The effect of renal function of an augmentation of the excretory renal mass was investigated in 10 dogs without drug treatment and in 10 animals with alpha-receptor blockade. In the untreated group, augmentation of excretory renal mass by transplantation into the neck of one pair of kidneys isolated from another animal caused the following changes in the kidneys in situ: marked elevation in CPAH, slight decrease in Cinulin, slight diminution of urine excretion and a pronounced fall in sodium excretion. The amount of urine and sodium excreted by the four kidneys was identical with that previously excreted by the two kidneys in situ. In animals with alpha-receptor blockade, augmentation of the excretory renal mass had the following consequences in the in situ kidneys, CPAH, and Cinulin remained unchanged while urine and sodium excretion decreased to the same extent as in the untreated control group. The amount of urine and of sodium excreted by the four kidneys was the same as that excreted by the kidneys in situ, prior to transplantation of isolated kidneys, i.e. before the augmentation of excretory renal mass. It seems that the decrease in sodium excretion of the kidneys in situ was not due to the haemodynamic changes evoked by the load on the circulation; it was rather consequence of some quick, presumably humoral, regulation. The diminution of sodium excretion in the kidneys in situ after augmentation of the excretory renal mass has been ascribed to an increased utilization by the four kidneys of the natriuretic factor(s), i.e. to a diminution in the plasma level of the natriuretic hormone.
Solutions of KCl (1%, 10% and 31.2%) administered into the pericardial fluid or applied onto the surface of the heart evoked a dome-like change of the ECG in dogs, rats and guinea-pigs and led to myocardial infarction in 3-5 days. Both the acute changes in ECG and the infarction itself could be prevented by the application of pericardial fluid samples and by administration of three synthetic compounds onto the heart surface. The same substances also inhibited the development of ECG changes elicited by general hypoxia due to stopping artificial respiration. The existence of a peculiar myocardial space beginning with outer pores and reaching the myocardial cells through connective tissue pathways is postulated. Earlier studies showed that 125I-labelled albumin applied to the epicardial surface through a filter paper reached the endomyocardium through some intramyocardial pathways beginning with epicardial pores. In the present experiments intrapericardial application of India ink led to obstruction of these pores and thus prevented the infarction elicited by intrapericardial administration of KCl solutions. This space, being distinct from that accessible from the coronary arteries, serves for transfer of various substances into the myocardium, while other compounds (e.g. noradrenaline) are not effective through this pathway. Oxygen reaching this space from the epicardial surface protects the myocardium from the damaging effects of hypoxia and KCl.
To determine whether renal prostaglandins participate in the regulation of renal blood flow, sodium and water excretion during "stress situation", renal function was investigated in two groups of anaesthetized dogs, subjected to minor and to more severe surgical stress under control conditions, and following the administration of 4 mg/kg indomethacin i.v. In the control studies, the renal haemodynamic parameters (CPAH, Cinulin), urine output and sodium excretion were not different in those animals in which the surgical traumatization was more severe from data obtained in similarly anaesthetized dogs. Extracellular volume expansion induced with i.v. infusion of Ringer solution enhanced sodium and water excretion in both groups, however, the increase of sodium excretion was less in the dogs subjected to more severe stress. During indomethacin infusion glomerular filtration did not change in either groups; CPAH decreased by 20-25% in the anaesthetized animals and 35-40% in dogs in which the surgical stress was more severe. In this group the total renal blood flow was reduced by 40% simultaneously with the haemodynamic changes; sodium and water excretion fell in both groups. After indomethacin infusion the diuretic response of the kidneys to extracellular volume expansion was markedly reduced in the anaesthetized dogs, the diuretic and natriuretic effects being almost completely inhibited in the animals subjected to more severe stress. These data suggest that in the anaesthetized dog endogenous prostaglandins may serve to maintain renal blood flow but not the glomerular filtration rate. Inhibition of prostaglandin synthesis during more severe stress results in increased renal vascular resistance and reduced renal blood flow. Accordingly, the data provide evidence that renal prostaglandins counteract in the kidney the vasoconstrictor mechanisms activated during more severe surgical traumatization. The data do not support the direct physiological role of prostaglandins in regulating tubular function.
The possibility of local recording of the electrical activity of the sinus node was investigated on 22 dogs. Using a small unipolar electrode positioned at the proximity of the sinus node and applying a 2-4-fold electric amplification, an early, slow and low-amplitude wave could be recorded 20-40 ms before the P wave. This early wave gradually decreased when the electrode was moved away from the sinus node and finally fused into the local P wave. Temporary arrest of sinus node activity by injection of adenosine into the sinus node artery, electrical stimulation of the vagal nerve by infiltration with phenol of the sinus node region made the local P wave to disappear. Similarly, no early action before the P wave could be seen if the sinus node was driven electrically. The early wave recorded in the proximity of the sinus node represents the depolarization of the sinus node, and it is suitable to study the pacemaker activity of the sinus node together with sinoauricular conduction.
Minced rat brain deprived of cerebellum was dissociated by trituration through stainless steel screen and nylon meshes, then by velocity sedimentation technique free-floating perikarya were separated from cell syncytia and cellular debris. The presence of Fc-receptor and C3b-receptor activities, as well as the absence of membrane-bound immunoglobulin and receptor for sheep blood cells were demonstrated on separated perikarya of the rat brain.
The effects of peripherally administered cholecystokinin octapeptide sulphate ester and its unsulphated form on the active avoidance behaviour of rats were studied. The acquisition of avoidance behaviour was impaired, while extinction was facilitated, following cholecystokinin octapeptide sulphate ester or unsulphated cholecystokinin octapeptide treatment. These peptides had no action on open-field activity. It is concluded that peripherally administered cholecystokinin octapeptide influences acquisition and extinction of active avoidance behaviour and this effect is unrelated to general motor activity of the animals.
Three fractions were isolated from the venom of Dendroaspis angusticeps by column chromatography on CM-Sephadex C-25. All the three fractions were shown to possess acetylcholinesterase inhibiting activity. The toxicity of the fractions as tested on mice were variable. Although the toxic signs were identical, fraction DaVI was highly lethal (LD50 1.9 microgram/g) whereas fractions DaIV and T39 were less lethal, the LD50 being 3.6 micrograms/g and 4.1 micrograms/g respectively. The three fractions significantly inhibited true acetylcholinesterase to the extent of 91-95%.
Hypotonic haemolysis of newborn and adult human red blood cells (RBC) is more intensive at 4 than at 37 degrees C. Newborn RBC are more resistant to the decrease of temperature than adult RBC. Transition temperature of the RBC membrane can well be determined by illustrating osmotic haemolysis as a function of temperature. This parameter characterizes well the microviscosity of the membrane. The inclination point of Arrhenius curves representing transition temperature occurred always at 25 degrees C both in the case of adult and newborn RBC. The similarity of the transition temperature indicates the similarity of membrane microviscosity of newborn and adult human RBC.
The effects of intracerebroventricular administration of two different cholecystokinin antisera were tested on acquisition and extinction of active avoidance behaviour as well as on acquisition, maintenance and extinction of conditioned feeding behaviour of rats. Both antisera delayed the extinction of active avoidance and conditioned feeding response, while they were ineffective on acquisition and maintenance. These data suggest that the endogenous CCK of the brain might be a physiological modulator of extinction processes.
The regulation of Na+ and water metabolism was studied in sheep with rumen fistula after water deprivation for 48 hours. Na+ and K+ concentrations were determined in blood plasma, blood, urine and saliva, with or without NaCl load. The results showed that the water content of the ruminal fluid plays an important role in the control of electrolyte and water metabolism. The absorption of water and Na+ from the rumen favours the maintenance of isosmolality and isovolaemia until the concentration of Na+ in the ruminal fluid has exceeded that in blood plasma. Thereafter the balance of water movement between rumen and extravascular space is shifted towards the rumen inhibiting thereby a further increase of Na+ concentration and ensuring the life conditions for the ruminal microbial population. During water deprivation not only water is lost but as a result of Na+ excretion relative hyponatraemia also ensues as can readily be assessed from the ratio of salivary Na+ and K+ concentrations. Upon NaCl load the salivary Na+/K+ ratio was increased indicating the extent of Na+ supply.
Differential distribution of gross, particulate and soluble forms of hexokinase in the cerebrum, cerebellum, pituitary, hypothalamus and thalamus and medulla oblongata was studied in 9 inland teleosts of different phylogenetic age to clarify the compartmentation of glucose metabolism. Enzyme activity (gross) was maximum in the cerebrum and minimum in the medulla oblongata, suggesting that glucose metabolism is more intensive in the former structure. The activity in the particulate fraction was highest in the cerebellum followed by the cerebrum, midbrain and medulla oblongata. Gross, particulate and soluble fraction of the enzyme was higher in major carp species than in cat fish or snake head species. Total particular and soluble fraction was highest in the cerebrum, cerebellum and midbrain. The distributional trend of the enzyme was similar in the 9 fishes.
In the experiments presented here, serum samples were collected both from psoriatic (PS) (n = 8) and non-psoriatic (NPS) patients (n = 8) and were analyzed by the combination of fractional precipitation (80% ethanol, pH 2) and gel filtration techniques as well as by chemical methods. It was demonstrated that, in comparison to the non psoriatic samples, concentration of the free alfa-amino group bearing and the Lowry positive components as well as total carbohydrate content was significantly elevated in the acidic ethanol soluble serum fraction of psoriatic samples. In psoriasis, the quantity of serum components with UV light absorbing capability at 206 nm, and with a molecular mass between 0.3 and 5.0 KD (estimated by chromatographic criteria) also was elevated in one of the fractions obtained by Sephadex SG-25 chromatography. Results presented in this paper indicate, that psoriasis is accompanied by changes in quality and in quantity of middle size molecular weight serum components with chemical properties suggesting their peptide--and/or glycopeptide-like character.
Sulfhydryl substances (cysteine, glutathione, cysteamine and BAL) provide protection against experimental gastric ulcer induced by indomethacin while being ulcerogenous in stress-ulcer. Experimental data indicate the necessity to distinguish between "real" and "occasional" cytoprotective drugs.
A number of changes in peptide components could be demonstrated in sera of patients with end stage malignant diseases. Total and free alfa amino-N content of such sera was shown to be significantly higher than those in sera of patients with no sign of malignancy. In addition, a significant increase was found in one of the serum fraction obtained by Sephadex G-25 chromatography. This increase was shown to be due to an increase in the amount of one of the isotachophoretically separated serum components of anionic character as well as to the appearance in sera of tumour bearing patients of two additional isotachophoretic components never detected in non tumour bearing patients. Based on their chromatographic behavior as well as on observations made in earlier experiments, the peptide nature of the two isotachophoretic serum components seemingly characteristic of sera of tumour bearing patients is highly probable.
The effect of native serum samples from schizophrenic and control patients on the electrically induced contractions of the isolated mouse vas deferens (MVD) preparations was investigated. It was demonstrated that only the samples of schizophrenic origin elicited a naloxone dependent inhibition on the contractions of the MVD preparations, while sera from healthy individuals and those from non schizophrenic but mentally ill patients proved to be ineffective in this respect. By using ultrafiltration and gel chromatographic techniques, four fractions disclosing MVD related biological activity could be separated from schizophrenic samples. Chemical analysis revealed an elevated quantity of ninhydrin and Lowry positive materials as well as of unidentified carbohydrate components in the active fractions. Molecular mass of the serum ingredients carrying opioid activity was found to range between 0.5 and 5.0 KD. It is speculated that new appearance or the accumulation in the sera of several, and partly at least, unknown peptides and glycopeptides disclosing opioid activity might be characteristic of schizophrenia.
Arterial blood pressure (BP) and heart rate (HR) were continuously recorded during lateral hypothalamic self-stimulation with optimal stimulus parameters in rats. Hyper-hypotensive, hypertensive and hypotensive reactions were observed during separate self-stimulation, and the biphasic type considerably prevailed over other types of reactions. During the single cycles of self-stimulation hyper-hypotensive and hypertensive reactions with different heart rate reactions also occurred. In this case the biphasic type was seen in 75% of all reactions, whereas the hypotensive type occurred in 25% of the cases. The main type of BP reaction (92%) during continuous self-stimulation for 60-240 min was a gradual increase of the mean BP level from 15 to 40 mm Hg against initial values (p less than 0.001), that depended on the duration of self-stimulation. Changes of HR were more variable: tachycardia and bradycardia were seen approximately with the same frequency. Comparative analysis of cardiovascular reactions during hypothalamic SS and escape reactions provoked by ventromedial hypothalamus stimulation revealed some peculiarities of autonomic manifestations during positive and negative emotional reactions. The results of this comparison raises the question of a stress-reaction during self-stimulation behaviour.
The new total herbicide Toxurazine was subjected to general toxicologic and neurotoxicologic examinations. Rats were treated with 1/80, 1/40 and 1/20 of the acute oral LD50 for three months. The animals showed a decrease in body weight and a transitional anaemia. The product had a slight liver damaging effect. Renal function tests and urine analysis were negative. With time, the learning ability of animals tested in maze for 42 days became impaired dose dependently. At the end of the treatment, both at rest and on flashlight stimulation, as well as in complex EEG activity and in each frequency band there was a decrease in electric activity. In electroneuromyographic tests no effect damaging the peripheral nervous system could be detected. The hot plate method showed the reaction time of the animals to be slightly extended. The results suggest that the compound should only be used in uncultivated areas.
In acute immobilized rats, the effect on the EEG of thermal and chemical (capsaicin microinjection) stimulation of the warm sensors in the preoptic region, mid-hypothalamic area and posterior hypothalamus were studied. Both localized heating and capsaicin resulted in a sleep-like EEG with spindles and slow waves. Stimulation of the posterior hypothalamus was the most effective and stimulation in the mid-hypothalamus was the least effective in inducing spindle activity. Since capsaicin is regarded as a specific stimulant for the hypothalamic warm sensors, the results suggest that the EEG effect, and probably the sleep-inducing effect, of heat are mediated via the central thermoreceptors, and cannot be due to a non-specific activation of the basal forebrain hypnogenic mechanisms.
