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People living with chronic kidney disease (CKD) frequently suffer from mild cognitive impairment and/or other neurocognitive disorders. This review in two parts will focus on adverse drug reactions resulting in cognitive impairment as a potentially modifiable risk factor in CKD patients. Many patients with CKD have a substantial burden of comorbidities leading to polypharmacy. A recent study found that patients seen by nephrologists were the most complex to treat because of their high number of comorbidities and medications. Due to polypharmacy, these patients may experience a wide range of adverse drug reactions. Along with CKD progression, the accumulation of uremic toxins may lead to blood–brain barrier (BBB) disruption and pharmacokinetic alterations, increasing the risk of adverse reactions affecting the central nervous system (CNS). In patients on dialysis, the excretion of drugs that depend on kidney function is severely reduced such that adverse and toxic levels of a drug or its metabolites may be reached at relatively low doses, unless dosing is adjusted. This first review will discuss how CKD represents a risk factor for adverse drug reactions affecting the CNS via (i) BBB disruption associated with CKD and (ii) the impact of reduced kidney function and dialysis itself on drug pharmacokinetics. [ABSTRACT FROM AUTHOR]

The relationship between chronic kidney disease (CKD) and cognitive function has received increased attention in recent years. Antibacterial agents (ABs) represent a critical component of therapy regimens in patients with CKD due to increased susceptibility to infections. Following our reviewing work on the neurocognitive impact of long-term medications in patients with CKD, we propose to focus on AB-induced direct and indirect consequences on cognitive function. Patients with CKD are predisposed to adverse drug reactions (ADRs) due to altered drug pharmacokinetics, glomerular filtration decline, and the potential disruption of the blood–brain barrier. ABs have been identified as a major cause of ADRs in vulnerable patient populations. This review examines the direct neurotoxic effects of AB classes (e.g. beta-lactams, fluoroquinolones, aminoglycosides, and metronidazole) on the central nervous system (CNS) in patients with CKD. We will mainly focus on the acute effects on the CNS associated with AB since they are the most extensively studied effects in CKD patients. Moreover, the review describes the modulation of the gut microbiota by ABs, potentially influencing CNS symptoms. The intricate brain–gut–kidney axis emerges as a pivotal focus, revealing the interplay between microbiota alterations induced by ABs and CNS manifestations in patients with CKD. The prevalence of antibiotic-associated encephalopathy in patients with CKD undergoing intravenous AB therapy supports the use of therapeutic drug monitoring for ABs to reduce the number and seriousness of ADRs in this patient population. In conclusion, elucidating AB-induced cognitive effects in patients with CKD demands a comprehensive understanding and tailored therapeutic strategies that account for altered pharmacokinetics and the brain–gut–kidney axis. [ABSTRACT FROM AUTHOR]

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Background: Physical exercise activates the hypothalamopituitary-adrenal (HPA) axis and induces the body's inflammatory response. Due to contemporary dietary habits and increased energy expenditure, athletes are susceptible to depletion of magnesium ions. The aim of our study was to investigate, through assessment of plasma ACTH, serum IL-6, and salivary/serum cortisol levels, if chronic magnesium supplementation might reduce damaging stress effects in amateur rugby players. Methods: Rugby players (N = 23) were randomly assigned to intervention and control group. Basal samples were collected before intervention group started a 4-week-long supplementation with magnesium (500 mg Mg/d). Blood and saliva sampling were done a day before the match (Day-1), on the morning of competition (Game), and during a six-day-long recovery period (Day1, Day3 and Day6). ACTH, serum/salivary cortisol, IL-6 and total/differential leukocytes counts were determined at each time point. Results: There was a statistically significant increase in ACTH concentration in intervention group compared to control group, while reductions in cortisol concentrations between the two groups were the greatest at Day-1 (p<0.01) and at the day of competition (Game) (p<0.01). Our results revealed that magnesium completely abolished the increase in IL-6 level noted in control group on Day1 and Day3 vs. Day-1 (p<0.01) and also diminished the rise in neutrophil/lymphocyte ratio in intervention group vs. control group (p<0.01). Conclusions: These results suggest the possibly important influence magnesium supplementation might have on the change of parameters of HPA axis activity and reduction of immune response activation following strenuous physical exercise such as a rugby game. [ABSTRACT FROM AUTHOR]

Clinical research has identified developmental delay and physical malformations in children prenatally exposed to the antiepileptic drug (AED) valproic acid (VPA). However, the early signs of neurodevelopmental deficits, their evolution during postnatal development and growth, and the dose effects of VPA are not well understood. The present study aimed to examine the influence of maternal exposure to a wide dose range (50, 100, 200 and 400 mg/kg/day) of VPA during breeding and gestation on early physical and neuromotor development in mice offspring. Body weight gain, eye opening, the surface righting reflex (SRR) and tail suspension test (TST) were examined in the offspring at postnatal days 5, 10 and 15. We observed that: (1) all tested doses of VPA reduced the body weight of the offspring and the timing of eye opening; (2) offspring exposed to VPA displayed immature forms of righting and required more time to complete the SRR; (3) latency for the first immobilization in the TST is shorter in offspring exposed to higher doses of VPA; however, mice in all groups exposed to VPA exhibited atypical changes in this parameter during the examined period of maturation; (4) irregularities in swinging and curling activities were observed in animals exposed to higher doses of VPA. This study points to delayed somatic development and postponed maturation of the motor system in all of the offspring prenatally exposed to VPA, with stronger effects observed at higher doses. The results implicate that the strategy of continuous monitoring of general health and achievements in motor milestones during the early postnatal development in prenatally VPA-exposed offspring, irrespectively of the dose applied, could help to recognize early developmental irregularities. [ABSTRACT FROM AUTHOR]

This study examined the influence of propofol anesthesia on the expression of activity-regulated molecules (BDNF and c-Fos) and synaptic plasticity markers (synaptophysin, GAP-43, drebrin) in the frontal cortex and thalamus of 7-day-old (P7) rats. Although these brain regions are the main targets of anesthetic action, they are contained in the cortico–striato–thalamo–cortical feedback loops, involved in naturally occurring and drug-induced psychoses. Therefore, functional integrity of these loops was examined in adolescent and adult rats through d -amphetamine-induced hyperactivity. Propofol treatment (25 mg/kg) decreased exon-specific and total BDNF mRNA expression in the frontal cortex and thalamus, in a time-dependent manner. BDNF protein level was increased in the frontal cortex and decreased in the thalamus, which was accompanied by the change of phospho-TrkB expression. Similarly to BDNF, the expression of c-Fos was decreased in the frontal cortex while it was changed only at the protein level in the thalamus. Synaptic plasticity markers changed in a time- and region-specific manner, indicating increased synaptogenesis in the frontal cortex and synapse elimination in the thalamus in P7 rats after the propofol anesthesia exposure. These early molecular changes were followed by time-related, increased motor reaction to d -amphetamine in adolescent, but not in adult rats. Our study revealed that exposure of immature brain to propofol anesthesia during the critical phase of development provoked immediate changes in activity-dependent processes and synaptic adjustment, influencing brain capacity to integrate later developmental events and resulting in temporary altered response to acute psychotropic stimulation during adolescence. [ABSTRACT FROM AUTHOR]

Propofol anesthesia can trigger pro- and anti-apoptotic signaling pathways in the rat brain. In our previous work, we demonstrated that propofol causes widespread apoptotic neurodegeneration in 7-postnatal-day-old (PND7) but not in PND14 rat neurons. The mechanism responsible for these opposing outcomes is unknown, apparently linked to the specific stage of brain development. The present study aims to elucidate the anti-apoptotic process that is activated in the cortex and thalamus of PND14 Wistar rats during the first 48 h after the onset of propofol anesthesia. We showed that the expression of tumor necrosis factor-α (TNF-α) and several components of its pathway, TNFR1 and caspase-8, was significantly increased in the cortex and thalamus. Nuclear factor kappa B (NF-κB) p65 was downregulated in the cortex and upregulated in the thalamus. The expression of c-Fos was upregulated only in the cortex, showing opposed profile compared to NF-κB p65. Double immunofluorescence staining revealed the colocalization of NF-κB p65 with neuronal marker (NeuN), but with predominantly cytoplasmic localization. Finally, X-linked inhibitor of apoptosis protein (XIAP) was upregulated in both examined structures. Immunohistochemical staining with Iba-1 revealed that the treatment did not induce changes in microglial morphology. Our results (i) reveal that the simultaneous activation of pro- and anti-apoptotic signaling occurs after propofol anesthesia, and (ii) pinpoint the potential neuroprotective role of XIAP in anesthesia-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Background: Sleep deprivation, malnutrition and lack of physical activity are contemporary stress-related factors present in the student population. Stress activates the HPA and often suppresses the HPG axis, but also influences cytokine synthesis and consequently regulates immune response. Since magnesium deficiency facilitates negative pathophysiological consequences, a reasonable question imposes, whether Mg supplementation might correct the adrenal/gonadal hormone balance and immuno-endocrine function. Methods: Fifteen male students were given 2 x 250 mg Mg for four weeks. Serum levels of FSH, LH, testosterone (T), ACTH and cortisol (C) were measured before and after supplementation and the T/C ratio was calculated. Furthermore, IL-6, red blood cells (RBC), hemoglobin (Hb), white blood cells (WBC) and the WBC differential were measured. Results: Despite no change in the serum level of ACTH, a statistically significant (p<0.05) decrease in the serum cortisol level appeared, accompanied with an IL-6 level reduction (p<0.05) after Mg supplementation. Analysis of the pituitarygonadal axis hormones showed an increasing trend of the FSH level (p=0.087), and a significant increase (p<0.05) in the T/C ratio. An RBC count increase (p<0.001) was found, along with a decrease in the percentage of neutrophils (p< 0.05), and a trend toward a lymphocyte percentage increase. Conclusions: The results suggest that chronic oral magnesium supplementation in male students improves the balance of pituitary-gonadal and pituitary-adrenal hormones and is involved in the regulation of the basal IL-6 level. [ABSTRACT FROM AUTHOR]

In the framework of wastewater treatment plants, sewage sludge can be directed to biochar production, which when coupled with an external iron source has the potential to be used as a carbon–iron composite material for treating various organic pollutants in advanced oxidation processes. In this research, "green" synthesized nano zero-valent iron (nZVI) supported on sewage sludge-based biochar (BC)–nZVI-BC was used in the Fenton process for the degradation of the recalcitrant organic molecule. In this way, the circular economy principles were supported within wastewater treatment with immediate loop closing; unlike previous papers, where only the water treatment was assessed, the authors proposed a new approach to wastewater treatment, combining solutions for both water and sludge. The following phases were implemented: synthesis and characterization of nano zero-valent iron supported on sewage sludge-based biochar (nZVI-BC); optimization of organic pollutant removal (Reactive Blue 4 as the model pollutant) by nZVI-BC in the Fenton process, using a Definitive Screening Design (DSD) model; reuse of the obtained Fenton sludge, as an additional catalytic material, under previously optimized conditions; and assessment of the exhausted Fenton sludge's ability to be used as a source of nutrients. nZVI-BC was used in the Fenton treatment for the degradation of Reactive Blue 4—a model substance containing a complex and stable anthraquinone structure. The DSD model proposes a high dye-removal efficiency of 95.02% under the following optimal conditions: [RB4] = 50 mg/L, [nZVI] = 200 mg/L, [H2O2] = 10 mM. pH correction was not performed (pH = 3.2). Afterwards, the remaining Fenton sludge, which was thermally treated (named FStreated), was applied as a heterogeneous catalyst under the same optimal conditions with a near-complete organic molecule degradation (99.56% ± 0.15). It could be clearly noticed that the cumulative amount of released nutrients significantly increased with the number of leaching experiments. The highest cumulative amounts of released K, Ca, Mg, Na, and P were therefore observed at the fifth leaching cycle (6.40, 1.66, 1.12, 0.62, 0.48 and 58.2 mg/g, respectively). According to the nutrient release and toxic metal content, FStreated proved to be viable for agricultural applications; these findings illustrated that the "green" synthesis of nZVI-BC not only provides innovative and efficient Fenton catalysts, but also constitutes a novel approach for the utilization of sewage sludge, supporting overall process sustainability. [ABSTRACT FROM AUTHOR]

Inorganic arsenic removal from water using low-cost adsorbents is presented in this paper. Selective removal of As(III) and As(V) from water was performed with natural materials (zeolite, bentonite, sepiolite, pyrolusite and limonite) and industrial by-products (waste filter sand as a water treatment residual and blast furnace slag from steel production); all inexpensive and locally available. Kinetic and equilibrium studies were realized using batch system techniques under conditions that are likely to occur in real water treatment systems. The natural zeolite and the industrial by-products were found to be good and inexpensive sorbents for arsenic while bentonite and sepiolite clays showed little affinity towards arsenic. The highest maximum sorption capacities were obtained for natural zeolite, 4.07 mg As(V) g-1, and waste iron slag, 4.04 mg As(V) g-1 [ABSTRACT FROM AUTHOR]

Mechanism and performances of arsenic(III) [As(III)] and arsenic(V) [As(V)] sorption Onto hydrated iron(III) oxide (HFO)-coated materials were investigated at neutral pH where arsenic occurs in both molecular and ionic forms. Arsenic sorption by HFO-coated materials was proven to be a multistage process consisting of both macropore and intraparticle diffusion. Higher mass-transfer velocities were obtained for As(III), which is attributed to the beneficial features of HFO. Equilibrium studies revealed the spontaneous and favorable nature of the arsenic sorption process. The maximum sorption capacity and the Gibbs free energy values indicated that HFO-coated materials exhibit more affinity towards As(IIl). The Langmuir and Freundlich isotherm models revealed both the chemical and physical nature of the sorption process, while the Dubinin-Radushkevich model indicated that physical sorption is a more dominant process with HFO-coated materials. [ABSTRACT FROM AUTHOR]

Abstract: The changes that occur during adolescence have a profound impact on the brain and behavior later in life. In this work we examined changes in motor activity during habituation to a novel environment and after treatment with MK-801 (0.025, 0.05, 0.1mg/kg) in peripubertal, pubertal and adult Wistar rats. The involvement of the motor cortex and striatum in motor activity was assessed by analyzing changes in c-Fos protein levels that served as an indicator of neuronal activity. During the habituation period, locomotor activity in peripubertal rats was higher during the first 10min than in other groups. The same amount of stereotypy-like movements was detected in all three groups. MK-801 induced dose- and age-dependent changes in motor activity. Peripubertal rats were the most sensitive to treatment with MK-801. We also report a surprising finding that systemic application of MK-801 induced a similar age-related profile of changes in motor activity and c-Fos protein expression in the motor cortex but no c-Fos induction in the striatum. Our results demonstrate that, depending on the phase of adolescence the same dose of MK-801 affected behavioral functions in a different manner and that activity of the motor cortex rather than striatal activity was linked to drug-motor activity interactions. [Copyright &y& Elsevier]

Abstract: The regenerative capacity of the adult central nervous system is limited. We investigated whether short-term food restriction (FR; 50% of the daily food intake lasting 3 months) modulates processes of brain plasticity after cortical injury. Quantitative changes of growth-associated protein 43 (GAP-43) and synaptophysin (SYP) mRNA levels in the ipsilateral cortex of the adult rat during the recovery period (from 2 to 28 days) after injury were investigated by real-time RT-PCR. Using Western blot and immunohistochemical analyses we examined the levels and localization of proteins involved in neuronal plasticity, SYP and GAP-43, as well as glial fibrillary acidic protein (GFAP), a marker of glial plasticity. A marked rise in GAP-43 and SYP immunoreactivity observed in the FR group on the 7th day after injury pointed to increases in axonal branching and synapses in the cortex surrounding the lesion. The appearance of reactive astrocytes was accompanied by the absence of immunoreactivity for GAP-43 and SYP in ad libitum fed animals. This finding supports the hypothesis that morphological hypertrophy of astrocytes associated with GFAP synthesis is responsible either directly or indirectly for the inhibitory role of activated glia on axonal regeneration. Examination of the effects of FR on serum corticosterone and glucose concentrations and GAP-43, SYP and GFAP expression revealed that FR facilitated recovery of the injured region by attenuating reactive astrogliosis and enhancing the expression of neuronal plasticity markers. [Copyright &y& Elsevier]

Abstract: Commonly used general anesthetics can have adverse effects on the developing brain by triggering apoptotic neurodegeneration, as has been documented in the rat. The rational of our study was to examine the molecular mechanisms that contribute to the apoptotic action of propofol anesthesia in the brain of 7-day-old (P7) rats. The down-regulation of nerve growth factor (NGF) mRNA and protein expression in the cortex and thalamus at defined time points between 1 and 24h after the propofol treatment, as well as a decrease of phosphorylated Akt were observed. The extrinsic apoptotic pathway was induced by over-expression of tumor necrosis factor (TNF) which led to the activation of caspase-3 in both examined structures. Neurodegeneration was confirmed by Fluoro-Jade B staining. Our findings provide direct experimental evidence that the anesthetic dose (25mg/kg) of propofol induces complex changes that are accompanied by cell death in the cortex and thalamus of the developing rat brain. [Copyright &y& Elsevier]

Abstract: In this paper we describe the effects of six different food restriction (FR) regimens on amphetamine (AMPH)-induced locomotor and nonlocomotor activities in male rats. Changes in serum corticosterone (CORT), insulin and glucose levels were also examined. Each regimen was implemented through different daily food allowance (50%, 25% and 12.5% of the daily food intake, referred to as 50%, 75% and 87.5% FR groups, respectively) and by a specific feeding regimen — either every day (ED) or every other day (EOD). AMPH injection led to a significant increase of locomotor activity in all rats subjected to FR compared to ad libitum fed rats. A significant increase of nonlocomotor activity was observed only in the 75% FR and 87.5% FR groups. The serum CORT levels were significantly elevated and the serum insulin and glucose levels were significantly decreased in all of the FR groups in comparison to the AL rats. The results presented in this paper suggest that the ED regimens produced changes in motor activity and biochemical parameters, which were more-or-less dependent on the degree of FR. In contrast, the EOD regimens induced very similar changes irrespective of the degree of FR degree. Our data support the possible mechanistic roles of CORT and insulin in the effect of FR on locomotor activity, since the most pronounced increase of serum CORT and more pronounced decrease in serum insulin concentration was observed in the groups that also exhibited the highest locomotor activities. [Copyright &y& Elsevier]

Abstract: To elucidate the effects of ageing on T-cell-maturation, in 3- and 18-month-old rats, we analysed the expression of: (i) CD4/CD8/TCRαβ and (ii) Thy-1, which is supposed to be a regulator of TCRαβ signalling, and thereby the thymocyte selection thresholds. Since an essential role for TCRαβ signalling in the development of CD4+25+Treg-cells was suggested, the frequency of these cells was also quantified. We demonstrated that, as for mice, early thymocyte differentiational steps within the CD4-8- double negative (DN) developmental stage are age-sensitive. Furthermore, we revealed that TCRαβ-dependent stages of T-cell development are affected by ageing, most likely due to an impaired expression of Thy-1 on TCRαβlow thymocytes entering selection processes. The diminished frequency of the post-selection CD4+8+ double positive (DP) cells in aged rats, together with an overrepresentation of mature single positive (SP) cells, most probably suggests more efficient differentiational transition from the DP TCRαβhigh to the SP TCRαβhigh developmental stage, which is followed by an increase in pre-migration proliferation of the mature SP cells. Moreover, the study indicated impaired intrathymic generation of CD4+25+Treg-cells in aged rats, thus providing a possible explanation for the increased frequency of autoimmune diseases in ageing. [Copyright &y& Elsevier]

Abstract: The effects of chronic (7 days) exposure to an extremely low frequency magnetic field (ELF-MF, 50Hz, 0.5mT) on spontaneous and amphetamine-induced (1.5mg/kg, i.p.) locomotor and stereotypic activities in adult rats were examined by open field test for 2h on exposure days 1, 3, and 7. After 1 day of exposure to ELF-MF, the spontaneous locomotor activity was increased clearly at the first hour of observation and significantly at the second one as compared to the corresponding values in other series with ELF-MF and sham-exposed animals. After 7 days of exposure to ELF-MF, an amphetamine enhancing effect on the locomotor activity was significantly reduced at the second hour of observation as compared to that in 1-day- and sham-exposed rats treated with amphetamine. In contrast to the locomotor activity, the amphetamine-induced stereotypic behaviour in 7-day pre-exposed rats was significantly reduced at the first hour versus sham-exposed rats. While at the second hour of observation this effect was significant as compared to 1- and 3-day exposed animals (but not sham-exposed rats). Our results indicate that an extremely low frequency magnetic field is able to affect differently two types of behaviour, which are dependent on both the time course of exposure and the imbalance in the brain mediatory systems. [Copyright &y& Elsevier]

The time-course of changes of basal and amphetamine (AMPH)-induced locomotor and stereotypic activities in adult male Wistar rats after a single ribavirin injection was studied. In the first set of experiments, 10, 20 or 30 mg ribavirin/kg body weight (b.w.) were injected i.p. to rats and their basal motor activities were recorded every 10 min for 2 h and compared with those of saline-treated controls. In the second set of experiments, the animals were pretreated with ribavirin and 20 min later i.p. injected with AMPH (1.5 mg/kg b.w.). The controls received AMPH 20 min after the saline injection. Motor activity was recorded after the first injection and until 120 min after AMPH administration. Ribavirin did not significantly affect the time-course of either basal locomotor or stereotypic activities. Pretreatment with any of the applied ribavirin doses decreased the AMPH-induced hyperlocomotor response. However, the most pronounced effect was observed with ribavirin doses of 20 mg/kg and 30 mg/kg when administered during the first 10 min and 30 min after the AMPH injection respectively. In contrast, the stereotypic activities of these animals were only slightly changed. These results indicate a different susceptibility of regions in the basal ganglia to ribavirin. [ABSTRACT FROM AUTHOR]

The effects of short-term (15 min) pre-exposure of rats to extremely low-frequency magnetic field (ELF-MF, 50 Hz, 6 mT) on their motor (locomotor and stereotypic) activity induced by d-amphetamine sulphate (AMPH) at different doses (0.5, 1.5 and 4.5 mg/kg, i.p.) were studied in the open field test. In saline-treated rats both parameters of motor activity were unaffected by ELF-MF irradiation. The rats pre-exposed to ELF-MF and injected with the lowest dose of AMPH showed the same locomotor activity as control animals, while their stereotypic behaviour was significantly elevated. ELF-MF in combination with AMPH at higher doses significantly enhanced motor activity when compared with values obtained in both control and combined experiments with the lowest dose of the drug. However, only combined locomotor effect at the middle dose of AMPH was significantly greater than those observed in corresponding experiments with AMPH alone. These results demonstrate that acute short-term exposure to ELF-MF is able to modify a motor activity in dependence on the extent of AMPH-induced neurotransmitter imbalance. [Copyright &y& Elsevier]

The effects of tiazofurin (TR; 2-β-d-ribofuranosylthiazole-4-carboxamide), a purine nucleoside analogue on basal and amphetamine (AMPH)-induced locomotor and stereotypic activity of adult Wistar rat males were studied. The animals were injected with low (3.75, 7.5, and 15 mg/kg ip) and high (62.5, 125, and 250 mg/kg ip) TR doses. Neither low nor high TR doses influenced basal locomotor and stereotypic activity in comparison with the corresponding controls treated with saline only. However, pretreatment with TR at any dose applied, except for the lowest one, significantly decreased AMPH-induced (1.5 mg/kg ip) locomotor activity, while AMPH-induced stereotypic activity was inhibited with the two highest TR doses. In addition, TR was detected in the brain by HPLC already 15 min after the injection (125 mg/kg ip) to reach a maximum 2 h after the administration and was detectable in this tissue during the next 4 h. Our results indicate that TR modifies central regulation of the motor activity, possibly by influencing dopaminergic (DA-ergic) transmission. [Copyright &y& Elsevier]

The aim of the present study was to examine motor effects of amphetamine (AMPH) in rats pretreated with either dizocilpine (MK-801) or phencyclidine (PCP), and to estimate possible differences in these effects. Our results showed that AMPH increases the duration of motor effects of PCP, while it does not change motor effects of MK-801. These findings may reflect different mechanisms of action of MK-801 and PCP, as well as selective influence of AMPH on metabolism of these drugs. [Copyright &y& Elsevier]

The aim of this paper is to evaluate the potential mechanisms of the absorption and distribution of metals in the aromatic herbs Mentha spicata and Mentha longifolia, as well as their potential for the bioaccumulation of these elements. The herbs were sampled from the slopes of Mount Bjelasica in Montenegro. After the microwave processing of the herb samples and the associated soil, the content of the investigated metals Cu, Zn, Ni, Fe and Mn were determined using atomic absorption spectrophotometry. Taking average values from various parts of both types of mint, the metals were present in the following descending order: Fe (570 mg/kg) Mn (54.0) Zn (30.6) Cu (27.2) Ni (2.45). The metals under investigation are most commonly present in the roots of the mint, except in the case of Ni in M. longifolia. Manganese is more commonly found in the tissues of M. longifolia than in M. spicata, while the other investigated metals are found relatively uniformly in both types of mint. The bioaccumulation potential of M. spicata, from the soil to the roots, is greatest for Cu and Fe, and generally uniform, with the next highest potential being shown by Zn. [ABSTRACT FROM AUTHOR]

Kidney dysfunction can profoundly influence many organ systems, and recent evidence suggests a potential role for increased albuminuria in the development of mild cognitive impairment (MCI) or dementia. Epidemiological studies conducted in different populations have demonstrated that the presence of increased albuminuria is associated with a higher relative risk of MCI or dementia both in cross-sectional analyses and in studies with long-term follow-up. The underlying pathophysiological mechanisms of albuminuria's effect are as yet insufficiently studied, with several important knowledge gaps still present in a complex relationship with other MCI and dementia risk factors. Both the kidney and the brain have microvascular similarities that make them sensitive to endothelial dysfunction involving different mechanisms, including oxidative stress and inflammation. The exact substrate of MCI and dementia is still under investigation, however available experimental data indicate that elevated albuminuria and low glomerular filtration rate are associated with significant neuroanatomical declines in hippocampal function and grey matter volume. Thus, albuminuria may be critical in the development of cognitive impairment and its progression to dementia. In this review, we summarize the available evidence on albuminuria's link to MCI and dementia, point to existing gaps in our knowledge and suggest actions to overcome them. The major question of whether interventions that target increased albuminuria could prevent cognitive decline remains unanswered. Our recommendations for future research are aimed at helping to plan clinical trials and to solve the complex conundrum outlined in this review, with the ultimate goal of improving the lives of patients with chronic kidney disease. [ABSTRACT FROM AUTHOR]

The use of wild herbs to relieve and treat many human diseases is increasing worldwide, due to their medicinal features and limited side effects. The content of metals in them is of great interest. Our objective was to determine the levels of Cu, Fe, Mn, Ni, and Zn in individual parts of four medicinal plant species (Achillea millefolium L., Origanum vulgare L., Thymus serpyllum L., and Hypericum perforatum L.) and their native soil. For the study, we selected four sites located at the foot of Mount Bjelasica in Montenegro. Microwave-assisted digestion was applied for the dissolution of the samples and the metal concentrations were determined using atomic absorption spectrometry (AAS). All the investigated metals are most concentrated in the roots of the tested herbs. The translocation of metal from the root to the aboveground parts is different and depends on the metal and the plant. All the tested plants contain the most Fe (except oregano) and the least Ni. The most significant levels of Zn (44.6-116 mg kg-1), Ni (0.10-26.3 mg kg-1) and Mn (28.4--329 mg kg-1) were found in O. vulgare, the largest concentration of Cu (20.6--85.4 mg kg-1) in H. perforatum and Fe (108-1324 mg kg-1) showed its largest value in T. serpyllum. [ABSTRACT FROM AUTHOR]

This research investigates the potential use of pyrite cinder (PC) as an efficient Fenton-like catalyst for the removal of the reactive azo dye Reactive Red 120 (RR120) from aqueous solutions. The characterization of its PC structure and composition confirmed its great potential to act as catalytic iron source in a heterogeneous Fenton system. Dye removal optimization was performed in terms of PC dosage (0.4–8 g/L), H2O2 concentration (2–25 mM), pH value (2–4.6), initial dye concentration (50–200 mg/L), and mixing time. The highest decolorization efficiency (92%) was achieved after a reaction time of 480 min under following conditions: RR120 = 50 mg/L, PC = 4 g/L, H2O2 = 10 mM, and pH = 3. After decolorization, an extensive analysis of the generated effluent was performed regarding metal leaching, mineralization, toxicity, and degradation product formation. The metal leaching indicated the necessity for a pH increase in order to remove the settled metal hydroxides. The mineralization efficiency was satisfactory, reaching 85% and 62% of the COD and TOC removal, respectively. The respirometry measurements and bioluminescence tests indicated the detoxification of the treated solution. The absorption spectra and GC/MS analysis confirmed the changes in the molecular structure in the form of the destruction of the azo bond, with a simpler aromatic and aliphatic intermediates formation. This study provides an effective method for removing azo dye in polluted water by employing waste tailings as alternative Fenton-like catalysts, while also using waste tailings as the secondary resource. [ABSTRACT FROM AUTHOR]

Aims: CYP2C19 transgenic mouse expresses the human CYP2C19 gene in the liver and developing brain, and it exhibits altered neurodevelopment associated with impairments in emotionality and locomotion. Because the validation of new animal models is essential for the understanding of the aetiology and pathophysiology of movement disorders, the objective was to characterise motoric phenotype in CYP2C19 transgenic mice and to investigate its validity as a new animal model of ataxia. Methods: The rotarod, paw-print and beam-walking tests were utilised to characterise the motoric phenotype. The volumes of 20 brain regions in CYP2C19 transgenic and wild-type mice were quantified by 9.4T gadolinium-enhanced post-mortem structural neuroimaging. Antioxidative enzymatic activity was quantified biochemically. Dopaminergic alterations were characterised by chromatographic quantification of concentrations of dopamine and its metabolites and by subsequent immunohistochemical analyses. The beam-walking test was repeated after the treatment with dopamine receptor antagonists ecopipam and raclopride. Results: CYP2C19 transgenic mice exhibit abnormal, unilateral ataxia-like gait, clasping reflex and 5.6-fold more paw-slips in the beam-walking test; the motoric phenotype was more pronounced in youth. Transgenic mice exhibited a profound reduction of 12% in cerebellar volume and a moderate reduction of 4% in hippocampal volume; both regions exhibited an increased antioxidative enzyme activity. CYP2C19 mice were hyperdopaminergic; however, the motoric impairment was not ameliorated by dopamine receptor antagonists, and there was no alteration in the number of midbrain dopaminergic neurons in CYP2C19 mice. Conclusions: Humanised CYP2C19 transgenic mice exhibit altered gait and functional motoric impairments; this phenotype is likely caused by an aberrant cerebellar development. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is one of the leading causes of death and disability in humans. Subsequent pathological events occurring in the brain after TBI, referred to as secondary injury, continue to damage surrounding tissue resulting in substantial neuronal loss. Using an animal model of TBI we examined the effect of dietary restriction (DR) on the neuroapoptosis and Bcl-2 family genes as the main regulators of the intrinsic apoptotic pathway. Bcl-2, Bcl-xl and Bax mRNA and protein expression in the ipsilateral cortex of adult Wistar rats exposed to DR before TBI were studied from 2 to 28 days post injury. Our results showed that DR suppressed neuroapoptosis and promoted significant upregulation of antiapoptotic Bcl-2 and Bcl-xl mRNAs in the ipsilateral cortex following injury. Expression of the proapoptotic Bax gene increased in ad libitum (AL) fed rats but remained unchanged in rats exposed to DR. Although the expression of Bcl-2, Bcl-xl and Bax proteins was changed in a similar manner in both experimental groups, DR promoted a continuous increase in the Bcl-2:Bax protein ratio throughout the recovery period. Together with our previous finding that DR mediates inhibition of the extrinsic apoptotic pathway the present work reveals that modulation of the intrinsic pathway contributes to the beneficial effect of DR in brain injury. These findings provide new insight into the effects of DR on pro-survival signaling after injury, lending further support to its neuroprotective effect. [ABSTRACT FROM AUTHOR]

A potential relationship between unrestricted sucrose intake (USI), overweight, and emotional/behavioral control has not been well documented. We examined the influence of USI and having less sweetness than expected on body weight (BW), motor/exploratory, anxiety-like, and social dominant behavior in adult C57BL/6J male mice. Animals had free access to water (group 1) or 32% sucrose and water (sucrose groups 2–5) for 10 days. Then, group 2 remained with 32% sucrose while groups 3–5 were subjected to the downshift (24 h access to 4%, 8%, or 16% sucrose). All experimental groups were weighed and tested in the novel-open arena (NA), elevated plus maze (EPM), and tube tests to assess BW, motor/exploratory, anxiety-like, and social dominance behavior, respectively. USI did not influence animals' BW but produced hyperactivity and anxiolytic-like behavior, which was evident in EPM but not in NA; the outcomes of the downshift were comparable. USI did not influence successes/wins in the tube test but altered emotions that drive the winning, favoring a less anxious behavioral phenotype; this was not evident in the downshifted groups. Observed findings suggest that USI promotes sensation-seeking and motivates dominance, without changing BW, while blunted emotional base of social dominance might be an early mark of the downshift. [ABSTRACT FROM AUTHOR]

Cyclic voltammetry was used to examine the kinetics of degradation of ascorbic acid (AA) at different temperatures. It has been shown that the reduction of the concentration of AA in all temperatures follow the kinetics of the first order reaction. The rate constant of the oxidation reaction increases with temperature as follows: 5x10-5, 2x10-4, 1x10-3, and 3x10-3 min-1 at temperatures of 25, 35, 65 and 90 °C, respectively. The temperature dependence of the rate constant follows the Arrhenius equation, and the value of activation energy of the reaction degradation is 48.2 kJ mol-1. The effect of storage time at a temperature of 90 °C on AA content in fresh juice of green peppers was investigated. It was shown that AA oxidation reaction in the juice is also the first order reaction, while the lower rate constant in relation to the pure AA (5x10-3 min-1 ) indicates the influence of other substances present in the peppers. [ABSTRACT FROM AUTHOR]

The purpose of this study is investigation of electrocoagulation (EC) as a treatment of municipal wastewater, integrating life cycle impact assessment (LCIA) for assessing its environmental performance of investigated treatment. The study evaluated the effectiveness of EC in removing physico-chemical and microbial parameters using aluminum (Al) and iron (Fe) electrodes in monopolar and bipolar modes. Bipolar arrangement of Al(−)/Al/Al/Al(+) electrodes achieved the highest removals: 70% COD, 72% BOD 5 followed by complete elimination of total phosphorous, turbidity and microbial parameters. This treatment was subject to investigation of the influence of reaction time (t = 10–60 min) on removals at higher current density (CD = 3.33 mA/cm2). In order to reduce energy consumption, the same reaction time range was used with a reduced CD = 2.33 mA/cm2. Following removal efficiencies obtained: 47–72% COD (higher CD) and 53–78% (lower CD); 69–75% BOD 5 (higher CD) and 55–74% CD (lower CD); 12–21% NH 4 − (higher CD) and 7–22% NH 4 − (lower CD). Total P, NO 3 − and NO 2 − compounds showed the same removals regardless the CD. Decrease in current density did not influence removals of total suspended matter, turbidity, salinity as well as microbial parameters. The bipolar arrangement of Al(−)/Al/Al/Al(+) electrodes, assuming a lower CD = 2.33 mA/cm2 and t = 30 min, was assessed with the Recipe 2016Midpoint (H) and USEtox v.2 LCIA methods to explore the environmental justification of using EC for wastewater treatment. The LCIA results revealed that the EC process significantly reduces water eutrophication and toxicity for freshwater and marine ecosystems, but has higher impacts in global warming, fossil fuel consumption, human toxicity, acidification, and terrestrial ecotoxicity due to high energy consumption. This can be mainly explained by the assumption in the study that the EC precipitate is dispersed to agricultural soil without any pre-treatment and material recovery, along with relatively high energy consumption during the process. [Display omitted] • Bipolar arrangement (Al(−)/Al/Al/Al(+)) with lower CD of 2.33 mA/cm2 and t = 30 min is the most successful one.. • LCIA revealed EC significantly reduces freshwater and marine eutrophication. • Technology improvement should include sustainable energy sources and environmental friendly electrodes. • The potential of EC precipitate and effluent needs optimization for overall process sustainability. [ABSTRACT FROM AUTHOR]

Purpose: To compare the effects of repeated exposure to extremely low frequency-modulated microwaves (ELF-MW) on cortical and hypothalamic electroencephalograms (EEG). Materials and methods: In 10 freely moving rats with carbon electrodes implanted into the cortex and dorsomedial hypothalamus, averaged frequency spectra (0.5–30 Hz) of the EEG were studied for five consecutive days either under sham exposures (five rats) or under mixed sham/MW-exposures (five rats). The rats were exposed to ELF-MW (915 MHz, 20-ms pulse duration, ∼0.3 mW/cm2, 4 Hz) intermittently (1-min ‘On’, 1-min ‘Off’) for 10 min (specific absorption rate, SAR, ∼0.7 mW/g on average) several times per day, with 10-min pre- and post-exposure periods. Results: In baseline EEG, the activities of 3.2–6.0 Hz and 17.8–30.5 Hz dominated in the cortex and of 6.0–17.8 Hz in the hypothalamus. This cortical-hypothalamic imbalance was relatively stable at sham-exposures and insensitive to ELF-MW in all frequency ranges but one. ELF-MW increased the beta2 (17.8–30.5 Hz) level in the hypothalamus to a greater extent than in the cortex, causing significant diminishing of the initial EEG bias between them. Moreover, a cumulative phenomenon under repeated exposures to ELF-MW was revealed. Conclusions: These results are in line with evidence that repeated low-level exposure to ELF-MW affects brain functioning and provide an additional approach when analysing underlying mechanisms. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) perturbs the crosstalk with others organs, with the interaction between the kidneys and the heart having been studied most intensively. However, a growing body of data indicates that there is an association between kidney dysfunction and disorders of the central nervous system. In epidemiological studies, CKD is associated with a high prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment and depression. Along with traditional cardiovascular risk factors (such as diabetes, inflammation, hypertension and dyslipidaemia), non-traditional risk factors related to kidney damage (such as uraemic toxins) may predispose patients with CKD to neurological disorders. There is increasing evidence to show that uraemic toxins, for example indoxyl sulphate, have a neurotoxic effect. A better understanding of factors responsible for the elevated prevalence of neurological disorders among patients with CKD might facilitate the development of novel treatments. Here, we review (i) the potential clinical impact of CKD on cerebrovascular and neurological complications, (ii) the mechanisms underlying the uraemic toxins' putative action (based on pre-clinical and clinical research) and (iii) the potential impact of these findings on patient care. [ABSTRACT FROM AUTHOR]

Kidney function has two important elements: glomerular filtration and tubular function (secretion and reabsorption). A persistent decrease in glomerular filtration rate (GFR), with or without proteinuria, is diagnostic of chronic kidney disease (CKD). While glomerular injury or disease is a major cause of CKD and usually associated with proteinuria, predominant tubular injury, with or without tubulointerstitial disease, is typically non-proteinuric. CKD has been linked with cognitive impairment, but it is unclear how much this depends on a decreased GFR, altered tubular function or the presence of proteinuria. Since CKD is often accompanied by tubular and interstitial dysfunction, we explore here for the first time the potential role of the tubular and tubulointerstitial compartments in cognitive dysfunction. To help address this issue we selected a group of primary tubular diseases with preserved GFR in which to review the evidence for any association with brain dysfunction. Cognition, mood, neurosensory and motor disturbances are not well characterized in tubular diseases, possibly because they are subclinical and less prominent than other clinical manifestations. The available literature suggests that brain dysfunction in tubular and tubulointerstitial diseases is usually mild and is more often seen in disorders of water handling. Brain dysfunction may occur when severe electrolyte and water disorders in young children persist over a long period of time before the diagnosis is made. We have chosen Bartter and Gitelman syndromes and nephrogenic diabetes insipidus as examples to highlight this topic. We discuss current published findings, some unanswered questions and propose topics for future research. [ABSTRACT FROM AUTHOR]

Clinically-related basic studies on the behavioral effects of ribavirin treatment are still lacking despite its wide use as an antiviral medication. This paper considers the effects of low ribavirin doses (10, 20 and 30 mg/kg/day) on psychomotor activity (novelty-induced exploratory behavior, d-amphetamine (AMPH, 1.5 mg/kg, intraperitoneal)-induced motor activity), and body weight gain in socially undisturbed adult male Wistar rats 24 h after the first, seventh and fourteenth once-a-day injection. Low doses of ribavirin were tested in an attempt to avoid the recognized systemic side effects related to high-dose usage. None of the singly applied ribavirin doses affected exploratory/spontaneous and AMPH-induced motor behavior (locomotion, stereotypy-like and vertical activity), however, body weight gain was significantly lower after treatment with 30 mg/kg of ribavirin. The 7- and 14-day treatments with 10 and 30 mg/kg/day of ribavirin significantly suppressed novelty-induced locomotion and body weight gain; the 14-day treatment with ribavirin at a dose of 30 mg/kg/day decreased AMPH-induced stereotypy. These findings indicate that repeated application (up to 14 days) of low ribavirin doses results in low novelty-induced locomotion along with reduced weight gain, accentuating the existence of a U-shaped dose-response relationship with a prolonged duration of ribavirin treatment. [ABSTRACT FROM AUTHOR]

Bilberry (Vaccinium myrtillus L., Ericaceae) is a rich source of different mineral elements that are important as essential trace elements, or that can be potentially toxic, depending on their concentration. The contents of sixteen elements: the major (Al, Ca, Fe, K and Mg) and trace elements (As, Ba, Cd, Co, Cu, Cr, Mn, Ni, Pb, Sr and Zn) in roots, stems, leaves and fruits of bilberry and the corresponding soil substrate were determined in order to investigate element mobility and availability in soil. Soil was subjected to sequential extraction procedure as proposed by the Community Bureau of Reference in order to fractionate acid-soluble/exchangeable, reducible, oxidizable and residual fractions. Analysis of water and ethanol extracts of bilberry aerial parts revealed a significant transfer of elements during the extraction procedure, with corresponding extraction coefficient values of up to 95.12%. Results showed that bilberry fruits could serve as a good dietary source of essential elements for humans, especially Mn and Cu. [ABSTRACT FROM AUTHOR]

Highlights • Neurological and oxidative stress impairments are risk factors for schizophrenia. • Glutathione peroxidase activity can lead to the neurological signs in schizophrenia. • Antipsychotics attenuate superoxide dismutase and catalase activity reductions. Abstract To determine the relationship between alterations in the activity of the enzymes participating in antioxidative defense system and neurological soft signs (NSS) in schizophrenic patients with the first episode psychosis (S FE , n = 19), patients in relapse (S R , n = 46), and healthy controls (HC, n = 20). NSS intensity and enzymatic plasma activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were compared between S FE , S R and HC subjects and a follow-up correlation analyses between the enzyme activities and NSS intensity was performed. NSS intensity was increased four times in schizophrenic patients compared with healthy controls. Activities of SOD and CAT were 40% decreased in S FE and these reductions were ameliorated by antipsychotic treatment. GPX activity was 20% decreased in both patient groups compared with controls. A negative correlation between NSS intensity and GPX activity was specifically found in the S FE patients. The data in this report argue that a reduction of GPX activity might be one of the causes for the emergence of NSS at the onset of schizophrenia, and provide the evidence that antipsychotic therapy can attenuate activity reductions of SOD and CAT, but not the activity reduction of GPX and the intensity of NSS. [ABSTRACT FROM AUTHOR]

Abstract 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. Highlights • In ACTH model of treatment-resistant depression Mg alleviates behavioral changes. • HPA axis hyperactivity induced by ACTH was attenuated in Mg-administered rats. • Study suggests involvement of Mg in central and peripheral turnover of monoamines. • In ACTH model of treatment-resistant depression Mg increases neurodevelopment. [ABSTRACT FROM AUTHOR]

Summary: Background: The effects of anesthetic drugs on postoperative cognitive function in children are not well defined and have not been experimentally addressed. Aims: The present study aimed to examine the influence of propofol anesthesia exposure on nonaversive hippocampus‐dependent learning and biochemical changes involved in memory process in the dorsal hippocampus, in peripubertal rats as the rodent model of periadolescence. Methods: The intersession spatial habituation and the novel object recognition tasks were used to assess spatial and nonspatial, nonaversive hippocampus‐dependent learning. The exposure to anesthesia was performed after comparably long acquisition phases in both tasks. Behavioral testing lasted for 2 consecutive days (24‐hour retention period). Changes in the expression of molecules involved in memory retrieval/reconsolidation were examined in the dorsal hippocampus by Western blot and immunohistochemistry, at the time of behavioral testing. Results: Exposure to propofol anesthesia resulted in inappropriate assessment of spatial novelty at the beginning of the test session and affected continuation of acquisition in the spatial habituation test. The treatment did not affect recognition of the novel object at the beginning of the test session but it attenuated overall preference to novelty, reflecting retrieval of a weak memory. The expression of phosphorylated extracellular signal‐regulated kinase 2 (involved in memory retrieval) was decreased while the level of phosphorylated Ca2+/calmodulin‐dependent protein kinase IIα and early growth response protein 1 (involved in memory reconsolidation) was increased in the dorsal hippocampus. The level of Finkel‐Biskis‐Jinkins murine osteosarcoma viral oncogene homolog B (neuronal activity indicator) was increased in the dorsal dentate gyrus. Enhanced exploratory activity was still evident in the propofol anesthesia exposure (PAE) group 48 hour after the treatment in both tasks. Conclusion: In peripubertal rats, propofol anesthesia exposure affects memory retrieval and acquisition of new learning in the spatial and nonspatial, nonaversive learning tasks 24 hour after the treatment, along with the expression of molecules that participate in memory retrieval/reconsolidation in the dorsal hippocampus. These results may have clinical implications, favoring control of basic cognitive functions in older children after the propofol exposure. [ABSTRACT FROM AUTHOR]

The Great Bačka Canal in Serbia is one of the most polluted waterways in Europe. Surface sediments from the canal were subject to systematic annual monitoring between 2007 and 2014 at 33 representative sampling sites. Eight heavy metals (Ni, Zn, Cd, Cr, Cu, Pb, As and Hg), mineral oils, 16 EPA PAHs and selected pesticides and polychlorinated biphenyls (PCB) were monitored. This study aims to evaluate the quality of the sediments and determine the potential ecological risks in order to establish pollutants of interest. The spatial and temporal influence of different and intense sources of pollution are investigated. The analysis includes multivariate statistical methods (factor analysis of principal component analysis (PCA/FA)) in order to assess the extent and origin (anthropogenic or natural, geogenic sources) of the contaminants detected in the sediment samples and the risks the present to the environment. Various sources, predominantly the food industry, were found to be responsible for most of the contamination by Cd, Cu, Cr and Zn, the mineral oils and PAHs (dibenzo[ a , h ]anthracene and benzo[ a ]pyrene contributed 86.0% of the total between 2007 and 2014). In contrast, the As was convincingly of geogenic origin, and the Hg, Pb and Ni present exhibit dual origins. Cd and Cu significantly raise the levels of potential ecological risk at all sampling locations, demonstrating the long-term effects of bioaccumulation and biomagnification. Significantly, the results of this work indicate that Cu, As and dibenzo[ a , h ]anthracene should be added to the EU watch list of emerging contaminants. This is supported by significant national and similar environmental data from countries in the region. [ABSTRACT FROM AUTHOR]

Background Propofol is commonly used in modern anesthesiology. Some findings suggest that it is highly addictive. Aim In this study it was examined whether propofol anesthesia exposure was able to induce behavioral alterations and brain molecular changes already described in addictive drug usage in peripubertal rats, during the onset of mid/periadolescence as a developmental period with increasing vulnerability to drug addiction. Methods The expression of D1 dopamine receptor, a dopamine, and cAMP-regulated phosphoprotein with a Mr 32 000; Ca2+/calmodulin-dependent protein kinase II α; and Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B was examined in peripubertal rats 4, 24, and 48 hour after propofol anesthesia exposure by Western blot and immunohistochemistry. Brain regions of interest were the medial prefrontal cortex, the striatum, and the thalamus. Anxiety and behavioral cross-sensitization to d-amphetamine were examined as well. Results Significant increase in the expression of dopamine and cAMP-regulated phosphoprotein with a Mr 32 000 phosphorylated at threonine 34, a postsynaptic marker of dopaminergic neurotransmission, and Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B, a marker of neuronal activity, was detected in the thalamus of experimental animals 4-24 hour after the treatment, with the accent on the paraventricular thalamic nucleus. Significant increase in the expression of Ca2+/calmodulin-dependent protein kinase II α phosphorylated at threonine 286, a sensor of synaptic activity, was observed in the prefrontal cortex and the striatum 24 hour after propofol anesthesia exposure. It was accompanied by a significant decrease in Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B expression in the striatum. Decreased behavioral inhibition in aversive environment and increased motor response to d-amphetamine in a context-independent manner were observed as well. Conclusion In peripubertal rats, propofol anesthesia exposure induces transient molecular and behavioral response that share similarities with those reported previously for addictive drugs. In the absence of additional pharmacological manipulation, all detected effects receded within 48 hour after the treatment. [ABSTRACT FROM AUTHOR]

Chronic stress conditions can lead to considerable and extensible changes in physiological and psychological performances, and in emergence of risk for various somatic diseases. On the other hand, the neuropeptide oxytocin is reported to increase the resistance of the organism to stress and modulate activity of autonomic nervous system. Chronic corticosterone administration is used as a rat model for a state observed in terms of chronic stress exposure, when negative feedback mechanism of hypothalamus-pituitary-adrenal axis activity is disrupted. In our study, we aimed to investigate whether chronic administration of oxytocin (10 IU/400 μL/day for 14 days, s.c. ) influenced adrenal gland morphology and activity in adult male Wistar rats during long-term corticosterone administration via drinking water (100 mg/L for 21 days). We examined the influence of treatments on the levels of adrenal gland hormones, corticosterone, adrenaline and noradrenaline, as well as their response to an acute stress challenge evoked by 15-min forced swimming. In addition, the expression of two main monoamine transporters, the noradrenaline transporter (NAT) and vesicular monoamine transporter 2 (VMAT2) in adrenal medulla was measured in the rats exposed to acute stress. Our results showed that oxytocin treatment prevented corticosterone-induced decrease in body weight gain, attenuated adrenal gland atrophy by increasing glandular weight, and the area of the zona fasciculate and reticularis. Chronic corticosterone intake blunted the response of all measured hormones to acute stress, whereas concomitant oxytocin treatment reversed adrenaline and noradrenaline response to acute stress. Furthermore, in adrenal medulla, oxytocin produced significant vasodilatation and stimulated expression of both catecholamine transporters detected both on mRNA and protein level. Our data suggest that oxytocin, by reducing atrophy of adrenal gland, and by increasing catecholamine storage capacity, may be beneficial in conditions accompanied with high glucocorticoid levels, such as chronic stress exposure. [ABSTRACT FROM AUTHOR]

Surface sediments were subject to systematic long-term monitoring (2002–2014) in the Republic of Serbia (Province of Vojvodina). Eight heavy metals (Ni, Zn, Cd, Cr, Cu, Pb, As and Hg), mineral oils (total petroleum hydrocarbons), 16 EPA PAHs, selected pesticides and polychlorinated biphenyls (PCB) were monitored. As part of this research, this paper presents a sediment contamination spatial and temporal trend study of diverse pollution sources and the ecological risk status of the alluvial sediments of Carska Bara at three representative sampling sites (S1 S3), in order to establish the status of contamination and recommend substances of interest for more widespread future monitoring. Multivariate statistical methods including factor analysis of principal component analysis (PCA/FA), Pearson correlation and several synthetic indicators were used to evaluate the extent and origin of contamination (anthropogenic or natural, geogenic sources) and potential ecological risks. Hg, Cd, As, mineral oils and PAHs (dominated by dibenzo(a,h)anthracene and benzo( a )pyrene, contributing 85.7% of the total) are derived from several anthropogenic sources, whereas Ni, Cu, Cr and Zn are convincingly of geogenic origin, and exhibit dual origins. Cd and Hg significantly raise the levels of potential ecological risk for all sampling locations, demonstrating the effect of long-term bioaccumulation and biomagnification. Pb is isolated from the other parameters, implying unique sources. This research suggests four heavy metals (Zn, Cr, Cu and As) and dibenzo(a,h)anthracene be added to the list of priority pollutants within the context of the application of the European Water Framework Directive (WFD), in accordance with significant national and similar environmental data from countries in the region. [ABSTRACT FROM AUTHOR]

Contemporary lifestyle is commonly associated with chronic stress, an environmental factor contributing to development of various psychological and somatic disorders. Increased levels of glucocorticoids, observed in the chronic stress, induce the production of reactive oxygen species leading to genotoxicity. The aim of this study was to investigate whether chronic administration of oxytocin (OXY) 10 IU/400 μL/day, s.c. , for 14 days, a hormone presumed to exert antioxidant effect, may prevent DNA damage in the comet assay of peripheral blood lymphocytes of Wistar rats treated chronically with corticosterone (CORT) 100 mg/L ad libitum, per os , for 21 days, as well as, to influence some plasma oxidative stress parameters, i.e. levels of total lipid hydroperoxide (LOOH), and malondialdehyde (MDA), and the activity of antioxidative enzyme superoxide dismutase (SOD). Even though there was no reduction in overall number of damaged cells after oxytocin treatment only, the marked increase in total comet score (TCS) after incubation with H 2 O 2 in CORT group compared to controls, was absent in the CORT + OXY experimental group. Furthermore, significant decrease of highly damaged cells compared to corticosterone group was noted. Chronic oxytocin administration thus protected lymphocytes from high intensity damage that leads to cellular death. In addition, treatment with OXY along with CORT, significantly decreased concentration of LOOH in plasma, and increased SOD compared to CORT treatment only. This finding corresponds well with current reports on beneficial effects of OXY in conditions of HPA axis hyperactivity, and supports the hypothesis of OXY-mediated antioxidant action. [ABSTRACT FROM AUTHOR]

Chemoresistance and invasion properties are severe limitations to efficient glioma therapy. Therefore, development of glioma in vivo models that more accurately resemble the situation observed in patients emerges. Previously, we established RC6 rat glioma cell line resistant to DNA damaging agents including antiglioma approved therapies such as 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide (TMZ). Herein, we evaluated the invasiveness of RC6 cells in vitro and in a new orthotopic animal model. For comparison, we used C6 cells from which RC6 cells originated. Differences in cell growth properties were assessed by real-time cell analyzer. Cells' invasive potential in vitro was studied in fluorescently labeled gelatin and by formation of multicellular spheroids in hydrogel. For animal studies, fluorescently labeled cells were inoculated into adult male Wistar rat brains. Consecutive coronal and sagittal brain sections were analyzed 10 and 25 days post-inoculation, while rats' behavior was recorded during three days in the open field test starting from 25th day post-inoculation. We demonstrated that development of chemoresistance induced invasive phenotype of RC6 cells with significant behavioral impediments implying usefulness of orthotopic RC6 glioma allograft in preclinical studies for the examination of new approaches to counteract both chemoresistance and invasion of glioma cells. [ABSTRACT FROM AUTHOR]

Highlights: [•] Significant natural purification of farm wastewaters takes place in the lagoons. [•] The major portion of metals from wastewater is concentrated in the solid manure. [•] Positive statistical correlation shows that shallow groundwaters on the farms are contaminated. [•] Shallow groundwater contains elevated amounts of organic matter and ammonia. [•] No deterioration of the quality of drinking water was detected in the deeper wells on the farms. [ABSTRACT FROM AUTHOR]

Highlights: [•] Cortisol predicts heart rate increase and maximal carbon-dioxide output. [•] ACTH during stress predicts maximal ventilatory efficiency. [•] HPA axis and NT-pro-BNP interface during stress. [•] HPA axis and NT-pro-BNP have possible integrative regulatory role in stress. [Copyright &y& Elsevier]

We investigated the influence of contact time, sorbent dose, and initial Cu(II) or Pb(II) concentrations on the removal of Cu(II) and Pb(II) from aqueous solution by the batch sorption technique using activated red mud (aBauxsol) as a low-cost sorbent. Sorption equilibrium was achieved after 1 h at pH 5.5 for both ions. Pseudo first and pseudo second order models were used for analyzing the kinetics of sorption processes. The rate of both sorption processes is controlled by diffusion in the film fluid and diffusion within particles. The processes of sorption follow the Langmuir model. [ABSTRACT FROM AUTHOR]

In this work, the simultaneous application of bipolar electrodes and a longer cathodic compartment length without agents addition was used as an enhanced electrokinetic treatment of Ni-, Cd-, and Pb-contaminated sediment. Conventional and enhanced treatments were investigated and their efficacy assessed by comparing the residual metals content in the sediment with values given by Dutch standards. After conventional treatment removals of 20%, 19%, and 31% for Ni, Cd, and Pb were achieved, whereas the enhanced treatment achieved removal efficacies of 36% for Ni, 42% for Cd, and 43% for Pb. Results indicate that the simultaneous application of the techniques mentioned is effective for removing Ni and Pb whereas Cd was not removed to the desired level. Here we show that the addition of chemicals is not necessary to increase the efficacies of electrokinetic sediment treatments, so the simultaneous application of the techniques mentioned can be described as environmentally friendly. [ABSTRACT FROM AUTHOR]