Synthesis and antiviral activity of phosphonoacetic and phosphonoformic acid esters of 5-bromo-2'-deoxyuridine and related pyrimidine nucleosides and acyclonucleosides

Phosphonoacetic acid (PAA, 1) was coupled with various acyclonucleosides, 2'-deoxyuridines, cytidines, and arabinosyluracils, with 2,4,6-triisopropylbenzenesulfonyl chloride (TPS) or dicyclohexylcarbodiimide (DCCI) as condensing agents, to give a range of phosphonate esters. The carboxylic ester linkage of PAA to the 5'-position of 5-bromo-2'-deoxyuridine (BUdR, 3) was achieved via the mixed anhydride formed from (diethylphosphono)acetic acid and trifluoroacetic anhydride. Phosphonoformic acid (PFA, 2) was coupled with BUdR by using the DCCI method to give the phosphonate ester. Of these compounds only phosphonate esters in the 2'-deoxyuridine series showed significant activity against herpes simplex virus types 1 and 2. The BUdR-PAA derivative and the BUdR-PFA derivative were highly active, especially the latter, which was more active than the parent nucleoside BUdR against the type 2 virus. The active compounds may exert their effects by extracellular or intracellular hydrolysis to the corresponding antiviral agents, but an intrinsic component of antiviral activity may also be involved.     

Serum concentrations of alkaline phosphatase isoenzymes and osteocalcin in normal pregnancy

We measured serum alkaline phosphatase isoenzymes and osteocalcin levels in 40 healthy women at 4-week intervals throughout uncomplicated pregnancies and 6 weeks after delivery in 17 women. Serum bone alkaline phosphatase was significantly higher in the third trimester than in early pregnancy (P less than 0.001), and this elevation was still apparent at the end of the puerperium, suggesting increased bone turnover. Serum osteocalcin was not detected (less than 0.2 micrograms/L) after the first trimester in the majority of women, and it reappeared within 48 h after delivery. The disappearance of osteocalcin after the first trimester and its rapid reappearance after delivery suggest placental clearance of this peptide. We conclude that serum osteocalcin measurements cannot be used as a marker of bone metabolism during pregnancy.     

Deep brain stimulation: a review of basic research and clinical studies

Deep brain stimulation for pain control in humans was first used almost 30 years ago and has continued to receive considerable attention. Despite the large number of clinical reports describing pain relief, numerous studies have indicated that the results of these procedures vary considerably. In addition, many neurosurgeons find the procedures unpredictable, and considerable disagreement still exists regarding important issues related to the technique itself. This review gives an historical overview of the relevant basic and clinical literature and provides a critical examination of the clinical efficacy, choice of stimulation sites, parameters of stimulation, and effects on experimental pain. Finally, we give suggestions for future research that could more definitively determine the usefulness of deep brain stimulation for pain control.     

Regional extraction of circulating norepinephrine, DOPA, and dihydroxyphenylglycol in humans

Dihydroxyphenylglycol (DHPG) is the main intraneuronal metabolite of the sympathetic neurotransmitter, norepinephrine (NE), and dihydroxyphenylalanine (DOPA) the immediate product of the rate-limiting step in catecholamine biosynthesis. Simultaneous measurements of regional rates of appearance (spillovers) of NE, DOPA, and DHPG in plasma have the potential to provide unique information about aspects of sympathoneural function but have not actually been measured in humans. In the present study, spillovers of DHPG, DOPA, and NE in the heart, head, leg, and lungs, were estimated from regional extraction fractions of infused [3H]-1-NE, DHPG, and [13C6]DOPA or unlabelled DOPA in humans during cardiac catheterization. There was little cardiac extraction of DHPG (7 +/- SEM 2%) or DOPA (8 +/- 4%) but substantial extraction of NE (69 +/- 4%). Values for cardiac spillover of DHPG and DOPA therefore were similar to values for the arteriovenous increment times plasma flow (arteriovenous production rate), whereas the cardiac spillover of NE averaged about 7-times the NE arteriovenous production rate. Cardiac DHPG spillover (28 +/- 3 ng/min) exceeded the spillovers of NE (9 +/- 2 ng/min) and DOPA (15 +/- 4 ng/min). In contrast, cranial DOPA spillover (159 ng/min) exceeded those of NE and DHPG by 8- and 2-fold and accounted for about 1/10 of the total spillover of DOPA into arterial plasma. In the femoral vascular bed, arteriovenous production rates of NE and DHPG were unrelated to femoral spillovers of NE and DHPG. Arterial and regional clearances of [13C6]DOPA were similar to those of unlabelled DOPA. The results suggest that (1) endogenous NE, DOPA, and DHPG all are released into the bloodstream by the heart, head, and limbs of humans; (2) DHPG and DOPA are not co-released with NE; (3) cardiac arteriovenous production rates of DOPA and DHPG can be used to indicate cardiac spillover of these catechols, whereas the cardiac NE arteriovenous production rate substantially underestimates cardiac NE spillover; and (4) estimates of limb spillover of NE and DHPG require concurrent measurements of the corresponding regional clearances.     

子宫内膜异位症患者血清中靶抗体的检测和应用

目的 :建立一种ELISA方法 ,以检测子宫内膜异位症患者血清中抗转铁蛋白抗体。　方法 :用转铁蛋白包被的间接ELISA方法检测血清中的抗转铁蛋白抗体。血清标本来自 96例正常体检女性 ,6 4例妊娠妇女 ,72例儿科女童 ,以及 2 4例子宫内膜异位症患者。　结果 :子宫内膜异位症患者血清中的抗转铁蛋白抗体阳性率远远高于对照组 ,特异性为 99.0 % ,敏感度为 95 .8% ,准确性为 99.2 %。　结论 :子宫内膜异位症患者血清抗转铁蛋白抗体阳性率明显高于对照组 ,抗转铁蛋白抗体检测可作为子宫内膜异位症的非创伤性诊断方法     

以杯[4]芳烃衍生物为载体的钾离子选择电极的研究

目的：研制新的以杯[4]芳烃衍生物为载体的PVC膜钾离子选择电极。方法：以3种杯[4]芳烃衍生物为载体，癸二酸二辛酯或邻苯二甲酸二辛酯为增塑剂，四（4－氯）苯硼钾为离子定域体制得了PVC膜钾离子选择电极，测试了该类电极对钾离子的响应性能和对7种阳离子的选择性系数。结果：以5，11，17，23－四叔丁基－25，26，27，28－四[2-(乙氧基羰基）苄氧基]杯[4]芳烃为载体所制得的电极（电极Ⅰ）对钾离子有良好的能斯特响应，该电极的选择性系数优于电极Ⅱ和Ⅲ。分别用电极Ⅰ，Ⅱ，Ⅲ对青霉素V钾中的钾含量进行了测定，其结果均与原子吸收法基本一致。结论：所制得的上述电极是一类新的钾离子选择电极，有实用价值。     

与时俱进 全面开展生活方式教育

该文从疾病谱和死因谱的改变、医学模式的转变、卫生经费的降低、自我保健意识的改变四个角度,论述了全面开展 生活方式教育的必要性和重要性;从以社区为依托、以医院为基础、以生活方式为指导三个方面,探讨了生活方式教 育的工作模式.     

Computed tomography in gunshot wounds to the neck: Can we predict vascular injury?

The purpose of this study was to evaluate the ability of helical computed tomography (CT) to detect arterial injuries in gunshot wounds to the neck. In a blinded retrospective review, 54 helical CT scans of the cervical spine were evaluated for bullet/bone fragments, subcutaneous air, bullet path, hematoma, spine fractures, and pharyngoesophageal compromise. The distance of fragments to a major vessel was calculated. CT findings that correlated significantly with major arterial injury included the presence of fragments (bullet/bone) close to a major vessel (2.5 mm) and spine fractures. Visualizing fragments <5 mm from a vessel or a transcervical bullet trajectory predicted 12 of 13 major arterial injuries. We conclude that CT clearly depicts anatomic damage. Specific findings, such as the location of fragments and bullet trajectory adjacent to a vessel and spine fractures, indicate a higher probability of vascular damage, thus directing more definitive evaluation.