Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of deep sea water on the fibrinolytic properties of human vascular endothelial cells was investigated. There was no difference in the growth ratio between human umbilical vein endothelial cells (HUVECs) cultured with growth medium (RPMI-1640 containing 20% fetal calf serum) prepared with Hawaii deep sea water (HDSW medium) and those with medium prepared with normal distilled water (control medium). The secretion of type 1 plasminogen activator inhibitor (PAI-1) from HUVECs was significantly reduced by about twofold. However, the levels of PAI-1 mRNA in HUVECs cultured with HDSW medium did not change when compared with those cultured with control medium. Though HDSW medium also reduced the secretion of tissue-type plasminogen activator, the suppressive effect was more prominent for PAI-1. Thus, the balance of fibrinolytic activity was turned toward anti-thrombotic in HUVECs. This was evidenced by the lysis of 125I-fibrin clot in the presence of plasminogen. That is, HUVECs cultured with HDSW medium degraded 125I-fibrin more efficiently than HUVECs with control medium. Such enhanced clot lysis was maintained as long as HDSW medium was present. The accelerated effect of HDSW medium on clot lysis disappeared after the exchange of HDSW medium to control medium. These findings suggest that HDSW may specifically and predominantly affect the process of molecular transfer of PAI-1 after its transcription, resulting in an enhanced fibrinolytic activity of HUVECs. Since HDSW reduces the thrombotic potential of cultured HUVECs, it is speculated that the materials contained in HDSW may prevent the incidence of thrombotic disorders.
 ...
PMID:Suppression of the release of type-1 plasminogen activator inhibitor from human vascular endothelial cells by Hawaii deep sea water. 1456 42

Chitosan has a variety of biological activities. However, little is known about how chitosan modulates the hard tissue forming cells. When we cultured an osteoblastic cell line in alpha-MEM supplemented with 10% FBS and 0.005% chitooligosaccharide for 3 days, alkaline phosphatase (ALP) activity was significantly high compared with the control culture group (p<0.05). This study was focused on gene expression in osteoblasts cultured with water-soluble chitooligosaccharide. cDNA probes were synthesized from isolated RNA and labeled with fluorescent dye. They were hybridized with Human 1.0((R)) cDNA microarray, and fluorescent signal was analyzed. cDNA microarray analysis revealed that 16 genes were expressed at >/=1.5-fold higher signal ratio levels in the experimental group compared with the control group after 3 days. RT-PCR analysis showed that chitosan oligomer induced an increase in the expression of two genes, CD56 antigen and tissue-type plasminogen activator. Furthermore, the expression of mRNAs for BMP-2 was almost identical in the experimental and control groups after 3 days of culture, but slightly increased after 7 days of culture with chitosan oligomer. These results suggest that a super-low concentration of chitooligosaccharide could modulate the activity of osteoblastic cells through mRNA levels and that the genes concerning cell proliferation and differentiation can be controlled by water-soluble chitosan.
 ...
PMID:Early gene expression analyzed by cDNA microarray and RT-PCR in osteoblasts cultured with water-soluble and low molecular chitooligosaccharide. 1473 37

This study investigated the contribution of endogenous suppression of fibrinolysis and increased fibrin deposition to intestinal dysfunction and injury in a rat model of intestinal ischemia/reperfusion (I/R), as fibrinolytic inhibition may lead to thrombotic obstructions that compromise microcirculation and promote intestinal injury. Circulatory fibrinolysis was enhanced by intravenous administration of recombinant tissue plasminogen activator (rt-PA) or by inhibition of PAI-I by administration of MA-33H1F7. Coagulation and fibrinolysis parameters obtained from portal blood were correlated to fibrin deposition (determined by anti-rat fibrin antibody staining), intestinal function (glucose/water clearance) and intestinal injury (histological evaluation by Park/Chiu score). Enhanced circulatory fibrinolytic activity, as evidenced by increased portal plasma plasminogen activator activity, elevated fibrin degradation products and decreased levels of PAI-I, did not reduce mucosal fibrin deposition and microthrombosis in postischemic intestinal tissue. Furthermore, rt-PA or anti-PAI-I antibody administration did not attenuate I/R-induced intestinal injury or dysfunction, as demonstrated by intestinal histopathology scores of 4.8+/-0.2 and 4.7+/-0.3 (control I/R group 4.7+/-0.2) and glucose clearances of 47+/-6 and 46+/-9 micro L/min g (control I/R group 30+/-8 micro L/min. g) after 40 minutes of intestinal ischemia and 3 hours of reperfusion, respectively. However, both interventions resulted in decreased levels of interleukin-6, which may indicate fibrin-induced modulation of inflammation. Attempts to enhance the fibrinolytic activity (either by rt-PA or by anti-PAI-I administration), indicated by increased portal plasma levels of released FDP, failed to decrease mucosal fibrin deposition and to attenuate intestinal I/R injury. Based on our observations and previous reports, the contribution of suppressed endogenous fibrinolysis to microcirculatory fibrin deposition and I/R-injury may be of limited importance.
 ...
PMID:Enhancement of endogenous fibrinolysis does not reduce local fibrin deposition, but modulates inflammation upon intestinal ischemia and reperfusion. 1498 25

Neurological sequela which occur with the medication and procedure to treat or prevent cerebrovascular diseases are reviewed. The report by the NINDS upon the recombinant tissue plasminogen activator (rt-PA) for cerebral infarction showed overall improved prognosis and increased number of cerebral hemorrhage from 1 to 9. Individual approach rather than statistical analysis should be applied to the adverse effect of the treatment. The rhabdomyolysis by statin, the HMG-CoA reductase inhibitor, is well known. The frequency of elevation in serum creatine kinase activity increases from water-soluble statin to lipid-soluble statin and to statin of longer half-life and with entero-hepatic recirculation. All of the interventional procedure such as embolization, stent, intravascular thrombolysis, endarterectomy and EC-IC bypass are possibly complicated by bleeding, arterial occlusion, distal embolism and so on. Guidelines are also a possible source of iatrogenic diseases. For example, 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension recommend at least 3 months of non-pharmacological treatment before starting the anti-hypertensive medications. The possibility to develop stroke within 3 months after the initial examination, however, is not zero. This is what can be called as guideline-induced neurological disease, of which practical physician should be reminded.
 ...
PMID:[Neurological complication due to the drug and the maneuver for the treatment and prevention of cerebrovascular diseases: iatrogenic neurology]. 1515 91

It has recently become apparent that tissue plasminogen activator (tPA) modulates inflammation in diseases such as rheumatoid arthritis (RA) and acute respiratory distress syndrome (ARDS). We have shown previously that tPA has anti-inflammatory activity in in vivo models of oedema or inflammation. The present study investigated the ability of exogenous recombinant tPA (rtPA) to reduce carrageenan-mediated oedema in mice lacking the tPA gene, testing the hypothesis that rtPA treatment may be beneficial in diseases such as RA and ARDS in which there is a paucity of endogenous tPA. Knockout mice deficient in the tPA gene and matching wild-type mice received an intraplantar injection (25 micro L) of carrageenan (1.5%, w/v) following either vehicle (sterile water for injection) or tPA (12 mg/kg). Footpad oedema was measured, an oedema index was calculated and tissue myeloperoxidase (MPO) activity was determined. Mean oedema indices were higher in untreated tPA (-/-) mice than untreated wild-type mice. Pretreatment with rtPA in either tPA (-/-) or wild-type mice reduced the mean measured peak footpad oedema index by 63 and 48%, respectively. Tissue MPO activity was not different between treatment groups. We conclude that exogenous rtPA has the ability to reduce acute oedema without altering neutrophil infiltration into the site of injury in both tPA (-/-) and wild-type mice and that endogenous tPA may participate in the inflammatory process, as evidenced by higher oedema indices in untreated tPA (-/-) mice. These data provide support for the potential clinical utility of exogenous rtPA in the treatment of inflammatory diseases, such as RA and ARDS, in which there is a paucity of tPA.
 ...
PMID:Administration of exogenous tissue plasminogen activator reduces oedema in mice lacking the tissue plasminogen activator gene. 1519 6

Angiostatin, a proteolytic fragment of plasminogen consisting of the first 3 or 4 kringle domains, reduces tumor growth by specifically inhibiting tumor angiogenesis. Angiostatin is generated in vitro in a 2-step process. First, plasminogen is converted to plasmin by plasminogen activators. Next, plasmin excises the angiostatin fragment from plasminogen, a process requiring molecules that are able to donate a free sulfhydryl group. In this study, we investigated whether stimulation of in vivo angiostatin generation by administration of plasminogen activator and a free sulfhydryl group donor (FSD) has anti-tumor activity. First, we determined the optimal conditions for in vitro angiostatin generation by incubating murine plasma with different concentrations of plasminogen activator and/or the FSD captopril. Angiostatin generation was monitored by western blot analysis. Our results were extrapolated to the in vivo situation by administering the optimal dose of tissue-type plasminogen activator (tPA, i.v. injection 3 times/week) and captopril (in drinking water) to mice and analyzing the presence of angiostatin in the circulation. Angiostatin was readily detectable in mice receiving both tPA and captopril, but not in mice receiving either one of the agents. Finally, the anti-tumor activity of the tPA/captopril treatment was tested in a human melanoma xenograft model. Administration of tPA alone had only a marginal effect on tumor growth. Captopril alone reduced tumor growth by about 60%, whereas treatment with both captopril and tPA resulted in 83% inhibition of tumor growth.
 ...
PMID:Anti-tumor activity of a combination of plasminogen activator and captopril in a human melanoma xenograft model. 1535 48

There have been anecdotal reports of the use of tPA for obstructed peritoneal dialysis catheters in both adults and children. This manuscript reviews the literature and summarizes common elements of the procedures used for tPA administration in peritoneal dialysis catheters. The Gambro New Haven experience with administration of tPA (8 mgs in 10 ml of sterile water injected into the catheter and allowed to dwell for 1 hour) in 29 cases of catheter obstruction in 18 patients is presented. Patency was restored in 24 instances with no adverse effects. In the 5 cases that did not respond, the primary cause of poor drain was catheter malposition in 2, constipation in 2, and adhesions in 1. tPA was also administered to 5 patients with relapsing peritonitis; 3 patients, all with Staphylococcus epidermidis, recovered and did not experience further recurrence.
 ...
PMID:Use of tissue plasminogen activator in peritoneal dialysis catheters: a literature review and one center's experience. 1568 39

Due to excessive salt and water retention, hypertension often becomes refractory in patients undergoing peritoneal dialysis (PD). Management of high blood pressure (BP) appears to be of particular importance in such patients because of its substantial impact on the patients' prognosis. However, attempts to control hypertension in PD patients have not been successful in most cases. In this regard, the present study aimed to address the adequacy of current antihypertensive therapy for PD patients. A new antihypertensive strategy expected to improve the outcome was tested on the assumption that treatment with either angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) in the evening together with alpha1-blocker at bed time and long-acting Ca channel blocker (CCB) in the morning might ameliorate BP control associated with morning hypertension. Enrolled in the present study were 40 patients whose BP was evaluated by both office and home measurement. Due to an emerging concern about morning hypertension, home BP measured early in the morning was used for the analysis. Each patient was categorized into the following four groups in accordance with office and home BP: well-controlled, poorly-controlled, white-coat and masked (opposite to white-coat), hypertension. After the observation period, 28 patients with refractory hypertension were allocated to intensive antihypertensive therapy in which ARB or ACE-I previously prescribed in the morning or daytime was shifted to the night. In addition, alpha1-blocker was given at bed time. Furthermore, long-acting CCB and diuretics were shifted to the morning. The patients were then followed up for 4-6 months. The results were as follows: 1) Of the total number of 40 PD patients, systolic hypertension was noted in 50% of cases by office BP and in 80% by home BP. The former was less frequent than the latter (p=0.0047, n=40). Similarly, diastolic hypertension was noted in 20% by office BP and in 45% by home BP. The former was less frequent than the latter (p=0.0045, n=40 by McNemar's analysis). The distribution of BP control categories was well-controlled in 11%, poorly-controlled in 42%, masked hypertension in 39% and white-coat hypertension in 8% when determined by systolic BP. The distribution was well-controlled in 45%, poorly-controlled in 13%, masked hypertension in 34% and white-coat hypertension in 8% of cases when determined by diastolic BP. 2) In 28 patients subjected to the intensive therapy, the control category of systolic BP was changed from 11 to 37% in well-controlled cases, from 42 to 30% in poorly-controlled cases, from 39 to 26% in masked hypertension cases and from 8 to 7% in white-coat hypertension cases. The shift in categories in both poorly-controlled and masked hypertension cases to the better category (well-controlled), was statistically significant (p=0.001, by Wilcoxon's signed rank test). Similarly, the control category of diastolic BP was changed from 45 to 43% in well-controlled cases, from 13 to 15% in poorly-controlled cases, from 34 to 32% in masked hypertension cases and from 8 to 10% in white-coat hypertension cases. There was a tendency for the prevalence of poorly-controlled and masked hypertension to improve to the well-controlled category in response to intensive therapy (p=0.0625, by Wilcoxon's signed rank test). 3) The plasma concentration of plasminogen activator inhibitor (PAI-1)/tissue plasminogen activator (t-PA) complex (total PAI-1 complex) was significantly decreased after intensive therapy (17.3+/-7.8 ng/ml vs. 13.5+/-4.6 ng/ml, n=28, p<0.01 by paired t-test). In contrast, the plasma concentration of t-PA was unchanged even after intensive therapy (4.8+/-3.9 ng/ml vs. 6.2+/-2.9 ng/ml, n=28, ns). These data suggest that home BP obtained in the morning is a useful measure for evaluating morning hypertension in PD patients, most of whom have refractory hypertension categorized as either poorly-controlled or masked hypertension. Intensive treatment with ACE-I/ARB given in the evening along with alpha1-blocker at bed time combined with a diuretic and/or long-acting CCB in the morning is efficacious in controlling the BP of patients with refractory hypertension in PD patients. The link between the reduction in plasma total PAI-1 levels and the intensive therapy may suggest that this therapeutic strategy could prevent thrombotic events associated with morning hypertension in patients on PD.
 ...
PMID:[Antihypertensive therapy for refractory morning hypertension in patients on peritoneal dialysis]. 1575 62

Combined docking and molecular dynamics (MD) simulations are carried out for the rational design of affinity peptide ligand of tissue-type plasminogen activator (t-PA). Ten amino acids that have high affinity to three different regions of t-PA are identified by the amino acids location method on the basis of candidate pocket structure of t-PA. Then, 14 tetrapeptides are built and docked into the candidate pocket of t-PA. The absolute value of the D(score) calculated from the docking simulation is used to assess the affinity of a peptide for t-PA. Consequently, six tetrapeptides that have high D(score) values are selected and linked to a spacer arm of [NH(CH(2))(6)NH(2)] that is present on EAH Sepharose gel. The linked compounds are further evaluated by docking into the candidate pocket of t-PA. As a result, the tetrapeptide QDES with the highest D(score) value is selected. Molecular surface analysis with the MOLCAD program reveals that electrostatic interactions and hydrogen bonds (H-bonds) contribute to the affinity interactions between the tetrapeptide and t-PA. MD simulations indicate that QDES-t-PA complex keeps stable, and the distances between the carboxyl groups of Asp189, Gln192 and Asp194 and the charged amino group of glutamine change little. Moreover, all the nine H-bonds found in the docking simulation are confirmed by the MD simulations. It is also found that three water molecules act as bridges between the ligand and the protein pocket by hydrogen bonding. Finally, high binding affinity and specificity of the peptide ligand are confirmed by the purification of t-PA from crude porcine heart extract using the immobilized-ligand column for affinity chromatography.
 ...
PMID:Rational design of peptide ligand for affinity chromatography of tissue-type plasminogen activator by the combination of docking and molecular dynamics simulations. 1799 43

Warm water bathing is a popular recreational activity and is frequently used in rehabilitation medicine. Although well tolerated in most cases, there are reports indicating an increased risk of thrombotic events after hot tub bathing. The effects of a 45 min thermoneutral bath followed by a 50 min bath with increasing water temperature (maximum 41 degrees C) until reaching a body core temperature of 39 degrees C on factors of blood coagulation and fibrinolysis were studied in eight healthy male volunteers. Blood was obtained after a 45-min resting period as control and after the thermoneutral and hyperthermic bath as well as after another 45 min recovery period at the end of the study. Hyperthermic immersion (HI) lead to a shortening of activated partial thromboplastin time (aPTT) (P < 0.05). Fibrinogen concentration decreased immediately after HI (P < 0.05) but increased during recovery (P < 0.05). Plasminogen activator inhibitor (PAI) activity decreased during HI (P < 0.05), D-dimer concentration was not found to change. Thrombocyte count increased (P < 0.05) during HI. The increases in tissue-type plasminogen activator concentration as well as leucocyte count during HI were due to haemoconcentration. Prothrombin time, PAI-activity and granulocyte count decreased during thermoneutral immersion (P < 0.05). Warm water bathing leads to haemoconcentration and minimal activation of coagulation. The PAI-1 activity is decreased. A marked risk for thrombotic or bleeding complications during warm water bathing in healthy males could not be ascertained.
 ...
PMID:Changes in the haemostatic system after thermoneutral and hyperthermic water immersion. 1804 35


<< Previous 1 2 3 4 5 6 7 8 9 Next >>