Half-life Values Research Articles

The Use of Typha Latifolia L. in Constructed Wetland Microcosms for the Remediation of Herbicide Terbuthylazine

Aim of this work is to study the capability of constructed wetlands to remediate the herbicide terbuthylazine (TER). For this purpose, eight surface-flow wetlands were constructed. Two types of substrates were used, sandy loam and mixture with zeolite. In addition, two levels of plant density were used, two and six rhizomes of Typha latifolia L (10 rhizomes/m2 and 30 rhizomes/m2, respectively). The randomized complete block design was used for statistical evaluation. The results revealed that the constructed wetlands remediate efficiently the herbicide with simultaneous increase of dealkylated metabolites deethyl-terbuthylazine (DET) and deisopropyl-atrazine (DIA) in surface water. The bigger is the density of marsh plant, the more intensive is the reduction of herbicide (7.3 to 23.4%). Regarding the rate of reduction of herbicide during the 44 days of the experiment, the half-life (t1/2) value was twofold in wetlands with 10 rhizomes/m2 of that of 30 rhizomes/m2, i.e., 61 and 30 days, respectively. Moreover, the herbicide and its metabolites were detected in plant tissues, indicating the capability of plant to uptake the xenobiotic substance from the rhizosphere (phytoextraction). The accumulation was greater in foliage samples than in roots. The average uptake of TER was 3219.5 ng/g (n = 8) in the foliage and 1088.6 ng/g (n = 8) in the root. This study clarifies for the first time the possible metabolic pathway by the detection and quantification of the major hydroxy and dealkylated metabolites of herbicide terbuthylazine in the two major wetland compartments such as water and plant tissues of Typha latifolia L. bioreactor.

Effect of Weed Treatment on Cereal Yield in Direct Seeding: A Challenge Between Soil Pollution and Seeds Quality

The study was conducted at Technical Institute of Cereals (ITGC- Setif) during the years 2014-2018 for understanding the effect of weed treatment in direct seeding on cereal yield, soil and seeds quality. Two horizons were considered: horizon one (0 less than H1 less than 20 cm) and horizon two (H2 less than 20 cm) and four herbicide doses were applied: D1 =1080g ha-1, D2= 900g ha-1, D3= 720 g ha-1 and D4= 540 g ha-1. The yield results depended on the herbicide doses applied before seeding. The highest yield responded to the highest dose of herbicide applied (1080g ha-1). Study indicated that glyphosate reached soil during weed treatment and transferred in deep soil layer and to harvested seeds. Half-live values (DT50) of glyphosate found under field conditions were high.

Biodegradability assessment of food additives using OECD 301F respirometric test.

The ready biodegradability of twenty food additives, belonging to the classes of artificial sweeteners, natural sweeteners, preservatives and colorings, was investigated using activated sludge as inoculum and OECD 301F respirometric test. According to the results, saccharin, aspartame, sodium cyclamate, xylitol, erythritol, maltitol, potassium sorbate, benzoic acid and sodium ascorbate are characterized as readily biodegradable compounds, partial biodegradation (<60% during the test) was noticed for steviol, inulin, alitame, curcumin, ponceau 4R and tartrazine, while no biodegradation was observed for the other five compounds. The duration of lag phase before the start of biodegradation varied between the target compounds, while their ultimate biodegradation half-life values ranged between 0.7 ± 0.1 days (benzoic acid) and 24.6 ± 1.0 days (curcumin). The expected removal of target compounds due to ultimate biodegradation mechanism was estimated for a biological wastewater treatment system operated at a retention time of one day and percentages higher than 40% were calculated for sodium cyclamate, potassium sorbate and benzoic acid. Higher removal percentages are expected in full-scale Sewage Treatment Plants (STPs) due to the contribution of other mechanisms such as sorption to suspended solids, (bio)transformation and co-metabolic phenomena. Further biodegradation experiments should be conducted under different experimental conditions for the food additives that did not fulfill the requirements of the applied protocol. Future studies should also focus on the occurrence and fate of food colorants and natural sweeteners in full-scale STPs.

Effects of water temperature on tissue depletion of florfenicol and its metabolite florfenicol amine in crucian carp (Carassius auratus gibelio) following multiple oral doses

Tissue depletion of florfenicol (FF) and its metabolite florfenicol amine (FFA) was investigated in crucian carp (Carassius auratus gibelio) following administration of 10 mg/kg body weight (BW) daily for five consecutive days by oral gavage at water temperatures of 10 and 25 °C. Plasma and tissue samples, including muscle with skin in natural proportions, liver, and kidney, were collected from 10 fish per sampling point. The concentrations of FF and FFA in each sample were simultaneously determined using high performance liquid chromatography (HPLC) with fluorescence detection. Depletion profiles at different temperatures were estimated and withdrawal periods were calculated. FF was more rapidly eliminated at 25 °C, with apparent elimination half-life (t1/2λz) values ranging from 8.1 h in skin-on muscle to 9.74 h in plasma, than at 10 °C. In contrast, water temperature did not affect FF withdrawal. At 10 °C, the withdrawal periods were calculated as 2.81 and 2.83 days based on the maximum residue limit (MRL) of FF plus FFA and the tolerance of FFA both at 1 μg/g in skin-on muscle, respectively. At 25 °C, the corresponding withdrawal periods were calculated as 2.15 and 2.41 days, respectively. Each withdrawal period was rounded to the next day (3 days).

Alpha half-lives calculation of superheavy nuclei with Qα-value predictions based on the Bayesian neural network approach

In this work, we performed a systematic study of the α-decay process by employing the Bayesian neural network approach. The Qα-value prediction of the ten parameter Duflo-Zuker mass model has been improved from a root-mean-square deviation relative to the experimental data σ = 0.43 MeV to σ = 0.122 MeV. This correction brought to light some missing physical aspects in the DZ mass model, so as to identify some magic numbers not present in the original model. By using a phenomenological effective model to deal with alpha decay half-lives, we were able to obtain the half-life values throughout the superheavy elements region. As a main result, we found that the region of greatest stability against the alpha-decay process for superheavy elements is between 106 ≤ Z ≤ 110 and 180 ≤ N ≤ 184.

1424The diagnosis of non-adherence in hypertension using a urine biochemical screen is unaffected by drug pharmacokinetics

Abstract Introduction Suboptimal drug adherence in hypertension is pandemic and traditional diagnostic tools to detect non-adherence have lacked accuracy and robustness. The inability to identify non-adherence has therefore driven the development of biochemical drug screening by liquid chromatography tandem mass spectrometry (LC- MS/MS) in urine and blood, which are the most accurate metrics presently available. Urinary antihypertensive testing is evidenced to improve non-adherence rates, significantly decrease blood pressure after physician intervention, and be cost effective. The European Society of Cardiology (ESC) and European Society of Hypertension (ESH) 2018 guidelines have recommended the use of biochemical testing for non-adherence diagnosis. However, it has been argued that the variable pharmacokinetic parameters of the medication (such as their half-lives and clearance rates) may affect the detection of medications in urine and hence the determination of adherence. We hypothesized that pharmacokinetic parameters do not affect the detection of antihypertensive medications in urine. Aim This study compared the pharmacokinetic parameters of the most commonly prescribed antihypertensive medications against their detection in urine by LC-MS/MS. Methods Results of urinary drug screens from 463 hypertensive patients (total prescribed medications N=1709) were collated. An adherence score termed as the C score (number of detected vs. prescribed medication) was generated for each of the 27 common antihypertensive medications. Pharmacokinetic parameters such as bioavailability, plasma concentration, volume of distribution, half-life, plasma clearance and urinary excretion values for each drug were obtained from published literature. Partial linear correlation was conducted between the C score of all the medications and each pharmacokinetic parameter studied. Results 40% of patients were non-adherent. The average number of prescribed medications was high (N=3.7, SD: 1.5), and the average number of drugs detected was lower (N=2.5, SD: 1.6). Amlodipine was the most prescribed (N=224), and clonidine was the least (N=10). The half-lives ranged from 0.87 to 39 hours for bumetanide and amlodipine respectively. The urinary excretion percentage varied from &lt;1% for nifedipine, and 94% for benfroflumethiazide. No significant correlation was found between any drug C score and their respective pharmacokinetic variables such as the medication half-lives (figure1). Half-life versus adherence score Conclusion This study reports no significant correlation between drug pharmacokinetics and adherence. To the best of our knowledge this is the first study of its kind. Urinary biochemical testing by LC-MS/MS for non-adherence remains a valid tool for diagnosis although further detailed pharmacokinetic studies are needed to confirm this finding. Acknowledgement/Funding None

1220P - Phase I study evaluating safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-428, first-in-class mesothelin (MSLN)-CD40 bispecific, in patients (pts) with advanced solid tumours

1220P - Phase I study evaluating safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-428, first-in-class mesothelin (MSLN)-CD40 bispecific, in patients (pts) with advanced solid tumours

Construction of a novel quinoxaline as a new class of Nrf2 activator

BackgroundThe transcription factor Nuclear factor erythroid-2-related factor 2 (NRF2) and its principal repressive regulator, Kelch-like ECH-associated protein 1 (KEAP1), are perilous in the regulation of inflammation, as well as maintenance of homeostasis. Thus, NRF2 activation is involved in cytoprotection against many inflammatory disorders. N′-Nicotinoylquinoxaline-2-carbohdyrazide (NQC) was structurally designed by the combination of important pharmacophoric features of bioactive compounds reported in the literature.MethodsNQC was synthesised and characterised using spectroscopic techniques. The compound was tested for its anti-inflammatory effect using Lipopolysaccharide from Escherichia coli (LPSEc) induced inflammation in mouse macrophages (RAW 264.7 cells). The effect of NQC on inflammatory cytokines was measured using enzyme-linked immune sorbent assay (ELISA). The Nrf2 activity of the compound NQC was determined using ‘Keap1:Nrf2 Inhibitor Screening Assay Kit’. To obtain the insights on NQC’s activity on Nrf2, molecular docking studies were performed using Schrödinger suite. The metabolic stability of NQC was determined using mouse, rat and human microsomes.ResultsNQC was found to be non-toxic at the dose of 50 µM on RAW 264.7 cells. NQC showed potent anti-inflammatory effect in an in vitro model of LPSEc stimulated murine macrophages (RAW 264.7 cells) with an IC50 value 26.13 ± 1.17 µM. NQC dose-dependently down-regulated the pro-inflammatory cytokines [interleukin (IL)-1β (13.27 ± 2.37 μM), IL-6 (10.13 ± 0.58 μM) and tumor necrosis factor (TNF)-α] (14.41 ± 1.83 μM); and inflammatory mediator, prostaglandin E2 (PGE2) with IC50 values, 15.23 ± 0.91 µM. Molecular docking studies confirmed the favourable binding of NQC at Kelch domain of Keap-1. It disrupts the Nrf2 interaction with kelch domain of keap 1 and its IC50 value was 4.21 ± 0.89 µM. The metabolic stability studies of NQC in human, rat and mouse liver microsomes revealed that it is quite stable with half-life values; 63.30 ± 1.73, 52.23 ± 0.81, 24.55 ± 1.13 min; microsomal intrinsic clearance values; 1.14 ± 0.31, 1.39 ± 0.87 and 2.96 ± 0.34 µL/min/g liver; respectively. It is observed that rat has comparable metabolic profile with human, thus, rat could be used as an in vivo model for prediction of pharmacokinetics and metabolism profiles of NQC in human.ConclusionNQC is a new class of NRF2 activator with potent in vitro anti-inflammatory activity and good metabolic stability.

Augmented Renal Clearance of Vancomycin in Hematologic Malignancy Patients

The pharmacokinetics of vancomycin (VAN) was retrospectively examined based on trough concentrations at large scale to identify pharmacokinetic differences between Japanese hematologic malignancy and non-malignancy patients. Data from 261 hematologic malignancy patients and 261 non-malignancy patients, including the patient's background, VAN dose, and pharmacokinetics of VAN estimated by an empirical Bayesian method, were collected and analyzed. Our results showed significantly higher values for VAN clearance and shorter elimination half-lives in patients with hematologic malignancies than non-malignancy patients. In addition, multiple regression analysis under adjusting for confounding factors by propensity score, showed that VAN clearance significantly increased in relation to hematologic malignancies. In conclusion, since in hematologic cancer patients VAN clearance is increased, the blood concentration of VAN becomes lower than expected and this may contribute to the survival of resistant bacteria when VAN is administered at low doses. These results suggest that early monitoring of VAN levels in hematologic cancer patients might be recommended to maintain desired effects without side-effects.

Half-life determination and comparison of activity standards of 231Pa

The results of an international comparison of activity measurements of a solution of 231Pa are reported and analysed. Prior to this, no known standardisation of 231Pa by activity measurement had been carried out. The comparison was run in 2017–2018 involving eight laboratories, and returned results with no identifiable inconsistencies between methods or laboratories. The results, including one mass determination, gave a231Pa activity concentration of 41.461(48) kBq g−1 and a231Pa atom concentration of 61.48(23) × 1015 atoms g−1, from which a half-life value of 32 570(130) years was derived.

Potential pesticide exposure during the post-breeding migration of the common toad (Bufo bufo) in a vineyard dominated landscape

Two important drivers of the global amphibian decline are habitat destruction due to an intensification of farming and a related increase of pesticide applications. Recent studies have shown that there might be an underestimated risk of pesticides on terrestrial amphibians. However, there are too few data on the terrestrial habitat use of amphibians in agricultural landscapes to estimate the exposure risk. To fill this knowledge gap, we used telemetry to investigate the post-breeding migration of 51 common toads (Bufo bufo) from a breeding pond in a vineyard-dominated landscape in Southern Palatinate (Germany). We expected most toads to migrate to the nearby Palatinate Forest as a terrestrial habitat. However, only four individuals reached the forest, suggesting that a part of the population is inhabiting the agricultural landscape over large parts of the year. Individuals were also found directly in the vineyards (15% of all relocations), but 23% less often than expected from a random choice and therefore tend to avoid vineyards as terrestrial habitat. To estimate a possible spatial–temporal overlap of toad migration and pesticide application, we combined telemetry data with information about pesticide applications from local wine growers. Seven individuals had a high probability (>75%) of being directly exposed to a pesticide application. Taking spray drift and the half-life values of applied pesticides into account, the number of toads potentially exposed raised to 15 individuals. We estimated that, on a single day up to 24% of the whole breeding population came in contact with pesticides, resulting in a high overall exposure risk. Pesticides can have negative effects on amphibians, and toads try to avoid vineyards as habitats. Therefore, we conclude that a heterogeneous cultural landscape, with buffer strips around ponds, uncultivated patches and migration corridors, might be the best management measure for sustaining amphibians in the agricultural landscape.

Long term decrease of 137Cs bioavailability in French pastures: Results from 25 years of monitoring

Long term radioactivity monitoring programs contribute to the understanding of the behavior of radionuclides in the environment. This work aims to investigate the long term behavior of Cesium-137 in pasture ecosystem (root soil, grass and cow's milk) by using of more than twenty five years monitoring data collected at ten of French pasture sites contaminated by atmospheric fallouts from Chernobyl and nuclear atmospheric tests. We estimated with a simple exponential model the long term effective half-lives of radiocesium in root soil, grass vegetation and cow's milk along with their associated uncertainties. The average values of the effective half-lives over all the investigated sites were determined as 17, 11 and 9 years for soil, grass and milk respectively. Those values compare favorably to those estimated in previous studies in literature. These findings further enable us to quantify the decrease of 137Cs bioavailability which ranges from 0.008 to 0.044 year−1 with an average value of 0.026 year−1 (i.e. effective half lives ranging from 16 to 87 years with an average value of 26 years in soil).

Cohnella sp. A01 laccase: thermostable, detergent resistant, anti-environmental and industrial pollutants enzyme

Laccase (EC 1.10.3.2; benzenediol; oxygen oxidoreductases) is a multi-copper oxidase that catalyzes the oxidation of phenols, polyphenols, aromatic amines, and different non-phenolic substrates with concomitant reduction of O2 to H2O. Enzymatic oxidation techniques have the potential of implementation in different areas of industrial fields. In this study, the Cohnella sp. A01 laccase gene was cloned into pET-26 (b+) vector and was transformed to E. coli BL21. Then it was purified using His tag affinity (Ni sepharose resin) chromatography. The estimated molecular weight was approximately 60 kDa using SDS-PAGE. The highest enzyme activity and best pH for 2,6-dimethoxyphenol (DMP) oxidation were recorded as 8 at 90 °C respectively. The calculated half-life and kinetic values including Km, Vmax, turn over number (kcat), and catalytic efficiency (kcat/Km) of the enzyme were 106 min at 90 °C and 686 μM, 10.69 U/ml, 20.3 S−, and 0.029 s−1 μM−1, respectively. The DMP was available as the substrate in all the calculations. Enzyme activity enhanced in the presence of Cu2+, NaCl, SDS, n-hexane, Triton X-100, tween 20, and tween 80, significantly. The binding residues were predicted and mapped upon the modeled tertiary structure of identified laccase. The remaining activity and structural properties of Cohnella sp. A01 laccase in extreme conditions such as high temperatures and presence of metals, detergents, and organic solvents suggest the potential of this enzyme in biotechnological and industrial applications. This process has been patented in Iranian Intellectual Property Centre under License No: 91325.

Systematic study of alpha decay half-lives using new universal decay law

We have performed a systematic calculation on the alpha decay half-lives of heavy mass nuclei with 106 [Formula: see text] 118, within the universal decay law (UDL) and modified universal decay law (MUDL). The calculated half-life values are found to be in agreement with the experimental data. The standard deviations of the logarithm of half-lives are found to be the least for MUDL in all cases of even–even, even–odd, odd–even and odd–odd, so the MUDL formula is better than UDL formula for alpha decay studies. We have predicted half-lives of some superheavy nuclei (SHN) in the region [Formula: see text]–118 that are not yet experimentally detected. The decay energies are computed using three different mass models. We hope this study will help future measurements on alpha decay half-lives of SHN.

Dissipation of fomesafen in fumigated, anaerobic soil disinfestation-treated, and organic-amended soil in Florida tomato production systems.

Fumigated, anaerobic soil disinfestation-treated (ASD), and organic-amended soil management strategies have been investigated as potential methyl bromide (MBr) alternatives for controlling diseases, nematodes, and weeds in soil. Nutsedge and broadleaf weed control using fomesafen has been reported to be comparable to MBr in normal cropping systems. There is no information on the fate of fomesafen used in combination with alternative practices. In this study, the fate of fomesafen in these alternative systems was measured byliquid chromatography-tandem mass spectrometry (LC/MS-MS) following extraction using a modifiedQuick Easy Cheap Effective Safe (QuEChERS) method. The reported half-life (DT50 ) values for fomesafen in the top 15 cm of soil were from 62.9 to 107.3 days. The DT50 values in organic-amended soil were higher than in ASD-treated soil in the top 15 cm. For all treatments, reductions in concentrations were positively correlated with lower redox potentials and organic matter content. Some leaching of fomesafen into the 16-30 cm zone was observed in all treatments. The DT50 values in this study were generally higher than those reported in previous studies performed at different locations. Due to increased losses of the herbicide and subsequent reduction in weed control, fomesafen is likely not to be suitable for effective weed control in systems using ASD techniques employing composted poultry litter and molasses. Integration of fomesafen using composted yard waste 1 (CYW1) and Soil Symphony Amendment (SSA) may result in acceptable weed control. Given that the soil was very sandy and the pH was higher than the pKa, fomesafen might leach deeper than 30 cm, particularly with the use of chemical soil fumigants (CSFs). © 2019 Society of Chemical Industry.

Residue analysis of the fumigant pesticide ethanedinitrile in different agricultural commodities using ether extraction and GC-MS

Ethanedinitrile (EDN) is used to fumigate logs and timber products, and it has the potential as an alternative fumigant for stored food products. Other work has demonstrated efficacy of EDN for controlling stored grain pests, but information on EDN residues in food commodities are needed to assess impacts on food safety. The present study developed and validated a method to determine EDN residues in whole wheat kernels, wheat flour, whole corn kernels, pinto beans and dried whole-leaf tobacco. EDN was extracted from commodities with diethyl ether and analyzed by quantitative GC-MS in selected ion monitoring (SIM). The method achieved a high level of selectivity and good precision with acceptable recoveries between 42.3 and 96.6% and relative standard deviation (RSD) < 20% when known concentrations were set at 0.00594, 0.0594 and 0.594 mg/L. The limit of detection (LOD) and limit of quantitation (LOQ) were 0.001 and 0.003 mg/L, respectively. Also, the actual residues of EDN were evaluated in the commodities at two levels of fumigation and after different aeration times. The initial deposits of EDN residues after 1 h ranged from 32.08 to 100.60 μg/kg following fumigation with 2.6 mg/L, and 56.30–154.78 μg/kg when fumigated at 4.8 mg/L. The dissipation of EDN in the fumigated commodities followed the first order kinetics model with half-life values ranged from 6.47 to 36.47 h at 2.6 mg/L and from 21.6 to 57.75 h at 4.8 mg/L. This research demonstrates that ether extraction followed by GC-MS generates useful residue data from EDN in grains and tobacco, and those residues can vary widely among these products. These findings are important as work moves forward to adopt EDN as a stored product fumigant.

Pharmacokinetics, bioavailability and tissue distribution studies of rhodojaponin III in mice using QTRAP LC–MS/MS

Rhodojaponin III is a bioactive diterpenoid isolated from the medicinal plant Rhododendron molle G. Don. Quantitative analysis of rhodojaponin III was challenging and the pharmacokinetics of oral rhodojaponin III remained to be investigated. Here, a rapid and sensitive liquid chromatography tandem mass spectrometric (LC-MS/MS) method was developed and validated. The calibration curve was linear over the concentration range of 1-200 ng/mL (r = 0.992). The method was further validated following internationally approved guidelines and all the issues including intra- and inter-day precision, accuracy, carryover, extraction recovery, matrix effects and stability met the recommended limits. The method was then applied to study the pharmacokinetics of rhodojaponin III in mice after intravenous (0.06 mg/kg) or oral (0.24 mg/kg) administration. The results showed that rhodojaponin III had fast oral absorption (time to peak concentration, 0.08 h) and good oral bioavailability (73.6%). In addition, rhodojaponin III was quickly eliminated after it was intravenously or orally administered, with half-life values of 0.19 and 0.76 h, respectively. After oral administration, it was widely distributed in tissues including kidney, lung, heart, spleen and thymus, but had extremely low concentrations in liver and brain. The data presented in this study is beneficial for the further study of rhodojaponin III.

A 4-bp deletion in the 5\u2019UTR of TaAFP-B is associated with seed dormancy in common wheat (Triticum aestivum L.)

BackgroundAFP is a negative regulator of ABA signaling that promotes ABI5 protein degradation and weakens regulation of ABA signaling by targeting upstream genes of ABI5, and TaABI5 gene was seed-specific, and accumulated during wheat grain maturation and dormancy acquisition, which played an important role in seed dormancy; TaAFP has a conserved domain with AFP, so TaAFP may also play an important role in seed dormancy in wheat.ResultsTwo allelic variants of TaAFP were identified on chromosome 2BS in common wheat, and designated as TaAFP-B1a and TaAFP-B1b. Sequence analysis showed a 4-bp deletion in the 5’UTR region of TaAFP-B1b compared with TaAFP-B1a. Based on the 4-bp deletion, a co-dominant functional marker of TaAFP-B was developed and designated as AFPB. The genotype generating a 203-bp fragment (TaAFP-B1b) was more resistant to pre-harvest sprouting than the genotype producing a 207-bp fragment (TaAFP-B1a) in a test of 91 white-grained Chinese wheat cultivars and advanced lines. The average germination index(GI) values of TaAFP-B1a and that of TaAFP-B1b were 45.18 and 30.72%, respectively, indicating a significant difference (P < 0.001). Moreover, the 4-bp deletion located in the 5’UTR not only affected the transcription level of TaAFP-B but also affected the mRNA decay, reduced the translation level of GUS and tdTomatoER and GUS activity in wheat leaves of transient expression. The transcript expression and the mRNA half-life value of TaAFP-B1a in developing seeds and mature seeds were much higher than those of TaAFP-B1b.ConclusionWe identified a 4-bp InDel in the 5’UTR of TaAFP-B, which affected the mRNA transcription level, mRNA decay, translation levels of GUS and tdTomatoER, GUS activity, and was significantly associated with seed dormancy in common wheat. A functional marker was developed and validated based on this InDel.

Aerobic dissipation of avermectins and moxidectin in subtropical soils and dissipation of abamectin in a field study

Avermectins and moxidectin are antiparasitics widely used as active pharmaceutical ingredients in veterinary medicine, as well as in pesticide formulations for pest control in agriculture. Although the use of these compounds provides benefits to agribusiness, they can impact the environment, since a large part of these substances may reach the soil and water from the excreta of treated animals and following direct applications to crops. The present work had the objective of evaluating the dissipation behaviors of abamectin, doramectin, eprinomectin, ivermectin, and moxidectin in four native Brazilian soils of different textural classes (clay, sandy-clay, sandy, and sandy-clay-loam), following OECD Guideline 307. The studies were conducted in a climate chamber at 22 °C, 71% relative humidity, and protected from light. The dissipation studies were carried out with all drugs together, since no difference was verified when studies were done with each drug separately. The concentrations of the drugs in the soils were determined using an ultra-high performance liquid chromatograph coupled to a fluorescence detector or a tandem mass spectrometer. The dissipation half-life (DT50) values ranged from 9 to 16 days and the calculated GUS index values were in the range from −1.10 to 0.08, indicating low mobility of the drugs in the soils evaluated and low tendency for leaching. In addition, a field study was carried out to evaluate the dissipation of abamectin after application of a foliar pesticide in an orange crop. A DT50 of 9 days was determined, which was similar to that obtained under controlled conditions in the climate chamber (12 days), indicating that biotransformation was the primary process influencing the overall dissipation.

In vitro and in vivo pharmacokinetic characterization of LMT-28 as a novel small molecular interleukin-6 inhibitor.

ObjectiveInterleukin-6 (IL-6) is a T cell-derived B cell stimulating factor which plays an important role in inflammatory diseases. In this study, the pharmacokinetic properties of LMT-28 including physicochemical property, in vitro liver microsomal stability and an in vivo pharmacokinetic study using BALB/c mice were characterized.MethodsLMT-28 has been synthesized and is being developed as a novel therapeutic IL-6 inhibitor. The physicochemical properties and in vitro pharmacokinetic profiles such as liver microsomal stability and Madin-Darby canine kidney (MDCK) cell permeability assay were examined. For in vivo pharmacokinetic studies, pharmacokinetic parameters using BALB/c mice were calculated.ResultsThe logarithm of the partition coefficient value (LogP; 3.65) and the apparent permeability coefficient values (Papp; 9.7×10−6 cm/s) showed that LMT-28 possesses a moderate-high cell permeability property across MDCK cell monolayers. The plasma protein binding rate of LMT-28 was 92.4% and mostly bound to serum albumin. The metabolic half-life (t1/2) values of LMT-28 were 15.3 min for rat and 21.9 min for human at the concentration 1 μM. The area under the plasma drug concentration-time curve and Cmax after oral administration (5 mg/kg) of LMT-28 were 302±209 h·ng/mL and 137±100 ng/mL, respectively.ConclusionThese data suggest that LMT-28 may have good physicochemical and pharmacokinetic properties and may be a novel oral drug candidate as the first synthetic IL-6 inhibitor to ameliorate mammalian inflammation.