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Biomedical subjects

A Jurkiewicz

Publications and source records attributed to A Jurkiewicz.

At least 73 records · Page 4Linked to original sources

The effect of propranolol on metabolism and on membrane-associated polysaccharide components of Herpetomonas muscarum muscarum.

The effects of propranolol on the metabolism (cell growth, cell differentiation and cell respiration) as well as on membrane-associated polysaccharide components of Herpetomonas muscarum muscarum were investigated. At the dose of 10(-2) and 10(-3) mM the drug increased significantly the number of the more differentiated opisthomastigote form of the protozoan, whereas at higher concentrations (10(-1) mM) total inhibition of growth occurred with gross cell lysis. Propranolol (10(-3) mM) enhanced the oxidation of glycerol and more markedly that of glucose, glutamic acid and proline. The pattern of the composition of membrane-associated polysaccharides was also substantially changed: the drug (10(-3) mM) induced a preferential synthesis of galactose and a marked decrease of xylose and mannose, whereas glucose content remained practically unchanged.

Animals↗

Contractile effect of vanadate and other vanadium compounds on the rat vas deferens.

Sodium metavanadate (NaVO3), vanadium pentoxide (V2O5) and vanadyl sulphate (VOSO4), evoked rhythmic and tonic contractions of the normal and reserpinized rat isolated vas deferens. Contractions were not observed by the use of vanadium trichloride (VCl3) The order of potency of these compounds, for their maximum contractile effects was NaVO3 greater than V2O5 greater than VOSO4 greater than VCl3. Differences in pD2 values were less than 0.5 long units in relation to the first compound. Vanadium-induced contractions were blocked by Ca2+ deprivation, nifedipine, Mg2+, Mn2+, Ni2+ and Co2+, indicating the involvement of a loosely bound or extracellular calcium-dependent mechanism. It is still unclear whether this calcium translocation was related, or not, to changes in Na+, K+-ATPase activity. Since ouabain blocked the action of vanadyl or vanadate non-competitively, it is concluded that vanadium compounds and ouabain induce their effects by interacting with different sites in vas deferens, both of which may or may not be located on the (Na+, K+)ATPase enzyme complex.

Animals↗

Changes in cell shape and induction of cell differentiation in the protozoan Herpetomonas samuelpessoai by cholinergic drugs.

Carbamylcholine, Pilocarpine and Atropine, but not Epinephrine, inhibited the motility of Herpetomonas samuelpessoai, when added to the suspension medium for 1 h. In addition, protozoan cells became spherical under the influence of atropine. This drug also induced the formation of the more differentiated opistomastigote form of the protozoan, in 60 per cent of growing cells, whereas these forms represented less than 5 per cent in untreated cultures. This may indicate that cholinergic receptors are present in this protozoan.

Animals↗

Relationship between modulation by estradiol, progesterone and calcium upon the pharmacological reactivity of uteri of dogs.

The influence of treatment with estradiol and progesterone, was studied on the contractions induced in immature dog uteri by histamine, acetylcholine, oxytocin and barium chloride, in vitro. Two parameters were measured from dose-response curves: rho and pD2. It was observed that although pD2 values were slightly affected by hormonal treatment, the values of rho for oxytocin and acetylcholine receptors were greatly reduced by estradiol treatment and further decreased by association of estradiol plus progesterone; the effects for histamine and barium chloride were less affected. Increasing Ca2+ concentration in the nutrient solution completely reverted the variations for rho values. The results indicate tat the effect of drugs on the dog uterus depends on the balance between the modulating actions of ovarian hormones and calcium.

Acetylcholine↗

Time-response curves for barium and noradrenaline in vas deferens of castrated rat.

Time-response curves for barium chloride and noradrenaline were obtained in the isolated vas deferens of 30-day castrated rats. The contractions induced by a maximal dose of barium chloride reached a peak after about 20-30 sec and then decreased to a lower level (fade). 5 min after drug addition the response had faded to about 20% of the peak contraction while in normal preparations it decreased to about 55%. When calcium was removed from the nutrient solution, both peak and 5-min effects of sequential doses were reduced, and fell progressively at a faster rate than in normal preparations. When Ca2+ concentration was increased from 1.8 mM up to 36.0 mM, fading was abolished. The data were analyzed on the basis of receptor changes involving the translocation of calcium in smooth muscle.

Animals↗

Relative responsiveness (rho): a critical analysis of a new method in receptor differentiation.

The rho ratio, which measures the capability of a receptor system to induce a maximal contraction after saturation by a full agonist was analysed from the standpoint of its variability considering the values obtained either for a given receptor system in the same type of preparation or for different types of preparation. This variability was discussed on the grounds of receptor theory, as the basis for a new method in receptor differentiation.

Animals↗

A comparative study of the effects induced by MCN-A-343 and acetylcholine on the isolated toad rectus abdominis.

McN-A-343 (McN), a non nicotinic ganglionic stimulant, induced slow contractile responses of the toad rectus abdominis. A relaxation was also observed when large doses were added in the presence of a contraction caused by acetylcholine (Ach). The relaxation induced by McN could not be overcome by increasing Ach concentration. Bell-shaped log dose-response curves were obtained for McN. d-Tubocurarine caused an unusual change on these curves, suggesting an indirect action of the agonist. This possibility was corroborated by the fact that hemicholinium, procaine, and cold storage of the muscle caused a marked decrease of the organ sensitivity to McN but not to ACh.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

Dual effect of alpha-adrenoceptor antagonists in rat isolated vas deferens.

1 In rat isolated vas deferens, the isotonic contractile responses to low doses of noradrenaline or adrenaline were antagonized, and those to high doses were potentiated, by yohimbine, piperoxan, phentolamine and tolazoline. Effects due to intermediate doses were not affected, or were potentiated within about 30 min, following an initial inhibition. 2 The alpha-adrenoceptor blockers thus caused a shift to the right and an increase of the maximum height of log dose-response curves of alpha-adrenoceptor stimulants. For a given dose of antagonist, the onset was slower for the potentiating than for the blocking effect. 3 The shift to the right induced by piperoxan and yohimbine on dose-response curves of noradrenaline and adrenaline was analysed with the Schild plot, and the slopes obtained, around 0.3, were lower than expected from receptor theory. When cocaine was used to block neuronal uptake, the slopes were close to 1.0. 4 The increase in maximum response to noradrenaline and adrenaline induced by alpha-adrenoceptor blockers was dependent on the time of incubation, on the dose of antagonist, and on the initial height of responses to the agonist. A less pronounced potentiation was also obtained when acetylcholine was used as agonist. 5 The findings are explained in terms of receptor theory as being due to a dual effect of alpha-adrenoceptor antagonists; competitive antagonism proper, which may be disclosed after blockade of neuronal uptake, and an interaction at a different locus, which results in potentiation of the effects of noradrenaline and adrenaline.

Adrenergic alpha-Antagonists↗

Effect of full agonists following calcium deprivation in rat vas deferens.

The contractile effects of maximum doses of adrenaline, noradrenaline, methacholine, acetylcholine, serotonin and barium chloride were studied following substitution of a medium without calcium for the normal nutrient solution. Except for the last agonist, the effects fall to about 10% within the first 3 min with prompt return to normal value upon reintroduction of regular fluid. This recovery is, however, slower if the previous incubation in Ca-free solution is prolonged. When barium chloride is used in a calcium-free medium, the maximum height of contractions falls exponentially at a t1/2 of about 180 min. This decay can be accelerated by giving successive 5-min doses of the agonist or by using EDTA. It is hypothesised that excitation--contraction coupling in rat vas deferens depends on at least two different calcium sources: a deep site associated with the effects of barium, and a superficial one, related to the other agonists. To explain the slow recovery after prolonged calcium lack, a third compartment in series with the latter is suggested. No indication is found that the biphasic effects of barium depend on two different calcium pools.

Acetylcholine↗

Autonomic dysfunction of rat jejunum submitted to cold ischemic preservation is prevented by heparin.

Previous studies suggest that cold ischemic preservation (CIP) employed in small bowel transplantation promotes loss of intestinal motility due to severe lesions in autonomic enteric nerves. This autonomic dysfunction may be prevented by antioxidant agents. In this work, we investigated whether preservation with heparin prevented autonomic dysfunction of rat jejunum submitted to CIP for a long time. Jejunal segments (2 cm) of Wistar rats (12 to 16 weeks old) were preserved at 4 degrees C in Ringer's lactate solution without (-) or with (+) 100 UI/mL heparin (H). After preservation for 12 hours, H+ and H- preparations were mounted in parallel in isolated organ baths containing 10 mL Tyrode's solution at 37 degrees C for the study of neurogenic contractions evoked by electrical field stimulation (EFS; 10-30 Hz, 1-ms duration, 60 V) or by stimulation of nicotinic (NIC) or muscarinic (carbachol, CCh) cholinoceptors. The effects of NIC (hexamethonium, HEX) and muscarinic (atropine, ATR) antagonists were studied on these contractions. Contractions induced by EFS (30 Hz) were four times greater in H+ (1.02 +/- 0.12 g) versus H- (0.26 +/- 0.07 g), while contractions induced by NIC (1 mmol/L) were also four times higher in H+ (1.07 +/- 0.10 g) than H- (0.25 +/- 0.09 g) preparations. In addition, contractions induced by CCh (1 mmol/L) were two times higher in H+ (1.21 +/- 0.13 g) than in H- (0.65 +/- 0.10 g). EFS, NIC, and CCh contractions were inhibited by pretreatment of jejunum with HEX or ATR (1 mumol/L/30 min), in H+ and H-. These results indicated that addition of heparin to a preservation solution attenuated the autonomic dysfunction of rat jejunum submitted to CIP for a long time.

Animals↗

Atenolol attenuates autonomic dysfunction of rat jejunum submitted to cold ischemic preservation.

In vitro studies have demonstrated that cold ischemic preservation (CIP) employed in small bowel transplantation produces loss of intestinal motility due to severe lesions of autonomic enteric nerves and that this autonomic dysfunction is attenuated by antioxidant agents. In this work, we investigated whether preservation with atenolol attenuated autonomic dysfunction of rat jejunum submitted to long-term CIP. Jejunal segments (2 cm) of Wistar rats (12 to 16 weeks old) were surgically isolated and preserved at 4 degrees C in Ringer's lactate solution without (-) or with (+) 1 mumol/L atenolol (AT). After preservation for 12 hours, AT+ and AT- preparations were mounted in parallel in isolated organ baths containing 10 mL Tyrode's solution at 37 degrees C for the study of neurogenic contractions evoked by electrical field stimulation (EFS; 10 to 30 Hz, 1-ms duration, 60 V) or by stimulation with nicotinic (nicotine, NIC) or muscarinic (carbachol, CCh) cholinoceptor agents as well as nicotine (hexamethonium, HEX) and muscarinic (atropine, ATR) antagonists. Contractions induced by EFS (30 Hz) were 46% higher in AT+ (0.38 +/- 0.02 g) than AT- (0.26 +/- 0.01 g), while contractions induced by NIC (1 mmol/L) were 84% higher in AT+ (0.46 +/- 0.03 g) than in AT- (0.25 +/- 0.02 g). In addition, contractions induced by CCh (1 mmol/L) were 34% higher in AT+ (0.87 +/- 0.06 g) than in AT- (0.65 +/- 0.08 g). EFS-, NIC-, and CCh-induced contractions were inhibited by pretreatment of jejunum with HEX or ATR (1 mumol/30 min), in AT+ and AT-. These results suggest that addition of atenolol in the preservation solution attenuated autonomic dysfunction of rat jejunum submitted to long-term CIP.

Adrenergic beta-Antagonists↗

Heterogeneity of late-infantile neuronal ceroid lipofuscinosis.

PURPOSE: Late-infantile neuronal ceroid lipofuscinosis (LINCL), an autosomal recessively inherited lysosomal storage disorder characterized by autofluorescent inclusions and rapid progression of neurodegeneration, is due to CLN2 gene mutations. However, CLN2 mutation analysis has failed to identify some clinically diagnosed "late-infantile" NCL cases. This study was conducted to further characterize genetic heterogeneity in families affected by LINCL. METHODS: DNA mutations in the CLN1, CLN2, and CLN3 genes that underlie INCL (infantile NCL), LINCL, and JNCL (juvenile NCL), respectively, were studied with molecular analyses. RESULTS: A total of 252 families affected by childhood NCL were studied. Of 109 families clinically diagnosed as having LINCL, 3 were determined to have either INCL or JNCL by identification of mutation(s) in CLN1 or CLN3. Six families diagnosed initially as having JNCL were found to have LINCL based on the finding of mutations in the CLN2 gene. In addition, several novel mutations were identified. CONCLUSIONS: Clinical and genetic heterogeneity of LINCL was demonstrated in nine LINCL families studied.

Aminopeptidases↗

Changes in cell surface anionogenic groups induced by propranolol in Herpetomonas muscarum muscarum.

The effects of propranolol (10(-3) mM) on the surface anionic groups of Herpetomonas muscarum muscarum were analysed by cell electrophoresis, by ultrastructural cytochemistry and by identification of sialic acids using paper chromatography. Differentiation of H. muscarum muscarum induced by propranolol treatment caused a significant increase in the net negative surface charge. Binding of cationized ferritin (CF) and colloidal iron hydroxide particles was observed at the cell surface of both untreated and propranolol-treated cells. In cells incubated in the presence of the drug the CF particles were distributed in all membrane regions. However, there were small areas where the particles were absent. In H. muscarum muscarum exposed to propranolol the density of residues of sialic acid per cell was higher, and the agglutinating activity with Sendai virus was more intense. However, the pattern of sialic acid, characterized by the presence of N-acetylneuraminic acid derivative, was not modified upon cell interaction with the drug. Treatment of both control and propranolol-treated protozoa with neuraminidase significantly reduced the surface charge. These findings suggest that sialic acid residues are the major anionogenic groups exposed on the surface of H. muscarum muscarum.

Agglutination↗