Carnosine

CARNOSINE, β-alanyl-histidine, N-CH₂CH(COOH)·NH-CO·CH_a·CH_a·NH₂ II II CH NH. The discovery of K. in meat extract (1900) by Gulevich and Amiradzhibi marked the beginning of a new direction in the study of extractive substances of the animal organism. K. in amounts of 0.05-1.12% is a specific component exclusively of striated muscles of all animals studied in this direction, except for some invertebrates, fish, and birds. K. is the first dipeptide found in the organism, a derivative of histidine, which was previously known in nature only in free form or as part of a protein molecule. K. is the only natural derivative of β-amino acid, whereas all other natural amino acids and their derivatives belong to α-isomers. In 1928, Ackerman with his colleagues found in goose meat methylcarnosine, which they named anserine: N-CH₂CH(COOH)·NH-CO·CH_a·CH_a·NH₂ II II CH NH. At the same time, Tolkaevskaya isolated this same base from chicken meat. Anserine is a component of the meat of all birds studied in this direction, as well as crocodile. The formation of anserine in the animal organism represents a new example of the remarkable ability of the organism to methylation. K. has a toxic effect similar to that of histamine, but much weaker, and causes strong secretion of intestinal juice, but does not have a secretory effect on the gastric glands in its pure form. K. is split by erepsin of intestinal juice into histidine and β-alanine, whereas pepsin and trypsin do not act on it. K. crystallizes in needles, very soluble in water, insoluble in alcohol; decomposes at 241-245°; [α]_D=+25.0° (for a 13% solution). K. has a sharply alkaline reaction, forms salts with both acids and bases (Cu, Ag, Hg). The isolation of K. is based on its ability to precipitate in an acidic solution with mercuric sulfate and to precipitate with silver nitrate with the addition of barium hydroxide.

V. Gulevich.

CAROTID GLAND (glandula carotica; synonyms: glomus caroticum, glomerulus caroticus, paraganglion intercaroticum, nodulus intercaroticus, corpuscule retrocarotidien), a special paired glandular organ located at the branching point of each common carotid artery (art. carotis) into its external and internal branches. In an adult, the carotid gland has the form of an elongated and slightly flattened body, 5-7 mm long, 2.5-4 mm wide, and 1.5 mm thick. In a newborn, it has the size of a pinhead, reaches its maximum size at about 20 years of age, and in old age undergoes some reduction. The surface of the carotid gland is slightly uneven, and the tissue color is rosy-gray. At the lower pole of the organ, a large amount of connective tissue and the entry of vessels are noticeable, which leads some to consider this lower pole as the gate of the gland. The lower pole of the carotid gland lies 1-2 mm above the branching point of the common carotid artery. The carotid gland does not lie strictly in the middle between both branches of the a. carotis com., but is somewhat protruded in the dorso-medial direction. - The microscopic structure of the carotid gland corresponds to that of an endocrine organ; its basis is formed by fibrous connective tissue, in which the parenchyma is laid in the form of glandular cells without any excretory ducts. The connective tissue, usually containing a large number of fat cells (Marchand), divides the carotid gland into separate parts called secondary lobules, and at the periphery forms a capsule of the gland. The glandular cells embedded in this connective tissue basis are completely filled with epithelium-like cells and have extremely diverse sizes: some are very small and seem to consist of only a few cells, while others are very large; the cells are not arranged regularly: in some lobules of the carotid gland they are closely adjacent to each other, in others they are separated by thick layers of connective tissue. The parenchymal elements, or the specific cells of the carotid gland that fill the cells, are large (20-30 µ) polygonal cells with light, weakly granular protoplasm and a bubble-like nucleus; the cells are not always completely uniform; among them, larger specimens with large nuclei are sometimes encountered. When fixing the carotid gland in solutions with chrome salts, the protoplasm of some of its specific cells gives a chromaffin reaction: however, this property concerns only some cells of the carotid gland and is very inconsistent; in particular, in humans, the cells of the carotid gland do not show a chromaffin reaction. Recent research by Castro (de Castro) rejects the chromaffin nature of the cells of the carotid gland also in various animals. - The carotid gland receives blood through a small artery, which is a branch of the common carotid artery, more rarely one of the larger branches of the latter; inside the gland the artery breaks up into small branches, and each lobule receives its own special arterial branch, the capillaries of which densely surround the cell nests. - The nerves of the carotid gland form a dense network of myelinated and non-myelinated fibers in its stroma; they originate partly from branches of sympathetic trunks, but for the most part depart as a special nerve--n. intercaroticus--from the nervus glossopharyngeus (Castro). Along the course of the nerves, ganglion cells are also encountered. Information about the development of the carotid gland, and in connection with this, the classification of its specific cells until the beginning of the 20th century was very uncertain and contradictory. The view of Stieda, who pointed out that the carotid glands develop from the epithelium of one of the pairs of gill clefts and that their cells therefore have an epithelial origin, proved to be erroneous. Likewise, the very widespread teaching at the end of the 19th century (Arnold, Marchand, Kaschenko, Paltauf) about the adventitial origin of the carotid gland and that its cells represent metamorphosed cells of the vascular wall (perithelium), and therefore have a mesodermal origin, was not confirmed. At present, it is considered established (Kohn, Zuckerkandl) that in its development the carotid gland is closely connected with the sympathetic nervous system; specifically--in an embryo 27 mm long, one can see that from the upper cervical sympathetic ganglion (to a lesser extent from the ganglion cervicale n. vagi) in the direction towards the place of division of the common carotid artery, nerve fibers extend, accompanied by rudimentary sympathetic ganglion cells; a particularly large group of the latter gradually becomes isolated in the angle between the diverging internal and external carotid arteries. From this group, during the differentiation of its cells into specific light cells, the carotid gland develops. The indicated course of development, close to the development of the so-called paraganglia, led Kohn and many subsequent researchers to attribute the carotid gland to the chromaffin system of paraganglia, however with the reservation that the cells of the carotid gland, due to their weak and far from constant chromaffinity, differ from the pheochromocytes of typical paraganglia and perhaps perform a somewhat different function. The question of the physiological function of the carotid gland is still not entirely clear. Most authors, considering them to belong to the chromaffin system, attribute to them, as to other parts of the adrenal system (adrenal medulla, retroperitoneal paraganglia), an influence on blood pressure and carbohydrate metabolism. Experimental data, however, do not fully confirm this: while Mulon, when administering extracts of the carotid gland to animals, indeed observed an increase in blood pressure, Vincent, Frugoni and others noted, on the contrary, a decrease in blood pressure under the same conditions. Experiments with destruction and extirpation of both carotid glands are also contradictory; Schmidt, when extirpating the carotid glands, observed in animals no deviations from normal, which inclined him to consider the carotid gland a rudimentary organ, not carrying any particularly important function. Klug came to the same results. On the other hand, however, experiments by some authors, especially Betke, and very recent ones by W. Fischer, establish that after extirpation of the carotid gland in animals, a fall in blood pressure is observed, and subsequently cachexia and clear signs of retarded development of bone tissue and teeth gradually develop. Betke and Fischer consider that the carotid gland, on the one hand, carries a function common to the entire chromaffin system, and on the other hand, has a definite relationship to the construction of the bone system, at least during the growth period. W. Fischer also observed after extirpation of the carotid gland hypertrophy of the adrenal glands and parathyroid glands, which proves the presence of a correlative relationship between the carotid gland and other endocrine organs. A quite new view on the function of the carotid gland has been recently put forward by Castro. On the basis of his histological and experimental research, Castro became convinced that the carotid gland does not belong to the paraganglia and to the glands of internal secretion, and that its cells are in close connection with special nerve apparatuses located in the wall of the dilated initial part of the a. carotis int. (the so-called bulbus or sinus caroticus) and in the walls of the arteries of the carotid gland itself; these apparatuses, playing the role of sensory receptors, are connected with the cells of the carotid gland by centripetal nerves and also further centripetally through the n. intercaroticus of the glossopharyngeus to the medulla oblongata. According to Castro, the carotid gland together with the above-mentioned nerve apparatuses is a complex mechanism that perceives fluctuations in blood pressure and possibly other qualitative changes in the blood in the internal carotid artery and reflexively regulates them ('systeme depresseur de la carotide interne'); one can think that this function has points of contact with the so-called 'Karotissinusreflex' (Hering). Pathological changes of the carotid gland are not uncommon. From circulatory disorders, hemorrhages into the tissue of the carotid gland are known, which in it spread mainly along the capsule and show no tendency to penetrate deep into the gland. Hemorrhages are observed in newborns as a result of birth trauma, in adults during operations on the neck, most often--during removal of the thyroid gland, also in various hemorrhagic diatheses. Long-standing venous congestion in the carotid gland, which is usually a partial expression of blood stagnation in heart failure, leads to atrophy of the gland parenchyma and proliferation of connective tissue. A very frequent change is the sclerotic atrophy of the carotid gland in arteriosclerotics; with general arteriosclerosis, there is usually a corresponding change in the arteries supplying the carotid gland, as a result of which atrophy of the parenchymal elements develops up to the complete disappearance of some cells and proliferation of the connective tissue stroma. - Inflammatory changes of the carotid gland in the form of purulent inflammation are observed only as a result of the spread of suppuration from adjacent tissues. Of greater importance are inflammatory-type changes manifested by infiltration of the interstitial tissue with lymphoid elements, polyblasts, and plasma cells along with degenerative and atrophic changes in the parenchymal cells. Such pictures are very often encountered in the carotid gland in various infectious diseases (typhoid, sepsis, endocarditis, tuberculosis, syphilis);

Pauntz found particularly marked changes of this kind in rabies. - A distinctive change of the K. j. is the growth of connective tissue in it, i.e., its sclerosis, observed in cirrhosis of the liver; according to Pauntz, in these cases the sclerotic changes in the K. j. and in the liver are coordinated not only in that they occur simultaneously and apparently depend on the same cause, but also in the type of connective tissue growth; on the latter basis Pauntz distinguishes, as is customary with respect to cirrhosis of the liver, atrophic (Laennec's) and hypertrophic (Hanot's) cirrhoses of the K. j. - The best-known pathological changes of the K. j. are tumors of it; in all, about 100 cases of tumors of the K. j. have been described (Birman), and it has been established that in all cases the tumors belonged to the same type of mature neoplasms, very similar in structure to the normal tissue of the K. j. Depending on the views on the origin of the cells of the K. j., these tumors were given one or other names; at the end of the 19th century (see above) they were designated as endotheliomas, peritheliomas, angiosarcomas; after Kon's research they began to be called paragangliomas, pheochromocytomas; in recent times the name - struma of the K. j. has been considered more correct. The growth of these tumors is slow, and the largest size that the tumor reaches is the volume of a goose egg. In most of the described cases, the tumor had a benign course; only in individual cases was rapid growth observed, infiltration of adjacent tissues, metastases, and histologically in some of such observations a picture of a sarcoma-like tumor was found. Strumas of the K. j. occur more often in women than in men; the largest number of them falls in the age of 30-50 years; before the age of 18 they have not been observed. - All the listed pathological changes of the K. j. during the life of patients do not manifest themselves with any special symptoms; in particular, and in cases of tumors of the K. j., only signs associated with pressure of the tumor on the carotid artery, nerve trunks and other organs of the neck are usually noted. (Surgery of the K. J. - see BRACHIOGENIC cancer.) A. Abrikosov. The K. j. is found only in terrestrial vertebrates and moreover undoubtedly only in amphibians and mammals. In mammals, and apparently also in amphibians, it arises partly in the form of an epithelial thickening of the second gill pouch, and partly (at least in mammals) in connection with the ganglia of the sympathetic nervous system. In amphibians, it certainly does not have the structure of a gland, but represents a spongy-cavernous tissue, the cavities of which are connected with the lumens of the common, internal and external carotid arteries, the walls of which are perforated in many places.