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
Aim： To assess the effect of estradiol-17β （E2） and bisphenol A （BPA） administered chronically by implanting a silicone tube throughout pregnancy and lactation on male pups＇ reproductive system in ICR mice. Met...Aim： To assess the effect of estradiol-17β （E2） and bisphenol A （BPA） administered chronically by implanting a silicone tube throughout pregnancy and lactation on male pups＇ reproductive system in ICR mice. Methods： Female mice were implanted with a tube filled with 10 ng, 500 ng, 1 μg, or 10 μg of E2, or 100 μg or 5 mg of BPA, before mating. The tube was kept in the mice throughout pregnancy and lactation, until the pups had weaned at 4 weeks of age. During the period, E2 was released from the tube at 120 pg or 6, 12 or 120 ng/day, and BPA at 1.2 or 60 μg/day. Results： Most of the mice given 1 μg and 10 lag of E2 did not maintain their pregnancy. However, the other groups showed high rates of birth, more than 70%. At age of 4 weeks, the male pups were killed. Body weight and reproductive organ weights （testes, epididymides and accessory reproductive glands） in the treated groups did not differ from the control values, whereas the percentage of seminiferous tubules in the testis with mature spermatids was significantly lower in the groups given 10 ng and 500 ng of E2 and 5 mg of BPA than that in the control. Conclusion： Chronic exposure to E2 and BPA might disrupt spermatogenesis in male pups. （Asian JAndrol 2008 Mar; 10： 271-276）展开更多
Oral administration of arsenic trioxide(3 and 6 mg/kg body weight/d) for 30 d caused, as compared with vehicle control, dose dependent significant reductions in body weight, absolute weight, protein, glycogen, as wel...Oral administration of arsenic trioxide(3 and 6 mg/kg body weight/d) for 30 d caused, as compared with vehicle control, dose dependent significant reductions in body weight, absolute weight, protein, glycogen, as well as, total, dehydro and reduced ascorbic acid contents both in the liver and kidney of arsenic treated mice. Succinic dehydrogenase(SDH) and phosphorylase only in the liver activities were significantly reduced in a dose dependent manner. Acid phosphatase activity was significantly decreased in the liver of low dose arsenic treated animals; however, significant rise in its activity was observed in high dose group. As compared with vehicle control, treatment also caused significant dose dependent reductions in SDH, alkaline phosphatase and acid phosphatase activities in the kidney of mice. Vitamin E cotreatment as well as, 30 d withdrawal of arsenic trioxide treatment with or without vitamin E caused significant amelioration in arsenic induced toxicity in mice. Administration of vitamin E during withdrawal of treatment also caused significant amelioration as compared from only withdrawal of the treatment. It is concluded that vitamin E ameliorates arsenic induced toxicities in the liver and kidney of mice.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
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.
文摘Aim： To assess the effect of estradiol-17β （E2） and bisphenol A （BPA） administered chronically by implanting a silicone tube throughout pregnancy and lactation on male pups＇ reproductive system in ICR mice. Methods： Female mice were implanted with a tube filled with 10 ng, 500 ng, 1 μg, or 10 μg of E2, or 100 μg or 5 mg of BPA, before mating. The tube was kept in the mice throughout pregnancy and lactation, until the pups had weaned at 4 weeks of age. During the period, E2 was released from the tube at 120 pg or 6, 12 or 120 ng/day, and BPA at 1.2 or 60 μg/day. Results： Most of the mice given 1 μg and 10 lag of E2 did not maintain their pregnancy. However, the other groups showed high rates of birth, more than 70%. At age of 4 weeks, the male pups were killed. Body weight and reproductive organ weights （testes, epididymides and accessory reproductive glands） in the treated groups did not differ from the control values, whereas the percentage of seminiferous tubules in the testis with mature spermatids was significantly lower in the groups given 10 ng and 500 ng of E2 and 5 mg of BPA than that in the control. Conclusion： Chronic exposure to E2 and BPA might disrupt spermatogenesis in male pups. （Asian JAndrol 2008 Mar; 10： 271-276）
文摘Oral administration of arsenic trioxide(3 and 6 mg/kg body weight/d) for 30 d caused, as compared with vehicle control, dose dependent significant reductions in body weight, absolute weight, protein, glycogen, as well as, total, dehydro and reduced ascorbic acid contents both in the liver and kidney of arsenic treated mice. Succinic dehydrogenase(SDH) and phosphorylase only in the liver activities were significantly reduced in a dose dependent manner. Acid phosphatase activity was significantly decreased in the liver of low dose arsenic treated animals; however, significant rise in its activity was observed in high dose group. As compared with vehicle control, treatment also caused significant dose dependent reductions in SDH, alkaline phosphatase and acid phosphatase activities in the kidney of mice. Vitamin E cotreatment as well as, 30 d withdrawal of arsenic trioxide treatment with or without vitamin E caused significant amelioration in arsenic induced toxicity in mice. Administration of vitamin E during withdrawal of treatment also caused significant amelioration as compared from only withdrawal of the treatment. It is concluded that vitamin E ameliorates arsenic induced toxicities in the liver and kidney of mice.
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.
