Primidone Research Articles

Morphometric study of the legs of the main Chagas vector, Triatoma infestans (Hemiptera: Reduviidae)

In triatomines, vectors of Chagas disease, active dispersal takes place by walking and flying. Flight has received more attention than walking although the last is the dispersal modality used by nymphs due to their lack of wings and also used by adults, which would facilitate the colonization and reinfestation of houses after vector control actions. The present work studied the morphometrical variation of Triatoma infestans legs, the main vector of Chagas disease the Southern Cone of South America. We described morphometric traits and the natural variation of each leg segment. Different linear, size and shape variables of each component of the three right legs of fifth instar nymphs of T. infestans were analyzed using morphometric tools. We analyzed differentiation, variation and correlation for each segment across the fore-, mid and hind legs using different statistical approaches such as general linear model, canonical variates analysis, test of equality of coefficient of variation and partial least square analysis. We also analyzed variation and correlation between segments within each leg with partial least square and morphometric disparity analyses. Our results showed that the segments differed between legs, as general trends, the dimensions (length, width and/or size) were greater in the hind legs, smaller in the forelegs and intermediate in the mid ones. The femur and tibia (length and/or width) showed differences in morphometric variation between legs and the femur and tibia showed the highest levels of correlation between legs. On the other hand, in the fore- and mid legs, the femur (length or width) showed similar variation with tibia and tarsus lengths, but in the hind legs, the femur showed similar variation with all segments and not with the tibia length, and there were strong correlations between linear measurement within each leg. Our results suggest that the femur and tibia could play a determining role in the coordination between the legs that determines the walking pattern. Considering that these segments would also be linked to the specific function that each leg has, this study suggests a preponderant role of the femur and tibia in the walking locomotion of T. infestans.

Degradation of micropollutants in secondary wastewater effluent using nonthermal plasma-based AOPs: The roles of free radicals and molecular oxidants

Emerging micropollutants (µPs) appearing in water bodies endanger aquatic animals, plants, microorganisms and humans. The nonthermal plasma-based advanced oxidation process is a promising technology for eliminating µPs in wastewater but still needs further development in view of full-scale industrial application. A novel cascade reactor design which consists of an ozonation chamber preceding a dielectric barrier discharge (DBD) plasma reactor with a falling water film on an activated carbon textile (Zorflex®) was used to remove a selection of µPs from secondary municipal wastewater effluent. Compare to previous plasma reactor, molecular oxidants degraded micropollutants again in an ozonation chamber in this study, and the utilization of different reactive oxygen species (ROS) was improved. A gas flow rate of 0.4 standard liter per minute (SLM), a water flow rate of 100 mL min−1, and a discharge power of 25 W are identified as the optimal plasma reactor parameters, and the µP degradation efficiency and electrical energy per order value (EE/O) are 84–98% and 2.4–5.3 kW/m³, respectively. The presence of ROS during plasma treatment was determined in view of the µPs removal mechanisms. The degradation of diuron (DIU), bisphenol A (BPA) and 2-n-octyl-4-isothiazolin-3-one (OIT) was mainly performed in ozonation chamber, while the degradation of atrazine (ATZ), alachlor (ALA) and primidone (PRD) occurred in entire cascade system. The ROS not only degrade the µPs, but also remove nitrite (90.5%), nitrate (69.6%), ammonium (39.6%) and bulk organics (11.4%). This study provides insights and optimal settings for an energy-efficient removal of µPs from secondary effluent using both free radicals and molecular oxidants generated by the plasma in view of full-scale application.

Synergistic Effect of Crystallization Control and Defect Passivation Induced by a Multifunctional Primidone Additive for High-Performance Perovskite Solar Cells

The ionic nature of organic–inorganic metal halide perovskites endows intrinsic defects at the surface of the polycrystalline films. Simultaneous defect passivation during the growth of perovskite films could inhibit defect formation to a great extent. Herein, the anticonvulsant drug primidone (PRM) is demonstrated as a novel additive to control the crystallization and defect passivation of perovskites. The spectroscopic measurements support theoretical predictions showing the strong interaction between active functional groups and PbI2. An amount of PRM is tuned to obtain the perfect perovskite films with improved grain size and crystallinity than their control counterparts. Efficient PbI antisite defect passivation suppresses the non-radiative recombinations, resulting in higher luminance intensity and significantly longer charge carrier lifetimes. The PRM-modified perovskite solar cells (PSCs) show a power conversion efficiency (PCE) of 18.73%, much higher than that of control PSCs (16.62%). The ambient stability of PRM-modified PSCs is meritoriously increased compared to control PSCs. The PRM-modified PSCs show stability retention of up to 85% of the initial PCE after 1000 h, while control PSCs retain only 25% of the initial PCE after 550 h. The multifunctional defect passivation approach with the PRM additive shows the effective way for the efficiency and stability improvement of PSCs.

OH/O3-initiated transformation of primidone in AOPs based on the theoretical calculations: Mechanisms, kinetics, and eco-toxicity assessments

Primidone (PMD), as the first-generation anticonvulsant, is attracting considerable attention due to its extensive persistence in aqueous environments. In this paper, the aquatic transformation mechanisms, kinetics, and eco-toxicity of PMD induced by OH/O3 have been investigated through density functional theory (DFT). The results indicated that the H atom of -CH2- group (H8), which is located on the pyrimidine ring, is more vulnerable to be abstracted by OH radicals. This led to the most dominant intermediate IM8, which could be converted into the primary products (P3, P4, P5, P8, and P16). Moreover, the OH-addition channels were also considered, where the routes to form IM12 and IM16 play important roles. In terms of the reaction between PMD and O3, the cyclo-addition and subsequent degradation pathway were researched, generating the main ozonation compound P35. In addition, the calculated ktotal of PMD reacting with OH radicals and O3 at 298 K were 2.81 × 109 and 2.55 × 10−1 M−1 s−1 respectively, indicating OH radicals represent higher universality than O3. The half-lives of PMD oxidized by OH radicals range from 0.19 to 30.12 s, while the values of O3-initiated reactions are within the scope of 0.05–2.15 h in the AOPs. The eco-toxicities of the primary degradation products, di-ketone compounds (P5 and P8), to aquatic organisms have decreased to harmless, while the developmental perniciousness of several metabolites (P3, P7, P9, and P12) still remain. This work will provide a deep insight into the behavior of PMD mineralization for the first time at the computational molecule.

Impact of EfOM in the elimination of PPCPs by UV/chlorine: Radical chemistry and toxicity bioassays

The UV/chlorine process as a potential tertiary municipal wastewater treatment alternative for removing refractory PPCPs has been widely investigated. However, the role of effluent organic matter (EfOM) on the radical chemistry and toxicity alteration is unclear. The elimination of two model PPCPs, primidone (PRM) and caffeine (CAF), by the co-exposure of UV and free chlorine was investigated to elucidate the impact of EfOM. Experimental results indicated that both •OH and reactive chlorine species (RCS) were importantly involved in the decay of PRM at acidic condition, while ClO• played dominant role at alkaline pH. The decay of CAF was dominated by ClO• under all conditions. Chlorine dose, initial contaminant concentration, solution pH, and water matrix affect the process efficiency at varying degree resulting from their specific effect on the radical speciation in the system. Presence of EfOM isolate remarkably inhibited the decay of PRM and CAF by preferentially scavenging RCS and particularly ClO•. Good correlations (linear for PRM and exponential for CAF) between UV absorbance at 254 nm and the observed pseudo first-order rate constants (k'obs) for all EfOM solutions were obtained, demonstrating the importance of aromatic moieties in inhibiting the degradation of targeted contaminants by UV/chlorine process. Degradation of PRM/CAF in reconstituted effluent spiked with the major effluent constituents (i.e., EfOM isolates, Cl-, HCO3-, and NO3-) was comparable to the results obtained with the real WWTP effluent and fit well to the correlation between k'obs and UV absorbance at 254 nm, suggesting that EfOM isolates can be used to determine the efficiency of UV/chlorine process in real effluent. EfOM serves as the main precursor of adsorbable organic chlorine in the UV/chlorine treatment. Bioassays indicated that chlorine-containing compounds could induce oxidative stress, mitochondrial dysfunction, and increase the cell DNA damage. Among evaluated treatment conditions, the nature of EfOM, hydrophobic versus transphilic fraction, is likely the predominant factor affecting the cytotoxicity. Meanwhile the UV/chlorine treatment can significantly reduce the cytotoxicity of EfOM isolates. However, adding high level of selected contaminants (e.g., PRM and CAF) can inhibit this phenomenon due to the competition with reactive radicals.

Comparison of loading and unloading of different small drugs on graphene and its oxide

Adsorption of drugs on graphene nanosheets can prevent enzymatic degradation. However, the mechanisms of graphene-drug complex permeating into the cell interior and the subsequent drug release remain unclear. In this work, we performed molecular dynamics simulations to investigate the drug delivery capability of pristine graphene (PG) and its oxide (graphene oxide, GO). Three drugs, namely, primidone (PRI), pregabalin (PRE) and bortezomib (BOR) were adopted as they have different molecular size and polarity. The results show that the adsorption intensity of GO is much stronger than that of PG, due to the electrostatic interactions or hydrogen bonding originated from the oxygen-containing groups on GO, which is confirmed by free energy calculations. And therefore, drug molecules are difficult to leave from GO surface after the complexes enter the membrane. Compared with PRE and BOR, PRI molecules are more suitable to be loaded and unloaded by both PG and GO. The results indicate that graphene and its oxide served as substrates to deliver particular drugs is theoretically feasible.

Evaluation and Prediction of Removal Efficiency of Pharmaceuticals in the Simulated O3 and UV/H2O2 Process for Drinking Water Treatment Process in the Downstream of Nakdong River

Objectives : In the case of pharmaceuticals with high possibility of inflow into the large drinking water treatment plant (DWTP) located in the downstream of the Nakdong River, we tried to evaluate the removal efficiency of pharmaceuticals in the both ozone (O3) and the UV/H2O2 treatment as an alternative of post-O3 process. It was intended to be used as data for the advanced WTP project by prediction of the removal efficiency in the O3 and UV/H2O2 processes with varying water quality conditions.Methods : O3 and UV/H2O2 process were performed for 19 kinds of pharmaceuticals in the sand-filtered water of DWTP. In order to evaluate the removal efficiency in deionized water (DI) and sand-filtered water (SFW) matrices, 19 pharmaceuticals were spiked at a concentration of 100 ng/L, respectively. In the O3 process, the specific O3 dose was 0.1∼2.0 gO3/gDOC (0.25∼5.0 mgO3/L). In the UV/H2O2 process, H2O2 (5 and 10 mg/L) was added to the sample before UV was irradiated (0∼1,500 mJ/cm2).Results and Discussion : In the case of simulated post-O3 process, the removal efficiency of high-ozone reactive pharmaceuticals (kO3 6.5×102∼2.6×106 M-1 s-1) was up to 92% at the specific O3 dose of 0.2 gO3/gDOC. However, the removal efficiency of iopromide (IPM) and primidone (PRM) was only 36∼45% in the same O3 dose (0.2 gO3/gDOC) due to the low O3 reactivity (kO3 < 1 M-1 s-1). A specific O3 dose of 2.0 gO3/gDOC (=5 mgO3/L) was required to achieve a removal efficiency of over 90% for IPM and PRM, indicating that these O3-refractory pharmaceuticals are difficult to control by O3 process. In the case of simulated UV/H2O2 (10 mg/L H2O2) process, the removal efficiency of 19 pharmaceuticals at the UV fluence of 500 and 1,000 mJ/cm2 were 63∼99% and 87∼99%, respectively, and caffeine (CFN) had the lowest removal efficiency. For the O3-refractory pharmaceuticals (i.e., IPM and PRM), the removal efficiency was higher in the UV/H2O2 process than that in the O3 process due to the high reactivity with OH radical (kOH = 3.3×109 and 5.2×109 M-1 s-1). Prediction of removal efficiency for pharmaceuticals in the O3 and UV/H2O2 process was performed using chemical kinetics model to evaluate the change in removal efficiency with varying DOM concentration. As a result of prediction model for O3, when the DOM concentration increased from 1.5 to 3.0 mg/L, the removal efficiency of IPM and PRM decreased by 22∼24% and 15∼24%, respectively. In the case of UV/H2O2 process (10 mg/L H2O2 and UV fluence of 500~1,000 mJ/cm2), the removal efficiency of 16 kinds of pharmaceuticals was reduced by 0∼29%, and the degree of reduction in the removal efficiency of CFN was the highest.Conclusions : As a result of evaluation and prediction of the removal efficiency of pharmaceuticals in the O3 and UV/H2O2 treatment processes, it is confirmed that the possibility of applying the UV/H2O2 treatment as an alternative process to the O3 to abatement of pharmaceuticals.

Use of biochar to produce reclaimed water for irrigation use

Emerging contaminants, especially, pharmaceutical and personal care products (PPCPs) are not removed well during conventional wastewater treatment and hence pose water quality risk to the environment and potentially to public health. Long-term use of reclaimed wastewater for irrigation can lead to accumulation of trace contaminants in the soil, ground water and their subsequent uptake by plants and potentially can enter human food chain. This paper uses biochar as an adsorbent to remove emerging contaminants from treated wastewater by performing fixed bed experiments. Ten emerging contaminants namely, carbamazepine (CBZ), caffeine, diethyltoluamide (DEET), diphenhydramine (DPH), meprobamate (MPB), primidone (PMD), sulfamethoxazole (SMX), fluoxetine (FXT), perfluorooctanoic acid (PFOA) and trimethoprim (TMP) were monitored during lab scale experiments. Results from the continuous flow runs showed that the breakthrough curve for compounds caffeine, CBZ, DEET and PFOA follow second order Thomas model with adsorption capacities of 396 μg g−1, 392 μg g−1, 1160 μg g−1 and 32 μg g−1 biochar, respectively. Whereas compounds such as DPH, TMP and FXT were completely removed throughout the column runs by biochar. Results for rest of the compounds were interfered by leaching of these compounds from biochar. It was observed that commercially available GAC performed much better than biochar for all the compounds considered. Even at 1% of obtained capacity, biochar amendment to soils where reclaimed water is used for irrigation can reduce the uptake of these compounds by plants.

Impact of DOM source and character on the degradation of primidone by UV/chlorine: Reaction kinetics and disinfection by-product formation

The presence of Dissolved Organic Matter (DOM) can exert a strong influence on the effectiveness of the UV/chlorine process. This study examined the impact of five DOM isolates with different characteristics on the degradation kinetics of model contaminant primidone (PM) during UV/chlorine treatment. The formation of Disinfection By-Products (DBPs) from DOM after 15-min UV/chlorine treatment followed by 24 h chlorination was investigated and compared with chlorination alone. The use of chemical probes and radical scavengers revealed that •OH and ClO• were the main radical species responsible for the loss of PM at acidic and alkaline conditions, respectively. All tested DOM isolates significantly inhibited the decay of PM. A strong negative correlation (>0.93) was observed between the decay rate constants of PM and SUVA of DOM isolates, except for EfOM isolate, which induced the strongest inhibitory effect due to its higher abundance in sulfur-containing functional groups (i.e., sink of •OH/Cl• radicals). Compared with chlorination, the formation of Adsorbable Organic Chlorine (AOCl) and Trichloromethane (TCM) during the UV/Chlorine process was enhanced and hindered for low SUVA isolates and high SUVA DOM, respectively. However, Dichloroacetonitrile (DCAN) formation was generally lower for all isolates except for Ribou Reservoir DOM at pH 8.4 because of its high reactive nitrogenous DBP precursors at caustic conditions. However, when normalized to the chlorine consumed, the UV/Chlorine process always led to a lower DBPs formation compared with chlorination alone.

Assessing the contribution of hydroxylation species in the photochemical transformation of primidone (pharmaceutical)

Pharmaceutical and personal care products (PPCPs) are a group of emerging contaminants that have frequently been detected in aqueous environments. Phototransformation driven by solar irradiation is one of the most important natural processes for the elimination of PPCPs. In this study, primidone (PMD) was chosen as a model “photorefractory” compound. A series of experiments were conducted to assess if reactive intermediates (RIs), such as hydroxyl radical (HO), singlet oxygen (1O2), and triplet states of dissolved organic matter (3DOM⁎), inhibited or enhanced the photochemical transformation of PMD under simulated solar irradiation. The results indicate that HO plays a key role in the photodegradation of PMD and that dissolved oxygen can affect the degradation rate of PMD by promoting HO formation. Our results demonstrated that PMD can not only react with free HO (HO-free) but also react with lower-energy hydroxylation agents (HO-like). The contributions of HO-free and HO-like to PMD degradation in various dissolved organic matter (DOM) solutions were estimated by a methane-quenching experiment. The results indicated that the HO-like species were important in the photodegradation of “photorefractory” compounds. The bimolecular reaction rate constant of the reaction of free HO with PMD was measured as (5.21 ± 0.02) × 109 M−1 s−1 by using electron pulse radiolysis. Furthermore, PMD was used as a probe to estimate the steady-state concentration of HO-free in various DOM solutions. Using the multivariate statistical strategies of orthogonal projection to latent structures discriminant analysis (OPLS-DA) and hierarchical clustering, 28 photochemical transformation products (TPs) of PMD were successfully identified from the DOM matrix.

Attenuation of pharmaceutically active compounds in aqueous solution by UV/CaO2 process: Influencing factors, degradation mechanism and pathways

As freshwater sources continue to be influenced by wastewater effluents, there is a dire need to develop advanced water treatment processes capable of treating the wastewater-derived contaminants, especially for pharmaceutically active compounds (PhACs). Ultraviolet light (UV) combined with calcium peroxide (CaO2) as an advanced oxidation process (AOP) to attenuate five widespread PhACs (carbamazepine (CBZ), primidone (PMD), phenobarbital (PBB), thiamphenicol (TAP) and florfenicol (FF)) was investigated in this paper. The degradation of these compounds followed pseudo-first-order kinetics (R2 > 0.96). The optimum CaO2 dosage was 0.1 g L−1 and lower initial contaminants concentration was beneficial to their degradation. The UV/CaO2 treatment of test PhACs was attributed to the combination of UV/H2O2 and UV-base-photolysis (UV/Ca(OH)2), and the degradation mechanism was recognized as both UV direct photolysis and indirect photolysis caused by reactive radicals (•OH, triplet states of dissolved organic matter (3DOM*), and 1O2). Furthermore, the tentative transformation pathways of the five PhACs were proposed based on the detected intermediates and the degradation mechanisms. The final products of inorganic carbon and nitrogen indicate UV/CaO2 treatment can significantly mineralize test PhACs. Also, the CaO2 addition significantly reduced the energy consumption of UV irradiation according to electrical energy per order. The effective removal of CBZ and PMD in a secondary wastewater effluent by UV/CaO2 treatment demonstrates the potential use of this AOP technology in advanced treatment of wastewater-derived PhACs.

MP-UV/CaO2 as a pretreatment method for the removal of carbamazepine and primidone in waste activated sludge and improving the solubilization of sludge

Medium-pressure ultraviolet light (MP-UV) combined with calcium peroxide (CaO2) as a pretreatment technology for removing carbamazepine (CBZ) and primidone (PMD) in waste active sludge (WAS) and improving the solubilization of sludge were investigated. CBZ and PMD were effectively removed and the removal fitted pseudo-first kinetics under MP-UV/CaO2 treatment with R2 > 0.97. The higher CaO2 dosage and lower initial volatile suspended solids (VSS) concentration were conductive to the removal of CBZ and PMD. Of the CaO2 hydrolysates, Ca(OH)2 played a more important role than H2O2 during MP-UV/CaO2 treatment. The removal of the target compounds was attributed to direct photolysis and indirect photolysis caused by •OH, 3DOM*, and 1O2, in which •OH played a vital role with > 62.2% contribution to the overall degradation rate. A model predicting the steady concentration of •OH in WAS ([VSS] ≈ 8.6 g L−1) under MP-UV/CaO2 treatment with CaO2 dosage ranging from 0 to 0.5 g g−1-VSS was proposed and validated. Moreover, major intermediates of CBZ and PMD were detected and the probable transformation pathways during MP-UV/CaO2 treatment were proposed. In addition, MP-UV/CaO2 promoted the sludge solubilization effectively. Considering both the pharmaceutical degradation and sludge solubilization, the optimum operation condition with 0.2 g-CaO2 g−1-VSS combined with 7 h MP-UV irradiation is recommended. Under this condition, more than 92.3% of CBZ and 90.3% of PMD were removed, and soluble chemical oxygen demand (SCOD) increased by 657% and 13.6% compared with sole 10 h CaO2 (0.2 g g−1-VSS) treatment and 7 h MP-UV treatment, respectively.

Reactivity of gluten proteins from spelt and bread wheat accessions towards A1 and G12 antibodies in the framework of celiac disease

In the framework of celiac disease, this research aims at evaluating the reactivity of 195 wheat accessions and 240 spelt accessions to A1 and G12 monoclonal antibodies. A great variability in reactivity was found among the accessions of both subspecies. On average, spelt showed very slightly higher reactivity than wheat but accessions with low reactivity were encountered in both subspecies. In both wheat and spelt, there was no significant difference in the level of reactivity between varieties and landraces. Similarly, there was no significant difference in reactivity between old, mid and new varieties of wheat. In contrast, new spelt varieties showed lower levels of reactivity than old and mid ones. No relationship could be established between level of reactivity, protein content and the Zeleny index. This research did not establish a link between the breeding strategies for baking quality improvement and A1-G12 antibodies reactivity.

Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child.

Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child.

Radiation induced degradation of antiepileptic drug primidone in aqueous solution

The present study was to determine the effectiveness of electron beam irradiation for degradation of the antiepileptic drug primidone (PMD) in aqueous solution. The results showed that PMD degradation followed pseudo-first-order kinetics. The dose constant determined in this study ranged from 1.26 to 4.59kGy−1, and decreased with an increase in the PMD initial concentration, whereas the initial radiation chemical yield for the loss of PMD decreased with increasing of absorbed dose and increased as the PMD concentration increased. The effects of medium pH, the presence of SO42−, SO32−, CO32−, HCO3−, NO3− and NO2− anions, H2O2, iso-propanol, and saturated solutions of N2, O2, N2O were also investigated. The results demonstrated that the OH took the most important role in the degradation of PMD, while the reductive eaq− and H took the less important role in PMD degradation. Major degradation products of PMD, including degradation intermediates, low weight organic acids and some inorganic ions were detected by LC/MS/MS and IC. Formic acid, acetic acid, oxalic acid, maleic acid and NO3−, NH4+ were identified in the irradiated solutions. Possible pathways for PMD decomposition by electron beam irradiation in aqueous solution were proposed.

Modulation of Cytokine Production by Drugs with Antiepileptic or Mood Stabilizer Properties in Anti-CD3- and Anti-CD40-Stimulated BloodIn Vitro

Increased cytokine production possibly due to oxidative stress has repeatedly been shown to play a pivotal role in the pathophysiology of epilepsy and bipolar disorder. Recent in vitro and animal studies of valproic acid (VPA) report antioxidative and anti-inflammatory properties, and suppression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. We tested the effect of drugs with antiepileptic or mood stabilizer properties, namely, primidone (PRM), carbamazepine (CBZ), levetiracetam (LEV), lamotrigine (LTG), VPA, oxcarbazepine (OXC), topiramate (TPM), phenobarbital (PB), and lithium on the production of the following cytokines in vitro: interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-17, IL-22, and TNF-α. We performed a whole blood assay with stimulated blood of 14 healthy female subjects. Anti-human CD3 monoclonal antibody OKT3, combined with 5C3 antibody against CD40, was used as stimulant. We found a significant reduction of IL-1 and IL-2 levels with all tested drugs other than lithium in the CD3/5C3-stimulated blood; VPA led to a decrease in IL-1β, IL-2, IL-4, IL-6, IL-17, and TNF-α production, which substantiates and adds knowledge to current hypotheses on VPA's anti-inflammatory properties.

Impact of mood stabilizers and antiepileptic drugs on cytokine production in-vitro

Changes within the immune system have been reported to contribute to the pathophysiology of bipolar disorder and epilepsy. Interestingly, overlapping results regarding the cytokine system have been found for both diseases, namely alterations of interleukins IL-1β, IL-2, IL-4, IL-6, and tumor necrosis factor-α (TNF-α). However, the effect of mood stabilizers and antiepileptic drugs (AEDs) on these cytokines has not been systematically evaluated, and their effect on IL-17 and IL-22, other immunologically important cytokines, has not been reported. Therefore, we systematically measured levels of IL-1β, IL-2, IL-4, IL-6, IL-17, IL-22 and TNF-α in stimulated blood of 14 healthy female subjects in a whole blood assay using the toxic shock syndrome toxin TSST-1 as stimulant. Blood was supplemented with the mood stabilizers or antiepileptic drugs primidone (PRM), carbamazepine (CBZ), levetiracetam (LEV), lamotrigine (LTG), valproic acid (VPA), oxcarbazepine (OXC), topiramate (TPM), phenobarbital (PB), lithium, or no drug. IL-1β production was significantly decreased by PRM, CBZ, LEV, LTG, OXC, PB and lithium. IL-2 significantly decreased by PRM, CBZ, LEV, LTG, VPA, OXC, TPM and PB. IL-22 significantly increased by PRM, CBZ, LEV, OXC, TPM and lithium and decreased by VPA. TNF-α production significantly decreased under all applied drugs. The mechanism of action and side effects of mood stabilizers and AEDs may involve modulation of IL-1β, IL-2, IL-22 and TNF-α signaling pathways. IL-22 may be a research target for specific therapeutic effects of mood stabilizers and AEDs. These drugs might influence cytokine production by modulating ion channels and γ-aminobutyric acid (GABA) receptors of immune cells.

First HPLC–UV method for rapid and simultaneous quantification of phenobarbital, primidone, phenytoin, carbamazepine, carbamazepine-10,11-epoxide, 10,11-trans-dihydroxy-10,11-dihydrocarbamazepine, lamotrigine, oxcarbazepine and licarbazepine in human plasma

A sensitive and fast high-performance liquid chromatographic method coupled with ultraviolet detection is herein reported for the simultaneous determination of human plasma concentration of six antiepileptic drugs frequently used in clinical practice [phenobarbital (PB), primidone (PRM), phenytoin (PHT), carbamazepine (CBZ), lamotrigine (LTG), oxcarbazepine (OXC)] and some of their main metabolites, carbamazepine-10,11-epoxide (CBZ-E), 10,11-trans-dihydroxy-10,11-dihydrocarbamazepine (trans-diol) and licarbazepine (Lic). Sample preparation consisted of a deproteinization step with methanol followed by a solid-phase extraction procedure. Chromatographic separation was achieved in approximately 15 min on a reversed-phase C18 column using a mobile phase composed by water-methanol-acetonitrile-triethylamine (68.7:25:6:0.3, v/v/v/v; pH 6.5) pumped isocratically at 1.0 mL/min. The detector was set at 237 nm. Calibration curves were linear with regression coefficients greater than 0.992 over the concentration ranges 0.25-100 μg/mL for PB, 0.4-50 μg/mL for PRM, 0.5-50 μg/mL for PHT, 0.1-50 μg/mL for CBZ, LTG and CBZ-E, 0.1-25 μg/mL for OXC, 0.25-10 μg/mL for trans-diol and 0.15-80 μg/mL for Lic. Inter- and intra-day imprecision did not exceed 12.15% and inaccuracy was within ±14.91%. Absolute mean recoveries ranged from 78.49 to 101.04% and no interferences were observed at the retention times of the analytes and internal standard (ketoprofen). This bioanalytical method was successfully applied to real plasma samples from epileptic patients and it seems to be a suitable tool for routine therapeutic drug monitoring and also to support other clinical pharmacokinetic-based studies.

Benefits for dominant red deer hinds under a competitive feeding system: food access behavior, diet and nutrient selection.

Social dominance is widely known to facilitate access to food resources in many animal species such as deer. However, research has paid little attention to dominance in ad libitum access to food because it was thought not to result in any benefit for dominant individuals. In this study we assessed if, even under ad libitum conditions, social rank may allow dominant hinds to consume the preferred components of food. Forty-four red deer hinds (Cervus elaphus) were allowed to consume ad libitum meal consisting of pellets of sunflower, lucerne and orange, and seeds of cereals, corn, cotton, and carob tree. The meal was placed only in one feeder, which reduced accessibility to a few individuals simultaneously. During seven days, feeding behavior (order of access, time to first feeding bout, total time spent feeding, and time per feeding bout) were assessed during the first hour. The relative abundance of each meal component was assessed at times 0, 1 and 5 h, as well as its nutritional composition. Social rank was positively related to the amount of time spent feeding during the 1st h (P = 0.048). Selection indices were positively correlated with energy (P = 0.018 during the 1st h and P = 0.047 from 1st to 5th) and fat (only during the 1st h; P = 0.036), but also negatively with certain minerals. Thus, dominant hinds could select high energy meal components for longer time under an ad libitum but restricted food access setting. Selection indices showed a higher selectivity when food availability was higher (1st hour respect to 1st to 5th). Finally, high and low ranking hinds had longer time per feeding bout than mid ones (P = 0.011), suggesting complex behavioral feeding tactics of low ranking social ungulates.

Novel micro‐extraction by packed sorbent procedure for the liquid chromatographic analysis of antiepileptic drugs in human plasma and urine

A method for the simultaneous determination of the antiepileptic drugs, phenobarbital (PHB), phenytoin (PTN), carbamazepine (CBZ), primidone (PRM) and oxcarbazepine (OXC) in human plasma and urine samples by using micro-extraction in a packed syringe as the sample preparation method connected with LC/UV (MEPS/LC/UV) is described. Micro-extraction in a packed syringe (MEPS) is a new miniaturized, solid-phase extraction technique that can be connected online to gas or liquid chromatography without any modifications. In MEPS approximately 1 mg of the solid packing material is inserted into a syringe (100-250 μL) as a plug. Sample preparation takes place on the packed bed. The bed can be coated to provide selective and suitable sampling conditions. The new method is very promising, easy to use, fully automated, inexpensive and quick. The standard curves were obtained within the concentration range 1-500 ng/mL in both plasma and urine samples. The results showed high correlation coefficients (R(2) >0.988) for all of the analytes within the calibration range. The extraction recovery was found to be between 88.56 and 99.38%. The limit of quantification was found to be between 0.132 and 1.956 ng/mL. The precision (RSD) values of quality control samples (QC) had a maximum deviation of 4.9%. A comparison of the detection limits with similar methods indicates high sensitivity of the present method. The method is applied for the analysis of these drugs in real urine and plasma samples of epileptic patients.