Capillary electrophoresis-mass spectrometry for creatinine analysis in residual clinical plasma samples and comparison with gold standard assay.

When hospitalized, infants, particularly preterm, are often subjected to multiple painful needle procedures to collect sufficient blood for metabolic screening or diagnostic purposes using standard clinical tests. For example, at least 100 µL of whole blood is required to perform one creatinine plasma measurement with enzymatic colorimetric assays. As capillary electrophoresis-mass spectrometry (CE-MS) utilizing a sheathless porous tip interface only requires limited amounts of sample for in-depth metabolic profiling studies, the aim of this work was to assess the utility of this method for the determination of creatinine in low amounts of plasma using residual blood samples from adults and infants. By using a starting amount of 5 µL of plasma and an injection volume of only 6.7 nL, a detection limit (S/N = 3) of 30 nM could be obtained for creatinine, and intra- and interday precisions (for peak area ratios) were below 3.2%. To shorten the electrophoretic separation time, a multi-segment injection (MSI) strategy was employed to analyze up to seven samples in one electrophoretic run. The findings obtained by CE-MS for creatinine in pretreated plasma were compared with the values acquired by an enzymatic colorimetric assay typically used in clinical laboratories for this purpose. The comparison revealed that CE-MS could be used in a reliable way for the determination of creatinine in residual plasma samples from infants and adults. Nevertheless, to underscore the clinical efficacy of this method, a subsequent investigation employing an expanded pool of plasma samples is imperative. This will not only enhance the method's diagnostic utility but also contribute to minimizing both the amount and frequency of blood collection required for diagnostic purposes.

Attitudes and opinions about ecopharmacovigilance from multi-disciplinary perspectives: a cross-sectional survey among academic researchers in China.

As a promising upstream strategy to reduce the environmental loads of pharmaceutical emerging contaminants (PECs) through source control, ecopharmacovigilance (EPV) is concerned with the set of activities to identify, evaluate, understand, and prevent against diverse PEC-related problems, and has been accepted as a multi-disciplinary and multi-stakeholder system. This cross-sectional observational survey aimed to assess the attitudes and opinions about EPV from multi-disciplinary perspectives among Chinese academic professors from four main EPV-related disciplines including pharmacy, management, clinical medicine, and environmental and ecological science based on a self-developed questionnaire. Forty-two usable survey instruments were acquired. Results showed that the responding Chinese academic researchers from different disciplines expressed consistently positive attitudes and strong intentions for EPV, in spite of several disparities existing among disciplinary groups showing that pharmacy and medical researchers felt more certain of the environmental adverse effects of PECs, and researchers in pharmacy and environmental and ecological science were more interested in EPV. A multi-disciplinary consensus was achieved in regard to the types of key stakeholders in EPV practices including the pharmaceutical manufacturers, the public, the drug safety authority, hospitals, and the environmental protection agency. The main roles and responsibilities of each stakeholder identity in EPV practices were summarized based on the expert opinions.

Quantification of endocannabinoids in human cerebrospinal fluid using a novel micro-flow liquid chromatography-mass spectrometry method.

The endocannabinoid system (ECS) is implicated in various brain disorders. Changes in the composition of the cerebrospinal fluid (CSF) may be associated with ECS-related pathologies. Endocannabinoids (eCBs) and their analogues are present at low concentrations in human CSF, which hampered the investigation of the ECS in this body fluid. In this study, we developed a highly sensitive and selective micro-flow liquid chromatography-tandem mass spectrometry (micro-LC-MS/MS) method for the analysis of eCBs and eCB analogues in human CSF. The developed method allowed for the quantitative analysis of 16 eCBs and their analogues in human CSF. Micro-LC-MS/MS analyses were performed at a flow-rate of 4 µL min-1 with a 0.3-mm inner diameter column. A minor modification of a novel spray needle was carried out to improve the robustness of our method. By using an injection volume of 3 µL, our method reached limits of detection in the range from 0.6 to 1293.4 pM and limits of quantification in range from 2.0 to 4311.3 pM while intra- and interday precisions were below 13.7%. The developed workflow was successfully used for the determination of eCBs in 288 human CSF samples. It is anticipated that the proposed approach will contribute to a deeper understanding of the role of ECS in various brain disorders.

Spatial-resolved metabolomics reveals tissue-specific metabolic reprogramming in diabetic nephropathy by using mass spectrometry imaging.

Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy (DN) is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies. In the present study, a spatial-resolved metabolomics approach based on air flow-assisted desorption electrospray ionization (AFADESI) and matrix-assisted laser desorption ionization (MALDI) integrated mass spectrometry imaging (MSI) was proposed to investigate tissue-specific metabolic alterations in the kidneys of high-fat diet-fed and streptozotocin (STZ)-treated DN rats and the therapeutic effect of astragaloside IV, a potential anti-diabetic drug, against DN. As a result, a wide range of functional metabolites including sugars, amino acids, nucleotides and their derivatives, fatty acids, phospholipids, sphingolipids, glycerides, carnitine and its derivatives, vitamins, peptides, and metal ions associated with DN were identified and their unique distribution patterns in the rat kidney were visualized with high chemical specificity and high spatial resolution. These region-specific metabolic disturbances were ameliorated by repeated oral administration of astragaloside IV (100 mg/kg) for 12 weeks. This study provided more comprehensive and detailed information about the tissue-specific metabolic reprogramming and molecular pathological signature in the kidney of diabetic rats. These findings highlighted the promising potential of AFADESI and MALDI integrated MSI based metabolomics approach for application in metabolic kidney diseases.

Impact of the COVID-19 pandemic on household disinfectant consumption behaviors and related environmental concerns: A questionnaire-based survey in China.

Considering the potential hazardous effects of disinfectant residues on environment, organisms and biodiversity, the sharp rise in use of disinfectants during COVID-19 pandemic has been considered highly likely to cause worldwide secondary disasters in ecosystems and human health. This questionnaire-based survey investigated the impact of COVID-19 outbreak on household disinfectant product consumption levels and behavior of 3667 Chinese residents. In particular, in the context that no strategy is currently available to minimize the disinfectant pollution, based on the similarities between disinfectants and pharmaceuticals, we proposed a perspective of ecopharmacovigilance (EPV), which is an effective measure to minimize the environmental risks posed by pharmaceuticals using drug administration protocols, for disinfectant environmental risk management. The public's environmental perceptions, attitudes and the related practices regarding household disinfectant consumption from an EPV perspective were also included in the study. The results showed that the COVID-19 outbreak caused a tremendous rise in the public's household disinfectant consumption and usage levels in China. After the COVID-19 outbreak, the chlorine-based and alcohol-based disinfectants were considered as the most preferred products for household disinfection and hand sanitization, respectively. Importantly, the Chinese public's environmental perceptions and practice on disinfectants were poor. Less than half respondents had positive attitudes toward the source control of disinfectant pollution. The population groups including females, the middle aged adults, those having healthcare professional background, as well as the higher-educated could be focused on to develop targeted efforts for the future control of disinfectant pollution in environment.

Environmental knowledge, behaviors, and attitudes regarding caffeine consumption among Chinese university students from the perspective of ecopharmacovigilance.

Caffeine is considered the most representative pharmaceutical emerging contaminant (PEC) because of its ubiquity, high environmental abundance, uncovered ecological risks, and its indicator property for anthropogenic environmental inputs of PECs. Ecopharmacovigilance (EPV) targeting caffeine has been proposed as an optimized measure for the control of caffeine pollution sources and the related anthropogenic behaviors from the perspective of pharmacy administration. This cross-sectional study was conducted to evaluate the environmental knowledge, behaviors, and attitudes regarding caffeine consumption among university students, one of the groups with high caffeine consumption, from an EPV perspective. Three hundred and seven usable survey instruments were acquired. The mean score for environmental knowledge about caffeine consumption was 3.66 out of a total of 7. The consumption frequency of caffeinated drinks, food, or drugs among student respondents was low. Throwing away in "household garbage" was an important disposal mechanism for unconsumed caffeinated products. Most students showed positive attitudes and strong intentions toward caffeine pollution control from the perspective of targeted EPV. These data suggested high acceptance of EPV program targeting caffeine among university students. However, more should be done to enhance their related knowledge, and some strengthening interventions for the effective removal of residual caffeine in garbage are needed.

Targeted eco-pharmacovigilance as an optimized management strategy for adverse effects of pharmaceuticals in the environment.

From a perspective of drug administration, eco-pharmacovigilance (EPV) has been proposed as a new approach to prevent the environmental risks posed by pharmaceutical emerging contaminants. However, it is impracticable to practice unitary and rigor EPV process for all the pharmaceutical substances with complex and diversified chemical, biological or toxicological properties. We proposed the "targeted EPV" that is the science and activities associated with the targeted detection, evaluation, understanding, and prevention of adverse effects of high-priority hazardous pharmaceuticals in the environment, especially focusing on the control of main anthropogenic sources of pharmaceutical emission among key stakeholders in high-risk areas could be used as an optimized management strategy for pharmaceutical pollution. "Targeted EPV" implementation should focus on the targeted monitoring of the occurrence of high-priority pharmaceuticals in environmental samples, the targeted reporting of over-standard discharge, the targeted management for main emission sources, the targeted legislation and researches on high-priority pharmaceutical pollutants, as well as the targeted educational strategies for specific key populations.

In situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging.

Understanding of the nephrotoxicity induced by drug candidates is vital to drug discovery and development. Herein, an in situ metabolomics method based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was established for direct analysis of metabolites in renal tissue sections. This method was subsequently applied to investigate spatially resolved metabolic profile changes in rat kidney after the administration of aristolochic acid I, a known nephrotoxic drug, aimed to discover metabolites associated with nephrotoxicity. As a result, 38 metabolites related to the arginine-creatinine metabolic pathway, the urea cycle, the serine synthesis pathway, metabolism of lipids, choline, histamine, lysine, and adenosine triphosphate were significantly changed in the group treated with aristolochic acid I. These metabolites exhibited a unique distribution in rat kidney and a good spatial match with histopathological renal lesions. This study provides new insights into the mechanisms underlying aristolochic acids nephrotoxicity and demonstrates that AFADESI-MSI-based in situ metabolomics is a promising technique for investigation of the molecular mechanism of drug toxicity.

Chinese physicians' attitudes toward eco-directed sustainable prescribing from the perspective of ecopharmacovigilance: a cross-sectional study.

INTRODUCTION: Eco-directed sustainable prescribing (EDSP) is an effective upstream way to reduce the environmental footprints of active pharmaceutical ingredients (APIs), a kind of emerging contaminants, from the patients' excretion. EDSP is one of the key steps in the programme of ecopharmacovigilance (EPV), a drug administration route on API pollution. OBJECTIVE: To assess the attitudes of physicians prescribing medicines regarding EDSP from the perspective of EPV. DESIGN: A cross-sectional study conducted from March 2019 to June 2019. SETTING: 5 government general hospitals in Hubei province, China. PARTICIPANTS: 405 physicians were randomly selected and 262 valid questionnaires were obtained. OUTCOME MEASURES: A self-developed questionnaire, which inquired about the participant characteristics, perceptions and attitudes toward API pollution, EPV and EDSP from an EPV perspective, was emailed to collect data from physicians. RESULTS: Most physicians agreed the existence of APIs in environment, worried about the potential environmental and ecological risks of API residues, supported the effectiveness and necessity of EDSP under an EPV perspective in decreasing environmental exposure of excreted APIs, and showed their willingness to participate in the EDSP practices. Nevertheless, no respondent identified the environmental impacts as the aspects regarding medicines affecting his(her) prescription decision, none was satisfied with knowledge on EDSP and showed confidence toward EDSP. The most important barrier to the effective implementation of EDSP was identified as 'poor awareness of EDSP and EPV'. Most responding physicians (97%) reported that they held the wait-and-see or conservative attitudes towards EDSP practice. The biggest concerns in low-dose prescribing and prescribing of drugs possessing environment-friendly excretion profiles, two EDSP approaches, were the possible negative impact on therapeutic outcomes and too complicated and professional drug evaluation process, respectively. CONCLUSIONS: Chinese physicians had positive attitudes towards EDSP from the perspective of EPV. However, their environmental consciousness during prescribing and the related education were insufficient.

Protective effect of ethyl acetate fraction from Semen sojae germinatum, the processed sprout of Chinese black soybean, on rat experimental osteoarthritis.

BACKGROUND: Our previous in vitro study reported that the ethyl acetate fraction (EAF) of Semen sojae germinatum (SSG), the processed sprout of Chinese black soybean, possessed the potent anti-inflammatory and chondroprotective properties. The aim of the present work was to verify the in vivo antiosteoarthritic effect of EAF from SSG on a rat osteoarthritis (OA) model . METHODS: A classical rat OA model was surgically induced by anterior cruciate ligament transaction (ACLT). The OA rats were intra-articularly administered EAF from SSG for 8 weeks. The cartilage and synovial tissues were stained with hematoxylin and eosin (HE) to observe the histopathological changes. Safranin O/fast green staining was used to assess the glycosaminoglycan content in cartilage tissue sections. The expression of type II collagen and matrix metalloproteinase (MMP)-13 in cartilage was measured by immunohistochemistry. The apoptotic chondrocytes in the cartilage sections were detected using TUNEL assay. The concentrations of interleukin (IL)-1ß and tumor necrosis factor (TNF)-ɑ in synovial fluid were determined using ELISA. RESULTS: Intra-articular administration of EAF from SSG well retained the structure and superficial layer of cartilage tissues, ameliorated cartilage lesion and the degradation of cartilage matrix, including proteoglycan and type II collagen, induced by ACLT operation. The ACLT-induced upregulation of MMP-13 expression in the cartilage tissues was resisted by EAF from SSG. Moreover, EAF from SSG inhibited the ACLT-induced chondrocyte apoptosis. Compared to OA model group, the inflammatory status of synovial membrane was improved, the levels of inflammatory cytokines IL-1ß and TNF-ɑ in synovial fluid were decreased in rats administrated with EAF from SSG. CONCLUSION: These data suggested that EAF from SSG displayed in vivo protective effect on OA development via preventing the degeneration of articular cartilage, inhibiting chondrocyte apoptosis and suppressing synovial inflammation.

Occurrence of caffeine in the freshwater environment: Implications for ecopharmacovigilance.

Owing to the substantial consumption of caffeinated food, beverages, and medicines worldwide, caffeine is considered the most representative pharmaceutically active compound (PhAC) pollutant based on its high abundance in the environment and its suitability as an indicator of the anthropogenic inputs of PhACs in water bodies. This review presents a worldwide analysis of 132 reports of caffeine residues in freshwater environments. The results indicated that more than 70% of the studies reported were from Asia and Europe, which have densely populated and industrially developed areas. However, caffeine pollution was also found to affect areas isolated from human influence, such as Antarctica. In addition, the maximum concentrations of caffeine in raw wastewater, treated wastewater, river, drinking water, groundwater, lake, catchment, reservoir, and rainwater samples were reported to be 3.60 mg/L, 55.5, 19.3, 3.39, 0.683, 174, 44.6, 4.87, and 5.40 µg/L, respectively. The seasonal variation in caffeine residues in the freshwater environment has been demonstrated. In addition, despite the fact that there was a small proportion of wastewater treatment plants in which the elimination rates of caffeine were below 60%, wastewater treatment is generally believed to have a high caffeine removal efficiency. From a pharmacy perspective, we proposed to adopt effective measures to minimize the environmental risks posed by PhACs, represented by caffeine, through a new concept known as ecopharmacovigilance (EPV). Some measures of EPV aimed at caffeine pollution have been advised, as follows: improving knowledge and perceptions about caffeine pollution among the public; listing caffeine as a high-priority PhAC pollutant, which should be targeted in EPV practices; promoting green design and production, rational consumption, and environmentally preferred disposal of caffeinated medicines, foods, and beverages; implementing intensive EPV measures in high-risk areas and during high-risk seasons; and integrating EPV into wastewater treatment programs.

Pyrophosphate-fructose 6-phosphate 1-phosphotransferase (PFP1) regulates starch biosynthesis and seed development via heterotetramer formation in rice (Oryza sativa L.).

Pyrophosphate-fructose 6-phosphate 1-phosphotransferase (PFP1) reversibly converts fructose 6-phosphate and pyrophosphate to fructose 1, 6-bisphosphate and orthophosphate during glycolysis, and has diverse functions in plants. However, mechanisms underlying the regulation of starch metabolism by PFP1 remain elusive. This study addressed the function of PFP1 in rice floury endosperm and defective grain filling. Compared with the wild type, pfp1-3 exhibited remarkably low grain weight and starch content, significantly increased protein and lipid content, and altered starch physicochemical properties and changes in embryo development. Map-based cloning revealed that pfp1-3 is a novel allele and encodes the regulatory ß-subunit of PFP1 (PFP1ß). Measurement of nicotinamide adenine dinucleotide (NAD+) showed that mutation of PFP1ß markedly decreased its enzyme activity. PFP1ß and three of four putative catalytic α-subunits of PFP1, PFP1α1, PFP1α2, and PFP1α4, interacted with each other to form a heterotetramer. Additionally, PFP1ß, PFP1α1 and PFP1α2 also formed homodimers. Furthermore, transcriptome analysis revealed that mutation of PFP1ß significantly altered expression of many essential enzymes in starch biosynthesis pathways. Concentrations of multiple lipid and glycolytic intermediates and trehalose metabolites were elevated in pfp1-3 endosperm, indicating that PFP1 modulates endosperm metabolism, potentially through reversible adjustments to metabolic fluxes. Taken together, these findings provide new insights into seed endosperm development and starch biosynthesis and will help in the breeding of rice cultivars with higher grain yield and quality.

Risks of caffeine residues in the environment: Necessity for a targeted ecopharmacovigilance program.

Due to the huge consumption of caffeinated food, beverages and medicines around the world, caffeine has been considered as a most representative pharmaceutically active compound (PhAC) pollutant based on its high abundance in environment and its indicator property for anthropogenic inputs of PhACs to water bodies. This review analyzed the existing literature about the bioaccumulation and environmental risks of caffeine residues in non-target organisms. There are 6 studies which were published in the last 5 years have reported the distribution of caffeine in tissues of aquatic organisms including fishes, clams, macroalgae and other aquatic plants, suggesting bioaccumulation of caffeine in organisms. The maximum detected levels of caffeine residues in tissues ranged from 1.55 to 344.9 ng/g. Importantly, definitive evidences have been provided that environmentally relevant caffeine concentrations exert adverse impacts on aquatic species and terrestrial insects, which included lethality, decreasing general stress, inducing oxidative stress and lipid peroxidation, affecting energy reserves and metabolic activity, neurotoxic effects, affecting reproduction and development, etc. In view of the severity and potential adverse impacts of caffeine pollution in the environment, we proposed that caffeine should be considered as a high-priority environmentally hazardous PhAC pollutant, and it is necessary to implement an ecopharmacovigilance (EPV) program targeting caffeine to minimize its environmental load from a pharmacy perspective.

Using a targeted ecopharmacovigilance intervention to control antibiotic pollution in a rural aquatic environment.

The "targeted ecopharmacovigilance (EPV)" strategy emphasizes the control of environmental pollution by high-priority hazardous pharmaceuticals from principal pollution sources especially in areas that are high risk as a result of drug administration. We conducted a prospective empirical study to explore the possibility of using a targeted EPV intervention as an optimized management tool for the control of aquatic pollution by antibiotics, a common type of pharmaceutical residue, in a rural area in China. Because of the notably high levels of ofloxacin in the studied aquatic environment and the well-accepted environmental risks posed by fluoroquinolone residues, ofloxacin was selected as the targeted high-priority antibiotic pollutant. Based on the main sources of antibiotic pollution in the studied rural aquatic environment, which had been traced previously, a five-step targeted EPV intervention was designed and conducted from Feb 2018 to Jan 2019. The results showed that the residual levels of ofloxacin in the studied Chinese rural aquatic environment significantly decreased during the targeted EPV intervention. Importantly, the EPV measures targeting ofloxacin were found to effectively reduce the environmental pollution by other non-targeted antibiotics. The data from a survey of 45 participants (42 residents and 3 clinicians) and 12 program committee members revealed that the targeted EPV intervention was acceptable to both participants and organizers and could be used as an economical and feasible solution for addressing antibiotic pollution in aquatic environments.

Involvement of TLR4 in the protective effect of intra-articular administration of curcumin on rat experimental osteoarthritis.

PURPOSE: In view of the principal role of Toll-like receptor 4 (TLR4) in mediating sterile inflammatory response contributing to osteoarthritis (OA) pathogenesis, we used lipopolysaccharide (LPS), a known TLR4 activator, to clarify whether modulation of TLR4 contributed to the protective actions of intra-articular administration of curcumin in a classical rat OA model surgically induced by anterior cruciate ligament transection (ACLT). METHODS: The rats underwent ACLT and received 50µl of curcumin at the concentration of 1 mg mL-1 and 10 µg LPS by intra-articular injection once a week for 8 weeks. Morphological changes of the cartilage and synovial tissues were observed. Apoptotic chondrocytes were detected using TUNEL assay. The concentrations of IL-1ß and TNF-ɑ in synovial fluid were determined using ELISA kits. The mRNA and protein expression levels of TLR4 and NF-κB p65 were detected by real-time PCR and Western blotting, respectively. RESULTS: Intra-articular administration of curcumin significantly improved articular cartilage injury, suppressed synovial inflammation and down-regulated the overexpression of TLR4 and its downstream NF-κB caused by LPS-induced TLR4 activation in rat osteoarthritic knees. CONCLUSION: The data suggested that the inhibition of TLR4 signal might be an important mechanism underlying a protective effect of local curcumin administration on OA.

The impact of chronic environmental metal and benzene exposure on human urinary metabolome among Chinese children and the elderly population.

The health effects of metals and benzene exposure have been extensively investigated; however, information on the impact of chronic environmental metal and benzene exposure on human urinary metabolome is limited. In this study, a total of 566 participants, including 352 elderly and 214 children, were split into the "exposed" and "control" groups. The urine samples of all the participants were collected and stored at - 80 °C until analysis. The urinary levels of 17 metals and S-phenylmercapturic acid (S-PMA) were determined by the ICP-MS and LC-MS/MS methods to comprehensively assess the personal metal and benzene exposure levels, respectively. Then, the individual levels of metal and benzene exposure were correlated to the metabolic consequences of ambient pollutant exposure, which were previously observed in our metabolomics study. As a result, multiple metals, including Cd, Co, Cr, Cu, Fe, Hg, Li, Mo, Ni, Pb, Se, and Zn, exhibited a significant linear dose-dependent association with one or more urinary metabolites, including two amino acids (pyroglutamic acid and 3-methylhistidine), three organic acids (azelaic acid, decenedioic acid, and hydroxytetradecanedioic acid), ten medium-chainacylcarnitines (heptenedioylcarnitine, octenedioylcarnitine, nonenedioylcarnitine, decenedioylglucuronide, 3-hydroxydecanoylcarnitine, dodecanedioylcarnitine, nonanoylcarnitine, decadienylcarnitine, hydroxydodecenoylcarnitine, dodecadienylcarnitine, and dodecenoylcarnitine), and one glucuronide conjugate (decenedioylglucuronide). These observations indicate that the increased environmental metal exposure has caused various oxidative stress-related effects, including the depletion of antioxidants, accelerated muscle proteolysis, elevated activity of UGTs, increased lipid peroxidation, and the disorder of mitochondrial lipid metabolism among exposed children and the elderly. The current study provides new insights into the biological effects induced by metal exposure in the environment.

Involvement of TLR4 in the protective effect of intra-articular administration of curcumin on rat experimental osteoarthritis

Abstract Purpose In view of the principal role of Toll-like receptor 4 (TLR4) in mediating sterile inflammatory response contributing to osteoarthritis (OA) pathogenesis, we used lipopolysaccharide (LPS), a known TLR4 activator, to clarify whether modulation of TLR4 contributed to the protective actions of intra-articular administration of curcumin in a classical rat OA model surgically induced by anterior cruciate ligament transection (ACLT). Methods The rats underwent ACLT and received 50μl of curcumin at the concentration of 1 mg mL-1 and 10 μg LPS by intra-articular injection once a week for 8 weeks. Morphological changes of the cartilage and synovial tissues were observed. Apoptotic chondrocytes were detected using TUNEL assay. The concentrations of IL-1β and TNF-ɑ in synovial fluid were determined using ELISA kits. The mRNA and protein expression levels of TLR4 and NF-κB p65 were detected by real-time PCR and Western blotting, respectively. Results Intra-articular administration of curcumin significantly improved articular cartilage injury, suppressed synovial inflammation and down-regulated the overexpression of TLR4 and its downstream NF-κB caused by LPS-induced TLR4 activation in rat osteoarthritic knees. Conclusion The data suggested that the inhibition of TLR4 signal might be an important mechanism underlying a protective effect of local curcumin administration on OA.

Adapting and applying common methods used in pharmacovigilance to the environment: A possible starting point for the implementation  of eco-pharmacovigilance.

Now, the occurrence of pharmaceuticals in natural environment has been frequently reported around the world. As a kind of biologically active compounds specially designed to be effective even at very low concentration levels, pharmaceuticals in the environment could have adverse impacts to the health of human beings or other non-targeted organisms due to long-term exposures. To minimize the pharmaceutical pollution from the perspective of drug administration, a new concept called as eco-pharmacovigilance (EPV) has been proposed as a kind of pharmacovigilance(PV) for the environment. However, as a new and comprehensive science, EPV has not sophisticated methods in practice and formalized implementation model up to now. Since EPV is a special kind of PV, it could be feasible to draw on the experience of PV as a possible and reasonable starting point for EPV. In this paper, we discussed the common methods and activities used in PV including spontaneous reporting, intensive monitoring, database studies, and their potential applicability to the environment. And we concluded that these common methods in PV could be adapted and applied to EPV. But there is still the need for organizational, technical and financial supports of the EPV system.

Preliminary Clinical Evaluation of Acupuncture Therapy in Patients With Postpartum Sciatica.

INTRODUCTION: This study evaluated clinical outcomes following acupuncture treatment of postpartum sciatica. METHODS: One hundred eleven women with postpartum sciatica were enrolled in an acupuncture group (n = 86) or a control group (n = 25), according to their preference. Participants in the acupuncture group attended acupuncture therapy sessions 3 times a week for 4 weeks, while participants in the control group were assigned to bed rest. Outcome measures included the Roland Disability Questionnaire for sciatica, a visual analog scale for leg pain, and patient-reported perceived recovery. In addition, participants were surveyed after treatment to assess the acceptability of acupuncture therapy. RESULTS: The outcome scores for disability and leg pain were significantly lower in the acupuncture group compared with the control group (P < .05). All 86 women in the treatment group stated that acupuncture improved their well-being after treatment. At one month after treatment, 98% of participants in the treatment group reported recovery compared with 24% of the control group participants (P < .001). After treatment, 95% of lactating women in the acupuncture group believed that acupuncture had no significant interference with breast milk production. No adverse effects of acupuncture were reported. All participants in the acupuncture group stated they would choose acupuncture in case of relapse. However, the recurrence rate of sciatica in the acupuncture group (32%) was comparable to that of the control group (35%) at the one-year follow-up interview. DISCUSSION: Compared with bed rest, acupuncture might be an effective and acceptable strategy to relieve symptoms of postpartum sciatica.

Targeted eco-pharmacovigilance for ketoprofen in the environment: Need, strategy and challenge.

Implementing "targeted" eco-pharmacovigilance(EPV) which focuses on individual or specific pharmaceuticals on a prioritised basis is a feasible, economical and customized approach to reduce the environmental concentrations and risks of pharmaceuticals. Non-steroidal anti-inflammatory drugs(NSAIDs) remaining in environment are a kind of priority hazard substances, due to a notable case that diclofenac residues caused the loss of more than 99% of vultures across the Indian sub-continent. Ketoprofen, as another widely used NSAID with comparable or even higher global consumption than diclofenac, in the environment has been shown to present a potential risk to non-target terrestrial and aquatic species. Based on the review of 85 articles reporting the analyses of ketoprofen residues in environment since 2010, we found that this NSAID frequently present in various environmental compartments around the world. Therefore, it is urgent to implement EPV targeting ketoprofen pollution. Here, we provide some recommendations for implementing the targeted EPV for ketoprofen, including: Closely monitoring ketoprofen in the natural environment; Reducing the residues of ketoprofen through source control; Encouraging urine source separation and treatment; Limiting the application of veterinary ketoprofen; Designing and constituting a framework system of targeted EPV. But some challenges, such as ambiguity in the accountability of the main bodies responsible for continued monitoring of ketoprofen residues, the lack of optimized urine source separation scenarios and procedure, the need for detailed design and application schemes of the framework system of targeted EPV, etc. should be addressed.