Elimination of amyloid precursor protein in senile plaques in the brain of a patient with Alzheimer-type dementia and Down syndrome

The average lifespan of individuals with Down syndrome has approximately doubled over the past three decades to 55–60?years. To reveal the pathogenic process of Alzheimer-type dementia in individuals with Down syndrome, we immunohistochemically examined senile plaque formation in the cerebral cortex in the autopsy brain and compared findings with our previous studies. We described a 52-year-old female with Down syndrome who developed progressively more frequent myoclonus following cognitive decline and died at the age of 59?years. Her karyotype [46XX, inv(9)(p12q13), i(21)(q10)] included triplication of the gene for amyloid precursor protein and the Down syndrome critical region. On microscopy, very few gamma-aminobutyric acid-ergic (GABAergic) neurons, in the form of small granular cells, in the cortex and Purkinje cells in the cerebellum were visible. In our previous study, amyloid precursor protein immunoreactivity was first noted in senile plaques at the age of 32?years. In this patient, even though amyloid β immunoreactivity was detected in the cores of senile plaques and diffuse plaques, amyloid precursor protein immunoreactivity was not noted in senile plaques in the frontal cortex. Amyloid precursor protein and its derivative amyloid-β play an important role in the formation of senile plaques and the time course of immunoreactive expression may be related to the pathogenic process of Alzheimer-type dementia.     

低频超声对牙菌斑生物膜促渗作用的研究进展

牙菌斑生物膜是一种细菌性生物膜,为基质包裹的互相粘附,或粘附于牙面、牙间或修复体表面的软而未矿化的细菌性群体,不能被水冲去或漱掉。它是一个具有结构、形态和代谢活动的独立微生态环境,其耐药性是浮游生物的许多倍。研究人员发现,低频率超声可以提高药物在生物膜中的渗透效应,从而更好地发挥杀菌作用。具有很好的临床应用前景。本文对低频超声对牙菌斑生物膜促渗作用的研究进展作一综述。     

Typical and atypical appearance of early‐onset Alzheimer's disease: A clinical,neuroimaging and neuropathological study

The International Working Group (IWG) has classified Alzheimer's disease (AD) as two different types, the typical form and the atypical form, but clinicopathological studies of atypical AD are limited. Because atypical AD cases usually present with early‐onset dementia, we investigated 12 patients with early‐onset AD, including two patients with typical AD and 10 patients with atypical AD. Of these patients, six had the posterior variant, three had the frontal variant and one had the logopenic variant mixed with semantic dementia. We reported MRI, single‐photon emission CT and neuropathological findings in six representative cases. We also described a “left temporal variant” of AD presenting with transcortical cortical sensory aphasia, which has not been reported previously and is another subtype of the posterior variant of AD. We found a significant correlation between regional cerebral blood flow and counts of NFTs in the cerebral cortices. An atypical presentation with focal neuropsychological symptoms roughly correlated with the density of NFTs in the cerebral cortex and more directly related to spongiform changes in the superficial layers of these areas. In contrast, the distribution of amyloid depositions was diffuse and did not necessarily correlate with focal neuropsychological symptoms. Braak staging or ABC score is not necessarily appropriate to evaluate atypical AD, and instead, spongiform changes in addition to tau pathology in the association cortices better explain the diversity of atypical AD. Interestingly, another patient with a posterior variant of AD had a novel type of atypical plaque, which we referred to as “lucent plaque”. They were recognizable with HE staining in the circumference and dystrophic neurites were abundant with Gallyas‐Braak staining. These plaques demonstrated intense immunoreactivity to both tau AT‐8 and amyloid β (Aβ), suggesting a peculiar coexistence pattern of amyloid and tau in these plaques. Clinicopathological studies of atypical AD will provide a new understanding of the pathophysiology of AD.     

高分辨率磁共振评价阿托伐他汀钙对颈动脉硬化不稳定斑块的影响

目的利用高分辨率磁共振评估不同剂量阿托伐他汀钙对人颈动脉硬化不稳定斑块的影响。方法选择有颈动脉不稳定斑块患者100例,随机分成高剂量组和低剂量组,分别给予20mg和10mg阿托伐他汀钙,于治疗前和治疗1a后行高分辨率磁共振检查,结合患者的血脂和超敏C反应蛋白水平,对不稳定斑块的数量和平均厚度进行分析。结果治疗1a后,患者血脂中的总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平均有所降低,高密度脂蛋白胆固醇水平升高;经高分辨磁共振检查,动脉硬化不稳定斑块的数量及平均厚度与治疗前相比明显降低(P0.05)。结论阿托伐他汀钙能够使患者的血脂、超敏C反应蛋白降低,具有抗动脉粥样硬化的作用。     

Randomized Trial of Plaque-Identifying Toothpaste: Decreasing Plaque and Inflammation

Background

Randomized data are sparse about whether a plaque-identifying toothpaste reduces dental plaque and nonexistent for inflammation. Inflammation is intimately involved in the pathogenesis of atherosclerosis and is accurately measured by high-sensitivity C-reactive protein (hs-CRP), a sensitive marker for cardiovascular disease. The hypotheses that Plaque HD (TJA Health LLC, Joliet, Ill), a plaque-identifying toothpaste, produces statistically significant reductions in dental plaque and hs-CRP were tested in this randomized trial.

雌激素及其受体调节剂对去势APOE基因敲除小鼠胸主动脉中NF-κB和MMP-9的影响

目的：观察雌激素及其受体调节剂对去势APOE基因敲除（APOE-/-）小鼠胸主动脉血管组织中NF-κB和MMP-9的影响。方法：44只APOE-/-小鼠喂养4 周, 确定动脉粥样硬化斑块形成后, 将其随机分成模型组和5组不同给药组：生理盐水0.2 mL/d（模型组）;戊酸雌二醇0.13 mL/d + 地屈孕酮0.13 mL/d（HT组）;ICI 皮下注射0.13 mL/周+戊酸雌二醇0.13 mL/d（ICI+E2组）;ICI 皮下注射0.13 mL/周+戊酸雌二醇0.13 mL/d+地屈孕酮0.13 mL/d（ICI+HT组）;戊酸雌二醇0.13 mL/d+PHTTP 0.13 mL/d（PHTTP+E2组）;戊酸雌二醇0.13 mL/d+地屈孕酮0.13 mL/d+PHTTP 0.13 mL/d（PHTTP+HT组）。8周后,获取动脉粥样硬化斑块的胸主动脉组织后行总RNA提取、逆转录,利用real-time PCR 检测小鼠胸主动脉NF-κB和MMP-9的mRNA含量。结果：各组NF-κB mRNA 的表达差异有统计学意义（P＜0.05）,而MMP-9 mRNA 的表达差异无统计学意义（P＞0.05）。与模型组相比,PHTTP+E2和PHTTP+HT组NF-κB表达显著升高（P=0.047和P=0.035）,ICI+HT组NF-κB的表达明显低于PHTTP+HT组（P=0.028）;模型组、HT组、ICI+E2组及ICI+HT组间NF-κB的表达差异不明显（与模型组相比,P分别为0.072,0.068和0.054）。结论：ERα介导的激素替代治疗（PHTTP+E2和PHTTP+HT）使NF-κB的表达升高,提示ERα可能对动脉粥样硬化斑块稳定性不利。     

ANTIPLAQUE AND ANTIGINGIVITIS EFFECT OF LIPPIA SIDOIDES. A DOUBLE-BLIND CLINICAL STUDY IN HUMANS

Objectives:

The antiplaque and antigingivitis effect of Lippia Sidoides (LS) was evaluated in this in vivo investigation.

Material and Methods:

Twenty-three subjects participated in a cross-over, double-blind clinical study, using 21-day partial-mouth experimental model of gingivitis. A toothshield was constructed for each volunteer, avoiding the brushing of the 4 experimental posterior teeth in the lower left quadrant. The subjects were randomly assigned initially to use either the placebo gel (control group) or the test gel, containing 10% LS (test group).

Results:

The clinical results showed statistically significant differences for plaque index (PLI) (p<0.01) between days 0 and 21 in both groups, however only the control group showed statistically significant difference (p<0.01) for the bleeding (IB) and gingival (GI) index within the experimental period of 21 days. On day 21, the test group presented significantly better results than the control group with regard to the GI (p<0.05).

Conclusions:

The test gel containing 10% LS was effective in the control of gingivitis.     

应用64排螺旋CT评价阿托伐他汀对冠状动脉斑块的影响

目的：评价阿托伐他汀对冠状动脉粥样斑块的影响。方法：对43例经64排螺旋CT冠脉CTA检测出的粥样斑块患者,给予阿托伐他汀20 mg/d口服,6个月后复查粥样斑块情况。结果：43例患者有119支冠状动脉存在132个粥样斑块,治疗后各种斑块大小有不同程度的下降,其中脂质斑块下降幅度16.4%,纤维斑块下降幅度8.1%,混合斑块下降幅度10.7%,而钙化斑块下降幅度不明显。结论：阿托伐他汀可逆转或稳定冠脉粥样斑块,从而降低急性冠状动脉事件的发生;64排螺旋CT可定量评价粥样斑块的变化,为临床治疗提供客观依据。     

Inhibition of inositol monophosphatase by lithium chloride induces selective macrophage apoptosis in atherosclerotic plaques

BACKGROUND AND PURPOSE

Lithium chloride (LiCl) inhibits inositol monophosphatase (IMPase) at therapeutic concentrations. Given that LiCl induces death in cultured macrophages and that macrophages play an active role in atherosclerotic plaque destabilization, we investigated whether LiCl would induce selective macrophage death to stabilize the structure of the plaque.

EXPERIMENTAL APPROACH

The effect of LiCl was assessed on macrophages and smooth muscle cells (SMCs) in culture, in isolated atherosclerotic carotid arteries from rabbits and after local in vivo treatment via osmotic minipumps to rabbits with collared atherosclerotic carotid arteries. In addition, in vitro experiments were performed to elucidate the mechanism of LiCl-induced macrophage death.

KEY RESULTS

In vitro, whereas SMCs were highly resistant, LiCl induced macrophage death characterized by externalization of phosphatidylserine, caspase-3 cleavage and DNA fragmentation, all indicative of apoptosis. LiCl reduced inositol-1,4,5-trisphosphate levels in macrophages. Moreover, the IMPase inhibitor L-690 330 as well as IMPase gene silencing induced macrophage apoptosis. Both in vitro treatment of rabbit atherosclerotic carotid arteries with LiCl and local in vivo administration of LiCl to the plaques decreased plaque macrophages through apoptosis, as shown by terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL), without affecting SMCs. Vasomotor studies in vitro showed that LiCl did not affect the functionality of SMCs and endothelial cells.

CONCLUSIONS AND IMPLICATIONS

LiCl selectively decreased the macrophage load in rabbit atherosclerotic plaques via IMPase inhibition without affecting the viability or functionality of SMCs and endothelial cells. These data provide evidence for local administration of an IMPase inhibitor to stabilize atherosclerotic plaques.