Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UNIPROT:P00750 (PLA)
16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of Demulen (ethinyl estradiol 0.05 mg and ethynodiol diacetate 1 mg) and exercise on the level of plasminogen activators was studied in 25 women (12 controls and 13 contraceptive users). Plasma plasminogen activator level was increased by the use of the oral contraceptive and further increased by exercise. Urine plasminogen activator level was unchanged by the use of Demulen but, in both groups of subjects, was decreased by exercise.
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PMID:Plasminogen activator levels in plasma and urine during exercise and oral contraceptive use. 70 3

Oophorectomy was found to decrease the plasminogen activator activity of rat mammary tumors induced by 7,12-dimethylbenz(a)anthracene (DMBA) to less than 7 per cent, while in vivo estradiol treatment restored its activity in a dose dependent fashion. The peroxidase activity was not changed either by oophorectomy or by the administration of estrogen. In the rat uterus, plasminogen activator activity was not changed by oophorectomy or by the administration of estrogen, however, its peroxidase activity decreased to less than 2 per cent following oophorectomy, while estrogen administration restored its activity. Estrogen regulated plasminogen activator activity in the DMBA-induced rat mammary tumors but not in the uterus and thus, the specific hormonal regulation of this enzyme may be an important factor for the hormonal dependent growth of such tumors.
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PMID:Hormonal regulation of plasminogen activator and peroxidase activities in 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors and the rat uterus. 164 4

Epidemiologic studies have suggested a relationship between the use of oral contraceptives and mortality from cardiovascular diseases in older women. Therefore we studied generation and resolution of fibrin in 28 healthy women above age 30 years, using oral contraceptives containing 30 to 50 micrograms of ethinyl estradiol. Thirty healthy nonusers served as control subjects. The oral contraceptive group had increased plasma concentration of thrombin-antithrombin III complexes (p less than 0.01), which indicated an enhanced generation of thrombin, increased plasma activity of tissue-type plasminogen activator (p less than 0.01), decreased plasma activity of plasminogen activator inhibition (p less than 0.01), and increased plasma concentration of fibrin degradation products (p less than 0.04). Interestingly, the ratio of thrombin-antithrombin III complexes/fibrin degradation products did not deviate significantly between groups. Twelve of the 28 women using oral contraceptives were light smokers, that is, less than 15 cigarettes per day. There were no differences in the determined variables between smokers and nonsmokers. Our study suggests that healthy women older than 30 years who use oral contraceptives containing 30 to 50 micrograms of ethinyl estradiol have an enhanced generation and resolution of fibrin, while the hemostatic balance is unaltered. These findings are unaffected by moderate cigarette smoking.
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PMID:Enhanced generation and resolution of fibrin in women above the age of 30 years using oral contraceptives low in estrogen. 237 37

2 groups of healthy, informed volunteers were studied to assess tissue-type plasminogen activator (t-PA) inhibition in plasma of women using oral contraception (OC) and in normal women. The women in the 1st group (n=10, age range 21-30 years) had used a combined OC with 30 mcg ethinyl estradiol and 150 mcg levonorgestrel daily for 21 days per cycle for 4 months. They began using pills on the 7th day of their cycle. The 2nd group was made up of 15 women, age 20-28 years, with a regular menstrual cycle (range of 28-31 days) and with hormone levels within the normal range. None of the women had evidence of liver disease or active thrombotic disease, and none was taking other drugs. Blood samples were obtained in the morning with a minimum of stasis from an antecubital vein from fasting subjects in the supine position after a brief rest. The t-PA inhibition in plasma was determined by amidolytic titration with purified melanoma 2-chain t-PA. The measured inhibition was arbitrarily expressed in percentages relative to a pool of normal plasma. The t-PA activity was determined on fibrin plates as the activity measured in the presence of excess of C1-inactivator as described elsewhere. The mean levels of inhibition during the cycle were lower in the OC than in the normal group. The difference were statistically significant. When the separate sampling periods were compared, a statistically significant difference between the 2 groups were obtained for periods 2-5. There were only minor and insignificant fluctuations during the normal menstrual cycle. In the OC group the inhibition decreased from periods 1-5 with a statistical significance. Within both groups the fluctuations in t-PA inhibition were almost inversely related to the t-PA activities.
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PMID:Inhibition of tissue-type plasminogen activator in plasma of women using oral contraceptives and in normal women during a menstrual cycle. 309 96

This study demonstrated that the normal increase in euglobulin fibrinolytic activity (NEF) that occurs in the morning was not affected by taking oral contraceptives. 11 women taking a combined pill of 30 mcg ethinyl estradiol and 150 mcg 1-norgestrel for 21 days were compared with 15 menstruating controls. The assay for NEF involved precipitating euglobulins and assaying on bovine fibrin plates. Extrinsic tissue plasminogen activator (t-PA) was that fibrinolysis obtained after adding pure C1-inactivator. NEF was higher in women taking pills, especially during the middle of the cycle. In controls, NEF fluctuated less, but was higher during menses and in late luteal phase. t-PA variations were much less remarkable, but generally reflected the pattern seen with NEF. The only significant difference was the relatively greater increase in morning values in the pill group during beginning and end of the cycle. When the assay was repeated with the addition of flufenamate, to inactivate the C-1 inactivator, results did not differ between the 2 groups. These data do not point to any element in this fibrinolytic system that might be associated with the increased incidence of thromboembolic episodes in women taking oral contraceptives.
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PMID:The diurnal increase in euglobulin fibrinolytic activity in women using oral contraceptives and in normal women, and the generation of intrinsic fibrinolytic activity. 310 Dec 21

We studied the effects on plasma levels of coagulation and fibrinolysis factors of two currently used "sub-50" oral contraceptive preparations (OCs), one containing 750 micrograms lynestrenol and 37.5 micrograms ethinyl estradiol (LYN-EE) and the other containing 150 micrograms levonorgestrel and 30 micrograms ethinyl estradiol (LNG-EE), in groups of about 25 women aged 21 +/- 2 years. After 3 months, plasminogen levels increased in the two experimental groups (LYN-EE and LNG-EE), by 40% and 32%, respectively. This change was positively correlated with changes in ceruloplasmin levels, indicating that an estrogenic effect might be involved. Histidine-rich glycoprotein concentration decreased by 26% and 16%, respectively. Tissue-type plasminogen activator (t-PA) activity increased by 260% and 167%; t-PA antigen decreased by 12% and 18%, and t-PA inhibitor activity decreased by 31% and 32%, respectively. In the coagulation system, in both groups factor XII increased by 47% and 34%, respectively. The main inhibitor of factor XII, C1-inactivator, decreased slightly, but this was significant only in the LNG-EE group. The von Willebrand factor antigen fell by 8% and 9%, whereas factor VIII activity did not change. Antithrombin III antigen decreased by 14% in both groups. Factor IX activity increased by 15% and 21%. The difference in hormonal effects of both preparations was reflected by the increases in sex hormone binding globulin (by 130% and 21%) and ceruloplasmin (by 98% and 51%), indicating that LYN-EE had a more estrogenic potency than LNG-EE. In a control group of 25 matched subjects, who were observed simultaneously, we found no significant changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of two low-dose oral contraceptives on circulating components of the coagulation and fibrinolytic systems. 310 29

Selected coagulation and fibrinolytic factors were measured in plasma from 72 women taking oral contraceptives in a longitudinal study. Specific pills and sampling schedules were: Anovlar (3 mg norethisterone acetate and .05 mg ethinyl estradiol, combined), taken by 40 women sampled before, after 1 and 3 weeks, and 1 week of interruption; Sequens (.1 mg mestranol and 1.5 mg chlormadinone acetate sequential), 21 women, sampled before and after 2 and 3 weeks, and after 1 week of interruption; Ro 6-3129 (6-16-ethylthioretroprogesterone, 8-12 mg, continuously), 11 women, sampled after 1 month; additional samples were taken after 2, 3, 5, 7, 9 and 11 months. The pills containing estrogen affected the following parameters of the extrinsic coagulation system: thrombotest increased (p less than .001). Cold activition (20 hours at 0 degrees C.) of factor 7 was positive in 65% of subjects after pills, but 9% before. Estrogen pills decreased cephalin time (p less than .05), a screening test for the intrinsic coagulation system. Factors 8 (p less than .05), IX (p less than .02), and fibrinogen (p less than .001) increased. In the fibrinolytic system the estrogen pills increased plasminogen (p less than .001), proteolytic capacity (p less than .001) and streptokinase activated plasminogen activator (p less than .001). Among proteinase inhibitors, antiplasmin activity (p less than .01), antithrombin 3 (p less than .001) and C'i inactivator (p less than .001) decreased. Progestagen alone, or added in sequentials had no effect. Since the activation of clotting factors is probably more important than increases in concentration of 1 or more factors, the increased cold activition of factor 7 was considered indicative of increased clotting tendency.
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PMID:Studies on plasma coagulation and fibrinolysis during oral contraception of various types with special reference to cold activation of factor VII. 483 27

Mammalian conceptuses must provide a chemical signal to the maternal system to insure maintenance of corpus luteum (CL) function and of progesterone production and continuation of uterine endometrial secretory activity. These events insure that the developing conceptus is provided with appropriate nutrients, regulatory enzymes and endocrine state to allow successful establishment and maintenance of pregnancy. Pig blastocysts begin to produce estrogens by Day 11 of pregnancy, which prevents secretion of the uterine luteolytic factor (PGF2 alpha) in an endocrine direction, but allows secretion in an exocrine direction, i.e., into the uterine lumen. Therefore, CL are "protected." Blastocyst estrogens also trigger secretion of a group of proteins, including uteroferrin, an iron transport protein, and a family of protease inhibitors whose biosynthesis within the uterine glandular epithelium is under the control of progesterone. Estrogen also appears to promote accumulation of glucose and fructose within the uterine lumen. A complex in vivo "culture medium" is thereby established to promote conceptus development. Pig blastocysts do not undergo invasive implantation within the uterine lumen although they produce the protease, plasminogen activator. Invasion may be prevented by endometrial secretion of progesterone-induced protease inhibitors which are produced in large amounts. In addition to estrogens of conceptus origin, calcium and prostaglandins PGF2 alpha and E2 may affect the uterine vasculature, water and electrolyte transport, capillary permeability, conceptus steroid production, and related events during pregnancy. The blastocysts of the large domestic animals also secrete proteins which include a large glycoprotein (Mr approximately 600,000) and a small acidic protein (Mr approximately 17,000). The latter has been purified from sheep and named ovine trophoblast protein I. These proteins may play unique roles in early pregnancy with respect to establishment and maintenance of pregnancy in the ewe, sow, mare, and cow.
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PMID:Biochemical aspects of conceptus--endometrial interactions. 636 10

This study investigated the influence of ethinyl-estradiol and d-norgestrel on the release of tissue-type plasminogen activator (t-PA) from incubated specimens from human veins. The concentrations of PA released into the media were determined by immunoradiometric assay. The initial release of t-PA was positively correlated to the weight of the vein specimens. Only traces of t-PA were liberated after the 3rd day of incubation. No significant differences in total release were noted between the steroid exposed groups and the control group. However, a significantly higer initial t-PA release (82%) was found in the d-norgestrel exposed group compared to the control group (exposed to ethanol only). The initial t-PA release was also stimulated in the group exposed to both contraceptive steroids (73%), but exposure to ethinyl estradiol alone had no significant effect (62%). The stimulation of t-PA release associated with artificial steroids may reflect their androgenic effect.
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PMID:Regulatory effect of contraceptive steroids on the release of tissue-type plasminogen activator in vitro. 654 83

The effects of contraceptive steroids on the expression of endothelial homeostasis were examined by direct and indirect measures in women with insulin-dependent diabetes mellitus (IDDM) in a prospective nonrandomized controlled study. Study subjects were 13 women with uncomplicated IDDM treated with a monophasic combination of 30 micrograms ethinyl estradiol and 75 micrograms gestodene for 12 consecutive cycles and 13 women of comparable diabetic status as control. During the study period, none of the participants developed increased renal albumin excretion, which was used as a direct measure of endothelial function. In the indirect assessment of endothelial function, we found a proportionate increase in plasma levels of thrombin-antithrombin III (TAT) complexes and D-dimer during treatment. Hormonal intake was followed by decreased antigen concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (type 1 [PAI-1]), whereas the activities of t-PA and PAI-1 were unchanged. Plasma levels of plasminogen and histidine-rich glycoprotein (HRG) increased and decreased, respectively, whereas an increase in von Willebrand factor was observed in the treatment group. No significant changes in direct or indirect measures were observed in the control group during the observation period of 12 months. In conclusion, no adverse effect on endothelial function was demonstrated by direct measures, but our findings suggest that a procoagulant state, compensated by enhanced activity of the fibrinolytic system, is induced by hormonal treatment. Clinical and metabolic monitoring is recommended if the use of oral contraceptives in women with IDDM is extended.
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PMID:Assessment of endothelial function during oral contraception in women with insulin-dependent diabetes mellitus. 796 93


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