RESUMO
The efficiency of a thermoelectric generator model under maximum conditions is presented for two optimization criteria proposed under the context of finite-time thermodynamics, namely, the efficient power criterion and the Omega function, where this last function represents a trade-off between useful and lost energy. The results are compared with the performance of the device at maximum power output. A macroscopic thermoelectric generator (TEG) model with three possible sources of irreversibilities is considered: (i) the electric resistance R for the Joule heating, (ii) the thermal conductances Kh and Kc of the heat exchangers between the thermal baths and the TEG, and (iii) the internal thermal conductance K for heat leakage. In particular, two configurations of the macroscopic TEG are studied: the so-called exoreversible case and the endoreversible limit. It shows that for both TEG configurations, the efficiency at maximum Omega function is always greater than that obtained in conditions of maximum efficient power, and this in turn is greater than that of the maximum power regime.
RESUMO
Symptoms of depressive disorders such as anhedonia and despair can be a product of an aberrant adaptation to stress conditions. Chronic unpredictable stress model (CUS) can generate an increase in the activity of the hypothalamic-pituitary-adrenal axis (HPA) and induce a reduction of neurotrophin signaling and the proliferation of neural progenitors in the adult dentate gyrus, together with increased oxidative stress. Levels of the endocannabinoid anandamide (AEA) seem to affect these depression-by-stress-related features and could be modulated by fatty acid amide hydrolase (FAAH). We aimed to evaluate the effects of FAAH inhibitor, URB597, on depressive-like behavior and neural proliferation of mice subjected to a model of CUS. URB597 was administered intraperitoneally at a dose of 0.2 mg/kg for 14 days after CUS. Depressive-like behaviors, anhedonia, and despair were evaluated in the splash and forced swimming tests, respectively. Alterations at the HPA axis level were analyzed using the relative weight of adrenal glands and serum corticosterone levels. Oxidative stress and brain-derived neurotrophic factor (BDNF) were also evaluated. Fluorescence immunohistochemistry tests were performed for the immunoreactivity of BrdU and Sox2 colabeling for comparison of neural precursors. The administration of URB597 was able to reverse the depressive-like behavior generated in mice after the model. Likewise, other physiological responses associated with CUS were reduced in the treated group, among them, increase in the relative weight of the adrenal glands, increased oxidative stress, and decreased BDNF and number of neural precursors. Most of these auspicious responses to enzyme inhibitor administration were blocked by employing a cannabinoid receptor antagonist. In conclusion, the chronic inhibition of FAAH generated an antidepressant effect, promoting neural progenitor proliferation and BDNF expression, while reducing adrenal gland weight and oxidative stress in mice under the CUS model.
Assuntos
Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Amidoidrolases , Animais , Proliferação de Células , Corticosterona , Giro Denteado , Modelos Animais de Doenças , Camundongos , Estresse Psicológico/tratamento farmacológicoRESUMO
Parkinson's disease (PD) is a neurodegenerative disorder, caused by the selective death of dopaminergic neurons in the substantia nigra pars compacta. ß-caryophyllene (BCP) is a phytocannabinoid with several pharmacological properties, producing anti-inflammatory and antihypertensive effects. In addition, BCP protects dopaminergic neurons from neuronal death induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), yet it remains unclear if this effect is due to its antioxidant activity. To assess whether this is the case, the effect of BCP on the expression and activity of NAD(P)H quinone oxidoreductase (NQO1) was evaluated in mice after the administration of MPTP. Male C57BL/6 J mice were divided into four groups, the first of which received saline solution i.p. in equivalent volume and served as a control group. The second group received MPTP. The second group received MPTP hydrochloride (5 mg/kg, i.p.) daily for seven consecutive days. The third group received BCP (10 mg/kg) for seven days, administered orally and finally, the fourth group received MPTP as described above and BCP for 7 days from the fourth day of MPTP administration. The results showed that BCP inhibits oxidative stress-induced cell death of dopaminergic neurons exposed to MPTP at the same time as it enhances the expression and enzymatic activity of NQO1. Also, the BCP treatment ameliorated motor dysfunction and protected the dopaminergic cells of the SNpc from damage induced by MPTP. Hence, BCP appears to achieve at least some of its antioxidant effects by augmenting NQO1 activity, which protects cells from MPTP toxicity. Accordingly, this phytocannabinoid may represent a promising pharmacological option to safeguard dopaminergic neurons and prevent the progression of PD.
Assuntos
Antioxidantes/uso terapêutico , Intoxicação por MPTP/metabolismo , Intoxicação por MPTP/prevenção & controle , NAD(P)H Desidrogenase (Quinona)/biossíntese , Sesquiterpenos Policíclicos/uso terapêutico , Animais , Antioxidantes/farmacologia , Intoxicação por MPTP/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Parte Compacta da Substância Negra/efeitos dos fármacos , Parte Compacta da Substância Negra/metabolismo , Parte Compacta da Substância Negra/patologia , Sesquiterpenos Policíclicos/farmacologia , Distribuição AleatóriaRESUMO
Introducción. La Fibrosis Quística es la enfermedad hereditaria con pronóstico reducido más frecuente en raza blanca. Su incidencia varía según etnias. En Chile, la incidencia estimada es de 1/10.000 habitantes y la evidencia nacional acerca de la magnitud y caracterización de defunciones es escasa. El objetivo de este estudio es determinar la evolución de mortalidad por fibrosis quística en Chile durante 1997-2017. Materiales y Métodos. Estudio descriptivo retrospectivo sobre la tendencia de mortalidad por fibrosis quística en Chile. A partir de bases de datos secundarias del sistema de estadísticas de mortalidad del país, se analizó la cohorte de fallecidos registrado en el certificado de defunción como fibrosis quística. Se calcularon tasas de mortalidad crudas y ajustadas para todos los años observados. Se realizó un análisis para las defunciones en menores 40 años; según las variables sexo, edad y región. Se estimó el cambio porcentual anual utilizando el programa Joinpoint-Regression. Resultados. Se registraron 198 defunciones (49% mujeres). La edad media y mediana de defunción aumentaron progresivamente, desde 1997-2001 con media 8,5 y mediana 6 años a 2013-2017 con media 19,6 y mediana 20 años (p-valor<0,05). La tasa de mortalidad en los menores de 1 año presentó una tendencia decreciente con un cambio porcentual anual de - 32,5%, estadísticamente significativo. La región de Atacama presentó un riesgo de muerte 6,12 veces mayor que el promedio del país. Discusión. En Chile, la edad de defunción por fibrosis quística ha aumentado progresivamente y la mortalidad en los <1 año ha disminuido a lo largo de los últimos años.
Introduction. Cystic Fibrosis is the most frequent hereditary disease in whites, with a reduced prognosis. Its incidence varies by ethnicity. In Chile, the estimated incidence is 1/10,000 inha-bitants and national evidence regarding the magnitude and characterization of deaths is scarce.The aim of this study es to describe the evolution of cystic fibrosis mortality in Chile during 1997-2017. Materials and Methods. Retrospective descriptive study on the mortality trend due to cystic fibrosis in Chile. From secondary databases of the country's mortality statistics system, the cohort of deceased due to cystic fibrosis, as registered in the death certificate was analyzed. Crude and adjusted mortality rates were calculated for all observed years. An analysis was performed for deaths in persons younger 40 years; according to the variables of sex, age and region. The annual percentage change was estimated using the Joinpoint-Regression program.Results. 198 deaths were registered (49% women). For those younger than 40 years at the time of death, the mean and median age of death increased progressively, from mean 8.5 and median 6 years in 1997 to 2001 to a mean of 19.6 and median of 20 years in 2013-2017 (p-value <0.05). The mortality rate in under 1 year of ages presented a decreasing trend with an annual percentage change of -32.5%. The Atacama region presented a risk of death 6.12 times higher than the country's average.Discussion. In Chile, the age of death due to cystic fibrosis has progressively increased and mortality in <1 year has decreased in recent years
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Adulto Jovem , Mortalidade/tendências , Fibrose Cística/mortalidade , Chile/epidemiologia , Mortalidade Infantil/tendências , Análise de Regressão , Estudos Retrospectivos , Distribuição por IdadeAssuntos
Neoplasias da Túnica Conjuntiva/diagnóstico , Neoplasias da Túnica Conjuntiva/terapia , Melanoma/diagnóstico , Melanoma/terapia , Idoso de 80 Anos ou mais , Âmnio/transplante , Proliferação de Células , Terapia Combinada , Neoplasias da Túnica Conjuntiva/patologia , Crioterapia , Feminino , Humanos , Achados Incidentais , Ceratectomia , Melanoma/patologia , Procedimentos de Cirurgia Plástica , Carga Tumoral/fisiologiaRESUMO
Hypoxia-inducible factor-1 alpha (HIF-1α) is a master transcription factor that regulates the response to hypoxia and ischemia and induces the expression of various genes, including vascular endothelial growth factor (VEGF) and erythropoietin (EPO). This study shows the systemic response of increased HIF-1α, EPO, and VEGF mRNA and protein. In addition, VEGF expression was increased in neurons and over-expressed in glial cells in a model of neuroexcitotoxicity in the hippocampus, in which rats were neonatally exposed to high glutamate concentrations. Simultaneous increases in HIF-1α, EPO and VEGF mRNA in peritoneal macrophages were also observed. Our study is consistent with the hypothesis that these genes exert a protective effect in response to neurotoxicity.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Hipocampo/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Macrófagos/metabolismo , Síndromes Neurotóxicas/patologia , Fatores Etários , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Eritropoetina/genética , Eritropoetina/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Ácido Glutâmico/toxicidade , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Macrófagos/efeitos dos fármacos , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Síndromes Neurotóxicas/etiologia , Neurotoxinas/toxicidade , Gravidez , RNA Mensageiro , Ratos , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Tryptophan (TRP), which plays an important role in immune system regulation, protein synthesis, serotonin (5-HT) and melatonin production, is a potent endogenous free radical scavenger and antioxidant. The aim of this work was to determine the efficacy of TRP in neuro-inflammation induced by systemic administration of lipopolysacharide (LPS, 20mg/kg) which promotes the synthesis of free radical (LPO: MDA and 4-HDA), and pro-inflammatory cytokine Interferon-γ (IFN-γ) in different brain regions (cerebral cortex and hippocampus) of rats. Experiments were performed on adult female, pregnant and lactating rats fed with a diet of TRP content (0.5mg/100g protein), cerebral cortex and hippocampus were evaluated for lipid peroxidation (LPO) products, nitrites, nitrates and plasmatic concentration of IFN-γ. LPO levels in LPS+TRP groups were significantly decreased than that obtained in the LPS group. However, there were no observed differences in plasmatic levels of nitrites and nitrates as well as IFN-γ, neither in the cerebral cortex or hippocampus. The TRP has protective effect in the oxidative damage in a model of endotoxic shock in the breading nurslings induced by the systemic administration of LPS, acting as a scavenger of free radicals. So, it can be proposed as an innocuous protector agent in the endotoxic shock process.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Fármacos Neuroprotetores/farmacologia , Triptofano/farmacologia , Animais , Antioxidantes/farmacologia , Córtex Cerebral/metabolismo , Interações Medicamentosas , Feminino , Sequestradores de Radicais Livres/metabolismo , Sequestradores de Radicais Livres/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Inflamação/sangue , Inflamação/metabolismo , Interferon gama/sangue , Lactação , Peroxidação de Lipídeos/efeitos dos fármacos , Nitratos/sangue , Nitritos/sangue , Gravidez , Ratos , Ratos Sprague-Dawley , Choque Séptico/sangue , Choque Séptico/tratamento farmacológico , Choque Séptico/metabolismoRESUMO
Corneal neovascularization is often accompanied by inflammatory response and loss of their immune privilege which leads to significant visual impairment and worsens the prognosis of a subsequent penetrating keratoplasty. Several types of treatment are currently used. However, there are some associated limitations and complications. The consumption of (-)-epigallocatechin 3-gallate (EGCG) has been studied extensively as a potential treatment for a variety of carcinogenic and degenerative diseases due to its ability to suppress a variety of inflammatory and angiogenic factors such as NF-κB, IL-1ß, COX2, VEGF, and matrix metalloproteinases. These factors are involved in the development of corneal neovascularization. The safety of long-term EGCG administration as well as the drug's high solubility in water urge further investigation of the therapeutic potential of this drug. Therefore, we propose that the administration of EGCG to the ocular surface represents a new chemopreventive alternative to suppress the corneal neovascularization induced by inflammation.
Assuntos
Catequina/análogos & derivados , Neovascularização da Córnea/tratamento farmacológico , Olho/metabolismo , Visão Ocular/efeitos dos fármacos , Animais , Catequina/farmacologia , Catequina/uso terapêutico , Humanos , Interleucina-1beta/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Fator de Transcrição RelAAssuntos
Fezes/microbiologia , Yersinia enterocolitica/isolamento & purificação , Argentina/epidemiologia , Criança , Pré-Escolar , Gastroenterite/diagnóstico , Gastroenterite/epidemiologia , Gastroenterite/microbiologia , Humanos , População Urbana/estatística & dados numéricos , Yersiniose/diagnóstico , Yersiniose/epidemiologia , Yersiniose/microbiologiaAssuntos
Criança , Pré-Escolar , Humanos , Fezes/microbiologia , Yersinia enterocolitica/isolamento & purificação , Argentina/epidemiologia , Gastroenterite/diagnóstico , Gastroenterite/epidemiologia , Gastroenterite/microbiologia , População Urbana/estatística & dados numéricos , Yersiniose/diagnóstico , Yersiniose/epidemiologia , Yersiniose/microbiologiaRESUMO
OBJECTIVES: HIF-1 alpha (hypoxia-inducible factor-1 alpha) mediates the responses of mammalian cells to hypoxia/ischemia by inducing the expression of adaptive gene products (e.g., vascular endothelial growth factor (VEGF) and erythropoietin (EPO)). Persistent pulmonary hypertension of the newborn (PPHN) and cyanotic congenital heart disease (CCHD) are common neonatal diseases considered as paradigms of hypoxemia. Since the expression HIF-1 alpha, VEGF and EPO in newborns diagnosed with these diseases has yet to be studied, we set out to define the expression of these genes in peripheral blood from newborn infants diagnosed with PPHN and CCHD. DESIGN AND METHODS: The mRNA transcripts encoding HIF-1 alpha, VEGF and EPO were measured by RT-PCR in healthy newborn infants and infants diagnosed with PPHN and CCHD. RESULTS: An important increase in HIF-1 alpha expression was observed in both pathological conditions, accompanied by significant increases in VEGF and EPO expression when compared to healthy infants. CONCLUSIONS: HIF-1 alpha mRNA expression increases in newborn infants with PPHN or CCHD, as does the expression of its target genes VEGF and EPO.
Assuntos
Eritropoetina , Cardiopatias , Subunidade alfa do Fator 1 Induzível por Hipóxia , Hipóxia , Síndrome da Persistência do Padrão de Circulação Fetal , Fator A de Crescimento do Endotélio Vascular , Eritropoetina/sangue , Eritropoetina/genética , Cardiopatias/sangue , Cardiopatias/congênito , Cardiopatias/fisiopatologia , Humanos , Hipóxia/sangue , Hipóxia/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Lactente , Recém-Nascido , Síndrome da Persistência do Padrão de Circulação Fetal/sangue , Síndrome da Persistência do Padrão de Circulação Fetal/genética , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Overactivation of NMDA-Rs may mediate excitotoxic cell death associated with epileptic seizures, and hypoxic-ischemic conditions. We assessed whether repeated subcutaneous administration of l-glutamate to neonatal rats affects the subunit composition of NMDA-Rs. Accordingly, cortical and hippocampal tissue from 14-day-old rats was analyzed by Western blotting and RT-PCR to quantify the protein and mRNA expression of different NMDA-R subunits. In addition, tissue sections were Nissl stained to assess the cell damage in this tissue. Early exposure of neonatal rats to L-glutamate differentially affects the expression of mRNA transcripts for NMDA-R subunits in the cerebral cortex and hippocampus. In the cerebral cortex, a decrease in NR2B subunit mRNA expression was observed, as well as a loss of NR1 and NR2A protein. By contrast, neonatal L-glutamate administration augmented the transcripts encoding the NR1, NR2B, and NR2C subunits in the hippocampal formation. The expression of mRNA encoding the NR2A subunit was not affected by neonatal L-glutamate administration in either of the brain regions examined. This differential expression of NMDA-R subunits following neonatal exposure to L-glutamate may represent an adaptive response of the glutamate receptors to overactivation in order to reduce the effect of high L-glutamate during the early period of life when the animal is more vulnerable to excitotoxicity.
Assuntos
Ácido Glutâmico/toxicidade , Hipocampo/efeitos dos fármacos , Neurotoxinas/toxicidade , Receptores de N-Metil-D-Aspartato/metabolismo , Análise de Variância , Animais , Western Blotting , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiologia , Expressão Gênica/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6 rises significantly during neuronal damage and activate the signaling p38 MAPK pathway, which is involved in the apoptotic (AP) neuronal death. Systemic administration of glutamate as monosodium salt (MSG) to newborn animals induces neuronal death, however whether neurons die by AP or necrosis through MAPK p38 pathway activation it is unknown. In this study, TNF-alpha, IL-1beta and IL-6 expression levels, AP neuronal death and cellular type that produces TNF-alpha was also identified in the cerebral cortex (CC) and striatum (St) of rats at 8, 10, and 14 days of age after neonatal exposure to MSG. TNF-alpha production and AP neuronal death was significantly increased in the CC at PD8-10, and in the St in all ages studied by excitotoxicity effect induced with MSG. This effect was completely inhibited by SB203580 (p38 inhibitor) in both regions studied. TNF-alpha, IL-1beta and IL-6 RNAm increased after MSG administration, whereas SB203580 did not modify their expression. These data indicates that neuronal death induced by excitotoxicity appears to be mediated through p38 signaling pathway activated by TNF-alpha and their inhibition may have an important neuroprotective role as part of anti-inflammatory therapeutic strategy.
Assuntos
Citocinas/genética , Glutamato de Sódio/toxicidade , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Gânglios da Base/efeitos dos fármacos , Gânglios da Base/metabolismo , Gânglios da Base/patologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Citocinas/metabolismo , Inibidores Enzimáticos/farmacologia , Feminino , Expressão Gênica/efeitos dos fármacos , Imidazóis/farmacologia , Imuno-Histoquímica , Injeções Subcutâneas , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Neuroglia/citologia , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Gravidez , Piridinas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Glutamato de Sódio/administração & dosagem , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidoresRESUMO
Excitotoxic neuronal death occurs through the activation of NMDA and non-NMDA glutamatergic receptors in the CNS. Glutamate also induces strong activation of p38 and indeed, cell death can be prevented by inhibitors of the p38 pathway. Furthermore, intracellular signals generated by AMPA receptors activate the stress sensitive MAP kinases implicated in apoptotic neuronal death, such as JNK and p38. To investigate the relationship between these elements, we have used immunohistochemistry to analyze the expression of GluR2 in the cerebral cortex of postnatal rats (postnatal Day [PD] 8 and 14) after administering them with monosodium glutamate (MSG; 4 mg/g body weight on PD1, 3, 5, and 7). Similarly, the expression of REST, Fas-L and Bcl-2 mRNA transcripts in animals exposed to a p38 inhibitor, SB203580 (0.42 microg/g body weight, administered subcutaneously) was determined by reverse transcriptase-PCR. The enhanced GluR2-expression in the cerebral cortex at PD8 and the down regulation of this receptor at PD14 was correlated with neuronal damage induced by excitotoxicity. In addition, the enhanced expression of REST at PD8 and PD14 suggests that the induction of REST transcription contributes to glutamate-induced excitotoxic neurodegeneration, possibly by modulating GluR2 expression. Fas-L and Bcl-2 over expression at PD8 and their subsequent down regulation at PD14 also suggests that Fas-L could be the direct effector of apoptosis in the cerebral cortex. On the other hand, the presence of Bcl-2 at PD8 could attenuate certain survival signals in neurons under these neurotoxic conditions. Thus, a change in glutamate receptor composition, and enhanced Fas-L and Bcl-2 expression, coupled with activation of the p38/SAPK pathway appear to be events involved in the neuronal apoptosis induced under neurotoxic conditions.
Assuntos
Córtex Cerebral/metabolismo , Ácido Glutâmico/fisiologia , Neurônios/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Animais Recém-Nascidos , Morte Celular , Ativação Enzimática , Proteína Ligante Fas , Feminino , Ácido Glutâmico/toxicidade , Imuno-Histoquímica , Glicoproteínas de Membrana/biossíntese , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Wistar , Receptores de AMPA/biossíntese , Glutamato de Sódio/toxicidade , Fatores de Necrose Tumoral/biossíntese , Receptor fas/biossínteseRESUMO
Cytotoxic proteins and prodigiosin obtained from Serratia marcescens strains are known to induce tumor cell death, nevertheless its combination has not been studied. In this paper we evaluate the combined effects of these molecules in a panel of tumor cell lines. The results showed a marked inhibitory effect on the growth of tumor cell lines derived from tumors (i.e., melanoma) which are highly resistant to conventional anticancer drugs, while normal cells were less sensitive than tumor cells. TUNEL (TdT-mediated dUTP nick end labeling) and electrophoresis of HEp-2 cell DNA treated with MG2327 preparation [containing the P50 protein belonging to the serralysins and prodigiosin, from S. marcescens CMIB4202] showed a pattern of DNA fragments typically associated with apoptosis. Interestingly, prodigiosin enhanced by 1.6-fold the cytotoxic effect of P50 when acting in combination on HEp-2 cells. The broad cytotoxic activity of the combination on tumor cells as well as its selectivity open new frontiers in cancer therapy.
Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Proteínas de Bactérias/farmacologia , Neoplasias/tratamento farmacológico , Prodigiosina/farmacologia , Serratia marcescens/química , Antibacterianos/isolamento & purificação , Apoptose , Proteínas de Bactérias/isolamento & purificação , DNA de Neoplasias/análise , Quimioterapia Combinada , Eletroforese em Gel de Ágar , Humanos , Marcação In Situ das Extremidades Cortadas , Prodigiosina/isolamento & purificação , Células Tumorais CultivadasRESUMO
Palladium, iridium, and rhodium are evaluated as possible chemical modifiers in the determination of As in digest solutions of biological materials (human hair and clam) by tungsten coil electrothermal atomic absorption spectrophotometry (TCA-AAS). The modifier in solution was applied onto the coil and thermally pre-reduced; the pre-reduction conditions, the amount of modifier, and the thermal program were optimized. Palladium was not satisfactory, whereas Ir and Rh were effective modifiers and rendered better relative sensitivity for As by a factor of 1.4 and 1.9, respectively compared to the case without modifier. Upon optimization of thermal conditions for As in pre-reduced Ir (2.0 microg) and Rh (2.0 microg) modifiers and in the digest solutions of the study matrices, Rh (2.0 microg) was more effective modifier and was selected as such. The mean within-day repeatability was 2.8% in consecutive measurements (25-100 microg L(-1)) (3 cycles, each of n=6) and confirmed good short-term stability of the absorbance measurements. The mean reproducibility was 4.4% (n=20 in a 3-day period) and the detection limit (3 sigmablank/slope) was 29 pg (n=15). The useful coil lifetime in Rh modifier was extended to 300-400 firings. Validation was by determination of As in the certified reference material (CRM) of "Oyster tissue" solution with a percentage relative error (Erel%) of 2% and percentage relative standard deviation (RSD%) of 3% (n=4), and by analytical recovery of As spiked in CRM of human hair [94 +/- 8% (n=4)]. The methodology is simple, fast (sample readout frequency 21 h(-1)), reliable, of low cost, and was applied to the determination of As in hair samples of exposed and unexposed workers.
Assuntos
Arsênio/análise , Irídio/química , Paládio/química , Ródio/química , Espectrofotometria Atômica/métodos , Tungstênio , Animais , Bivalves/química , Cabelo/química , Humanos , Espectrofotometria Atômica/instrumentação , TemperaturaRESUMO
Neuronal death and lactate dehydrogenase (LDH) activity were evaluated in the cerebral cortices of neonatal rats after exposure to monosodium L-glutamate (MSG) to induce neuroexcitotoxicity. A time-response profile for tumor necrosis factor-alpha (TNF-alpha) expression was drawn, with measurements taken every 6 h after the first dose of MSG during the first 8 postnatal days, and at days 10 and 14 after birth. An increase in neuronal loss accompanied by high LDH activity and high TNF-alpha levels was observed at 8 and 10 days. These results indicate that neuronal loss may occur via an apoptosis-like mechanism directed selectively against neurons that express glutamate receptors, mainly the N-methyl-D-aspartate, which it may be strengthen by high TNF-alpha levels through a feedback mechanism to induce cell death via apoptosis.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Aminoácidos Excitatórios/farmacologia , Neurônios/efeitos dos fármacos , Glutamato de Sódio/farmacologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Morte Celular , Córtex Cerebral/metabolismo , L-Lactato Desidrogenase/efeitos dos fármacos , L-Lactato Desidrogenase/metabolismo , Masculino , Neurônios/metabolismo , Neurônios/patologia , Ratos , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Sticholysin I (St-I) and sticholysin II (St-II) are cytolysins purified from the sea anemone Stichodactyla helianthus with a high degree of sequence identity (93%) but clearly differenced in their hemolytic activity. In order to go further into the structural determinants for the different behavior of St-I and St-II, we report here the complete amino acid sequences and the consensus secondary structure prediction of both proteins. The complete determination of St-II primary structure confirms the partial revision of cytolysin III amino acid sequence. All nonconservative changes between St-I and St-II are located at the N-terminal. According to our prediction these changes could be located at the same face of an alpha-helix during pore formation events and could account for the observed differences in hemolytic activity between St-I and St-II.
Assuntos
Venenos de Cnidários/química , Proteínas Hemolisinas/química , Hemólise/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Venenos de Cnidários/toxicidade , Proteínas Hemolisinas/toxicidade , Dados de Sequência Molecular , Compostos Orgânicos , Estrutura Secundária de ProteínaRESUMO
Two hemolysins, Sticholysin I (St I) and Sticholysin II (St II) were purified from the sea anemone Stichodactyla helianthus combining gel filtration and ion exchange chromatography. The amino acid composition of both cytolysins was determined revealing a high proportion of glycine, lysine, tyrosine and non-polar amino acids (alanine, leucine and valine). Cysteine was not found in either polypeptide. Molecular masses of St I and St II were 19401 and 19290 Da, respectively. N-terminal sequence analysis of St I and St II showed a high homology between them suggesting they are isoforms of the same cytolysin. Compared with other sea anemone cytolysins, St I and St II contain a 22 amino acid insertion fragment also present in Eq T II/Tn C and probably in CaT I and Hm T and absent in C III, the major hemolysin previously reported in this anemone.