RESUMO
Leptin, an adipose-secreted hormone, links metabolism and immunity. Our aim was to determine whether leptin affects the alloimmune response. We used an allogeneic skin transplant model as a means to analyze the allograft immune response in Lep(ob/ob) and wild-type mice. Leptin deficiency results in an increased frequency of Treg and Th2 cells and a prolonged graft survival. These effects of leptin deficiency indicate the importance of leptin and obesity in modulating the allograft immune responses. Our data suggest a possible explanation for the increased susceptibility of hyperleptinemic obese patients to acute and chronic graft rejection.
Assuntos
Sobrevivência de Enxerto/fisiologia , Leptina/fisiologia , Células Th2/imunologia , Animais , Citometria de Fluxo , Teste de Cultura Mista de Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase , Transplante HomólogoRESUMO
The innate immune system plays an important role as a first response to tissue injury. This first response is carried out via germline-encoded receptors. They can recognize exogenous Pathogen-Associated Molecular Patterns and endogenous Dangers-Associated Molecular Patterns. The Toll-Like Receptor (TLR) family is well-studied, but more recently another family in the cytoplasmic compartment, called nod-like receptor (NLR), was discovered. In addition to being present in inflammatory cells, these receptors are widely distributed in various cell types, including renal tissue, where these receptors have an important role in triggering the inflammatory response during renal diseases. This review summarizes the present data regarding the role of TLRs and NLRs in the course and development of various kidney pathologies.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/imunologia , Nefropatias/imunologia , Receptores Toll-Like/imunologia , Animais , Humanos , Imunidade Inata/imunologiaRESUMO
Apoptosis and necrosis are considered conceptually and morphologically distinct forms of cell death. Here, we report that demise of human T cells caused by two classic apoptotic triggers (staurosporin and CD95 stimulation) changed from apoptosis to necrosis, when cells were preemptied of adenosine triphosphate (ATP). Nuclear condensation and DNA fragmentation did not occur in cells predepleted of ATP and treated with either of the two inducers, although the kinetics of cell death were unchanged. Selective and graded repletion of the extramitochondrial ATP/pool with glucose prevented necrosis and restored the ability of the cells to undergo apoptosis. Pulsed ATP/depletion/repletion experiments also showed that ATP generation either by glycolysis or by mitochondria was required for the active execution of the final phase of apoptosis, which involves nuclear condensation and DNA degradation.
Assuntos
Trifosfato de Adenosina/metabolismo , Apoptose , Morte Celular , Necrose , Linhagem Celular , Núcleo Celular/metabolismo , Cisteína Endopeptidases/metabolismo , Humanos , Laminas , Mitocôndrias/metabolismo , Proteínas Nucleares/metabolismoRESUMO
Serum carbohydrate-deficient transferrin (CDT) is the most specific marker of chronic alcohol abuse so far. The performance of commercial HPLC over the ELISA method for measurement of CDT was evaluated on a series of 105 serum samples obtained from subjects referred to the Toxicology Laboratory of Salvatore Maugeri Hospital for alcohol-related problems. Compared to ELISA, HPLC analysis was more valuable for determining alcohol-related patterns of CDT isoforms and quantifying serum levels of disialotransferrin that better reflect chronic heavy drinking. Other significant advantages of the HPLC method included reproducible separation and easier detection of glycoform types and genetic transferrin variants that are known to cause falsely high or low results in sera examined by immunoassay. Current scientific evidence indicates that disialotransferrin is the target analyte for CDT determination and HPLC the current CDT analysis reference method. Systematic studies for early assessment of excessive alcohol intake or abuse of alcoholic substances in workers are recommended by the Italian legislation in accordance with the European Alcohol Action Plan (EAAP) launched by the WHO Regional Committee for Europe. These studies are advisable given their potential role in preventing negative effects of alcohol abuse in workplace. A research strategy combining CDT and other laboratory markers with questionnaire and physician interview is recommended for examining subjects with alcohol related problems and the diagnosis of alcoholism. This approach can be applied for alcohol abuse in workplace surveillance.
Assuntos
Transtornos Relacionados ao Uso de Álcool/sangue , Cromatografia Líquida de Alta Pressão , Ensaio de Imunoadsorção Enzimática , Saúde Ocupacional , Transferrina/análogos & derivados , Feminino , Humanos , Masculino , Isoformas de Proteínas , Risco , Transferrina/análiseRESUMO
In this paper, we investigate the use of nonlinear distortion of the electrical post-detection signal in order to design simple, yet very effective, maximum likelihood sequence detection (MLSD) receivers for optical communications with direct photo-detection. This distortion enables the use of standard Euclidean branch metrics in the Viterbi algorithm which implements MLSD. Our results suggest that the nonlinear characteristic can be optimized with respect to the uncompensated chromatic dispersion and other relevant system parameters, such as the extinction ratio. The proposed schemes with optimized distortion exhibit the same performance of more sophisticated MLSD schemes, still guaranteeing more efficient Viterbi algorithm implementation.
RESUMO
Styrene-7,8-oxide (SO) is the main metabolite of styrene, a neurotoxic volatile organic compound used industrially. Here we report the novel observation that several markers of oxidative stress were affected in SK-N-MC cells exposed for 16 h to concentrations of SO that induce apoptotic cell death. The production of Thiobarbituric Acid Reactive Substances (TBARS), rose from 69.1 +/- 15.7 nmol/g protein (control) to 119.3 +/- 39.2 and 102.0 +/- 17.3 nmol/g protein after exposure to 0.3 and 1 mM SO, respectively. Carbonyl group levels were significantly enhanced by SO at both concentrations. The lower dose also decreased sulphydryl groups. SO caused a marked oxidative DNA damage, as shown by a fivefold increase in 8-hydroxy-2(')-deoxyguanosine (8-OHdG). In addition, SO exposure resulted in alterations of scavenging abilities, given the reduction of both glutathione (GSH) and glutathione-S-transferase (GST) activity. Induction of expression of the oxidative stress response gene heme-oxygenase-1 (HO-1) and an increased HO-1 activity were also observed. These data provide compelling evidence that oxidative stress significantly contributes to SO toxicity in neuronal cells.
Assuntos
Carcinógenos/toxicidade , Desoxiguanosina/análogos & derivados , Compostos de Epóxi/toxicidade , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , 8-Hidroxi-2'-Desoxiguanosina , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Dano ao DNA , Desoxiguanosina/metabolismo , Relação Dose-Resposta a Droga , Sequestradores de Radicais Livres/metabolismo , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Humanos , Neuroblastoma , Neurônios/metabolismo , Neurônios/patologia , Oxirredução/efeitos dos fármacos , Proteínas/efeitos dos fármacos , Proteínas/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Predictive in vitro hematotoxicity assays using human cells will provide estimation of tolerable level and aid considerably the development of agents with greater therapeutic activity and less toxicity. Human hematopoietic cells can be derived from three sources: human bone marrow by sternal or femoral aspiration, mobilized peripheral blood, or umbilical cord blood samples collected from placentas after deliveries. Because of the difficulties to have a continuous supply of bone marrow cells from normal human donors and the related ethical problems, we performed a study to compare the sensitivity of human bone marrow cells (h-BMC) and human cord blood cells (h-CBC) to chemicals in order to confirm if h-CBC can readily replace bone marrow cells in checking the sensitivity of GM-CFU progenitors to drugs as preliminarily reported in literature. Our results showed that the prediction of IC50 values in human model is quite similar by using h-BMC or h-CBC. On the contrary, the type of medium influenced in a significant way the ICs determination of some drugs.
Assuntos
Células da Medula Óssea/efeitos dos fármacos , Sangue Fetal/citologia , Granulócitos/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Avaliação Pré-Clínica de Medicamentos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Interleucina-3/farmacologia , Interleucina-6/farmacologia , Fator de Células-Tronco/farmacologiaRESUMO
The presence of muscarinic acetylcholine receptors on lymphocytes has been demonstrated by radioligand binding experiments. Although the specific subtype(s) of muscarinic acetylcholine receptors expressed in lymphocytes is still unknown, some reports suggest the presence of the m2 subtype. In this study we analyzed the expression of m2 subtype mRNA in rat mononuclear cells, B lymphocytes and T lymphocytes by Northern blot hybridization and reverse transcription-polymerase chain reaction. Positive signals for the presence of m2 mRNA were found in rat heart, brainstem, cerebral cortex, corpus striatum and hippocampus, which were used as positive controls. On the other hand, no expression of m2 was detected in lymphocytes. These results indicate that mRNA for the m2 subtype is absent in rat lymphocytes and that one or more other subtypes may be responsible for the reported results in binding experiments.
Assuntos
Linfócitos/química , RNA Mensageiro/análise , Receptores Muscarínicos/genética , Animais , Sequência de Bases , Feminino , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Ratos , Ratos Sprague-DawleyRESUMO
In human isolated detrusor strips, submaximal contractile responses evoked by electrical stimulation were resistant to hexamethonium (30 microM) and abolished by tetrodotoxin (0.6 microM) and hyoscine (1 microM), indicating the activation of postganglionic cholinergic nerves. In methysergide (1 microM) and ondansetron (3 microM) pretreated tissues, 5-hydroxytryptamine (5-HT) (0.3 nM-1 microM) caused a concentration-dependent increase in the amplitude of contractions (pEC50 = 8.1), which was antagonized by the selective 5-HT4 receptor antagonist GR 113808 (3, 10 and 30 nM) in a competitive manner. Schild analysis yielded a pA2 estimate of 8.9, a value comparable to that reported for GR 113808 in other animal and human peripheral tissues (8.8-9.7). Our findings indicate that neuromuscular cholinergic transmission in human isolated detrusor muscle is facilitated by neural 5-HT receptors belonging to the 5-HT4 subtype. The human urinary bladder can thus be regarded as an additional site in which 5-HT4 receptors are distributed.
Assuntos
Músculo Liso/fisiologia , Junção Neuromuscular/fisiologia , Sistema Nervoso Parassimpático/fisiologia , Receptores de Serotonina/fisiologia , Transmissão Sináptica/fisiologia , Estimulação Elétrica , Humanos , Técnicas In Vitro , Indóis/farmacologia , Contração Isométrica/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/inervação , Junção Neuromuscular/efeitos dos fármacos , Sistema Nervoso Parassimpático/efeitos dos fármacos , Receptores de Serotonina/efeitos dos fármacos , Antagonistas da Serotonina/farmacologia , Sulfonamidas/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/inervação , Bexiga Urinária/fisiologiaRESUMO
Because of the wide use of pesticides for domestic and industrial purposes, the evaluation of their potential effects is of major concern for public health. The myelotoxicity of the herbicide propanil (3,4-dichloroproprioanilide) and its metabolite 3,4-dichloroaniline (DCA) is well documented in mice, but evidence that pesticides may severely compromise hematopoiesis in humans is lacking. In this study, an interspecies comparison of in vitro toxicity of these two compounds on murine and human burst- and colony-forming unit-erythrocyte (BFU-E, CFU-E) and colony-forming unit-granulocyte/macrophage (CFU-GM) progenitors, has been carried out. Murine bone marrow progenitors and human cord blood cells were exposed to propanil or DCA in doses ranging from 10 micro M to 1000 micro M, and the toxic effect was detected by a clonogenic assay with continuous exposure to the compounds. The results on murine cells indicate that the erythrocytic lineage is the most sensitive target for propanil and DCA. On the other hand, human progenitors seem to be less sensitive to the toxic effects of both compounds than murine progenitors at the same concentrations (IC(50) values are 305.2 +/- 22.6 micro M [total erythroid colonies] and >500 micro M [CFU-GM] for propanil). Propanil was significantly more toxic to human erythroid progenitors than to human CFU-GM progenitors, as was found for the murine cells, emphasizing the role of the heme pathway as the target for propanil. These data confirm the evidence that the compounds investigated interfere with erythroid colony formation at different stages of the differentiation pathway and have different effects according to the dose.
Assuntos
Compostos de Anilina/toxicidade , Doenças da Medula Óssea/induzido quimicamente , Células Precursoras Eritroides/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Herbicidas/toxicidade , Propanil/toxicidade , Animais , Separação Celular , Sobrevivência Celular/efeitos dos fármacos , Ensaio de Unidades Formadoras de Colônias , Granulócitos/efeitos dos fármacos , Humanos , Camundongos , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacosRESUMO
In rat primary cortical cultures, carbachol caused a time- and concentration-dependent increase in guanosine cyclic 3',5'-monophosphate (cGMP) levels, which was antagonized by the muscarinic antagonist atropine. Glutamate and sodium nitroprusside also caused large increases in cGMP levels, as previously reported. Two nitric oxide (NO) synthase inhibitors, L-NG-nitroarginine and L-NG-monomethylarginine, were tested for their ability to inhibit the carbachol- and the glutamate-induced cGMP formation. The cGMP response to carbachol was decreased by both compounds in a dose-dependent fashion. The effect of L-NG-nitroarginine was competitively reversed by addition of an excess of L-arginine. Similarly, the stimulatory effect of glutamate on cGMP levels was antagonized by L-NG-nitroarginine and L-NG-monomethylarginine. Hemoglobin, a scavenger of NO, also blocked the carbachol-stimulated cGMP production. These results indicate that muscarinic receptor-stimulated cGMP formation in rat cerebral cortex is mediated by NO.
Assuntos
Córtex Cerebral/metabolismo , GMP Cíclico/biossíntese , Óxido Nítrico/metabolismo , Receptores Muscarínicos/fisiologia , Aminoácido Oxirredutases/antagonistas & inibidores , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Células Cultivadas , Córtex Cerebral/citologia , Óxido Nítrico Sintase , Nitroarginina , Ratos , Ratos Sprague-DawleyRESUMO
Exposure of mature rat cerebellar granule neurons to non-depolarizing conditions (5 mM K+) for 24 h resulted in the onset of apoptosis. NMDA, forskolin, carbachol and GABA attenuated low K+-induced toxicity, although to a different extent, with NMDA and GABA being the most effective agents. When cells were co-exposed for 24 h to ethanol, the survival promoting action of NMDA and carbachol, but not that of forskolin and GABA, was attenuated. By contrast, a 24 h cell pre-treatment with ethanol, followed by its removal prior to K+ deprivation, was ineffective towards the neurotrophic action of NMDA and carbachol. The concomitant presence of alcohol and neurotrophic factors was not required for the pro-apoptotic effect of ethanol to be manifest after a long-term alcohol exposure: inhibition of NMDA- and carbachol-mediated neurotrophism was still observed when cells were pre-exposed for 72 h to alcohol in depolarizing conditions, prior to the challenge with 5 mM K+-containing medium and the test compounds in the absence of ethanol. The present study shows that ethanol promotes apoptotic cell death of cultured cerebellar neurons by selectively inhibiting the neurotrophic effect of NMDA and carbachol, and suggests that alcohol may cause permanent changes in the control mechanisms of apoptosis: this finding may have significant implications for the in vivo toxicity of prenatal ethanol exposure on the developing cerebellum.
Assuntos
Carbacol/farmacologia , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Agonistas Muscarínicos/farmacologia , N-Metilaspartato/farmacologia , Neurônios/citologia , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cerebelo/citologia , Colforsina/farmacologia , Interações Medicamentosas , Microscopia Eletrônica , Neurônios/química , Neurônios/ultraestrutura , Potássio/farmacologia , Ratos , Ratos Sprague-Dawley , Ácido gama-Aminobutírico/farmacologiaRESUMO
The developing brain is extremely sensitive to the neurotoxicity of ethanol; however, the mechanism(s) of its developmental neurotoxicity are still elusive. In the developing rat brain, ethanol exerts an age-, brain region-, and receptor-specific inhibitory effect on muscarinic receptor-stimulated phosphoinositide metabolism, which may be linked to some of the neurotoxic effects of ethanol found in children with fetal alcohol syndrome. Since some studies have suggested that the ethanol metabolite acetaldehyde may mediate, at least in part, the developmental effects of ethanol, in the present study we have examined whether acetaldehyde would inhibit carbachol-stimulated phosphoinositide metabolism in brain slices from immature rats. We also tested propionaldehyde, the corresponding aldehyde of n-propanol, another alcohol shown to cause microencephaly and to affect phosphoinositide metabolism in the developing rat. Neither acetaldehyde nor propionaldehyde, at concentrations up to 1 mM, had any inhibitory effect on this system, while the two alcohols did, as previously reported. These results suggest that ethanol itself may be the primary agent responsible for its developmental neurotoxicity.
Assuntos
Acetaldeído/toxicidade , Envelhecimento/fisiologia , Encéfalo/metabolismo , Carbacol/farmacologia , Etanol/toxicidade , Fosfatidilinositóis/metabolismo , Receptores Muscarínicos/fisiologia , 1-Propanol/toxicidade , Aldeídos/toxicidade , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Cerebelo/metabolismo , Córtex Cerebral/metabolismo , Relação Dose-Resposta a Droga , Feminino , Hipocampo/metabolismo , Técnicas In Vitro , Cinética , Masculino , Especificidade de Órgãos , Ratos , Ratos Sprague-Dawley , Receptores Muscarínicos/efeitos dos fármacosRESUMO
The neurotoxicity of high levels of methylmercury (MeHg) and the high susceptibility of the developing brain are well established both in humans and experimental animals. Prenatally poisoned children display a range of effects varying from severe cerebral palsy to subtle developmental delays. Still unknown is the lowest dose that impairs neurodevelopment. The primary source of human exposure is the fish. The data obtained so far from epidemiological studies on fish-eating populations are not consistent. A reference dose of 0.1 microg MeHg/kg per day has been established by the U.S. Environmental Protection Agency based on a study on Iraqi children exposed to MeHg in utero. However, these exposures occurred at high level for a limited period of time, and consequently were not typical of lower chronic exposure levels associated with fish consumption. Major obstacles for estimation of a threshold dose for MeHg include the delayed appearance of the neurodevelopmental effects following prenatal exposure and limited knowledge of cellular and molecular processes underlying these neurological changes. In this respect, a strategy which aims at identifying sensitive molecular targets of MeHg at environmentally relevant levels may prove particularly useful to risk assessment. Here some examples of MeHg molecular effects occurring at low doses/concentrations are presented.
Assuntos
Exposição Ambiental/efeitos adversos , Intoxicação do Sistema Nervoso por Mercúrio/metabolismo , Compostos de Metilmercúrio/toxicidade , Neurotoxinas/toxicidade , Animais , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Feminino , Humanos , Intoxicação do Sistema Nervoso por Mercúrio/patologia , Intoxicação do Sistema Nervoso por Mercúrio/fisiopatologia , Proteínas do Tecido Nervoso/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Sistema Nervoso/efeitos dos fármacos , Sistema Nervoso/crescimento & desenvolvimento , Sistema Nervoso/patologia , Gravidez , Efeitos Tardios da Exposição Pré-NatalRESUMO
Aluminum (Al) is believed to exert a primary role in the neurotoxicity associated with dialysis encephalopathy and has been suggested to be involved in a number of other neurological disorders, including Alzheimer's disease. Al, complexed with fluoride to form fluoroaluminate (AlF4-), can activate the GTP-binding (G) proteins of the adenylate cyclase and retinal cyclic GMP phosphodiesterase systems. Since an involvement of G-proteins with cerebral phosphoinositide (PtdIns) metabolism has also been suggested, in this study we investigated the interaction of the stable GTP analogue GTP(S), Al salts and NaF with this system. In rat cerebral cortical membranes, GTP(S) dose-dependently stimulated [3H]inositol phosphates ([3H]InsPs) accumulation. This effect was potentiated by carbachol and was partially prevented by the GTP-binding antagonist GDP(S), indicating that CNS muscarinic receptor activation is coupled to PtdIns hydrolysis via putative G-protein(s). GTP(S) stimulation was also inhibited by phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, which is known to exert a negative feedback control on agonist-stimulated PtdIns metabolism. Both Al salts and NaF mimicked the action of GTP(S) in stimulating PtdIns turnover. Their actions were highly synergistic, suggesting that AlF4- could be the active stimulatory species. However, the stimulatory effects of AlCl3 and/or NaF were not potentiated by carbachol and were not inhibited by GDP(S) and PMA, suggesting that separate sites of action might exist for GTP(S) and AlF4-. In the nervous tissue, activation of PtdIns hydrolysis by Al (probably as AlF4-) may be mediated by activating a regulatory G-protein at a location distinct from the GTP-binding site or by a direct stimulation of phospholipase C.
Assuntos
Compostos de Alumínio , Alumínio/farmacologia , Córtex Cerebral/metabolismo , Cloretos/farmacologia , Fosfatos de Inositol/metabolismo , Cloreto de Alumínio , Animais , Carbacol/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Córtex Cerebral/efeitos dos fármacos , Sinergismo Farmacológico , Guanosina 5'-O-(3-Tiotrifosfato)/farmacologia , Masculino , Antagonistas Muscarínicos , Ratos , Ratos Endogâmicos , Receptores Muscarínicos/efeitos dos fármacos , Fluoreto de Sódio/farmacologiaRESUMO
The in vitro effects of mercuric chloride (HgCl2) and methylmercury (CH3HgOH) on the M1 and M2 muscarinic receptor subtypes were investigated in rat brain cortical membranes. HgCl2 and CH3HgOH were almost equipotent in inhibiting the binding of [3H]telenzepine to M1 receptors (IC50s = 2.2 and 3.4 microM, respectively). Conversely, HgCl2 was a thirty-fold more potent inhibitor of [3H]AF-DX 384 binding to M2 sites than CH3HgOH (lC50s = 5 and 149 microM, respectively). In all cases HgCl2 showed steep and monophasic inhibition curves, whereas those of CH3HgOH were biphasic (M1) or shallow (M2). CH3HgOH-induced inhibition of both [3H]telenzepine and [3H]AF-DX 384 binding was of the competitive type, while HgCl2 caused a pronounced reduction of the Bmax value associated with a small change in affinity. CH3HgOH also decreased the affinity of the agonist carbachol for M1 and M2 receptors, while inorganic mercury had minimal effects on the carbachol dose-response curves. These results indicate that inorganic and organic mercury differ in their interaction with muscarinic receptor subtypes and that M1 receptors may represent a preferential target for their effects.
Assuntos
Encéfalo/efeitos dos fármacos , Compostos de Mercúrio/farmacologia , Receptores Muscarínicos/efeitos dos fármacos , Animais , Carbacol/farmacologia , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Interactions of chemicals with cerebral neurotransmitters, receptors, and second messenger systems are often accompanied by similar changes involving components in non-neural tissues. On this basis, indirect strategies have been developed to investigate neural cell function parameters by methods using accessible cells such as platelets or peripheral blood lymphocytes. The validity of certain surrogate markers of biochemical events occurring in the nervous system has been documented by recent studies in both laboratory animals and humans. Although experience with neurotoxicants is still limited, advantages and limitations of methods using peripheral blood cells as indicators of chemically-induced nervous system changes have been documented by a number of studies in psychopharmacology and biological psychiatry. Applicability of this approach in conventional population studies of environmental chemicals remains to be demonstrated. However, recent data regarding the action of low doses of mercury and organophosphates on receptors and signal transduction pathways in peripheral lymphocytes suggest useful applications of certain surrogate markers in mechanistic studies of neurotoxicity in vivo and, possibly, in assessing early biochemical effects of neurotoxicants in humans.
Assuntos
Monitoramento Ambiental/métodos , Sistema Nervoso/efeitos dos fármacos , Toxicologia/métodos , Biomarcadores/análise , Humanos , Linfócitos/efeitos dos fármacos , Mercúrio/efeitos adversos , Transdução de Sinais/efeitos dos fármacosRESUMO
Many environmental and occupational chemicals are known to affect the central and/or peripheral nervous system, causing changes that may result in neurological and psychiatric disorders. Because of the limited accessibility of the mammalian nervous tissue, new strategies are being developed to identify biochemical parameters of neuronal cell function, which can be measured in easily obtained tissues, such as blood cells, as potential markers of the chemically-induced alterations occurring in the nervous system. This review includes a comparative analysis of the effects of mercurials on calcium signalling in the neuroadrenergic PC12 cells and rat splenic T lymphocytes in an attempt to characterize this second messenger system as a potential indicator of subclinical toxicity. The suitability of neurotransmitter receptors in blood cells, such as the sigma binding sites, as biological markers of psychiatric disorders is also discussed.
Assuntos
Biomarcadores , Exposição Ambiental , Poluentes Ambientais/intoxicação , Animais , Encéfalo/metabolismo , Cálcio/metabolismo , Células/metabolismo , Humanos , Rim/metabolismo , Linfócitos/metabolismo , Compostos de Mercúrio/intoxicaçãoRESUMO
A survey is presented of the most important facets of toxicity due to chemical elements as well as of the mechanisms through which it may be triggered. In particular, a detailed discussion is made on the characteristics shown by arsenic, cadmium, chromium, lead, mercury, barium and beryllium, with specific reference to the influence exerted by physiological, environmental and life-style factors.
Assuntos
Metais/efeitos adversos , Adulto , Animais , Criança , Poluentes Ambientais/efeitos adversos , Feminino , Humanos , Masculino , Gravidez , Oligoelementos/efeitos adversosRESUMO
The electronics employed around particle accelerators can be disturbed or damaged because of single event effects (SEE). The most likely effect is the single event upset (SEU) which may affect all memory devices. In the case of high energy accelerators, SEUs are mostly produced by secondary charged particles generated by neutron interactions. The measurement of the energy and the lineal energy distribution of these neutron-induced charged particles was proposed. As a first approach, a commercial p-i-n photodiode was employed. This device was irradiated with thermal and monoenergetic fast neutrons. Some effects limiting the use of such a detector as a SEE spectrometer were observed, giving guidelines for the design of an application specific integrated circuit (ASIC). The possibility of creating a solid state microdosemeter by coupling the ASIC with a tissue-equivalent radiator is discussed. Moreover, the p-i-n photodiode covered with a hydrogenated plastic radiator may be employed as a proton-recoil spectrometer.