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1.
Behav Brain Res ; 416: 113578, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34508769

RESUMO

Positive allosteric modulators (PAMs) of α5GABAA receptors (α5GABAARs) are emerging as potential therapeutics for a range of neuropsychiatric disorders. However, their role in memory processing of healthy animals is not sufficiently examined. We tested the effects of MP-III-022 (1 mg/kg, 2.5 mg/kg and 10 mg/kg), a PAM known to be selective for α5GABAARs and devoid of prominent side-effects, in different behavioral paradigms (Morris water maze, novel object recognition test and social novelty discrimination) and on GABRA5 expression in Wistar rats, 30 min and 24 h after intraperitoneal treatment administration. The lowest dose tested worsened short-term object memory. The same dose, administered two times in a span of 24 h, improved spatial and impaired object and, at a trend level, social memory. The highest dose had a detrimental effect on all types of long-term memory (object memory at a trend level) and short-term spatial memory, but improved short-term object and social memory. Distinct sets of expression changes were detected in both prefrontal cortex and two regions of the hippocampus, but the latter ones could be assessed as more consequential. An increase of GABRA5 mRNA in CA2 occurred in parallel with improvement of object and social, but impairment of spatial memory, while the opposite happened with a trend level change in CA1. Our study demonstrates the variability of the roles of the α5GABAAR based on its level of expression and localization, in dependence on the type and protocol of cognitive tasks, as well as the respective timing of pharmacological modulation and testing.

2.
Waste Manag Res ; 39(10): 1302-1316, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34581643

RESUMO

Waste electrical and electronic equipment (WEEE) represent one of the growing waste streams in Europe, whose content of hazardous substances and valuable materials focus on how it is handled. However, there are differences between countries regarding e-waste management system in Europe. This paper analyses and presents data regarding the e-waste management system in Italy, one of the founding countries of the EU and Serbia - EU candidate country. Within this work, the following aspects were considered: legislative framework and EU directive goals in terms of e-waste, institutional setup, collection system, and existing recycling and treatment technologies. In addition, material flow analysis is used to model mass balance within WEEE treatment plants in both countries. Finally, through assessment and comparison of current systems in both countries, problems and shortages of Serbia's e-waste management system are addressed.


Assuntos
Resíduo Eletrônico , Gerenciamento de Resíduos , Resíduo Eletrônico/análise , Eletrônica , Itália , Reciclagem , Sérvia
3.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360758

RESUMO

The current study describes the experimental design guided development of PEGylated nanoemulsions as parenteral delivery systems for curcumin, a powerful antioxidant, as well as the evaluation of their physicochemical characteristics and antioxidant activity during the two years of storage. Experimental design setup helped development of nanoemulsion templates with critical quality attributes in line with parenteral application route. Curcumin-loaded nanoemulsions showed mean droplet size about 105 nm, polydispersity index <0.15, zeta potential of -40 mV, and acceptable osmolality of about 550 mOsm/kg. After two years of storage at room temperature, all formulations remained stable. Moreover, antioxidant activity remained intact, as demonstrated by DPPH (IC50 values 0.078-0.075 mg/mL after two years) and FRAPS assays. In vitro release testing proved that PEGylated phospholipids slowed down the curcumin release from nanoemulsions. The nanoemulsion carrier has been proven safe by the MTT test conducted with MRC-5 cell line, and effective on LS cell line. Results from the pharmacokinetic pilot study implied the PEGylated nanoemulsions improved plasma residence of curcumin 20 min after intravenous administration, compared to the non-PEGylated nanoemulsion (two-fold higher) or curcumin solution (three-fold higher). Overall, conclusion suggests that developed PEGylated nanoemulsions present an acceptable delivery system for parenteral administration of curcumin, being effective in preserving its stability and antioxidant capacity at the level highly comparable to the initial findings.


Assuntos
Antioxidantes , Curcumina , Portadores de Fármacos , Nanoestruturas , Animais , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Disponibilidade Biológica , Linhagem Celular Tumoral , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Emulsões , Humanos , Masculino , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Projetos Piloto , Ratos , Ratos Sprague-Dawley
4.
Waste Manag Res ; 39(5): 720-730, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33866873

RESUMO

Efficient collection systems and information about the characteristics and quality of collected secondary plastic waste flows are of fundamental importance for the development of circular economies. In order to assess the effectiveness of the implementation of separate collection systems for plastic packaging, especially polyethylene terephthalate (PET) bottles, characteristic of the collected PET bottles in street mesh containers were studied in the city of Perm, Russia. The share of extraneous fractions was assessed and differentiation was carried out by volume, type of product, label presence, shape, content of solid and liquid impurities and colour. These results indicate that PET composition in different seasons is very similar, despite the assumption that the consumption of PET bottles in the spring and autumn seasons varies. In the mesh containers, up to 34% of the items were foreign objects, considering that only PET bottles should be collected. In each dimensional flow of PET bottles, the proportion of transparent bottles prevailed; it ranged from 31% to 70%. Based on the results of the experiment, almost all PET bottle categories had a standard shape, except packaging for food products and household chemicals, in which 26-27% of PET bottles had a non-standard shape. The results about charactersitic of source-separated PET bottles are fundamental for goal-oriented design and implementation of collection, recycling technologies, secondary separation facilities, the economics of recycling intitatives and reverse vending machines for collecting materials.


Assuntos
Polietilenotereftalatos , Reciclagem , Cidades , Plásticos , Federação Russa
5.
Psychoneuroendocrinology ; 129: 105234, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33930757

RESUMO

Intranasal treatment with oxytocin showed beneficial effects in post-traumatic stress disorder and autism spectrum disorders; however, it was not investigated as much in depression. Keeping in mind the favorable effects of oxytocin on animal models of anxiety and depression, we postulated that synergy between prescribed first choice drugs, selective serotonin reuptake inhibitors (SSRIs) and oxytocin could improve the treatment outcome compared with SSRI monotherapy. Our previous in vitro genome-wide transcriptomic study on human lymphoblastoid cell lines exposed to paroxetine resulted in increase of integrin ß3 (ITGB3) gene expression, and further, ITGB3/CHL1 expression ratio was hypothesized to influence the sensitivity to SSRIs. The aim of this report was to explore molecular mechanisms behind the antidepressant-like oxytocin effect, alone and in synergy with citalopram, on behavioral and molecular level in corticosterone treated rats, a paradigm used to model anxiety and depression in animals. Oxytocin treatment (1) ameliorated corticosterone-induced reduction of neurogenesis and number of parvalbumin-positive interneurons in the hippocampal CA1 region, (2) enhanced anxiolytic- and antidepressant-like effects of citalopram in the open field test, and (3) the SSRI/oxytocin synergy persisted in reversing the reduction of the Itgb3 gene expression and increased Itgb3/Chl1 ratio in the prefrontal cortices. These results support the existence of synergy between citalopram and oxytocin in reversing the molecular and behavioral changes induced by corticosterone treatment and point to possible molecular mechanisms behind antidepressant-like effect of oxytocin.

6.
Environ Res ; 194: 110728, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33444608

RESUMO

Recycling of electric and electronic waste products (e-waste) which amounted to more than 50 million metric tonnes per year worldwide is a massive and global operation. Unfortunately, an estimated 70-80% of this waste has not been properly managed because the waste went from developed to low-income countries to be dumped into landfills or informally recycled. Such recycling has been carried out either directly on landfill sites or in small, often family-run recycling shops without much regulations or oversights. The process traditionally involved manual dismantling, cleaning with hazardous solvents, burning and melting on open fires, etc., which would generate a variety of toxic substances and exposure/hazards to applicators, family members, proximate residents and the environment. The situation clearly calls for global responsibility to reduce the impact on human health and the environment, especially in developing countries where poor residents have been shouldering the hazardous burden. On the other hand, formal e-waste recycling has been mainly conducted in small scales in industrialized countries. Whether the latter process would impose less risk to populations and environment has not been determined yet. Therefore, the main objectives of this review are: 1. to address current trends and emerging threats of not only informal but also formal e-waste management practices, and 2. to propose adequate measures and interventions. A major recommendation is to conduct independent surveillance of compliance with e-waste trading and processing according to the Basel Ban Amendment. The recycling industry needs to be carefully evaluated by joint effort from international agencies, producing industries and other stakeholders to develop better processes. Subsequent transition to more sustainable and equitable e-waste management solutions should result in more effective use of natural resources, and in prevention of adverse effects on health and the environment.


Assuntos
Resíduo Eletrônico , Gerenciamento de Resíduos , Resíduo Eletrônico/análise , Eletrônica , Humanos , Reciclagem
7.
Waste Manag ; 87: 51-61, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31109551

RESUMO

Over the last years, emerging incentives for secondary production of high tech-metals, found in e-waste, are created because of their increasing demand and economic issues associated with their primary production. Due to the very low share of these metals in e-waste, pre-treatment methods can result in an output fraction rich in the metals of interest and may, therefore, be essential. To this scope, the present article evaluates and compares the efficiency of four different pre-treatment approaches containing various steps for recovering indium (In) from liquid crystal displays (LCDs) in laptop computers. The pre-treatment steps, used in various combinations, are (a) dry mechanical crushing and sieving, (b) pyrolysis, (c) thermal shock and (d) gravimetric process. Also, in all approaches, liquid crystals were removed from the samples, before applying the mechanical crushing step, as these are toxic and potentially harmful to human health and the environment. The removal was achieved by ultrasonic irradiation or mild agitation and optimized in terms of time, temperature and solvent type and concentration. Then, the feasibility of each pre-treatment approach was evaluated based on two parameters: (a) the content of In in the resulting sample after pre-treatment and (b) the separated mass share (%) with larger indium content as compared to the original LCD panel. The results showed that In is highly liberated in the fractions consisting of finest particles (<25 µm and <53 µm) after dry mechanical crushing and sieving with a maximum content of 234 mg/kg, which is twice as much as in the raw material. However, these particles represented only about 14 wt% of the original LCD panel mass. On the contrary, thermal shock results indicated that this was the most efficient pre-treatment approach, as both the content of In and the separated LCD mass (%) remained in high levels. Finally, some economic aspects associated with the processes are presented.


Assuntos
Resíduo Eletrônico , Cristais Líquidos , Índio , Reciclagem , Ultrassom
8.
Eur J Pharm Sci ; 125: 110-119, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30287408

RESUMO

This study aimed to investigate the potential of lecithin-based nanoemulsions costabilized by sucrose esters, with and without skin pretreatment with stainless steel microneedles, to improve delivery of aceclofenac, as a model drug, into/across the skin. The characterization revealed favorable droplet size (about 180 nm), narrow size distribution (<0.15), high surface charge (about -40 mV) and satisfying long-term stability (one year at 4 ±â€¯1 °C) of the formulation costabilized by sucrose palmitate, demonstrating a similar trend observed for the reference stabilized by widely used lecithin/polysorbate 80 combination. In vitro release/permeation testing and differential stripping on the porcine ear proved the superiority of the sucrose ester- over polysorbate-based nanoemulsion. However, in vitro findings were not fully indicative of the in vivo performances - no significant differences were observed between investigated formulations in pharmacokinetic profile and total amount of aceclofenac deposited in the rat skin 24 h after dosing, simultaneously pointing to delayed aceclofenac delivery into the systemic circulation. In addition, the ratio of plasma concentrations of aceclofenac and its major metabolite in rats, diclofenac, was remarkably changed after topical application of tested nanoemulsions compared to intravenous administration of aceclofenac solution. Finally, skin pretreatment with microneedles improved aceclofenac delivery into/across the rat skin from tested formulations, resulting in 1.4-2.1-fold increased bioavailability and 1.2-1.7-fold enhanced level of aceclofenac retained in the skin, as measured 24 h after administration. Moreover, the plasma concentrations of aceclofenac 24 h after application of tested formulations (lecithin/sucrose palmitate vs. lecithin/polysorbate 80) combined with microneedles (173.37 ±â€¯40.50 ng/ml vs. 259.23 ±â€¯73.18 ng/ml) were significantly higher than those obtained through intact skin (105.69 ±â€¯19.53 ng/ml vs. 88.38 ±â€¯14.46 ng/ml). However, obtained results suggest that combination of microneedles and sucrose palmitate-costabilized nanoemulsion could be useful to attain higher skin concentration, while combination of microneedles with polysorbate 80-costabilized nanoemulsion could be a preferable option for enhancing drug delivery into the bloodstream.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Diclofenaco/análogos & derivados , Sistemas de Liberação de Medicamentos , Nanopartículas/administração & dosagem , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Transporte Biológico , Diclofenaco/administração & dosagem , Diclofenaco/farmacocinética , Liberação Controlada de Fármacos , Emulsões , Microinjeções , Agulhas , Ratos Wistar , Pele/metabolismo , Absorção Cutânea , Sacarose/administração & dosagem , Sacarose/análogos & derivados , Sacarose/farmacocinética , Suínos
9.
Magnes Res ; 31(1): 24-32, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29991463

RESUMO

Although a magnesium-mediated attenuation of memory deficits was reported in animal models of ageing and traumatic brain injury, a possible memory enhancement in healthy subjects has not been investigated yet. We used novel object recognition test (NORT) to examine the effects of acute (30 mg/kg) and chronic (50 mg/kg, 28 days) Mg-sulfate treatment on the long-term memory (LTM) in healthy adult male rats, and to test the sustainability of magnesium effects in the models of acute and chronic (21 days) ACTH administration (10 µg/animal), mimicking the stress- and depression-like conditions. A single dose of Mg-sulfate enhanced the LTM retrieval in the 24 h inter-trial NORT protocol, in healthy, as well as in rats acutely treated with ACTH. Memory enhancement was also detected after 4-week long Mg-sulfate intake, in both healthy and rats chronically treated with ACTH. While the present findings on procognitive effects of chronic Mg-sulfate treatment corroborate with those from studies on the therapeutic potential of Mg-threonate, the current study is the first to report on memory enhancement induced by a single dose of magnesium.


Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Magnésio/administração & dosagem , Magnésio/farmacologia , Memória de Longo Prazo/efeitos dos fármacos , Reconhecimento Psicológico/efeitos dos fármacos , Hormônio Adrenocorticotrópico/sangue , Animais , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Masculino , Ratos Wistar
10.
Horm Behav ; 105: 1-10, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30025718

RESUMO

Magnesium (Mg), is not only a modulator of the glutamatergic NMDA receptors' affinity, it also prevents HPA axis hyperactivity, thus possibly being implicated in neurobiological features of mood disorders. Further uncovering of molecular mechanisms underlying magnesium's proposed effects is needed due to the recent shift in research of treatment resistant depression (TRD) towards glutamatergic pathways. Here, we applied Mg via drinking water for 28 days (50 mg/kg/day), in ACTH-treated rats, an established animal model of depression resistant to tricyclic antidepressants. Using this model in male rats we measured (1) changes in hippocampal neurogenesis and behavioral alterations, (2) adrenal hormones response to acute stress challenge and (3) levels of biometals involved in regulation of monoamines turnover in rat prefrontal cortex. Our results support beneficial behavioral impact of Mg in TRD model together with increased hippocampal neurogenesis and BDNF expression. Furthermore, Mg prevented ACTH-induced disruption in HPA axis function, by normalizing the levels of plasma ACTH, corticosterone and interleukin-6, and by increasing the peripheral release of adrenaline, noradrenaline and serotonin after the acute stress challenge. Finally, the influence on copper/zinc ratio suggested probable magnesium's involvement in monoamine turnover in PFC. Our findings provide further insights into the possible pathways implicated in the behavioral modulation effects of Mg, as well as its central and peripheral effects in ACTH-induced TRD model. Thus, further investigation of molecular signaling related to the glutamatergic transmission and role of Mg, could reveal prospects to novel treatment strategies that could be of particular importance for patients suffering from TRD.


Assuntos
Antidepressivos Tricíclicos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Depressão , Magnésio/farmacologia , Sistemas Neurossecretores/efeitos dos fármacos , Hormônio Adrenocorticotrópico , Animais , Corticosterona/sangue , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Depressão/patologia , Modelos Animais de Doenças , Resistência a Medicamentos/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Magnésio/administração & dosagem , Masculino , Neurogênese/efeitos dos fármacos , Sistemas Neurossecretores/fisiologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Ratos , Ratos Wistar , Fatores de Tempo , Falha de Tratamento
11.
Eur Neuropsychopharmacol ; 28(8): 903-914, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29891214

RESUMO

It is unclear whether GABAA receptors (GABAARs) that contain the α3-subunit are substantially involved in the anxiolytic effects of benzodiazepines (BDZs). In the present study, we tested YT-III-31, a newer BDZ ligand with functional preference for α3ßγ2 GABAARs, in two paradigms of unconditioned anxiety, the open field and elevated plus maze in rats. The effective dose of YT-III-31 (2 mg/kg) displayed a clear anxiolytic-like profile, unhampered by sedative action, in both tests. At a higher dose (10 mg/kg), YT-III-31 induced ataxia in the rotarod and sedation in spontaneous locomotor activity test. The latter effect was preventable by flumazenil and ßCCt, the non-selective and α1ßγ2 GABAAR affinity-selective antagonist, respectively, demonstrating that sedative properties of YT-III-31, when attained, are mediated by the α1γ2 site. To elucidate the receptor substrate of subtle behavioral differences between YT-III-31 and diazepam, we approximated in vivo receptor potentiation for both ligands, based on estimated unbound concentrations in rat brains. Far different from diazepam, YT-III-31 has significantly lower affinity for the α1γ2 over other BDZ-sensitive sites, and at lower doses (1-2 mg/kg) was devoid of potentiation at α1ßγ2 GABAARs. The approximation approach revealed a modest selectivity of YT-III-31 for α3γ2- in comparison to α2γ2 and α5γ2 binding sites, suggesting that its anxiolytic-like activity may not necessarily or predominantly reflect potentiation at α3ßγ2 GABAARs. Nonetheless, as the anxiolytic effects are achievable at a dose devoid of any sedative potential, and having favorable safety (cytotoxicity) and metabolic stability profile, YT-III-31 represents a valuable candidate for further translational research.


Assuntos
GABAérgicos/farmacologia , Receptores de GABA-A/metabolismo , Animais , Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Ansiedade/metabolismo , Benzodiazepinas/farmacologia , Sítios de Ligação , Ligação Competitiva , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Hipnóticos e Sedativos/farmacologia , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Ratos Wistar
12.
Int J Dev Neurosci ; 61: 31-39, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28610974

RESUMO

We previously demonstrated that lipopolysaccharide (LPS) administered intraperitoneally (i.p.) to pregnant Wistar rat dams, at embryonic days 15 and 16 (E15/16), induced a decrease of baseline locomotor activity and diminished reactivity to amphetamine in adult female offspring. In the present study we aimed to assess the duration of LPS-induced maternal immune activation (MIA) and investigate possible changes in levels of main neurotransmitters in fetal brain during MIA. We hypothesized that the observed behavioral changes may be linked with MIA-induced disturbance of prenatal GABAergic system development, especially with α5 GABAA receptors (α5GABAARs), expression of which takes place between E14 and E17. Thereafter, we set to investigate if later potentiation of α5GABAARs in offspring's preadolescence (from postnatal day 22-28) could prevent the deficit in locomotor reactivity to amphetamine observed in adulthood, at postnatal day P60. The elevation of IL-6 in amniotic fluid 6h after LPS treatment (100µg/kg, i.p.) at E15 was concurrent with a significant increase of GABA and decrease of glutamate concentration in fetal brain. Moreover, repeated administration of MP-III-022, a selective positive allosteric modulator of α5GABAARs, at a dose (2mg/kg daily, i.p.) derived from a separate pharmacokinetic study, prevented the LPS-induced decrease in locomotor reactivity to amphetamine (0.5mg/kg, i.p.) in adult females. These results were not mirrored in the parallel set of experiments with male offspring from LPS-treated rats. The results suggest that pharmacological potentiation of α5GABAARs activity in preadolescence may ameliorate at least some of adverse consequences of exposure to MIA in utero.


Assuntos
Anfetamina/toxicidade , Encéfalo , Lipopolissacarídeos/toxicidade , Locomoção/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Receptores de GABA-A/metabolismo , Fatores Etários , Regulação Alostérica , Animais , Animais Recém-Nascidos , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Estimulantes do Sistema Nervoso Central/toxicidade , Modelos Animais de Doenças , Embrião de Mamíferos , Feminino , GABAérgicos/farmacologia , Ácido Glutâmico/metabolismo , Humanos , Masculino , Neurotransmissores/metabolismo , Gravidez , Ratos , Ácido gama-Aminobutírico/metabolismo
13.
Waste Manag Res ; 34(9): 923-32, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27357561

RESUMO

This paper outlines the approach that can assist decision makers to have first preliminary insights regarding costs of complying with requested European Union municipal waste management goals in transition and developing countries. Serbia, as a joining member of European Union, must confront itself with the challenges resulting from European Union waste management directives. Implementation of waste separation units and the construction of sanitary landfills is already in place in Serbia. However, new waste management practice will need additional transformation and will require implementation of waste treatment technologies for additional management of generated waste. Implementation of analyzed best available technology/techniques for waste treatment can support the country's effort in reaching the policy goals. However, the question here is how much will the implementation of additional waste treatments influence the overall waste management costs? Results of the scenario's financial viability show that composting and sanitary landfill are the most viable solutions regarding the costs, even under increasing discount rates. Although different discount rates influence the overall gate fees and net present values, the level of affordability for different scenarios remains the same.


Assuntos
Instalações de Eliminação de Resíduos , Gerenciamento de Resíduos/economia , Gerenciamento de Resíduos/métodos , União Europeia , Objetivos , Eliminação de Resíduos/economia , Eliminação de Resíduos/instrumentação , Sérvia , Gerenciamento de Resíduos/instrumentação
14.
Oxid Med Cell Longev ; 2016: 2019643, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27042258

RESUMO

Sedentary lifestyle is highly associated with increased risk of cardiovascular disease, obesity, and type 2 diabetes. It is known that regular physical activity has positive effects on health; however several studies have shown that acute and strenuous exercise can induce oxidative stress and lead to DNA damage. As magnesium is essential in maintaining DNA integrity, the aim of this study was to determine whether four-week-long magnesium supplementation in students with sedentary lifestyle and rugby players could prevent or diminish impairment of DNA. By using the comet assay, our study demonstrated that the number of peripheral blood lymphocytes (PBL) with basal endogenous DNA damage is significantly higher in rugby players compared to students with sedentary lifestyle. On the other hand, magnesium supplementation significantly decreased the number of cells with high DNA damage, in the presence of exogenous H2O2, in PBL from both students and rugby players, and markedly reduced the number of cells with medium DNA damage in rugby players compared to corresponding control nonsupplemented group. Accordingly, the results of our study suggest that four-week-long magnesium supplementation has marked effects in protecting the DNA from oxidative damage in both rugby players and in young men with sedentary lifestyle. Clinical trial is registered at ANZCTR Trial Id: ACTRN12615001237572.


Assuntos
Atletas , Dano ao DNA/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Magnésio/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Comportamento Sedentário , Adulto , Suplementos Nutricionais , Futebol Americano , Humanos , Peróxido de Hidrogênio/farmacologia , Linfócitos/metabolismo , Masculino , Adulto Jovem
15.
Behav Brain Res ; 299: 72-80, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26620494

RESUMO

Numerous basic and epidemiological studies have connected prenatal maternal immune activation with the occurrence of schizophrenia and/or autism. Depending on subtle differences in protocols of the used animal model, a variety of behavioral abnormalities has been reported. This study investigated behavioral differences in Wistar rat offspring of both genders, exposed to the 100 µg/kg per day dose of lipopolysaccharide (LPS) in late embryogenesis (embryonic days 15 and 16), while tested at their adolescent and young adult age (postnatal days 40 and 60, respectively). Immune activation was confirmed by detecting high levels of TNF-α and IL-6 in dam blood withdrawn 2h after the first dose of LPS. The animals were assessed in three consecutive trials of locomotor activity (novelty exploration, response to i.p. saline injection and challenge with 0.5mg/kg amphetamine), Morris water maze and social interaction tests. Overt behavioral dysfunction was perceived in adult rats only, and these changes were gender-distinctive. When compared with control rats, LPS females displayed baseline hypolocomotion and a decreased reactivity to amphetamine, while LPS males exhibited spatial learning (acquisition trials) and memory (probe trial) impairments. Prenatal treatment did not affect the time spent in social interaction. As maternal exposure to LPS in late gestation resulted in behavioral changes in offspring in early adulthood, it may model schizophrenia-like, but not autism-like endophenotypes. However, lack of a potentiated response to amphetamine testified that this model could not mimic positive symptoms, but rather certain traits of cognitive dysfunction and deficit symptoms, in males and females, respectively.


Assuntos
Cognição/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Anfetamina/administração & dosagem , Animais , Transtorno Autístico/etiologia , Comportamento Animal , Modelos Animais de Doenças , Feminino , Interleucina-6/sangue , Interleucina-6/imunologia , Masculino , Atividade Motora/imunologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos Wistar , Esquizofrenia/etiologia , Fatores Sexuais , Fator de Necrose Tumoral alfa/sangue
16.
Int J Pharm ; 496(2): 931-41, 2015 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-26497615

RESUMO

To elaborate the decisive role of surfactants in promotion of aceclofenac' skin absorption, potentially avoiding irritation, we developed non-ionic microemulsions varying natural or synthetic surfactants: sucrose esters (laurate or myristate) vs. polysorbate 80. A comprehensive physicochemical characterization indicated no significant influence of the solubilized nonsteroidal anti-inflammatory drug on the bicontinuous structure of blank formulations. To evaluate skin tolerability of isopropyl alcohol, a sucrose ester-based microemulsion containing transcutol P as a cosurfactant was also developed. The measured skin parameters strongly depended on the (co)surfactant type, showing higher compatibility of the microemulsions containing sucrose ester and isopropyl alcohol. In vitro release results, in vivo tape stripping and pharmacokinetics in rats confirmed superiority of the sucrose ester- over polysorbate-based microemulsions (total amounts of aceclofenac penetrated 60.81±5.97 and 60.86±3.67 vs. 27.00±5.09µg/cm(2), and its maximum plasma concentrations 275.57±109.49 and 281.31±76.76 vs. 150.23±69.74ng/ml for sucrose laurate- and myristate- vs. polysorbate 80-based microemulsions, respectively). Hence, sugar-based excipients increased delivery of aceclofenac through stratum corneum by increasing its fluidity, showing overall more satisfying safety profiles. In conclusion, sucrose ester-based microemulsions proved to be promising carriers for dermal/transdermal aceclofenac delivery.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Diclofenaco/análogos & derivados , Absorção Cutânea , Tensoativos/farmacologia , Adulto , Animais , Materiais Biocompatíveis , Varredura Diferencial de Calorimetria , Diclofenaco/química , Diclofenaco/farmacocinética , Emulsões , Feminino , Humanos , Irritantes/farmacologia , Masculino , Ratos , Ratos Wistar , Solubilidade , Sacarose/química
17.
Waste Manag Res ; 33(6): 550-60, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26060233

RESUMO

In this paper, attention is shifted from larger cities and regions to the important role of small municipalities in large-scale capacity waste management systems. The motivation of this analysis is to understand how small municipalities can be prepared for future inclusion in regional waste management. For the first time, solutions that include integrated treatment of municipal, agricultural, and industrial waste generated by small-scale municipalities are developed and assessed. For this purpose, five small Serbian municipalities with populations up to 30,000 inhabitants were chosen as case studies. The methodology integrates field data with material flow analysis (MFA) to analyze and evaluate future scenarios. A set of indicators which reflect the goals of waste management, including the total costs, was chosen for scenario comparison and evaluation. It was found that delivering generated waste to regional waste management centers can result in the most affordable environmental benefits for the representative municipalities. More advanced solutions, which include composting and joint treatment of municipal, agricultural, and industrial waste, can contribute to reaching waste management goals, but are more costly (217% and 652% comparing to delivering generated waste to regions). These results can be regarded as a representative for similar municipalities and can serve to support pre-planning decisions in other countries with problems in establishing regional waste management systems.


Assuntos
Técnicas de Apoio para a Decisão , Modelos Teóricos , Resíduos Sólidos/análise , Gerenciamento de Resíduos/métodos , Eliminação de Resíduos , Sérvia
18.
Brain Res Bull ; 104: 1-6, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24695241

RESUMO

Long-term use of benzodiazepine-type drugs may lead to physical dependence, manifested by withdrawal syndrome after abrupt cessation of treatment. The aim of the present study was to investigate the influence of duration of treatment, as well as the role of α1-containing GABAA receptors, in development of physical dependence to diazepam, assessed through the level of anxiety and susceptibility to pentylenetetrazole (PTZ)-induced seizures, 24h after withdrawal from protracted treatment in rats. Withdrawal of 2mg/kg diazepam after 28, but not after 14 or 21 days of administration led to an anxiety-like behavior in the elevated plus maze. Antagonism of the diazepam effects at α1-containing GABAA receptors, achieved by daily administration of the neutral modulator ßCCt (5mg/kg), did not affect the anxiety level during withdrawal. An increased susceptibility to PTZ-induced seizures was observed during diazepam withdrawal after 21 and 28 days of treatment. Daily co-administration of ßCCt further decreased the PTZ-seizure threshold after 21 days of treatment, whilst it prevented the diazepam withdrawal-elicited decrease of the PTZ threshold after 28 days of treatment. In conclusion, the current study suggests that the role of α1-containing GABAA receptors in mediating the development of physical dependence may vary based on the effect being studied and duration of protracted treatment. Moreover, the present data supports previous findings that the lack of activity at α1-containing GABAA receptors is not sufficient to eliminate physical dependence liability of ligands of the benzodiazepine type.


Assuntos
Ansiedade/induzido quimicamente , Diazepam/toxicidade , Agonistas de Receptores de GABA-A/toxicidade , Receptores de GABA-A/metabolismo , Convulsões/induzido quimicamente , Síndrome de Abstinência a Substâncias/psicologia , Animais , Diazepam/administração & dosagem , Agonistas de Receptores de GABA-A/administração & dosagem , Masculino , Atividade Motora/efeitos dos fármacos , Subunidades Proteicas , Ratos , Ratos Wistar
19.
Brain Res ; 1554: 36-48, 2014 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-24472579

RESUMO

Enormous progress in understanding the role of four populations of benzodiazepine-sensitive GABAA receptors was paralleled by the puzzling findings suggesting that substantial separation of behavioral effects may be accomplished by apparently non-selective modulators. We report on SH-I-048A, a newly synthesized chiral positive modulator of GABAA receptors characterized by exceptional subnanomolar affinity, high efficacy and non-selectivity. Its influence on behavior was assessed in Wistar rats and contrasted to that obtained with 2mg/kg diazepam. SH-I-048A reached micromolar concentrations in brain tissue, while the unbound fraction in brain homogenate was around 1.5%. The approximated electrophysiological responses, which estimated free concentrations of SH-I-048A or diazepam are able to elicit, suggested a similarity between the 10mg/kg dose of the novel ligand and 2mg/kg diazepam; however, SH-I-048A was relatively more active at α1- and α5-containing GABAA receptors. Behaviorally, SH-I-048A induced sedative, muscle relaxant and ataxic effects, reversed mechanical hyperalgesia 24h after injury, while it was devoid of clear anxiolytic actions and did not affect water-maze performance. While lack of clear anxiolytic actions may be connected with an enhanced potentiation at α1-containing GABAA receptors, the observed behavior in the rotarod, water maze and peripheral nerve injury tests was possibly affected by its prominent action at receptors containing the α5 subunit. The current results encourage further innovative approaches aimed at linking in vitro and in vivo data in order to help define fine-tuning mechanisms at four sensitive receptor populations that underlie subtle differences in behavioral profiles of benzodiazepine site ligands.


Assuntos
Benzodiazepinonas/farmacologia , Agonistas de Receptores de GABA-A/farmacologia , Receptores de GABA-A/metabolismo , Animais , Benzodiazepinas/farmacocinética , Benzodiazepinas/farmacologia , Sítios de Ligação , Encéfalo/efeitos dos fármacos , Diazepam/farmacocinética , Diazepam/farmacologia , Moduladores GABAérgicos/farmacocinética , Moduladores GABAérgicos/farmacologia , Agonistas de Receptores de GABA-A/farmacocinética , Células HEK293 , Humanos , Hiperalgesia/tratamento farmacológico , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Atividade Motora/efeitos dos fármacos , Força Muscular/efeitos dos fármacos , Ratos , Ratos Wistar , Xenopus laevis
20.
Behav Brain Res ; 241: 198-205, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23261388

RESUMO

Amnesia is one of the most discussed properties of the benzodiazepine class of drugs. The effects of benzodiazepines on human memory are usually anterograde, while changes in retrograde memory functions were seldom reported. Such inconsistent findings have prompted numerous animal studies investigating the influences of these positive modulators of inhibitory neurotransmission on different stages of memory. Among the benzodiazepines, memory effects of midazolam are of special interest due to its many and varied clinical applications. The present Morris water maze study in adult male Wistar rats was performed in three experiments in which midazolam was administered at doses of 0.5, 1 and 2 mg/kg intraperitoneally, before or immediately after each of five daily learning sessions, with two trials in a session, as well as before the probe test. Midazolam impaired acquisition and subsequent retention of spatial learning of the position of the hidden platform even at a pre-training dose of 0.5 mg/kg. This low dose was not associated with impairment of the procedural component of learning, manifested by increased time spent in the periphery of the pool. The lack of midazolam effect on consolidation has not been confounded by the observed below-chance performance of the control group since our additional experiment using diazepam also administered immediately after each of five learning sessions has revealed a similar pattern of results. Finally, midazolam administered before the probe test impaired retrieval of reference memory at all tested doses. Hence, induction of retrograde, besides anterograde amnesia should be kept in mind as a possibility when midazolam is used in clinical settings.


Assuntos
Moduladores GABAérgicos/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Midazolam/farmacologia , Animais , Diazepam/farmacologia , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Wistar
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