Evaluation of non-invasive techniques to assess vasoconstriction in healthy volunteers using methoxamine as a probe drug

Non-invasive methods for assessment of the vascular effects of antimigraine drugs were evaluated with respect to their utility, variability and sensitivity in a double-blind, placebo-controlled, three-period crossover study in six healthy volunteers using an intravenous vasoconstrictor, methoxamine, as a probe drug. Changes in the internal diameter of the brachial and radial arteries were measured using ultrasound which had low between-day and within-day coefficients of variation. Peak systolic velocity (PSV), time-averaged velocity (TAV), total flow, resistance (RI) and pulsatility indices (PI) were measured by Doppler from one arterial wave form. Whilst PSV and TAV increased with methoxamine, because of bradycardia, changes in PI and RI were difficult to interpret. An automatic oscillametric cuff, a mercury-in-silastic strain gauge method and the "Finapres", finger arterial blood pressure monitor were used to follow changes in systolic blood pressure (SBP). The strain gauge technique underestimated arm SBP compared to the oscillometric method but clearly showed drug-related increases whilst the Finapres did not reflect changes in blood pressure detected by the other methods.     

Properties of vertebrate glutamate receptors: calcium mobilization and desensitization.

Glutamate is now recognized as a major excitatory neurotransmitter in the vertebrate CNS, participating in a number of physiological and pathological processes. The importance of glutamate in the mobilization of intracellular Ca2+ as well as the relationship between excitatory and toxic properties has made it important to understand factors that regulate the responsivity of glutamate receptors. In recent years considerable insight has been gained about regulatory sites on NMDA receptors, with the recognition that these receptors are modulated by multiple endogenous and exogenous agents. Less is known about the regulation of responses mediated by AMPA, kainate, ACPD or APB receptors. Desensitization represents a potentially powerful means by which glutamate responses may be regulated. Indeed, two agents closely linked to the physiology of NMDA receptors, glycine and Ca2+, appear to modulate different types of desensitization. In the case of glycine, alteration of a rapid form of desensitization may be important in the role of this amino acid as a necessary cofactor for NMDA receptor activation. Additionally, changes in the affinity of the receptor complex for glycine may underlie the use-dependent decline in NMDA responses under certain conditions. Likewise, Ca2+ is a crucial player in the synaptic and toxic effects mediated by NMDA receptors, and is involved in a slower form of desensitization, in effect helping to regulate its own influx into neurons. The site and mechanism of the Ca2+ regulatory effects remain uncertain with evidence supporting both intracellular and ion channel sites of action. A clear role for Ca(2+)-dependent desensitization in the function of NMDA receptors under physiological conditions has not yet been demonstrated. AMPA receptor desensitization has been an area of intense investigation in recent years. The rapidity and degree of this process, coupled with its apparent rapid recovery, has suggested that desensitization is a key mechanism for the short-term regulation of responses mediated by these receptors. Furthermore, rapid desensitization appears to be one factor determining the time course and efficacy of fast excitatory synaptic transmission mediated by AMPA receptors, highlighting the physiological relevance of the process. The molecular mechanisms underlying desensitization remain uncertain. Traditionally, desensitization, like inactivation of voltage-gated channels, has been thought to represent a conformational change in the ion channel complex (Ochoa et al., 1989). However, it is unknown to what extent desensitization, in particular rapid AMPA receptor desensitization, has mechanistic features in common with inactivation. In voltage-gated channels, conformational changes in the channel protein restrict ion flow through the channel (Stuhmer, 1991).(ABSTRACT TRUNCATED AT 400 WORDS)     

五味子中联苯环辛二烯木脂素类化合物的质谱研究

本文通过低分辨和高分辨质谱和亚稳分析,对五味子甲素(schisandrin A,1)等23个从五味子科(Schisandraceae)植物中分离出的联苯环辛二烯木脂素类化合物进行了质谱裂解方式研究,总结了重要的质谱特征,为今后继续研究五味子科植物及类似新化合物的结构测定提供了可靠依据。     

Practical and technical considerations in establishing an intraoperative radiation therapy program in the community practice

The Radiation Oncology Center in Sacramento, California, has developed a procedure for establishing an intraoperative radiation therapy facility in a community practice. The logistics pertaining to personnel, equipment, physical measurements, and quality assurance are presented. Particular emphasis is given to the most effective means of acquiring the large quantity of data needed to ensure a program of acceptable quality.     

Hyperlipidemia, hypercoagulability, and accelerated thrombosis: studies in congenitally hyperlipidemic rats and in rats and monkeys with induced hyperlipidemia

Inbred Carworth Farms Nelson (CFN) congenitally hyperlipidemic rats had significantly shorter coagulation and prothrombin times and higher levels of coagulation factors, II, V, VII, VIII, and X than did controls. Conversely, congenitally hypolipidemic rats of the same strain had significantly longer coagulation and prothrombin times and lower levels of factors II, V, VII, X and XII and of blood platelets than did controls. A loop-shaped polyethylene cannula was inserted into the aorta to assess the potential for thrombosis. The hyperlipidemic group obstructed this significantly faster and the hypolipidemic group slower than did the controls. Normal CFN rats made hypertensive by unilateral renal artery clip developed hypertension together with significantly elevated serum cholesterol and factor VII and X levels. Rhesus monkeys with diet-induced hyperlipidemia showed shorter prothrombin times and higher factor X levels than did controls on normal diet. By selective breeding, two groups of squirrel monkeys were obtained. Both groups had similar serum cholesterol levels on a normal diet but one group (hyperresponders) showed higher serum cholesterol levels on a cholesterol-containing diet than did the other (hyporesponder) group. Both groups showed significantly elevated levels of factors II, V, VII, IX and X on a cholesterol-containing diet. There was good correlation between the levels of many coagulation factors and serum cholesterol in both rats and monkeys. If thrombosis is important in the genesis of atherosclerosis, these findings could indicate that elevation of plasma lipids may play a role, via the coagulation pathway, in the production of human vascular disease.     

异戊塞平和克塞平对大鼠脑内各受体亲和力的比较及慢性给药后的受体下调作用

用放射配体受体结合法测定表明:克塞平对多巴胺D_1受体的亲和力较异戊塞平高近20倍。两药对其它各受体的亲和力差別不大。慢性给药后,异戊塞平和克塞平均能使大鼠脑皮层5-HT_2受体的密度显著下降,而亲和力变化不明显。这种下调5-HT_2受体的作用发生在给异戊塞平后1～2周之间,给克塞平后的2～3周之间。慢性给药3周,异戊塞平和克塞平均未使大鼠脑皮层的β受体密度及亲和力产生显著变化。