RESUMO
- New estimates of partial α-decay half-life, T1/2, for 156-162,174,176Hf isotopes by a semi-empirical, one-parameter model are given. The used model is based on the quantum mechanical tunneling mechanism through a potential barrier, where the Coulomb, centrifugal and overlapping components to the barrier have been considered within the spherical nucleus approximation. This approach enables to reproduce, within a factor 2, the measured T1/2 of ground-state to ground-state (gs-gs) α-transitions for the artificially produced 156-162Hf isotopes. Half-life predictions for α-transitions from the ground-state of 159,161Hf isotopes to the first gamma-excited level of 155,157Yb isotopes are reported for the first time. The model also provides T1/2-values of (2.43±0.28)×1016 a and (1.47±0.19)×1020 a for the naturally occurring 174Hf and 176Hf isotopes, respectively, in quite good agreement with a number of estimates by other authors. In addition, the present methodology indicates that 174,176Hf isotopes exhibit α-transition to the first gamma-excited level of their daughter Ytterbium isotopes which half-lives are found (0.9±0.1)×1018 a and (0.72±0.08)×1022 a, respectively, with a chance of being measured by improved α-detection and α-spectrometry methods available nowadays.
RESUMO
This paper reports on the morphological and electrical characterization at the nanometer scale and the investigation of the field emission characteristics of glassy carbon (GC) plates which underwent H-induced physical/chemical processes occurring in a dual-mode MW-RF plasma reactor. Plasma treatment produced on the GC surface arrays of vertically aligned conically shaped nanostructures, with density and height depending on the plasma characteristics. Two kinds of samples obtained under two different bias regimes have been deeply analyzed using an AFM apparatus equipped with tools for electric forces and surface potential measurements. The features of electron emission via the Field Emission (FE) mechanism have been correlated with the morphology and the structure at the nanoscale of the treated glassy carbon samples. The measured current density and the characteristics of the emission, which follow the Fowler-Nordheim law, indicate that the plasma-based methodology utilized for the engineering of the GC surfaces is able to turn conventional GC plates into efficient emission devices. The outstanding properties of GC suggest the use of such nanostructured materials for the assembling of cold cathodes to be used in a harsh environment and under extreme P/T conditions.
RESUMO
Nanodiamonds are a novel class of nanomaterials which have raised much attention for application in biomedical field, as they combine the possibility of being produced on large scale using relatively inexpensive synthetic processes, of being fluorescent as a consequence of the presence of nitrogen vacancies, of having their surfaces functionalized, and of having good biocompatibility. Among other applications, we mainly focus on drug delivery, including cell interaction, targeting, cancer therapy, gene and protein delivery. In addition, nanodiamonds for bone and dental implants and for antibacterial use is discussed. Techniques for detection and imaging of nanodiamonds in biological tissues are also reviewed, including electron microscopy, fluorescence microscopy, Raman mapping, atomic force microscopy, thermal imaging, magnetic resonance imaging, and positron emission tomography, either in vitro, in vivo, or ex vivo. Toxicological aspects related to the use of nanodiamonds are also discussed. Finally, patents, preclinical and clinical trials based on the use of nanodiamonds for biomedical applications are reviewed.
Assuntos
Microscopia de Fluorescência/métodos , Nanocápsulas/química , Nanodiamantes/uso terapêutico , Próteses e Implantes , Composição de Medicamentos/métodos , Nanocápsulas/ultraestrutura , Nanodiamantes/químicaRESUMO
In this paper we present some strategies that are being developed in our labs towards enabling nanodiamond-based applications for drug delivery. Rhodamine B (RhB) has been choosen as model molecule to study the loading of nanodiamonds with active moieties and the conditions for their controlled release. In order to test the chemical/physical interactions between functionalized detonation nanodiamond (DND) and complex molecules, we prepared and tested different RhB@DND systems, with RhB adsorbed or linked by ionic bonding to the DND surface. The chemical state of the DND surfaces before conjugation with the RhB molecules, and the chemical features of the DND-RhB interactions have been deeply analysed by coupling DND with Au nanoparticles and taking advantage of surface enhanced Raman spectroscopy SERS. The effects due to temperature and pH variations on the process of RhB release from the DND carrier have been also investigated. The amounts of released molecules are consistent with those required for effective drug action in conventional therapeutic applications, and this makes the DND promising nanostructured cargos for drug delivery applications.
Assuntos
Nanocápsulas/química , Nanocápsulas/ultraestrutura , Nanodiamantes/química , Nanodiamantes/ultraestrutura , Rodaminas/análise , Rodaminas/química , Espectrometria de Fluorescência/métodos , Difusão , Composição de Medicamentos/métodos , Corantes Fluorescentes/análise , Corantes Fluorescentes/químicaRESUMO
We compare, over wide temperature ranges, the transport properties of single-wall carbon nanotubes arranged in the form of aligned arrays or in the form of fibres. The experimental data show that both the forms of aggregates present a crossover in the transport mechanism from three-dimensional hopping of the electrons between localized states at high temperature to fluctuation-induced tunnelling across potential barriers at low temperature. The role of the junctions formed between the bundles in the array and between the nanotubes inside the fibres is discussed on the basis of the experimental results.
Assuntos
Condutividade Elétrica , Nanotubos de Carbono , Temperatura , Impedância Elétrica , Fenômenos MagnéticosRESUMO
Deposits of individual diamond grains and continuous polycrystalline diamond layers have been generated by means of a HFCVD technique onto different types of untreated or seeded NbN surfaces. To test the feasibility of using diamond layers as protective coatings for aerospace applications, we carried out diamond deposition onto the lithographically defined NbN microelectrodes of a NbN/SiO2 multifinger device. The morphological and structural features of the diamond deposits and of the substrates were characterized by FE-SEM, XRD and Raman spectroscopy. The preferential growth of diamond on the superconductive NbN enables the selective coating of the NbN microstripes sputtered on the insulating SiO2. Moreover the diamond coating procedure is able to preserve the structural integrity of the substrate material and to retain the shaped architecture of the device. For the polycrystalline diamond layers grown on NbN a residual stress of -9.8 GPa, largely due to thermal stress, has been estimated by Raman analysis. The diamond coatings of the NbN-based architectures result to be mechanically stable.
RESUMO
Electrochemical Double Layer Capacitors (EDLC), also known as supercapacitors, have been fabricated using Single Walled Carbon Nanotubes (SWCNTs) as active material for electrode assembling. In particular a new way of fabrication of ultra-thin electrodes (< or = 25 microm) directly formed on the separator has been proposed, and a prototype of EDLC has been realized and tested. For such devices the specific capacitance is in the range 40-45 F/g and the internal resistances in the range 6-8 omega x cm2, at current density of 2 mA x cm-2.
RESUMO
We investigate experimentally the transport properties of single-walled carbon nanotube bundles as a function of temperature and applied current over broad intervals of these variables. The analysis is performed on arrays of nanotube bundles whose axes are aligned along the direction of the externally supplied bias current. The data are found consistent with a charge transport model governed by the tunneling between metallic regions occurring through potential barriers generated by a nanotube's contact areas or bundle surfaces. Based on this model and on experimental data, we describe quantitatively the dependencies of the height of these barriers upon bias current and temperature.
RESUMO
The field emission behaviour of a series of nanocrystalline N-doped diamond films has been investigated and interpreted on the basis of the structural and compositional characteristics of the layers. The diamond films, formed by crystallites with grain size in the range 20-100 nm were produced from CH4/H2 mixtures using a HF-CVD apparatus. Nitrogen was added to the gaseous reactants in form of both N2 and of Urea. Micro-Raman spectroscopy and cathodoluminescence have been used to define the structure of the deposits on a nanometric scale. The field emission measurements have been carried out under a pressure of 10(-6) mbar using a sphere-to-plane anode-cathode configuration. The characteristics of the emission from the various nanodiamond samples and from different regions of the same sample are discussed in terms of field threshold, current density, current stability.
RESUMO
The field emission properties of hybrid carbon nanotubes/nanodiamond structures produced by one-step chemical vapor deposition (CVD) process have been investigated in order to assess their application as electron emitters for cold cathodes. The electron emission properties of a series of samples have been investigated by current-pressure, current-voltage and current-time measurements with the aim of testing the emission stability under working conditions relevant to technological applications. Stable emission, high values of current density and lack of arcing have been observed during prolonged working cycles, and without degradation of the material structure.
Assuntos
Cristalização/métodos , Diamante/química , Microeletrodos , Nanotecnologia/métodos , Nanotubos de Carbono/química , Nanotubos de Carbono/ultraestrutura , Condutividade Elétrica , Eletrodos , Transporte de Elétrons , Substâncias Macromoleculares/química , Teste de Materiais , Conformação Molecular , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
Surface assisted self-assembly of detonation nanodiamond particles (with typical sizes in the range 4-10 nm) has been obtained using different fractions of colloidal aqueous dispersions as starting material. The relationship between dispersion properties and structure/geometry of the aggregates deposited on Si or glass plates has been investigated. A series of differently shaped free-standing nanodiamond structures has been prepared, analysed and used as templates for the growth of polycrystalline diamond layers by the chemical vapour deposition (CVD) technique. The possibility of obtaining textured coating with a relatively strong [Formula: see text] preferred orientation (within a solid angle of about 0.6 srad) is also reported. Overall, the coupling of nanodiamond self-assembling to the CVD diamond growth enables one to produce specimens with complex 3D architectures. The proposed microfabrication methodology could represent a viable route for the production of free-standing all-diamond microcomponents, with tailored shapes and predefined crystalline features, to be used for advanced electronic applications.
RESUMO
Conductive polymer nanotubules of 1,2-diaminobenzene (1,2-DAB) were prepared using a porous polycarbonate membrane template, placed on a Pt foil and used to support the polymer, then, the electropolymerisation was performed by chronocoulometry. The obtained conductive polymer nanostructures were then placed on Pt electrode and used to support highly dispersed prussian blue (PB), which acts as the active component for H2O2 detection. The observed good stability of PB as catalyst of H2O2 was related to the presence of organic non-conventional conducting polymers in a composite nanostructured film. These nanostructured polymer/PB composite films were also characterised by scanning electron microscopy (SEM) and Raman spectroscopy. The non-conventional conducting polymer nanotubules/PB modified Pt electrodes were tested by cyclic voltammeter for stability at different pH values, then, by amperometry, for hydrogen peroxide, ascorbic acid, acetaminophen, uric acid and acetylcholine. Glucose oxidase (GOD), lactate oxidase (LOD), L-amino acid oxidase (L-AAOD), alcohol oxidase (AOD), glycerol-3-phosphate oxidase (GPO), lysine oxidase (LyOx), and choline oxidase (ChOx) were immobilised on PB layer supported on 1,2-diaminobenzene (1,2-DAB) nanotubules onto the Pt electrodes. Different strategies for enzyme immobilisation were performed and used. Analytical parameters such as reproducibility, interference rejection, response time, storage and operational stability of the sensors have been studied and optimised. Results provide a guide to design high sensitive, stable and interference-free biosensors. The glucose biosensors assembled with nanostructured poly(1,2-DAB) showed a detection limit of 5 x 10(-5) mol l(-1), a wide linearity range (5 x 10(-5) to 5 x 10(-3) mol l(-1)), a high selectivity, a stability of 3 months at 4 degrees C, and at least 4 weeks at room temperature. Similar analytical parameters and stability were also studied for L-(+)-lactic acid, L-leucine, ethanol, glycerol-3-phosphate, lysine, and choline biosensors.
Assuntos
Técnicas Biossensoriais/instrumentação , Eletroquímica/instrumentação , Ferrocianetos/química , Glucose Oxidase/química , Glucose/análise , Nanotubos/química , Platina/química , Técnicas Biossensoriais/métodos , Materiais Revestidos Biocompatíveis/química , Cristalização/métodos , Eletroquímica/métodos , Ativação Enzimática , Desenho de Equipamento , Análise de Falha de Equipamento , Concentração de Íons de Hidrogênio , Nanotubos/ultraestrutura , Polímeros/químicaRESUMO
The environmental stimulus of weaning has been shown to affect both the developmental expression of social behavior and the maturation of the opioid delta-receptors' subpopulation in altricial rodents. The aim of this study was to address both these issues by using the social interaction paradigm. Separate groups of male and female mice were randomly assigned to three different weaning ages -- early (Wean-15), regular (Wean-20), and delayed (Wean-25) -- and assessed when 30 days old under intraperitoneal administration of the selective delta-opioid agonist SNC80 (0, 0.1, or 0.3 mg/kg). Wean-15 male and female subjects were much more involved in investigating the partner as well as the cage environment compared to the regular Wean-20 group. An increased social investigation was also found as a consequence of delayed weaning in the female group. The neurobehavioral changes induced by the manipulation of weaning age were also reflected in an altered responsivity to the effects of SNC80 administration. The drug-induced increase in the expression of investigative and affiliative social interactions was further magnified by early weaning. A delayed weaning time was instead associated with reduced sensitivity to the drug, which suggests a delayed maturation of the system. As a whole, the present results indicate that the time of weaning is able to markedly affect the expression of social interactions of adolescent mice by possibly exerting a direct modulatory role on the development of the still plastic delta-opioid system.
Assuntos
Envelhecimento/psicologia , Analgésicos Opioides/farmacologia , Relações Interpessoais , Receptores Opioides delta/agonistas , Animais , Benzamidas/farmacologia , Peso Corporal/efeitos dos fármacos , Comportamento Exploratório/efeitos dos fármacos , Feminino , Asseio Animal , Masculino , Camundongos , Piperazinas/farmacologia , Comportamento SocialRESUMO
BACKGROUND AND AIMS: Inflammatory bowel disease is characterised by oxidative and nitrosative stress, leucocyte infiltration, upregulation of expression of intercellular adhesion molecule 1 (ICAM-1), and upregulation of P-selectin in the colon. The aim of the present study was to examine the effects of calpain inhibitor I in rats subjected to experimental colitis. METHODS: Colitis was induced in rats by intracolonic instillation of dinitrobenzene sulphonic acid (DNBS). RESULTS: Rats experienced haemorrhagic diarrhoea and weight loss. Four days after administration of DNAB, the mucosa of the colon exhibited large areas of necrosis. Neutrophil infiltration (determined by histology as well as by an increase in myeloperoxidase activity in the mucosa) was associated with upregulation of ICAM-1 and P-selectin as well as high tissue levels of malondialdehyde. Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) polymerase (PARP) showed intense staining in the inflamed colon. Staining of sections of colon obtained from DNBS treated rats with an anti-cyclooxygenase 2 antibody showed diffuse staining of the inflamed tissue. Furthermore, expression of inducible nitric oxide synthase was found mainly in macrophages located within the inflamed colon of DNBS treated rats. Calpain inhibitor I (5 mg/kg daily intraperitoneally) significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. Calpain inhibitor I also caused a substantial reduction in (i) degree of colon injury, (ii) rise in myeloperoxidase activity (mucosa), (iii) increase in tissue levels of malondialdehyde, (iv) increase in staining (immunohistochemistry) for nitrotyrosine and PARP, as well as (v) upregulation of ICAM-1 and P-selectin caused by DNBS in the colon. CONCLUSION: Calpain inhibitor I reduces the degree of colitis caused by DNBS. We propose that calpain inhibitor I may be useful in the treatment of inflammatory bowel disease.
Assuntos
Inibidores de Cisteína Proteinase/uso terapêutico , Glicoproteínas/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Tirosina/análogos & derivados , Adenosina Difosfato Ribose/farmacologia , Análise de Variância , Animais , Dinitrobenzenos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/metabolismo , Molécula 1 de Adesão Intercelular/efeitos dos fármacos , Masculino , Malondialdeído/farmacologia , Óxido Nítrico Sintase/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II , Selectina-P/efeitos dos fármacos , Peroxidase/efeitos dos fármacos , Prostaglandina-Endoperóxido Sintases/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Ácidos Sulfônicos , Tirosina/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
BACKGROUND AND METHODS: We investigated the effects of tempol, a membrane-permeable radical scavenger, on the multiple organ failure (MOF) caused by zymosan in the rat. Zymosan (500 mg/kg, suspended in saline solution, ip) enhances formation of reactive oxygen species, which contribute to the pathophysiology of MOF. After zymosan or saline administration, animals were monitored for 12 days. RESULTS: Treatment of rats with tempol (10, 30, or 100 mg/kg ip, 1 and 6 hrs after zymosan) attenuated the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan in a dose-dependent fashion. Tempol also attenuated the lung, liver, and intestinal injury (histology) as well as the increase in the concentrations of myeloperoxidase and malondialdehyde caused by zymosan in the lung, liver, and intestine. Immunohistochemical analysis for nitrotyrosine and for poly(adenosine 5'-diphosphate-ribose)synthetase demonstrated a positive staining in lung, liver, and intestine from zymosan-treated rats. The degree of staining for nitrotyrosine and for poly(adenosine 5'-diphosphate-ribose) synthetase was markedly reduced in tissue sections obtained from zymosan-treated rats that had received tempol (100 mg/kg ip). Furthermore, treatment of rats with tempol significantly reduced the following: a) the formation of peroxynitrite, b) the DNA damage, c) the impairment in mitochondrial respiration, and d) the decrease in the cellular concentration of oxidized nicotinamide adenine dinucleotide observed in macrophages harvested from the peritoneal cavity of rats treated with zymosan. CONCLUSION: This study provides the first evidence that tempol, a small molecule that permeates biological membranes and scavenges reactive oxygen species, attenuates the degree of MOF associated with zymosan-induced peritonitis in the rat.
Assuntos
Óxidos N-Cíclicos/uso terapêutico , Sequestradores de Radicais Livres/uso terapêutico , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Tirosina/análogos & derivados , Análise de Variância , Animais , Técnicas In Vitro , Intestino Delgado/patologia , Fígado/patologia , Pulmão/patologia , Masculino , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Poli(ADP-Ribose) Polimerases/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Marcadores de Spin , Estatísticas não Paramétricas , Tirosina/metabolismo , Zimosan/intoxicaçãoRESUMO
Inflammatory bowel disease (IBD) is characterized by oxidative and nitrosative stress, leukocyte infiltration, and up-regulation of intercellular adhesion molecule 1 (ICAM-1) expression in the colon. The aim of this study was to examine the effects of the pineal secretory product melatonin in rats subjected to experimental colitis. Colitis was induced in rats by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). Rats experienced bloody diarrhea and a significant loss of body weight. Four days after DNBS administration, the colon damage was characterized by areas of mucosal necrosis. Neutrophil infiltration (indicated by myeloperoxidase [MPO] activity in the mucosa) was associated with up-regulation of ICAM-1, expression of P-selectin, and high levels of malondialdehyde (MDA). Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) synthetase (PARS) showed an intense staining in the inflamed colon. Staining of colon tissue sections obtained from DNBS-treated rats with an anti-cycloxygenase-2 (COX-2) antibody showed a diffuse staining of the inflamed tissue. Furthermore, expression of inducible nitric oxide synthase (iNOS) was found mainly in the macrophages of the inflamed colons from DNBS-treated rats. Treatment with melatonin (15 mg/kg daily, intraperitoneally) significantly reduced the appearance of diarrhea and the loss of body weight. This was associated with a remarkable amelioration of the disruption of the colonic architecture, as well as a significant reduction of colonic MPO activity and MDA levels. Melatonin also reduced the appearance of nitrotyrosine and PARS immunoreactivity in the colon, as well as reducing the up-regulation of ICAM-1 and the expression of P-selectin. The intensity and degree of the stainings for COX-2 and iNOS were markedly reduced in tissue sections obtained from melatonin-treated rats. The results of the this study suggest that the administration of melatonin might be beneficial for the treatment of IBD.
Assuntos
Colite/tratamento farmacológico , Dinitrofluorbenzeno/análogos & derivados , Sequestradores de Radicais Livres/uso terapêutico , Melatonina/uso terapêutico , Tirosina/análogos & derivados , Animais , Colite/induzido quimicamente , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Dinitrofluorbenzeno/toxicidade , Técnica Indireta de Fluorescência para Anticorpo , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Selectina-P/metabolismo , Peroxidase/metabolismo , Poli Adenosina Difosfato Ribose/metabolismo , Ratos , Ratos Sprague-Dawley , Tirosina/metabolismoRESUMO
Adolescence is associated with an increased risk of developing drug abuse/dependence. During this ontogenetic phase, brain and hormonal systems are still undergoing crucial maturational rearrangements, which take place together with significant modifications in psychosocial development. However, the neurohormonal and behavioural facets of adolescence have been poorly investigated in relation to the vulnerability to psychostimulants such as MDMA ("ecstasy") and amphetamine. Novelty-seeking, a temperamental/behavioural trait that is typical of this age period, might substantially contribute to psychobiological vulnerability to drugs. In animal models of periadolescence, the search for novel stimuli and sensations actually shares a common neurobiological substrate (the reward-related brain mesolimbic pathways) with psychostimulants. Periadolescent mice are characterized by an unbalanced and "extremes-oriented" behaviour and by elevated levels of novelty-seeking. A deeper understanding of psychostimulant effects during adolescence, and the interaction between genetic, neurobiologic, psychosocial, and environmental factors, will lead to earlier and more effective prevention strategies.
Assuntos
Psicotrópicos/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/etiologia , Adolescente , Fatores Etários , Animais , Humanos , Camundongos , Modelos Animais , Psicologia do Adolescente , Fatores de Risco , Assunção de Riscos , Transtornos Relacionados ao Uso de Substâncias/psicologiaRESUMO
Inflammatory bowel disease is characterized by oxidative and nitrosative stress, leukocyte infiltration, up-regulation of the expression of intercellular adhesion molecule-1 (ICAM-1), and up-regulation of P-selectin in the colon. Here we investigate the effects of the tyrosine kinase inhibitor, Tyrphostin AG 126, in rats subjected to experimental colitis. Colitis was induced in rats by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). Rats experienced hemorrhagic diarrhea and weight loss. Four days after administration of DNBS, the mucosa of the colon exhibited large areas of necrosis. Neutrophil infiltration (determined by histology as well as an increase in myeloperoxidase activity in the mucosa) was associated with up-regulation of ICAM-1 and P-selectin, as well as high tissue levels of malondialdehyde. Immunohistochemistry for nitrotyrosine and poly(ADP-ribose) polymerase showed an intense staining in the inflamed colon. Staining with an anti-COX-2 antibody of sections of colon obtained from DNBS-treated rats showed a diffuse staining of the inflamed tissue. Furthermore, expression of inducible nitric oxide synthase was found mainly in macrophages located within the inflamed colon of DNBS-treated rats. Tyrphostin AG 126 (5 mg/kg daily ip) significantly reduced the degree of hemorrhagic diarrhea and weight loss caused by administration of DNBS. Tyrphostin AG 126 also caused a substantial reduction of (1) the phosphorylation of tyrosine residues of proteins (immunoblots of inflamed colon), (2) the degree of colonic injury, (3) the rise in myeloperoxidase activity (mucosa), (4) the increase in the tissue levels of malondialdehyde, (5) the increase in staining (immunohistochemistry) for nitrotyrosine and poly(ADP-ribose) polymerase, as well as (6) the up-regulation of ICAM-1 and P-selectin caused by DNBS in the colon. Thus, we provide the first evidence that the tyrosine kinase inhibitor Tyrphostin AG126 reduces the degree of colitis caused by DNBS.
Assuntos
Colite/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Tirfostinas/uso terapêutico , Animais , Peso Corporal/efeitos dos fármacos , Colite/patologia , Ciclo-Oxigenase 2 , Citocinas/biossíntese , Isoenzimas/biossíntese , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico Sintase Tipo II , Peroxidase/metabolismo , Prostaglandina-Endoperóxido Sintases/biossíntese , Ratos , Ratos Sprague-Dawley , Tirosina/análogos & derivados , Tirosina/biossínteseRESUMO
Inflammatory bowel disease is characterized by oxidative and nitrosative stress, leukocyte infiltration, and up-regulation of intercellular adhesion molecule 1 (ICAM-1) expression in the colon. The aim of the present study was to examine the effects of tempol, a membrane-permeable radical scavenger, in rats subjected to experimental colitis. Colitis was induced in rats by intracolonic instillation of dinitrobenzene sulfonic acid. Rats experienced bloody diarrhea and significant loss of body weight. At 4 days after the administration of dinitrobenzene sulfonic acid, the colon injury comprised of large areas of mucosal necrosis. Neutrophil infiltration (measured as increase in myeloperoxidase activity in the mucosa) was associated with up-regulation of ICAM-1 and expression of P-selectin and high levels of malondialdehyde (an indicator of lipid peroxidation). Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) synthetase showed an intense staining in the inflamed colon. Treatment of rats with tempol (15 mg/kg daily i.p.) significantly reduced the appearance of diarrhea and the loss in body weight. This was associated with a remarkable amelioration of the disruption of the colonic architecture as well as a significant reduction in the degree of both neutrophil infiltration and lipid peroxidation in the inflamed colon. Tempol also reduced the appearance of nitrotyrosine and poly (ADP-ribose) synthetase immunoreactivity in the colon as well as the up-regulation of ICAM-1 and P-selectin. The results of this study suggest that membrane-permeable radical scavengers, such as tempol, exert beneficial effects in experimental colitis and may, hence, be useful in the treatment of inflammatory bowel disease.