Management of the depressive component of bipolar disorder

Acute bipolar depression (ABD) and breakthrough depression occurring during maintenance therapy of bipolar disorder are associated with significant morbidity and an increased risk of suicide. Lithium is an effective mood stabilizer for ABD, but its onset of antidepressant action is slow and additional antidepressant therapy is often prescribed. The extent to which other mood stabilizers (e.g., carbamazepine and valproate) have antidepressant activity is unclear. Preliminary initial research suggests three potential advantages that selective serotonin reuptake inhibitors have over tricyclic antidepressant for ABD: possibly greater efficacy, fewer adverse effects, and a lower frequency of antidepressant-induced mania. Bupropion may also have significant advantages. However, further research is needed to confirm these findings. Monoamine oxidase inhibitors are the antidepressant of choice for atypical bipolar depression. Electroconvulsive therapy (ECT) has the highest response rate of all treatments for ABD. Further research is needed to explore combination treatments with mood stabilizers and antidepressants for the effective treatment of ABD. Depression and Anxiety 4:190–198, 1996/1997. © 1997 Wiley-Liss, Inc.     

Eupalinilide B as a novel anti-cancer agent that inhibits proliferation and epithelial–mesenchymal transition in laryngeal cancer cells

ObjectiveTo investigate the anti-cancer effects and potential mechanisms of eupalinilide B in laryngeal cancer cells.MethodsLaryngeal cancer cell lines were selected to study the anti-tumor effects of eupalinilide B in vitro and in vivo. Lysine-specific demethylase 1 (LSD1) activity was assessed in vitro and dialysis experiments were performed to identify the anti-tumor target of the drug.ResultsEupalinilide B concentration-dependently inhibited the proliferation of laryngeal cancer cells, exhibiting potent inhibitory activity against TU686 (IC₅₀ = 6.73 µM), TU212 (IC₅₀ = 1.03 µM), M4e (IC₅₀ = 3.12 µM), AMC-HN-8 (IC₅₀ = 2.13 µM), Hep-2 (IC₅₀ = 9.07 µM), and LCC cells (IC₅₀ = 4.20 µM). Subsequent target verification experiments demonstrated that eupalinilide B selectively and reversibly inhibited LSD1. Furthermore, eupalinilide B, as a natural product, suppressed epithelial–mesenchymal transition in TU212 cells. An in vivo experiment further indicated that eupalinilide B could significantly reduce the growth of tumors in TU212 xenograft mouse models.ConclusionsEupalinilide B might be a novel LSD1 inhibitor for treating laryngeal cancer.     

定振丸对帕金森病大鼠神经递质及黑质多巴胺能神经元氧化应激的改善作用

目的探讨定振丸对帕金森病大鼠儿茶酚胺类神经递质及黑质多巴胺能神经元氧化应激的改善作用。方法利用6-羟多巴胺建立帕金森病大鼠模型,大鼠随机分为假手术组,模型组,定振丸低、中、高剂量组(11.03、22.05、44.10 mg/kg)及阳性组(美多芭1.67 mg/kg),1次/d,连续灌胃给药15 d。ELISA法检测脑黑质中DA、DOPAC、HVA、5-HT水平;应用硫代巴比妥那比色法、邻苯三酚自氧化法和二硫代二硝基苯甲酸直接法分别检测脑黑质匀浆上清液中MDA、SOD及GSH-Px水平;免疫组化法检测TH阳性率;TUNEL染色检测多巴胺能神经元细胞凋亡率;Western blot法检测Bax、Bcl-2、caspase-3蛋白表达。结果与模型组比较,定振丸组DA、DOPAC、HVA、5-HT、SOD、GSH-Px水平,TH阳性率及Bcl-2蛋白表达均升高(P<0.05);MDA水平、多巴胺能神经元凋亡率、Bax及caspase-3蛋白表达降低(P<0.05)。结论定振丸能改善帕金森大鼠儿茶酚胺类神经递质及黑质多巴胺能神经元氧化应激的作用,下调Bax、caspase-3蛋白表达,上调Bcl-2蛋白表达,从而促进TH表达、抑制多巴胺能神经元凋亡。     

电针对慢性应激抑郁模型大鼠脑单胺类神经递质的影响

目的　探讨电针刺激百会、印堂穴对慢性应激抑郁模型大鼠脑内单胺类神经递质的影响及治疗抑郁症的机理。方法　将２４ 只ＳｐｒａｇｕｅＤａｗｌｅｙ 雄性大鼠随机分为对照组、抑郁模型组、抑郁模型加电针组和抑郁模型加阿米替林组,每组６ 只。用高效液相电化学法测定大鼠脑内单胺类神经递质及其代谢产物的含量,比较含量的比值。结果　抑郁模型组大鼠脑皮层５羟色胺（５ＨＴ）／５羟吲哚乙酸（５ＨＩＡＡ） 、纹状体多巴胺（ＤＡ）／３,４二羟基苯乙酸（ＤＯＰＡＣ） 分别为０－５０ ±０－１７,１０－３７ ±１－４０,低于对照组（ 分别为０－８８±０－２５ ,１２－３６ ±１－５０）,Ｐ＜ ０－０５ ;皮层去甲肾上腺素（ＮＥ）／５ＨＴ（２－８８ ±１－００） 高于对照组（１－７３±０－４０） ,Ｐ＜ ０－０５。电针刺激百会、印堂穴可使模型大鼠脑皮层５ＨＴ／５ＨＩＡＡ 与ＮＥ／５ＨＴ恢复正常（Ｐ＜０－０５） ,对纹状体ＤＡ／ＤＯＰＡＣ 的降低无影响（ Ｐ＞ ０－０５）。结论　提示电针刺激百会、印堂穴通过降低皮层５ＨＴ的代谢,提高５ＨＴ能神经的活性,并协调ＮＥ 与５ＨＴ之间的平衡来发挥抗抑郁作用。     

帕金森病非运动症状与纹状体囊泡单胺转运蛋白2密度的相关性

目的:探讨帕金森病(PD)患者非运动症状(NMSs)和纹状体部位的囊泡单胺转运蛋白2(VMAT2)密度之间的相关性。方法:2018年12月至2019年12月从中山大学附属第一医院共前瞻性招募29名健康受试者[男16名,女13名,年龄(48.8±14.2)岁]和67例PD患者,PD患者包括31例改良Hoehn-Yahr(...     

脑梗死后遗症大鼠模型脑组织ATP、ADP及单胺类神经递质含量的变化

目的 研究脑梗死后遗症大鼠模型脑组织ATP、ADP及单胺类神经递质含量的变化。方法 建立脑梗死后遗症大鼠模型，用高效液相色谱（HPLC）法测定大鼠脑组织ATP、ADP及单胺类神经递质含量。结果 刺激组（SG）毛发相对黯淡无光、卷曲，精神萎靡，惊恐，消瘦，肢体无力，摄食减少，饮水减少，手术伤口愈合迟缓，符合中医脑梗死后遗症征候。正常组（NG）大鼠脑组织ATP、ADP含量显著高于SG组、术后不刺激组（SG）（P〈0．01），同时NSG组大鼠脑组织ATP、ADP含量显著高于SG组（P〈0．05）。SG组大鼠脑组织NE、DA和5-HT含量显著低于NG组（P〈0．01），NSG组（P〈0．05）；NSG组大鼠脑组织DA含量显著低于NG组（P〈0．05）。结论 脑梗死后遗症大鼠由于能量代谢障碍而出现脑组织的ATP、ADP含量降低，并且伴有大脑释放单胺类递质增加及脑细胞内的单胺类递质含量减少，单胺类递质分泌增加又加重了脑组织的损伤，加剧ATP、ADP等能量物质代谢障碍，形成恶性循环。     

The relevance to clinical care of recent research in neurobiology

Progress continues to be made in clarifying neurobiological factors in alcoholism and other chemical dependencies. Research in animal behavioral genetics and human genetics has revealed substantial genetic predispositions for some cases of alcoholism. Studies of neurotransmitters suggest that some alcoholics may have antecedent deficiencies in one or more important neurochemical systems. Cocaine dependence is considered to be related to biphasic change in sopaminergic neurons and receptor systems. Condensation products such as salsolinol, tetrahydropapaveroline, and beta carbolines can alter alcoholic preference and motivate heavy ethanol consumption in animals. However, hypothesized theoretical mechanisms underlying such increased drinking with infusions of condensation products are unclear and may require revision. New pharmacological treatments stemming from advances in neurobiological research have been applied successfully to treatment of withdrawal states, but none have been demonstrated to be appropriate for long-term maintenance of abstinence.     

Neuroendocrinology of mast cells: Challenges and controversies

Mast cells (MC) are hemotopoietically derived tissue immune cells that are ubiquitous in the body, including neuroendocrine organs such as the hypothalamus, pineal, pituitary, ovaries, pancreas and uterus where their action is not well understood. Mast cells have historically been associated with allergies because of their rich content of histamine and tryptase, but more recently with regulation of immunity and inflammation due to their synthesis and release of numerous cytokines and chemokines. Mast cells are located perivascularly and express numerous receptors for diverse ligands such as allergens, pathogens, neurotransmitters, neuropeptides and hormones including acetylcholine, calcitonin gene‐related peptide (CGRP), corticosteroids, corticotropin‐releasing hormone (CRH), β‐endorphin, epinephrine, 17β‐oestradiol, gonadotrophins, hemokinin‐A (HKA), leptin, melatonin, neurotensin (NT), parathyroid hormone (PTH), substance P (SP) and vasoactive intestinal peptide (VIP). Moreover, MC can synthesize and release most of their neurohormonal triggers, including adrenocorticotropin hormone (ACTH), CRH, endorphins, HKA, leptin, melatonin, NT, SP and VIP. Animal experiments have shown that diencephalic MC increase in number during courting in doves, while stimulation of brain and nasal MC leads to activation of the hypothalamic‐pituitary‐adrenal (HPA) axis. Recent evidence indicates that MC reactivity exhibits diurnal variations, and it is interesting that melatonin appears to regulate MC secretion. However, the way MC change their phenotype or secrete specific molecules selectively at different pathophysiological settings still remains unknown. Mast cells developed over 500 million years ago and may have served as the original prototype neuroimmunoendocrine cell and then evolved into a master regulator of such interactions, especially as most of the known diseases involve neuroinflammation that worsens with stress.     

Effect of Antibodies to Glutamate and GABA on the Stress Response in C57Bl/6 Mice

We studied the effect of antibodies to glutamate and GABA (active immunization with conjugates of glutamate—bovine serum albumin and GABA—bovine serum albumin) on the course of combined water-immersion stress in C57Bl/6 mice. Preimmunization of animals with the conjugate of glutamate—bovine serum albumin was accompanied by strong production of antibodies to glutamate, which reduced the majority of signs of the stress response. Antibodies to GABA had no effect on the development of stress. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 3, pp. 272–275, March, 2009