Intrauterine device increases the fibrinolytic activity of the rat endometrium at deciduation,a new aspect of its contraceptive effect

Summary The fibrinolytic activity of the endometrium of the two uterine horns in the rat was histochemically determined. One of the horns contained a plastic-IUD, the other served as control. The endometrium of the control horn was almost inactive in contrast with that of the IUD-horn in which fibrinolytic activity was apparent. The fibrinolytic activity induced by the IUD might be involved in the prevention of ova implantation.Supported by grants from WHO No. H 9/181/126 C and the Swedish Medical Research Council (No. B 76-17X-04523-02A).     

Evidence that the establishment of pregnancy requires activation of lipoxygenase and phospholipase-A2

The present work investigates the possibility that lipoxygenase products are involved in the biochemical mechanisms of blastocyst implantation by utilizing nordihydroguaiaretic acid (NDGA) and caffeic acid (CA), inhibitors of lipoxygenase enzymes, and quinacrine (QU), an inhibitor of phospholipase-A2. It has been shown previously that inhibition of cyclooxygenase results in blockade of implantation. The inhibitors were dissolved in a standard medium and 5 microliter of the solutions were micro-injected into the uterine horns of day-4 pregnant mice. The contralateral horns acted as controls and received only vehicle. A sham-operated group provided normal controls. In 14 NDGA-treated mice, the control horns contained 40 implantations while the treated horns contained only 6 small implantations and 8 resorbing sites. These control horns were comparable to the sham controls. In 14 CA-treated mice, treated horns contained 17 small implantations plus 4 resorptions, whereas the control horns contained 26 small implantations and 4 resorptions. Twelve QU-treated mice exhibited 7 small implantations and 4 resorptions in the treated horns, plus 24 small sites and no resorptions in the control horns. Fourteen sham-operated mice had 95 implantation sites and no resorptions in their 28 horns. The results provide evidence for the involvement of the lipoxygenase enzymes and phospholipase-A2 in the initial implantation process and in the subsequent development of early pregnancy.     

Evidence that the establishment of pregnancy requires activation of lipoxygenase and phospholipase-A2

Summary The present work investigates the possibility that lipoxygenase products are involved in the biochemical mechanisms of blastocyst implantation by utilizing nordihydroguaiaretic acid (NDGA) and caffeic acid (CA), inhibitors of lipoxygenase enzymes, and quinacrine (QU), an inhibitor of phospholipase-A₂. It has been shown previously that inhibition of cyclooxygenase results in blockade of implantation. The inhibitors were dissolved in a standard medium and 5 l of the solutions were micro-injected into the uterine horns of day-4 pregnant mice. The contralateral horns acted as controls and received only vehicle. A sham-operated group provided normal controls. In 14 NDGA-treated mice, the control horns contained 40 implantations while the treated horns contained only 6 small implantations and 8 resorbing sites. These control horns were comparable to the sham controls. In 14 CA-treated mice, treated horns contained 17 small implantations plus 4 resorptions, whereas the control horns contained 26 small implantations and 4 resorptions. Twelve QU-treated mice exhibited 7 small implantations and 4 resorptions in the treated horns, plus 24 small sites and no resorptions in the control horns. Fourteen sham-operated mice had 95 implantation sites and no resorptions in their 28 horns. The results provide evidence for the involvement of the lipoxygenase enzymes and phospholipase-A₂ in the initial implantation process and in the subsequent development of early pregnancy.     

A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet

Summary A strong fibrinolytic activity was demonstrated in the vegetable cheese Natto, which is a typical soybean food eaten in Japan. The average activity was calculated at about 40 CU (plasmin units)/g wet weight. This novel fibrinolytic enzyme, named nattokinase, was easily extracted with saline. The mol. wt and pI were about 20,000 and 8.6, respectively. Nattokinase not only digested fibrin but also the plasmin substrate H-D-Val-Leu-Lys-pNA (S-2251), which was more sensitive to the enzyme than other substrates tried. Diisopropyl fluorophosphate and 2,2,2-trichloro-1-hydroxyethyl-o,o-dimethylphosphate strongly inhibited this fibrinolytic enzyme.     

A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet

A strong fibrinolytic activity was demonstrated in the vegetable cheese Natto, which is a typical soybean food eaten in Japan. The average activity was calculated at about 40 CU (plasmin units)/g wet weight. This novel fibrinolytic enzyme, named nattokinase, was easily extracted with saline. The mol. wt and pI were about 20,000 and 8.6, respectively. Nattokinase not only digested fibrin but also the plasmin substrate H-D-Val-Leu-Lys-pNA (S-2251), which was more sensitive to the enzyme than other substrates tried. Diisopropyl fluorophosphate and 2,2,2-trichloro-1-hydroxyethyl-o,o-dimethylphosphate strongly inhibited this fibrinolytic enzyme.     

Histochemistry of the lumenal cell surfaces of the mucosa of the oviducts and the uterus of the rat. Changes in prepuberty, estrous cycle, castration, hormone replacement and pseudopregnancy.

The lumenal surface coat of the rat oviducts and uterine horns have been histochemically characterized at prepuberty, estrous cycle, castration, hormone replacement and pseudopregnancy. Under the EM, the coat was made up of filamentous and globular structures. Histochemical variations suggested that coat components are under endocrine control.     

Protein anabolism in endometrium and myometrium during the growth of induced deciduoma in rats

Summary Protein anabolism in the endometrium and myometrium was studied during the growth of induced deciduoma in terms of incorporation of [¹⁴C]-leucine into proteins. The data show that the specific activity of the proteins was highest 2 days after decidualisation. Protein synthesis in the endometrium studied on that day as a function of time after injection of the labelled amino acid showed a steady increase during the first 2 h. Cycloheximide (2 mg/kg b.wt) administration produced nearly 95% inhibition of protein synthesis in endometrium as well as in myometrium.     

Local haemostasis in brain tumours.

The thromboplastic activity and the fibrinolytic activity were examined in 7 human meningiomas and 6 gliomas obtained at neurosurgery. Two different haemostatic patterns emerged, meningiomas having lower thromboplastic and higher fibrinolytic activity than that of gliomas. This difference might help to explain the better haemostatic capacity of gliomas during and after operation than that of meningiomas.     

Local haemostasis in brain tumours

Summary The thromboplastic activity and the fibrinolytic activity were examined in 7 human meningiomas and 6 gliomas obtained at neurosurgery. Two different haemostatic patterns emerged, meningiomas having lower thromboplastic and higher fibrinolytic activity than that of gliomas. This difference might help to explain the better haemostatic capacity of gliomas during and after operation than that of meningiomas. Supported by Tore Nilson's Fund for Medical Research.     

Substance P-induced fibrinolysis in the forearm of healthy humans

Physiological saline with or without substance P (50 ng/ml) was infused into the humeral artery in 6 healthy males. Indices of fibrinolytic activity (whole blood diluted lysis time, euglobulin lysis time, lysis areas in non-heated fibrin plates produced by plasma or euglobulin precipitate, plasminogen plasma levels, ₂-macroglobulin, Cl-inhibitor, and ₂-antiplasmin) were evaluated in the homolateral antecubital vein before and after 5 min of substance P or saline infusion. After substance P the fibrinolytic activity increased, as can be seen from the shortening of lysis times (p<0.01) and enlargement of the lysis areas (p<0.01). A reduction of plasminogen plasma levels (p<0.01), associated with a decrease in ₂-anitplasmin (p<0.01), was also found. Alpha₂-macroglobulin and Cl-inhibitor were instead unaltered by the peptide. The saline infusion, on the other hand, was unable to modify any of the examined indices. We concluded that exogenous substance P given intra-arterially increases fibrinolytic activity in locally-sampled venous blood through a mechanism which remains to be elucidated.     

Deficiency of fibrinolytic enzyme activities in the serum of patients with Alzheimer-type dementia

Previously we reported that there is a kallikrein deficiency in the cerebral tissue of patients with Alzheimer-type dementia. The present study was performed to investigate protease changes in the serum of these patients. The results showed that the kallikrein activity was normal, but that the activities of plasmin and urokinase were significantly low. The present findings indicate a derangement in the clotting and fibrinolytic systems in Alzheimer patients.     

Characterization and antithrombotic action of tissue plasminogen activator

Summary An extractive fibrinolytic enzyme has been characterized and found to belong to the class of vascular plasminogen activators. The agent has been found to have an antithrombotic action in the rabbit.Provided by Dr L. Dussourd d'Hinterland, Laboratoires Pierre Fabre, Castres, France. 1000 units have a fibrinolytic activity of about 15 PU urokinase.     

Deficiency of fibrinolytic enzyme activities in the serum of patients with Alzheimer-type dementia.

Previously we reported that there is a kallikrein deficiency in the cerebral tissue of patients with Alzheimer-type dementia. The present study was performed to investigate protease changes in the serum of these patients. The results showed that the kallikrein activity was normal, but that the activities of plasmin and urokinase were significantly low. The present findings indicate a derangement in the clotting and fibrinolytic systems in Alzheimer patients.     

Fibrinolyse im Kammerwasser menschlicher und tierischer Augen

Summary In the aqueous humour of human subjects and of various animals species, a fibrinolytic system has been demonstrated which, as regards streptokinase, shows the same properties as the corresponding plasma. Presumably the actual fibrinolytic activity in the aqueous humour is greater than in the plasma.     

Sex related fibrinolytic activity in rat tissues

Histochemical study of many organs of male and female adult Wistar rats of the same age showed no difference in fibrinolytic activity (plasminogen activator activity) between the sexes.     

Sex related fibrinolytic activity in rat tissues

Summary Histochemical study of many organs of male and female adult Wistar rats of the same age showed no difference in fibrinolytic activity (plasminogen activator activity) between the sexes.     

Relation between fibrinolytic activity and prostacyclin generation of atherosclerotic artery and dacron prosthetic graft

Summary The newly formed tissue of dacron vascular prosthetic grafts implanted in humans demonstrates prostacyclin generation and fibrinolytic activity comparable to that of the atherosclerotic artery in the vicinity. This provides some evidence that both activities important for haemostasis run parallel.     

Relation between fibrinolytic activity and prostacyclin generation of atherosclerotic artery and dacron prosthetic graft.

The newly formed tissue of dacron vascular prosthetic grafts implanted in humans demonstrates prostacyclin generation and fibrinolytic activity comparable to that of the atherosclerotic artery in the vicinity. This provides some evidence that both activities important for haemostasis run parallel.     

Progesterone regulation of implantation-related genes: new insights into the role of oestrogen

Genomic profiling was performed on explants of late proliferative phase human endometrium after 24-h treatment with progesterone (P) or oestradiol and progesterone (17β-E₂+P) and on explants of menstrual phase endometrium treated with 17β-E₂+P. Gene expression was validated with real-time PCR in the samples used for the arrays, in endometrium collected from early and mid-secretory phase endometrium, and in additional experiments performed on new samples collected in the menstrual and late proliferative phase. The results show that late proliferative phase human endometrium is more responsive to progestins than menstrual phase endometrium, that the expression of several genes associated with embryo implantation (i.e. thrombomodulin, monoamine oxidase A, SPARC-like 1) can be induced by P in vitro, and that genes that are fully dependent on the continuous presence of 17β-E₂ during P exposure can be distinguished from those that are P-dependent to a lesser extent. Therefore, 17β-E₂ selectively primes implantation-related genes for the effects of P. H. Dassen, C. Punyadeera: These authors contributed equally. Received 18 December 2006; received after revision 6 February 2007; accepted 8 March 2007