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A racemic mixture of R and S enantiomers of praziquantel (PZQ) is currently the treatment of choice for schistosomiasis. Though the S enantiomer and the metabolites are presumed to contribute only a little to the activity of the drug, in-depth side-by-side studies are lacking. The aim of this study was to investigate the in vitro activities of PZQ and its main metabolites, namely, R- and S-cis- and R- and S-trans-4′-hydroxypraziquantel, against adult worms and newly transformed schistosomula (NTS). Additionally, we explored the in vivo activity and hepatic shift (i.e., the migration of the worms to the liver) produced by each PZQ enantiomer in mice. Fifty percent inhibitory concentrations of R-PZQ, S-PZQ, and R-trans- and R-cis-4′-hydroxypraziquantel of 0.02, 5.85, 4.08, and 2.42 μg/ml, respectively, for adult S. mansoni were determined in vitro. S-trans- and S-cis-4′-hydroxypraziquantel were not active at 100 μg/ml. These results are consistent with microcalorimetry data and studies with NTS. In vivo, single 400-mg/kg oral doses of R-PZQ and S-PZQ achieved worm burden reductions of 100 and 19%, respectively. Moreover, worms treated in vivo with S-PZQ displayed an only transient hepatic shift and returned to the mesenteric veins within 24 h. Our data confirm that R-PZQ is the main effector molecule, while S-PZQ and the metabolites do not play a significant role in the antischistosomal properties of PZQ.  相似文献   
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Currently, considerable efforts have been devoted to the detection and quantification of hazardous multi-analytes using a single probe. Herein, we have developed a simple, environment-friendly colourimetric sensor for the sensitive, selective and rapid detection of Ni2+ and Cu2+ ions using a simple organic Schiff base ligand L in methanol–Tris–HCl buffer (1 : 1 v/v, 10 mM, pH = 7.2). The probe L exhibited a binding-induced colour change from colourless to yellow and fluorescence quenching in the presence of both Ni2+ and Cu2+ ions. The interactions between L and the respective metal ions were studied by Job''s plot, electrospray ionisation-mass spectrometry (ESI-MS), Fourier-transform infrared spectroscopy (FT-IR), density functional theory (DFT) and time-dependent density functional theory (TDDFT) calculations. The limit of detection (LOD) of L towards Ni2+ and Cu2+ was calculated to be 7.4 × 10−7 M and 4.9 × 10−7 M, respectively. Furthermore, the L–Cu2+ complex could be used as a new cascade fluorescent-colourimetric sensor to detect CN ions with a very low level of detection (40 nM). Additionally, L could operate in a wide pH range, and thus was successfully applied for the detection and quantification of Ni2+ and Cu2+ in environmental samples, and for building OR- and IMPLICATION-type logic gates.

A novel colorimetric chemosensor L has been developed for the detection of Ni2+ and Cu2+ ions. The obtained L–Cu2+ complex can be used as a new cascade fluorescent-colorimetric sensor for the nanomolar detection of CN ions. This chemosensor has practical application.  相似文献   
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Substituting an ion of different size from that of the host element introduces lattice strain and defects. However, this mismatch may be significantly reduced by substituting an additional ion with a compensating size relative to the dopant. Such a double substitution might offer better solubility irrespective of the local distortions as well as the formation of defects in the valence states. Fe-substituted ZnO has been widely reported with conflicting results primarily arising from lack of chemical and structural homogeneity originating from preparation techniques, compositional fluctuations, and equivocal comprehension of actual solubility limits of the dopants. In this study, Ag ion has been incorporated in Fe-substituted ZnO to compensate the ionic size of Zn1−x[Fe0.8Ag0.2]xO (0 ≤ x ≤ 0.03125) by determining the solubility limit of the homogeneous material and their corresponding structural, mechanical, optical and magnetic properties have been investigated thoroughly. Co-substitution rearranges the lattice and leads to better crystal structures with tunable properties related to the amount of substitution.

Substituting an ion of different size from that of the host element introduces lattice strain and defects.  相似文献   
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The spontaneously hypertensive rat (SHR) has been proposed as an overactive bladder model, driven, at least partially, by alterations in bladder innervation. To assess the functional role of sensory bladder afferents we evaluated the conscious cystometric response to prostaglandin E(2) (PGE(2)) or acetic acid (AA) bladder infusion. SHR demonstrated a hypersensitivity to PGE(2) and AA, as indicated by a greater reduction in both void volume (VV) and micturition interval (MI) compared with Sprague-Dawley controls. The heightened PGE(2) and AA responses in the SHR were inhibited by capsaicin desensitization, supporting a role for bladder afferents in facilitating the hypersensitivity. Furthermore, we characterized the SHR pharmacologically using overactive bladder therapeutic agents. In the SHR, both darifenacin and oxybutynin (M(3)-selective and nonselective muscarinic antagonists, respectively) reduced micturition pressure (MP) and functional bladder capacity (VV and MI). In sharp contrast, functional bladder capacity was significantly enhanced by β(3)-adrenoceptor agonism [5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL316243)], and by gabapentin, without effect on MP. These data provide the first functional evidence for hypersensitive bladder afferents in the SHR and provide a pharmacological benchmark in this model for overactive bladder therapeutics. These data also support the idea that β(3)-adrenoceptor agonism and gabapentin may provide a more effective overactive bladder therapy than muscarinic antagonism.  相似文献   
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Varying degrees of lead (Pb) poisoning was recorded in cows and buffaloes near a primary lead-zinc smelter in India. Affected animals had history of clinical signs characterized by head pressing, violent movement, blindness and salivation. These animals revealed considerably high lead levels in blood (1.43 +/- 0.07 ppm) and milk (0.75 +/- 0.19 ppm). Animals from the same place without the history of clinical signs suggestive of Pb poisoning recorded lower blood Pb levels than the affected animals; however, their blood Pb was higher than that reported for cattle in rural and urban areas of India. Affected animals also carried high levels of cadmium (Cd) in blood (0.11 +/- 0.01 ppm) and milk (0.05 +/- 0.01 ppm). These values were considerably higher than those for rural cattle in India. The findings indicated varying degrees of exposure of animals to Pb and Cd in the vicinity of the smelter.  相似文献   
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