[Clinical efficacy and safety of levocarbastine++ in the therapy in children suffering from seasonal allergic rhinitis and conjunctivitis who are less than 12 year of age]. / Ocena skutecznosci klinicznej i bezpieczenstwa lewokabastyny w leczeniu pylkowicy u dzieci ponizej 12. roku zycia.

Levocabastine is an antihistaminic agent for topical application. It is without not advisable general side-effects and since many years is widely used for the treatment of pollinosis in adults and children more than 12 years of age. The group of 32 children aged from 5 to 11 years suffering from seasonal allergic rhinitis and conjunctivitis were treated by means of levocabastine applied topically by 20 days during the period of natural exposition to grass pollen. The clinical efficacy and tolerability including potential side-effects, were evaluated on the basis of clinical-laryngological investigations, visual analogs scales and diary cards filed in by parents of examined children. Levocabastine has been demonstrated to have rapid onset of action in children with SAR and the topical application of the drug does not irritate the mucosa of conjunctivas and nasal cavities.

Antagonistic properties of four suramin-related compounds at vascular purine P2X receptors in the pithed rat.

The dose-response curve for the vasopressor effect of alpha, beta-methylene ATP in pithed rats was influenced by four suramin-related drugs (each at 100 mumol/kg). The curve was shifted to the right by a factor of 8 by 'compound 3' and by a factor of 2 by two other derivatives, but was not affected by the fourth analogue. Compound 3 had no effect on the vasopressor response to noradrenaline or neuropeptide Y. In conclusion, compound 3 is a purine P2X receptor antagonist which is approximately as potent as suramin, and which, like suramin, does not exhibit antagonistic properties at alpha-adrenoceptors and neuropeptide y receptors.

ATP, alpha,beta-methylene ATP and suramin as tools for characterization of vascular P2x receptors in the pithed rat.

1. In pithed rats, the blood pressure effects of ATP, alpha,beta-methylene ATP (mATP), alpha-adrenoreceptor agonists and of electrical stimulation of the thoracolumbar sympathetic outflow were studied in the absence and presence of mATP, suramin and adrenoreceptor antagonists. 2. ATP elicited an initial rise in mean blood pressure followed by a decrease and a second increase. mATP produced a short-lived increase in blood pressure, whereas equieffective doses of noradrenaline, methoxamine and B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(5,4-d)-azepine) produced a more prolonged, biphasic pressor response. 3. In the presence of high doses of prazosin, rauwolscine plus propranolol, the initial vasopressor and the vasodepressor effect to ATP were not affected, whereas the delayed vasopressor response to ATP, the vasopressor response to electrical stimulation and even more so that to noradrenaline were suppressed. 4. Suramin, which by itself produced a short-lived decrease, followed by a persistent increase in blood pressure, decreased the pressor responses to ATP (initial phase), to mATP and to electrical stimulation without affecting the fall and second rise in blood pressure elicited by ATP and the pressor response to noradrenaline. 5. Desensitization of P2x receptors by a low dose of mATP abolished the initial vasopressor response to ATP but failed to affect the subsequent blood pressure effects of ATP as well as the pressor responses to noradrenaline and electrical stimulation. A high dose of mATP, in addition, decreased the vasopressor responses to noradrenaline, methoxamine, B-HT 920 and electrical stimulation; the delayed effects of ATP on blood pressure were not changed. 6. The electrically induced increase in blood pressure subsequent to administration of high doses of prazosin, rauwolscine plus propranolol was diminished by suramin and by the low and high dose of mATP. 7. The present study suggests that under certain circumstances ATP, which, added exogenously, has a triphasic effect on mean blood pressure, contributes to the electrically induced vasopressor response by activation of P2x receptors.

[Comparative study on myocardial damage in irradiated for a long time and nonirradiated rats after administration of FCOL]. / Vergleichende Studie über Myokardschädigungen nach Applikation von FCOL an langzeitbestrahlten und unbestrahlten Ratten.

The trials were made to assess the effect of FCOL (9-alpha-fluorocortisol + Na2HPO4) and the effect of K and Mg asparaginates and their mixtures on the modifications of Ca2+, Na+, and K+ ions and of the K/Na ratio in the myocardium of rats not irradiated or submitted to permanent whole-body irradiation (gamma irradiation with 0.57 Gy per day during 25 days, total accumulated dose 14.25 Gy; the trials were performed 25 days after the irradiation). The totality of reversible and irreversible functional modifications of the myocardium, expressed by the quantitative assessment of the K/Na ratio and the concentration of Ca2+ ions, was evaluated in order to determine the cardiotoxicity or cardioprotection. It was demonstrated that irradiation alone causes a slight irreversible modification in the myocardium which is not found in non-irradiated rats. FCOL itself increases the rate of Ca2+ and Na+ ions in irradiated and non-irradiated rats, but does not influence the quantity of K+ ions. Severe irreversible myocardial damages are caused by FCOL, but these damages are considerably lower in irradiated rats. Neither in irradiated nor in non-irradiated rats, the isomers of Mg asparaginate show any protective action against the cardiotoxic effect of FCOL. The isomers of K asparaginate, also combined with Mg asparaginates, as well as the preparation Inzolen exert a demonstrable protective effect against myocardial ion modifications following to application of FCOL. The protection is more efficient in irradiated rats.

Control and driving of pneumatic total artificial hearts TNS-BRNO-II and -III in long-term experiments.

Hemodynamic analysis was carried out during long-term experiments with the pneumatic total artificial hearts TNS-BRNO-II and TNS-BRNO-III to determine standard methods of starting artificial hearts and criteria for their long-term operation in vivo. In long-term experiments, regulatory mechanisms automatically regulating the systole length and diastolic aspiration pressure have also been verified. Comparison of hemodynamic variables obtained from invasive measurements with pneumatic pressure curves permitted the control and monitoring of the experiment in its entirety by noninvasive methods only. The control of the artificial heart using the Chirasist TN 3 and Chirasist TN 4 was adapted to specific properties of the pumps, above all to the functions of the atypical inlet valves. The terminal stages of the experiments have shown that a 100-ml pump can ensure survival of experimental calves up to 210 kg body weight.

Innervation of atrial stumps in calves living with the TNS-Brno II artificial heart.

The remnant stumps of the atria in six calves surviving with the artificial TNS-Brno II methacrylate heart for up to 5 months were examined by means of the Bodian silver-impregnating technique and by the formalin-induced fluorescence technique visualizing noradrenaline in monoaminergic nerve terminals. The degeneration of the nerve terminal system detected in animals surviving for 2 days and 1 week was followed by regeneration of the vegetative nerve system in four animals surviving for greater than 1 month. Moreover, thick myelinated nerves afferent in character were detected within the atrium of one animal surviving for 5 months.

Mechanisms causing the death of 8 calves surviving with implanted artificial heart from 31 to 173 days.

Causes of the death of four animals from the total of eight were technical failures (diaphragm perforations, disconnection of the quick-connector, and a failure of the supply of electric current which could not be prevented). Causes of the death of the remaining four animals were embolisation in the brain stem, embolisation in the superior mesenteric artery leading to diffuse peritonitis, ruptures of aorta and hemocoagulation disorder causing fatal gastrointestinal bleeding.

A comparative study of a group of eight calves, surviving longer than 1 month with the total artificial heart.

Over the last 2 1/2 years, eight calves with implanted total artificial hearts (from experimental group IV) have survived for greater than 1 month. In this group two subgroups were further differentiated, subgroup IVa, including three calves surviving 31, 35, and 75 days, and subgroup IVb, with five calves surviving 104, 142, 150, and 155 days and one calf still surviving greater than 160 days. Mean survival in the fourth group was greater than 106.5 days. The artificial ventricles used were the TNS-BRNO-II made of polymethylmethacrylate (seven calves) and the TNS-BRNO-III, made of segmented polyetherurethane (one calf). The controller and driving units were of our own design. The Chirasist-TN-3 and TN-4 worked without trouble over the total duration of the studies in all calves. Autoregulation of suction was used in three of these calves. All calves survived in good physiological condition; however, some common changes were observed in all of them, such as a gradual central venous pressure increase and liver enlargement. Anticoagulation therapy was used in all calves. Causes of death were technical in three cases and biological in four. Body weight gains were normal in the majority of these calves, with slight individual differences observed. Diaphragm mineralization of various degrees was observed in three cases. In one of them it was directly related to the cause of death. These results are very encouraging for further development of the total artificial heart research in our center.

Some problems associated with the implantation of a cardiac prosthesis and with early postoperative care in animals with a total artificial heart.

The progress in the methods and techniques for surgical implantation of the TAH has progressed in parallel with the technology and design of the cardiac prosthesis. During the period from December 1974 to May 1982 the authors performed altogether 75 orthotopic implantations of eight types of TAH in calves. The Soviet TAH type KEDR I-III was implanted in 26 calves, type MODUL to one calf. The American TAH JARVIK 3 was implanted in one calf and Czechoslovak TAH type TNS BRNO I-III in 47 calves. The modification of blood pump and improved system of its control provided for the limitation of the range of surgery and to shorten the time of operation and cardiopulmonary bypass. The methods of preoperative care, anaesthesia, cardiopulmonary bypass and postoperative care in our laboratory were gradually improving in parallel. This was associated with maximum survival time of animals in the course of the research period which gradually increased from 5.5 h in 1974 to 173 days in 1982. The chief experiences acquired from all experiments performed are presented and problems associated with the investigation of the TAH in general are discussed in this paper.

Reperfusion of coronary arteries after temporary occlusion in dogs.

The influence of previous pharmacotherapy or intra-aortic balloon counterpulsation (with thiamine infusion) on the effectiveness of reperfusion of the left anterior descending (LAD) coronary artery after 150 minutes of occlusion has been studied in dogs. The infarct size was determined by morphometric method 20 hours after the onset of ischaemia. Reperfusion 150 minutes after the occlusion of the LAD coronary artery resulted in a smaller infarct; however, no protective effect from pharmacological or mechanical heart support during the period of ischaemia was observed.

BRNO-I, an implantable, diaphragm-type total artificial heart: technical aspects of design.

The technical aspects of artificialheart design for experiments on calves are presented in this paper. The object of the design was to verify the basic anatomic and hemodynamic criteria for the design of more perfect cardiac prostheses. Each of the ventricles has a 100-ml stroke volume and is dismountable. Rigid parts are made of polymethylmethacrylate. The inlet valve has the shape of a flap. The outlet valve has two polyurethane reinforcing leaves. The diaphragm is also made of polyurethane. During tests using artificial circulation, a maximum cardiac output of 14.6 L/min was achieved. Typical sensitivity of flow on the atrial pressure is 0.3 L/min/torr at a frequency of 90 pulses per minute.

Determination of cardiac output of the artificial heart from the drive air flow.

An indication chamber, inserted between the right heart drive and the pump proper, was designed to provide continual measurement of the quantity of blood pumped by the pneumatic artificial heart. The flow is evaluated from the motion of a piston provided with a photoelectric transducer. The effect of compressibility of the drive gas on measurement accuracy is eliminated. The indication chamber provides for automatic replenishment of gas that escapes by diffusion and through minor leakage. During testing in an artificial circulation within the range of physiological conditions, measurement in accuracies did not exceed 5%.

The effect of preirradiation application of aspartic acid salts on hemopoietic recovery in X-irradiated mice.

The possibility of radioprotective action of K and Mg aspartate administered in tap water for ten days prior to X-irradiation was investigated in male mice of the strain C 57 Bl/10. In normal animals, thymus weight was found to be increased by 10-day treatment with K and Mg aspartate. The postirradiation regeneration of spleen weight and incorporation of radioactive iron into the spleen and femoral marrow following sublethal irradiation was favorably modified by the treatment used. Pretreatment of mice with K and Mg aspartate delays the onset of early deaths at irradiation with an absolutely lethal X-ray exposure and raises the percentage of surviving animals after nearly lethal exposures.

The effect of postirradiation application of aspartic acid salts on hemopoietic recovery in sublethally X-irradiated mice.

The effect of aspartic acid salts, especially of K and Mg aspartates, on certain hematological changes in the peripheral blood and hemopoietic organs of sublethally X-irradiated male mice of the strain C57Bl/10 was investigated. Salts of aspartic acid were administered in tap water after irradiation. A favorable effect of aspartic acid salts on erythropoietic recovery and on regeneration of thymus weight was found during the first two weeks after irradiation.