RESUMO
The ideal immunosuppressive regimen should provide for excellent immunosuppression with no side effects. Yet, current immunosuppressive therapy regimens commonly used in clinical applications fail to meet this criterion. One of the complications caused by immunosuppressive drugs is mineralization disorders in hard tissues. In this study, we evaluated the effects of three immunosuppressive therapies used after transplantation on the levels of potassium, iron, chromium, zinc, aluminum, sodium and molybdenum in the bones and teeth of female rats and their offspring. The study was conducted on 32 female Wistar rats, subjected to immunosuppressive regimens (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; and cyclosporine A, everolimus and prednisone). The hard tissues of rats were analyzed using inductively coupled plasma optical emission spectrometry (ICP-OES, ICAP 7400 Duo, Thermo Scientific) equipped with a concentric nebulizer and a cyclonic spray chamber. All the immunosuppressive regimens included in the study affected the concentrations of the studied minerals in hard tissues of female rats and their offspring. The therapy based on cyclosporine A, everolimus and prednisone led to a decline in the levels of iron in bone, zinc in teeth, and molybdenum in the bone and teeth of mothers, while in the offspring, it caused a decline of bone potassium, with a decrease in iron and increase of molybdenum in teeth. Moreover, the regimen caused an increase in aluminum and chromium in the teeth and aluminum in the bones of the offspring, and consequently, it seems to be the therapy with the most negative impact on the mineral metabolism in hard tissues.
Assuntos
Imunossupressores/farmacologia , Minerais/metabolismo , Especificidade de Órgãos , Alumínio/metabolismo , Animais , Osso e Ossos/metabolismo , Cromo/metabolismo , Feminino , Ferro/metabolismo , Molibdênio/metabolismo , Potássio/metabolismo , Gravidez , Ratos Wistar , Sódio/metabolismo , Zinco/metabolismoRESUMO
About 20 %-35 % of mandibular fractures occur in the condylar process, a complication frequently associated with craniofacial traumas. Compared to other craniofacial fractures, some controversy remains around the effectiveness of the various treatment methods. It has been suggested that condylar osteosynthesis using mini-plates - a technique widely used by maxillofacial surgeons - may activate a pro-inflammatory response which is mediated by interleukins, later involved in bone remodelling and tissue regeneration. This study aimed at examining the influence of three-dimensional (3D) titanium mini-plate systems and the dedicated screws used in the surgical treatment of condylar fractions on the concentrations of interleukin 1(IL-1) and interleukin 6 (IL-6) in macrophages obtained from THP-1 monocytes. The cells were cultured for 24 h and 48 h with the 3D titanium condylar plates and dedicated screws (Synthes, Martin, Medartis manufacturer). The concentrations of IL-1 and IL-6 were measured using the ELISA method. Incubation of macrophages with plates did not cause a significant increase in IL-1 (for: Synthes 0.89-0.86 pg/mg protein; Martin 1.10-0.80 pg/mg protein; Medartis 1.20-0.84 pg/mg protein) and IL-6 (for Synthes 16.00-14.00 pg/mg protein, Martin 13.0-10.0 pg/mg protein; Medartis 9.0-12.0 pg/mg protein) expression for any of the plates used, compared to THP-1 macrophages incubated for 48 h under control conditions. Neither three-dimensional titanium mini-plates nor dedicated screws caused any changes in IL-1 and IL-6 expression in THP-1 macrophages, which is an important observation for clinicians treating condylar fractures. It confirms that titanium plates can be a safe/neutral material for humans, especially considering their significant influence on the osteoclast functions and bone remodelling processes after implantation.
Assuntos
Placas Ósseas , Fraturas Ósseas/cirurgia , Imageamento Tridimensional , Interleucina-1/farmacologia , Interleucina-6/farmacologia , Macrófagos/metabolismo , Titânio/farmacologia , Humanos , Macrófagos/efeitos dos fármacos , Células THP-1RESUMO
The effects of fluoride on endocrine tissues has not been sufficiently explored to date. The current body of knowledge suggest significant effects of that mineral on reducing sex hormone levels, which may consequently impair fertility and disrupt puberty. The majority of studies confirm that sodium fluoride increases TSH levels and decreases the concentrations of T3 and T4 produced by the thyroid. Moreover, a correlation was observed between NaF and increased secretion of PTH by the parathyroid glands, without a significant impact on body calcium levels. Probably, fluoride may exert adverse effects on insulin levels, impairing pancreatic function and resulting in abnormal glucose tolerance. Observations also include decreased levels of cortisol secreted by the adrenal glands. In light of the few existing studies, the mechanism of fluoride toxicity on the endocrine system has been described.
Assuntos
Sistema Endócrino/efeitos dos fármacos , Fluoretos/farmacologia , Glândulas Suprarrenais/metabolismo , Animais , Fluoretos/efeitos adversos , Fluoretos/toxicidade , Humanos , Hidrocortisona/metabolismo , Insulina/análise , Glândulas Paratireoides/efeitos dos fármacos , Glândulas Paratireoides/metabolismo , Fluoreto de Sódio/farmacologia , Fluoreto de Sódio/toxicidade , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismoRESUMO
The expression of desaturases is higher in many types of cancer, and despite their recognized role in oncogenesis, there has been no research on the expression of desaturases in glioblastoma multiforme (GBM). Tumor tissue samples were collected during surgery from 28 patients (16 men and 12 women) diagnosed with GBM. The effect of necrotic conditions and nutritional deficiency (mimicking conditions in the studied tumor zones) was studied in an in vitro culture of human brain (glioblastoma astrocytoma) U-87 MG cells. Analysis of desaturase expression was made by qRT-PCR and the immunohistochemistry method. In the tumor, the expression of stearoyl-coenzyme A desaturase (SCD) and fatty acid desaturases 2 (FADS2) was lower than in the peritumoral area. The expression of other desaturases did not differ in between the distinguished zones. We found no differences in the expression of SCD, fatty acid desaturases 1 (FADS1), or FADS2 between the sexes. Necrotic conditions and nutritional deficiency increased the expression of the studied desaturase in human brain (glioblastoma astrocytoma) U-87 MG cells. The obtained results suggest that (i) biosynthesis of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) in a GBM tumor is less intense than in the peritumoral area; (ii) expressions of SCD, SCD5, FADS1, and FADS2 correlate with each other in the necrotic core, growing tumor area, and peritumoral area; (iii) expressions of desaturases in a GBM tumor do not differ between the sexes; and (iv) nutritional deficiency increases the biosynthesis of MUFA and PUFA in GBM cells.
Assuntos
Neoplasias Encefálicas/metabolismo , Ácidos Graxos Dessaturases/metabolismo , Glioblastoma/metabolismo , Estearoil-CoA Dessaturase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Dessaturase de Ácido Graxo Delta-5 , Ácidos Graxos Dessaturases/genética , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Pessoa de Meia-Idade , Necrose , Estearoil-CoA Dessaturase/genéticaRESUMO
Addiction is a pressing social problem worldwide and opioid dependence can be considered the strongest and most difficult addiction to treat. Mesolimbic and mesocortical dopaminergic pathways play an important role in modulation of cognitive processes and decision making and, therefore, changes in dopamine metabolism are considered the central basis for the development of dependence. Disturbances caused by excesses or deficiency of certain elements have a significant impact on the functioning of the central nervous system (CNS) both in physiological conditions and in pathology and can affect the cerebral reward system and therefore, may modulate processes associated with the development of addiction. In this paper we review the mechanisms of interactions between morphine and zinc, manganese, chromium, cadmium, lead, fluoride, their impact on neural pathways associated with addiction, and on antinociception and morphine tolerance and dependence.
Assuntos
Dependência de Morfina/metabolismo , Morfina/metabolismo , Elementos de Transição/metabolismo , Animais , Humanos , Morfina/química , Vias Neurais/metabolismo , Elementos de Transição/químicaRESUMO
The aim of this study was to assess the influence of lead (Pb) at low concentrations (imitating Pb levels in human blood in chronic environmental exposure to this metal) on interleukin 1ß (IL-1ß) and interleukin 6 (IL-6) concentrations and the activity and expression of COX-1 and COX-2 in THP-1 macrophages. Macrophages were cultured in vitro in the presence of Pb at concentrations of: 1.25 µg/dL; 2.5 µg/dL; 5 µg/dL; 10 µg/dL. The first two concentrations of Pb were selected on the basis of our earlier study, which showed that Pb concentration in whole blood (PbB) of young women living in the northern regions of Poland and in the cord blood of their newborn children was within this range (a dose imitating environmental exposure). Concentrations of 5 µg/dL and 10 µg/dL correspond to the previously permissible PbB concentrations in children or pregnant women, and adults. Our results indicate that even low concentrations of Pb cause an increase in production of inflammatory interleukins (IL-1ß and IL-6), increases expression of COX-1 and COX-2, and increases thromboxane B2 and prostaglandin E2 concentration in macrophages. This clearly suggests that the development of inflammation is associated not only with COX-2 but also with COX-1, which, until recently, had only been attributed constitutive expression. It can be concluded that environmental Pb concentrations are able to activate the monocytes/macrophages similarly to the manner observed during inflammation.
Assuntos
Chumbo/farmacologia , Ativação de Macrófagos , Macrófagos/efeitos dos fármacos , Adulto , Células Cultivadas , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Feminino , Humanos , Interleucinas/genética , Interleucinas/metabolismo , Chumbo/toxicidade , Macrófagos/metabolismo , Células THP-1RESUMO
Lead (Pb) is a heavy metal with a proven neurotoxic effect. Exposure is particularly dangerous to the developing brain in the pre- and neonatal periods. One postulated mechanism of its neurotoxicity is induction of inflammation. This study analyzed the effect of exposure of rat pups to Pb during periods of brain development on the concentrations of selected cytokines and prostanoids in the forebrain cortex, hippocampus and cerebellum. METHODS: Administration of 0.1% lead acetate (PbAc) in drinking water ad libitum, from the first day of gestation to postnatal day 21, resulted in blood Pb in rat pups reaching levels below the threshold considered safe for humans by the Centers for Disease Control and Prevention (10 µg/dL). Enzyme-linked immunosorbent assay (ELISA) method was used to determine the levels of interleukins IL-1ß, IL-6, transforming growth factor-ß (TGF-ß), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2). Western blot and quantitative real-time PCR were used to determine the expression levels of cyclooxygenases COX-1 and COX-2. Finally, Western blot was used to determine the level of nuclear factor kappa B (NF-κB). RESULTS: In all studied brain structures (forebrain cortex, hippocampus and cerebellum), the administration of Pb caused a significant increase in all studied cytokines and prostanoids (IL-1ß, IL-6, TGF-ß, PGE2 and TXB2). The protein and mRNA expression of COX-1 and COX-2 increased in all studied brain structures, as did NF-κB expression. CONCLUSIONS: Chronic pre- and neonatal exposure to Pb induces neuroinflammation in the forebrain cortex, hippocampus and cerebellum of rat pups.
Assuntos
Cerebelo/imunologia , Encefalite/induzido quimicamente , Hipocampo/imunologia , Chumbo/toxicidade , Efeitos Tardios da Exposição Pré-Natal/imunologia , Prosencéfalo/imunologia , Animais , Animais Recém-Nascidos , Biomarcadores/metabolismo , Cerebelo/efeitos dos fármacos , Dinoprostona/metabolismo , Modelos Animais de Doenças , Encefalite/imunologia , Feminino , Hipocampo/efeitos dos fármacos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Gravidez , Prosencéfalo/efeitos dos fármacos , Ratos , Tromboxano B2/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
Despite numerous studies concerning the pathophysiology of migraine, the exact molecular mechanism of disturbances underlying migraine is still unknown. Furthermore, oxidative stress is considered to play a significant role in migraine pathogenesis. The notion of oxidative stress in migraine patients has been discussed for several decades. Over the past few years, among the substances that could potentially be used for migraine treatment, particular attention has been paid to the so-called nutraceutics, including antioxidants. Antioxidants supplied with food prevent oxidative stress by inhibiting initiation, propagation, and the oxidative chain reaction itself. Additionally, the agents used so far in the prevention of migraine indeed show some anti-oxidative action. The antioxidants discussed in the present paper are increasingly more often used by migraine patients not only due to mild or even a lack of side effects but also because of their effectiveness (decreased frequency of migraine episodes or shortening of an episode duration). The present review provides a summary of the studies on nutraceuticals with antioxidative properties.
RESUMO
Studies on the ingredients of energy drinks and isotonic drinks focus mainly on the evaluation of their content in terms of substances modulating the body's metabolism or those regarded as food additives. Having regard to the widespread availability of these beverages, their diversity and the limited number of studies in this area, the aim of this study was to analyse the contents of F, Al, Cd, Cr, Mn, V, Co, Ni, Zn, Bi and Na in the energy drinks and isotonic drinks available in the Polish market. Fluorine concentration was analysed using an ion-selective electrode. The other elements were analysed using ICP-OES. Obtained results showed that functional beverages need to be taken into account as a source of macroelements and microelements in human nutrition, particularly when ingested often and in large quantities (which applies particularly to the young population). Moreover, due caution needs to be maintained in consumer choices.
Assuntos
Bebidas Energéticas , Oligoelementos , Bebidas , Fluoretos , Humanos , Minerais/análise , Polônia , Oligoelementos/análiseRESUMO
Persistent organic pollutants (POPs) released from plastics into water, soil and air are significant environmental and health problem. Continuous exposure of humans to these substances results not only from the slow biodegradation of plastics but also from their ubiquitous use as industrial materials and everyday products. Exposure to POPs may lead to neurodegenerative disorders, induce inflammation, hepatotoxicity, nephrotoxicity, insulin resistance, allergies, metabolic diseases, and carcinogenesis. This has spurred an increasing intense search for natural compounds with protective effects against the harmful components of plastics. In this paper, we discuss the current state of knowledge concerning the protective functions of polyphenols against the toxic effects of POPs: acrylonitrile, polychlorinated biphenyls, dioxins, phthalates and bisphenol A. We review in detail papers from the last two decades, analyzing POPs in terms of their sources of exposure and demonstrate how polyphenols may be used to counteract the harmful environmental effects of POPs. The protective effect of polyphenols results from their impact on the level and activity of the components of the antioxidant system, enzymes involved in the elimination of xenobiotics, and as a consequence - on the level of reactive oxygen species (ROS). Polyphenols present in daily diet may play a protective role against the harmful effects of POPs derived from plastics, and this interaction is related, among others, to the antioxidant properties of these compounds. To our knowledge, this is the first extensive review of in vitro and in vivo studies concerning the molecular mechanisms of interactions between selected environmental toxins and polyphenols.
Assuntos
Poluentes Ambientais/toxicidade , Plásticos/toxicidade , Polifenóis/toxicidade , Compostos Benzidrílicos , Dioxinas , Monitoramento Ambiental/métodos , Poluentes Ambientais/análise , Substâncias Perigosas , Humanos , Doenças Metabólicas/induzido quimicamente , Fenóis , Bifenilos Policlorados/análise , SoloRESUMO
Osteosynthesis with the use of three-dimensional (3D) titanium mini-plate systems in the treatment of condylar fractures is a technique commonly used by maxillofacial surgeons. It is increasingly often mentioned in the literature, especially in the context of bone regeneration. The break in tissue continuity associated with this technique causes activation of pro-inflammatory responses mediated by matrix metalloproteinases MMP-2 and MMP-9, enzymes which are also involved in the subsequent bone remodelling. This study showed that the use of 3D titanium mini-plates did not alter the expression of these enzymes in THP-1 macrophages.
Assuntos
Placas Ósseas , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Macrófagos/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Titânio/uso terapêutico , Regeneração Óssea/fisiologia , Citocinas/metabolismo , Humanos , Inflamação/metabolismo , Óxido Nítrico/metabolismo , Procedimentos de Cirurgia Plástica/métodos , Células THP-1RESUMO
It has been reported that donepezil and rivastigmine, the acetylcholinesterase (AchE) inhibitors commonly used in the treatment of Alzheimer's disease (AD), do not only inhibit AChE but also have antioxidant properties. As oxidative stress is involved in AD pathogenesis, in our study we attempted to examine the influence of donepezil and rivastigmine on the activity of antioxidant enzymes and glutathione concentration in macrophages-an important source of reactive oxygen species and crucial for oxidative stress progression. The macrophages were exposed to sodium fluoride induced oxidative stress. The antioxidant enzymes activity and concentration of glutathione were measured spectrophotometrically. The generation of reactive oxygen species was visualized by confocal microscopy. The results of our study showed that donepezil and rivastigmine had a stimulating effect on catalase activity. However, when exposed to fluoride-induced oxidative stress, the drugs reduced the activity of some antioxidant enzymes (Cat, SOD, GR). These observations suggest that the fluoride-induced oxidative stress may suppress the antioxidant action of AChE inhibitors. Our results may have significance in the clinical practice of treatment of AD and other dementia diseases.
Assuntos
Antioxidantes/metabolismo , Inibidores da Colinesterase/farmacologia , Glutationa/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Células THP-1/efeitos dos fármacos , Doença de Alzheimer , Donepezila/farmacologia , Fluoretos/farmacologia , Humanos , Oxirredução/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Rivastigmina/farmacologiaRESUMO
The etiopathogenesis of Alzheimer's disease has not been fully explained. Now, the disease is widely attributed both to genetic and environmental factors. It is believed that only a small percentage of new AD cases result solely from genetic mutations, with most cases attributed to environmental factors or to the interaction of environmental factors with preexistent genetic determinants. Fluoride is widespread in the environment and it easily crosses the bloodâ»brain barrier. In the brain fluoride affects cellular energy metabolism, synthesis of inflammatory factors, neurotransmitter metabolism, microglial activation, and the expression of proteins involved in neuronal maturation. Finally, and of specific importance to its role in Alzheimer's disease, studies report fluoride-induced apoptosis and inflammation within the central nervous system. This review attempts to elucidate the potential relationship between the effects of fluoride exposure and the pathogenesis of Alzheimer's disease. We describe the impact of fluoride-induced oxidative stress and inflammation in the pathogenesis of AD and demonstrate a role for apoptosis in disease progression, as well as a mechanism for its initiation by fluoride. The influence of fluoride on processes of AD initiation and progression is complex and warrants further investigation, especially considering growing environmental fluoride pollution.
Assuntos
Doença de Alzheimer/induzido quimicamente , Fluoretos/efeitos adversos , Animais , Encéfalo/patologia , Humanos , Inflamação/patologia , Neurotoxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacosRESUMO
Inflammation is an important factor in the development of many diseases of the central nervous system, including Alzheimer's disease and other types of dementia. âªGiven that acetylcholinesterase inhibitors are also currently believed to have anti-inflammatory properties, the purpose of this study was to investigate the effect of acetylcholinesterase inhibitors (rivastigmine, donepezil) on cyclooxygenase activity and expression using the proinflammatory action of fluoride (F-) on cultured macrophages obtained from THP-1 monocytes. COX-1 and COX-2 activity was determined through measurement of the products of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) in cell culture supernatants. Expression of COX-1 and COX-2 proteins was examined immunocytochemically, and mRNA expression was determined by qRT PCR. âªâª Our study confirmed the inhibitory effects of donepezil and rivastigmine on the production of PGE2, TXB2, COX-1 and COX-2 mRNA and protein expression in macrophages. We also demonstrated that the pro-inflammatory effect of fluoride may be reduced by the use of both drugs. The additive effect of these drugs cannot be ruled out, and effects other than those observed in the use of one drug should also be taken into account.
Assuntos
Inibidores da Colinesterase/farmacologia , Ciclo-Oxigenase 1/biossíntese , Ciclo-Oxigenase 2/biossíntese , Donepezila/farmacologia , Fluoretos/toxicidade , Rivastigmina/farmacologia , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 2/genética , Regulação Enzimológica da Expressão Gênica , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Monócitos/efeitos dos fármacos , Monócitos/enzimologia , Células THP-1RESUMO
Recent years have seen considerable progress in understanding the biochemistry of cancer. For example, more significance is now assigned to the tumor microenvironment, especially with regard to intercellular signaling in the tumor niche which depends on many factors secreted by tumor cells. In addition, great progress has been made in understanding the influence of factors such as neurotensin, growth differentiation factor-15 (GDF-15), sphingosine-1-phosphate (S1P), and infection with cytomegalovirus (CMV) on the 'hallmarks of cancer' in glioblastoma multiforme. Therefore, in the present work we describe the influence of these factors on the proliferation and apoptosis of neoplastic cells, cancer stem cells, angiogenesis, migration and invasion, and cancer immune evasion in a glioblastoma multiforme tumor. In particular, we discuss the effect of neurotensin, GDF-15, S1P (including the drug FTY720), and infection with CMV on tumor-associated macrophages (TAM), microglial cells, neutrophil and regulatory T cells (Treg), on the tumor microenvironment. In order to better understand the role of the aforementioned factors in tumoral processes, we outline the latest models of intratumoral heterogeneity in glioblastoma multiforme. Based on the most recent reports, we discuss the problems of multi-drug therapy in treating glioblastoma multiforme.
RESUMO
Lead (Pb) is an environmental neurotoxin which particularly affects the developing brain but the molecular mechanism of its neurotoxicity still needs clarification. The aim of this paper was to examine whether pre- and neonatal exposure to Pb (concentration of Pb in rat offspring blood below the "threshold level") may affect the brain's energy metabolism in neurons and astrocytes via the amount of available glycogen. We investigated the glycogen concentration in the brain, as well as the expression of the key enzymes involved in glycogen metabolism in brain: glycogen synthase 1 (Gys1), glycogen phosphorylase (PYGM, an isoform active in astrocytes; and PYGB, an isoform active in neurons) and phosphorylase kinase ß (PHKB). Moreover, the expression of connexin 43 (Cx43) was evaluated to analyze whether Pb poisoning during the early phase of life may affect the neuron-astrocytes' metabolic cooperation. This work shows for the first time that exposure to Pb in early life can impair brain energy metabolism by reducing the amount of glycogen and decreasing the rate of its metabolism. This reduction in brain glycogen level was accompanied by a decrease in Gys1 expression. We noted a reduction in the immunoreactivity and the gene expression of both PYGB and PYGM isoform, as well as an increase in the expression of PHKB in Pb-treated rats. Moreover, exposure to Pb induced decrease in connexin 43 immunoexpression in all the brain structures analyzed, both in astrocytes as well as in neurons. Our data suggests that exposure to Pb in the pre- and neonatal periods results in a decrease in the level of brain glycogen and a reduction in the rate of its metabolism, thereby reducing glucose availability, which as a further consequence may lead to the impairment of brain energy metabolism and the metabolic cooperation between neurons and astrocytes.
Assuntos
Astrócitos/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Glicogênio/metabolismo , Intoxicação do Sistema Nervoso por Chumbo na Infância/etiologia , Neurônios/efeitos dos fármacos , Compostos Organometálicos/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Fatores Etários , Animais , Animais Recém-Nascidos , Astrócitos/metabolismo , Astrócitos/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Comunicação Celular/efeitos dos fármacos , Conexina 43/metabolismo , Feminino , Idade Gestacional , Glucose/metabolismo , Glicogênio Fosforilase Encefálica/genética , Glicogênio Fosforilase Encefálica/metabolismo , Glicogênio Sintase/genética , Glicogênio Sintase/metabolismo , Intoxicação do Sistema Nervoso por Chumbo na Infância/genética , Intoxicação do Sistema Nervoso por Chumbo na Infância/metabolismo , Intoxicação do Sistema Nervoso por Chumbo na Infância/patologia , Neurônios/metabolismo , Neurônios/patologia , Fosforilase Quinase/genética , Fosforilase Quinase/metabolismo , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos WistarRESUMO
Recent studies have shown promising results concerning the effectiveness of 3D plates in terms of stabilization of condylar fractures. Despite the use of new techniques and new materials, we can still observe certain side effects, including the immune reaction of the body, which may lead to the excessive inflammation. The aim of this paper was to determine how the production of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) in THP-1 monocytes/macrophages is influenced by the titanium 3D plates and dedicated screws. The experiments were conducted on THP-1 monocytic cell line and macrophages derived from a THP-1cells. The concentrations of PGE2 and TXB2 released were measured by using immunoassay kit. Verification of plate-induced activation of THP-1 monocytes and macrophages and initiation of inflammatory reaction was conducted by flow cytometry. Despite some differences in the content of the implant devices our results showed that these plates did not statistically significantly increase the production of these prostanoids. Osteosynthesis of condylar fractures using 3D titanium mini-plates seems to be a good alternative to traditional plates due to their lack of stimulating the cyclooxygenase-dependent production of prostanoids; limiting the development of inflammatory reactions.
Assuntos
Dinoprostona/metabolismo , Fraturas Ósseas/cirurgia , Inflamação/metabolismo , Côndilo Mandibular/cirurgia , Tromboxano B2/metabolismo , Parafusos Ósseos/efeitos adversos , Técnicas de Cultura de Células , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Citometria de Fluxo , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/genética , Fraturas Ósseas/fisiopatologia , Humanos , Imunoensaio , Inflamação/patologia , Macrófagos/efeitos dos fármacos , Côndilo Mandibular/metabolismo , Côndilo Mandibular/fisiopatologia , Monócitos/efeitos dos fármacos , Titânio/uso terapêuticoRESUMO
That the nervous system is the main target of lead (Pb) has long been considered an established fact until recent evidence has linked the Pb effect on the immune system to the toxic effects of Pb on the nervous system. In this paper, we present recent literature reports on the effect of Pb on the inflammatory processes in the brain, particularly the expression of selected cytokines in the brain (interleukin 6, TGF-ß1, interleukin 16, interleukin 18, and interleukin 10); expression and activity of enzymes participating in the inflammatory processes, such as cyclooxygenase 2, caspase 1, nitrogen oxide synthase (NOS 2) and proteases (carboxypeptidases, metalloproteinases and chymotrypsin); and the expression of purine receptors P2X4 and P2X7. A significant role in the development of inflammatory processes in the brain is also played by microglia (residual macrophages in the brain and the spinal cord), which act as the first line of defense in the central nervous system, and astrocytes-Whose most important function is to maintain homeostasis for the proper functioning of neurons. In this paper, we also present evidence that exposure to Pb may result in micro and astrogliosis by triggering TLR4-MyD88-NF-κB signaling cascade and the production of pro-inflammatory cytokines.
Assuntos
Astrócitos/patologia , Encéfalo/patologia , Inflamação/induzido quimicamente , Chumbo/toxicidade , Microglia/patologia , Animais , Astrócitos/imunologia , Caspase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Humanos , Inflamação/imunologia , Camundongos , Microglia/imunologia , Óxido Nítrico Sintase Tipo II/metabolismo , Peptídeo Hidrolases/metabolismo , Ratos , Receptores Purinérgicos/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
The aim of this study was to determine cadmium concentration in mothers' blood, milk, and newborns' blood from Szczecin (Poland) as a result of environmental cadmium exposure and evaluate the correlation (1) between cadmium levels in analyzed matrices, (2) between cadmium and fatty acids in those matrices, and (3) between cadmium and some selected personal variables, such as anthropometric characteristics, mothers' smoking status, and fruit and fish consumption by mothers. The concentration of cadmium in whole blood and milk of mothers and in the umbilical cord blood of newborns was determined by atomic absorption spectrometry with graphite furnace atomization and Zeeman correction. The fatty acid concentrations were determined by gas chromatography in our previous study. The mean concentrations of cadmium in maternal blood, newborn's blood, and breast milk were 0.61 ± 0.62 µg/L, 0.05 ± 0.04 µg/L, and 0.11 ± 0.07 µg/L, respectively, and differed significantly between analyzed matrices. Cadmium concentrations in the umbilical cord blood were 15 % (range 0-83 %) of the concentration in maternal blood, whereas cadmium concentrations in breast milk constituted 35 % (range 3-142 %) of the concentration in mothers' blood. No correlation was found between cadmium levels in three analyzed matrices. The correlation analysis revealed significant low positive correlation between maternal blood cadmium concentrations and concentrations of elaidic, oleic, and cis-vaccenic acids in mothers' milk (correlation coefficients 0.30, 0.32, and 0.31, respectively). Mothers' blood cadmium correlated with mothers' age (r = -0.26, p = 0.03), maternal smoking before pregnancy (r = 0.55, p < 0.000), maternal smoking during pregnancy (r = 0.58, p < 0.000), and fruit consumption by mothers after delivery (r = -0.44, p = 0.003). Mothers' height was the only variable that correlated significantly with breast milk cadmium levels. Newborns' blood cadmium concentrations correlated significantly with mothers' height (r = 0.28, p = 0.02), newborns' birth weight (r = 0.26, p = 0.03), maternal smoking during pregnancy (r = 0.24, p = 0.048), and fish consumption by mothers after delivery (r = 0.37, p = 0.02). The concentrations of cadmium in Polish mother-newborn pairs are among the lowest in Europe and within the norms established by different institutions. The results of our study confirm the existence of effective partial barriers (such as the placenta and mammary gland) restricting cadmium passage from mother to newborn. The significant positive correlations between maternal blood Cd and concentrations of oleic, elaidic, and cis-vaccenic acids in breast milk might suggest the increased cadmium toxicity to infant, taking into consideration even low cadmium passage to milk. Maternal smoking during pregnancy increases both maternal and newborn's blood cadmium level. Promotion of nonsmoking among pregnant women could substantially reduce prenatal and neonatal exposure to cadmium. Moreover, the results of our study point to the need of establishing complex biomonitoring of cadmium in mother-infant pairs in order to better protect children from this toxic and carcinogenic metal exposure.
Assuntos
Cádmio/sangue , Ácidos Graxos/sangue , Leite Humano/metabolismo , Fumar/sangue , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , PolôniaRESUMO
Significant progress in understanding the effects of the neurotoxic action of lead (Pb) in young organisms had led to reduction of "safe" level in the blood (Pb-B) to 5 µg/dL in children and pregnant women. Prolonged exposure to relatively low levels of Pb, generally asymptomatic and subclinical (i.e., microintoxication), is currently the dominant form of environmental poisoning, and its negative effects on health may appear after many years, e.g., secondary contamination from Pb bone deposits released in pregnancy. Therefore, the aim of this study was to investigate the effect of environmental exposure (urban areas) of mothers to Pb, on its levels in their milk and blood and in the blood of newborns. Moreover, the aim was to determine the fatty acid profile in the mothers' blood and milk and in the blood of newborns. We also wanted to find if infant birth weight depends on Pb blood levels, as well as on Pb and fatty acid levels in the blood and milk of the mothers. Finally, we examined if the mothers' weight and body mass index (BMI) before pregnancy influenced the concentration of Pb and fatty acid profile in the blood and milk of mothers and in the blood of their children. Analysis of fatty acids elaidic (C18:1, 9t), oleic (C18:1, 9c), vaccenic (C18:1, 11t), cis-vaccenic (C18:1, 11c), linoleic (C18:2, cis), γ-linolenic (C18:3, n-6), α-linolenic (C18:3, n-3), arachidonic (C20:4, n-6), eicosapentaenoic (C20:5, n-3), and docosahexaenoic (C22:6, n-3) was conducted by gas chromatography. The concentration of Pb in the whole blood and milk were determined by atomic absorption spectrometry with graphite furnace atomization and Zeeman correction. Our study established a significant and strong correlation between the content of Pb in the blood of the mother and the child. This supports the assumption that the transport of Pb through the placenta is neither regulated nor selective. Environmental maternal exposure to lead resulting in Pb-B levels considered safe for pregnant women had no effect on infant birth weight, the concentration of fatty acids in the blood and milk of mothers, or in the blood of newborns. Mothers' weight and BMI before pregnancy had no effect on the concentration of Pb and studied fatty acid profile.