Differential modification of muscarinic cholinergic receptors in the hippocampus of patients with Alzheimer''s disease: an autoradiographic study

We have used quantitative light microscopic autoradiographic techniques to analyze changes in muscarinic cholinergic receptors in the hippocampus in Alzheimer type dementia (ATD). The density and distribution of muscarinic cholinergic receptors has been correlated with the density of neurons, neuritic plaques and neurofibrillary tangles in the CA1 subfield of the hippocampus of control and ATD patients. The number of pyramidal cells per mm² in the CA1 sector was significantly decreased in ATD cases as compared to controls, although there were large variations among cases. The most marked reductions in cell counts were observed in patients with a history of profound dementia. The densities of muscarinic receptors, as well as the proportions of M₁ and M₂ subtypes, in the CA1 sector and dentate gyrus were not significantly different between ATD and old non-demented patients. Neuritic plaques, even in high numbers, did not affect the density of muscarinic receptors; moreover, the densities of receptors over the neuritic plaques did not differ from the surrounding neuropil. However, in some ATD cases there was a marked decrease in the concentration of these receptors in the CA1 sector and subiculum, with no change in the proportions of muscarinic receptor subtypes. These patients exhibited frequent extracellular remnants of neurofibrillary tangles (ghost tangles), but scarce neuritic plaques, and were those showing severe losses of pyramidal cells. There was a significant positive correlation between the total concentration of muscarinic receptors in the CA1 and the density of pyramidal cells, suggesting that decreases in receptor concentration result from a severe neuronal loss. We observed that the ratio of muscarinic receptors per pyramidal cell was significantly increased in ATD patients. This might indicate a possible upregulatory mechanism for muscarinic receptors in the population of remaining neurons in ATD. However, decreases of receptor numbers following severe neuronal fall out suggest that compensatory mechanisms are no longer possible in such cases. The question is raised whether these differences between cases reflect different diseases or different stages of the same disease.     

Exudative discoid and lichenoid chronic dermatosis (Sulzberger-Garbe): presentation with a puzzling penile plaque*

Objective Report of two cases of exudative discoid and lichenoid dermatosis (Sulzberger-Garbe), with typical penile lesions. Differential diagnosis of persistent penile plaques. Background Following remission of the generalized eruption of exudative discoid and lichenoid dermatosis (Sulzberger-Garbe), it is not unusual to see a single remaining lesion localized on the penis. Since Sulzberger et al. (Sulzberger MB, Witten VH, Hunt JA. Puzzling persistent penile plaques. Arch Dermatol 1956:73:101-109) reviewed dermatoses presenting with puzzling persistent penile plaques in 1955, further dermatoses have evolved as important differential diagnoses. Much controversy has arisen as to the justification of exudative discoid and lichenoid dermatosis (Sulzberger-Garbe) as a disease entity. Conclusions Diagnosis of most cases of persistent plaques of dermatitis on the penis is possible with a careful examination of the entire skin, and a thorough history to discover past lesions. The possibility of malignancy makes a biopsy mandatory. Exudative discoid and lichenoid chronic dermatosis (Sulzberger-Garbe) typically responds well to systemic steroids. Intrale-sional triamcinolone acetonide has been demonstrated to be effective in the treatment of a persistent penile plaque in exudative discoid and lichenoid dermatosis (Sulzberger-Garbe), and may be helpful in discontinuing or reducing systemic therapy to a level compatible with long-term treatment.     

The monoclonal antibody Alz-50, used to reveal cytoskeletal changes in Alzheimer's disease, also reacts with a large subpopulation of somatostatin neurons in the normal human hypothalamus and adjoining areas

The monoclonal antibody Alz-50 is directed against Alzheimer's disease-related modified tau proteins and reveals cytoskeletal changes, i.e. neurofibrillary tangles and dystrophic neurites. The present study shows that, in the hypothalamus of non-demented control subjects, this same antibody gives a distinctive staining pattern of a subpopulation of somatostatin neurons and beaded fibers. Furthermore, Alz-50 occasionally recognizes somatostatin-containing cell bodies and dystrophic neurite-like fibers in the (neuritic) senile plaques of AD patients. These observations have direct consequences for the interpretation of Alz-50 staining in diagnostic usage and for the assessment of Alzheimer's disease-like changes induced by β-amyloid in experimental animal brains. On dot spotting, Alz-50 was found to bind to a number of fragments from the somatostatin precursor, of which somatostatin_15–28 stained best. Preadsorption of Alz-50 by somatostatin_15–28, as well as other specificity tests, failed, however, to provide any clue to the nature of the unknown compound(s) stained in the control hypothalamus.     

妊娠相关血浆蛋白A水平与不稳定心绞痛患者冠状动脉狭窄病变形态的关系

[目的]探讨不稳定型心绞痛患者妊娠相关血浆蛋白(PAPP-A)水平与高敏C-反应蛋白(hs-CRP)及动脉粥样硬化斑块稳定性的关系.[方法]不稳定型心绞痛组患者42例,稳定型心绞痛组38例.冠状动脉造影前检测PAPP-A和hs-CRP,根据造影结果将冠状动脉病变分为复杂狭窄和光滑狭窄.[结果]稳定型心绞痛组有28例(74%)患者至少有1支血管狭窄≥70%,多于不稳定型心绞痛组的24例(57%),P＜0.05;不稳定型心绞痛组中33例(79%)有1处以上的复杂狭窄,多于稳定型心绞痛组(22例,58%,P＜0.05);PAPP-A与hs-CRP正相关(r=0.44,P＜0.001);不稳定型心绞痛组与稳定型心绞痛组相比,hs-CRP(4.40 mg/L±0.003 mg/L vs 0.48 mg/L±0.016mg/L,P＜0.001)和PAPP-A(18.40×10-3 U/L±0.002×10-3U/Lvs 7.79×10-3 U/L±0.001×10-3 U/L,P＜0.001),差异均有统计学意义;两组中有复杂狭窄者的PAPP-A和hs-CRP水平显著高于无复杂狭窄者.[结论]PAPP-A可作为评估冠状动脉斑块稳定性的血清学指标之一.     

The bactericidal activity of pulsed Nd-YAG laser radiation in vitro

Pulsed Nd-YAG laser irradiation of bacteria has been suggested as a possible means of treating contaminated intra-oral sites although relatively few studies have been conducted. In this investigation, the antimicrobial activity of a pulsed Nd-YAG laser was assessed in vitro for a range of oral bacteria using several pulse energies and exposure durations. Pure cultures of each organism were lased in saline suspensions followed by standard colony counting techniques for test and control samples. Microbial inhibition was found to be organism-dependent and varied with energy dose and pulse energy. For all nine test species 120-mJ laser pulses proved more efficient than 80-mJ pulses, with 99.9% kills compared with around 90% kills after exposure to 1800 pulses. These killing activity levels compare favourably with those achieved with other lasers in vitro.     

Lysosomal abnormalities in degenerating neurons link neuronal compromise to senile plaque development in Alzheimer disease

Antibodies to the lysosomal hydrolases, cathepsins B and D and β-hexosaminidase A, revealed alterations of the endosomal-lysosomal system in neurons of the Alzheimer disease brain, which preceded evident degenerative changes and became marked as atrophy, neurofibrillary pathology, or chromatolysis developed. At the earliest stages of cell atrophy, hydrolase-positive lysosomas accumulated at the basal pole and then massively throughout the perikarya and proximal dendrites of affected pyramidal neurons in Alzheimer prefrontal cortex and hippocampus, far exceeding the changes of normal aging. Secondary lysosomes as well as tertiary residual bodies (lysosomes/lipofuscin) increased implying stimulated, autophagocytosis and lysosomal system activation. Less affected brain regions, such as the thalamus, displayed similar though less extensive alterations. Certain thalamic neurons exhibited a distinctive lysosome-related abnormality characterized by the presence of cell surface blebs of varying size and number filled with intense hydrolase immunoreactivity. At more advanced stages of degeneration in still intact neurons, hydrolase-positive lipofuscin, particularly in the form of abnormal large aggregates, nearly filled the cytoplasm. Similar lipofuscin aggregates were oberved in abundance in the extracellular space following cell lysis and were usually associated with deposits of the β-amyloid protein. Degenerating neurons and their processes were the major source of these aggregates within senile plaques which contained high concentrations of acid hydrolases. We have shown in previous studies that these lysosomal hydrolases in plaques are enzymatically-active. The persistence of lysosomal structures in the brain parenchyma after neurons hyve degenerated is a striking and potentially diagnostic feature of Alzheimer disease which has not been observed, to our knowledge, in other degenerative diseases. The lysosomal response in degerating Alzheimer neurons represents a probable link between an early activation of the lysosomal system in at-risk, normal-appearing neurons and the end-stage contribution of lysosomes to senile plaque formation of emphasizes a slowly progressive disturbance of the lysosomal system throughout the development of Alzheimer disease.     

卒中高危人群糖化血红蛋白与颈动脉粥样硬化斑块的关系研究

目的 分析卒中高危人群糖化血红蛋白与颈动脉粥样硬化斑块的关系。
方法 2018年5-6月由孝感市中心医院按整群随机抽样方法，随机抽取孝感市城乡各1个社区居民
进行筛查，通过问卷调查、体格检查、实验室检查、颈部血管超声检查筛选卒中高危人群纳入研究。
根据颈动脉超声检测结果将卒中高危人群分为非斑块组和斑块组（颈动脉）。分别采用单因素和多
因素Logistic回归，分析糖化血红蛋白与颈动脉斑块的关系，并根据年龄（60岁）、BM（I 24 kg/m2）、是
否有高血压对研究人群进行分层分析，研究不同特征的卒中高危人群中糖化血红蛋白与颈动脉斑块
的关系。
结果 最终纳入卒中高危人群629例，男性338例（53.74%），平均54.85±8.97岁，糖化血红蛋白平
均浓度为4.70%±1.02%。其中斑块组患者215例（34.18%），非斑块组患者414例（65.82%）。与非斑
块组患者相比，斑块组患者男性、卒中、TIA、高血压、超重患者比例更高，年龄更大，BMI、血压、空
腹血糖、糖化血红蛋白、TC水平更高（均P＜0.01）。校正其他危险因素后，糖化血红蛋白是颈动脉
粥样硬化斑块发生的独立影响因素（每升高1%，OR 1.16，95%CI 1.01～1.31，P =0.018）。分层分析显
示，年龄≥60岁（OR 1.48，95%CI 1.09～2.01，P =0.016）、BMI≥24 kg/m2（OR 1.97，95%CI 1.07～3.64，
P =0.030）、高血压人群（OR 1.31，95%CI 1.06～1.62，P =0.013）中糖化血红蛋白均是颈动脉斑块发生
的独立危险因素。
结论 卒中高危人群糖化血红蛋白与颈动脉斑块的发生密切相关，特别是在年龄≥6 0岁、
BMI≥24 kg/m2和高血压人群中。     

对急性冠状动脉综合征的新认识和治疗对策

近几年来，由于基础实验研究的迅速发展，对急性冠状动脉综合征(ACS)的认识和治疗取得了重大进展。作者就ACS分子生物学和细胞学基础、不稳定斑块的治疗对策、ACS的危险分层及治疗方法作一综述。     

Ultrasound for the assessment of the embolic risk of carotid plaques

In a prospective study we compared duplex-ultrasound characteristics of symptomatic internal carotid artery (ICA) stenoses with cranial computerized tomographic (CCT) findings in 82 patients suffering from completed or transient middle cerebral artery symptoms. The aim was to assess the pathogenic role of ICA plaque morphology and the potential embolic risk of ICA plaques. The degree of carotid stenosis was estimated by spectral analysis of the pulsed Doppler signal. The CCT findings were classified as being either normal, lacunar lesions, hemodynamically induced low-perfusion infarctions, or territorial embolic infarctions. According to their ultrasonic features we characterized the ICA plaque surface as smooth or irregular and their structure as homogeneous or heterogeneous. Plaques with an irregular surface and heterogeneous echogenicity dominated significantly in CCT-territorial infarctions (p < 0.01), whereas hemodynamically induced low-perfusion infarctions showed no relationship with any plaque characteristic. High degree ICA stenoses (> 50>%) dominated in both territorial infarctions and low-perfusion infarctions, as compared to ipsilateral normal CCT or lacunes (p < 0.05). Normal CCT and lacunar infarctions were associated with homogeneous and smooth plaques (both p < 0.05). We conclude that > 50% ICA stenoses can cause both hemodynamically induced low-perfusion infarctions as well as thromboembolic territorial infarctions, whereas ulcerated and heterogeneous plaques constitute a high risk factor for arterio-arterial embolic stroke. Furthermore, carotid ultrasound may help to estimate the clinical significance of carotid lesions.     

A clinical comparison of 2 electric toothbrush designs

Abstract A single blind 30 day study compared the reduction of plaque and gingivitis for the Hapika® Powerbrush to the Interplak® ultra 10 tuft. A longitudinal parallel group design was utilized and screening evaluation was performed to determine patient eligibility prior to study enrollment. 66 subjects were entered into the study and assigned to 1 of 2 groups, each using one of the toothbrushes. At baseline, subjects received an oral soft tissue exam, a dental hard tissue exam, and were scored by the Lobene modification of the Löe and Silness gingival index (GI). Plaque was then disclosed and scored both pre and post brushing using the modified Turesky plaque/debris examination and an interproximal bleeding examination was performed post-brushing. On days 15 and 30, after an oral soft tissue and GI examination, plaque was graded by the Modified Turesky plaque/debris exam. Subjects then brushed and were graded by the Modified Turesky plaque/debris examination and an interproximal bleeding index examination. The results showed that both brushes provided a similar change in clinical indices. All produced a statistically significant reduction from baseline to day 30 for the gingival index (26.5-29.1%), the bleeding index (13.8-24.1%), and the plaque index (16.9-19.4%), A comparison of pre and post brushing scores for the plaque index at 30 showed that both brushes reduced plaque similarly with a statistically significant reduction (P<0.05) from their pre-brushing plaque index scores at all time periods.