ABSTRACT
The influence two original derivatives of a therapeutically important peptide, bearing arachidonic acid residue with semax and proglyprol, upon platelet aggregation have been studied in vitro. It is established that both derivatives, in contrast to the parent peptide, possess moderate anti-aggregant properties and produce a dose-dependent decrease in the interplatelet interaction induced by ADP, epinephrine, and arachidonic acid within the concentration range of 0.018 - 1.8 mM. This activity was more pronounced for arachidonoylsemax in comparison with arachidonoylproglyprol.
Subject(s)
Adrenocorticotropic Hormone/analogs & derivatives , Arachidonic Acid/chemistry , Neuroprotective Agents/chemical synthesis , Oligopeptides/chemical synthesis , Peptide Fragments/chemical synthesis , Platelet Aggregation Inhibitors/chemical synthesis , Platelet Aggregation/drug effects , Proline/analogs & derivatives , Adenosine Diphosphate/pharmacology , Adrenocorticotropic Hormone/chemical synthesis , Adrenocorticotropic Hormone/pharmacology , Arachidonic Acid/pharmacology , Blood Platelets/cytology , Blood Platelets/drug effects , Cells, Cultured , Drug Design , Epinephrine/pharmacology , Humans , Neuroprotective Agents/pharmacology , Oligopeptides/pharmacology , Peptide Fragments/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Proline/chemical synthesis , Proline/pharmacology , Structure-Activity RelationshipABSTRACT
The effectiveness of planning polychemotherapy (PCT) for cancer patients depends on the functional state of the liver. The use of remaxol was studied in 100 patients with advanced forms of cancer (including breast cancer) in a preventive mode in comparison with the control group (100 patients, essentiale group of 40 patients) and in the process of PCT. Remaxol, compared with the control group, allowed reducing the frequency of drug hepatotoxicity by 30 +/- 3.7% and by 6.5 +/- 2.9% in comparison with the group of patients who received essentiale.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/prevention & control , Neoplasms/drug therapy , Protective Agents/therapeutic use , Succinates/therapeutic use , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antioxidants/therapeutic use , Chemical and Drug Induced Liver Injury/etiology , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Patient Selection , Phosphatidylcholines/therapeutic use , Protective Agents/administration & dosage , Succinates/administration & dosage , Treatment OutcomeABSTRACT
Ovary cancer treatment often presents clinical promlems due to frequent occurence of late diagnostics (III-IV stages), severe treatment complications in patients with ascitis and tumor intoxication. Reamberin can be used as supportive therapy aimed at decrease of intoxication, which is one of the main hindrances for antitumor therapy. In the current study reamberin was used in 89 stage III-IV (FIGO) ovary cancer patients with ascitis, age 42 to 79, CP or CAP chemotherapy recipients after prior cytoreductive surgery. The occurrence of hematological complications (grade 1-2 anemia and neutropenia) and cardiac dysfunctions in the study group was much lower, than in the control group. This difference is statistically valid (p < 0.01 and p < 0.05). The patients receiving reamberin prior to chemotherapy or during chemotherapy rarely (in 3.7% of cases) displayed raised creatinine values. In the control group grade 1-3 renal impairment was observed in 41.4% cases, in 12 cases the therapy had to be ceased. This difference between the groups is statistically valid (p < 0.001). Patients receiving reamberin displayed more rapid rate of CA-125 tumor marker serum concentration decrease. Therefore, reamberin is an effective drug for prevention of chemotherapy side effects and alleviation of intoxication allowing the more rigid chemotherapy schedule without an increase in toxicity.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Meglumine/analogs & derivatives , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Primary Prevention/methods , Protective Agents/therapeutic use , Succinates/therapeutic use , Adult , Aged , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/pathology , Female , Humans , Meglumine/therapeutic use , Middle Aged , Neoplasm Staging , Remission InductionABSTRACT
The influence of new original 1,3,4-thiadiazines on the human platelet aggregation in vitro was studied. All substances inhibited the platelet aggregation induced by both ADP and arachidonic acid. 1,3,4-Thiadiazines L-19, H-30 and L-37 were the most effective inhibitors. Effect of the intravenous injection of L-19 in various doses on platelet aggregation and some parameters of plasmatic hemostasis were studied ex vivo.
Subject(s)
Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Thiadiazines/pharmacology , Adenosine Diphosphate/pharmacology , Animals , Arachidonic Acid/pharmacology , Drug Evaluation, Preclinical , Rabbits , Thiadiazines/chemistryABSTRACT
A series of new 1,3,4-thiadiazine derivatives have been synthesized and their effect on the human platelet aggregation in vitro has been studied. All the tested substances inhibit the human platelet aggregation induced by ADP and arachidonic acid in a broad concentration range. The most active 1,3,4-thiadiazines (L-19, L-28 and L-31) effectively inhibit platelet aggregation at concentrations within 0.01-1 mM.
Subject(s)
Blood Platelets/metabolism , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Thiadiazines/pharmacology , Adenosine Diphosphate/pharmacology , Arachidonic Acid/pharmacology , Blood Platelets/cytology , Dose-Response Relationship, Drug , HumansABSTRACT
The effects of GABA - docosahexaenoyldopamine (DHED) conjugate on the cerebral haemodynamics and thrombocyte aggregation were evaluated and compared to these of docosahexaenoyldopamine alone. The GABA - DHED conjugate was shown to significantly enhance the cerebral circulation in rats with a model of global transient cerebral ischemia, as compared to the intact animals. Administered alone, DHED increased the blood supply of both intact and ischemic brains to an equal extent. The GABA-DHED conjugate demonstrated the antiaggregative activity, but the effect was less expressed than that of DHED alone.
Subject(s)
Cerebrovascular Circulation/drug effects , Dopamine/analogs & derivatives , Platelet Activating Factor/drug effects , gamma-Aminobutyric Acid/analogs & derivatives , Animals , Dopamine/pharmacology , Humans , Male , Rats , gamma-Aminobutyric Acid/pharmacologyABSTRACT
The influence of new synthetic peptides ARGDS-NH2 and RGD-dFK (synthesized by the fermentative method) and VPNLRGDLQVLA (a fragment of the foot-and-mouth virus's surface peptide) on the ADP-induced human platelet aggregation in vitro was studied. All peptides were found to inhibit the human platelet aggregation, but the synthetic peptides (ARGDS-NH2 and RGD-dFK) showed the most pronounced effect. Significant decrease in the platelet aggregation was observed at their concentrations within 0.1-10 mM. ARGDS-NH2 and RGD-dFK inhibited the platelet aggregation stronger than the reference drug pentoxifylline at equivalent concentrations.
Subject(s)
Oligopeptides/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Foot-and-Mouth Disease Virus , Humans , In Vitro Techniques , Oligopeptides/chemistry , Pentoxifylline/pharmacology , Platelet Aggregation Inhibitors/chemistry , Platelet Function Tests , Viral Core Proteins/chemistryABSTRACT
The effect of the new antimigraine drug tropoxin - the serotonin receptor (5-HT2) antagonist - on the human platelet aggregation in vitro induced by ADP (1 x 10(-5) M) and epinephrine (2.5 x 10(-6) M) was studied. Tropoxin reliably inhibited the ADP-induced platelet aggregation in a concentration range of 0.01 - 7 mg/ml. A significant inhibition effect with respect to the epinephrine-induced platelet aggregation was observed in a drug concentration range of 2 - 7 mg/ml, although a reliable antiaggregant activity was also observed below 2 mg/ml. A bolus administration of tropoxin (10 mg/kg) in rabbits decreased the ADP-induced platelet aggregation ex vivo by a factor of 1.2 - 1.4. The effect appeared 45 min after treatment and was observed during subsequent 30 min.
Subject(s)
Aza Compounds/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Platelet Aggregation/drug effects , Serotonin Antagonists/pharmacology , Adenosine Diphosphate/pharmacology , Animals , Aza Compounds/administration & dosage , Aza Compounds/therapeutic use , Blood Platelets/drug effects , Bridged Bicyclo Compounds, Heterocyclic/administration & dosage , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Epinephrine/pharmacology , Humans , Migraine Disorders/drug therapy , Rabbits , Serotonin Antagonists/administration & dosage , Serotonin Antagonists/therapeutic useABSTRACT
A series of six new synthetic dinitroglycerol esters of fatty acids on the human platelet aggregation was studied in vitro. Inclusion of the dinitroglycerol moiety into the molecule of arachidonic acid deprived this acid from pro-aggregant activity. All six compounds produced moderate (dose-dependent) inhibition of the platelet aggregation process induced by arachidonic acid (1 x 10(-3) M). Platelet aggregation was most significantly affected by dinitroglycerol esters of arachidonic and docosahexaenoic acids. This is probably explained by the influence of these esters on the oxidative metabolism of arachidonic acid to eicosanoids playing the role of proaggregants. In the presence of vessel wall (rat aorta fragments), dinitroglycerol esters of arachidonic and docosahexaenoic acids incubated with platelets (5 min, 37 degrees C) significantly reduced their aggregation induced by arachidonic acid (1 x 10(-3) M) or docosahexaenoic acid (1 x 10(-5) M) under the conditions of endothelial cyclooxygenase suppressed by acetylsalicylic acid (10 mg/ml). The pronounced antiaggregant effect of the synthetic dinitroglycerol esters studied is probably related to their ability to act as NO donors suppressing the activity of thrombocytes (provided that the NO production activity is present in the system).
Subject(s)
Fatty Acids/pharmacology , Glycerol/analogs & derivatives , Glycerol/pharmacology , Nitro Compounds/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Animals , Aorta , Cyclooxygenase Inhibitors/pharmacology , Endothelium, Vascular/drug effects , Endothelium, Vascular/enzymology , Esters , Fatty Acids/chemistry , Glycerol/chemistry , Humans , In Vitro Techniques , Nitro Compounds/chemistry , Rats , Structure-Activity RelationshipABSTRACT
A series of original dopaminamides of polyunsaturated fatty acids were synthesized and characterized with respect to antiaggregant and cerebrovascular stimulant properties. It was established that dopaminamides of linolic, dimethyllinolic, docosapentaenoic, docosahexaenoic (DHEA) and stearidonic (C18:4 and C18:3) acids decrease ADP and arachidonic acid (AA) induced human thrombocyte aggregation in vitro. The most pronounced antiaggregant effect was observed for DHEA dopaminamide: in a dose of 10 mg/kg, this agent produced a significant decrease in the AA induced thrombocyte aggregation. DHEA per se in the same dose increases the activated partial thromboplastin time (APTT), while not affecting the prothrombin time. The synthesized dopaminamides of arachidonic, eicosapentaenoic, and docosahexaenoic acids stimulate local circulation in the cerebral cortex. The most pronounced cerebrovascular effect was also produced by DHEA dopaminamide.
