A significant amount of evidence indicates that microRNAs （miRNAs） play an important role in drug addiction. The nucleus accumbens （NAc） is a critical part of the brain’s reward circuit and is involved in a varie...A significant amount of evidence indicates that microRNAs （miRNAs） play an important role in drug addiction. The nucleus accumbens （NAc） is a critical part of the brain’s reward circuit and is involved in a variety of psychiatric disorders, including depression, anxiety, and drug addiction. However, few studies have examined the expression of miRNAs and their functional roles in the NAc under conditions of morphine addiction. In this study, mice were intravenously infused with morphine （0.01, 0.03, 0.3, 1 and 3 mg/kg/infusion） and showed inverted U-shaped response. After morphine self-administration, NAc was used to analyze the functional networks of altered miRNAs and their putative target mRNAs in the NAc following intravenous self-administration of morphine. We utilized several bioinformatics tools, including Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway mapping and CyTargetLinker. We found that 62 miRNAs were altered and exhibited differential expression patterns. The putative targets were related to diverse regulatory functions, such as neurogenesis, neurodegeneration, and synaptic plasticity, as well as the pharmacological effects of morphine （receptor internalization/endocytosis）. The present findings provide novel insights into the regulatory mechanisms of accumbal molecules under conditions of morphine addiction and identify several novel biomarkers associated with morphine addiction.展开更多
Outpatient subcutaneous (s.c.) therapies are becoming more and more common in the treatment of different diseases. The effectiveness of community-pharmacy-based interventions in preventing problems that arise during s...Outpatient subcutaneous (s.c.) therapies are becoming more and more common in the treatment of different diseases. The effectiveness of community-pharmacy-based interventions in preventing problems that arise during s.c. self-injections of low-molecular-weight heparins (LMWH) is unknown. Our objective was to provide a standard operating procedure (SOP) for community pharmacists and to compare pharmaceutical vs. standard care in both clinical and daily life settings. We hypothesized that: pharmaceutical care results in improved adherence, safety, and satisfaction, and in fewer complications;the interventions used are feasible in daily life;and the results achieved in clinical and daily life settings are comparable. In the clinical setting (randomized controlled trial), patients were recruited sequentially in hospital wards;in the daily life setting (quasi-experimental design with a comparison group), recruitment took place in community pharmacies by pharmacists and trained master students during their internship. Interventions were offered according to patient needs. Data were collected by means of a monitored self-injection at home and structured questionnaire-based telephone interviews at the beginning and the end of the LMWH treatment. The main outcome measures were: scores to assess patient’s skills;syringe count to assess adherence;and frequency, effectiveness, and patient’s assessment of received interventions. The results show a median age of the 139 patients of 54 years. Interventions resulted in improved application quality (p p = 0.03). Oral instructions were pivotal for improving patients’ application quality. We found no significant score differences between the intervention groups in the clinical and daily life settings. Patients’ baseline skills were high, with the lowest score being 0.86 (score range ?2.00 to +2.00). Adherence rate was high (95.8%). In conclusion, our SOP for pharmacist interventions was of good quality, adequate, appreciated, and feasible in daily life. Patients are capable of managing s.c. injection therapies if adequate assistance is provided.展开更多
Individual differences in behavioral characteristics or initial responses to abused drugs had been recently demonstrated to have predictive value in the propensity of later abuse. The research described here was initi...Individual differences in behavioral characteristics or initial responses to abused drugs had been recently demonstrated to have predictive value in the propensity of later abuse. The research described here was initiated to determine the initial response of rats to administration of morphine if the physiological response has predictive value for the propensity of the animals to later self-administration. The initial response of extracellular fluid levels of the biogenic monoamine neurotransmitters in the anterior cingulate cortex (aCC) was assessed in drug rats with in vivo microdialysis following administration of morphine. Rats that did not acquire morphine self-administration (NSA) had higher baseline levels of aCC extracellular fluid levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) than animals that developed stable morphine self-administration (SA). However, the response independent administration of morphine resulted in a dramatic increase in (DA) in aCC in the SA group, while the morphine injection in the NSA rats increased extracellular fluid levels of noradrenaline (NA). It is possible that these differences might be related to the development of physical dependence. Therefore, the development of physical dependence was observed in these animals. There was no relationship between the propensity to self-administration morphine and the development of physical dependence. Rats that showed the highest withdrawal scores had lower extracellular fluid levels of serotonin (5-HT) compared to rats showing low withdrawal scores. Thus, monoamine neuronal innervations of the aCC respond to an initial dose of morphine that is predictive of the later propensity to self-administration and the resistance and predisposition to the formation of opiate dependence, but there is no relationship between these two indices in individual animals. These data add to a growing body of evidence for the involvement of neuronal systems in the aCC in the actions of opiates.展开更多
This paper describes the self—adjustment of some tuning-knobs of the generalized predictive controller(GPC).A three feedforward neural network was utilized to on line learn two key tuning-knobs of GPC,and BP algorith...This paper describes the self—adjustment of some tuning-knobs of the generalized predictive controller(GPC).A three feedforward neural network was utilized to on line learn two key tuning-knobs of GPC,and BP algorithm was used for the training of the linking-weights of the neural network.Hence it gets rid of the difficulty of choosing these tuning-knobs manually and provides easier condition for the wide applications of GPC on industrial plants.Simulation results illustrated the effectiveness of the method.展开更多
The relation between structures and properties of polyurethane are investigated by modern physical and chemical methods.The results obtained are as follows:the effects of the content of self-crosslinking agent on the ...The relation between structures and properties of polyurethane are investigated by modern physical and chemical methods.The results obtained are as follows:the effects of the content of self-crosslinking agent on the properties of polyurethane,i.e.,dispersion stability,dynamical viscoelasticity and mechanical properties are discussed.It is found that the optimum molar ratio of epichlorohydrin and diethylenetriamine is 1:2.A mois-展开更多
The Belt and Road Initiative contains the aspiration of Chinese nation to pursue ideological freedom and desire of strengthening international exchanges and cooperation. This paper takes the Belt and Road Initiative f...The Belt and Road Initiative contains the aspiration of Chinese nation to pursue ideological freedom and desire of strengthening international exchanges and cooperation. This paper takes the Belt and Road Initiative for example,emphasizing the interpretation of the inheritance and development of Chinese culture so as to study the importance of Culture Self-Consciousness in Chinese Philosophy,in the context of English globalization. That is to say,this paper stresses the spirits and the stand of nation 's demonstration on pursuing peace,cooperation and sustainable development in the civilization continuity from traditional China to the contemporary China,with practical philosophic view.展开更多
With the development of economy and society, our country is on the road of rule by law, the legal system is progressing constantly. At the same time, we should also see that the administration according to law is not ...With the development of economy and society, our country is on the road of rule by law, the legal system is progressing constantly. At the same time, we should also see that the administration according to law is not perfect, and its shortcomings exist in different degree and need to be further improved. Based on the analysis of the status quo of grass-roots administrative law enforcement in China, this paper tries to put forward corresponding countermeasures, so as to promote the work of law-based administration for the corresponding study.展开更多
AIM:To study the potential role of dependence statuson CB_(1)-mediated blockade of ethanol self-administra-tion.METHODS:We examined the effects of thecannabinoid antagonist SR141716A(0,0.03,0.3,and 3 mg/kg)on pperant ...AIM:To study the potential role of dependence statuson CB_(1)-mediated blockade of ethanol self-administra-tion.METHODS:We examined the effects of thecannabinoid antagonist SR141716A(0,0.03,0.3,and 3 mg/kg)on pperant ethanol(10%v/v)self-administration in male Wistar rats that were madeethanol-dependent by chronic(14 d)exposure toethanol vapor-chambers or exposed to air in identicalvapor chambers.RESULTS:Dependent animalsresponded more for ethanol than did air controlnondependent tats.The acute administration of a 3mg/kg dose of SR141716A almost suppressed ethanolself-administration ouly in ethanol dependent animals.However,operant responses for food were not afected by the administration of SR141716A.CONCLU.SION:These results further support that cannabinoid CB_(1) receptor blockade may have a potential utility for the treatment of alcobolism.展开更多
OBJECTIVE Wide spread abuse of synthetic cathinones found in bath salts preparations has resulted in regulation of some cathinones internationally.Chemists skirt these laws by altering the chemical structures of first...OBJECTIVE Wide spread abuse of synthetic cathinones found in bath salts preparations has resulted in regulation of some cathinones internationally.Chemists skirt these laws by altering the chemical structures of first-generation cathinones(ie,MDPV,methylone,and mephedrone),resulting in second-generation cathinones(eg,α-PVP,α-PPP,MDPPP,and MDPBP).Although MDPV is a more effective reinforcer than cocaine,little is known about the reinforcing effectiveness of secondgeneration cathinones.To test the hypothesis that synthetic cathinones with higher selectivity for DAT relative to SERT are more effective reinforcers.METHODS Monoamine transporter inhibition was determined using synaptosomes prepared from rat brains.The relative reinforcing effectiveness of intravenously self-administered MDPV,MDPBP,MDPPP,α-PVP,α-PPP,and cocaine were directly compared through evaluations of (1)dose-response curves under a progressive ratio(PR)schedule of reinforcement and (2)demand curves obtained for each drug in male Sprague-Dawley rats.RESULTS Rank order selectivity for DAT/SERT wasα-PVP>MDPV>α-PPP≈MDPBP>MDPPP>cocaine.Comparisons of the maximum number of infusions obtained under a PR schedule of reinforcement(α-PVP>MDPV>α-PPP>MDPBP≈MDPPP>cocaine)and the essential value obtained for each drug in demand analyses(α-PVP>MDPV>α-PPP≈MDPBP≈MDPPP>cocaine)suggest relative reinforcing effectiveness is related to DAT/SERT selectivity.CONCLUSION These data provide evidence that DAT/SERT selectivity accounts for select synthetic cathinones functioning as more effective reinforcers than cocaine and may predict the abuse-related effects of novel synthetic cathinones in humans.展开更多
基金funded by the National Research Council of Science & Technology(NST)grant by the Korean government(MSIP)(No.CRC-15-04-KIST)the National Research Foundation of Korea under the grant(No.NRF-2017R1A2B200399Mid-career Researcher Program)
文摘A significant amount of evidence indicates that microRNAs （miRNAs） play an important role in drug addiction. The nucleus accumbens （NAc） is a critical part of the brain’s reward circuit and is involved in a variety of psychiatric disorders, including depression, anxiety, and drug addiction. However, few studies have examined the expression of miRNAs and their functional roles in the NAc under conditions of morphine addiction. In this study, mice were intravenously infused with morphine （0.01, 0.03, 0.3, 1 and 3 mg/kg/infusion） and showed inverted U-shaped response. After morphine self-administration, NAc was used to analyze the functional networks of altered miRNAs and their putative target mRNAs in the NAc following intravenous self-administration of morphine. We utilized several bioinformatics tools, including Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway mapping and CyTargetLinker. We found that 62 miRNAs were altered and exhibited differential expression patterns. The putative targets were related to diverse regulatory functions, such as neurogenesis, neurodegeneration, and synaptic plasticity, as well as the pharmacological effects of morphine （receptor internalization/endocytosis）. The present findings provide novel insights into the regulatory mechanisms of accumbal molecules under conditions of morphine addiction and identify several novel biomarkers associated with morphine addiction.
文摘Outpatient subcutaneous (s.c.) therapies are becoming more and more common in the treatment of different diseases. The effectiveness of community-pharmacy-based interventions in preventing problems that arise during s.c. self-injections of low-molecular-weight heparins (LMWH) is unknown. Our objective was to provide a standard operating procedure (SOP) for community pharmacists and to compare pharmaceutical vs. standard care in both clinical and daily life settings. We hypothesized that: pharmaceutical care results in improved adherence, safety, and satisfaction, and in fewer complications;the interventions used are feasible in daily life;and the results achieved in clinical and daily life settings are comparable. In the clinical setting (randomized controlled trial), patients were recruited sequentially in hospital wards;in the daily life setting (quasi-experimental design with a comparison group), recruitment took place in community pharmacies by pharmacists and trained master students during their internship. Interventions were offered according to patient needs. Data were collected by means of a monitored self-injection at home and structured questionnaire-based telephone interviews at the beginning and the end of the LMWH treatment. The main outcome measures were: scores to assess patient’s skills;syringe count to assess adherence;and frequency, effectiveness, and patient’s assessment of received interventions. The results show a median age of the 139 patients of 54 years. Interventions resulted in improved application quality (p p = 0.03). Oral instructions were pivotal for improving patients’ application quality. We found no significant score differences between the intervention groups in the clinical and daily life settings. Patients’ baseline skills were high, with the lowest score being 0.86 (score range ?2.00 to +2.00). Adherence rate was high (95.8%). In conclusion, our SOP for pharmacist interventions was of good quality, adequate, appreciated, and feasible in daily life. Patients are capable of managing s.c. injection therapies if adequate assistance is provided.
文摘Individual differences in behavioral characteristics or initial responses to abused drugs had been recently demonstrated to have predictive value in the propensity of later abuse. The research described here was initiated to determine the initial response of rats to administration of morphine if the physiological response has predictive value for the propensity of the animals to later self-administration. The initial response of extracellular fluid levels of the biogenic monoamine neurotransmitters in the anterior cingulate cortex (aCC) was assessed in drug rats with in vivo microdialysis following administration of morphine. Rats that did not acquire morphine self-administration (NSA) had higher baseline levels of aCC extracellular fluid levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) than animals that developed stable morphine self-administration (SA). However, the response independent administration of morphine resulted in a dramatic increase in (DA) in aCC in the SA group, while the morphine injection in the NSA rats increased extracellular fluid levels of noradrenaline (NA). It is possible that these differences might be related to the development of physical dependence. Therefore, the development of physical dependence was observed in these animals. There was no relationship between the propensity to self-administration morphine and the development of physical dependence. Rats that showed the highest withdrawal scores had lower extracellular fluid levels of serotonin (5-HT) compared to rats showing low withdrawal scores. Thus, monoamine neuronal innervations of the aCC respond to an initial dose of morphine that is predictive of the later propensity to self-administration and the resistance and predisposition to the formation of opiate dependence, but there is no relationship between these two indices in individual animals. These data add to a growing body of evidence for the involvement of neuronal systems in the aCC in the actions of opiates.
基金Supported by the National 863 CIMS Project Foundation(863-511-010)Tianjin Natural Science Foundation(983602011)Backbone Young Teacher Project Foundation of Ministry of Education
文摘This paper describes the self—adjustment of some tuning-knobs of the generalized predictive controller(GPC).A three feedforward neural network was utilized to on line learn two key tuning-knobs of GPC,and BP algorithm was used for the training of the linking-weights of the neural network.Hence it gets rid of the difficulty of choosing these tuning-knobs manually and provides easier condition for the wide applications of GPC on industrial plants.Simulation results illustrated the effectiveness of the method.
文摘The relation between structures and properties of polyurethane are investigated by modern physical and chemical methods.The results obtained are as follows:the effects of the content of self-crosslinking agent on the properties of polyurethane,i.e.,dispersion stability,dynamical viscoelasticity and mechanical properties are discussed.It is found that the optimum molar ratio of epichlorohydrin and diethylenetriamine is 1:2.A mois-
文摘The Belt and Road Initiative contains the aspiration of Chinese nation to pursue ideological freedom and desire of strengthening international exchanges and cooperation. This paper takes the Belt and Road Initiative for example,emphasizing the interpretation of the inheritance and development of Chinese culture so as to study the importance of Culture Self-Consciousness in Chinese Philosophy,in the context of English globalization. That is to say,this paper stresses the spirits and the stand of nation 's demonstration on pursuing peace,cooperation and sustainable development in the civilization continuity from traditional China to the contemporary China,with practical philosophic view.
文摘With the development of economy and society, our country is on the road of rule by law, the legal system is progressing constantly. At the same time, we should also see that the administration according to law is not perfect, and its shortcomings exist in different degree and need to be further improved. Based on the analysis of the status quo of grass-roots administrative law enforcement in China, this paper tries to put forward corresponding countermeasures, so as to promote the work of law-based administration for the corresponding study.
基金DGICYT PM 96/0047,Comunidad de Madrid and Plan Nacional Sobre Drogas(MN,FRF)National Institutes of Health grants AA 06420AA 08459 from the National Institute on Alcohol Abuse and Alcoholism(GFK and AJR)
文摘AIM:To study the potential role of dependence statuson CB_(1)-mediated blockade of ethanol self-administra-tion.METHODS:We examined the effects of thecannabinoid antagonist SR141716A(0,0.03,0.3,and 3 mg/kg)on pperant ethanol(10%v/v)self-administration in male Wistar rats that were madeethanol-dependent by chronic(14 d)exposure toethanol vapor-chambers or exposed to air in identicalvapor chambers.RESULTS:Dependent animalsresponded more for ethanol than did air controlnondependent tats.The acute administration of a 3mg/kg dose of SR141716A almost suppressed ethanolself-administration ouly in ethanol dependent animals.However,operant responses for food were not afected by the administration of SR141716A.CONCLU.SION:These results further support that cannabinoid CB_(1) receptor blockade may have a potential utility for the treatment of alcobolism.
基金supported by NIH and NIDA(R01DA039146T32DA031115)NIH Intramural Research Programs
文摘OBJECTIVE Wide spread abuse of synthetic cathinones found in bath salts preparations has resulted in regulation of some cathinones internationally.Chemists skirt these laws by altering the chemical structures of first-generation cathinones(ie,MDPV,methylone,and mephedrone),resulting in second-generation cathinones(eg,α-PVP,α-PPP,MDPPP,and MDPBP).Although MDPV is a more effective reinforcer than cocaine,little is known about the reinforcing effectiveness of secondgeneration cathinones.To test the hypothesis that synthetic cathinones with higher selectivity for DAT relative to SERT are more effective reinforcers.METHODS Monoamine transporter inhibition was determined using synaptosomes prepared from rat brains.The relative reinforcing effectiveness of intravenously self-administered MDPV,MDPBP,MDPPP,α-PVP,α-PPP,and cocaine were directly compared through evaluations of (1)dose-response curves under a progressive ratio(PR)schedule of reinforcement and (2)demand curves obtained for each drug in male Sprague-Dawley rats.RESULTS Rank order selectivity for DAT/SERT wasα-PVP>MDPV>α-PPP≈MDPBP>MDPPP>cocaine.Comparisons of the maximum number of infusions obtained under a PR schedule of reinforcement(α-PVP>MDPV>α-PPP>MDPBP≈MDPPP>cocaine)and the essential value obtained for each drug in demand analyses(α-PVP>MDPV>α-PPP≈MDPBP≈MDPPP>cocaine)suggest relative reinforcing effectiveness is related to DAT/SERT selectivity.CONCLUSION These data provide evidence that DAT/SERT selectivity accounts for select synthetic cathinones functioning as more effective reinforcers than cocaine and may predict the abuse-related effects of novel synthetic cathinones in humans.
