Search Results (4)

Compound 7–16 was designed and synthesized in our previous study and was identified as a more potential selective 5-HT_2A receptor antagonist and inverse agonist for treating Parkinson’s disease psychosis (PDP). Then, the metabolism, disposition, and excretion properties of 7–16 and its potential inhibition on transporters were investigated in this study to highlight advancements in the understanding of its therapeutic mechanisms. The results indicate that a total of 10 metabolites of 7–16/[¹⁴C]7–16 were identified and determined in five species of liver microsomes and in rats using UPLC-Q Exactive high-resolution mass spectrometry combined with radioanalysis. Metabolites formed in human liver microsomes could be covered by animal species. 7–16 is mainly metabolized through mono-oxidation (M470-2) and N-demethylation (M440), and the CYP3A4 isozyme was responsible for both metabolic reactions. Based on the excretion data in bile and urine, the absorption rate of 7–16 was at least 74.7%. 7–16 had weak inhibition on P-glycoprotein and no effect on the transport activity of OATP1B1, OATP1B3, OAT1, OAT3, and OCT2 transporters. The comprehensive pharmacokinetic properties indicate that 7–16 deserves further development as a new treatment drug for PDP. Full article

Ribwort plantain (Plantago lanceolata L.) is a common weed in the winter rainfall region of South Africa. This weed is widespread across vineyards, orchards, and roadsides in the region. The weed has already evolved resistance to glyphosate and paraquat; however, the mechanism of paraquat resistance has not been documented. This study aimed to investigate the resistance mechanisms in this resistant (R) biotype. Dose–response trials conducted with R biotypes from the Robertson area reconfirmed paraquat resistance. Dose–response trials established that the paraquat rate causing 50% mortality (LD₅₀) for the R biotype is three times greater than for the susceptible (S) biotype. To find out how paraquat affected the photosynthetic performance of P. lanceolata, the quantum yield of photosystem II was measured. The photosystem reaction centres of the R biotype recovered 24 h after paraquat treatment. To evaluate paraquat transport in the plant cell, selective transport inhibitors were applied. Plantago lanceolata (S) biotypes had the highest electrolyte leakage after paraquat treatment. A combined radio/UV-HPLC was used for the separation and identification of paraquat and its metabolites. Paraquat degradation was not observed, indicating that metabolism was not a resistance mechanism within the R biotype. To assess leaf absorption and translocation, [¹⁴C]-labelled paraquat was applied to fully expanded leaves. There were no significant differences in paraquat absorption. However, paraquat translocation differed significantly across the R and S biotypes, indicating that non-target site resistance through reduced paraquat translocation was the main mechanism of resistance in the R biotype. As the resistance of weed species to post-emergence herbicides continues to increase, achieving sustainable weed management necessitates the implementation of diversified weed control strategies. Full article

This study is part of the ongoing environmental monitoring program of the abandoned Mecsek uranium mine. On the mine’s recultivated spoil deposit No. I, anomalies that refer to possible migration alongside the slope were detected. The present study was conducted to supplement the ongoing monitoring study with a sampling strategy and analytical methods that can characterize the mobility of potentially toxic elements and radionuclides. A sampling strategy was developed: the vegetation and soil core samples were collected from the slope from top to bottom of the deposit, and nearby this spoil deposit, water samples were collected. Elemental analyses were conducted: the pseudo-total analysis, a total concentration of uranium in water, and the BCR sequential extraction analysis. The radionuclides were determined by gamma spectrometry and alphaGUARD. Additionally, the soil and plant moisture content, soil organic matter, pH, and cation exchange capacity (CEC) were determined. The Pearson correlation analysis and the principal component analysis, considering all possible influencing factors, verified that the elemental concentration increase from the top to the bottom direction of the deposit is strongly influenced by the soil pH, CEC, and Ca content. The mobility of Cd, Co, Mn, Pb, and U is relatively high and significantly migrates down the slope. Full article

Substance P (SP) is a small peptide commonly known as a preferential endogenous ligand for the transmembrane neurokinin-1 receptor. Nuclear Medicine procedures currently involve radiolabeled SP derivatives in peptide radioligand endotherapy of inoperable glioblastoma. Promising clinical results sparked the demand for facile production strategies for a functionalized 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[Thi⁸, Met(O₂)¹¹]-SP to allow for rapid Gallium-68 or Bismuth-213 complexation. Therefore, we provide a simple kit-like radiotracer preparation method that caters for the gallium-68 activity eluted from a SnO₂ generator matrix as well as preliminary results on the adaptability to produce [²¹³Bi]Bi-DOTA-[Thi⁸, Met(O₂)¹¹]SP from the same vials containing the same starting material. Following a phase of radioanalysis for complexation of gallium-68 to DOTA-[Thi⁸, Met(O₂)¹¹]SP and assessing the radiolabeling parameters, the vials containing appropriate kit-prototype material were produced in freeze-dried batches. The facile radiolabeling performance was tested and parameters for future human application were calculated to meet the criteria for theranostic loco-regional co-administration of activity doses comprising [⁶⁸Ga]Ga-DOTA-[Thi⁸, Met(O₂)¹¹]SP mixed with [²¹³Bi]Bi-DOTA-[Thi⁸, Met(O₂)¹¹]SP. [⁶⁸Ga]Ga-DOTA-[Thi⁸, Met(O₂)¹¹]SP was prepared quantitatively from lyophilized starting material within 25 min providing the required molar activity (18 ± 4 GBq/µmol) and activity concentration (98 ± 24 MBq/mL), radiochemical purity (>95%) and sustained radiolabeling performance (4 months at >95% LE) as well as acceptable product quality (>95% for 120 min). Additionally, vials of the same starting materials were successfully adapted to a labeling strategy available for preparation of [²¹³Bi]Bi-DOTA-[Thi⁸, Met(O₂)¹¹]SP providing sufficient activity for 1–2 human doses. The resultant formulation of [⁶⁸Ga]Ga-/[²¹³Bi]Bi-DOTA-[Thi⁸, Met(O₂)¹¹]SP activity doses was considered of adequate radiochemical quality for administration. This investigation proposes a simple kit-like formulation of DOTA-[Thi⁸, Met(O₂)¹¹]SP—a first-line investigation into a user friendly, straightforward tracer preparation that would warrant efficient clinical investigations in the future. Quantitative radiolabeling was accomplished for [⁶⁸Ga]Ga-DOTA-[Thi⁸, Met(O₂)¹¹]SP and [²¹³Bi]Bi-DOTA-[Thi⁸, Met(O₂)¹¹]SP preparations; a key requirement when addressing the specific route of catheter-assisted co-injection directly into the intratumoral cavities. Full article