jr. Emergencias en anestesia general, John B. McVeigh. Establecimiento de un pasaje de aire de emergencia, Leo Korchin. Manejo de pacientes dentales embarazadas, Leonard Z. Lyon, Melvyn S. Wishan. Emergencias quirúrgicas en la práctica dental, Robert B. Shira. Tratamiento de emergencia en lesiones maxilofaciales, Lowell E. McKelvey. Prevención y tratamiento de las hemorragias dentales, L. W. Reeve. Extracción de raíces fracturadas, Ralph G. OBrien Jr. Involucración quirúrgica del seno maxilar, Arthur R. Dewey. Tratamiento de urgencia de dientes anteriores permanentes, Robert G. Andrews. Emergencias cardiovasculares y otras emergencias médicas en el consultorio dental, Frank M. Mc Carthy. Paro cardiopulmonar, W. B. Kouwenhoven, James R. Jude. Intoxicación por drogas, Robert Bruce Steiner. Drogas de emergencia del consultorio dental, W. Howard Davis. Oxigenoterapia, presión sanguínea y determinación del pulso y técnica de venipunctura, John Hagen. Tratamiento del shock por el odontólogo general, William B. Kinney. Nociones de primeros auxilios, I. Joseph Kumin. Aspectos legales de las emergencias dentales, G. A. Sheppard
Assuntos
Assistência Ambulatorial , OdontologiaRESUMO
Prefacio, Frank M. McCarthy. Valoración física previa al tratamiento en el consultorio dental. Diagnóstico de dolor maxilofacial agudo, Gustav O. Kruger, Donald C. Reynolds. Lesiones agudas de la cavidad bucal. Raymond F. Huesbsch. Complicaciones de la anestesia local, Niels Bjorn Jorgensen, Jess Hayden Jr. Emergencias en anestesia general, John B. McVeigh. Establecimiento de un pasaje de aire de emergencia, Leo Korchin. Manejo de pacientes dentales embarazadas, Leonard Z. Lyon, Melvyn S. Wishan. Emergencias quirúrgicas en la práctica dental, Robert B. Shira. Tratamiento de emergencia en lesiones maxilofaciales, Lowell E. McKelvey. Prevención y tratamiento de las hemorragias dentales, L. W. Reeve. Extracción de raíces fracturadas, Ralph G. OBrien Jr. Involucración quirúrgica del seno maxilar, Arthur R. Dewey. Tratamiento de urgencia de dientes anteriores permanentes, Robert G. Andrews. Emergencias cardiovasculares y otras emergencias médicas en el consultorio dental, Frank M. Mc Carthy. Paro cardiopulmonar, W. B. Kouwenhoven, James R. Jude. Intoxicación por drogas, Robert Bruce Steiner. Drogas de emergencia del consultorio dental, W. Howard Davis. Oxigenoterapia, presión sanguínea y determinación del pulso y técnica de venipunctura, John Hagen. Tratamiento del shock por el odontólogo general, William B. Kinney. Nociones de primeros auxilios, I. Joseph Kumin. Aspectos legales de las emergencias dentales, G. A. Sheppard
Assuntos
Assistência Ambulatorial , OdontologiaRESUMO
Prefacio, Frank M. McCarthy. Valoración física previa al tratamiento en el consultorio dental. Diagnóstico de dolor maxilofacial agudo, Gustav O. Kruger, Donald C. Reynolds. Lesiones agudas de la cavidad bucal. Raymond F. Huesbsch. Complicaciones de la anestesia local, Niels Bjorn Jorgensen, Jess Hayden Jr. Emergencias en anestesia general, John B. McVeigh. Establecimiento de un pasaje de aire de emergencia, Leo Korchin. Manejo de pacientes dentales embarazadas, Leonard Z. Lyon, Melvyn S. Wishan. Emergencias quirúrgicas en la práctica dental, Robert B. Shira. Tratamiento de emergencia en lesiones maxilofaciales, Lowell E. McKelvey. Prevención y tratamiento de las hemorragias dentales, L. W. Reeve. Extracción de raíces fracturadas, Ralph G. OBrien Jr. Involucración quirúrgica del seno maxilar, Arthur R. Dewey. Tratamiento de urgencia de dientes anteriores permanentes, Robert G. Andrews. Emergencias cardiovasculares y otras emergencias médicas en el consultorio dental, Frank M. Mc Carthy. Paro cardiopulmonar, W. B. Kouwenhoven, James R. Jude. Intoxicación por drogas, Robert Bruce Steiner. Drogas de emergencia del consultorio dental, W. Howard Davis. Oxigenoterapia, presión sanguínea y determinación del pulso y técnica de venipunctura, John Hagen. Tratamiento del shock por el odontólogo general, William B. Kinney. Nociones de primeros auxilios, I. Joseph Kumin. Aspectos legales de las emergencias dentales, G. A. Sheppard
Assuntos
Assistência Ambulatorial , OdontologiaRESUMO
Prefacio, Frank M. McCarthy. Valoración física previa al tratamiento en el consultorio dental. Diagnóstico de dolor maxilofacial agudo, Gustav O. Kruger, Donald C. Reynolds. Lesiones agudas de la cavidad bucal. Raymond F. Huesbsch. Complicaciones de la anestesia local, Niels Bjorn Jorgensen, Jess Hayden Jr. Emergencias en anestesia general, John B. McVeigh. Establecimiento de un pasaje de aire de emergencia, Leo Korchin. Manejo de pacientes dentales embarazadas, Leonard Z. Lyon, Melvyn S. Wishan. Emergencias quirúrgicas en la práctica dental, Robert B. Shira. Tratamiento de emergencia en lesiones maxilofaciales, Lowell E. McKelvey. Prevención y tratamiento de las hemorragias dentales, L. W. Reeve. Extracción de raíces fracturadas, Ralph G. OBrien Jr. Involucración quirúrgica del seno maxilar, Arthur R. Dewey. Tratamiento de urgencia de dientes anteriores permanentes, Robert G. Andrews. Emergencias cardiovasculares y otras emergencias médicas en el consultorio dental, Frank M. Mc Carthy. Paro cardiopulmonar, W. B. Kouwenhoven, James R. Jude. Intoxicación por drogas, Robert Bruce Steiner. Drogas de emergencia del consultorio dental, W. Howard Davis. Oxigenoterapia, presión sanguínea y determinación del pulso y técnica de venipunctura, John Hagen. Tratamiento del shock por el odontólogo general, William B. Kinney. Nociones de primeros auxilios, I. Joseph Kumin. Aspectos legales de las emergencias dentales, G. A. Sheppard