Péter Tóth

Depolarization promotes caffeine induced [3H]-noradrenaline release in calcium-free solution from peripheral sympathetic nerves

The transmitter releasing action of caffeine was studied in the absence of extracellular Ca2+ from the peripheral sympathetic nerves of the rabbit main pulmonary artery. Caffeine (10 mM) increased the release of [3H]-noradrenaline moderately, but not significantly in Ca2(+)-free (+1 mM EGTA) Krebs solution. When peripheral nerve endings/varicosities were depolarized by elevating extracellular K+ to 47.2 mM and 70.8 mM in Ca2(+)-free solution, the transmitter releasing effect of 10 mM caffeine became significant. Ca2+ removal itself transiently increased the [3H]-noradrenaline outflow. In the individual experiments the amount of the caffeine evoked transmitter release at 47.2 mM and 70.8 mM K(+)-depolarization was inversely correlated to the release evoked by Ca2(+)-removal. Our results suggest that caffeine-sensitive calcium stores are present in peripheral nerve terminals of rabbit pulmonary artery, and part of the caffeine sensitive calcium stores may discharge during Ca2(+)-removal from the extracellular solution.

[3H]Noradrenaline-releasing action of vinpocetine in the isolated main pulmonary artery of the rabbit

Vinpocetine (10−6 − 3 × 10−5 M) increased both the resting and the nerve stimulation‐evoked release of [3H]noradrenaline from the isolated main pulmonary artery of the rabbit in the presence of uptake blockers (cocaine, 3 × 10−5 M; corticosterone, 5 × 10−5 M), and inhibited the nerve stimulation‐evoked postsynaptic response. The resting transmitter releasing action of vinpocetine increased in the absence of cocaine. Exogenously applied (−)noradrenaline [(−)NA] (10−6 M) or clonidine (10−6 M) inhibited the vinpocetine (3 × 10−5 M)‐potentiated [3H]NA release and contracted the circular muscle. The clonidine‐induced contraction was abolished by 10−7 M prazosin. The inhibitory action of (−)‐NA on vinpocetine‐potentiated [3H]NA release was partly antagonized by 3 × 10−7 M yohimbine, a preferential α2‐adrenoceptor blocker. In Ca‐free Krebs solution containing 1 mM EGTA the neurotransmitter releasing action of vinpocetine was abolished, however, its stimulating action on the resting [3H]NA outflow was not changed. In Na‐pump‐inhibited arteries (K‐free solution), where both the resting and the nerve stimulation‐evoked release of neurotransmitter had already been increased, vinpocetine further enhanced the nerve stimulation‐evoked release of [3H]NA. It is concluded that vinpocetine may have α2‐ and α1‐adrenoceptor blocking action, as well as a tyramine‐like effect. The presynaptic neurotransmitter releasing action of vinpocetine is presumably the consequence of its inhibitory action on the Ca‐pump which is suggested by the finding that in K‐free solution vinpocetine was able to enhance further the release of neurotransmitter.

The action of excess potassium and calcium on ouabain‐evoked [3H]‐noradrenaline release from the rabbit pulmonary artery

1 [3H]‐noradrenaline ([3H]‐NA) release from the main pulmonary artery of the rabbit has been measured in the presence of neuronal (cocaine, 3 × 10−5 M) and extraneuronal (corticosterone, 5 × 10−5 M) uptake blockers. 2 Removal of K from the external medium increased the [3H]‐NA release. In the absence of external K, ouabain (10−4 M) further enhanced the neurotransmitter release. The ‘K‐free’ stimulated [3H]‐NA release was inhibited by an increase of external Ca (7.5 mM), an action antagonized by ouabain. 3 After preperfusion of the preparations for 30 min with either excess K (23.6 mM) or excess Ca (7.5 mM), the ouabain‐stimulated [3H]‐NA release was inhibited by about 50%; the rates of inhibition did not differ significantly from each other. However, the characteristic initial delay before ouabain‐evoked neurotransmitter release was shortened in excess K, and prolonged in excess Ca‐containing solution. 4 When both excess K and Ca were applied together 30 min before ouabain perfusion, the action of ouabain in releasing neurotransmitter was also inhibited but the rate of inhibition did not differ significantly from that seen when K or Ca were applied separately. The action of K in shortening the initial delay was partly antagonized by Ca. 5 Excess Ca antagonized the inhibition of ouabain‐stimulated [3H]‐NA release caused by excess K when Ca and ouabain were applied together after 30 min preperfusion with excess K‐containing solution. Again excess Ca failed to inhibit the ouabain‐evoked neurotransmitter release if ouabain and excess K were applied together after excess Ca preperfusion (30 min). In both cases the initial delay of ouabain action was greatly shortened. 6 The results suggest a Na‐Ca competition at the external activation site of the nerve terminal sodium‐pump similar to that of Na‐K competition. Furthermore it seems that there is a sort of K‐Ca competition as well, suggested by the finding that excess Ca prevented the inhibition caused by excess K of ouabain‐evoked noradrenaline release and vice versa.

Transmitter releasing action of selegiline ((—)‐deprenyl) from peripheral sympathetic nerves under different experimental conditions

A high concentration of selegiline ((—)‐deprenyl; 10−4M) potentiated low frequency (2 Hz) nerve stimulation‐evoked release of [3H]noradrenaline from the isolated main pulmonary artery of the rabbit in the presence of neuronal (cocaine, 3 times 10−5M) and extraneuronal (corticosterone, 5 times 10−5M) uptake blockers, and inhibited the postsynaptic response. The transmitter‐releasing action of 10−4M selegiline was inhibited by a moderate increase of external K+ (23ṁ6mM). Excess K+ by itself abolished the nerve‐evoked release of [3H]noradrenaline but did not increase the resting outflow of radioactivity. Excess Ca2+ (7ṁ mM) increased the stimulation‐evoked transmitter release. In the presence of excess Ca2+, selegiline (10−4M) was effective in increasing the [3H]noradrenaline release in response to nerve‐stimulation. Excess Ca2+ partly antagonized the postsynaptic inhibitory action of selegiline. In Ca2+‐free, 1 mM EGTA‐containing Krebs solution both the nerve‐evoked 3H release and the transmitter releasing action of selegiline were abolished, in agreement with the ‘Ca‐hypothesis’. The voltage‐dependent K+‐channel blocker, 4‐ami‐nopyridine (10−5M), increased the nerve‐stimulation‐evoked release of tritium from arteries. If selegiline was also present in the perfusion medium the nerve‐evoked transmitter release further increased. 4‐Aminopyridine completely antagonized the inhibitory action of selegiline on the postsynaptic contraction.

Dependence of release of [3H]noradrenaline from rabbit pulmonary artery on internal sodium.

1. [3H]Noradrenaline ([3H]NA) release from the isolated main pulmonary artery of the rabbit has been measured in the presence of uptake blockers (cocaine, 3 x 10(‐5) M, and corticosterone, 5 x 10(‐5) M) and after blocking the monoamine oxidase enzyme by pargyline (1.2 x 10(‐4) M). 2. In normal Krebs solution Mn2+ (2 mM) significantly inhibited both [3H]NA release (approximately 80%; P < 0.001) and the contraction following 2 Hz field stimulation. 3. In Ca(2+)‐free, EGTA (1 mM)‐containing solution, the Na+ pump was inhibited by removal of K+ from the external medium. In Na+ pump‐inhibited arteries, 2 mM Mn2+ (free Mn2+, 1 mM) increased the spontaneous release of [3H]NA according to the time of Na+ loading. TTX (10(‐7) M) did not inhibit significantly the Mn(2+)‐induced [3H]NA release from Na(+)‐loaded preparations (percentage inhibition, approximately 24; P > 0.30). 4. Without Na+ loading (Ca2+ free, EGTA alone), Mn2+ failed to promote 3H release from arteries. 5. With constant Na+ loading (120 min ‘K(+)‐free’ perfusion in Ca(2+)‐free, 1 mM EGTA‐containing solution), the release of 3H was also directly dependent on free Mn2+ concentration (0.2, 0.6 and 1 mM). 6. The Mn2+ (2 mM; free Mn2+, 1 mM)‐induced 3H release from Na(+)‐loaded nerves (120 min ‘K(+)‐free’, perfusion) was further enhanced, when external Na+ was simultaneously reduced from 139.2 to 26.2 mM (choline+ or sucrose substitution). 7. Diphenylhydantoin (DPH, 10(‐4) M) significantly reduced the Mn(2+)‐evoked 3H release (approximately 44%; P < 0.02) when it was present during ‘K(+)‐free’, perfusion. 8. Mn2+ was ineffective in releasing 3H if the Na+ pump was previously reactivated by readmission of K+ to Na(+)‐loaded arteries. 9. It is concluded that in Ca(2+)‐free solution Mn2+ releases neurotransmitter in a manner which depends on the degree of loading with internal Na+. The results suggest this depends at least partly on a block of Ca2+ efflux.

Prognosztikai faktorok komplex vizsgálata krónikus lymphocytás leukémiában

INTRODUCTION Many new prognostic factors established in recent years in chronic lymphocytic leukemia. May help predicting survival. AIMS The goal of the present study was to determine the frequency and the correlation of these novel prognostic factors in samples of 419 leukemia patients. METHODS The mutation status of the IgH gene was evaluated in 160 cases. RESULTS In 62% of cases, non-mutated IgH gene was found, the heavy chain family usage was different in mutated and non-mutated cases. The CD38 expression demonstrated 78% concordance with the mutation status, the ZAP-70 expression failed to show any correlation. Cytogenetic abnormalities were seen in 76% of cases, the most frequent were del(13q) (57%), trisomy 12 (15%), del(11q) (12%) and del(17p) (6%). 95% of cases with del(11q) harbored non-mutated, 74% of cases with del(13q) as the sole anomaly demonstrated mutated IgH genes. CONCLUSIONS The parameters analysed are not independent of each other, utilization of them in the clinical routine needs careful planning.

Myocardial infarction in an young patient associated with oral contraceptive, smoking and elevated cholesterol level.

This case report focuses on the association of smoking and elevated cholesterol levels as risk factors for how improper use of oral contraceptive could lead to myocardial infarction in a young patient. The report discusses risk factors for myocardial infarction and the increase in risk of cardiovascular disease due to smoking. Included in the report is a summary of guidelines by the American college of cardiology for prescribing contraceptives for patients at increased risk for cardiovascular disease whose use could help in better care of patients seeking contraceptive advice and to avoid serious adverse events.

Myocardial infarction associated with oral contraceptive use, smoking and elevated cholesterol level in a young patient

Oral hormonal contraceptives are the safest methods for young patients to avoid unwanted pregnancy. They are well accepted and have certain beneficial effects; however, physicians should pay attention to risk factors even when applied in young age. Obesity, dyslipidemia, smoking and oral contraceptive pills alone or in combination may lead to serious adverse events. Authors present a young woman who developed acute myocardial infarction in association with several unconsidered risk factors including the use of contraceptive pills.

Spontaneous aortic rupture during pregnancy

Aortic dissection is a rare entity. Half of the aortic dissection cases occur during pregnancy in women under the age of 40. The authors report a case of a multiparous woman at the third trimester of her sixth pregnancy, who died from a sudden and intractable cardiovascular shock. Autopsy revealed the dissection of the ascending aorta. The case is interesting, especially because in the pregnant womans family it was not the first sudden death during pregnancy. Authors review the relevant literature regarding the symptoms and the genetic basis of this rare but potentially lethal complication of pregnancy.

High early uterine vascular resistance values increase the risk of adverse pregnancy outcome independently from placental VEGF and VEGFR1 reactivities.

OBJECTIVE From data in the literature, we hypothesized that high vascular resistance values in the uterine arteries at the end of the first trimester would increase adverse pregnancy outcomes and therefore might be accompanied by changes in VEGF/VEGFR1 immunoreactivities. STUDY DESIGN In our university hospital 82 women (Study I n=62 and Study II n=20) were divided into two groups according to their uterine vascular resistance values. Uterine vascular resistance values were measured in the 10-13th weeks of gestation by color-Doppler ultrasonography. Women were divided into low and high vascular resistance groups. In the prospective follow-up study (Study I) the data of the pregnancy outcome were recorded. In cross-sectional study (Study II), VEGF and VEGFR1 immunoreactivities were measured on the tissue samples from women who underwent termination of pregnancy. RESULTS In the high vascular resistance group (PI>2.3), the probability of adverse pregnancy outcome was significantly higher (40.0% vs. 12.8%). No differences in VEGF and VEGFR1 immunoreactivities were observed between groups. In both groups, intense VEGF immunoreactivity was observed in the maternal glandular epithelium and in the decidual cells. Weak reactivity was observed in the villous trophoblast. VEGFR1 immunoreactivity was intense in all regions. CONCLUSIONS Our data suggest that high vascular resistance values in the first trimester are independent from VEGF/VEGFR1 immunoreactivities and markedly increase the probability of adverse pregnancy outcomes. This may be used for early screening of pregnant women in the first trimester.