Heparin cofactor II inhibits arterial thrombosis after endothelial injury

Heparin cofactor II (HCII) is a plasma protein that inhibits thrombin rapidly in the presence of dermatan sulfate, heparan sulfate, or heparin. HCII has been proposed to regulate coagulation or to participate in processes such as inflammation, atherosclerosis, and wound repair. To investigate the physiologic function of HCII, about 2 kb of the mouse HCII gene, encoding the N-terminal half of the protein, was deleted by homologous recombination in embryonic stem cells. Crosses of F1 HCII(+/-) animals produced HCII(-/-) offspring at the expected mendelian frequency. Biochemical assays confirmed the absence of dermatan sulfate-dependent thrombin inhibition in the plasma of HCII(-/-) animals. Crosses of HCII(-/-) animals produced litters similar in size to those obtained from heterozygous matings. At 1 year of age, HCII-deficient animals were grossly indistinguishable from their wild-type littermates in weight and survival, and they did not appear to have spontaneous thrombosis or other morphologic abnormalities. In comparison with wild-type animals, however, they demonstrated a significantly shorter time to thrombotic occlusion of the carotid artery after photochemically induced endothelial cell injury. This abnormality was corrected by infusion of purified HCII but not ovalbumin. These observations suggest that HCII might inhibit thrombosis in the arterial circulation.     

Changes in human plasma alpha-D-mannosidase activity during pregnancy

There are significant and progressive increases in plasma acidic (pH optimum 4.2) and intermediate (pH optimum 5.6) alpha-mannosidase during pregnancy. The acidic alpha-mannosidase in plasma from pregnant women binds to concanavalin A and has the same apparent molecular weight as the acidic alpha-mannosidase in control plasma. The 2-3-fold increase in acidic alpha-mannosidase in pregnancy is due to an increase in the most negatively charged form of acidic alpha-mannosidase, B2, which is slightly more negatively charged than its counterpart in the control plasma. The intermediate alpha-mannosidase, which increases by approximately 50% during pregnancy, can be resolved by a combination of chromatography on concanavalin A and gel filtration into the same forms found in control plasma.     

妊娠高血压综合征分娩前,后血浆肝素辅助因子Ⅱ的动态变化？…

目的 揭示肝素辅助因子Ⅱ（ＨＣⅡ）体内抗凝的生理意义,探讨妊娠高血压综合征（妊高征）并发血栓形成时的部分发病机制。方法 （１）采用发色底物法测定１８名正常人,１８例正常妊娠及２９例妊高征分娩前,后血浆ＨＣⅡ活性。（２）用Ｗｅｓｔｅｒｎ印迹法检测２９例妊高征分娩前,后血浆ＨＣⅡ抗原;（３）免疫荧光定位检测ＨＣⅡ在胎盘组织上的分布。结果 妊高征产前血浆ＨＣⅡ活性及抗原含量显降低,其降低程度与妊高征分     

The effect of oral contraceptive use and pregnancy on the daily rhythm of cortisol and cortisone

The effect of oral contraceptives and of pregnancy on the daily rhythm of cortisol, and its metabolite cortisone in plasma and saliva has been investigated. In both conditions the total plasma cortisol levels were raised to the same extent, the mean values in saliva in the oral contraceptive users being intermediate between those in pregnancy and in the controls, particularly in the morning. Salivary cortisone levels were more related to salivary cortisol than to total plasma cortisone which exhibited a rather flat daily rhythm. There was a shift in peak values for salivary cortisol and cortisone towards late morning: this may be due to a delay in the daily activation of the hypothalamic-pituitary-adrenal axis in these patients.     

Ischemic colitis associated with naratriptan and oral contraceptive use

Ischemic colitis has not been reported in association with naratriptan therapy. We describe the occurrence of ischemic colitis in a patient who was treated with abortive doses of naratriptan for migraine and was also taking long-term oral contraceptives. Concurrent use of naratriptan and oral contraceptives should probably be avoided.     

Female sex and oral contraceptive use accelerate nicotine metabolism

BACKGROUND: Several studies have reported that female smokers have a higher risk of lung cancer than male smokers. This could be related to sex differences in nicotine metabolism and related smoking behavior. This study tested the hypothesis that women metabolize nicotine more rapidly than men and that, among women, oral contraceptive users metabolize nicotine more rapidly than nonusers of oral contraceptives. METHODS: Two hundred seventy-eight healthy volunteers who were twins and 16 who were siblings of twins, recruited from the Northern California Twin Registry, received an infusion of deuterium-labeled nicotine and cotinine with frequent blood sampling. The plasma clearances of nicotine and cotinine, the clearance of nicotine to cotinine (an index of cytochrome P450 [CYP] 2A6 activity), and the ratio of trans-3'-hydroxycotinine to cotinine (another indicator of CYP2A6 activity) were measured. RESULTS: The clearances of nicotine and cotinine, the clearance of nicotine to cotinine, and the trans-3'-hydroxycotinine/cotinine ratio were significantly higher in women than in men (nicotine clearance, 15.6 +/- 4.3 mL.min(-1).kg(-1) in men versus 18.8 +/- 6.6 mL.min(-1).kg(-1) in women; P < .001); they were also higher among women taking oral contraceptives than in those who were not taking oral contraceptives (nicotine clearance, 22.5 +/- 6.6 mL.min(-1).kg(-1) in women taking oral contraceptives versus 17.6 +/- 6.1 mL.min(-1).kg(-1) in those who were not; P < .05). Women who were menopausal or postmenopausal were not different from men. Among oral contraceptive users, nicotine metabolism was accelerated among those taking combined and estrogen-only contraceptives but not progesterone-only contraceptives. CONCLUSIONS: Sex hormones influence nicotine metabolism. Nicotine and cotinine metabolism is faster in women than in men and is faster in women taking oral contraceptives compared with those who are not. Accelerated nicotine metabolism appears to be a result of estrogen. Sex-related differences in nicotine clearance could affect smoking behaviors, as well as response to nicotine medications, and could be a marker for altered metabolism of nicotine-derived carcinogens.     

血栓疾病患者血浆肝素辅因子Ⅱ活性和抗原水平检测及意义

目的　了解肝素辅因子Ⅱ (HCⅡ )活性及抗原水平在动、静脉血栓性疾病中的变化及其与动、静脉血栓性疾病之间的关系。方法　用发色底物法测定 5 0名正常人 ,75例脑梗死、5 0例心肌梗死及 36例深静脉血栓患者血浆HCⅡ活性 ;发色底物法检测深静脉血栓患者中HCⅡ缺乏者血浆抗凝血酶 (AT)活性 ;Westernblot检测部分样品 (每组 36例 )血浆HCⅡ抗原含量。结果　血浆HCⅡ活性与其抗原呈平行变化 ;正常对照组血浆HCⅡ活性及抗原水平分别为 (96 .80± 2 0 .11) % ,0 .93± 0 .19与脑梗死组 [(99.97± 2 1.14 ) % ,0 .96± 0 .2 4 ]、心肌梗死组 [(98.18± 2 9.35 ) % ,0 .95± 0 .2 0 ]及深静脉血栓形成组 [(89.5 7± 17.12 ) % ,0 .87± 0 .18]比较 ,差异无显著性 ,但深静脉血栓形成组HCⅡ活性和抗原均呈降低趋势 ;HCⅡ明显减低者在正常人及患者之间的分布频度无显著差异 ;深静脉血栓中HCⅡ缺乏者血浆抗凝血酶活性及纤维蛋白原浓度正常。结论　血浆HCⅡ变化可能不是中国湖南汉族人心、脑血栓病的危险因子 ;是否与静脉血栓形成相关有待进一步证实。     

Acute renal vein thrombosis, oral contraceptive use, and hyperhomocysteinemia

Oral contraceptive use and hyperhomocysteinemia are considered to be relatively weak risk factors for venous thromboembolism. We report a case of acute renal vein thrombosis, a rare and aggressive form of thromboembolism, that occurred in a 21-year-old woman taking oral contraceptives, who was subsequently found to have marked hyperhomocysteinemia. This case suggests that the oral contraceptive and hyperhomocysteinemia may interact in a synergistic manner in the pathogenesis of thrombosis. In oral contraceptive users who develop venous thrombosis in the absence of other risk factors, clinicians should consider investigations for an underlying prothrombotic biochemical disorder.     

Alcohol use during pregnancy

Heavy alcohol intake during pregnancy is associated with numerous adverse effects on the fetus, including low birth weight, congenital anomalies, mental retardation, and behavioral and learning disabilities. There is increasing evidence that moderate drinking also may cause these problems, but to a lesser degree. Less is known about the effects of a single drink or a single alcoholic binge, but no absolutely safe level of alcohol consumption has been determined for pregnant women.     

Steroid use during pregnancy

Health care providers and pregnant women share a concern for protecting the fetus from unnecessary and potentially teratogenic influences. Since the introduction of steroids for the induction of fetal surfactant production, there has been considerable experience in the use of corticosteroids during pregnancy. While the use of corticosteroids for surfactant induction in the preterm fetus has become commonplace, steroids are used for other obstetric and medical indications during pregnancy. Thus, finding a balance between drug benefits and possible side effects remains a critical issue.     

Anticonvulsant use during pregnancy

Although antiepileptic medications may play a role in fetal malformations, this risk appears no greater than the risk associated with either the seizures themselves or a change in medication during pregnancy. In general, the number and the dose of antiepileptic medications should be minimized during pregnancy. Potential complications during the pregnancy must be anticipated. Drug levels must be monitored. Because the fetus is at a somewhat higher risk, ultrasound studies may be useful in monitoring the pregnancy. Delivery should take place in a center where appropriate facilities are available if intervention is required during labor or if the baby is malformed. Both the infant and the mother should be monitored closely after the delivery.     

Interaction between oral contraceptive use and coagulation factor levels in deep venous thrombosis

Summary.  Deep venous thrombosis is a multicausal disease, i.e. more than one risk factor needs to be present to cause the disease. Oral contraceptive use increases the risk of venous thrombosis but since not all women using oral contraceptives develop thrombosis, the presence of additional risk factors in patients is likely. The aim of this study was to assess the joint effect of oral contraceptive use and the levels of procoagulant factors (F)(FII, FV, FVII, FVIII, FIX, FX, FXI, FXII, FXIII and fibrinogen). Data of premenopausal women were re-analyzed in the Leiden Thrombophilia Study. The highest relative risks were observed for the combination of oral contraceptive use and high levels (>90th percentile) of FII (Odds Ratio [OR]_OC+FII 10.1; 95% confidence interval [CI] 3.5–29.0), FV (OR_OC+FV 12.6; 95% CI 3.8–41.5), and FXI (OR_OC+FXI 11.9; 95% CI 3.6–39.2) and low levels (< 10th percentile) of FXII (OR_OC+FXII 12.3; 95% CI 2.4–63.0). No interaction was observed between oral contraceptive use and high levels of the other coagulation factors, i.e. the joint effect of these risk factors did not exceed the sum of the separate effects. The results of this study indicate that the risk for the joint effects of oral contraceptive use and coagulation factor levels are minor compared with the joint effect of oral contraceptive use and the FV Leiden mutation (RR > 30).     

The relationship between acculturation and oral contraceptive use among Korean immigrant women

We explored the relationship between acculturation and beliefs, attitudes, norms, and intention regarding oral contraceptive use among Korean immigrant women using acculturation and the theory of reasoned action (TRA) as the frameworks. A total of 1,494 Korean surname-based telephone numbers were sampled in New York City. One hundred forty-five Korean immigrant women completed a telephone survey. The findings support the assumption that acculturation affects intention to use oral contraceptives indirectly only through one or more of the TRA components. Acculturation could function as an antecedent to changes in beliefs, attitudes, norms, and intention in this population. Acculturation assessment tools could provide health professionals insight into how to better approach this population on such culturally sensitive health issues as contraceptive use.