Despite the high efficiency of remote sensing methods for rapid and large-scale detection of subsidence phenomena,this technique has limitations such as atmospheric impact and temporal and spatial decorrelation that a...Despite the high efficiency of remote sensing methods for rapid and large-scale detection of subsidence phenomena,this technique has limitations such as atmospheric impact and temporal and spatial decorrelation that affect the accuracy of the results.This paper proposes a method based on an artificial neural network to improve the results of monitoring land subsidence due to groundwater overexploitation by radar interferometry in the Aliabad plain(Central Iran).In this regard,vertical ground deformations were monitored over 18 months using the Sentinel-1A SAR images.To model the land subsidence by a multilayer perceptron(MLP)artificial neural network,four parameters,including groundwater level,alluvial thickness,elastic modulus,and transmissivity have been applied.The model's generalizability was assessed using data derived for 144 days.According to the results,the neural network estimates the land subsidence at each ground point with an accuracy of 6.8 mm.A comparison between the predicted and actual values indicated a significant agreement.The MLP model can be used to improve the results of subsidence detection in the study area or other areas with similar characteristics.展开更多
Phenibut(β-phenyl-γ-aminobutyric acid)is a psychoactive gamma-aminobutyric acid(GABA)analog marketed online as a nutritional and nootropic(cognition enhancing)supplement.Phenibut consumption poses a high risk of pot...Phenibut(β-phenyl-γ-aminobutyric acid)is a psychoactive gamma-aminobutyric acid(GABA)analog marketed online as a nutritional and nootropic(cognition enhancing)supplement.Phenibut consumption poses a high risk of potential abuse.Withdrawal from phenibut mimics benzodiazepine and alcohol withdrawal and can be dangerous.A number of approaches have been described for phenibut withdrawal,including protocols that include baclofen,but for inpatient and outpatient use.Here we describe a 30-year-old male who presented to an emergency department(ED)with insomnia,anxiety and palpitations after he stopped taking phenibut.展开更多
The effective use of land in Northeast China is of great significance for ensuring national food security and regional rural revitalization.In this study,based on the survey data collected from Jilin Province,Northeas...The effective use of land in Northeast China is of great significance for ensuring national food security and regional rural revitalization.In this study,based on the survey data collected from Jilin Province,Northeast China,we analyzed the vacancy rates of rural homesteads in suburban,outer suburban,and remote villages,as well as the withdrawal intention of rural-settled farmers,urbansettled farmers,and farmers with urban and rural dual residency from vacant homesteads.From the perspective of farmers’perceptions,this study constructed a theoretical framework of the influence mechanism of their withdrawal intention and analyzed such mechanism by constructing a structural equation model.The results indicated that:1)rural homestead vacancy rates increased with distance from the village to the city.2)rural-settled farmers showed a low withdrawal intention for vacant rural homesteads,followed by urban and rural dual-residence farmers,and urban-settled farmers showed the highest withdrawal intention.3)the relative importance of the factors influencing withdrawal intention is in the following order:policy awareness>interest perception>living environment perception>family characteristics.Finally,this study discussed the reformation of the homestead system and rural homestead transition in Northeast China,which can provide policy support to increase the potential of cultivated land and promote sustainable rural development and urban-rural coordination.展开更多
In order to grasp the relationship between farmers'willingness and behavior to withdraw from rural homesteads,based on the theory of planned behavior,a survey was conducted in Jizhou District,Tianjin using conveni...In order to grasp the relationship between farmers'willingness and behavior to withdraw from rural homesteads,based on the theory of planned behavior,a survey was conducted in Jizhou District,Tianjin using convenience sampling method.A total of 443 valid questionnaires were collected and they were analyzed by SPSS.The results are as follows.(i)The willingness of farmers to withdraw from rural homesteads is affected by pre-cognitive factors such as behavioral attitude,subject norm and perceived behavior control.(ii)Among the benefits that can be brought by the withdrawal of homesteads,farmers value the improvement of the housing environment the most.(iii)Family members'view and relatives and neighbors'withdrawing from homesteads also exerts greater pressure on farmers.(iv)Farmers generally lack trust in the village committees or government departments'claims.(v)The cost of relocation also restricts the perceived behavior control of farmers'homesteads withdrawing.Based on above result,the following suggestions are made:strengthening policy publicity,raising farmers'awareness of policies related to the withdrawal of homesteads,fully respecting farmers'wishes,promoting the withdrawal of rural homesteads in an orderly manner,expanding the scope of compensation for withdrawal of rural homesteads,and enriching compensation methods.展开更多
Two tests initiated by unscrammed control rod withdrawal were performed on the High Temperature GasCooled Reactor-Test Module(HTR-10) in November 2003 after the reactor achieved its full power, and the test conditions...Two tests initiated by unscrammed control rod withdrawal were performed on the High Temperature GasCooled Reactor-Test Module(HTR-10) in November 2003 after the reactor achieved its full power, and the test conditions represented a typical transient scenario of modular high-temperature reactors(HTRs), called pressurized loss of forced cooling, and anticipated transient without scram.Based on the test parameters, the HTR-10 thermal behaviors under the test conditions were studied with the help of the system analysis code THERMIX. The combination of the test results and the investigation results makes the HTR-10 safety potential better understood. Key phenomena, such as the helium natural circulation and the temperature redistribution in the reactor, were revealed. As the safety feature of most significance, there is a large margin between the maximum fuel temperature and its safety limit in each test. Temperatures of thermocouples in different components were calculated by THERMIX and compared with the test values. The applicability of the code was verified by good agreement obtained from the comparison.展开更多
The global community has prepared for the withdrawal of the U.S. from the Paris Agreement since Donald Trump was elected as the president of the U.S. However, Trump's formal declaration of withdrawal still caused ...The global community has prepared for the withdrawal of the U.S. from the Paris Agreement since Donald Trump was elected as the president of the U.S. However, Trump's formal declaration of withdrawal still caused worldwide reaction. Trump will use the withdrawal to build his political reputation and to renegotiate the Paris Agreement despite its negative effects on the political credibility, international relationships, and potential long-term economic growth of the U.S. In general, the withdrawal of the U.S. from the Paris Agreement will not change the development of low-carbon technologies and the transformation trend of the global climate governance regime. However, the long-term goals and international cooperation on climate change will be affected by budget cuts in American climate change research and the cancelation of donations from the multilateral environmental fund of the U.S. If the Paris Agreement is renegotiated, the common but differentiated principle of responsibility of the United Nations Framework Convention on Climate Change will be challenged again. Nevertheless, climate change governance remains a main theme of future sustainable development. Instead of national governments, local governments and non-governmental organizations will develop strategies for technical innovation and emphasize pragmatic cooperation, thus expanding their roles in climate change governance. The capacity building on climate change research and public awareness should be enhanced as a long-term objective of global climate change governance.展开更多
Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel disease.However, this treatment is associated with high costs and the possibility of severe adverse events represent...Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel disease.However, this treatment is associated with high costs and the possibility of severe adverse events representing a true challenge for patients, clinicians and health care systems.Consequently, a crucial question is raised namely if therapy can be stopped once remission is achieved and if so, how and in whom.Additionally, in a real-life clinical setting, discontinuation may also be considered for other reasons such as the patient's preference, pregnancy, social reasons as moving to countries or continents with less access, or different local policy or reimbursement.In contrast to initiation of anti-TNFα therapy guidelines regarding stopping of this treatment are missing.As a result, the decision of discontinuation is still a challenging aspect in the use of anti-TNFα therapy.Currently this is typically based on an estimated, case-by-case, benefit-risk ratio.This editorial is intended to provide an overview of recent data on this topic and shed light on the proposed drug withdrawal strategies.展开更多
BACKGROUND: Following morphine withdrawal, anxiety is associated with abnormal norepinephrine content change. However, increasing blood lactic acid content can induce anxiety or panic in patients with anxiety disorde...BACKGROUND: Following morphine withdrawal, anxiety is associated with abnormal norepinephrine content change. However, increasing blood lactic acid content can induce anxiety or panic in patients with anxiety disorder or endogenous opioid peptide functional disorder. OBJECTIVE: This study was designed to observe the effects of electro-acupuncture, at the "Sanyinjiao" point (SP 6), on brain tissue norepinephrine and blood lactic acid content in anxiety-model mice after morphine withdrawal. DESIGN: A randomized controlled animal experiment. SETTING: This study was performed in the Laboratory of Acupuncture, Electro-acupuncture & Tuina College, Chengdu University of Traditional Chinese Medicine, from June to September 2001. MATERIALS: A total of 50 healthy Kunming male mice were provided by the Laboratory Animal Center of Chengdu University of Traditional Chinese Medicine. The protocol was performed in accordance with ethical guidelines stated in the Guide for the use and care of laboratory animals, approved by the Committee on the Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources Commission on Life Sciences, National Research Council, China (1985). Experimental reagents and equipment used were as follows: morphine hydrochloride (Lot No. 930503, Shenyang No.1 Pharmaceutical Factory, China), norepinephrine (Sigma Chemical Company, USA), fluorospectrophotometer (RF-510, Shimadzu Corporation, Japan), Han electro-acupuncture apparatus (WQ 1002, No. zun (91)-227270-588, Beijing Anlong Photoelectricity-Technique Company, China), and T-maze (self-made). METHODS: A total of 50 mice were randomly divided into 5 groups, with 10 mice in each group: blank control, T-maze, model, model + electro-acupuncture, and electro-acupuncture groups. Establishment of anxiety model after morphine withdrawal: the mouse hot plate assay was used to detect the activity of morphine. The median effective dose of morphine, 2.95 mg/kg, was defined as the base. Mice were subcutaneously administered morphine, 3 times a day, for 4 days successively (initially 2.95 mg/kg, then increased day by day, as described below). Interventions: In the model + electro-acupuncture group, after model induction, mice were subjected electro-acupuncture at bilateral "Sanyinjiao" (SP6) points using a Han electro-acupuncture apparatus with sparse-dense waves and frequency of 2-100 Hz, once a day, for 6 days. In the model group, after anxiety-model induction, mice were subjected to fixation as same as model + electro-acupuncture group within 6 days of model induction. In the electro-acupuncture group, the anxiety model was not induced and mice were subjected to fixation, electro-acupuncture and the T-maze test. In the T-maze group, the anxiety model was not induced and mice were subjected to fixation. The T-maze test was performed in the 4 groups after experiment. In the blank control group, the anxiety model was not induced and mice were subjected to fixation only. MAIN OUTCOME MEASURES: Brain tissue norepinephrine content of morphine-withdrawal anxiety mice was detected by fluorospectrophotometry after 6 days of electro-acupuncture. Blood lactic acid content was detected by visible spectrophotometry. RESULTS: A total of 50 mice were included in the final analysis. Brain norepinephrine content was significantly greater in the model group compared to the T-maze, blank control, electro-acupuncture and model + electro-acupuncture groups, (P 〈 0.05-0.01). Brain norepinephrine content was similar between the model + electro-acupuncture and the blank control groups (P 〉 0.05). There was no significant difference in blood lactic acid content among the groups (P 〉 0.05). CONCLUSION: Electro-acupuncture lowers brain norepinephrine content but does not influence peripheral blood lactic acid content in morphine-withdrawn, anxiety-modeled mice. These results demonstrate that anxiety-inhibiting effects of electro-acupuncture, after morphine withdrawal, might be related to regulation of norepinephrine release.展开更多
Anti-virus prophylactic therapy may be not nec- essary for the prevention of hepatitis B virus (HBV) recur- rence after HBV-related liver transplantation (LT). However, studies on completely stopping the hepatitis...Anti-virus prophylactic therapy may be not nec- essary for the prevention of hepatitis B virus (HBV) recur- rence after HBV-related liver transplantation (LT). However, studies on completely stopping the hepatitis B immune globu- lin (HBIG) and nucleos(t)ide analogs (NUC) after LT are few. The aim of the current study was to evaluate the safety of anti- virus prophylaxis withdrawal in liver recipients whose serum hepatitis B e antigen (HBeAg) and HBV DNA are negative. We analyzed 190 patients undergone LT for HBV-related liver dis- ease from 2006 to 2012 and found that 10 patients completely stopped the HBIG and NUC due to poor compliance. These patients were liver biopsied and checked monthly with serum HBV markers, HBV DNA and liver function. Among the 10 patients, 9 did not show the signs of HBV recurrence after a mean follow-up of 51.6 months (range 20-73) after with- drawal of the HBIG and NUC. The average time from LT to the withdrawal of the anti-virus drug was 23.8 (13-42) months; one patient showed hepatitis B surface antigen-positive and detectable HBV DNA after stopping anti-virus drugs and this patient was successfully treated with entecavir. Our data sug- gested that complete withdrawal of anti-virus prophylaxis was safe and feasible for patients whose serum HBeAg and HBV DNA were negative at the time of LT.展开更多
Based on the Computable General Equilibrium (CGE) model and scenario analysis, the impacts of the U.S. withdrawal from the Paris Agreement on the carbon emission space and mitigation cost in China, European Union (EU)...Based on the Computable General Equilibrium (CGE) model and scenario analysis, the impacts of the U.S. withdrawal from the Paris Agreement on the carbon emission space and mitigation cost in China, European Union (EU), and Japan are assessed under Nationally Determined Contributions (NDCs) and 2 C scenarios due to the changed emission pathway of the U.S. The results show that, under the condition of constant global cumulative carbon emissions and a fixed burden-sharing scheme among countries, the failure of the U.S. to honor its NDC commitment to different degrees will increase the U.S. carbon emission space and decrease its mitigation cost. However, the carbon emission space of other parties, including China, EU, and Japan, will be reduced and their mitigation costs will be increased. In 2030, under the 2 C target, the carbon price will increase by 4.4e14.6 US$ t1 in China, by 9.7e35.4 US$ t1 in the EU, and by 16.0e53.5 US$ t1 in Japan. In addition, China, EU, and Japan will incur additional Gross Domestic Production (GDP) loss. Under the 2 C target, the GDP loss of China would increase by US$22.0e71.1 billion (equivalent to 16.4e53.1 US$ per capita), the EU's GDP loss would increase by US$9.4e32.1 billion (equivalent to 20.7e71.1 US$ per capita), and Japan's GDP loss will increase by US$4.1e13.5 billion (equivalent to 34.3e111.6 US$ per capita).展开更多
BACKGROUND: Immunosuppression reagents have side effects and cause considerable long-term morbidity and mortality in patients after liver transplantation. Sufficient evidences showed that minimization or withdrawal o...BACKGROUND: Immunosuppression reagents have side effects and cause considerable long-term morbidity and mortality in patients after liver transplantation. Sufficient evidences showed that minimization or withdrawal of immunosuppression reagents does not deteriorate the recipient's immune response and physiological function and therefore, is feasible in some recipients of liver transplantation. However, the mechanisms are not clear. The present review was to update the current status of immunosuppression in liver transplantation and the mechanism of minimization or withdrawal of immunosuppression in liver recipients.DATA SOURCES: We searched articles in English on minimization or withdrawal of immunosuppression in liver transplantation in Pub Med. We focused on the basic mechanisms of immune tolerance in liver transplantation. Studies on immunosuppression minimization or withdrawal protocols and biomarker in tolerant recipients were also analyzed.RESULTS: Minimization or withdrawal of immunosuppression can be achieved by the induction of immune tolerance, which may not be permanent and can be affected by various factors. However, accurately evaluating immune status post-transplant is a prerequisite to achieve individualized immunosuppression. Numerous mechanisms for immune tolerance have been found, including immunophenotypic shift of memory CD8+ T cells and CD4+ T cell subsets. Activation of the inflammasome through apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain(ASC) in dendritic cells is associated with rejection after liver transplantation. CONCLUSIONS: Minimization or withdrawal of immunosuppression can be achieved by the induction of immune toler-ance via different mechanisms. This process could be affected by immunophenotypic shift of memory CD8+ T cells and CD4+ T cell subsets, which may be correlated with activation of the inflammasome through ASC in dendritic cells.展开更多
In this study, we consider the heat-induced withdrawal reflex caused by exposure to an electromagnetic beam. We propose a concise dose-response relation for predicting the occurrence of withdrawal reflex from a given ...In this study, we consider the heat-induced withdrawal reflex caused by exposure to an electromagnetic beam. We propose a concise dose-response relation for predicting the occurrence of withdrawal reflex from a given spatial temperature profile. Our model is distilled from sub-step components in the ADT CHEETEH-E model developed at the Institute for Defense Analyses. Our model has only two parameters: the activation temperature of nociceptors and the critical threshold on the activated volume. When the spatial temperature profile is measurable, the two parameters can be determined from test data. We connect this dose-response relation to a temperature evolution model for electromagnetic heating. The resulting composite model governs the process from the electromagnetic beam deposited on the skin to the binary outcome of subject’s reflex response. We carry out non-dimensionalization in the time evolution model. The temperature solution of the non-dimensional system is the product of the applied power density and a parameter-free function. The effects of physical parameters are contained in non-dimensional time and depth. Scaling the physical temperature distribution into a parameter-free function greatly simplifies the analytical solution, and helps to pinpoint the effects of beam spot area and applied power density. With this formulation, we study the theoretical behaviors of the system, including the time of reflex, effect of heat conduction, biological latency in observed reflex, energy consumption by the time of reflex, and the strategy of selecting test conditions in experiments for the purpose of inferring model parameters from test data.展开更多
Methylene blue (MB), a tricyclic phenothiazine drug, has been reported to enhance mitochondrial functions including mitochondrial respiration. By comparison, stress associated with abrupt ethanol withdrawal (EW) imped...Methylene blue (MB), a tricyclic phenothiazine drug, has been reported to enhance mitochondrial functions including mitochondrial respiration. By comparison, stress associated with abrupt ethanol withdrawal (EW) impedes mitochondrial functions. We investigated whether MB protects mitochondrial respiration and cell survival from EW stress through a key mitochondrial enzyme, cytochrome c oxidase (COX). We also investigated whether the MB’s protection involves the inhibition of an excitatory neurotransmitter, glutamate. Male rats were exposed to and withdrawn from ethanol-diet (7.5%, 5 weeks). MB (0.5 mg/kg, intraperitoneal) was injected for the last 5 days of ethanol-diet and on the first day of EW. Cerebellum was then harvested to measure mitochondrial respiration and COX expression using real-time XF respirometer and immunohistochemistry, respectively. Separately, HT22 cells (a murine hippocampal cell line) were exposed to and abruptly withdrawn for 4 hours from chronic ethanol (100 mM, 3 days). MB was administered during EW with or without a COX inhibitor (NaN3) or glutamate. Mitochondrial respiration, COX content, and cell viability were then assessed using real-time XF respirometer, an immunoblot method, and Calcein assay, respectively. MB attenuated the suppressing effects of EW on mitochondrial respiration, COX content, and cell survival. This protection was reduced after NaN3 or glutamate cotreatment. These results suggest that MB treatment help maintain mitochondrial respiratory and cellular integrity through COX-upregulation and glutamateinhibition upon EW stress. MB treatment may help identify mitochondrial mechanisms underlying hyperexcitatory CNS disorders.展开更多
To study steroid withdrawal in immunosuppresion after liver transplantation (LTx).Methods Fifty-eight consecutive patients undergoing primary LTx,under cyclosporine and steroid immunosuppresion,10 additional patients ...To study steroid withdrawal in immunosuppresion after liver transplantation (LTx).Methods Fifty-eight consecutive patients undergoing primary LTx,under cyclosporine and steroid immunosuppresion,10 additional patients treated with mycophemolate mofetil (MMF),were included in this study.If there was no evidence of rejection and the patient’s liver function tests were nearly normal,the steroid weaning process started 2 to 3 weeks after LTx.Results During a mean follow-up period of 9.3±5.5 months after LTx,54 patients survived and 4 died.Steroids could be withdrawn in 72.2% patients at 3rd month post-transplant,in 76.2% at 6th month and in 77.8% at first year,respectively.In 3 patients with rejection after steroid withdrawal,the steroid dose before withdrawal was given.After the rejection was reversed the steroid was withdrawn.Freedom from steroids was thus observed in 10 additional patients treated with MMF at 3rd to 4th month post-transplant.Conclusion Cyclosporine-based immunosuppression allows safe early steroid withdrawal in some patients of LTx.3 refs,1 tab.展开更多
BACKGROUND: Studies have demonstrated that exogenous neurosteroid treatment prevents the development of morphine tolerance and dependence, and attenuates abstinence behavior in mice. However, there are few studies on...BACKGROUND: Studies have demonstrated that exogenous neurosteroid treatment prevents the development of morphine tolerance and dependence, and attenuates abstinence behavior in mice. However, there are few studies on whether the levels of endogenous neurosteroids can be changed by morphine dependence and withdrawal. OBJECTIVE: To investigate the levels of various neurosteroids in rat brain following morphine dependence and withdrawal. To evaluate the expressions of steroidogenic enzyme mRNAs and proteins. To identify the relationship between neurosteroids and morphine dependence at the whole animal behavior, neural biochemistry, and molecular levels. DESIGN, TIME AND SETTING: A randomized, controlled study. Experiments were performed at the Department of Pharmacology of Hebei Medical University and Department of Pharmacology of Beathune International Peace Hospital, China, from June 2004 to October 2007. MATERIALS: Morphine hydrochloride injection (Shenyang First Pharmaceutical Factory, China), naloxone hydrochloride (Hunan Yiqiao Pharmaceutical Co., China) and a gas chromatography-mass spectrometry system (Agilent, CA, USA) were used in this study. METHODS: Healthy adult Sprague Dawley rats were randomly divided into three groups: a morphine dependence group, morphine withdrawal group and control group (n = 20). The rats in the morphine dependence and morphine withdrawal groups were given increasing doses of morphine (5, 10, 15, 20, 30, 40 and 50 mg/kg, intraperitoneal) to create morphine dependence. The rats in the morphine withdrawal group were injected with 2 mg/kg naloxone to precipitate withdrawal 1 hour after the last morphine injection. Rats in the control group were treated with an equal volume of saline. MAIN OUTCOME MEASURES: Following morphine dependence and withdrawal, brain levels of the neurosteroids pregnenolone, progesterone and allopregnanolone were analyzed using gas chromatography-mass spectrometry. The mRNA expression of two key steroidogenic enzymes, P450 side-chain cleavage enzyme (P450scc) and 3[B-hydroxysteroid dehydrogenase (313-HSD), were determined in rat brain regions using reverse transcription-polymerase chain reaction. The distribution and expression of P450scc protein were visualized in brain regions associated with addiction by immunohistochemistry. RESULTS: In brain tissue from the morphine dependence group, the levels of pregnenolone and progesterone were decreased by 62% (P 〈 0.01) and 92% (P 〈 0.01 ) respectively, compared with the control group. In the morphine dependence group, the key steroidogenic enzyme P450scc mRNA was decreased in striatum (P 〈 0.05), while 3-HSD mRNA was decreased in amygdala (P 〈 0.05), striatum (P 〈 0.05) and frontal cortex (P 〈 0.05) compared with the control group. Morphine withdrawal induced a significant increase in the neurosteroid levels compared with the control group (P 〈 0.01). However, there was no significant difference in the expressions of P450scc and 36-HSD mRNAs between the morphine withdrawal and control groups (P 〉 0.05). CONCLUSION: The neurosteroid levels and expressions of steroidogenic enzymes changed similarly in morphine dependent rats, suggesting that the morphine dependence-induced decrease in neurosteroids might depend on local expression of steroidogenic enzymes in the central nervous system. However, the changes in neurosteroids in morphine withdrawal rats were not in accordance with the changes in the expression of steroidogenic enzymes, suggesting that the effects of morphine withdrawal on brain neurosteroid levels may not depend primarily on the local expression of steroidogenic enzymes in the central nervous system.展开更多
Aim: To determine whether testosterone is involved in morphine withdrawal syndrome (WS). Methods: In order to induce dependency, rats were treated with subcutaneous injection of morphine (days 1-2, 5 mg/kg; days ...Aim: To determine whether testosterone is involved in morphine withdrawal syndrome (WS). Methods: In order to induce dependency, rats were treated with subcutaneous injection of morphine (days 1-2, 5 mg/kg; days 3-5, 7.5 mg/kg; days 6-8, 10 mg/kg), and after the last dose of morphine (day 8) WS was induced by intraperitoneal injection of naloxone (1 mg/kg). Wet dog shake (WDS), abdomen writhing (AW), and jumps (J) were recorded as indicators of WS. Results: The severity of WDS, AW, and J in male rats was greater than that in females. Accordingly, in 4-week castrated and flutamide-treated (10 mg/kg/day for 8 days, i.p.) male rats, WDS, AW, and J were significantly decreased compared to male control rats. Testosterone replacement therapy (10 mg/kg/day for 8 days, i.m.) in 4-week castrated rats restored the severity of WDS, AW, and J behaviors to the level of non-castrated male rats, whereas testosterone potentiated the WDS behavior in non-castrated male rats. Conclusion: It can be concluded that testosterone might be effectively involved in morphine WS.展开更多
The present study analyzed the effects of Sidiming, a Chinese herbal compound, on withdrawal syndrome, body weight loss, and serum levels of nitric oxide and its synthase in morphine- dependent rats and rhesus monkeys...The present study analyzed the effects of Sidiming, a Chinese herbal compound, on withdrawal syndrome, body weight loss, and serum levels of nitric oxide and its synthase in morphine- dependent rats and rhesus monkeys. These effects were compared with clonidine, an active control drug used for clinical treatment. Results showed that 4 and 8 g/kg Sidiming, respectively, significantly suppressed morphine withdrawal syndrome and reduced body mass loss in morphine-dependent rats. In addition, 2.4 and 4.8 g/kg Sidiming, respectively, significantly attenuated withdrawal syndrome in rhesus monkeys. High-dose Sidiming (8 g/kg in rats and 4.8 g/kg in rhesus monkeys) led to significantly inhibited serum levels of nitric oxide and its synthase in morphine-dependent rats and rhesus monkeys, which were greater than clonidine. These findings suggested that Sidiming treatment attenuated withdrawal syndrome in morphine-dependent rats and rhesus monkeys by inhibiting serum nitric oxide and its synthase.展开更多
Objective: To evaluate the effects of Oscimum sanctum L(O. sanctum), an important medicinal herb, on alcohol withdrawal syndrome in Wistar rats. Methods: Liquid diet with 7.2%, v/v ethanol was administered to the rats...Objective: To evaluate the effects of Oscimum sanctum L(O. sanctum), an important medicinal herb, on alcohol withdrawal syndrome in Wistar rats. Methods: Liquid diet with 7.2%, v/v ethanol was administered to the rats for 21 d. Control group animals received sucrose as an isocaloric liquid diet. After alcohol withdrawal, rats were examined at 6 th and 24 th hour for major withdrawal signs that included anxiety and hyper locomotor activity. Ethanol withdrawal anxiety was tested using elevated plus maze, light and dark model; the hyper locomotor activity using actophotometer. O. sanctum leaf extract(100, 200 and 300 mg/kg, oral) and diazepam(2 mg/kg, i.p) were administered to the treatment group animals 30 min before alcohol withdrawal estimation. Drug treatment was also given 30 min before the second observation at 24 th hour. On the last day of the protocol, rats were sacrificed by cervical dislocation liver, kidney and brain were isolated and preserved in formalin for further histopathological examination. Results: Findings from the present study revealed that O. Sanctum leaf extract treatment at doses 100, 200 and 300 mg/kg, oral had a significant protective effect on signs and symptoms of ethanol withdrawal in alcohol-dependent rats. However, no remarkable pathological and microscopic alterations were observed in histopathological examination. Conclusions: O. sanctum seems to be an active drug for the treatment of alcohol abstinence syndrome.展开更多
In this study, the key technologies of a 6-m long bearing steel ingot produced by electroslag remelting withdrawing(ESRW) process, including bifilar mode supply, slag system development, and design of mold, were studi...In this study, the key technologies of a 6-m long bearing steel ingot produced by electroslag remelting withdrawing(ESRW) process, including bifilar mode supply, slag system development, and design of mold, were studied based on the laboratory research achievements. The 6-m long ingot of bearing steel GGr15 with a cross-section of 300 mm × 340 mm was produced using the ESRW process with a bifilar mode and a multi-taper T-mold in a plant. The testing results show that the melting rate using the ESRW bifilar mode technology is three times faster than traditional electroslag remelting(ESR), and the power consumption is only 1,320 k Wh per ton steel. Through testing for the chemical composition, macrostructure and inclusions of remelted ingot, it can be concluded that the ESRW bifilar mode technology not only retains the characteristics of traditional ESR, but also improves the production efficiency and reduces the cost compared to traditional ESR.展开更多
Al-4.5wt.%Cu alloy has been directionally solidified at constant and abruptly changing withdrawal rates, respectively. The effects of the withdrawal rate on solidification microstructure, primary dendrite arm spacing(...Al-4.5wt.%Cu alloy has been directionally solidified at constant and abruptly changing withdrawal rates, respectively. The effects of the withdrawal rate on solidification microstructure, primary dendrite arm spacing(PDAS) and liquid solute distribution in front of the solid-liquid interface were investigated. The experimental results for the PDAS at a constant withdrawal rate agree well with the values calculated by the Hunt, Trivedi and Hunt-Lu models. At an abrupt change in the withdrawal rate, the maximum to minimum ratio of the PDAS at a given solidification parameter, i.e. λ1max/λ1min, is more than 2, and the PDAS values are remarkably history-dependent. Further, the liquid-solute distribution curve based on theoretical calculation shows that the larger the initial withdrawal rate is, the smaller the minimum of liquid solute concentration in front of the solid-liquid interface is after the abrupt change in withdrawal rate.展开更多
文摘Despite the high efficiency of remote sensing methods for rapid and large-scale detection of subsidence phenomena,this technique has limitations such as atmospheric impact and temporal and spatial decorrelation that affect the accuracy of the results.This paper proposes a method based on an artificial neural network to improve the results of monitoring land subsidence due to groundwater overexploitation by radar interferometry in the Aliabad plain(Central Iran).In this regard,vertical ground deformations were monitored over 18 months using the Sentinel-1A SAR images.To model the land subsidence by a multilayer perceptron(MLP)artificial neural network,four parameters,including groundwater level,alluvial thickness,elastic modulus,and transmissivity have been applied.The model's generalizability was assessed using data derived for 144 days.According to the results,the neural network estimates the land subsidence at each ground point with an accuracy of 6.8 mm.A comparison between the predicted and actual values indicated a significant agreement.The MLP model can be used to improve the results of subsidence detection in the study area or other areas with similar characteristics.
文摘Phenibut(β-phenyl-γ-aminobutyric acid)is a psychoactive gamma-aminobutyric acid(GABA)analog marketed online as a nutritional and nootropic(cognition enhancing)supplement.Phenibut consumption poses a high risk of potential abuse.Withdrawal from phenibut mimics benzodiazepine and alcohol withdrawal and can be dangerous.A number of approaches have been described for phenibut withdrawal,including protocols that include baclofen,but for inpatient and outpatient use.Here we describe a 30-year-old male who presented to an emergency department(ED)with insomnia,anxiety and palpitations after he stopped taking phenibut.
基金Under the auspices of Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDA28100405,XDA28020403)National Natural Science Foundation of China (No. 41771179, 42071275)+1 种基金Talents Training Project Supported by the Central Government for the Reform and Development of Local UniversitiesYoung Scientist Group Project of Northeast Institute of Geography and Agroecology,Chinese Academy of Sciences (No. 2022QNXZ02)
文摘The effective use of land in Northeast China is of great significance for ensuring national food security and regional rural revitalization.In this study,based on the survey data collected from Jilin Province,Northeast China,we analyzed the vacancy rates of rural homesteads in suburban,outer suburban,and remote villages,as well as the withdrawal intention of rural-settled farmers,urbansettled farmers,and farmers with urban and rural dual residency from vacant homesteads.From the perspective of farmers’perceptions,this study constructed a theoretical framework of the influence mechanism of their withdrawal intention and analyzed such mechanism by constructing a structural equation model.The results indicated that:1)rural homestead vacancy rates increased with distance from the village to the city.2)rural-settled farmers showed a low withdrawal intention for vacant rural homesteads,followed by urban and rural dual-residence farmers,and urban-settled farmers showed the highest withdrawal intention.3)the relative importance of the factors influencing withdrawal intention is in the following order:policy awareness>interest perception>living environment perception>family characteristics.Finally,this study discussed the reformation of the homestead system and rural homestead transition in Northeast China,which can provide policy support to increase the potential of cultivated land and promote sustainable rural development and urban-rural coordination.
基金Tianjin Suburban Development Investigation and Research Project in 2019:Research on Rural Collective Property Rights System Reform and Development in Jizhou District.
文摘In order to grasp the relationship between farmers'willingness and behavior to withdraw from rural homesteads,based on the theory of planned behavior,a survey was conducted in Jizhou District,Tianjin using convenience sampling method.A total of 443 valid questionnaires were collected and they were analyzed by SPSS.The results are as follows.(i)The willingness of farmers to withdraw from rural homesteads is affected by pre-cognitive factors such as behavioral attitude,subject norm and perceived behavior control.(ii)Among the benefits that can be brought by the withdrawal of homesteads,farmers value the improvement of the housing environment the most.(iii)Family members'view and relatives and neighbors'withdrawing from homesteads also exerts greater pressure on farmers.(iv)Farmers generally lack trust in the village committees or government departments'claims.(v)The cost of relocation also restricts the perceived behavior control of farmers'homesteads withdrawing.Based on above result,the following suggestions are made:strengthening policy publicity,raising farmers'awareness of policies related to the withdrawal of homesteads,fully respecting farmers'wishes,promoting the withdrawal of rural homesteads in an orderly manner,expanding the scope of compensation for withdrawal of rural homesteads,and enriching compensation methods.
基金supported by the Chinese National S&T Major Project(No.ZX069)
文摘Two tests initiated by unscrammed control rod withdrawal were performed on the High Temperature GasCooled Reactor-Test Module(HTR-10) in November 2003 after the reactor achieved its full power, and the test conditions represented a typical transient scenario of modular high-temperature reactors(HTRs), called pressurized loss of forced cooling, and anticipated transient without scram.Based on the test parameters, the HTR-10 thermal behaviors under the test conditions were studied with the help of the system analysis code THERMIX. The combination of the test results and the investigation results makes the HTR-10 safety potential better understood. Key phenomena, such as the helium natural circulation and the temperature redistribution in the reactor, were revealed. As the safety feature of most significance, there is a large margin between the maximum fuel temperature and its safety limit in each test. Temperatures of thermocouples in different components were calculated by THERMIX and compared with the test values. The applicability of the code was verified by good agreement obtained from the comparison.
文摘The global community has prepared for the withdrawal of the U.S. from the Paris Agreement since Donald Trump was elected as the president of the U.S. However, Trump's formal declaration of withdrawal still caused worldwide reaction. Trump will use the withdrawal to build his political reputation and to renegotiate the Paris Agreement despite its negative effects on the political credibility, international relationships, and potential long-term economic growth of the U.S. In general, the withdrawal of the U.S. from the Paris Agreement will not change the development of low-carbon technologies and the transformation trend of the global climate governance regime. However, the long-term goals and international cooperation on climate change will be affected by budget cuts in American climate change research and the cancelation of donations from the multilateral environmental fund of the U.S. If the Paris Agreement is renegotiated, the common but differentiated principle of responsibility of the United Nations Framework Convention on Climate Change will be challenged again. Nevertheless, climate change governance remains a main theme of future sustainable development. Instead of national governments, local governments and non-governmental organizations will develop strategies for technical innovation and emphasize pragmatic cooperation, thus expanding their roles in climate change governance. The capacity building on climate change research and public awareness should be enhanced as a long-term objective of global climate change governance.
文摘Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel disease.However, this treatment is associated with high costs and the possibility of severe adverse events representing a true challenge for patients, clinicians and health care systems.Consequently, a crucial question is raised namely if therapy can be stopped once remission is achieved and if so, how and in whom.Additionally, in a real-life clinical setting, discontinuation may also be considered for other reasons such as the patient's preference, pregnancy, social reasons as moving to countries or continents with less access, or different local policy or reimbursement.In contrast to initiation of anti-TNFα therapy guidelines regarding stopping of this treatment are missing.As a result, the decision of discontinuation is still a challenging aspect in the use of anti-TNFα therapy.Currently this is typically based on an estimated, case-by-case, benefit-risk ratio.This editorial is intended to provide an overview of recent data on this topic and shed light on the proposed drug withdrawal strategies.
基金the Grant from Administration of Traditional Chinese Medicine of Sichuan Province, No. 2000-48
文摘BACKGROUND: Following morphine withdrawal, anxiety is associated with abnormal norepinephrine content change. However, increasing blood lactic acid content can induce anxiety or panic in patients with anxiety disorder or endogenous opioid peptide functional disorder. OBJECTIVE: This study was designed to observe the effects of electro-acupuncture, at the "Sanyinjiao" point (SP 6), on brain tissue norepinephrine and blood lactic acid content in anxiety-model mice after morphine withdrawal. DESIGN: A randomized controlled animal experiment. SETTING: This study was performed in the Laboratory of Acupuncture, Electro-acupuncture & Tuina College, Chengdu University of Traditional Chinese Medicine, from June to September 2001. MATERIALS: A total of 50 healthy Kunming male mice were provided by the Laboratory Animal Center of Chengdu University of Traditional Chinese Medicine. The protocol was performed in accordance with ethical guidelines stated in the Guide for the use and care of laboratory animals, approved by the Committee on the Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources Commission on Life Sciences, National Research Council, China (1985). Experimental reagents and equipment used were as follows: morphine hydrochloride (Lot No. 930503, Shenyang No.1 Pharmaceutical Factory, China), norepinephrine (Sigma Chemical Company, USA), fluorospectrophotometer (RF-510, Shimadzu Corporation, Japan), Han electro-acupuncture apparatus (WQ 1002, No. zun (91)-227270-588, Beijing Anlong Photoelectricity-Technique Company, China), and T-maze (self-made). METHODS: A total of 50 mice were randomly divided into 5 groups, with 10 mice in each group: blank control, T-maze, model, model + electro-acupuncture, and electro-acupuncture groups. Establishment of anxiety model after morphine withdrawal: the mouse hot plate assay was used to detect the activity of morphine. The median effective dose of morphine, 2.95 mg/kg, was defined as the base. Mice were subcutaneously administered morphine, 3 times a day, for 4 days successively (initially 2.95 mg/kg, then increased day by day, as described below). Interventions: In the model + electro-acupuncture group, after model induction, mice were subjected electro-acupuncture at bilateral "Sanyinjiao" (SP6) points using a Han electro-acupuncture apparatus with sparse-dense waves and frequency of 2-100 Hz, once a day, for 6 days. In the model group, after anxiety-model induction, mice were subjected to fixation as same as model + electro-acupuncture group within 6 days of model induction. In the electro-acupuncture group, the anxiety model was not induced and mice were subjected to fixation, electro-acupuncture and the T-maze test. In the T-maze group, the anxiety model was not induced and mice were subjected to fixation. The T-maze test was performed in the 4 groups after experiment. In the blank control group, the anxiety model was not induced and mice were subjected to fixation only. MAIN OUTCOME MEASURES: Brain tissue norepinephrine content of morphine-withdrawal anxiety mice was detected by fluorospectrophotometry after 6 days of electro-acupuncture. Blood lactic acid content was detected by visible spectrophotometry. RESULTS: A total of 50 mice were included in the final analysis. Brain norepinephrine content was significantly greater in the model group compared to the T-maze, blank control, electro-acupuncture and model + electro-acupuncture groups, (P 〈 0.05-0.01). Brain norepinephrine content was similar between the model + electro-acupuncture and the blank control groups (P 〉 0.05). There was no significant difference in blood lactic acid content among the groups (P 〉 0.05). CONCLUSION: Electro-acupuncture lowers brain norepinephrine content but does not influence peripheral blood lactic acid content in morphine-withdrawn, anxiety-modeled mice. These results demonstrate that anxiety-inhibiting effects of electro-acupuncture, after morphine withdrawal, might be related to regulation of norepinephrine release.
基金supported by grants from the National Natural Science Foundation of China(81373160 and 81400673)Zhejiang Provincial Natural Science Foundation of China(LQ15H030003 and LY14H160022)
文摘Anti-virus prophylactic therapy may be not nec- essary for the prevention of hepatitis B virus (HBV) recur- rence after HBV-related liver transplantation (LT). However, studies on completely stopping the hepatitis B immune globu- lin (HBIG) and nucleos(t)ide analogs (NUC) after LT are few. The aim of the current study was to evaluate the safety of anti- virus prophylaxis withdrawal in liver recipients whose serum hepatitis B e antigen (HBeAg) and HBV DNA are negative. We analyzed 190 patients undergone LT for HBV-related liver dis- ease from 2006 to 2012 and found that 10 patients completely stopped the HBIG and NUC due to poor compliance. These patients were liver biopsied and checked monthly with serum HBV markers, HBV DNA and liver function. Among the 10 patients, 9 did not show the signs of HBV recurrence after a mean follow-up of 51.6 months (range 20-73) after with- drawal of the HBIG and NUC. The average time from LT to the withdrawal of the anti-virus drug was 23.8 (13-42) months; one patient showed hepatitis B surface antigen-positive and detectable HBV DNA after stopping anti-virus drugs and this patient was successfully treated with entecavir. Our data sug- gested that complete withdrawal of anti-virus prophylaxis was safe and feasible for patients whose serum HBeAg and HBV DNA were negative at the time of LT.
基金This study was supported by the 2017 National Natural Science Foundation Project “The Impacts of U.S. Withdrawal from Paris Agreement on Global Climate Governance and China's Response”.
文摘Based on the Computable General Equilibrium (CGE) model and scenario analysis, the impacts of the U.S. withdrawal from the Paris Agreement on the carbon emission space and mitigation cost in China, European Union (EU), and Japan are assessed under Nationally Determined Contributions (NDCs) and 2 C scenarios due to the changed emission pathway of the U.S. The results show that, under the condition of constant global cumulative carbon emissions and a fixed burden-sharing scheme among countries, the failure of the U.S. to honor its NDC commitment to different degrees will increase the U.S. carbon emission space and decrease its mitigation cost. However, the carbon emission space of other parties, including China, EU, and Japan, will be reduced and their mitigation costs will be increased. In 2030, under the 2 C target, the carbon price will increase by 4.4e14.6 US$ t1 in China, by 9.7e35.4 US$ t1 in the EU, and by 16.0e53.5 US$ t1 in Japan. In addition, China, EU, and Japan will incur additional Gross Domestic Production (GDP) loss. Under the 2 C target, the GDP loss of China would increase by US$22.0e71.1 billion (equivalent to 16.4e53.1 US$ per capita), the EU's GDP loss would increase by US$9.4e32.1 billion (equivalent to 20.7e71.1 US$ per capita), and Japan's GDP loss will increase by US$4.1e13.5 billion (equivalent to 34.3e111.6 US$ per capita).
基金supported by grants from the National Natural Science Foundation of China(81100304)Science and Technology Bureau of Zhengzhou(131PLJRC658)
文摘BACKGROUND: Immunosuppression reagents have side effects and cause considerable long-term morbidity and mortality in patients after liver transplantation. Sufficient evidences showed that minimization or withdrawal of immunosuppression reagents does not deteriorate the recipient's immune response and physiological function and therefore, is feasible in some recipients of liver transplantation. However, the mechanisms are not clear. The present review was to update the current status of immunosuppression in liver transplantation and the mechanism of minimization or withdrawal of immunosuppression in liver recipients.DATA SOURCES: We searched articles in English on minimization or withdrawal of immunosuppression in liver transplantation in Pub Med. We focused on the basic mechanisms of immune tolerance in liver transplantation. Studies on immunosuppression minimization or withdrawal protocols and biomarker in tolerant recipients were also analyzed.RESULTS: Minimization or withdrawal of immunosuppression can be achieved by the induction of immune tolerance, which may not be permanent and can be affected by various factors. However, accurately evaluating immune status post-transplant is a prerequisite to achieve individualized immunosuppression. Numerous mechanisms for immune tolerance have been found, including immunophenotypic shift of memory CD8+ T cells and CD4+ T cell subsets. Activation of the inflammasome through apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain(ASC) in dendritic cells is associated with rejection after liver transplantation. CONCLUSIONS: Minimization or withdrawal of immunosuppression can be achieved by the induction of immune toler-ance via different mechanisms. This process could be affected by immunophenotypic shift of memory CD8+ T cells and CD4+ T cell subsets, which may be correlated with activation of the inflammasome through ASC in dendritic cells.
文摘In this study, we consider the heat-induced withdrawal reflex caused by exposure to an electromagnetic beam. We propose a concise dose-response relation for predicting the occurrence of withdrawal reflex from a given spatial temperature profile. Our model is distilled from sub-step components in the ADT CHEETEH-E model developed at the Institute for Defense Analyses. Our model has only two parameters: the activation temperature of nociceptors and the critical threshold on the activated volume. When the spatial temperature profile is measurable, the two parameters can be determined from test data. We connect this dose-response relation to a temperature evolution model for electromagnetic heating. The resulting composite model governs the process from the electromagnetic beam deposited on the skin to the binary outcome of subject’s reflex response. We carry out non-dimensionalization in the time evolution model. The temperature solution of the non-dimensional system is the product of the applied power density and a parameter-free function. The effects of physical parameters are contained in non-dimensional time and depth. Scaling the physical temperature distribution into a parameter-free function greatly simplifies the analytical solution, and helps to pinpoint the effects of beam spot area and applied power density. With this formulation, we study the theoretical behaviors of the system, including the time of reflex, effect of heat conduction, biological latency in observed reflex, energy consumption by the time of reflex, and the strategy of selecting test conditions in experiments for the purpose of inferring model parameters from test data.
文摘Methylene blue (MB), a tricyclic phenothiazine drug, has been reported to enhance mitochondrial functions including mitochondrial respiration. By comparison, stress associated with abrupt ethanol withdrawal (EW) impedes mitochondrial functions. We investigated whether MB protects mitochondrial respiration and cell survival from EW stress through a key mitochondrial enzyme, cytochrome c oxidase (COX). We also investigated whether the MB’s protection involves the inhibition of an excitatory neurotransmitter, glutamate. Male rats were exposed to and withdrawn from ethanol-diet (7.5%, 5 weeks). MB (0.5 mg/kg, intraperitoneal) was injected for the last 5 days of ethanol-diet and on the first day of EW. Cerebellum was then harvested to measure mitochondrial respiration and COX expression using real-time XF respirometer and immunohistochemistry, respectively. Separately, HT22 cells (a murine hippocampal cell line) were exposed to and abruptly withdrawn for 4 hours from chronic ethanol (100 mM, 3 days). MB was administered during EW with or without a COX inhibitor (NaN3) or glutamate. Mitochondrial respiration, COX content, and cell viability were then assessed using real-time XF respirometer, an immunoblot method, and Calcein assay, respectively. MB attenuated the suppressing effects of EW on mitochondrial respiration, COX content, and cell survival. This protection was reduced after NaN3 or glutamate cotreatment. These results suggest that MB treatment help maintain mitochondrial respiratory and cellular integrity through COX-upregulation and glutamateinhibition upon EW stress. MB treatment may help identify mitochondrial mechanisms underlying hyperexcitatory CNS disorders.
文摘To study steroid withdrawal in immunosuppresion after liver transplantation (LTx).Methods Fifty-eight consecutive patients undergoing primary LTx,under cyclosporine and steroid immunosuppresion,10 additional patients treated with mycophemolate mofetil (MMF),were included in this study.If there was no evidence of rejection and the patient’s liver function tests were nearly normal,the steroid weaning process started 2 to 3 weeks after LTx.Results During a mean follow-up period of 9.3±5.5 months after LTx,54 patients survived and 4 died.Steroids could be withdrawn in 72.2% patients at 3rd month post-transplant,in 76.2% at 6th month and in 77.8% at first year,respectively.In 3 patients with rejection after steroid withdrawal,the steroid dose before withdrawal was given.After the rejection was reversed the steroid was withdrawn.Freedom from steroids was thus observed in 10 additional patients treated with MMF at 3rd to 4th month post-transplant.Conclusion Cyclosporine-based immunosuppression allows safe early steroid withdrawal in some patients of LTx.3 refs,1 tab.
基金the National Natural Science Foundation of China, No. 30772082the Natural Science Foundation of Hebei Province of China, No. C2005000834
文摘BACKGROUND: Studies have demonstrated that exogenous neurosteroid treatment prevents the development of morphine tolerance and dependence, and attenuates abstinence behavior in mice. However, there are few studies on whether the levels of endogenous neurosteroids can be changed by morphine dependence and withdrawal. OBJECTIVE: To investigate the levels of various neurosteroids in rat brain following morphine dependence and withdrawal. To evaluate the expressions of steroidogenic enzyme mRNAs and proteins. To identify the relationship between neurosteroids and morphine dependence at the whole animal behavior, neural biochemistry, and molecular levels. DESIGN, TIME AND SETTING: A randomized, controlled study. Experiments were performed at the Department of Pharmacology of Hebei Medical University and Department of Pharmacology of Beathune International Peace Hospital, China, from June 2004 to October 2007. MATERIALS: Morphine hydrochloride injection (Shenyang First Pharmaceutical Factory, China), naloxone hydrochloride (Hunan Yiqiao Pharmaceutical Co., China) and a gas chromatography-mass spectrometry system (Agilent, CA, USA) were used in this study. METHODS: Healthy adult Sprague Dawley rats were randomly divided into three groups: a morphine dependence group, morphine withdrawal group and control group (n = 20). The rats in the morphine dependence and morphine withdrawal groups were given increasing doses of morphine (5, 10, 15, 20, 30, 40 and 50 mg/kg, intraperitoneal) to create morphine dependence. The rats in the morphine withdrawal group were injected with 2 mg/kg naloxone to precipitate withdrawal 1 hour after the last morphine injection. Rats in the control group were treated with an equal volume of saline. MAIN OUTCOME MEASURES: Following morphine dependence and withdrawal, brain levels of the neurosteroids pregnenolone, progesterone and allopregnanolone were analyzed using gas chromatography-mass spectrometry. The mRNA expression of two key steroidogenic enzymes, P450 side-chain cleavage enzyme (P450scc) and 3[B-hydroxysteroid dehydrogenase (313-HSD), were determined in rat brain regions using reverse transcription-polymerase chain reaction. The distribution and expression of P450scc protein were visualized in brain regions associated with addiction by immunohistochemistry. RESULTS: In brain tissue from the morphine dependence group, the levels of pregnenolone and progesterone were decreased by 62% (P 〈 0.01) and 92% (P 〈 0.01 ) respectively, compared with the control group. In the morphine dependence group, the key steroidogenic enzyme P450scc mRNA was decreased in striatum (P 〈 0.05), while 3-HSD mRNA was decreased in amygdala (P 〈 0.05), striatum (P 〈 0.05) and frontal cortex (P 〈 0.05) compared with the control group. Morphine withdrawal induced a significant increase in the neurosteroid levels compared with the control group (P 〈 0.01). However, there was no significant difference in the expressions of P450scc and 36-HSD mRNAs between the morphine withdrawal and control groups (P 〉 0.05). CONCLUSION: The neurosteroid levels and expressions of steroidogenic enzymes changed similarly in morphine dependent rats, suggesting that the morphine dependence-induced decrease in neurosteroids might depend on local expression of steroidogenic enzymes in the central nervous system. However, the changes in neurosteroids in morphine withdrawal rats were not in accordance with the changes in the expression of steroidogenic enzymes, suggesting that the effects of morphine withdrawal on brain neurosteroid levels may not depend primarily on the local expression of steroidogenic enzymes in the central nervous system.
文摘Aim: To determine whether testosterone is involved in morphine withdrawal syndrome (WS). Methods: In order to induce dependency, rats were treated with subcutaneous injection of morphine (days 1-2, 5 mg/kg; days 3-5, 7.5 mg/kg; days 6-8, 10 mg/kg), and after the last dose of morphine (day 8) WS was induced by intraperitoneal injection of naloxone (1 mg/kg). Wet dog shake (WDS), abdomen writhing (AW), and jumps (J) were recorded as indicators of WS. Results: The severity of WDS, AW, and J in male rats was greater than that in females. Accordingly, in 4-week castrated and flutamide-treated (10 mg/kg/day for 8 days, i.p.) male rats, WDS, AW, and J were significantly decreased compared to male control rats. Testosterone replacement therapy (10 mg/kg/day for 8 days, i.m.) in 4-week castrated rats restored the severity of WDS, AW, and J behaviors to the level of non-castrated male rats, whereas testosterone potentiated the WDS behavior in non-castrated male rats. Conclusion: It can be concluded that testosterone might be effectively involved in morphine WS.
基金the Natural Science Foundation of Guangxi Zhuang Autonomous Region, No.0575066
文摘The present study analyzed the effects of Sidiming, a Chinese herbal compound, on withdrawal syndrome, body weight loss, and serum levels of nitric oxide and its synthase in morphine- dependent rats and rhesus monkeys. These effects were compared with clonidine, an active control drug used for clinical treatment. Results showed that 4 and 8 g/kg Sidiming, respectively, significantly suppressed morphine withdrawal syndrome and reduced body mass loss in morphine-dependent rats. In addition, 2.4 and 4.8 g/kg Sidiming, respectively, significantly attenuated withdrawal syndrome in rhesus monkeys. High-dose Sidiming (8 g/kg in rats and 4.8 g/kg in rhesus monkeys) led to significantly inhibited serum levels of nitric oxide and its synthase in morphine-dependent rats and rhesus monkeys, which were greater than clonidine. These findings suggested that Sidiming treatment attenuated withdrawal syndrome in morphine-dependent rats and rhesus monkeys by inhibiting serum nitric oxide and its synthase.
基金supported by Science and Engineering Research Board(SERB)Department of Science and Technology,Government of India(SR/FT/LS–07/2012)
文摘Objective: To evaluate the effects of Oscimum sanctum L(O. sanctum), an important medicinal herb, on alcohol withdrawal syndrome in Wistar rats. Methods: Liquid diet with 7.2%, v/v ethanol was administered to the rats for 21 d. Control group animals received sucrose as an isocaloric liquid diet. After alcohol withdrawal, rats were examined at 6 th and 24 th hour for major withdrawal signs that included anxiety and hyper locomotor activity. Ethanol withdrawal anxiety was tested using elevated plus maze, light and dark model; the hyper locomotor activity using actophotometer. O. sanctum leaf extract(100, 200 and 300 mg/kg, oral) and diazepam(2 mg/kg, i.p) were administered to the treatment group animals 30 min before alcohol withdrawal estimation. Drug treatment was also given 30 min before the second observation at 24 th hour. On the last day of the protocol, rats were sacrificed by cervical dislocation liver, kidney and brain were isolated and preserved in formalin for further histopathological examination. Results: Findings from the present study revealed that O. Sanctum leaf extract treatment at doses 100, 200 and 300 mg/kg, oral had a significant protective effect on signs and symptoms of ethanol withdrawal in alcohol-dependent rats. However, no remarkable pathological and microscopic alterations were observed in histopathological examination. Conclusions: O. sanctum seems to be an active drug for the treatment of alcohol abstinence syndrome.
基金financially supported by the National Natural Science Foundation of China(No.51474126)the Science and Technology Commission of Liaoning,China(No.L2013125)
文摘In this study, the key technologies of a 6-m long bearing steel ingot produced by electroslag remelting withdrawing(ESRW) process, including bifilar mode supply, slag system development, and design of mold, were studied based on the laboratory research achievements. The 6-m long ingot of bearing steel GGr15 with a cross-section of 300 mm × 340 mm was produced using the ESRW process with a bifilar mode and a multi-taper T-mold in a plant. The testing results show that the melting rate using the ESRW bifilar mode technology is three times faster than traditional electroslag remelting(ESR), and the power consumption is only 1,320 k Wh per ton steel. Through testing for the chemical composition, macrostructure and inclusions of remelted ingot, it can be concluded that the ESRW bifilar mode technology not only retains the characteristics of traditional ESR, but also improves the production efficiency and reduces the cost compared to traditional ESR.
基金financially supported by the National Natural Science Foundation of China(No.50971101)the Specialized Research Fund for the Doctoral Program of Higher Education(No.20136102110014)
文摘Al-4.5wt.%Cu alloy has been directionally solidified at constant and abruptly changing withdrawal rates, respectively. The effects of the withdrawal rate on solidification microstructure, primary dendrite arm spacing(PDAS) and liquid solute distribution in front of the solid-liquid interface were investigated. The experimental results for the PDAS at a constant withdrawal rate agree well with the values calculated by the Hunt, Trivedi and Hunt-Lu models. At an abrupt change in the withdrawal rate, the maximum to minimum ratio of the PDAS at a given solidification parameter, i.e. λ1max/λ1min, is more than 2, and the PDAS values are remarkably history-dependent. Further, the liquid-solute distribution curve based on theoretical calculation shows that the larger the initial withdrawal rate is, the smaller the minimum of liquid solute concentration in front of the solid-liquid interface is after the abrupt change in withdrawal rate.