ABSTRACT
The reaction of high temperature solid state catalytic isotope exchange in peptides and proteins under the action of catalyst-activated spillover hydrogen was studied. The reaction of human gene-engineered insulin with deuterium and tritium was conducted at 120-140° C to produce insulin samples containing 2-6 hydrogen isotope atoms. To determine the distribution of the isotope label over tritium-labeled insulin's amino acid residues, oxidation of the S-S bonds of insulin by performic acid was performed and polypeptide chains isolated; then their acid hydrolysis, amino acid analysis and liquid scintillation counts of tritium in the amino acids were conducted. The isotope label was shown to be incorporated in all amino acids of the protein, with the peptide fragment FVNQHLCGSHLVE of the insulin ß-chain showing the largest incorporation. About 45% of the total protein isotope label was incorporated in His5 and His10 of this fragment. For the analysis of isotope label distribution in labeled insulin's peptide fragments, the recovery of the S-S bonds by mercaptoethanol, the enzymatic hydrolysis by glutamyl endopeptidase from Bacillus intermedius and HPLC division of the resulting peptides were carried out. Attribution of the peptide fragments formed due to hydrolysis at the Glu-X bond in the ß-chain was accomplished by mass spectrometry. Mass spectrometry analysis data of the deuterium-labeled insulin samples' isotopomeric composition showed that the studied solid state isotope exchange reaction equally involved all the protein molecules. Biological studying of tritium-labeled insulin showed its physiological activity to be completely retained.
Subject(s)
Deuterium , Insulin, Regular, Human/chemistry , Tritium , Amino Acid Sequence , Catalysis , Deuterium Exchange Measurement , Histidine/chemistry , Hydrolysis , Insulin, Regular, Human/genetics , Isotope Labeling/methods , Molecular Sequence Data , Peptide Fragments/chemistry , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
Atherosclerotic plaque formation and vascular calcinosis were modeled in a subchronic experiment. Reduced HDL and elevated LDL concentrations, increased atherogenic index and albumin toxicity index, and high blood levels of triglycerides and uric acid were early markers of pathology. Xydiphone in combination with vitamin D effectively reduced these changes and the degree of vascular calcinosis.
Subject(s)
Atherosclerosis/drug therapy , Biomarkers/metabolism , Etidronic Acid/therapeutic use , Vascular Calcification/drug therapy , Alkaline Phosphatase/blood , Animals , Atherosclerosis/pathology , Cholesterol, LDL/blood , Creatine Kinase/blood , Creatinine/blood , Etidronic Acid/pharmacology , L-Lactate Dehydrogenase/blood , Lipid Peroxidation/physiology , Male , Rats , Serum Albumin , Triglycerides/blood , Uric Acid/blood , Vascular Calcification/pathology , Vitamin D/pharmacology , Vitamin D/therapeutic useSubject(s)
Hypertension/therapy , Myocardium/ultrastructure , Photons/therapeutic use , Phototherapy , Animals , Heart/radiation effects , Light , Male , Rats , Rats, Inbred SHR , Rats, Inbred WKYABSTRACT
The administration of moxonidine for two weeks in a daily dose of 2 or 10 mg/kg (p.o.) reduced the cardiac sympathetic tone in stroke-prone spontaneously hypertensive rats (SHR-SP) by 24.3 +/- 7.3 and 32.2 +/- 10.2%, respectively. In addition, the treatment influenced the cardiac baroreflex by decreasing the bradycardic plateau and increasing both bradycardic and tachycardic range. The baroreflex gain increased in a dose-dependent manner by 41.6 +/- 12.1 and 103.0 +/- 3.9%, respectively. These data indicate that moxonidine can modulate the cardiac autonomic (tonic and reflex) chronotropic control.
Subject(s)
Antihypertensive Agents/pharmacology , Baroreflex/drug effects , Blood Pressure/drug effects , Heart Rate/drug effects , Imidazoles/pharmacology , Adrenergic beta-Antagonists/pharmacology , Animals , Atenolol/pharmacology , Atropine/pharmacology , Male , Muscarinic Antagonists/pharmacology , Parasympatholytics/pharmacology , Rats , Rats, Inbred SHR , Receptors, Adrenergic, beta-1/drug effects , Sympatholytics/pharmacologyABSTRACT
The effect of daflon administration (100 mg/kg/day, p.o., over 8 days) upon the transcapillary fluid shift in the hind extremities of narcotized rats was studied. The effect was evaluated by the arterio-venous difference of the blood density (orthostatic versus antiorthostatic). The treatment reduced the level of fluid filtration from the vascular channel to the interstitial space, but did not affect the level of reabsorption.
Subject(s)
Body Fluids/metabolism , Diosmin/pharmacology , Hesperidin/pharmacology , Hindlimb/blood supply , Animals , Blood/drug effects , Capillaries/metabolism , Densitometry , Posture , Rats , Rats, WistarABSTRACT
An experimental model was developed for the study of antiedemic drug activity in anesthetized rats. The effect of furosemide upon the transcapillary fluid shift was studied. It is shown that the character of changes in the arterio-venous difference of blood density in response to postural (orthostatic versus antiorthostatic) changes can be used to udge on the filtration and reabsorption processes in the microcirculation bed of hind extremities in anesthetized rats.
