红景天苷对肌萎缩侧索硬化症的保护机制

目的探讨红景天苷在肌萎缩侧索硬化症细胞模型中的保护作用及其机制。方法阳离子脂质体转染法,转染(NSC)-34细胞,构建肌萎缩侧索硬化症细胞模型;对NSC-34细胞进行随机分组:对照组、空载组、转染组和转染组+(30/60/120)μmol/L红景天苷处理组。通过检测丙二醛(MDA)水平,反映各组线粒体氧化水平。通过Western印迹检测分裂半胱氨酸天冬氨酸蛋白酶(cleaved caspase)3、磷酸化蛋白激酶B(p-Akt)、Akt的表达水平,来反映细胞凋亡和上调磷脂酰肌醇3-激酶(PI3K)/Akt情况。结果成功构建肌萎缩侧索硬化细胞模型,该细胞模型中细胞凋亡与活性氧水平显著增高(P0.05),红景天苷在120μmol/L时,可以明显抑制细胞凋亡(P0.05)和活性氧水平(P0.05),并上调p-Akt水平(P0.01)。结论红景天苷可以抑制细胞凋亡和氧化应激,可能通过PI3K/Akt信号通路保护肌萎缩侧索硬化中受损的神经元细胞。     

Dyspnea as a main symptom for visiting of amyotrophic lateral sclerosis (ALS) :a case report and literature review

目的 了解肌萎缩侧索硬化症患者呼吸系统障碍的临床特点和治疗方法.方法 通过对1例以呼吸困难为首诊症状肌萎缩侧索硬化症患者的诊治经过分析,结合相关文献进行讨论.结果 患者为57岁男性,因“进行性呼吸困难2年”来院就诊.以劳力性呼吸困难和端坐呼吸为主要表现.动脉血气分析提示Ⅱ型呼吸衰竭.肺功能检查表现为限制性为主的通气功能障碍.体检和X线检查提示双侧膈肌活动减弱.多导睡眠图检查示患者重度睡眠呼吸暂停综合征.肌电图和神经专科体检示多区域的运动神经元变性表现.经神经科会诊,患者诊断为肌萎缩侧索硬化症.结论 对以呼吸困难为首诊症状的肌萎缩侧索硬化症患者快速正确诊断存在一定难度.对于不能解释的呼吸困难和呼吸衰竭患者,要考虑神经源性疾病.有呼吸困难的肌萎缩侧索硬化症患者应该进行睡眠障碍相关检查.正确使用机械通气治疗,对患者有益.     

前庭神经炎患者自发性眼震及受累半规管频率特征的分析

目的观察前庭神经炎(VN)患者自发性眼震(SN)及受累半规管频率特征。方法横断面研究。选取2020年6月至2021年10月山西白求恩医院神经内科收治的临床确诊的61例VN患者, 其中男性39例`、女性22例, 平均年龄(46±13)岁, 男女比例1.77∶1。根据SN特点分为无眼震组(nSN)、水平眼震组(hSN)及水平伴扭转眼震组(htSN)。收集患者临床资料, 以SN、单侧减弱指数(UW)、优势偏向(DP), 视频头脉冲试验(vHIT)增益为观察指标进行分析。采用SPSS23.0软件进行统计学分析, 正态分布的定量资料(年龄、半规管增益、SN强度)使用xˉ±s表示, 非正态分布的定量资料(发病天数、UW、DP)使用M(Q₁, Q₃)表示, 定性资料使用率及构成比表示, 采用单因素方差分析、秩和检验、卡方检验或Fisher确切概率法进行差异分析, P<0.05为差异有统计学意义。结果 (1)nSN、hSN、htSN三组患者病程分别为7.0(4.0, 12.5), 6.0(3.5, 11.5), 3.0(2.0, 6.5)d, 差异有统...     

美托洛尔对心肌梗死兔自主神经重构的影响

目的探讨β受体阻滞剂美托洛尔治疗对心肌梗死后心脏自主神经重构的改善作用。方法通过结扎新西兰大白兔冠状动脉前降支制作心肌梗死模型,随机分成心肌梗死 美托洛尔组[(10mg/(kg·d),治疗组)、心肌梗死组(模型组)和假手术组。8周后所有成活兔均进行统一的电生理检查,诱发室性心律失常。并处死实验动物,取心肌采用免疫组织化学的方法观察心室神经纤维的形态、密度及生长活性。结果模型组室性心律失常诱发率明显高于假手术组(58.3%比16.7%,P<0.001),而美托洛尔治疗后其诱发率降至8.3%。模型组梗死灶周S100及GAP43阳性神经纤维密度分别达到3889±521μm2/mm2和3090±622μm2/mm2,明显高于假手术组(1727±304μm2/mm2和718±177μm2/mm2;P均<0.01),且神经纤维空间分布紊乱;而治疗组梗死灶周S100及GAP43阳性神经纤维密度降至2725±283μm2/mm2和1922±508μm2/mm2,与模型组比差异均有统计学意义(P<0.05),且神经形态及分布更类似于假手术组,非梗死左心室游离壁心肌梗死后密度上调的S100及GAP43阳性神经纤维经美托洛尔治疗后也明显下降(P<0.05)。结论美托洛尔可改善心肌梗死动物模型的神经重构,从而可能预防心肌梗死后室性心律失常的发生。     

肌萎缩侧索硬化患者脑脊液及血清神经丝轻链水平与疾病进展关系的研究

目的探讨肌萎缩侧索硬化(ALS)患者脑脊液及血清神经丝轻链(NFL)水平与疾病进展的关系。方法纳入ALS患者90例为ALS组,其中40例患者留取了脑脊液;另选择年龄和性别相匹配的非炎症性神经系统疾病患者40例为对照组,采用ELISA法检测入选者血清及脑脊液NFL水平,采用疾病进展率(DPR)评估疾病总体进展速度,采用全面进展时间(TTG)评估早期进展情况。结果 ALS组脑脊液及血清NFL水平明显高于对照组,差异有统计学意义[2934.0(1953.0,3268.0)ng/L vs 411.0(211.8,812.5)ng/L,951.2(669.1,1161.0)ng/L vs 410.1(289.3,491.2)ng/L,P<0.01];ALS患者脑脊液和血清NFL水平与DPR呈正相关,与TTG呈负相关(P<0.01)。Kaplan-Meier生存分析显示,脑脊液和血清高水平NFL患者全面进展率明显高于低水平NFL患者(P<0.05,P<0.01)。结论 ALS患者脑脊液和血清NFL水平增高,其是评估ALS患者疾病进展的指标之一。     

运动神经元病临床神经电生理检查的研究进展

运动神经元病（motor neuron disease,MND）是以损害脊髓前角、脑干脑神经运动核和锥体束为主的一组慢性进行性变性疾病,包括了肌萎缩侧索硬化症（ALS）、进行性脊髓性肌萎缩症（PSMA）、脊髓性肌萎缩症（SMA）、进行性延髓麻痹（PBP）、原发性侧索硬化症（PLS）。发病率为2～3/10万,目前没有确实有效的治疗手段,从有症状开始,平均仅能存活3～5年。临床诊断主要依靠临床表现、神经电生理检查和神经影像学检查。     

运动神经元病患者脑脊液及血清碱性成纤维细胞生长因子2与临床关系的研究

目的探讨运动神经元病(MND)患者脑脊液及血清碱性成纤维细胞生长因子2(FGF-2)水平变化及其与临床指标的关系。方法选择MND患者91例(MND组),其中肌萎缩侧索硬化症(ALS)患者70例,进行性肌肉萎缩(PMA)患者9例,进行性延髓麻痹(PBP)患者7例,原发性侧索硬化(PLS)患者5例。采用酶联免疫吸附法检测MND患者血清及脑脊液FGF-2水平,另选择同期非炎症性神经系统疾病患者40例为对照组。采用改良版肌萎缩侧索硬化功能量表评估ALS患者神经功能缺损程度,疾病进展率评估患者疾病进展水平,同时随访ALS患者的生存时间。结果 MND组ALS、PMA、PLS患者血清FGF-2水平明显高于对照组(P0.01)。MND组ALS患者脑脊液FGF-2水平明显高于对照组[(319.2±105.9)ng/L vs(241.7±34.3)ng/L,P0.01]。ALS患者血清和脑脊液FGF-2与疾病病程呈正相关,与疾病进展率呈负相关(P0.01)。MND患者的生存分析结果提示,累积生存率PMAPLSALSPBP,差异有统计学意义(P=0.000)。高FGF-2水平ALS患者累积生存率明显高于低FGF-2水平患者(P=0.002)。结论血清和脑脊液FGF-2水平在部分MND患者中增高,其可能是疾病分型及评估疾病进展、预测生存的生物学标志物之一。     

干燥综合征患者角膜神经纤维改变和炎性浸润程度与干眼症状相关性研究

目的 应用活体共聚焦显微镜(IVCM)观察干燥综合征(SS)患者角膜神经纤维改变情况和炎性浸润程度,并探讨其与干眼症状之间的相关性.方法 选择2017年1月至2019年10月该院眼科收治的SS患者22例(观察组),另选择同期健康志愿者22名(对照组),均应用IVCM对其角膜中央区域的神经纤维形态、朗格汉斯细胞密度进行观...     

β-淀粉样前体蛋白mRNA异构体在大鼠组织中差异性表达

β-淀粉样前体蛋白(APP)是细胞骨架蛋白的重要组成部分,具有多种异构体形式,不同的异构体可能具有不同的生物学作用和中间代谢途径并在疾病如阿尔茨海默病(AD)、肌萎缩侧索硬化症等的发生中发挥不同的作用。为此,我们用RT-多聚酶链反应(RT-PCR)检测了APP在大鼠端脑、脊髓和肾脏中的差异表达模式。     

兔右房快速起搏后交感神经重构的动态变化

目的:动态观察快速起搏右房后心房肌神经生长因子(NGF)和酪氨酸羟化酶(TH)的动态表达,从分子水平揭示心房颤动(房颤)交感神经动态重构的规律。方法:从快速起搏后的兔右心房和左心房取材,通过免疫组化并结合计算机图像处理技术对心肌中NGF蛋白表达及交感神经支配进行研究。结果:与假手术组比较,快速起搏后4h,NGF蛋白的表达在右心房[(412.75±7.49)μm2/mm2∶(563.87±15.53)μm2/mm2]和左心房[(275.87±16.74)μm2/mm2∶(449.75±17.58)μm2/mm2]心肌中明显增加(P0.05);TH阳性神经纤维平均密度[右心房(72.00±8.02)μm2/mm2∶(83.87±7.18)μm2/mm2,左心房(58.00±10.65)μm2/mm2∶(70.50±6.65)μm2/mm2,P0.05]均显著增加;且右心房和左心房中交感神经支配与NGF蛋白的表达呈正相关(r=0.53,P0.05)。快速起搏后12h,兔心房中NGF蛋白的表达[右心房(869.50±17.28)μm2/mm2,左心房(830.75±11.73)μm2/mm2]与TH阳性神经纤维平均密度[右心房(120.87±8.57)μm2/mm2,左心房(100.25±10.25)μm2/mm2]均明显高于假手术组及快速起搏后4h组(P0.05~0.01),且二者呈正相关(r=0.69,P0.05)。快速起搏后24h,NGF蛋白表达[右心房(1115.7±92.35)μm2/mm2,左心房(949.12±43.20)μm2/mm2]及TH阳性神经纤维平均密度[右心房(158.12±11.28)μm2/mm2,左心房(121.12±14.71)μm2/mm2]均明显高于快速起搏后4h、12h(P0.01~0.001)。结论:快速起搏后心肌中神经生长因子蛋白呈动态表达,并与交感神经支配相关,提示神经生长因子可能在心肌局部发挥神经营养作用,进而参与交感神经的重构。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Variabilité des concentrations plasmatiques de l’angiotensinogène et risque d’hypertension artérielle chez le rat transgénique

Aim

Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5 mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors.

Methods

Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n = 3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction).

Results

At baseline, transgenic rats had +18 mmHg higher bood pressure and –8% lower body weight compared to non-transgenic rats (P < 0.05) without significant changes for the vehicle groups throughout the study (P > 0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P < 0.05) in transgenic and +25%, +5.3% and +6.7% (P > 0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P > 0.05).

Conclusion

Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.     

Morphological and immunocytochemical heterogeneity of cultured pinealocytes from one-week-and two-month-old rats: Planimetric and densitometric investigations

Abstract: In vitro preparations of rat pinealocytes are widely used for biochemical analyses of signal transduction processes. This paper deals with morphological and immunocytochemical features of such preparations. Special attention was paid to the problems of whether pinealocytes represent a heterogeneous cell population and how such heterogeneity may develop during ontogeny. The investigations were performed with cells which were obtained from the pineal organ of one-week-and two-month-old rats, attached to synthetic peptide-coated coverslips or tissue culture chamber slides, and maintained under in vitro conditions overnight. The attached cells were then fixed with paraformaldehyde. These preparations yielded monolayers of spherical cells of different sizes; most cells were isolated, but some of them were aggregated and formed small clusters. On the average, the cells from the one-week-old animals were smaller than the cells from the two-month-old animals. Immunocytochemical demonstration of S-antigen, a pinealocyte-specific marker, showed that the majority of the cells from two-month-old animals were intensely or moderately labelled. Pinealocytes from one-week-old animals were less S-antigen immunoreactive. Only very few cells (less than 1% displayed glial fibrillary acidic protein (GFAP)-immunoreactivity. Planimetric investigations of the cell size and semiquantitative densitometric investigations of the intensity of the S-antigen immunoreaction revealed that (i) pinealocytes kept in vitro form a heterogeneous cell population, and that (ii) this heterogeneity increases during postnatal development from one-week-old to two-month-old animals. Two groups of pinealocytes can be distinguished based on their developmental fate: pinealocytes of one group grow dramatically, but show only a moderate increase in S-antigen immunoreactivity, and pinealocytes of the other group retain their size, but display a distinct increment in S-antigen immunoreacti vitv.     

Effects of pinealectomy and melatonin administration on certain indices of ovarian hyperplasia and/or hypertrophy in rats with both ovaries intact or after unilateral ovariectomy

Abstract: In earlier studies from other laboratories it was shown that melatonin decreased ovarian weight in rats and inhibited compensatory hypertrophy of the remaining ovary after unilateral ovariectomy. This study was designed to examine the influence of melatonin on certain indices of ovarian hyperplasia and/or hypertrophy in adult female rats with both ovaries preserved and with either an intact pineal gland or with the pineal gland removed (pinealectomy, PX) or, finally, in sham-PX animals. Similar studies were conducted on rats after unilateral ovariectomy, referring the examined parameters to the remaining intact ovary. The studies included mitotic activity of granulosa layer cells and corpus luteum cells, ovarian weight, ovarian cross-sectional area, cross-sectional area of the granulosa layer of all the Graafian follicles and the cross-sectional areas of the corpora lutea, visible on the ovarian cross-section. On the basis of results, we conclude that: 1) the effect of PX on the processes of ovarian hyperplasia and hypertrophy may vary; analogously, exogenous melatonin administration may influence ovarian hyperplasia and hypertrophy in different ways; 2) PX and exogenous melatonin may, under certain conditions, exert similar biological effects, even synergistic effects; 3) melatonin inhibits ovarian growth processes, while the effects of PX are variable; 4) the results indicate that in experiments performed on rats, with the use of two control groups, i.e., intact and sham-PX, melatonin effects on these two groups may differ.