骨膜间质干细胞移植时机的实验和临床研究

目的 研究骨膜间质干细胞异体移植时机。方法 根据骨缺损内纤维组织生长时间的不同，将从大鼠骨膜分离培养的细胞分别分批植入，在植入的第2、3、4和8周时动态观察其成骨量，即骨小梁体积比；另将幼儿骨膜间质干细胞悬液，移植于26例长管状骨干骨折2周后的缺损内，观察骨折临床愈合的时间。结果 大鼠骨缺损后2周以内移植干细胞其骨小梁体积比大，愈合快，2周以后与对照组比无显著差异；临床应用9个月内病人骨折缺损愈合15例(57．7％)，骨不愈合者11例(42．3％)。结论 大鼠骨缺损2周以内移植干细胞其疗效好，大鼠实验和临床上骨缺损2周以后移植骨膜间质干细胞不能明显促进骨缺损愈合。     

Cholinergic balance in dementia with Lewy bodies: reversible worsening of Parkinsonism at rivastigmine dosage modulation

We describe a patient with probable dementia with Lewy bodies (DLB) whose Parkinsonism worsened after administration of rivastigmine within the therapeutic dose range. Some extrapyramidal signs (EPS) then reversed to pre-treatment level after rivastigmine dose reduction. We draw attention to the need of EPS monitoring during titration of cholinesterase inhibitors in patients with DLB. This is the first report to our knowledge of iatrogenic worsening of Parkinsonism which was successfully managed by dose reduction.

---

Sommario Si descrive il caso di un paziente affetto da Demenza a corpi di Lewy (Dementia with Lewy Bodies, DLB) probabile, in cui si è assistito ad un peggioramento del parkinsonismo dopo somministrazione di rivastigmina a dosi terapeutiche. Alcuni segni extrapiramidali sono regrediti al livello pre-trattamento con una riduzione posologica di rivastigmina. Si sottolinea la necessità di un monitoraggio dei segni extrapiramidali durante la titolazione della terapia con inibitori dell’acetilcolinesterasi cerebrale in pazienti con DLB. Questo è il primo caso descritto, a nostra conoscenza, di un peggioramento iatrogeno di parkinsonismo efficacemente gestito con una riduzione posologica della terapia con rivastigmina.

     

Renal interstitial pressure and tubuloglomerular feedback control in rats during infusion of atrial natriuretic peptide (ANP)

Atrial natriuretic peptide (ANP), injected at physiological concentrations, is known to induce both natriuresis and diuresis. It has been suggested by some investigators that these changes result from an increasing glomerular filtration rate (GFR), but others have been unable to demonstrate an increased GFR. The tubuloglomerular feedback (TGF) mechanism is an important regulator of GFR, and the sensitivity of TGF is decreased during ANP administration. Furthermore, resetting of TGF is, in most instances, related to changes in renal interstitial hydrostatic and oncotic pressures. It is also known that ANP may increase capillary permeability which may change renal interstitial pressure. The present study was performed to examine renal interstitial pressures and the TGF mechanism during ANP infusion. In accordance with previous studies, TGF sensitivity was found to be decreased. The tubular flow rate which elicited half the maximal drop in stop-flow pressure (P_sf) was increased from 18.5 to 25.7 nl min^-1. In contrast, ANP infusion resulted in a decreased interstitial hydrostatic pressure and an increased interstitial oncotic pressure. From previous experiments, such changes in interstitial pressures would be expected to increase TGF sensitivity. The changes in interstitial pressure cannot, therefore, directly explain the resetting of the feedback mechanism. In conclusion, the present paper shows a decreased renal net interstial pressure after intravenous administration of ANP.     

Z-3-(2-羟基丁烯基)苯酞的合成研究

研究目的探讨苯酞类天然产物的合成方法及其生物活性。研究方法以邻苯二甲酐为底物，首先引入丁烯基，再进行烯丙位氧化，制得目标化合物。结果通过丁基锂反应，得到了具有药物活性的丁烯基苯酞，然后利用SeO2烯丙位氧化，首次合成了Z－3－（2－羟基丁烯基）苯酞。结论此合成方法原料易得，方法简便，为苯酞类化合物的合成研究提供了一个新的途径。     

Does ageing have an effect on midbrain premotor nuclei for vertical eye movements?

Currently, there is debate in the clinical literature as to whether defects in vertical gaze are a consequence of normal ageing or a component of an underlying neurodegenerative disorder. Although pathological changes have been demonstrated in diseased subjects, no study to date has addressed the question of normal ageing effects. In this retrospective study, we examined 23 neurologically and pathologically normal subjects (age 18-91). Using an unbiased, frame-based sampling method, we quantified neuronal and glial cell densities in 10 young (<50) and 13 aged (>65) subjects in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), the key premotor substrate in the vertical gaze pathway. We found no statistically significant difference in neuronal density, glial cell density, or neuron-to-glial cell ratios between the young and the aged. We conclude, therefore, that neuronal loss, neuronal atrophy, or gliosis in the riMLF are not consequences of normal ageing.     

Single-dose and steady-state pharmacokinetics of sabeluzole in senile dementia of Alzheimer type patients

Summary The single- and repeated-dose pharmacokinetics of sabeluzole have been determined in six elderly patients with [senile] dementia of the Alzheimer type.After a single oral dose of 10 mg sabeluzole, the peak plasma concentration was attained at 1 to 4 h; it averaged 42 ng·ml^–1. On repeated dosing (10 mg b. d.), steady-state was virtually attained after 3 days of treatment. Steadystate mean trough and peak plasma concentrations fluctuated between 53 and 94 ng·ml^–1. The mean terminal half-life after a single dose and at steady-state was of the order of 33 h.Sabeluzole was well tolerated and at the end of treatment, no systematic changes in blood haematology, biochemistry or urinalysis were seen.     

The haemodynamic response to the insertion of the laryngeal mask airway: a comparison with laryngoscopy and tracheal intubation

The haemodynamic response to the insertion of the laryngeal mask airway (LMA) was assessed and compared to that of laryngoscopy and tracheal intubation in a study of forty patients (ASA 1) randomly allocated into two groups and anaesthetised using a standard balanced anaesthetic technique. The results show that the changes in all cardiovascular parameters measured following LMA insertion were significantly less (P<0.05) when compared with those following laryngoscopy and tracheal intubation. We conclude that airway management with the LMA may be used to avoid the haemodynamic response to tracheal intubation where such a response is undersirable.     

急性心肌梗死静脉溶栓后cTnT浓度比值对判断冠脉再通的价值

目的　探讨血清心肌肌钙蛋白T(cTnT) 3h 2h的浓度比值对急性心肌梗死 (AMI)溶栓后判定冠状动脉再通的价值。方法　采用ELISA法动态检测了 5 7例接受尿激酶静脉溶栓治疗的AMI患者和 31例正常健康对照血清cTnT ,CK MB及CK水平 ,并计算溶栓后 3h与 2h血清cTnT浓度比值。结果　①cTnT释放呈现两种特征 ,再通组呈双峰型 ,未通组呈单峰型 ,且再通组后期峰值较未通组峰值低 (P <0 .0 1)。②cTnT浓度 3h 2h比值再通组明显高于未通组 (P <0 .0 1) ,以该比值 >1.4 8作为判定再通的标准 ,其对判定冠状动脉再通的敏感性、特异性、预测值分别为 83.3% ,90 .5 % ,93.8%。与峰值时间判定冠脉再通比较差异无显著性 (P >0 .0 5 )。结论　cTnT的动态检测可有效地判定对AMI溶栓后再通与否 ,特别是溶栓后 3h 2h浓度比值 >1.4 8可作为早期判定冠脉再通的标准 ,且具有迅速、省时等优点 ,值得推广应用     

Pharmacology of KB‐R7943: A Na+–Ca2+ exchange inhibitor

The Na⁺–Ca²⁺ exchange (NCX) system plays a pivotal role in regulating intracellular Ca²⁺ concentration in cardiomyocytes, neuronal cells, kidney and a variety of other cells. It performs a particularly important function in regulating cardiac contractility and electrical activity. One of the leading NCX inhibitors is KB‐R9743 (KBR) that appears to exhibit selectivity for Ca²⁺‐influx‐mode NCX activity (reverse mode of NCX). In this article we reviewed pharmacology of KBR and provide a brief summary of studies with other NCX inhibitors, such as SEA0400 (SEA) and SN‐6 (SN). Potential clinical usefulness of KBR and other NCX inhibitors is still controversial but the reviewed findings may be helpful in designing more selective and clinically useful NCX inhibitors for the treatment of cardiac, neuronal and kidney diseases.