Cholinergic responses of ileal longitudinal muscle under short-lasting exposure to cupric ions.

1 The effect of short-term exposure to cupric ions (Cu2+) on electric field-stimulated (EFS) or agonist-induced contractions of guinea-pig isolated ileum was studied. 2 EFS elicited tetrodotoxin- and atropine-sensitive contractions that were concentration dependently inhibited by Cu2+ (IC50 = 14.7 +/- 4.2 microm). Maximal inhibition (90.4 +/- 3.1% of baseline contractions) was attained with 30 microm Cu2+. 3 Carbachol induced concentration-dependent contractions (EC50 = 0.021 +/- 0.004 microm) that were inhibited by 0.3 microm atropine to a non-competitive manner (decreased maximal response, EC50 value = 0.26 +/- 0.04 microm, K(e) = 0.026 microm). Cu2+ (15 microm) potentiated contractions induced by carbachol, such that the maximum response was increased by 30.3 +/- 10.4%. 4 Histamine induced concentration-dependent contractions of the longitudinal muscle (EC50 = 0.11 +/- 0.03 microm). Dyphenhydramine (0.1 microm) decreased the maximum response to histamine and shifted the curve to the right (EC50 value = 4.71 +/- 0.35 microm, K(e) = 0.0024 microm). Cu2+ (15 microm) caused a rightward shift of the histamine concentration-response curve (EC50 = 0.61 +/- 0.1 microm) without changing the maximum response. Serotonin induced concentration-dependent contractions at concentrations higher than 10 nM (EC50 value of 0.34 +/- 0.12 microm) were not significantly affected by 15 microm Cu2+. 5 Our results suggest that in ileal longitudinal muscle, Cu2+ inhibits cholinergic neurotransmission but also facilitates postsynaptic muscarinic receptor responses.

Time-related heart autonomic balance characteristics in healthy subjects.

Changes of the heart autonomic balance between morning (8-9 h) and afternoon (14-15 h) measurements were studied in 22 healthy subjects. The selection of these two daytime periods was substantiated by the established higher risk of cardiovascular incidents in the morning and the relative balance of the vegetative nervous system in the afternoon hours. The changes were analysed by RR-variability indices from ECG recordings in the resting state and with vegetative nervous system stimulation by the handgrip test and Valsalva manoeuvre. It was shown that there were no significant differences between the morning and afternoon values of the respective indices, between morning and afternoon handgrip tests and between morning and afternoon Valsalva manoeuvres. However, there were significant differences in comparison of the index values between resting state and handgrip test and resting state and Valsalva manoeuvre, both from morning and afternoon measurements. Moreover, the significantly differing indices were clustered in different groupings, when comparing resting state recordings with morning and afternoon stimulation tests. For this reason, the authors introduced an indicator for time-related autonomic balance changes. The indicator evaluates the power of each RR-variability index to respond to changes in the autonomic control, in comparisons between resting state and stimulation data in the morning and afternoon measurements. These evaluations showed low power of the frequency-domain indices to respond to time-related autonomic balance changes in stimulation, with respect to the resting state. The time-domain indices have considerably higher power to react to relative morning and afternoon changes in the two vegetative nervous system components. Based on the estimations of the RR-variability indices obtained by the introduced indicator, a profile was constructed to represent time-related heart autonomic balance changes in healthy subjects. It was established that in spite of the relative stability of the vegetative nervous system in healthy subjects, hypersympatheticotonia and relatively lower parasympathetic tone were present in the risky morning hours.

[Studies on restraint ulcers in rats in conditions of acute copper deficiency]. / Studovi imobilizatsionni iazvi pri plukhove v usloviiata na ostur meden defitsit.

In the present experiment, we have investigated the impact of the acute copper deficiency on the pathogenesis of stress ulcers' formation in rats during cold-restraint stress. A powdered milk diet, lasting for 5 days, causes a significantly decrease of stomach copper content in rat, comparing to content in rats receiving standard laboratory diet. The severity of mucosal disturbances, expressed as total number and area of stress ulcers, is most prominent in animals receiving hypocupric diet. Their treatment with Ranitidine extends the morphological disturbances in the stomach mucosa and produces highest level of lipid peroxidation and lowest activity of superoxide dismutase in the stomach compared to the other groups. In conclusion, the appropriate copper balance plays an essential role for the natural resistance of the stomach mucosa and Ranitidine, in conditions of acute copper deficiency, makes deeper the disturbances produced by stress.

[The effect of the zinc-containing preparation Oxyrich in the treatment of chronic saturnism (preliminary results)]. / Pouchvane efekta na tsink-sudurzhashtiia preparat Oxyrich pri lechenie na khronichen saturnizum (predvaritelni rezultati).

Under indoor conditions the effect of the Bulgarian zinc-containing preparation Oxyrich was studied in the treatment of 12 workers (males) with chronic saturnism. The preparation was orally administered in a dose of 150 mg (0.45 mmol Zn++) daily for 10 days in three equal receivings, after which three day antidotal therapy with CaNa2 EDTA was carried out according to the classic schedule. The complex investigation of the workers besides the clinical exmination included some key indices of the porphirine metabolism (5-ALK-D, 5-ALK, free protoporphirine in the red bolld cells), as well as the content of zinc and lead in the blood and their excretion with the urine prior and post the administration of Oxyrich and CaNa2 EDTA. The results of the carried out study revealed that the therapy with Oxyrich demonstrated a tendency to normalization of the activity of 5-ALK-D and decrease of the elimination of 5-ALK. This gave grounds for further study with higher doses of Oxyrich, as well as enlargement of the spectrum of the indices of the porphirine metabolism.

[Crow-Fukase syndrome--the first case report in Bulgaria]. / Sindrom na Crow--Fukase--opisanie na purviia sluchai u nas.

A case of a 53 years old woman with Crow-Fukase's syndrome, the first case diagnosed and described in Bulgaria, is presented. The patient presented with polyneuropathy (predominantly locomotor, better expressed in the legs and less expressed in the hands, with hyperproteinorachia), anasarca (peripherial edema, ascites, hydrothorax), skin changes (hyperpigmentations), endocrinopathy (transitory carbohydrate intolerance), dysglobulinemia, organomegaly (hepatomegaly).

[Ischemic heart disease--clinical, biochemical and immunobiological parallels]. / Iskhemichna bolest na surtseto--klinichni, biokhimichni i imunobiologichni paraleli.

In patients with various forms of ischemic heart disease the following indices were examined by radial immunodiffusion: alpha-1-acid glycoprotein, alpha-1-antitrypsin, haptoglobin, alpha-2-glycoprotein, beta-2-glycoprotein, immunoglobulin, C3 and C4 complement fractions. The changes in the serum glycoproteins during the acute phase of myocardial infarction are pointed out. The changes in the immunoglobulins and the complement fractions in patients with ischemic heart disease are discussed. Their determination in patients with stenocardia and past myocardial infarction is of no diagnostic value.

[Clinical studies of celiprolol in the treatment of arterial hypertension]. / Klinichni prouchvaniia na tseliprolol pri lechenie naarterialna khipertoniia.

The antihypertensive effect of the preparation celiprolol was studied in a double blind experiment versus acebutolol in 60 patients (30 males and 30 females), with an average age 40 years. Only patients with hypertonic diseases, stage I-II, according to WHO classification were included in the study. The treatment Lasted 4 weeks. The criteria for a good effect were the normalization of the blood pressure and the absence of adverse effects. There was no statistically significant difference between the percentages of the reduced blood pressure, attained by both preparations. By the end of 4th week, 56.7 per cent of the treated with celiprolol were with normalized blood pressure, and 46,7 per cent--with acebutolol. The following adverse effects were observed: light gastrointestinal manifestations, weakness, dizziness, tremor, impotence. In some of the patients those effects were transitory but in 4 patients, treated with acebutolol, the treatment was discontinued because of the adverse effects.

[Possible role of apometallothioneins]. / Vuzmozhna rolia na apometalotioneinite.

A hypothesis is proposed admitting the participation of apometallothioneines (AMT) as a common link in the etiopathogenesis of hypertonic disease (HD) and some diseases with polygene heredity. The preconditions of the hypothesis are discussed (role of genetic disposition, external factors as salt, stress, tobacco smoking, alcohol, microelements--V and Cd and glucocorticoids in the origination of arterial hypertension). AMT homeostasis is discussed as well as the possible connection with the metabolism of Zn and Cu and Cu in organism. The chelating capacity of AMT makes it a potential regulatory protein, associated with the activity of Zn- and Cu-dependent enzymes and metalloenzymes. The mosaicism of pathology is explained with the genetic polymorphism of those enzymes (D beta H, MAO, etc), regardless of the common etiopathogenetic link. Some schemes are presented illustrating the hypothesis. The tendencies of the future studies are outlined in searching of direct proofs of the hypothesis.

[Viskaldix in the treatment of arterial hypertension]. / Viskaldix v lechenieto na arterialna khipertoniia.

Viskaldix, a combination of Pindolol (Visken)--10 mg with Clopamide--5 mg, was administered to 15 patients with arterial hypertension. The follow up of the patients was according to a previous plan, the preparation administered according, to a schedule. In the determination of the stage of the disease, consideration was mainly given to the values of the diastolic pressure, measured in a lying position. The patients examined were of the following age: to 40--I patient; to 50-7 patients; to 60--7 patients. Seven patients were at the stage I, 4 patients--stage OII and 4 patients--stage III. Reduction of systolic and diastolic pressure with more than 1.33 kPa (10 mm Hg column) both in a lying and standing position were recorded in 2/3 of the patients with the treatment carried out. The effect on the blood pressure, was noticed to develop in 1/3 of the patients with the administration of 2 tablets daily. The blood pressure of only one patient failed to respond to the treatment.

[Changes in the gonads and reproductive capacity of white rats after oral maneb poisoning]. / Promeni v gonadite i v sposobnostta za reproduktsiia na beli plukhove sled oralna intoksikatsiia s maneb.

Changes in the gonads and reproduction capacity of white rats following oral intoxication with maneb are studied. The preparation at doses 1/10, 1/50, 1/100 and 1/5000 LD50 is administered to the starting generation of white rats twice weekly. Changes in the gonads--biochemical, histological, histoenzymatic and electron microscopic--are established, as well as a capacity for reproduction of the starting I and II offspring. The results show a clearcut gonadotropic effect of the preparation, manifested by morphological changes in the starting generation, and by changes in fertility, gestation, survival and lactation of the starting I and II offspring.