Experimental neurosis and gastric secretion in dogs

In four dogs (2 males and 2 females from one litter) with established gastric cannula gastric secretion was studied in control experiments and in induced experimental neurosis. Gastric secretion was stimulated by insulin. We monitored in individual 15 min. portions the amount of gastric juice, total HCl output, output of acid gastric proteinases, mucoproteins and some ions. The gastric juice was dialyzed and freeze dried. 50 mg of the lyophilisate was separated on Sephadex G 100. Macromolecular substances were fractionated into glycoproteins (peak I), acid gastric proteinases (peak II) and glycopeptides and polypeptides (peak III). The ratio of these individual macromolecular substances remainded constant in the same dog in all control experiments. However, there were significant differences between individual animals. Induction of experimental neurosis (by collision of the alimentary and avoidance reflex) gave rise to changes not only in the output of HCl and gastric proteinases, but also in the ratio of macromolecular substances. In the series of observed parameters these changes were of a different nature in males and females.     

Cortical influences on thyroid and sex gland function in neurotic dogs

Disturbances of higher nervous activity charactetized by the development of an experimental neurosis were elicited in three male dogs by means of functional influences. This was accompanied by an increase, decrease or no change in the level of total thyroxine in the blood with greater fluctuations of its content on different days. An euthyreoid state persisted in the dogs throughout all periods of the neurosis, which is testified by the absence of changes of the free thyroxine coefficient. In the first three to four weeks of the experimental neurosis the testosterone content in the blood plasma was enhanced, its level not correlating with the variations of thyroxine content in the blood.     

Compensation of exocrine pancreatic insufficiency during its partial, subtotal and total resection

Chronic experiments on dogs have shown that the damage of extra-secretory pancreatic function by duct ligation caused marked compensatory changes of stomach function. The increase in gastric juice secretion and gastric juice proteolytic activity was accompanied by the reduction in its acidity. In addition to quantitative changes, qualitative shifts were revealed (amylolytic activity in strongly acid pH-reaction), never observed in the gastric juice of intact animals. Partial pancreas resection (up to 75%) both in control and test animals 10-14 months after pancreatic duct ligation was not accompanied by significant changes in gastric juice secretion. Total pancreas resection in dogs with previous pancreatic duct ligation caused neither prompt animal death, as in the control, nor the inhibition of compensatory reactions of gastric juice secretion.     

Adaptogenic role of serotonin in dogs coming out of an experimental neurosis

In a study carried out on dogs by means of alimentary salivary conditioned reflexes, it was found out that serotonin injection into the anterior limbic cortex and the action of neurogenous stimuli lead neither to the development of experimental neurosis nor to the usual for the neurosis increase of blood serotonin level. At the treatment of experimental neurosis by small doses of 5-oxytryptophan, the therapeutic effect of this serotonin predecessor appeared only in the days of its injection. In the subsequent period, the neurotic changes in the higher nervous activity continued, and the blood serotonin level remained increased. These data as well as materials earlier obtained on the increase of the blood serotonin level at neurosis in dogs, give reason to consider the increase of activity of the serotoninergic system at neurosis as one of adaptogenous factors contributing to the coming out of neurosis.     

Typological characteristics of dogs in the initial period of the development of neurosis

In the initial period of neurosis, significant differences were found in changes of motor and vegetative reactions in dogs of dissimilar typology. Animals with strong type of the nervous system displayed cyclic transitions from the normal state to the initial stage of pathology and vice versa. Such transitions were practically absent in dogs of the weak type. A method is proposed providing efficient classification of experimental dogs according to their types of higher nervous activity and differentiation of the normal state and the initial stage of neurosis.     

Quantitative changes in gastric juice proteases in dogs during ulcer formation in the stomach]

Disc-electrophoretic investigation of proteases of the gastric juice of dogs under normal conditions and in experimental atophan ulcer of the stomach demonstrated that in fasting dogs ulceration was accompanied by marked quantitative changes in the protease spectrum. Fraction No. 6 showed a significant elevation against the background of total reduction of proteolytic fraction of the gastric juice in sham feeding of ulcerated dogs. Sham feeding replete ulcerated dogs indicated a marked increase of fractions No.1 and No.2. The noted changes of the gastric juice protease spectrum may be of ulcerogenic significance.     

Patterns in the transition from normal to neurosis in dogs with different typological traits in food and defensive situations

At comparison of the formation of neurosis in dogs with different typological characteristics in conditions with alimentary and pain reinforcement, a resemblance was revealed of transition from norm to the initial stage of pathology. In strong animals a development was seen of compensatory tachycardia at circular changes of conditioned activity. Weak type dogs are characterized by a lowering or full disappearance of reflexes in combination with bradycardia. The method of differentiation, allowing in situations with alimentary reinforcement to classify the tested animals according to the type of higher nervous activity and differentiate the states of "norm" and "initial stage of neurosis", proved to be effective for the analogous aims also in studies with defensive reinforcement.     

A Technique for Inducing Experimental Neurosis in Small Laboratory Animals

Research in the mechanism of endocrine disorders in functional disturbances of the central regulatory apparatus requires the development of an appropriate model of the affection. The employment of an experimental neurosis would seem to be promising in this regard. The Pavlov school has thoroughly elaborated techniques of inducing experimental neuroses in dogs, but when small laboratory animals (mice, rats) are employed in large-scale experiments, existing techniques do not provide a means of inducing a long-lasting pathological condition of the higher centers of the central nervous system.     

Disruption of situational reflexes in experimental neurosis brought on by changes in the space factor

Motor activity elaborated in dogs and consisting of delayed choice reactions in a stochastic system (methods developed by Beritashvili, Hunter) and of rhythmic stereotypes of motor situational reflexes (Kupalov method) was not impaired by changes in spatial parameters of unconditioned stimulus in the stochastic system of choosing one feeding trough out of five. The changes in the spatial arrangement of conditioned and unconditioned stimuli in stable stereotypes led to changes in the behaviour of the animals and experimental neurosis with long-lasting disturbances in the situational conditioned reflexes and the short-term memory.     

Experimental neuroses in dogs caused by an increase in the intensity of (light) stimuli conditions

The influence of enhanced intensity of general illumination on conditioned reactions of a different degree of complexity was studied on dogs by the classical method of secretory conditioned reflexes. In most of the dogs, increase of general illumination from 30 to 300 luxes leads to more intensive secretory conditioned and unconditioned reactions, a smaller number of errors in differentiation, and stabilization of parameters of conditioned activity, which testifies to the improved general functional state of the brain. In two animals in the same conditions of the experiment, an experimental neurosis set it, not connected with the complexity of the elaborated activity. It is assumed that the neurotizing agent was the superfluous situational (photic) stimulation which presented excessive requirements to the mechanisms regulating the general functional state of the brain.     

Studies on heterogeneity of human gastric zymogens

THE PEPTIC ZYMOGENS OF HUMAN GASTRIC MUCOSA HAVE BEEN STUDIED IN THE PAST BY THREE DIFFERENT TECHNIQUES: phosphate-gradient chromatography on a column of DEAE-cellulose, chloride-gradient chromatography on DEAE-cellulose and agar-gel electrophoresis. These techniques have given different results, each suggesting the presence of a different number of pepsin zymogens in human gastric mucosa. In the present experiments gastric mucosal homogenates were subjected to analysis by all three techniques. The two major zymogen peaks obtained from phosphate-gradient chromatography were found to be composed of the three fractions found on chloride-gradient chromatography; these fractions in turn were shown to be heterogeneous on agar-gel electrophoresis. The latter technique demonstrated the presence of seven separable enzymically active components in human gastric mucosal homogenates. The relationships of the components separated by the three techniques are discussed.     

Characteristics of endocrine disorders in the early stages of the development of chronic experimental pancreatitis

The experiments on normal mongrel dogs and those with chronic experimental pancreatitis were performed to reveal the early changes of the endocrine pancreas function. The concentration of immunoreactive insulin and glucagon were studied in afferent vessels of the organ after intraarterial glucose-loading during pancreatic perfusion in situ. The data obtained have shown that in chronic pancreatitis the maximum secretion of insulin is decreased and delayed, as compared to normal animals. At the same time insulin-glucagon secretion ratio remains unchanged. That was indicative of the normal alpha-cell function at the early stages of the disease.     

Measurement of gastric blood flow with radioactive microspheres.

The validity of using radioactive microspheres (15 +/- 5-mum diameter) to measure gastric blood flow and its partition between gastric wall layers was investigated in anesthetized dogs with a chambered segment of gastric corpus. Total flow measured by a venous effluent technique demonstrated close correlation with microsphere-measured flow (r = 0.98, slope = 0.95) in 12 dogs given histamine, gastrin, or isoproterenol. In 12 histamine-stimulated dogs, mucosal flow measured by aminopyrine clearance and by microspheres also showed good agreement (r = 0.96, slope = 0.83). No evidence was found to indicate that microspheres altered hemodynamic or gastric function. In all experiments less than 1% of the total gastric radioactivity passed through arteriovenous shunts. The mucosa always contained a statistically adequate number of spheres (greater than 400), but the submucosa and muscularis frequently did not. Microspheres of all sizes mixed adequately in large arteries, but a significant difference was found in the distribution of 16- and 26 mum spheres between mucosa and submucosa, presumably because of streaming of the larger spheres past mucosal arteries. It was concluded that, with the techniques developed in our laboratory, microspheres could be a highly useful tool for quantitating gastric regional blood flow under a variety of experimental conditions.     

Further characterization of Renibacterium salmoninarum extracellular products.

Renibacterium salmoninarum, the agent of bacterial kidney disease in salmonids, releases high concentrations of extracellular protein in tissues of infected fish. The extracellular protein consists almost entirely of a 57-kDa protein and derivatives of degradation and aggregation of the same molecule. The 57-kDa protein and its derivatives were fractionated into defined ranges of molecular mass. Separated fractions continued to produce degradation and aggregation products. One-dimensional electrophoretic separation of extracellular protein revealed a number of proteolytically active bands from > 100 to approximately 18 kDa associated with various 57-kDa protein derivatives in the different molecular mass fractions. Two-dimensional separation of extracellular protein showed that continued degradation and aggregation, similar both in location and behavior to some of the 57-kDa protein derivatives, was also displayed by the proteolytically active bands after their separation. Effects of reducing agents and sulfhydryl group proteinase inhibitors indicated a common mechanism for the proteolytically active polypeptides characteristic of a thiol proteinase. The results suggested that the 57-kDa protein and some of its derivatives undergo autolytic cleavage, releasing a proteolytically active polypeptide(s) of at least 18 kDa. Soluble polysaccharide-like material also was detected in extracellular products and tissue from infected fish. Antiserum to the polysaccharide-like material cross-reacted with O-polysaccharide of the fish pathogen Aeromonas salmonicida, suggesting some structural similarity between these polysaccharides. The polysaccharide and the proteolytic activity associated with the 57-kDa protein derivatives should be investigated with respect to the pathogenesis of R. salmoninarum infections.     

Choice of precursors for the measurement of protein turnover by the double-isotope method. Application to the study of mitochondrial proteins.

1. The double-isotope concept [Arias, Doyle & Schimke (1969) J. Biol. Chem. 224, 3303--3315] for the measurement of protein turnover was used to estimate the turnover of proteins in subcellular and submitochondrial fractions prepared from rat liver. 2. Double-isotope experiments with [3H]leucine as first precursor and [14C]leucine as second precursor were used to measure the turnover rates of proteins in subcellular and submitochondrial fractions. Solvent extraction procedures designed to remove lipids and nucleic acids from trichloroacetic acid precipitates only changed the isotope ratio of the microsomal fraction. It was not possible to measure turnover of proteins in mitochondrial and submitochondrial fractions with these precursors. 3. Double-isotope experiments were designed to minimize first-precursor reutilization by employing NaH14CO3. [3H]Arginine was used as second precursor. The turnover rates of protein in subcellular and submitochondrial fractions was measured. Solvent extraction procedures designed to remove lipids and nucleic acids showed changes in the isotope ratio for all subcellular fractions, especially in microsomal and detergent-soluble mitochondrial fractions. Isotope ratios of precipitates after solvent extraction indicate that, whereas considerable heterogeneity exists for the average rates of protein turnover in subcellular fractions, little heterogeneity is observed in the average rates of protein turnover in submitochondrial fractions.     

The role of cholinergic mechanisms in memory processes in experimental neurosis in dogs

In experiments on dogs the role was studied of cholinergic mechanisms in memory processes at different stages of neurosis. Predominance was shown in initial state of M-cholinergic mechanisms which also in conditions of neurotic inhibition of conditioned activity decrease the level of functioning less than N-cholinergic link. In the postneurotic period excessive activity of N-cholinergic memory mechanism was revealed. The supposed mechanisms are discussed of cholinergic system disturbances in neurosis dynamics and possibility of their pharmacological correction.     

Effects of pectin-induced passive linkage of gastric H+ on the gastric acid secretion on the development of ethanol- and salicylate-induced gastric mucosal lesions in rats.

The aim of this study was to evaluate the effects of intragastrically given pectin-induced physicochemical properties and actions on active gastric acid secretion and on the development of ethanol- and aspirin-induced gastric mucosal lesions. The observations were carried out on CFY-strain rats, fasted for 24 h before the experiments with water ad libitum. The observations were carried out in two experimental series. A) The gastric mucosal lesions were produced by intragastrically given 96% ethanol or aspirin prepared with 0.2 M HCl. Different doses of pectin (100, 50 and 25 mg x kg(-1), respectively) were administered intragastrically 30 min before giving necrotizing agents. The number of gastric lesions was noted 1 h after the administration, while the severity of gastric mucosal lesions was scored by semi-quantitative scale. B) The effects of pectin were studied on the volume and H+ secretion of the stomach in 4-h pylorus-ligated rats. It has been found that: 1) the gastric mucosal lesions could be produced in 100% of rats by the application of both necrotizing agents. 2) Pectin in doses of 50-100 mg x kg(-1) increased the number of gastric mucosal lesions in both models, while no increase was produced by the application of 25-mg x kg(-1) dose. 3) The severity of mucosal lesions increased significantly after the administration of all doses of pectin. 4) The pectin-induced increase of gastric lesions (number) showed a dose-response effect. 5) The pectin produced a significant increase in the volume of gastric secretion and gastric H+ secretion. It has been concluded that: a) pectin-induced physicochemical changes are able to enhance the aggression to gastric mucosa produced by ethanol and aspirin; b) a positive correlation exists between the linkage of H+ to pectin and significant active metabolic response in the rat stomach; c) pectin alone stimulates the active metabolic process of the gastric H+ secretion.     

Diaphragm function and respiratory response after upper abdominal surgery in dogs

Decreased diaphragm activity has been demonstrated after cholecystectomy in humans (Am. Rev. Respir. Dis. 127: 431-436, 1983). To investigate the mechanism(s) of postoperative diaphragm dysfunction we have established a dog model. Three groups of mongrel dogs were studied under general anesthesia: six dogs received no surgery (control); nine dogs underwent upper abdominal surgery (cholecystectomy); and six dogs underwent lower abdominal surgery (pseudoappendectomy). Diaphragm function was assessed by changes in transdiaphragmatic pressure swings, the ratio of changes in gastric to esophageal pressure swings, and the ratio of changes in abdominal to rib cage diameters during quiet tidal breathing. In the upper abdominal surgery group there were significant postoperative decreases in all parameters of diaphragm function and an increase in minute ventilation and respiratory frequency. However, there were no significant postoperative changes in the parameters of diaphragm function in the control or lower abdominal surgery groups. These studies establish that general anesthesia is not responsible for the reduced diaphragm activity seen postoperatively and that diaphragm function is not affected by lower abdominal surgery in dogs.     

Neurogenic (Hysteroid) Motor Disorders in Hamadryas Baboons

Pavlov's teaching on experimental neuroses is of prime importance for gaining insight into human neurosis. Pavlov devoted special attention to hysteria (1). His concept of the possibility of creating a model of this human neurosis in dogs was not constant, although the reproduction of individual symptoms of hysteria, especially of paralytic motor disorders, is an indisputable experimental fact, and can be explained within the framework of the principles of higher nervous activity established with respect to dogs.