Progress in understanding electro-mechanical signalling in the myometrium.

In this review, we give a state-of-the-art account of uterine contractility, focussing on excitation-contraction (electro-mechanical) coupling (ECC). This will show how electrophysiological data and intracellular calcium measurements can be related to more modern techniques such as confocal microscopy and molecular biology, to advance our understanding of mechanical output and its modulation in the smooth muscle of the uterus, the myometrium. This new knowledge and understanding, for example concerning the role of the sarcoplasmic reticulum (SR), or stretch-activated K channels, when linked to biochemical and molecular pathways, provides a clearer and better informed basis for the development of new drugs and targets. These are urgently needed to combat dysfunctions in excitation-contraction coupling that are clinically challenging, such as preterm labour, slow to progress labours and post-partum haemorrhage. It remains the case that scientific progress still needs to be made in areas such as pacemaking and understanding interactions between the uterine environment and ion channel activity.

[Kinetic model of spermine effect on the Mg2+, ATP-dependent transport of Ca ions in the smooth muscle mitochondria].

In experiments, carried out with the use of a radioactive label (45Ca2+) on suspension of rat uterus myocytes treated with digitonin solution (0.1 mg/ml), influence of spermine on the Mg2+, ATP-dependent Ca2+ transport in the mitochondria was investigated. Ca2+ accumulation in the mitochondria was tested as such which was blocked by ruthenium red (10 microM) and was not sensitive to thapsigargin (100 nM). It was shown, that dependence of initial speed of Ca ions accumulation in the mitochondria on spermine concentration (0.1-10 mm) is described by a bell-shaped curve. Spermine concentration being increased in the range of 0.1-1 mM the stimulation of Ca2+ accumulation was observed, at the further increase in polyamine concentration up to 10 mM the suppression of this process took place. On the basis of the analysis of the authors' experimental results and the literature data the model of complex spermine action on Ca2+ accumulation in mitochondria was proposed and analyzed. The existence of two spermine binding sites on mitochondrial membrane--S1 and S2 occupation of which is connected to activation and inhibition of Ca(2+)-unipoter, accordingly, was taken into account. The kinetic analysis of the model which has been made in an equilibrium mode, allowed to calculate some important quantitative parameters describing spermine influence on Ca ions accumulation in mitochondria. It is supposed, that the proposed model can be useful in the further research of polyamine influence on transmembrane exchange of Ca ions in mitochondria.

[Modelling of Mg2+, ATP-dependent mitochondrial Ca ions transport in smooth muscle cells using protonophore CCCP-sensitive fluorescent tetracycline]. / Chutlyva do protonoforu CCCP zmina fluorestsentsiï tetratsiklinu za umov modeliuvannia Mg2+, ATP-zalezhnoho transportuvannia ioniv Ca v mitokhondriiakh hladen'koho m'iaza.

Mg2+, ATP-dependent Ca2+ accumulation in the rat myometrial mitochondria was investigated in complex experiment using Ca2+ isotope (45Ca2+) and Ca(2+)-sensitive label tetracycline. Monotonous increase of the fluorescence signal, insensitive to thapsigargin (100 nM) was observed with following establishing the stationary state of incubation at 2 min. which correlates with results obtained using isotope technique. Experiments with isotope label signify, that protonophore CCCP, ruthenium red and sodium azide, in concentration 1 microM, 10 microM and 10 mM respectively, totally inhibits the accumulation of the Ca ions in mitochondria. At the same time, in conditions of Mg2+, ATP-dependent Ca2+ accumulation modeling in these cellular structures, CCCP and sodium azide, used in the same concentration, diminished tetracycline fluorescence signal increase. In the same conditions, the introduction of the CCCP (1 mM) into the incubation medium at 75 sec. after initiation of the transport process induced reversible quenching of the tetracycline fluorescence signal to the level, observed in case of initial CCCP presence in the medium. According to data obtained in the experiment, using Ca2+ isotope, Ca(2+)-ionophore A-23187 induces both the reversible release of previously accumulated Ca ions, and cause reversible quenching of the tetracycline fluorescence signal to the level, observed in case of initial CCCP (1 mM) and sodium azide (10 mM) presence in the incubation medium. Conclusion was drawn that the thapsigargin-insensitive and CCCP, sodium azide and A-23187-sensitive tetracycline fluorescence increasing in case of modeling of Mg2+, ATP-dependent Ca2+ accumulation in myometrial mitochondria reflect the Ca2+ uniporter functioning in those subcellular structures.

[Allergization of the organism by Neisseria meningitidis. II. studies concerning the results of vaccine therapy in diseases caused by bacterial allergy (author's transl)]. / Allergisierung des Organismus durch Neisseria meningitidis II. Verfolgung der Ergebnisse der Vakzinotherapie bei Krankheiten auf Basis bakterieller Allergie.

A three years' study was performed regarding the influencing of vaccine therapy in 360 patients affected with diseases caused by bacterial allergy. An evaluation was made concerning the effects obtained by treatment with autovaccines in 110 patients, with stock vaccines in 60 patients, with autovaccines enriched with strain Neisseria meningitidis (N.m) in 60 patients, and with stock vaccines enriched with N.m. in 130 patients. N.m. was added to the vaccines because of its highly positive reaction in skin tests and its frequent occurrence in asthma patients (15.45%). A possible allergization of the organism by this microorganism was studied. A comparison between the final therapeutical results showed statistically far better treatment results through autovaccines enriched with N.m. (74.9%) in contrast to treatment with autovaccines where the percentage amounted to 71.7%, with stock vaccines to 64.9%, and stock vaccines enriched with N.m. to 64.6%. Our studies led to the suggestion that more attention should be paid to the presence of N.m. in patients affected with diseases caused by bacterial allergy and that studies on a possible contribution of the above microorganism in the sensibilization of the organism should be continued.

[Allergization of the body by Neisseria meningitidis. I. The problem of the occurrence of N. meningitidis in cases of bronchial asthma of bacterial etiology (author's transl)]. / Allergisierung des Organismus durch Neisseria meningitidis. I. Zur Problematik des Vorkommens von Neisseria meningitidis beim Asthma bronchiale bakterieller Atiologie.

The object of the authors work was the examination of nasopharyngeal swabs on the prevalence of Neisseria meningitidis. A group of 222 patients suffering from asthma bronchiale of bacteriological etiology was under observation in order to be able to prepare an autovaccine. Nasopharyngeal swabs were inoculated on special nutrient media. Neisseria meningitidis was found in 22%, mainly from nasopharyngeal swabs, together with Haemophilus sp. and Streptococcus pneumoniae. In 59% of examined cases the positive findings lasted longer than 1 year. 46% of isolated strains belonged to group B, about 30% of strains were untypable. The problem of allergisation of people suffering from asthma bronchiale with these strains and the question of preparing an autovaccine from Neisseria meningitidis is discussed.