Biomedical subjects
Publications and source records attributed to C Ebert.
Statistical methods of optimization were applied to the enzymatic semisynthesis of ampicillin catalyzed by penicillin acylase. Since the traditional approach fails in determining both the presence of interactions between the variables and their magnitude, the reaction was reconsidered by means of chemometric techniques. In this work we determined the interaction between temperature and pH for the first time.
The aim of this study is to investigate the hydrolysis of 1,3-di(p-carboxyphenyl)triazene dipotassium salt, AVIS (1), over a pH range of 2.60-8.50. This compound decomposes into p-aminobenzoic acid and the corresponding diazonium cation with no formation of alkylcarbo cations; the same compounds are formed from hydrolyses of DM-COOK (2), an antimetastatic agent, and of its possible demethylated metabolite, MM-COOK (3), a chemical xenogenization inducer. In these latter cases, however, a methylcarbo cation is formed. The pH dependence of the pseudo-first-order rate constants is intermediate between 2 and 3. Preliminary data on its toxicity and antitumor activity on both Lewis lung carcinoma and TLX5 lymphoma seem to indicate the essential role of alkylcarbo cation in mediating the antitumor action of aryldimethyltriazenes.
The hydrolysis of p-(3,3-dimethyl-l-triazeno)benzoic acid potassium salt (1;DM-COOK) a highly active antimetastatic and anti-disseminative agent, has been studied in buffered aqueous solution over a pH range of 2.8-8.8 degrees C. The pH dependence of the pseudo first-order rate constants showed two different routes. Under physiological conditions the hydrolysis reactions are carried out by acid catalysis. A procedure based on fourth-order derivative UV spectroscopy (D4) has been developed for the calculation of the kinetic constants at pH greater than or equal to 4.00 and no spectral interferences resulted from decomposition products. The application of derivative UV spectroscopy proved to be suitable fpr rapid, sensitive and reproducible studies of hydrolysis of this class of compounds.
Over a six-month period, 62 endometriosis patients were given 600 mg per day of the ethisterone derivative danazol. Blood count and coagulation status were checked before and during treatment. There was a significant increase (p less than 0.05) in hemoglobin and hematocrit. There were no changes in RBC, leukocyte count, or thrombocyte count; the mean cellular erythrocyte volume, thrombin time, thromboplastin time, and partial thromboplastin time also remained unchanged, as did factors VII, VIII, X, XII, and alpha-1-antitrypsin. Antithrombin III levels increased, while alpha-2-macroglobulin values decreased. Only the drop in fibrinogen, to pathologic values, and the increase in plasminogen reached significant levels (p less than 0.01). These in part contradictory changes suggest that hypocoagulability occurs under danazol medication; however, its clinical relevance is unclear.
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The reaction of halothane in subnarcotic dosage (0.25-0.5 Vol.-%) e.g. with the cooperative patient, was tested at 32 patients with chronic obstructive pulmonary affection (from them 26 patients with pathological increased resistance of the respiratory system) concerning bronchial obstruction. The significant decrease of the respiratory rate and of the resistance of the respiratory system as well as the significant increase of the volume of the breath inspiration unambiguously prove, beside the influence on the subjective health and on the auscultatory findings, a bronchial-enlarging effect of halothane. At 10 patients with serious acute bronchial obstruction, which could not be cured by means of conventional medicamentous therapy, halothane was employed in subnarcotic dosage. In spite of the difficulties in the assessment of the halothane effect by pretreatment we relate the impressive, subjective and objective improvement in these patients to its bronchospasmolytic effect because of the immediate temporal association with the halothane inhalation. In case that there are missing contraindications and an insufficient effect of the conventional medicamentous therapy the use of halothane in subnarcotic dosage with acute serious bronchial obstruction is indicated.
The kinetics of hydrolysis of indomethacin and related compounds was studied in an alkaline medium at 25 degrees C in the presence of anionic (sodium dodecyl sulfate) and cationic (hexadecyltrimethylammonium bromide) surfactants. The rate-surfactant profiles for rate inhibition in the presence of sodium dodecyl sulfate and rate enhancement in the presence of hexadecyltrimethylammonium bromide were analyzed in terms of the current theory of micellar effects.
A review of the data from studies of oral contraceptives on coagulation and the fibrinolytic enzyme systems reveal an increase of a variety of coagulation factors. This is dose dependent and related to estrogens and appreciable above a dose of 0.5 micrograms of ethynylestradiol. Smaller amounts are less effective or not at all active. The mechanism of this increase is unknown. The pathophysiological significance is not yet clear. There is no available data that associate the increase of coagulation factors with disseminated intravascular coagulation. Conclusive evidence that low dose progesterone has any effect on the coagulation system is lacking.
Twelve patients are presented with the symptomatology of haemolysis, elevated liver enzymes and low platelet count (HELLP syndrome). Only 3 patients experienced a progressive course; the rest did not differ from a group of 130 patients suffering from severe preeclampsia. There was no significant difference in the concentration of plasma fibrinogen, fibrinogen monomer complex and antithrombin III. Two patients were treated with heparin without improvement of the coagulation data or the severity of the disease. The subgrouping of very severe preeclampsia may be desirable, but it is felt that this group is insufficiently characterized by the symptomatology of HELLP. The evaluation of better criteria may allow identification of subgroups of preeclamptic patients with severe prognostic criteria.
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The hydrolysis of 1-(4-nitrophenyl)-3-methyltriazene in aqueous solution has been studied over a pH range of 3-14. The effect of the anionic and cationic surfactants (sodium lauryl sulfate and hexadecyltrimethylammonium bromide) on the rate of hydrolysis was investigated. The quaternary ammonium bromide causes a rate decrease at all pH values studied, while sodium lauryl sulfate enhances the acid-catalyzed hydrolysis and decreases the observed rate constants in the pH-independent region. The results are discussed in terms of the current theory of micellar effects.
The kinetics of the hydrolysis of indomethacin and related compounds were studied in an alkaline medium at 25 degrees. The pseudo-first-order rate constants were evaluated from log absorbance versus time plots in the ultraviolet. These compounds showed a second-order rate constant at low concentrations of hydroxide ion and a first-order rate constant at higher concentrations of hydroxide ion.
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Thrombocyte function was studied in pregnant and non-pregnant rabbits which had received fenoterol injections, doses being ten times as high as those therapeutically used on human patients. In rabbits, fenoterol failed to show any recordable effect on platelet number and function.
In 20 cases of normal pregnancy and 9 cases of foetal monstrosities the immunoglobulins G, A, M and albumin C3C and alpha 2MG were determined in the amniotic fluid. In neural tube defects the IgG, IgA and albumin concentrations were clearly above those found in normal pregnancies. IgM was not found in any of the cases, whereas alpha 2MG occurred in two cases of foetal monstrosity. There was no difference in C3C concentrations of both groups.
Soluble fibrin monomer complexes were assayed by agarose gel filtration and by ultracentrifugation. Increased values of SFMC were found in the normal third-trimester pregnancies. They were considerably higher in plasma of patients with pre-eclampsia. Concentrations were higher using ultracentrifugation as compared to gel chromatography. Using ultracentrifugation 4 components were identified, indicating that SFMC in this disease are not a homogeneous group.
In 46 women the alpha1-fetoprotein content, the soluble fibrin monomer complexes (LFMK), and the coagulation status were determined in the maternal serum at the beginning of the second trimester before and after amniocentesis. Increases of AFP by more than 100% of the original level pointed to fetomaternal microtransfusion, the quantity of which was calculated by means of a formula. Overall coagulation tests did not show any change after the puncture. A moderate LFMK increase was seen (p less than 0.05), which, however, was not clearly correlated with the AFP increase.
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