Neurogenic Dystrophies Research Articles

On the history of the study of the nervous trophism mechanisms, disorders, and correction in the Institute of Experimental Medicine (100<sup>th</sup> anniversary of the S.V. Anichkov Department of Pharmacology)

The study of the nervous regulation of trophism and its disorders neurogenic dystrophy of internal organs, and its prevention was one of the main research directions in the Department of Pharmacology of the Institute of Experimental Medicine of the USSR Academy of Medical Sciences. Since the mid-1950s, research has been conducted under the supervision of the departments head, Academician of the USSR Academy of Medical Sciences, S.V. Anichkov. He emphasized that the study of nervous trophism and its disorders was a major focus of the research of domestic scientists (I.P. Pavlov, L.A. Orbeli, A.D. Speransky, and G.V. Folbort, e.g.).
 This paper aims to review the research on the nervous regulation of trophic processes in internal organs (nervous trophism) and correction of its reflex disorders (neurogenic dystrophy) conducted by the staff of the Department of Pharmacology of the Institute of Experimental Medicine of the USSR Academy of Medical Sciences.
 The analysis of scientific publications of the Department of Pharmacology in the Institute of Experimental Medicine (Leningrad Saint Petersburg) within 19482010 was conducted.
 The study of neurogenic dystrophy of the stomach wall caused by irritation in experimental animals (rats, guinea pigs, and rabbits) of the reflexogenic zone of the pyloroduodenal region or 3-h electroexpression of immobilized rats receives the most attention. Pharmacological, biochemical, and morphological data on the critical role of the sympathetic nervous system in the development and reversal of dystrophic changes in the gastric mucosa, myocardium, liver, and pancreas are presented. The results of successful clinical trials of pharmacological agents restoring sympathetic regulation of gastric and cardiac trophism in treating patients with peptic ulcer disease and myocardial infarction are presented.
 Studies on neurogenic dystrophies of internal organs and search of drugs for their prevention and treatment are actual up to now.

The role of autonomic nervous system imbalance in the pathogenesis of hyperplastic laryngitis

A decrease in the mediator activity of nerve structures in organ tissues leads to the development of neurodystrophic changes and an increase in their sensitivity to certain influences. In these planets, it is important to assess the morphological characteristics of target structures, taking into account the neurodystrophic component of the disease. The aim of the study was to determine the activity of the peripheral adrenergic link of the trophic reflex and assessing the morphological features of the mucous membrane of the vocal folds in chronic hypertrophic laryngitis in patients with neurovegetative disorders. Materials and methods: the study involved 45 patients (37 men and 8 women) aged 23 to 72 years with a diagnosis of chronic hypertrophic laryngitis. An objective study of the upper respiratory tract, a cytological study of reprinted smears from the affected areas of the larynx, a study of the functional state of the ANS, as well as a histological and histochemical study of the removed tissue were carried out. Results. The examined patients were found to have dysfunction of the ANS in the form of insufficient or excessive autonomic support of activity. Morphological signs of keratinization of the epithelium of the mucous membrane of the vocal folds and its active proliferation, as well as dystrophic and atypical changes in cellular elements revealed as a sign of insufficient, tact and a sign of excessive vegetative support of activity. It was found that with insufficient vegetative support of activity, the proliferative activity of epithelial cells is more pronounced than that of a chemer with excess. The same applies to keratosis with atypia and dystrophic changes in the epithelium. Conclusions. The activity of the interstitial adrenergic nerve structures of the mucous membrane of the vocal folds correlates with the characteristics of autonomic activity. The weakening of the processes of synthesis, accumulation and excretion of neurotransmitter is associated with insufficient vegetative support of activity, and their strengthening is associated with excessive. The amount of neurotransmitter in peripheral nerve fibers and endings depends on the nature and intensity of manifestations of neurogenic dystrophies developing in executive tissues – targets of adrenergic innervation.

Patriarch of the Soviet pharmacology (to 125 anniversary of S.V. Anichkov)

Academician of the USSR Academy of Medical Sciences Professor Sergei Viktorovich Anichkov (1892-1981) is a great Soviet scientist pharmacologist, the founder of Soviet neuropharmacology. Educated in Military Medical Academy, Kazan Medical Institute, Petrograd Woman’s Medical Institute. The famous Russian Professors I.P. Pavlov, V.N. Boldyrev, N.P. Kravkov and A.A. Likhachev were his teachers. Headed Department of Pharmacology in Military Medical Academy, Leningrad (1924-1937), Department of Pharmacology in Institute of Experimental Medicine, the USSR Academy of Medical Sciences (1948-1981). The main studies of S.V. Anichkov were devoted to pharmacology of chemoreceptors of the carotid bodies, cholinergic regulation of physiological functions, pharmacology of endocrine regulation, pharmacotherapy of neurogenic dystrophies, toxicology of military toxic compounds. Published more 250 papers including 10 monographs. Under his leadership, more 10 drugs (ethimizol, sygetine, metamizil, paramion etc) were developed and adopted for wide medical practice in the USSR. Founded one of the big scientific school in the field of pharmacology in the USSR. Laureate of Lenin and State prices of the USSR.

Mechanisms of neurogenic dystrophies induced by activation and deprivation of the sympathetic nervous system

Entry of abnormal nervous stimuli after sciatic nerve transection proved to affect the functioning of renal mineralocorticoid receptors as a result of inadequate neurotrophic support of this organ. Drug blockade of both neural and humoral transmission of the abnormal stimuli from the injured nerve to the kidney prevented development of trophic disorders as indicated by the status of the renal mineralocorticoid receptor system. At the same time, drug stimulation of the sympathetic nervous system further affected aldosterone reception by this organ. beta-Blocker propranolol was shown to exert an antidystrophic effect in the case of local injuries of the neural system and, thus, prevented the development of neurogenic dystrophies.

On the Role of β-Adrenoreceptors in Mechanisms Underlying Neurogenic Dystrophies

Sciatic nerve damage led to a defective functioning of the renal mineralocorticoid receptors due to the disturbed neurotrophic supply of this organ: the reception of distorted nervous stimuli. The pharmacological blockade of both the neurotransmitter and the humoral pathways of the pathological stimuli from the damaged nerve to the kidney prevented the development of trophic disturbances as tested by the state of the renal mineralocorticoid receptor system. At the same time, the pharmacological stimulation of the sympathetic nervous system leads to an even more defective aldosterone reception by the kidney. Propranolol exerted an antidystrophic effect in the case of local damages of the nervous system and, thereby, prevented the development of neurogenic dystrophies.

Dental and occlusal characteristics of children with neuromuscular disease

Seventy-nine pediatric patients with neuromuscular diseases were examined for dental and occlusal characteristics. Fifty-six patients suffered from primary muscle disease (myopathies) including 43 with Duchenne's muscular dystrophy. The neuromuscular disorders in 19 patients were of neuropathic origin, while four were caused by a fault in the neuromuscular junction. Posterior crossbites occurred more often in the myopathies (57%) as compared with the neurogenic dystrophies (14%) ( P < 0.003). Although not statistically significant, the prevalence of open bite was also higher in the combined myopathies (21%) as compared with neurogenic disorders (9%). The Duchenne patients exhibited a statistically significant delay in dental emergence (1.06 years), unlike the other myopathies (0.31 years) and the neurogenic disorders groups (−0.03 years). This study emphasizes the influence of muscular environment on dental development in general. The dentition may be more affected in muscular dystrophies stemming from degenerative or inflammatory muscle damage than in those originating from nerve malfunction or disorder of the neuromuscular junction.

Changes in the nicotinamide nucleotide content in the brain and myocardium of rats exposed to factors inducing neurogenic dystrophies

The content of nicotinamide nucleotides in the brain and myocardium of rats was investigated during electrical stimulation of the animals and administration of toxic doses of noradrenalin. The level of total nicotinamide nucleotides and their oxidized forms was reduced but the content and rate of synthesis of nicotinamide nucleotide-phosphates were increased. The results point to a disturbance of oxidation-reduction processes and to an increase in the activity of the pentose pathway of carbohydrate utilization in the tissues in neurogenic dystrophies caused by extremal stimulation.

Changes in the nucleic acid and cyclic AMP content in neurogenic dystrophies of the stomach

A decrease in the RNA content was found in the stomach tissue of rats following degenerative changes in the organ induced by injury to the duodenum. A sharp fall in the cyclic AMP level in the gastric mucosa of rabbits was found under the same experimental conditions. The role of these changes in the mechanism of development of destructive and metabolic disturbances during the formation of neurogenic dystrophies caused by extraordinary stimulation is analyzed.

Trophic influences of the nervous system: their biochemical basis and disturbance in skeletal muscle.

Experimentally based views on the role of neural impulses in regulation of the rates of synthesis and concentration of enzyme and isoenzyme proteins in the skeletal muscles of rabbits and rats are presented. Published data and original observations on changes in isoenzyme spectra in the skeletal muscles of animals with experimental muscular dystrophies and of patients with various muscular diseases also are given. The similarity between the changes in the isoenzyme composition in the muscles, with reversion to the embryonic type, found both in muscular dystrophies of neurogenic origin and in primary lesions (myopathies) of the muscle itself is explained on the grounds that in neurogenic dystrophies it is due to disturbance of the conduction of neural impulses up to and into the muscle, while in the myopathy although the damaged muscle receives the neural impulses it cannot respond adequately to them.

The influence of epinephrine and of strong electrical stimulation on the nucleic acids of rat liver

Large doses of epinephrine lead to diminution of RNA contents in the cytoplasmic and mitochondrial fractions of the hepatic cells in rats. Histological analysis showed that epinephrine provoked dystrophic changes in the liver of rats similar to those induced by strong stimulation. Changes in RNA contents are also similar in both cases. The received data exposing the similarity of organic reactions to stimulation and to treatment with epinephrine indicate the significant participation of the sympathetic nervous system and of catecholamines in the development of these neurogenic dystrophies in liver.

Mitochondrial changes in gastric mucosa and liver under neurogenic dystrophies.

Mitochondrial changes in gastric mucosa and liver under neurogenic dystrophies.