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Temporal Requirement for the Protective Effect of Dietary Cholesterol against Alcohol-Induced Vasoconstriction. 膳食胆固醇对酒精性血管收缩保护作用的时间需求。
Q4 Psychology Pub Date : 2020-01-01 Epub Date: 2020-10-20
Olga Seleverstov, Kelsey North, Maria Simakova, Shivantika Bisen, Alexandra Bickenbach, Zoran Bursac, Alex M Dopico, Anna N Bukiya

Moderate-to-heavy episodic alcohol drinking resulting in 30-80 mM of ethanol in blood constricts cerebral arteries and constitutes a risk factor for cerebrovascular disease. Alcohol-induced constriction of cerebral arteries in vivo and ex vivo has been shown to be blunted by dietary cholesterol (CLR) in a rat model of a high-CLR diet. Such protection has been proposed to arise from the high-CLR diet-driven increase in blood CLR levels and accompanying buildup of CLR within the cerebral artery smooth muscle. Here we used a rat model of high-CLR feeding in vivo and pressurized cerebral arteries ex vivo to examine whether the degree and time-course of alcohol-induced constriction are related to blood CLR levels. We demonstrate that subjecting young (3 weeks-old, 50 g) male Sprague-Dawley rats to a high- CLR feeding up to 41 weeks, resulted in an age-dependent increase in total blood CLR levels, when compared to those of age-matched rats on isocaloric (control) chow. This increase was paralleled by a high-CLR diet-driven elevation of blood low-density lipoproteins whereas high-density lipoprotein levels matched those of age-matched, chow-fed controls. Alcohol-induced constriction was only blunted by high-CLR dietary intake when high-CLR chow was taken for up to 8-12 and 18-23 weeks. However, alcohol-constriciton was not blunted when high-CLR chow intake lasted for longer times, such as 28-32 and 38-41 weeks. Thus, alcohol-induced constriction of rat middle cerebral arteries did not critically depend on the total blood CLR levels. Alcohol-induced constriction seemed unrelated to the natural, progressive elevation of the total blood CLR level in control- or high-CLR-fed animals over time. Thus, neither the exogenously nor endogenously driven increases in blood CLR could predict cerebral artery susceptibility to alcohol-induced constriction. However, we identified a temporal requirement for the protective effect of dietary CLR against alcohol, that could be governed by the young age of the high- CLR chow recipients (3 weeks of age) and/or the short duration of high-CLR chow feeding lasting for up to 23 weeks.

中度至重度间歇性饮酒导致血液中30-80毫米乙醇收缩脑动脉,构成脑血管疾病的危险因素。在高CLR饮食的大鼠模型中,酒精诱导的体内和体外脑动脉收缩被膳食胆固醇(CLR)所钝化。这种保护被认为是由高CLR饮食驱动的血液CLR水平的增加和伴随的脑动脉平滑肌内CLR的积累引起的。本研究采用体内高CLR饲养和体外加压脑动脉的大鼠模型,研究酒精诱导的收缩程度和时间过程是否与血液CLR水平有关。我们证明,将年轻(3周大,50克)雄性Sprague-Dawley大鼠喂食高CLR至41周,与年龄匹配的大鼠喂食等热量(对照)食物相比,会导致总血液CLR水平的年龄依赖性增加。这种增加与高clr饮食驱动的血液低密度脂蛋白升高相平行,而高密度脂蛋白水平与年龄匹配的低密度脂蛋白水平相匹配。在8-12周和18-23周内,高clr食物摄入只会减弱酒精引起的收缩。然而,当高clr食物摄入持续较长时间(如28-32周和38-41周)时,酒精收缩并未减弱。因此,酒精诱导的大鼠大脑中动脉收缩并不完全依赖于总血CLR水平。在对照组或高CLR喂养的动物中,酒精诱导的收缩似乎与随时间推移血液总CLR水平的自然渐进升高无关。因此,无论是外源性还是内源性驱动的血液CLR升高都不能预测脑动脉对酒精引起的收缩的易感性。然而,我们确定了饮食中CLR对酒精的保护作用的时间要求,这可能是由高CLR饲料接受者的年龄小(3周龄)和/或高CLR饲料喂养时间短(长达23周)决定的。
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引用次数: 0
Bi-directional Acceleration of Alcohol Use and Opioid Use Disorder 酒精使用和阿片类药物使用障碍双向加速
Q4 Psychology Pub Date : 2019-10-18 DOI: 10.4303/JDAR/236084
Wenfei Huang, Erika P. Penaherrera, Danaika F. Desir, Dominick L. Gamarro, J. Cottrell, Tinchun Chu, Sulie L. Chang
Alcohol is the most widely used addictive substance. Severe alcohol abuse is diagnosed as “alcohol use disorder” (AUD). A common and harmful drinking pattern is binge drinking that elevates a person’s blood alcohol concentration to ≥ 0.08%. Such drinking may be an early indicator of AUD. Opioid misuse and dependence have become worldwide crises. Patterned consumption of various opioids can develop into opioid use disorder (OUD). An intertwined epidemic exists between opioid abuse, alcohol addiction, and binge drinking. Currently, studies on the interaction of AUD and OUD are limited and the underlying mechanisms linking these disorders remains unclear. We reviewed studies on AUD and OUD and utilized Ingenuity Pathway Analysis (IPA) to identify mechanisms of AUD and OUD interaction and potential gene targets for therapeutic agents. According to IPA Canonical Pathways Analysis, Gamma-aminobutyric Acid (GABA) Receptor Signaling, Neuroinflammation Signaling Pathway, Opioid Signaling Pathway and Dopamine-DARPP32 Feedback in cAMP Signaling are potential contributors to the interaction of AUD and OUD.
酒精是使用最广泛的成瘾物质。严重酒精滥用被诊断为“酒精使用障碍”(AUD)。一种常见且有害的饮酒模式是酗酒,将人的血液酒精浓度提高到≥0.08%。这样的饮酒可能是AUD的早期指标。阿片类药物滥用和依赖已成为全球性危机。各种阿片类药物的模式消费可发展为阿片类药物使用障碍(OUD)。阿片类药物滥用、酒精成瘾和酗酒之间存在着一种相互交织的流行病。目前,关于AUD和OUD相互作用的研究有限,连接这些疾病的潜在机制尚不清楚。我们回顾了AUD和OUD的研究,并利用独创性途径分析(Ingenuity Pathway Analysis, IPA)来确定AUD和OUD相互作用的机制和治疗药物的潜在基因靶点。根据IPA典型通路分析,γ -氨基丁酸(GABA)受体信号通路、神经炎症信号通路、阿片信号通路和cAMP信号通路中的多巴胺- darpp32反馈是AUD和OUD相互作用的潜在因素。
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引用次数: 2
Bi-directional Acceleration of Alcohol Use and Opioid Use Disorder. 酒精使用和阿片类药物使用障碍双向加速。
Q4 Psychology Pub Date : 2019-10-18
Wenfei Huang, Erika P Penaherrera, Danaika F Desir, Dominick L Gamarro, Jessica Cottrell, Tinchun Chu, Sulie L Chang

Alcohol is the most widely used addictive substance. Severe alcohol abuse is diagnosed as "alcohol use disorder" (AUD). A common and harmful drinking pattern is binge drinking that elevates a person's blood alcohol concentration to ≥ 0.08%. Such drinking may be an early indicator of AUD. Opioid misuse and dependence have become worldwide crises. Patterned consumption of various opioids can develop into opioid use disorder (OUD). An intertwined epidemic exists between opioid abuse, alcohol addiction, and binge drinking. Currently, studies on the interaction of AUD and OUD are limited and the underlying mechanisms linking these disorders remains unclear. We reviewed studies on AUD and OUD and utilized Ingenuity Pathway Analysis (IPA) to identify mechanisms of AUD and OUD interaction and potential gene targets for therapeutic agents. According to IPA Canonical Pathways Analysis, Gamma-aminobutyric Acid (GABA) Receptor Signaling, Neuroinflammation Signaling Pathway, Opioid Signaling Pathway and Dopamine-DARPP32 Feedback in cAMP Signaling are potential contributors to the interaction of AUD and OUD.

酒精是使用最广泛的成瘾物质。严重酒精滥用被诊断为“酒精使用障碍”(AUD)。一种常见且有害的饮酒模式是酗酒,将人的血液酒精浓度提高到≥0.08%。这样的饮酒可能是AUD的早期指标。阿片类药物滥用和依赖已成为全球性危机。各种阿片类药物的模式消费可发展为阿片类药物使用障碍(OUD)。阿片类药物滥用、酒精成瘾和酗酒之间存在着一种相互交织的流行病。目前,关于AUD和OUD相互作用的研究有限,连接这些疾病的潜在机制尚不清楚。我们回顾了AUD和OUD的研究,并利用独创性途径分析(Ingenuity Pathway Analysis, IPA)来确定AUD和OUD相互作用的机制和治疗药物的潜在基因靶点。根据IPA典型通路分析,γ -氨基丁酸(GABA)受体信号通路、神经炎症信号通路、阿片信号通路和cAMP信号通路中的多巴胺- darpp32反馈是AUD和OUD相互作用的潜在因素。
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引用次数: 0
Both Ketamine and NBQX Attenuate Alcohol-Withdrawal Induced Depression in Male Rats. 氯胺酮和 NBQX 均可减轻雄性大鼠在酒精戒断后产生的抑郁情绪
Q4 Psychology Pub Date : 2019-01-01 DOI: 10.4303/jdar/236069
Bruk Getachew, Yousef Tizabi

The co-morbidity between heavy drinking and depression can negatively influence successful cessation of alcohol use. Since ketamine, a glutamatergic NMDA receptor antagonist, has shown promise as a quick-acting antidepressant, we studied its effects specifically on alcohol withdrawal-induced depression. We also evaluated the effects of NBQX an AMPA/kainate receptor antagonist, because some of the effects of ketamine are proposed to be indirectly mediated through these receptors. Adult male Wistar rats were exposed daily to ethanol via inhalation chambers 4 h/day for 7 days (blood alcohol concentration=160 mg%), followed by daily intraperitoneal injections of ketamine (2.5 mg/kg), NBQX (5mg/kg), alone or in combination. Eighteen hours later, open field locomotor activity (OFLA) followed by forced swim test (FST) were performed. The animals were sacrificed 2 h later for evaluation of brain-derived neurotrophic factor (BDNF) in the hippocampus. Alcohol withdrawal did not affect OFLA, but caused an increase in immobility in FST, suggesting induction of "depressive-like" helplessness. Both ketamine and NBQX normalized the swimming score in FST. The combination of the two drugs, however, cancelled each other's effect. Parallel to these behavioral observations, both ketamine and NBQX normalized the reduction in hippocampal BDNF caused by alcohol withdrawal. Here also, the combination of the two drugs cancelled each other's effect. These results suggest that either NMDA or AMPA/kainate receptor antagonists, acting at least partially through hippocampal BDNF, may be of therapeutic potential in alcohol use disorder.

大量饮酒与抑郁共存会对成功戒酒产生负面影响。氯胺酮是一种谷氨酸能 NMDA 受体拮抗剂,有望成为一种速效抗抑郁药,因此我们专门研究了氯胺酮对戒酒引起的抑郁症的影响。我们还评估了 AMPA/kainate 受体拮抗剂 NBQX 的作用,因为氯胺酮的某些作用被认为是通过这些受体间接介导的。成年雄性 Wistar 大鼠每天通过吸入室暴露于乙醇中 4 小时,持续 7 天(血液中酒精浓度=160 毫克%),然后每天腹腔注射氯胺酮(2.5 毫克/千克)、NBQX(5 毫克/千克),单独或混合使用。18 小时后,进行开阔地运动试验(OFLA)和强迫游泳试验(FST)。2 小时后,动物被处死,以评估海马中的脑源性神经营养因子(BDNF)。戒酒不会影响OFLA,但会导致FST中的不移动性增加,这表明诱导了 "类似抑郁 "的无助感。氯胺酮和 NBQX 都能使 FST 中的游泳得分正常化。然而,两种药物联合使用会相互抵消作用。与这些行为观察结果类似,氯胺酮和 NBQX 也能使因戒酒导致的海马 BDNF 减少恢复正常。在这种情况下,两种药物的联合作用也会相互抵消。这些结果表明,NMDA或AMPA/kainate受体拮抗剂至少部分通过海马BDNF发挥作用,可能对酒精使用障碍具有治疗潜力。
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引用次数: 0
Gestational Age-Dependent Interplay between Endocannabinoid Receptors and Alcohol in Fetal Cerebral Arteries. 胎儿脑动脉中内源性大麻素受体与酒精的相互作用与妊娠年龄有关
Q4 Psychology Pub Date : 2019-01-01 DOI: 10.4303/jdar/236068
Maria Simakova, Ana Tobiasz, Ryan D Sullivan, Shivantika Bisen, Jose Duncan, J Pierce Sullivan, Steven Davison, Danielle L Tate, Stacey Barnett, Giancarlo Mari, Alex M Dopico, Anna N Bukiya

Alcohol (ethanol) is one of the most widely consumed drugs. Alcohol consumption by pregnant women may result in a range of fetal abnormalities termed fetal alcohol spectrum disorders (FASDs). The cerebrovascular system is emerging as a critical target of alcohol in the developing brain. We recently showed that three episodes of prenatal alcohol exposure resulting in 80 mg/dL alcohol in maternal blood during mid-pregnancy up-regulated anandamide-induced dilation of fetal cerebral arteries. Moreover, ethanol dilated fetal cerebral arteries via cannabinoid (CB) receptors. Whether a critical role of fetal cerebral artery CB system in responses to alcohol was maintained throughout the gestation, remains unknow.

Main methods: Pregnant baboons (second trimester equivalent) were subjected to three episodes of either alcohol or control drink infusion via gavage. Cerebral arteries from mothers and near-term female fetuses were in vitro pressurized for diameter monitoring.

Key findings: Near-term fetal and maternal arteries exhibited similar ability to develop myogenic tone, to constrict in presence of 60 mM KCl, and to respond to 10 µM anandamide. Fetal and maternal arteries largely failed to dilate in presence of 63 mM ethanol. No differences were detected between arteries from control and alcohol-exposed baboon donors. Therefore, previously observed ethanol-induced dilation of fetal cerebral arteries and up-regulation of CB components in response to fetal alcohol exposure during mid-pregnancy was transient and disappeared by near-term.

酒精(乙醇)是消费最广泛的药物之一。孕妇饮酒可能导致胎儿出现一系列畸形,被称为胎儿酒精谱系障碍(FASD)。脑血管系统正在成为酒精在大脑发育过程中的一个关键靶点。我们最近的研究表明,在妊娠中期,三次产前酒精暴露导致母体血液中酒精含量达到 80 毫克/分升,会上调安乃近诱导的胎儿脑动脉扩张。此外,乙醇通过大麻素(CB)受体扩张胎儿的脑动脉。胎儿大脑动脉CB系统对酒精反应的关键作用是否会在整个妊娠期内持续,目前仍不得而知:主要方法:妊娠狒狒(相当于怀孕后三个月)通过灌胃的方式接受三次酒精或对照组饮料的注射。对母体和近足月雌性胎儿的脑动脉进行体外加压,以进行直径监测:主要发现:近龄胎儿和母体动脉表现出相似的肌张力、在 60 mM KCl 存在下收缩的能力以及对 10 µM 苯甲酰胺的反应能力。胎儿动脉和母体动脉在 63 毫摩尔乙醇条件下基本无法扩张。对照组和暴露于酒精的狒狒供体的动脉之间未发现差异。因此,之前观察到的乙醇诱导的胎儿脑动脉扩张和CB成分上调对妊娠中期胎儿酒精暴露的反应是短暂的,并在临近分娩时消失。
{"title":"Gestational Age-Dependent Interplay between Endocannabinoid Receptors and Alcohol in Fetal Cerebral Arteries.","authors":"Maria Simakova, Ana Tobiasz, Ryan D Sullivan, Shivantika Bisen, Jose Duncan, J Pierce Sullivan, Steven Davison, Danielle L Tate, Stacey Barnett, Giancarlo Mari, Alex M Dopico, Anna N Bukiya","doi":"10.4303/jdar/236068","DOIUrl":"10.4303/jdar/236068","url":null,"abstract":"<p><p>Alcohol (ethanol) is one of the most widely consumed drugs. Alcohol consumption by pregnant women may result in a range of fetal abnormalities termed fetal alcohol spectrum disorders (FASDs). The cerebrovascular system is emerging as a critical target of alcohol in the developing brain. We recently showed that three episodes of prenatal alcohol exposure resulting in 80 mg/dL alcohol in maternal blood during mid-pregnancy up-regulated anandamide-induced dilation of fetal cerebral arteries. Moreover, ethanol dilated fetal cerebral arteries via cannabinoid (CB) receptors. Whether a critical role of fetal cerebral artery CB system in responses to alcohol was maintained throughout the gestation, remains unknow.</p><p><strong>Main methods: </strong>Pregnant baboons (second trimester equivalent) were subjected to three episodes of either alcohol or control drink infusion via gavage. Cerebral arteries from mothers and near-term female fetuses were <i>in vitro</i> pressurized for diameter monitoring.</p><p><strong>Key findings: </strong>Near-term fetal and maternal arteries exhibited similar ability to develop myogenic tone, to constrict in presence of 60 mM KCl, and to respond to 10 µM anandamide. Fetal and maternal arteries largely failed to dilate in presence of 63 mM ethanol. No differences were detected between arteries from control and alcohol-exposed baboon donors. Therefore, previously observed ethanol-induced dilation of fetal cerebral arteries and up-regulation of CB components in response to fetal alcohol exposure during mid-pregnancy was transient and disappeared by near-term.</p>","PeriodicalId":37818,"journal":{"name":"Journal of Drug and Alcohol Research","volume":"8 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37214235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prenatal Alcohol Exposure, Anesthesia, and Fetal Loss in Baboon Model of Pregnancy. 产前酒精暴露、麻醉和狒狒妊娠模型的胎儿丢失
Q4 Psychology Pub Date : 2018-06-01
Kelsey North, Ana Tobiasz, Ryan D Sullivan, Zoran Bursac, Jose Duncan, J Pierce Sullivan, Steven Davison, Danielle L Tate, Stacey Barnett, Giancarlo Mari, Anna N Bukiya

Approximately half of pregnant women engage in alcohol consumption some time during pregnancy. On the other hand, a small percentage of pregnant women undergo surgery and anesthesia at some time during pregnancy. In emergencies, anesthesia has to be administered to patients who are under alcohol intoxication. Anesthetic management during pregnancy while patients are intoxicated with alcohol is challenging. Here, we utilized a retrospective analysis of data available from 17 pregnant baboons that underwent anesthesia with alcohol exposure during mid-pregnancy. The analysis was designed to answer three questions: whether maternal vital signs remained stable under anesthesia combined with alcohol, whether maternal vital signs that were routinely monitored under anesthesia could serve as predictor(s) of fetal loss, and what the impact of the combined application of anesthesia and alcohol was on fetal loss. For the purpose of this retrospective analysis, we utilized vital sign (heart and respiratory rates, temperature, oxygen, carbon dioxide, systolic and diastolic blood pressure) and pregnancy outcome (miscarriage versus fetal survival through second trimester-equivalent of human pregnancy) records from 17 pregnant baboons that underwent gastric infusion of either control or alcohol-containing drink under isoflurane anesthesia during the second trimester-equivalent of human pregnancy. Half of the dams underwent a brief prior anesthetic episode for the purpose of gestational age confirmation. Thus, in our analysis, baboons were divided into four groups: "Control" without prior anesthesia, "Control" with prior anesthesia, "Alcohol" without prior anesthesia, and "Alcohol" with prior anesthesia. We did not detect any maternal vital sign in any of the groups that would be predictive of a fetal loss. However, prior anesthesia predisposed dams to the risk of lowering maternal systolic blood pressure and to a significant decrease in maternal oxygen level during the combined application of anesthesia and alcohol. Conceivably, our data showed the largest fetal loss in this group. The disruptive nature of anesthesia and alcohol on maternal vital parameters warns against the use of anesthesia in combination with alcohol during pregnancy.

大约一半的孕妇在怀孕期间会饮酒。另一方面,一小部分孕妇在怀孕期间接受手术和麻醉。在紧急情况下,必须对酒精中毒的病人实施麻醉。怀孕期间的麻醉管理,而患者醉酒是具有挑战性的。在这里,我们对17只怀孕狒狒的数据进行了回顾性分析,这些狒狒在怀孕中期接受了酒精麻醉。分析旨在回答三个问题:麻醉联合酒精下产妇生命体征是否保持稳定;麻醉下常规监测的产妇生命体征是否可以作为胎儿丢失的预测指标;麻醉和酒精联合应用对胎儿丢失的影响。为了进行回顾性分析,我们利用了17只怀孕狒狒的生命体征(心脏和呼吸频率、体温、氧气、二氧化碳、收缩压和舒张压)和妊娠结局(流产与妊娠中期胎儿存活率的对比)记录,这些狒狒在妊娠中期(相当于人类妊娠)在异氟醚麻醉下接受了对照或含酒精饮料的胃输注。为了确认胎龄,一半的母鼠接受了短暂的麻醉。因此,在我们的分析中,狒狒被分为四组:没有事先麻醉的“对照组”、事先麻醉的“对照组”、没有事先麻醉的“酒精组”和事先麻醉的“酒精组”。在任何一组中,我们都没有发现任何母体生命体征可以预测胎儿的损失。然而,在麻醉和酒精联合应用期间,先前的麻醉易导致产妇收缩压降低和产妇氧水平显著降低的风险。可想而知,我们的数据显示,这组胎儿损失最大。麻醉和酒精对产妇生命参数的破坏性质警告怀孕期间不要将麻醉与酒精结合使用。
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引用次数: 0
Prenatal Alcohol Exposure, Anesthesia, and Fetal Loss in Baboon Model of Pregnancy 产前酒精暴露、麻醉和狒狒妊娠模型的胎儿丢失
Q4 Psychology Pub Date : 2018-06-01 DOI: 10.4303/JDAR/236064
Kelsey C. North, A. Tobiasz, Ryan D. Sullivan, Z. Bursac, J. Duncan, J. P. Sullivan, Steven Davison, D. Tate, Stacey Barnett, G. Mari, A. Bukiya
Approximately half of pregnant women engage in alcohol consumption some time during pregnancy. On the other hand, a small percentage of pregnant women undergo surgery and anesthesia at some time during pregnancy. In emergencies, anesthesia has to be administered to patients who are under alcohol intoxication. Anesthetic management during pregnancy while patients are intoxicated with alcohol is challenging. Here, we utilized a retrospective analysis of data available from 17 pregnant baboons that underwent anesthesia with alcohol exposure during mid-pregnancy. The analysis was designed to answer three questions: whether maternal vital signs remained stable under anesthesia combined with alcohol, whether maternal vital signs that were routinely monitored under anesthesia could serve as predictor(s) of fetal loss, and what the impact of the combined application of anesthesia and alcohol was on fetal loss. For the purpose of this retrospective analysis, we utilized vital sign (heart and respiratory rates, temperature, oxygen, carbon dioxide, systolic and diastolic blood pressure) and pregnancy outcome (miscarriage versus fetal survival through second trimester-equivalent of human pregnancy) records from 17 pregnant baboons that underwent gastric infusion of either control or alcohol-containing drink under isoflurane anesthesia during the second trimester-equivalent of human pregnancy. Half of the dams underwent a brief prior anesthetic episode for the purpose of gestational age confirmation. Thus, in our analysis, baboons were divided into four groups: “Control” without prior anesthesia, “Control” with prior anesthesia, “Alcohol” without prior anesthesia, and “Alcohol” with prior anesthesia. We did not detect any maternal vital sign in any of the groups that would be predictive of a fetal loss. However, prior anesthesia predisposed dams to the risk of lowering maternal systolic blood pressure and to a significant decrease in maternal oxygen level during the combined application of anesthesia and alcohol. Conceivably, our data showed the largest fetal loss in this group. The disruptive nature of anesthesia and alcohol on maternal vital parameters warns against the use of anesthesia in combination with alcohol during pregnancy.
大约一半的孕妇在怀孕期间会饮酒。另一方面,一小部分孕妇在怀孕期间接受手术和麻醉。在紧急情况下,必须对酒精中毒的病人实施麻醉。怀孕期间的麻醉管理,而患者醉酒是具有挑战性的。在这里,我们对17只怀孕狒狒的数据进行了回顾性分析,这些狒狒在怀孕中期接受了酒精麻醉。分析旨在回答三个问题:麻醉联合酒精下产妇生命体征是否保持稳定;麻醉下常规监测的产妇生命体征是否可以作为胎儿丢失的预测指标;麻醉和酒精联合应用对胎儿丢失的影响。为了进行回顾性分析,我们利用了17只怀孕狒狒的生命体征(心脏和呼吸频率、体温、氧气、二氧化碳、收缩压和舒张压)和妊娠结局(流产与妊娠中期胎儿存活率的对比)记录,这些狒狒在妊娠中期(相当于人类妊娠)在异氟醚麻醉下接受了对照或含酒精饮料的胃输注。为了确认胎龄,一半的母鼠接受了短暂的麻醉。因此,在我们的分析中,狒狒被分为四组:没有事先麻醉的“对照组”、事先麻醉的“对照组”、没有事先麻醉的“酒精组”和事先麻醉的“酒精组”。在任何一组中,我们都没有发现任何母体生命体征可以预测胎儿的损失。然而,在麻醉和酒精联合应用期间,先前的麻醉易导致产妇收缩压降低和产妇氧水平显著降低的风险。可想而知,我们的数据显示,这组胎儿损失最大。麻醉和酒精对产妇生命参数的破坏性质警告怀孕期间不要将麻醉与酒精结合使用。
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引用次数: 3
Alcohol-Induced Hepatic Steatosis: A Comparative Study to Identify Possible Indicator(s) of Alcoholic Fatty Liver Disease. 酒精性肝脂肪变性:确定酒精性脂肪性肝病可能指标的比较研究
Q4 Psychology Pub Date : 2018-01-01 DOI: 10.4303/jdar/236040
Harshica Fernando, Kamlesh K Bhopale, Shakuntala S Kondraganti, Bhupendra S Kaphalia, G A Shakeel Ansari

Background: Fatty liver is an early sign of both nonalcoholic and alcoholic fatty liver diseases. Ethanol feeding using a Lieber-DeCarli liquid diet (LD) model which contains 35% fat to rats or mice is a well-established model for alcoholic fatty liver. However, LD diet alone can also induce fatty liver and its differential metabolic profile may be able to differentiate steatosis induced by LD versus LD plus ethanol.

Purpose: We investigated the lipidomic differences in the livers of Sprague-Dawley (SD) rats fed a pellet diet (PD), LD and liquid ethanol diet (LED) for six weeks.

Study design: Male Sprague Dawley rats were fed with nonalcoholic diets PD, LD or LED (ethanol in LD) for six weeks. Lipids were extracted and analyzed by nuclear magnetic resonance (NMR)- based metabolomics. The NMR data obtained was analyzed by multivariate Principal Component Analysis (PCA) and Spotfire DecisionSite 9.0 software to compare PD versus LD and LD versus LED groups.

Results: PCA of the NMR spectral data of livers of both comparisons showed a clear separation of PD from LD group and LD from LED group indicating differences in lipid profiles which corresponded with changes in total lipid weights. LD showed increases for cholesterol, esterified cholesterol, cholesterol acetate and triglycerides with decreases for fatty acyl chain, diallylic and allylic protons, while the LED showed increases in esterified cholesterol, cholesterol acetate, fatty acid methyl esters, allylic protons and some triglyceride protons with decreases in free cholesterol and phosphatidylcholine (PC).

Conclusion: Our data suggest that altered lipid signature or PC levels could be an indicator to differentiate between nonalcoholic versus alcoholic fatty liver.

背景:脂肪肝是非酒精性和酒精性脂肪肝疾病的早期征兆。用含35%脂肪的Lieber-DeCarli液体饲粮(LD)模型进行酒精性脂肪肝的乙醇喂养是一种成熟的酒精性脂肪肝模型。然而,LD饮食本身也可以诱导脂肪肝,其不同的代谢谱可能能够区分LD诱导的脂肪变性与LD加乙醇诱导的脂肪变性。目的:研究SD (Sprague-Dawley)大鼠分别饲喂颗粒饲料(PD)、LD和液体乙醇饲料(LED) 6周后肝脏脂质组学的差异。研究设计:雄性斯普拉格·道利大鼠分别饲喂不含酒精的PD、LD或LED (LD中含有乙醇)6周。脂质提取并通过核磁共振(NMR)代谢组学进行分析。获得的核磁共振数据通过多元主成分分析(PCA)和Spotfire DecisionSite 9.0软件进行分析,比较PD组与LD组以及LD组与LED组。结果:两组比较的肝脏核磁共振谱数据PCA显示PD与LD组和LD与LED组明显分离,表明脂质谱的差异与总脂质重量的变化相对应。LD显示胆固醇、酯化胆固醇、醋酸胆固醇和甘油三酯增加,脂肪酰基链、二烯丙基和烯丙基质子减少;LED显示酯化胆固醇、醋酸胆固醇、脂肪酸甲酯、烯丙基质子和部分甘油三酯质子增加,游离胆固醇和磷脂酰胆碱(PC)减少。结论:我们的数据表明,脂质特征或PC水平的改变可能是区分非酒精性和酒精性脂肪肝的一个指标。
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引用次数: 2
Ketamine Differentially Attenuates Alcohol Intake in Male Versus Female Alcohol Preferring (P) Rats. 氯胺酮对雄性和雌性酒精偏好(P)大鼠的酒精摄入有不同程度的抑制作用。
Q4 Psychology Pub Date : 2017-01-01 Epub Date: 2017-07-28 DOI: 10.4303/jdar/236030
Amir H Rezvani, Edward D Levin, Marty Cauley, Bruk Getachew, Yousef Tizabi

Background: Although various pharmacological tools in combating addiction to alcohol are available, their efficacy is limited. Hence, there is a critical need for development of more effective medications. Recent advances in the field have identified the glutamatergic system as a potential novel target for intervention in addictive behaviors.

Purpose: Hence, we evaluated the effects of acute administration of low (subanesthetic) doses of ketamine, an NMDA receptor antagonist, on alcohol intake and alcohol preference in both male and female rats.

Study design: Adult alcohol preferring (P) rats were exposed to two-bottle choice (ethanol 10% and water) for at least three weeks following a nine-day training period and the effects of various doses of ketamine (5 mg/kg, 7.5 mg/kg, and 10 mg/kg, injected subcutaneously, SC) on consumption of alcohol over various time periods during a 24 h interval were measured.

Results: Our results indicate that ketamine treatment significantly reduced both alcohol intake and preference in a time- and dose-dependent manner in both sexes. Moreover, a differential sensitivity between the sexes was observed. Thus, although alcohol intake was higher in males, female rats responded much more strongly to the highest dose of ketamine than males in the initial time periods.

Conclusion: It is concluded that glutamatergic receptor manipulations may be of therapeutic potential in addiction to alcohol and that different sexes may respond differentially to such treatments.

背景:尽管目前已有多种药物工具可用于对抗酒瘾,但其疗效有限。因此,亟需开发更有效的药物。目的:因此,我们评估了急性给予低剂量(亚麻醉)氯胺酮(一种 NMDA 受体拮抗剂)对雄性和雌性大鼠酒精摄入量和酒精偏好的影响:研究设计:成年酒精偏好(P)大鼠在经过为期九天的训练后,至少有三周的时间暴露于双瓶选择(10%乙醇和水)的环境中,测量不同剂量氯胺酮(5 毫克/千克、7.5 毫克/千克和 10 毫克/千克,皮下注射,SC)对 24 小时间隔内不同时间段酒精摄入量的影响:结果:我们的研究结果表明,氯胺酮治疗能显著降低酒精摄入量和酒精偏好,且对时间和剂量均有依赖性。此外,我们还观察到了两性之间不同的敏感性。因此,虽然雄性大鼠的酒精摄入量较高,但在最初的一段时间内,雌性大鼠对最高剂量氯胺酮的反应比雄性大鼠强烈得多:结论:对谷氨酸能受体的操作可能具有治疗酒精成瘾的潜力,不同性别的大鼠对这种治疗方法的反应可能不同。
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引用次数: 0
Alcohol-Induced Increases in Inflammatory Cytokines Are Attenuated by Nicotine in Region-Selective Manner in Male Rats. 尼古丁在雄性大鼠体内的区域选择性作用可减轻酒精诱导的炎症细胞因子增加。
Q4 Psychology Pub Date : 2017-01-01 Epub Date: 2017-09-16 DOI: 10.4303/jdar/236036
Olubukola Kalejaiye, Bruk Getachew, Clifford L Ferguson, Robert E Taylor, Yousef Tizabi

Background: Heavy use of alcohol is commonly associated with heavy smoking (nicotine intake). Although many factors, including mood effects of these two drugs may contribute to their co-use, the exact neurobiological underpinnings are far from clear. It is well known that chronic alcohol exposure induces neuroinflammation that may precipitate depressive-like behavior, which is considered an important factor in alcohol relapse. Nicotine, on the other hand, possesses anti-inflammatory and antidepressant effects.

Purpose: In this study, we sought to determine which proinflammatory markers may be associated with the depressogenic effects of chronic alcohol and whether nicotine pretreatment may normalize these changes.

Study design: For this purpose, we treated adult male Wistar rats with alcohol (1.0 g/kg, IP), nicotine (0.3 mg/kg, IP) or their combination once daily for 14 days. Two prominent proinflammatory cytokines (IL-1β and TNF-α) in two primary brain regions, namely the hippocampus and frontal cortex that are intimately involved in mood regulation, were evaluated.

Results: Chronic alcohol resulted in increases in both cytokines in both regions as determined by Western blot. Nicotine completely blocked alcohol-induced effects in the hippocampus, but not in the frontal cortex. These data suggest that nicotine may mitigate the inflammatory effects of alcohol in brain-selective region. Hence, the previously observed depressogenic effects of alcohol and the antidepressant effects of nicotine may at least be partially mediated through manipulations of proinflammatory cytokines in the hippocampus.

Conclusion: These findings suggest possible therapeutic potential of anti-inflammatory cytokines in combating alcohol-induced depression and/or relapse.

背景:大量饮酒通常与大量吸烟(尼古丁摄入)有关。尽管包括这两种药物对情绪的影响在内的许多因素都可能导致这两种药物的共同使用,但其确切的神经生物学基础却远不清楚。众所周知,长期接触酒精会诱发神经炎症,从而引发类似抑郁的行为,这被认为是酒精复发的一个重要因素。目的:在这项研究中,我们试图确定哪些促炎标志物可能与慢性酒精的抑郁效应有关,以及尼古丁预处理是否可以使这些变化正常化:为此,我们用酒精(1.0 克/千克,IP)、尼古丁(0.3 毫克/千克,IP)或它们的组合给成年雄性 Wistar 大鼠治疗,每天一次,连续 14 天。结果发现,慢性酒精会导致两种主要促炎细胞因子(IL-1β和TNF-α)在两个主要脑区(即与情绪调节密切相关的海马区和额叶皮层)的升高:结果:通过 Western 印迹法测定,慢性酒精会导致这两个区域的两种细胞因子增加。尼古丁能完全阻断酒精对海马区的影响,但不能阻断对额叶皮层的影响。这些数据表明,尼古丁可减轻酒精在大脑选择性区域的炎症效应。因此,之前观察到的酒精的致抑郁效应和尼古丁的抗抑郁效应可能至少部分是通过操纵海马中的促炎细胞因子介导的:这些研究结果表明,抗炎细胞因子在对抗酒精引起的抑郁和/或复发方面可能具有治疗潜力。
{"title":"Alcohol-Induced Increases in Inflammatory Cytokines Are Attenuated by Nicotine in Region-Selective Manner in Male Rats.","authors":"Olubukola Kalejaiye, Bruk Getachew, Clifford L Ferguson, Robert E Taylor, Yousef Tizabi","doi":"10.4303/jdar/236036","DOIUrl":"10.4303/jdar/236036","url":null,"abstract":"<p><strong>Background: </strong>Heavy use of alcohol is commonly associated with heavy smoking (nicotine intake). Although many factors, including mood effects of these two drugs may contribute to their co-use, the exact neurobiological underpinnings are far from clear. It is well known that chronic alcohol exposure induces neuroinflammation that may precipitate depressive-like behavior, which is considered an important factor in alcohol relapse. Nicotine, on the other hand, possesses anti-inflammatory and antidepressant effects.</p><p><strong>Purpose: </strong>In this study, we sought to determine which proinflammatory markers may be associated with the depressogenic effects of chronic alcohol and whether nicotine pretreatment may normalize these changes.</p><p><strong>Study design: </strong>For this purpose, we treated adult male Wistar rats with alcohol (1.0 g/kg, IP), nicotine (0.3 mg/kg, IP) or their combination once daily for 14 days. Two prominent proinflammatory cytokines (IL-1<i>β</i> and TNF-<i>α</i>) in two primary brain regions, namely the hippocampus and frontal cortex that are intimately involved in mood regulation, were evaluated.</p><p><strong>Results: </strong>Chronic alcohol resulted in increases in both cytokines in both regions as determined by Western blot. Nicotine completely blocked alcohol-induced effects in the hippocampus, but not in the frontal cortex. These data suggest that nicotine may mitigate the inflammatory effects of alcohol in brain-selective region. Hence, the previously observed depressogenic effects of alcohol and the antidepressant effects of nicotine may at least be partially mediated through manipulations of proinflammatory cytokines in the hippocampus.</p><p><strong>Conclusion: </strong>These findings suggest possible therapeutic potential of anti-inflammatory cytokines in combating alcohol-induced depression and/or relapse.</p>","PeriodicalId":37818,"journal":{"name":"Journal of Drug and Alcohol Research","volume":"6 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35806552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of Drug and Alcohol Research
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