On the Action Mechanism of Some Fibrinolysis Inhibitors

1967 ◽  
Vol 18 (03/04) ◽  
pp. 439-446 ◽  
Author(s):  
L Donner ◽  
J Housková
Keyword(s):  
Body Weight ◽  
Inhibitory Activity ◽  
Inhibitory Effect ◽  
Inhibiting Activity ◽  
Action Mechanism ◽  
Intravenous Injections ◽  
Individual Variations ◽  
Therapeutic Doses ◽  
Antitryptic Activity

Summary1. Both p-aminomethylcyclohexanecarboxylic acid (AMCA) and p-aminomethylbenzoic acid (PAMBA) exhibit a significant inhibiting activity on the fibrinolysis. The inhibition conldbe observed already at concentrations as low as 10-4 M. The inhibition was higher in a system activated by urokinase than in a system activated by streptokinase. By comparing the same concentrations the greatest inhibitory activity was observed in AMCA, a lesser one in PAMBA, and the least one in EACA.2. AMCA exhibited mostly an antiactivator effect; the inhibition of pi asm in was very weak.3. Intravenous injections of either AMCA, in recommended therapeutic doses of 15-20 mg/kg body weight, or PAMBA, in recommended therapeutic doses of 1.5 mg/kg body weight, exhibited an inhibitive effect on the fibrinolysis in vivo. Their effects set on, on the average, inside 30-60 min, and lasted 2-6 hrs. Great individual variations were found. AMCA had the highest inhibitory effect.4. AMCA inhibits not only the blood activator but also the tissue activator. AMCA possesses, apart from the antifibrinolytic and antifibrinogenolytic activity, also a significant antitryptic activity.

scholarly journals In vivo hypotensive effect and in vitro inhibitory activity of some Cyperaceae species

2013 ◽  
Vol 49 (4) ◽  
pp. 803-809
Author(s):  
Monica Lacerda Lopes Martins ◽  
Henrique Poltronieri Pacheco ◽  
Iara Giuberti Perini ◽  
Dominik Lenz ◽  
Tadeu Uggere de Andrade ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Colorimetric Assay ◽  
Hypotensive Effect ◽  
Ace Inhibition ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Total Phenolic ◽  
Before And After

In 1820, French naturalist August Saint Hillaire, during a visit in Espírito Santo (ES), a state in southeastern Brazil, reported a popular use of Cyperaceae species as antidote to snake bites. The plant may even have a hypotensive effect, though it was never properly researched. The in vitro inhibitory of the angiotensin converting enzyme (ACE) activity of eigth ethanolic extracts of Cyperaceae was evaluated by colorimetric assay. Total phenolic and flavonoids were determined using colorimetric assay. The hypotensive effect of the active specie (Rhychonospora exaltata, ERE) and the in vivo ACE assay was measured in vivo using male Wistar Kyoto (ERE, 0.01-100mg/kg), with acetylcholine (ACh) as positive control (5 µg/kg, i.v.). The evaluation of ACE in vivo inhibitory effect was performed comparing the mean arterial pressure before and after ERE (10 mg/kg) in animals which received injection of angiotensin I (ANG I; 0,03, 03 and 300 µg/kg, i.v.). Captopril (30 mg/kg) was used as positive control. Bulbostylis capillaris (86.89 ± 15.20%) and ERE (74.89 ± 11.95%, ERE) were considered active in the in vitro ACE inhibition assay, at 100 µg/mL concentration. ACh lead to a hypotensive effect before and after ERE's curve (-40±5% and -41±3%). ERE showed a dose-dependent hypotensive effect and a in vivo ACE inhibitory effect. Cyperaceae species showed an inhibitory activity of ACE, in vitro, as well as high content of total phenolic and flavonoids. ERE exhibited an inhibitory effect on both in vitro and in vivo ACE. The selection of species used in popular medicine as antidotes, along with the in vitro assay of ACE inhibition, might be a biomonitoring method for the screening of new medicinal plants with hypotensive properties.

Phytochemical Screening and Anti-Diabetic Efficacy of O. Sanctum Seed Extract on Streptozotocin Induced Diabetic Rats

2017 ◽  
Vol 54 (3) ◽  
pp. 336
Author(s):  
Kavitha K. ◽  
Ponne S.
Keyword(s):  
Body Weight ◽  
Digestive Enzymes ◽  
Fasting Blood Glucose ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Seed Extract ◽  
Phytochemical Screening ◽  
Weight Changes

The present study was designed to assess the in vitro and in vivo anti-diabetic efficacy of <em>O. sanctum</em> seed and its phytochemical screening. In vitro inhibitory effect on carbohydrate digestive enzymes like α-amylase and α-glucosidase and in vivo parameters such as fasting blood glucose and body weight changes were studied, a potent inhibitory effect was observed on activities of digestive enzymes and a marked decrease in the glucose level in the <em>O. sanctum</em> seed extract treated streptozotocin induced diabetic rats was noted. Further a marked reduction in body weight was also observed.

HEPARIN AND NON-ANTICOAGULANT HEPARINS INHIBIT HEPARANASE ACTIVITY IN NORMAL AND MALIGNANT CELLS:POSSIBLE THERAPEUTIC USE IN PREVENTION OF EXTRAVASATION AND DISSEMINATION OF BLOOD BORNE CELLS

1987 ◽  
Author(s):  
A Eldor ◽  
M Bar-Ner ◽  
L Wasserman ◽  
Y matzner ◽  
Z Fuks ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Inhibitory Activity ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Therapeutic Use ◽  
Lymphoma Cells ◽  
In Vivo Experiments ◽  
Acetyl Group ◽  
Mouse Lymphoma

Degradation of vascular subendothelium occurs in_vivo during the process of inflammation and tumor invasion. Various observations suggest that the capacity of some blood-borne cells to extravasate may depend in part on their ability to express hepara-nase activity. Incubation of human platelets, human nc-utrophils, or highly metastatic mouse lymphoma cells with sulfate-labeled extracellular matrix (ECM) results in heparanase mediated release of labeled heparan sulfate cleavage fragments (0.5<Kav<0.85 on Sepharose 5B) (J. Clin.Invest. 74: 1842 and 76: 1306; Cancer Res. 43: 2704). The present study was undertaken to test the heparanase inhibitory effect of heparin and non-anticoagulant species of heparin that might havea potential therapeutic use in preventing heparanase mediated extravasation ofblood-borne cells. We prepared totallyor N-desulfated heparins which were either left with their N-position exposed or were subsequently N-acetylated or N-resulfated. These heparins exhibited less than 5% of the anticoagulant activityof native heparin. It was found that total desulfation of heparin abolished its heparanase inhibitory activity whether desulfation was followed by N-acetylation or not. Inhibitory effect was restored by resulfation of the N-position. When only the N-sulfate group was desulfated, inhibitory activity was lost but could be restored by acetylation of the N-position. These results indicate that N-sulfate groups of heparin are necessary for its heparanase inhibitory activity but can be substituted by an acetyl group provided that the 0-sulfate groups are retained. Low Mr heparins (main Mr species of 2500 and 4500 daltons) and heparin fragments as small as the tetrasaccharide inhibited degradation of heparan sulfate in the ECM, albeit to a lower extent than native heparin. Similar effects of the different heparins were observed with heparanase activities from platelets, neutrophils and lymphoma cells. Preliminary in vivo experiments suggest that non-anticoagulant heparins interfere with tumor metastasis and experimental autoimmune diseases (some heparins were kindly provided by Inst. Choay, Paris and Kabi Vitrum, Stockholm).

scholarly journals Neutrophil recruitment inhibitory factor: a possible candidate for a novel cytokine

1992 ◽  
Vol 1 (1) ◽  
pp. 49-54 ◽  
Author(s):  
W. M. S. C. Tamashiro ◽  
B. M. Tavares-Murta ◽  
F. Q. Cunha ◽  
M. C. Roque-Barreira ◽  
R. M. D. Nogueira ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Inflammatory Responses ◽  
Neutrophil Migration ◽  
Gel Filtration ◽  
Inhibitory Effect ◽  
Neutrophil Recruitment ◽  
Tnf Α ◽  
Inflammatory Stimuli

Inhibitory effect upon neutrophil migration to the inflammatory focus was previously detected in the cell-free incubation fluid of lipopolysaccharide (LPS)-stimulated macrophage monolayers. In the present study we showed that the neutrophil recruitment inhibitory activity from this supernatant was mainly detected in a fraction (P2) obtained by gel filtration chromatography on Sephacryl S-300. P2 fraction was able to inhibit ‘in vivo’ neutrophil emigration induced by different inflammatory stimuli, but it did not affect ‘in vitro’ neutrophil chemotaxis induced by FMLP. When injected intravenously, P2 inhibited oedema induced by carrageenin or immunological stimulus but not the oedema induced by dextran, thus affecting cell-dependent inflammatory responses. It was observed that P2 also induced neutrophil migration when injected locally in peritoneal cavities. This activity was significantly reduced by pretreatment of the animals with dexamethasone. Cytokines, such as IL-8 and TNF-α that are known to exhibit inhibitory effect upon neutrophil migration, were not detected in P2 fraction by highly sensitive assays. Overall the results suggest the existence of a novel cytokine exhibiting ‘in vivo’ neutrophil inhibitory activity, referred as NRIF.

Growth hormone (GH) autofeedback action in the neonatal rat: involvement of GH-releasing hormone and somatostatin

1990 ◽  
Vol 124 (2) ◽  
pp. 199-205 ◽  
Author(s):  
S. G. Cella ◽  
V. De Gennaro Colonna ◽  
V. Locatelli ◽  
V. Moiraghi ◽  
S. Loche ◽  
...  
Keyword(s):  
Body Weight ◽  
Inhibitory Effect ◽  
Postnatal Period ◽  
Neonatal Rat ◽  
Gh Treatment ◽  
Adult Rats ◽  
Releasing Hormone ◽  
Term Administration

ABSTRACT It is known that in adult rats, GH by itself and by promoting secretion of the somatomedins acts at the level of the hypothalamus to trigger release of somatostatin and decrease output of GH-releasing hormone (GHRH), thereby inhibiting further secretion of GH. To assess whether these mechanisms are already operative in the early postnatal period, we have evaluated the effect of short-term administration of GH in 10-day-old rats. Twice-daily s.c. administration of 25 μg human GH/rat, from days 5 to 9 of life, significantly reduced pituitary content of GH, decreased hypothalamic levels of GHRH mRNA and abolished the in-vivo GH response to a challenge dose of GHRH (20 ng/100 g body weight, s.c.). GHRH (20 ng/100 g body weight, twice daily, s.c.) given concomitantly with the GH treatment, completely counteracted the inhibitory effect of the latter on pituitary content of GH and restored to normal the in-vivo GH response to the GHRH challenge. These data indicate that impaired secretion of GHRH is involved in the inhibitory effect elicited by GH treatment in infant rats. However, concomitant involvement of hypothalamic somatostatin as a result of GH treatment cannot be ruled out. In fact, pituitaries from rats pretreated with GH responded in the same manner as pituitaries from control rats to the GHRH challenge in vitro. Journal of Endocrinology (1990) 124, 199–205

scholarly journals Effects of ovariectomy and oestradiol-17beta replacement on brain tyrosine hydroxylase in the catfish Heteropneustes fossilis: changes in in vivo activity and kinetic parameters

2002 ◽  
Vol 175 (2) ◽  
pp. 329-342 ◽  
Author(s):  
R Chaube ◽  
KP Joy
Keyword(s):  
Body Weight ◽  
Tyrosine Hydroxylase ◽  
Brain Regions ◽  
Inhibitory Effect ◽  
Heteropneustes Fossilis ◽  
Gonadotrophin Secretion ◽  
Tyrosine Hydroxylation ◽  
Brain Tyrosine Hydroxylase ◽  
Biphasic Responses

In Heteropneustes fossilis, ovariectomy inhibited in vivo brain (hypothalamus-pituitary, telencephalon and medulla oblongata) tyrosine hydroxylase (TH) activity with significant effects in weeks 2, 3, 4 and 5 of the gonadal resting phase and in weeks 3, 4 and 5 of the prespawning phase (P<0.05, Tukey's test). Oestradiol-17beta (OE(2)) replacement in 3-week ovariectomised fish produced biphasic responses in both seasons; the low dosages of 0.05 and 0.5 micro g/g body weight (BW) elevated TH activity, whereas the high dosages of 1.0 and 2.0 micro g/g BW decreased it. The magnitude of the inhibition was higher in the resting phase than in the prespawning phase. The inhibitory effect of ovariectomy may be produced by elevating the apparent K(m) values (decreased affinity) of the enzyme for both L-tyrosine (substrate) and dimethyltetrahydropteridine (cofactor) and consequently decreasing the V(max). Significant changes (P<0.05) in both these parameters were noticed but showed minor differences with regard to the length of ovariectomy, season or brain regions. The biphasic effects of OE(2) replacement on TH activity seemed to be produced by differential effects on apparent K(m) and V(max). The stimulatory effect of the low dosages of OE(2) coincides with a decrease in the apparent K(m) values (increased affinity) for both substrate and cofactor and an increase in the V(max) of the enzyme. The inhibitory effect of the high dosages of OE(2) correlated with an increase in the apparent K(m) values (decreased affinity) for both substrate and cofactor, and a decrease in the V(max) compared with the lower dosage groups. The results strongly suggested that OE(2) can modulate brain catecholaminergic activity at the level of tyrosine hydroxylation which, in turn, may alter gonadotrophin secretion. OE(2) may elicit biphasic effects by differentially altering the enzyme affinity towards the substrate and cofactor.

Inhibitory effects of (-)-Epigallocatechin-3-gallate from green tea on the growth of Babesia parasites

Parasitology ◽  
2009 ◽  
Vol 137 (5) ◽  
pp. 785-791 ◽  
Author(s):  
M. ABOULAILA ◽  
N. YOKOYAMA ◽  
I. IGARASHI
Keyword(s):  
Body Weight ◽  
Green Tea ◽  
Inhibitory Effect ◽  
Post Inoculation ◽  
Chemotherapeutic Drug ◽  
Inhibitory Effects ◽  
Viability Test ◽  
Anti Cancer

SUMMARY(-)-Epigallocatechin-3-gallate (EGCG) is the major tea catechin and accounts for 50–80% of the total catechin in green tea. (-)-Epigallocatechin-3-gallate has antioxidant, anti-inflammatory, anti-microbial, anti-cancer, and anti-trypanocidal activities. This report describes the inhibitory effect of (-)-Epigallocatechin-3-gallate on the in vitro growth of bovine Babesia parasites and the in vivo growth of the mouse-adapted rodent babesia B. microti. The in vitro growth of the Babesia species was significantly (P<0·05) inhibited in the presence of micromolar concentrations of EGCG (IC50 values=18 and 25 μM for B. bovis, and B. bigemina, respectively). The parasites showed no re-growth at 25 μM for B. bovis and B. bigemina in the subsequent viability test. The drug significantly (P<0·05) inhibited the growth of B. microti at doses of 5 and 10 mg/kg body weight, and the parasites completely cleared on day 14 and 16 post-inoculation in the 5 and 10 mg/kg treated groups, respectively. These findings highlight the potentiality of (-)-Epigallocatechin-3-gallate as a chemotherapeutic drug for the treatment of babesiosis.

scholarly journals Evaluation ofα-Glucosidase Inhibitory Effect of 50% Ethanolic Standardized Extract ofOrthosiphon stamineusBenth in Normal and Streptozotocin-Induced Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Elsnoussi Ali Mohamed ◽  
Mariam Ahmad ◽  
Lee Fung Ang ◽  
Mohd. Zaini Asmawi ◽  
Mun Fei Yam
Keyword(s):  
Plasma Glucose ◽  
Inhibitory Activity ◽  
Ethanolic Extract ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Lower Plasma ◽  
Antidiabetic Effect ◽  
Glucose Levels ◽  
Lower Plasma Glucose

In the present study, a 50% ethanolic extract ofOrthosiphon stamineuswas tested for itsα-glucosidase inhibitory activity.In vivoassays of the extract (containing 1.02%, 3.76%, and 3.03% of 3′hydroxy-5,6,7,4′-tetramethoxyflavone, sinensetin, and eupatorin, resp.) showed that it possessed an inhibitory activity againstα-glucosidase in normal rats loaded with starch and sucrose. The results showed that 1000 mg/kg of the 50% ethanolic extract ofO. stamineussignificantly (P<0.05) decreased the plasma glucose levels of the experimental animals in a manner resembling the effect of acarbose. In streptozotocin-induced diabetic rats, only the group treated with 1000 mg/kg of the extract showed significantly (P<0.05) lower plasma glucose levels after starch loading. Hence,α-glucosidase inhibition might be one of the mechanisms by whichO. stamineusextract exerts its antidiabetic effect. Furthermore, our findings indicated that the 50% ethanolic extract ofO. stamineuscan be considered as a potential agent for the management of diabetes mellitus.

Effects of Indomethacin, Dexamethasone, and Erythromycin on Endotoxin-Induced Intraepithelial Mucus Production of Rat Nasal Epithelium

1997 ◽  
Vol 106 (8) ◽  
pp. 683-687 ◽  
Author(s):  
Yukimitsu Takahashi ◽  
Takeshi Shimizu ◽  
Yasuo Sakakura
Keyword(s):  
Body Weight ◽  
Intraperitoneal Injection ◽  
Goblet Cells ◽  
Inhibitory Effect ◽  
Respiratory Epithelium ◽  
Mucus Production ◽  
Inflammatory Drugs ◽  
In Vivo Effects ◽  
Intranasal Instillation

We produced hypertrophic and metaplastic changes of goblet cells in rat nasal respiratory epithelium by the intranasal instillation of endotoxin (ETN). In the present study, we examined in vivo effects of indomethacin (IND), dexamethasone (DEX), and erythromycin (EM) on intraepithelial mucus production using this animal model. Intraperitoneal injection of IND (2 to 4 mg/kg body weight x 4 days) or DEX (4 to 8 mg/kg body weight x 4 days) significantly inhibited intraepithelial mucus production induced after 3 days of ETN instillations. Intraperitoneal injection of EM (100 mg/kg body weight x 8 days), aminobenzylpenicillin (ABPC, 200 mg/kg body weight x 8 days), and cephalothin (CET, 200 mg/kg body weight x 8 days) also inhibited intraepithelial mucus production induced after 7 days of ETN instillations. When compared with ABPC and CET, EM had a greater inhibitory effect. These results indicate that ETN-induced intraepithelial mucus production can be inhibited by treatment with the anti-inflammatory drugs IND and DEX. Antibiotics such as EM, ABPC, and CET will also be effective, probably by preventing secondary bacterial infection, and EM has an additional inhibitory effect on intraepithelial mucus production.

scholarly journals Macrophage-derived neutrophil chemotactic factor is involved in the neutrophil recruitment inhibitory activity present in the supernatants of LPS-stimulated macrophages

1996 ◽  
Vol 5 (2) ◽  
pp. 116-120 ◽  
Author(s):  
B. M. Tavares-Murta ◽  
F. Q. Cunha ◽  
M. Dias-Baruffi ◽  
M. C. Roque-Barreira ◽  
S. H. Ferreira
Keyword(s):  
Affinity Chromatography ◽  
Inhibitory Activity ◽  
Neutrophil Migration ◽  
Gel Filtration ◽  
Inhibitory Effect ◽  
Neutrophil Recruitment ◽  
Chemotactic Factor ◽  
Tnf Α ◽  
Neutrophil Chemotactic Factor

In a previous study, we demonstrated the presence of a neutrophil recruitment inhibitory factor (NRIF) in the supernatants of LPS-stimulated macrophages. Recently, the purification of a 54 kDa protein, identified as the macrophage-derived neutrophil chemotactic factor (MNCF) was reported. Since NRIF and MNCF are obtained under the same conditions, and, since the intravenous administration of TNF-α and IL-8 inhibits neutrophil migration, we have investigated whether MNCF could be responsible for this inhibitory activity. After affinity chromatography of the macrophage supernatants on a D-galactose column, the inhibitory activity was recovered in both the unbound (D-gal−) and bound (D-gal+) fractions, with MNCF being found in the D-gal+fraction. Further gel filtration of the latter on Superdex 75 yielded a single peak containing both activities. In a cytotoxicity assay, most of the TNF found in the crude supernatants was recovered in the D-gal−fraction. Furthermore, the incubation of the D-gal−fraction with anti-TNF-α plus anti-IL-8 antisera partially prevents its inhibitory effect on neutrophil migration, but had no effect on the D-gal+activity. Overall, these results suggest that the D-gal−inhibitory effect is partially mediated by TNF-α and IL-8, and that MNCF accounts for the inhibition of neutrophil migrationin vivoby the D-gal+fraction.

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