Wastewater surveillance for 168 pharmaceuticals and metabolites in a WWTP: Occurrence, temporal variations and feasibility of metabolic biomarkers for intake estimation.

Wastewater-based epidemiology (WBE) is amply used for mining information about public health such as the estimation of consumption/intake of certain substances. Yet, proper biomarker selection is critical to obtain reliable data. This study measured a broad range of pharmaceuticals and metabolites in a wastewater treatment plant in Beijing, China, and evaluated their suitability as consumption estimation biomarkers. Wastewater sampling was conducted during a normal week and two holiday weeks to assess the impact of the holiday on population normalized daily mass loads (PNDLs). One hundred and forty-nine out of 168 pharmaceuticals were detected, with 94 analytes being quantified in all sampling events. Moreover, digestive drug cimetidine (

Efficient multiresidue determination method for 168 pharmaceuticals and metabolites: Optimization and application to raw wastewater, wastewater effluent, and surface water in Beijing, China.

New analytical methods are needed to efficiently measure the growing list of priority pharmaceuticals in environmental samples. In this regard, a rapid, sensitive, and robust method was developed for quantitation of 168 pharmaceuticals and pharmaceutical metabolites using solid-phase extraction (SPE) and liquid chromatography with tandem mass spectrometry. The extraction protocol and instrumental efficiency were specifically addressed to increase analytical workload and throughput. The optimized protocols, which are five times more efficient than US EPA Method 1694, enabled analyte recoveries that ranged from 77% to 117% for 162 analytes with method quantitation limits (MQLs) as low as 0.1 ng L-1. To verify the suitability of the improved analytical method for environmental samples, 24-h composite samples of raw wastewater and wastewater effluent, along with downstream surface water, were analyzed. Overall, 143/168 target compounds were identified in at least one of the samples, and 130/168 analytes were present at concentrations above their MQLs. The total mass concentration of the measured analytes decreased by 93% during wastewater treatment. The analyte concentrations in the wastewater effluent were comparable to those measured in surface water 1 km downstream of the wastewater discharge point. Ultimately, the comprehensive method will serve as an important tool to inform the occurrence, fate, transport, and toxicity of a large suite of priority pharmaceuticals and pharmaceutical metabolites in natural and engineered systems.

MicroRNA-204 silencing relieves pain of cervical spondylotic radiculopathy by targeting GDNF.

Cervical spondylosis may cause chronic neck pain, radiculopathy and/or myelopathy, and consequently results in severe brain damage. Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for motoneurons. Accumulating microRNAs (miRNAs) have highlighted as critical regulators of GDNF signaling in the mediation of neuroinflammation and neuropathic pain. Hence, we performed this study to investigate the potential role of miR-204 in the neuropathic pain of cervical spondylotic radiculopathy (CSR) by targeting GDNF. A rat model of spinal cord compression (SCC) was established to stimulate a pathologic lesion. RT-qPCR and western blot assays characterized the downregulation of GDNF and the upregulation of miR-204 in spinal cord tissues of rats under the conditions of SCC. Moreover, miR-204 could directly target GDNF, as evidenced by dual-luciferase reporter gene assay. In order to elucidate the roles of miR-204 and GDNF in SCC-induced neuropathic pain, miR-204 sponge, GDNF, or shRNA against GDNF was introduced to the rats, followed by measurements for SCC-induced neuroinflammation and neuropathic pain. GDNF upregulation or miR-204 silencing was identified to reduce the spontaneous pain score, gait scores and cell apoptosis. Furthermore, GDNF upregulation or miR-204 silencing resulted in elevated amplitude of sensory-evoked potentials (SEPs), number of motoneurons, release of pro-inflammatory factors, TNF-α, and IL-1ß in addition to an increase in the anti-inflammatory factor BDNF. Taken together, upregulation of GDNF induced by miR-204 silencing confers protection against SCC-induced pain in rat models, suggesting a potential therapeutic target for CSR treatment.

Radiofrequency Thermocoagulation in Relieving Refractory Pain of Knee Osteoarthritis.

To investigate the efficacy of radiofrequency thermocoagulation (RFTC) in relieving refractory pain of knee osteoarthritis (OA), we selected 54 patients with chronic knee OA pain, 27 treated with RFTC (case group) and 27 receiving regular treatments (control group). Response evaluations were conducted before treatment, and at the termination of treatment, and 3-month follow-up, applying the visual analog scale, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and American Knee Society Score (AKSS). Data analyses were performed with SPSS 21.0. At the termination of treatments and 3-month follow-ups, cases gained significantly increased scores in vitality, bodily pain, general health perceptions, physical functioning, and social role functioning by SF-36 scaling and in pain, range of motion, stability, walking, and stair climbing by AKSS (all P < 0.05). Controls received higher scores by AKSS in pain at the termination of treatments and in pain, range of motion, and walking at the termination of 3-month follow-ups (all P < 0.05). Both cases and controls presented significant difference between visual analog scale scores before treatments and those at the termination of 3-month follow-ups (both P < 0.05). All patients felt less pain after treatments, cases presenting better improvement (P < 0.05). Pain was stronger in females compared with males and in a positive correlation with age while had no obvious relation to disease course. In conclusion, RFTC may have better efficacy in relieving refractory pain and promoting function recovery in patients with knee OA than regular treatment.

Quantitative determination of tiopronin in human plasma by LC-MS/MS without derivatization.

Tiopronin (TP) is a synthetic thiol compound without chromophore. By optimizing the chromatographic conditions and sample preparation processes, an improved LC-MS/MS analytical method without derivatization has been developed and validated to determine TP concentrations in human plasma. After reduction with 1,4-dithiothreitol, plasma samples were deproteinized with 10% perchloric acid. The post-treatment samples were analyzed on a C8 column interfaced with a triple quadrupole tandem mass spectrometer in negative electrospray ionization mode. Methanol-5 mmol/L ammonium acetate (20:80, v/v) was used as the isocratic mobile phase. The assay was linear over the concentration range of 40.0-5000 ng/mL. The intra- and inter-day precisions were within 12.9% in terms of relative standard deviation and the accuracy within 5.6% in terms of relative error. This simple and sensitive LC-MS/MS method with short analytical time (3.5 min each sample) was successfully applied to the pharmacokinetic study of TP in healthy Chinese male volunteers after an oral dose of 300 mg TP.