孕妇血清钙及白蛋白测定的临床意义

目的 :了解测定血清钙、白蛋白的变化对孕妇影响的临床意义。方法 :采用邻甲酚酞络合酮、离子选择性电极法、溴甲酚绿法测定。结果 :孕妇组血清总钙、离子钙、白蛋白的含量明显低于非孕妇组 ,差异有非常显著性 (P<0 .0 1) ,中孕妇组与晚孕妇组比较血清总钙、离子钙没有差异 (P>0 .0 5 )。白蛋白含量晚孕妇组明显低于中孕妇组 ,差异有显著性 (P<0 .0 1)。结论 :血清总钙、离子钙、白蛋白对孕妇尤为重要。动态监测 ,及时补充可提高孕妇及胎儿的健康     

Synthesis and antimalarial activity of new atovaquone derivatives

In this paper we describe the design and synthesis of 18 derivatives of the antimicrobial atovaquone which were substituted at the 3-hydroxy group by ester and ether functions. The compounds were evaluated in vitro for their activity against the growth of Plasmodium falciparum, the malaria causing parasite. All the compounds showed potent activity, with IC₅₀ values in the range of 1.25–50 nM, comparable to those of atovaquone and much higher than chloroquine or quinine.     

Genetic segregation analysis of red blood cell (RBC) histamine N-methyltransferase (HNMT) activity

Methylation is an important pathway in the biotransformation of many drugs, neurotransmitters, and xenobiotic compounds. Histamine N-methyltransferase (HNMT) catalyzes the Nτ-methylation of histamine and structurally related compounds. Measurement of HNMT activity in the RBC makes it possible to access variation in the enzyme activity that may reflect differences in less accessible tissues such as brain. Previously reported high family correlations for RBC HNMT activity suggested that genetic inheritance plays a major role in the regulation of variation in this enzyme. In the present study we completed complex segregation analyses of RBC HNMT activity of 241 individuals in 51 nuclear families that were randomly ascertained through children in the Rochester, Minnesota public school system in order to characterize the mode of inheritance of this important enzyme. We found evidence for major gene influence on the regulation of RBC HNMT activity. Both transformed and untransformed data support the presence of Mendelian major gene segregation, but the gene frequency differences do not indicate a direct correspondence between genotypes inferred from the two sets of analyses. Analyses of the skewed untransformed data indicated the presence of a relatively rare (Q = 0.121) additive major gene for high activity, with the three overlapping genotype distributions representing 77, 21, and 2 % of individuals. Analyses of the normalized transformed data indicated the presence of a common (Q = 0.71) additive major gene for high activity, with the three overlapping genotype distributions accounting for 9, 41, and 50 % of individuals. The analyses of transformed data give the best fit as well as the most parsimonious Mendelian major gene model. However, we cannot rule out the possibility of multiple alleles, and analyses of untransformed data provide some support for a third allele. Molecular studies will be needed to validate and characterize the alleles that regulate RBC HNMT activity levels in humans. © 1993 Wiley-Liss. Inc.     

Cholecystokinin Excites Neostriatal Neurons in Rats via CCKA or CCKB Receptors

The effect of iontophoretically applied cholecystokinin (CCK) on neurons of the neostriatum was studied in rats anaesthetized with urethane. The most frequently observed effect of the sulphated octapeptide (CCK-8S) on striatal neurons was excitation. Spontaneously active neurons responded more often to CCK-8S than quiescent cells. Silent, primarily non-responsive neurons could often be stimulated with CCK-8S using glutamate to induce an ongoing discharge. Thus, 45.8% of the 177 neurons studied changed their discharge rate by more than 30%. Certain CCK receptor antagonists could prevent the effect of CCK-8S, fully or at least partly, in the majority of CCK-responsive neurons. The data suggest that cholecystokinin modulates the firing of active neostriatal neurons via the CCKA or the CCKB receptor type. Furthermore, we compared neuronal responses to glutamate with those recorded during concomitant administration of CCK-8S in order to study the interaction of both transmitters, which may be colocalized in striatal afferents. CCK-8S mainly enhanced the excitatory effect of glutamate on striatal neurons, but in several neurons the response to glutamate was reduced. The CCKB receptor antagonist could prevent CCK-8S from increasing the glutamate-induced activation.     

Lesional elastase activity in psoriasis

Human leukocyte elastase, a neutrophil-derived serine protease, is present in psoriatic lesions in an enzymatically active form. Our purpose was to assess the significance of human leukocyte elastase determinations in estimating the inflammatory activity of psoriatic lesions. A standardized method was used to analyse lesional elastase activity. Elastase activities were correlated with erythema, induration and hyperkeratosis of psoriatic lesions in 54 patients. Lesional elastase activities were also determined during treatment with salt-water bathing and UVB irradiation. Lesional elastase activity correlated with skin induration and was inversely correlated with hyperkeratosis of the lesions. Psoriatic lesions with high elastase activity responded well to therapy, whereas lesions with low elastase activity appeared to be comparatively resistant. This study shows that by quantitative determination of lesional elastase activities it is possible to distinguish predominantly inflammatory from predominantly hyperproliferative psoriasis. The latter shows delayed responsiveness to topical therapy with salt-water bathing plus UVB irradiation.     

低分子量肝素化学及生物活性的不均一性

综述了低分子量肝素的化学和生物活性的不均一性,以及药理作用,药物动力学、临床应用等方面的差异。     

The heat shock/oxidative stress connection

Involvement of free-radical oxidations in the aging process has been a topic of interest since Harman's original contribution. Because of the close association between aging and Alzheimer disease (AD) and the qualitative similarity in the neuropathology of both conditions, it has been proposed by many investigators that oxidative stress may be important in AD. If such modality of injury was indeed involved, one should expect to find markers of oxidation and heat shock (since free radicals are key mediators of heat-shock induction) in brains of patients with AD. In fact, several studies documented abnormal expression of antioxidant enzymes and heat-shock proteins (HSP) along with other markers of oxidation in AD brains. We showed that abnormally expressed antioxidant enzymes are topographically associated with senile plaques and neurofibrillary tangles, and that the activity of these enzymes is (contrary to what one would expect) markedly reduced. These findings have recently been confirmed by other investigators. Despite a large amount of evidence that suggests an association between oxidative stress and the pathogenesis of AD, it is not yet known whether oxidative stress is a cause or consequence of the disorder. Future research efforts regarding the oxidative stress hypothesis of AD should include attempts, at generating AD pathology by oxidative means in laboratory animals, determining the role and integrity of the heat-shock response in AD, as well as that of various antioxidant systems, growth factors, and hormones with antioxidant and neuroprotective properties.     

Neurons labeled from locomotor-related ventrolateral funiculus stimulus sites in the neonatal rat spinal cord.

Spinal cord/brainstem preparations from 5- to 8-day-old rats, maintained in vitro, were used to determine the cells of origin and regions of termination of fibers in the superficial ventrolateral funiculus (VLF) at a site from which rhythmic locomotor-like activity can be induced. Rhythmic locomotor-like activity was recorded from lumbar ventral roots after short trains of stimuli (50 Hz for 0.5-2 seconds) delivered to the VLF. Field potential mapping revealed that single VLF stimuli elicited responses in the ipsilateral ventrolateral medulla. Tract-tracing experiments by using biocytin, pressure-injected into the VLF, showed that only a small number of brainstem neurons were labeled and these were scattered bilaterally in the ventrolateral and lateral medulla. Dense concentrations of nerve terminals were found in the lateral reticular nucleus ipsilateral to the stimulation site. Labeled spinal cord neurons included a primary population of large cells distributed bilaterally in lamina VII from T13 to L4, with peak numbers in L2 ipsilaterally and in L3 contralaterally. Intracellular recordings revealed that some L2 and L3 neurons with rhythmic responses to VLF stimulation could be activated antidromically from the VLF, with latencies of less than 1.0 msec. These observations led us to speculate that the superficial VLF carries a locomotor-related tract originating bilaterally in lumbar lamina VII and terminating in the ipsilateral medulla, including the lateral reticular nucleus. This pathway may be part of the spinoreticular or spinoreticulotectal pathway that has been described in many species, the function of which has only loosely been ascribed.     

Effects of air-jet stress on renal blood flow in spontaneously hypertensive rats

Background Stressful psychological stimuli produce an increase in renal sympathetic nerve activity (RSNA) and a decrease in renal blood flow. Very few direct analyses of the relationship between RSNA and renal blood flow during the application of psychological stimuli have been conducted by recording these 2 measurements simultaneously in the same individual animals. Methods We simultaneously measured RSNA and renal blood flow as a Doppler shift in conscious, unrestrained, spontaneously hypertensive rats. The rats were stressed by directing a continuous air jet at their faces for 20 seconds. Results Air-jet stimulus increased RSNA 81%±15% (mean±standard error of the mean, n=10), mean arterial pressure (21±3 mm Hg), and renal vascular resistance (37%±6%), and decreased renal blood flow (−15%±2%). The percentage change in RSNA correlated positively with the change in mean arterial pressure (r=0.934,P<0.001) and percentage change in renal vascular resistance (r=0.912), and negatively with the percentage change in renal blood flow (r=−0.804). The denervation of renal nerves prevented renal blood flow from decreasing in response to air-jet stress. Conclusions A reduction in renal blood flow in response to short-term air-jet stress is elicited mainly by neural mechanisms in spontaneously hypertensive rats. Enhancement of RSNA by air-jet stimulus exerts a potent constricting effect on the renal vascular bed, resulting in a reduction in renal blood flow.     

Dose dependent effects of S-20098, a melatonin agonist,on direction of re-entrainment of rat circadian activity rhythms

The chronobiotic properties of melatonin are well documented. For example, following an 8-h phase advance of the light-dark cycle daily injections of melatonin administered at the pre-shift dark onset alter the direction of re-entrainment of rat activity rhythms. Using this 8-h phase advance paradigm, the effects of the melatonin agonist S-20098 (1 mg/kg and 3 mg/kg) on the rat circadian system were compared with those of melatonin. S-20098 altered the direction of reentrainment in the same manner as melatonin. A study using lower doses of S-20098 showed that the effect on direction of re-entrainment was dose-dependent, with 100% of rats responding at a dose of 100 µg/kg. S-20098 may, therefore, have therapeutic potential as a chronobiotic in the treatment of circadian disorders in humans.