Identification of 5,6-trans-epoxyeicosatrienoic acid in the phospholipids of red blood cells.

A novel eicosanoid, 5,6-trans-epoxy-8Z,11Z,14Z-eicosatrienoic acid (5,6-trans-EET), was identified in rat red blood cells. Characterization of 5,6-trans-EET in the sn-2 position of the phospholipids was accomplished by hydrolysis with phospholipase A(2) followed by gas chromatography/mass spectrometry as well as electrospray ionization-tandem mass spectrometry analyses. The electron ionization spectrum of 5,6-erythro-dihydroxyeicosatrienoic acid (5,6-erythro-DHET), converted from 5,6-trans-EET in the samples, matches that of the authentic standard. Hydrogenation of the extracted 5,6-erythro-DHET with platinum(IV) oxide/hydrogen resulted in an increase of the molecular mass by 6 daltons and the same retention time shift as an authentic standard in gas chromatography, suggesting the existence of three olefins as well as the 5,6-erythro-dihydroxyl structure in the metabolite. Match of retention times by chromatography indicated identity of the stereochemistry of the red blood cell 5,6-erythro-DHET vis à vis the synthetic standard. High pressure liquid chromatography-electrospray ionization-tandem mass spectrometry analysis of the phospholipase A(2)-hydrolyzed lipid extracts from red blood cells revealed match of the mass spectrum and retention time of the compound with the authentic 5,6-trans-EET standard, providing direct evidence of the existence of 5,6-trans-EET in red blood cells. The presence of other trans-EETs was also demonstrated. The ability of both 5,6-trans-EET and its product 5,6-erythro-DHET to relax preconstricted renal interlobar arteries was significantly greater than that of 5,6-cis-EET. In contrast, 5,6-cis-EET and 5,6-trans-EET were equipotent in their capacity to inhibit collagen-induced rat platelet aggregation, whereas 5,6-erythro-DHET was without effect. We propose that the red blood cells serve as a reservoir for epoxides which on release may act in a vasoregulatory capacity

Gastric Lavage in Acute Organophosphorus Pesticide poisoning (GLAOP) – a randomised controlled trial of multiple vs. single gastric lavage in unselected acute organophosphorus pesticide poisoning

BACKGROUND: Organophosphorus (OP) pesticide poisoning is the most common form of pesticide poisoning in many Asian countries. Guidelines in western countries for management of poisoning indicate that gastric lavage should be performed only if two criteria are met: within one hour of poison ingestion and substantial ingested amount. But the evidence on which these guidelines are based is from medicine overdoses in developed countries and may be irrelevant to OP poisoning in Asia. Chinese clinical experience suggests that OP remains in the stomach for several hours or even days after ingestion. Thus, there may be reasons for doing single or multiple gastric lavages for OP poisoning. There have been no randomised controlled trials (RCTs) to assess this practice of multiple lavages. Since it is currently standard therapy in China, we cannot perform a RCT of no lavage vs. a single lavage vs. multiple lavages. We will compare a single gastric lavage with three gastric lavages as the first stage to assess the role of gastric lavage in OP poisoning. METHODS/DESIGN: We have designed an RCT assessing the effectiveness of multiple gastric lavages in adult OP self-poisoning patients admitted to three Chinese hospitals within 12 hrs of ingestion. Patients will be randomised to standard treatment plus either a single gastric lavage on admission or three gastric lavages at four hour intervals. The primary outcome is in-hospital mortality. Analysis will be on an intention-to-treat basis. On the basis of the historical incidence of OP at the study sites, we expect to enroll 908 patients over three years. This projected sample size provides sufficient power to evaluate the death rate; and a variety of other exposure and outcome variables, including particular OPs and ingestion time. Changes of OP level will be analyzed in order to provide some toxic kinetic data. DISCUSSION: the GLAOP study is a novel, prospective cohort study that will explore to the toxic kinetics of OP and effects of gastric lavage on it. Given the poor information about the impact of gastric lavage on clinical outcomes for OP patients, this study can provide important information to inform clinical practice

ROS-dependent catalytic mechanism of melatonin metabolism and its application in the measurement of reactive oxygen

Melatonin (Mel) is an endogenous active molecule whose metabolism progress significantly influences its bioactivity. However, the detailed metabolic pathway of Mel in the pathological state has not yet been fully illustrated. In this study, 16 metabolites of Mel in cancer cells and human liver microsomes were identified, of which seven novel metabolites were newly discovered. Among them, 2-hydroxymelatonin (2-O-Mel), as the major metabolite in cancer cells, was revealed for the first time, which was different from the metabolite found in the human liver. Furthermore, CYP1A1/1A2- and reactive oxygen species (ROS)-mediated 2-hydroxylation reactions of Mel were verified to be the two metabolic pathways in the liver and cancer cells, respectively. ROS-dependent formation of 2-O-Mel was the major pathway in cancer cells. Furthermore, the underlying catalytic mechanism of Mel to 2-O-Mel in the presence of ROS was fully elucidated using computational chemistry analysis. Therefore, the generation of 2-O-Mel from Mel could serve as another index for the endogenous reactive oxygen level. Finally, based on the ROS-dependent production of 2-O-Mel, Mel was successfully used for detecting the oxygen-carrying capacity of hemoglobin in human blood. Our investigation further enriched the metabolic pathway of Mel, especially for the ROS-dependent formation of 2-O-Mel that serves as a diagnostic and therapeutic target for the rational use of Mel in clinics

Tannin extracts from immature fruits of Terminalia chebula Fructus Retz. promote cutaneous wound healing in rats

<p>Abstract</p> <p>Background</p> <p>Tannins extracted from immature fruits of <it>Terminalia chebula Fructus Retz</it>. are considered as effective components promoting the process of wound healing. The objective of this study is to explore the optimal extraction and purification technology (OEPT) of tannins, while studying the use of this drug in the treatment of a cutaneous wound of rat as well as its antibacterial effects.</p> <p>Methods</p> <p>The content of tannin extracts was measured by the casein method, and antibacterial ability was studied by the micro-dilution method in vitro. In wound healing experiment, animals in group Ⅰ, Ⅱ and Ⅲ were treated with vaseline ointment, tannin extracts (tannin content: 81%) and erythromycin ointment, respectively (5 mg of ointment were applied on each wound). To evaluate the process of wound healing, selected pharmacological and biochemical parameters were applied.</p> <p>Results</p> <p>After optimal extraction and purification, content of tannin extracts was increased to 81%. Tannin extracts showed the inhibition of <it>Staphylococcus aureus </it>and <it>Klebsiella Pneumonia </it>in vitro. After excision of wounds, on days 7 and 10, the percent of wound contraction of group Ⅱ was higher than that of group Ⅰ. After being hurt with wounds, on days 3, 7, and 10, the wound healing quality of group Ⅱ was found to be better than that of group Ⅰ in terms of granulation formation and collagen organization. After wound creation, on day 3, the vascular endothelial growth factor expression of group Ⅱ was higher than that of group Ⅰ.</p> <p>Conclusion</p> <p>The results suggest that tannin extracts from dried immature fruits of <it>Terminalia chebula Fructus Retz</it>. can promote cutaneous wound healing in rats, probably resulting from a powerful anti-bacterial and angiogenic activity of the extracts.</p

The Impact of Atmospheric Pollutants on Human Health and Economic Loss Assessment

The impact of air pollution on human health is becoming increasingly severe, and economic losses are a significant impediment to economic and social development. This paper investigates the impact of air pollutants on the respiratory system and its action mechanism by using information on inpatients with respiratory diseases from two IIIA (highest) hospitals in Wuhan from 2015 to 2019, information on air pollutants, and meteorological data, as well as relevant demographic and economic data in China. This paper describes the specific conditions of air pollutant concentrations and respiratory diseases, quantifies the degree of correlation between the two, and then provides a more comprehensive assessment of the economic losses using descriptive statistical methods, the generalized additive model (GAM), cost of illness approach (COI), and scenario analysis. According to the findings, the economic losses caused by PM2.5, PM10, SO2, NO2, and CO exposure are USD 103.17 million, USD 70.54 million, USD 98.02 million, USD 40.35 million, and USD 142.38 million, for a total of USD 454.46 billion, or approximately 0.20% of Wuhan&rsquo;s GDP in 2019. If the government tightens control of major air pollutants and meets the WHO-recommended criterion values, the annual evitable economic losses would be approximately USD 69.4 million or approximately 0.03% of Wuhan&rsquo;s GDP in 2019. As a result, the relevant government departments must strengthen air pollution control to mitigate the impact of air pollution on population health and the associated economic losses

Multiobjective Reinforcement Learning for Traffic Signal Control Using Vehicular Ad Hoc Network

We propose a new multiobjective control algorithm based on reinforcement learning for urban traffic signal control, named multi-RL. A multiagent structure is used to describe the traffic system. A vehicular ad hoc network is used for the data exchange among agents. A reinforcement learning algorithm is applied to predict the overall value of the optimization objective given vehicles' states. The policy which minimizes the cumulative value of the optimization objective is regarded as the optimal one. In order to make the method adaptive to various traffic conditions, we also introduce a multiobjective control scheme in which the optimization objective is selected adaptively to real-time traffic states. The optimization objectives include the vehicle stops, the average waiting time, and the maximum queue length of the next intersection. In addition, we also accommodate a priority control to the buses and the emergency vehicles through our model. The simulation results indicated that our algorithm could perform more efficiently than traditional traffic light control methods.</p

Application of comprehensive pharmaceutical care program in identifying and addressing drug-related problems in hospitalized patients with osteoporosis

Abstract Background More information about the impacts of comprehensive pharmaceutical care program (CPCP) on the identification and resolution of drug-related problems (DRPs) is needed. This study aimed at researching the characteristics of DRPs in osteoporosis patients and evaluating the effect of CPCP in identifying and addressing DRPs. Methods We performed a prospective interventional study in a teaching hospital. CPCP was established and conducted to identify and resolve DRPs by a multidisciplinary team (MDT) based on the Pharmaceutical Care Network Europe (PCNE) classification V9.0. Six pharmacists and one doctor worked directly in the study. All data was obtained from electronic medical records, direct observation and visits. The statistical analyses were performed using the SPSS Statistics software version 26.0. Results Two hundred nineteen patients with osteoporosis were included in the final analysis. A total of 343 DRPs were identified, with an average of 1.57 DRPs per patient. The most common DRPs identified were “treatment safety P2” (66.8%; 229/343), followed by “other P3” (21.0%; 72/343) and “treatment effectiveness, P1” (12.2%; 42/343). The primary causes of DRPs were “dose selection C3” (35.9%; 211/588), followed by “drug use process C6” (28.9%; 170/588) and “drug selection C1” (12.6%; 74/588). Seven hundred eleven interventions were proposed to address the 343 DRPs, with an average of 2.1 interventions per DRP. The acceptance rate reached 95.9, and 91.0% of these accepted interventions were fully implemented. As a result, only 30 DRPs were unsolved before discharge. Additionally, the number of drugs was found to be associated with the number of DRPs significantly (p = 0.023). Conclusion DRPs frequently occurred in hospitalized osteoporosis patients. CPCP could be an effect option to solve and reduce DRPs for osteoporosis patients and should be implemented widely to increase patient safety

The Impact of Atmospheric Pollutants on Human Health and Economic Loss Assessment

The impact of air pollution on human health is becoming increasingly severe, and economic losses are a significant impediment to economic and social development. This paper investigates the impact of air pollutants on the respiratory system and its action mechanism by using information on inpatients with respiratory diseases from two IIIA (highest) hospitals in Wuhan from 2015 to 2019, information on air pollutants, and meteorological data, as well as relevant demographic and economic data in China. This paper describes the specific conditions of air pollutant concentrations and respiratory diseases, quantifies the degree of correlation between the two, and then provides a more comprehensive assessment of the economic losses using descriptive statistical methods, the generalized additive model (GAM), cost of illness approach (COI), and scenario analysis. According to the findings, the economic losses caused by PM2.5, PM10, SO2, NO2, and CO exposure are USD 103.17 million, USD 70.54 million, USD 98.02 million, USD 40.35 million, and USD 142.38 million, for a total of USD 454.46 billion, or approximately 0.20% of Wuhan’s GDP in 2019. If the government tightens control of major air pollutants and meets the WHO-recommended criterion values, the annual evitable economic losses would be approximately USD 69.4 million or approximately 0.03% of Wuhan’s GDP in 2019. As a result, the relevant government departments must strengthen air pollution control to mitigate the impact of air pollution on population health and the associated economic losses