Effect of long-term administration of ACTH and adrenocortical hormones on the course of hydrazide convulsions.
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Biomedical subjects
Publications and source records attributed to A Mrozikiewicz.
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The discovery of opioid receptors and endogenous substances capable of specific binding to these receptors, i.e. endorphin and enkephalin, is one of the most spectacular indications suggesting that the presence of a receptor for a certain drug in the organism authenticates searching for an endogenous substances with high affinity at this receptor. Later, further studies were undertaken to detect other endogenous drug-like factors. Some experiments led to the discovery of digoxin-like factor in blood which could bind to a specific receptor on Na+, K(+)-ATPase subunit, showing also the affinity for cardiac glucosides. Digoxin-like factor was detected in blood of healthy people who did not receive any drug treatments. It has been estimated to be present in 15% of the population but in some diseases this value is much higher, e.g. digoxin-like factor was detected in 90% of patients with IDDM, and it can be used as a risk factor of the occurrence of vascular complications. In cases with NIDDM, the digoxin-like factor was detected in patients with insulin-resistance. The presence of digoxin-like factor was ascertained in patients with heart failure who did not take digitalis preparations. Endogenous digoxin-like factor can contribute to the detection of falsely increased digoxin blood concentrations during the monitoring of drug level in the course of the therapy. In our studies we ascertained the presence of the quinidine-, cyclosporin-, theophylline- and phenytoin-like substances in the blood of the healthy people who did not receive any drugs. It seems that these endogenous substances resembling drugs are synthesized in human organism when they are needed for maintaining the physiological equilibrium. We can suggest that stimulation of the production of drug-like factors in the organism can be used in the future in the therapy of some diseases.
Circadian changes in blood serum magnesium levels in healthy individuals. We examined circadian changes of the serum magnesium in 20 healthy subjects. Blood samples were taken every second hour during the 24 hours. Male serum magnesium concentrations increased from the lowest level (0.810 +/- 0.035 mmol/l) observed at 8.00 am to the highest level (1.028 +/- 0.084 mmol/l) at 6.00 pm. Female-we observed two peaks of serum magnesium concentrations: first at 8.00 pm (0.992 +/- 0.103 mmol/l) and second at 4.00 am. (0.982 +/- 0.094 mmol/l) with the lowest level at noon) 0.789 +/- 0.043 mmol/l. Differences between extreme levels were statistically significant.
Cardioversion is one of the most effective treatment in cardiac arrhythmias. However, this technique is painful it requires proper anaesthesia assuring stable circulatory and respiratory functions. The authors compared two anaesthetics: etomidate and propanidid. No significant difference in their effects on both circulation and respiration has been noted. Some differences between both drugs in the produced adverse reactions were however noted. Etomidate caused pain at the site of injection, propanidid allergic reactions in the form of skin rash.
This work aimed at establishing whether liver ability to biotransformation of drugs expressed by antipyrine kinetics is disturbed in peritoneally dialysed patients with end-stage renal failure. The investigations were carried out in 10 uraemic patients using the antipyrine test and comparing antipyrine kinetics with those obtained in 13 healthy individuals. At the time of investigations, standard clinical tests of liver function were normal and HBs antigen was absent in all patients. It was shown that peritoneally dialysed patients with end-stage renal failure had not significantly changed antipyrine elimination as compared with the group of healthy controls: t0.5 = 13.2 +/- 6.8 v. 11.8 +/- 8.1 h, plasma clearance = 50 +/- 30 v. 34 +/- 21 ml/min (x +/- SD). The obtained results indicate that antipyrine kinetics is within normal range in uraemic patients regularly dialysed suggesting cytochrome P-450 in microsomes not being markedly reduced.
In order to examine the circulatory and bronchospasmolytic activity, new 7-beta-hydroxy-gamma-N4-alkylpiperazinopropyl-8- benzylaminotheophyllines (1, 2, 3) were synthesized and converted to the water soluble dihydrochlorides (1a, 2a, 3a). They showed hypotensive and bronchodilatory effect.
The following novel compounds were synthesized: 1H-2, 3, 4, 9-tetrahydropyrido-[2, 3-e] [1, 4]-diazepino-2, 3, 9-trione 1a, 2-methyl-3, 4-dihydropyrido-[2, 3-d]-pyrimidin-4-one 2a, and their derivatives: N-methylmorpholino 1b and 2b, N-methylpiperidino 1c and 2c, N-(beta-hydroxy-gamma-morpholinopropyl) 1d and 2d, N-(beta-diethylaminoethyl) 1e and 2e, and 2-styryl 3a, 2-p-chlorotyryl 3b, and 3', 4', 5'-trimethoxystyryl 3c. The most potent hypotensive action was exerted by compound 2c (in a dose of 10 mg/kg), 2d (30 mg/kg), and 3a-3c (50 mg/kg).
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3 (3'-Morpholino-2'-hydroxypropoxy)--7--9 as well as 3 (3'-morpholino-2'-hydroxypropyloamino) 14 -- 16 derivatives of 1-methyl and 1-phenyl pyrazo-[3,4-b]-pyridines were prepared and screened for expected circulatory activity. Compounds 7, 11--14, 20 mg/kg, produced hypotension in cats; Compounds 7 and 14, 50--80 mg/kg, had antiarrhytmic action in BaCl2 -- induced arrhytmic in the rabbit.
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By aminoalkylation with diethylaminoethyl chloride of 3-hydroxypyrazo-[3,4-b]-pyridine 1 and its phenyl derivative 2 as well as 3-aminopyrazo-[3,4-b]-pyridine 7 and its phenyl derivative 8, basic ethers 5, 6 and aminoalkanoloamines 9 and 10 have been obtained. Compounds 5, 6 and 10 increased coronary blood flow of the isolated cat heart. At the concentration of 5 +/- 2 mg/ml shoved spasmolytic activity.
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