The Effect of Area HMO Market Share on Cancer Screening

Objective. Managed care may have widespread impacts on health care delivery for all patients in the areas where they operate. We examine the relationship between area managed care activity and screening for breast, cervical, and prostate cancer among patients enrolled in more managed care plans and patients who are enrolled in less managed plans.
Data and Methods. Data on cancer screening from the 1996 Medical Expenditure Panel Survey (MEPS) were linked to data on health maintenance organization (HMO) and preferred provider organization (PPO) market share and HMO competition at the metropolitan statistical area (MSA) level. Logistic regression analysis was used to examine the relationship between area managed care prevalence and the use of mammography, clinical breast examination, Pap smear, and prostate cancer screening in the past two years, controlling for important covariates.
Results. Among all patients, increases in area-level HMO market share are associated with increases in the appropriate use of mammography, clinical breast exam, and Pap smear (OR for high relative to low managed care areas are 1.75, p <.01, for mammography, 1.58, p <.05, for clinical breast exam, and 1.71, p <.01, for Pap smear). In analyses of subgroups, the relationship is significant only for individuals who are enrolled in the nonmanaged plans; there is no relationship for individuals in more managed plans. No relationship is observed between area HMO market share and prostate cancer screening in any analysis. Neither the level of competition between area HMOs nor area PPO market share is associated with screening rates.
Conclusions. Area-level managed care activity can influence preventive care treatment patterns.     

Metabolism and physiologically based pharmacokinetic modeling of flumioxazin in pregnant animals

A physiologically based pharmacokinetic (PBPK) model was developed to predict the concentration of flumioxazin, in the blood and fetus of pregnant humans during a theoretical accidental intake (1000 mg/kg). The data on flumioxazin concentration in pregnant rats (30 mg/kg po) was used to develop the PBPK model in pregnant rats using physiological parameters and chemical specific parameters. The rat PBPK model developed was extrapolated to a human model. Liver microsomes of female rats and a mixed gender of humans were used for the in vitro metabolism study. To determine the % of flumioxazin absorbed after administration at a dose of 1000 mg/kg assuming maximum accidental intake, the biliary excretion study of [phenyl-U-¹⁴C]flumioxazin was conducted in bile duct-cannulated female rats (Crl:CD (SD)) to collect and analyze the bile, urine, feces, gastrointestinal tract, and residual carcass. The % of flumioxazin absorbed at a dose of 1000 mg/kg in rats was low (12.3%) by summing up ¹⁴C of the urine, bile, and residual carcass. The pregnant human model that was developed demonstrated that the maximum flumioxazin concentration in the blood and fetus of a pregnant human at a dose of 1000 mg/kg po was 0.86 μg/mL and 0.68 μg/mL, respectively, which is much lower than K_m (202.4 μg/mL). Because the metabolism was not saturated and the absorption rate was low at a dose of 1000 mg/kg, the calculated flumioxazin concentration in pregnant humans was thought to be relatively low, considering the flumioxazin concentration in pregnant rats at a dose of 30 mg/kg. For the safety assessment of flumioxazin, these results would be useful for further in vitro toxicology experiments.     

黄芩愈伤组织中多酚氧化酶活性与黄芩苷合成的关系研究

目的 研究黄芩愈伤组织中多酚氧化酶活性变化规律及其与黄芩苷次生合成之间的关系.方法 采用紫外分光光度法测定多酚氧化酶活性,采用高效液相色谱法测定黄芩苷的量.研究不同添加物(抗坏血酸、氯化钠、苯甲酸、聚乙烯吡咯烷酮、硫酸铜)对多酚氧化酶和黄芩苷量的影响.结果 在黄芩愈伤组织生长周期的前20 d,黄芩苷基本没有合成,多酚氧化酶的活性低水平表达;20～35 d,黄芩苷大量合成,多酚氧化酶的活性有所降低,但降低趋势较小;35～50 d,多酚氧化酶活性高水平表达,黄芩苷次生合成受到抑制.结论 多酚氧化酶的高水平表达不利于黄芩苷的次生合成,抗坏血酸、氯化钠、苯甲酸等均可抑制多酚氧化酶的活性,促进黄芩苷次生合成,其中以添加0.02%的抗坏血酸效果最为明显,可使黄芩苷的量提高17.6%(82.3 mg/g),而聚乙烯吡咯烷酮、硫酸铜对多酚氧化酶的活性有着明显的促进作用,抑制了黄芩苷的积累.     

A comparative study on the effects of alpha-hexachlorocyclohexane and its metabolite beta-pentachlorocyclohexene on growth and monooxygenase activities in rat liver

The present study adds support to the hypothesis that β-pentachlorocyclohexene (β-PCH) is a primary intermediate in α-hexachlorocyclohexane (α-HCH)4 metabolism in the rat. Degradation of α-HCH to β-PCH was shown to occur in vitro and in vivo, partially by non-enzymic catalysis. β-PCH accumulated in liver and adipose tissue of α-HCH treated rats, which had received the glutathione-lowering agent diethyl maleate. β-PCH disappears from the body much more rapidly than the parent compound α-HCH: about 50 per cent of a single i.p. dose were degraded within 2.5 hr, while half-life of α-HCH is known to be approximately 130 hr. To maintain equimolar liver concentrations, β-PCH must be given in doses 100-fold higher than α-HCH. β-PCH and α-HCH were fed for a period of ten days at various dose levels to give steady-state liver concentrations. It was found that β-PCH has similar hepatic effects to α-HCH: both agents induced liver growth and a phenobarbital-type pattern of monooxygenase activities, as measured by the following substrates: aminopyrine, ethylmorphine, benzphetamine, 4-nitroanisole, aniline, benzo[α]pyrene, ethoxyresorufin and 2,5-diphenyl-oxazole. Threshold doses for these effects were 30–43 μmoles/kg/day for β-PCH and 1.0–1.7 μmoles/kg/day for α-HCH. However, on the basis of molar hepatic concentrations β-PCH was a more potent inducer than α-HCH (2–10 times). Threshold concentrations ranged from 0.4 to 0.6 nmoles β-PCH/g liver and from 0.7 to 1.5 nmoles α-HCH/g liver. β-PCH concentrations in livers of rats treated even with high doses of α-HCH were below the threshold for induction of liver growth and of monooxygenase increases. It is, therefore, highly unlikely that β-PCH is responsible for the effect of α-HCH on rat livers.     

Skin penetration by 2,4-diaminoanisole in the rat

The absorption of ¹⁴C-labelled 2,4-diaminoanisole together with its reaction products was investigated after application to the skin of rats. 2,4-Diamino[¹⁴C]anisole was applied as an ingredient of three different hair-dyeing formulations using procedures approximating to realistic conditions of use. Percutaneous absorption of the compound ranged from 0.26 to 1.1% of the administered dose, according to the formulation used. Elimination occurred mainly in the urine, with a smaller proportion in the faeces. Very small amounts were detected in the expired air. Complementary investigations involving subcutaneous or oral application of a solution of 2,4-diamino[¹⁴C]anisole. 2HCl showed that radioactivity was rapidly eliminated in the urine and faeces. Biliary excretion was demonstrated after oral administration.     

半夏干燥过程中褐变机制的研究

目的研究导致半夏干燥过程中发生褐变的机制。方法采用紫外分光光度法检测干燥过程中半夏中多酚氧化酶活性的变化,使用色彩色差计测量半夏表面颜色的变化值,考察酶促反应是否是发生褐变的唯一机制。采用HPLC-ELSD法检测半夏中还原性糖的种类及含量,分析半夏中的氨基酸种类,判断其发生羰氨反应的可能性。结果导致半夏褐变的反应并不唯一,酶促反应对其颜色变化的影响主要发生在干燥前期,羰氨反应对半夏褐变也有影响。结论导致半夏干燥过程中发生褐变的机制并不单一,酶促反应和羰氨反应均对其颜色变化有影响。     

广东芝麻香蕉加工中的酶褐变研究（Ⅰ）──多酚氧化酶的提取、分离及其特性研究

由于香蕉加工中的酶褐变主要是多酚氧化酶引起的，因此本文研究了多酚氧化酶的提取及其特性和交联葡聚糖Ｇ－７５（ＳＥＰＨＡＤＥＸＧ－７５）分离纯化；比较了加入ＰＶＰ（聚乙烯吡咯酮）和ＰＥＧ（聚乙二醇）的效果，发现对酶特性有一定的影响。通过差热扫描分析，由ＳＥＰＨＡＤＥＳＧ－７５分离的两种不同形式的多酚氧化酶蛋白的变性温度分别为９３．０３℃和８９．４２℃；最适ｐＨ分别为６．８和５．９．多酚氧化酶与邻－二酚反应产物在λ＝４１４ｎｍ下有最高吸收。     

Selectivity of PEO‐block‐PPO Diblock Copolymers in the Microwave‐Accelerated,Anionic Ring‐Opening Polymerization of Propylene Oxide with PEG as Initiator

Diblock copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) were synthesized by the anionic ring‐opening polymerization of propylene oxide (PO), with controlled microwave heating in sealed vessels. A detailed study was carried out to investigate the effects of different parameters on the formation of unwanted byproducts. Parameters that were considered include temperature; the concentration of NaH, monomer and hydroxy groups in the feed; and the polarity of the reaction medium. A continuous decrease of internal pressure during the sealed‐vessel experiment reflected the consumption of PO monomer and the completion of the reaction was confirmed by a drop of the internal pressure to zero when reactions were performed in bulk. The products were characterized by using different chromatographic techniques. A comparison of the reaction times and composition of the polymers prepared by microwave and conductive heating is given.

     

Novel serotonin receptors in Fasciola: Characterization by studies on adenylate cyclase activation and [3H]LSD binding

Serotonin (5-HT) receptors coupled to adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] in the liver fluke Fasciola hepatica have been characterized by adenylate cyclase activation studies and by direct binding studies using $\text{[}{}^3\text{H}\text{]-d-}\text{lysergic acid}$ diethylamide ([³H]LSD) as a radioligand. Inhibition of 5-HT stimulation of adenylate cyclase by a series of 5-HT antagonists revealed a potency order of LSD = 2-bromo-LSD > methiothepin > metergoline = cyproheptadine > methysergide > spiroperidol. [³H]LSD binding to a cell-free fluke particle preparation was rapid, stereospecific, and proportional to protein concentration. Scatchard analysis indicated multiple binding sites which, when resolved into two components, gave for the high affinity site an apparent dissociation constant of 25 nM and a receptor concentration of 160 fmoles/mg protein. The ability of a series of compounds to compete for [³H]LSD binding sites correlated closely with their ability to inhibit 5-HT stimulation of adenylate cyclase. [³H]LSD binding sites were most concentrated in the anterior region of the fluke which was consistent with the higher levels of 5-HT activated adenylate cyclase found in this region. GTP and 5′-guanylyl imidophosphate, a poorly hydrolyzable GTP analog, decreased the affinity of the agonist 5-HT for the binding sites but had little effect on the affinity of the antagonist 2-bromo-LSD. Calcium at concentrations above 300 μM significantly reduced both [³H]LSD binding and 5-HT activation of adenylate cyclase. The results indicate that [³H]LSD can be used to label the 5-HT receptors coupled to adenylate cyclase activity. The pharmacological specificity and other characteristics of the fluke receptors appear to differ from the properties of reported mammalian 5-HT receptors. As a result, serotonin receptors in the flukes represent sites that may be amenable to selective manipulation by new chemotherapeutic agents useful in the treatment of these parasite infections.     

7-Ethoxycoumarin O-deethylase induction by phenobarbitone and 1,2-benzanthracene in primary maintenance cultures of adult rat hepatocytes

The microsomal monooxygenase system of adult rat hepatocytes in short-term non-proliferating culture could be induced by phenobarbitone and benzanthracene. Differences in the kinetics of induction and the additive nature of the inductions indicated that induction by the two agents occurred by different mechanisms and the use of haemoprotein-selective inhibitors demonstrated the induction of different haemoproteins by the two agents. The type of haemoprotein present in the cells altered during a four day culture period.