Overcoming qEEG Abnormalities and Reward Gene Deficits during Protracted Abstinence in Male Psychostimulant and Polydrug Abusers Utilizing Putative Dopamine D2 Agonist Therapy: Part 2

Abstract

Background: It is well established that in both food- and drug-addicted individuals there is “dopamine resistance” associated with the DRD2 gene A1 allele. Based on earlier studies, evidence is emerging wherein the potential of utilizing a natural, nonaddicting, safe, putative D2 agonist may play a significant role in the recovery of individuals with reward deficiency syndrome, including those addicted to psychoactive chemicals. Findings: Positive outcomes demonstrated by quantitative electroencephalographic (qEEG) imaging in a randomized, triple-blind, placebo-controlled, crossover study involving oral Synaptose Complex KB220Z? showed an increase of alpha waves and low beta wave activity in the parietal brain region. Using t statistics, significant differences observed between placebo and Synaptose Complex KB220Z? consistently occurred in the frontal regions after week 1 and then again after week 2 of analyses (P = 0.03). This is the first report to demonstrate involvement of the prefrontal cortex in the qEEG response to a natural putative D2 agonist (Synaptose Complex KB220Z?), especially evident in dopamine D2 A1 allele subjects. Independently, we have further supported this finding with an additional study of 3 serious polydrug abusers undergoing protracted abstinence who carried the DRD2 A1 allele. Significant qEEG differences were found between those who received 1 dose of placebo compared with those who were administered Synaptose Complex KB220Z?. Synaptose Complex KB220Z? induced positive regulation of the dysregulated electrical activity of the brain in these addicts. The results are indicative of a phase change from low amplitude or low power in the brain to a more regulated state by increasing an average of 6.169 mV² across the prefrontal cortical region. In the first experiment we found that while 50% of the subjects carried the DRD2 A1 allele, 100% carried ≥ 1 risk allele. Specifically, based on the proposed addiction risk score for these 14 subjects, 72% had moderate-to-severe addiction risk. Similar findings were obtained by repeating the experiment in 3 additional currently abstinent polydrug abusers carrying the DRD2 A1 allele. Conclusion: This seminal work will provide important information that may ultimately lead to significant improvement in the recovery of individuals with psychostimulant and polydrug abuse problems, specifically those with genetically induced dopamine deficiency. Based on this small sample size, we are proposing that with necessary large populations supporting these initial results, and possibly even additional candidate genes and single nucleotide polymorphisms, we may eventually have the clinical ability to classify severity according to genotype and possession of risk alleles, along with offering a safe, nonaddicting, natural dopaminergic receptor agonist that potentially upregulates instead of downregulates dopaminergic receptors, preferably the D2 subtype.     

NF-κB调控可卡因行为敏化的BDNF机制简

目的獉獉：探讨脑源性神经营养因子（BDNF）是否作为核因子NF-κB的靶基因,参与NF-κB对可卡因行为敏化的影响。方法獉獉：建立NF-κB抑制剂DDTC作用下的小鼠可卡因诱导行为敏化模型,用Real-time PCR检测海马、前额叶皮质、伏隔核中Bdnf的表达。结果獉獉：可卡因可诱导伏隔核和海马（而非前额叶皮质）中Bdnf的上调,而在DDTC的作用下,总Bdnf及BdnfⅣ在伏隔核、海马和前额叶皮质中分别表达下调、不变和上调。结论獉獉：在不同的脑区NF-κB作用的机制可能不同,在伏隔核中,Bdnf可能作为NF-κB的靶基因参与可卡因行为敏化的形成。     

siRNA沉默COX-2基因对KB/VCR细胞的增殖及侵袭的影响

目的:观察siRNA沉默口腔癌耐长春新碱细胞株KB/VCR细胞COX-2基因后,对KB/VCR细胞增殖及侵袭能力的影响。方法:将KB/VCR细胞分为COX-2 siRNA组、阴性对照组及空白对照组,采用RT-PCR检测各组细胞COX-2 mRNA的表达,蛋白印迹法检测COX-2蛋白的表达,MTT法检测各组细胞的生长抑制率,Transwell小室测定各组细胞侵袭能力的变化。结果:COX-2 siRNA组细胞的COX-2蛋白和mRNA的表达明显低于阴性对照组和空白对照组(P<0.01)。COX-2 siRNA组细胞的生长抑制率明显高于阴性对照组和空白对照组(P<0.01)。COX-2 siRNA组细胞的侵袭能力也明显降低。结论:COX-2 siRNA能特异性沉默KB/VCR细胞的COX-2基因,使KB/VCR细胞生长得到抑制,并减弱其侵袭能力。     

药学知识库发展与建设

介绍药学知识库内涵,分析建立药学知识库的必要性、意义、发展情况,从数据来源、模型构建、设计要点及应用几方面阐述其构建方法,提出未来发展方向。     

头孢吡肟对医院分离的革兰阴性杆菌的体外抗菌活性的四种方法学评价

目的词查四川大学华西医院2004年9月～11月301株临床常见革兰阴性杆菌对第四代头孢菌素头孢吡肟的耐药状况，评价我院现采用的MICROSCAN细菌鉴定药敏系统中快速接种法的准确性。方法用琼脂稀释法、纸片扩散法、标准浊度法和MICROSCAN快速接种法测定头孢毗肟对301株细菌的体外抑菌活性。以琼脂稀释法为标准参考方法，比较其它三种方法与其一致性。结果琼脂稀释法测定301株革兰阴性杆菌对头孢吡肟的体外总敏感率为78．1％；纸片扩散法、标准浊度法和MICROSCAN快速接种法与标准参考方法的一致率分别为：99．00%、98．3％和95．3％。纸片扩散法、标准浊度法与琼脂稀释法无统计学差异，MICROSCAN快速接种法与琼脂稀释法有统计学差异。结论头孢吡肟对大部分临床常见革兰阴性杆菌具有良好的体外抗菌活性。纸片扩散法及标准浊度法结果准确性较高。我院现采用的MICROSCAN快速接种法的准确性有待进一步探讨。     

ent-Kaur-16-en-19-oic acid,a KB cells cytotoxic diterpenoid from Elaeoselinum foetidum

Toxic and cytotoxic activities of the toxic plant Elaeoselinum foetidum (Apiaceae) were evaluated using the brine shrimp toxicity (BST) and KB cell cytotoxicity assays. The active chloroform extract was subjected to a bioactivity-directed fractionation, monitored by the BST assay, that led to the isolation of the diterpenoid ent-kaur-16-en-19-oic acid. This compound was potent against the brine shrimp (LC(50) = 4.8 microg/mL) and KB cells (IC(50) = 1.6 microg/mL).     

Biologic therapy of inflammatory bowel disease

Advancing knowledge regarding the biology of chronic inflammation has led to the development of specific biologic therapies that mechanistically target individual inflammatory pathways. Many biologic therapies are being evaluated for the treatment of the chronic inflammatory bowel diseases, Crohn's disease and ulcerative colitis. Biologic compounds proven to be effective for Crohn's disease include monoclonal antibodies to tumor necrosis factor (infliximab and CDP571) and to the leukocyte adhesion molecule alpha4 integrin (natalizumab). Other biologic compounds for which there is insufficient evidence to judge efficacy for inflammatory bowel disease include: p55 tumor necrosis factor binding protein (onercept); interferon alpha; interferon beta-1a; anti-interferon gamma antibody; anti-interleukin 12 antibody; p65 anti-sense oligonucleotide (blocks NF-kappaB); granulocyte colony stimulating factor, and granulocyte macrophage colony stimulating factor; anti-interleukin 2 receptor antibody; epidermal growth factor; keratinocyte growth factor 2 (repifermin); human growth hormone; anti-CD4 antibody; and anti-alpha4beta7 antibody. Biologic therapies that have been proven ineffective for inflammatory bowel disease include: interleukin 10; interleukin 11; anti-sense intercellular adhesion molecule-1; and the tumor necrosis factor receptor fusion protein etanercept. Based on the early successes of infliximab, CDP571 and natalizumab, it seems certain that biologic therapy will play an important role in the future treatment of inflammatory bowel disease.     

氯化两面针碱体外诱导人口腔鳞癌KB细胞G2／M期阻滞及凋亡的研究

目的探讨氯化两面针碱对人口腔鳞癌KB细胞周期和凋亡的影响及相互关系。方法应用MTT比色法测定氯化两面针碱对细胞增殖的抑制作用;流式细胞术(FCM)检测氯化两面针碱对细胞周期的影响;Hoechst33258检测细胞凋亡;透射电镜观察细胞超微结构。结果氯化两面针碱在体外呈浓度依赖性显著抑制KB细胞的生长,48hIC_(50)为(2.36±0.22)μg/ml;与空白组相比,经3μg/ml氯化两面针碱作用,G_2/M期细胞比例显著增多;6μg/ml时凋亡细胞比例最高,可见典型的核染色质凝集、碎裂;9μg/ml时,细胞凋亡率明显下降,同时镜下可见大量坏死细胞。结论氯化两面针碱抗KB细胞的方式与其剂量密切相关,低浓度时以G_2/M期阻滞为主,中浓度时诱导凋亡,高浓度时则致其坏死。     

黄连温胆汤对代谢综合征大鼠核转录因子及肿瘤坏死因子的影响

目的:通过对代谢综合征大鼠主动脉核转录因子及肿瘤坏死因子的检测,探讨黄连温胆汤对该指标的影响及其机制。方法:将8周龄雄性SD大鼠分组采用膳食饲料喂养,建立MS大鼠模型后将MS大鼠随机分为模型组,格华止组,黄连温胆汤高、低剂量组,灌胃4周后,检测体质量、血压、血糖、血清胰岛素、血脂、TNF-α,计算lee's指数和胰岛素敏感指数,测定大鼠主动脉NF-κB的表达。结果:与空白组比较,MS组大鼠体质量、空腹血糖、血脂等差异均有统计学意义(P0.05)。黄连温胆汤高剂量组体质量、血脂、Lee's指数、HOMA-IR、TNF-α,与MS组大鼠比较均有统计学意义(P0.05),并且三组大鼠主动脉NF-κB表达均有统计学意义(P0.05)。结论:黄连温胆汤MS大鼠各组分有治疗作用,并且可以降低MS大鼠血清TNF-α,改善主动脉NF-κB的表达,其机制可能与核转录因子分子通路有关。