不同浓度氯氮平对小鼠空腹血糖和骨骼肌葡萄糖转运蛋白4基因表达的影响

目的探讨氯氮平对雄性C57BL/6小鼠空腹血糖和骨骼肌葡萄糖转运蛋白4(GLUT4)基因表达的影响。方法将63只雄性C57BL/6小鼠随机分为3组,每组21只,分别灌胃给予蒸馏水、氯氮平4mg/kg及氯氮平20mg/kg,于给药后3h、1周、4周以试纸法测定各组空腹血糖,用逆转录-聚合酶链反应测定GLUT4mRNA表达。结果(1)灌药后3h、1周氯氮平4mg/kg组和氯氮平20mg/kg组空腹血糖和GLUT4mRNA的表达与空白对照组相比,差异无统计学意义(P>0.05);(2)灌药后4周氯氮平4mg/kg组和20mg/kg组的空腹血糖值[(5.6±0.5)mmol/L和(5.8±0.5)mmol/L]高于空白对照组[(4.6±0.6)mmol/L],而GLUT4mRNA的表达(0.50±0.14和0.48±0.12)却低于空白对照组(0.85±0.27),差异均有统计学意义(P<0.01)。结论氯氮平可以慢性升高空腹血糖,降低GLUT4mRNA的表达,可能是抗精神病药长期应用后血糖升高的发生机制之一。     

抑郁症焦虑症状和焦虑症的抑郁症状

目的　探讨抑郁症和焦虑症的抑郁和焦虑症状的差异 ,为鉴别诊断提供依据。方法　使用HAMD和HAMA对5 5例抑郁症患者和 2 0例焦虑症患者进行评定。结果　 (1)抑郁症组绝大部分为中、重度抑郁 (92 .7% ) ,焦虑症组无一例为重度抑郁 ;(2 )抑郁症组的HAMD总分和除焦虑 /躯体化以外的因子分均显著高于焦虑症组 (P <0 .0 5或P <0 .0 1) ,(3)抑郁症患者和焦虑症患者的HAMD和HAMA评分均呈显著性正相关 (P <0 .0 0 1)。结论　HAMD总分有助于鉴别抑郁症和焦虑症。     

Toward a revision of criteria for the dementias

This article critically considers current diagnostic criteria for dementia and reports recommendations approved by at least 80% of experts attending the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD3). There was consensus that many of the features proposed as essential to a diagnosis of dementia in the 1980s no longer are relevant (for example, the requirements for memory impairment, electroencephalogram and cerebrospinal fluid studies, age-specific exclusions). In addition, other syndromes such as frontotemporal dementia have been recognized and need to inform new dementia criteria. It is also recognized that a diagnosis of depression need not exclude a dementia diagnosis. Other proposals, such as neuropathology should be considered as additional evidence and not as a gold standard or that some people with dementia have prolonged plateaus so that progressive decline need not be a criterion for Alzheimer’s disease (AD), were more controversial and did not receive similar support. Given the evidence of the last three decades, there is merit in reconsidering the criteria by which dementia and AD are diagnosed.     

The flavonoid rutin and its aglycone quercetin modulate the microglia inflammatory profile improving antiglioma activity

Microglia cells are the immune effector in the Central Nervous System (CNS). However, studies have showed that they contribute more to glioma progression than to its elimination. Rutin and its aglycone quercetin are flavonoids present in many fruits as well as plants and have been demonstrated to bear anti-inflammatory, antioxidant and antitumor properties also to human glioblastoma cell lines. Previous studies also demonstrated that rutin, isolated from the Brazilian plant Dimorphandra mollis Bent., presents immunomodulatory effect on astrocytes and microglia. In this study, we investigate the antitumor and immunomodulatory properties of rutin and its aglycone quercetin on the viability of glioma cells alone and under direct and indirect interaction with microglia. Flavonoid treatment of rat C6 glioma cells induced inhibition of proliferation and migration, and also induced microglia chemotaxis that was associated to the up regulation of tumor necrosis factor (TNF) and the down regulation of Interleukin 10 (IL-10) at protein and mRNA expression levels, regulation of mRNA expression for chemokines CCL2, CCL5 and CX3CL1, and Heparin Binding Growth Factor (HDGF), Insulin-like growth factor (IGF) and Glial cell-derived neurotrophic factor (GDNF) growth factors. Treatment of human U251 and TG1 glioblastoma cells with both flavonoids also modulated negatively the expression of mRNA for IL-6 and IL-10 and positively the expression of mRNA for TNF characterizing changes to the immune regulatory profile. Treatment of microglia and C6 cells either in co-cultures or during indirect interaction, via conditioned media from glioma cells treated with flavonoids or via conditioned media from microglia treated with flavonoids reduced proliferation and migration of glioma cells. It also directed microglia towards an inflammatory profile with increased expression of mRNA for IL-1β, IL-6, IL-18 and decreased expression of mRNA for nitric oxide synthase 2 (NOS2) and prostaglandin-endoperoxide synthase 2 (PTGS2), arginase and transforming growth factor beta (TGF-β), as well as Insulin-like growth factor (IGF). Treatment of U251 cells with flavonoids also reduced tumorigenesis when the cells were xenotransplanted in rat brains, and directed microglia and also astrocytes in the microenvironment of tumor cell implantation as well as in the brain parenchyma to a not favorable molecular inflammatory profile to the glioma growth, as observed in cultures. Together these results demonstrate that the flavonoid rutin and its aglycone quercetin present antiglioma effects related to the property of modulating the microglial inflammatory profile and may be considered for molecular and preclinical studies as adjuvant molecules for treatment of gliomas.