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power of forming a specific organic compound of iodine, and it is possible that its influence upon body-metabolism may be connected with this fact. Baumann and Roos' state that the iodothyrin is contained within the gland mainly in a state of combination with proteid bodies, from which it may be separated by digestion with gastric juice or by boiling with acids. Most of the substance is combined with an albuminous proteid, while a smaller part is united with a globulin-like proteid. There can be little doubt that the authors have succeeded in isolating at least one of the really effective substances of thyroid extracts. If the distinction made between the functions of the thyroids and parathyroids proves to be correct, and if each of these glands exercises its functions by means of an internal secretion, we may hope

that future work will be able to isolate the distinctive substance or substances characteristic of each gland.

Adrenal Bodies.-The adrenal bodies-or, as they are frequently called in human anatomy, the suprarenal capsules-belong to the group of ductless glands. Their histology as well as their physiology is incompletely known. It was shown first by Brown-Séquard (1856) that removal of these bodies is followed rapidly by death. This result has been confirmed by many experimenters, and so far as the observations go the effect of complete removal is the same in all animals. The fatal effect is more rapid than in the case of removal of the thyroids, death following the operation usually in two to three days, or, according to some accounts, within a few hours. The symptoms preceding death are great prostration, muscular weakness, and marked diminution in vascular tone. These symptoms are said to resemble those occurring in Addison's disease in man, a disease which clinical evidence has shown to be associated with pathological lesions in the suprarenal capsules. It has been expected, therefore, that the results obtained for thyroid treatment of myxoedema might be repeated in cases of Addison's disease by the use of adrenal These expectations seem to have been realized in part, but complete and satisfactory reports are yet lacking. The physiology of the adrenals has usually been explained upon the auto-intoxication theory. The death that comes after their removal has been accounted for upon the supposition that during life they remove or destroy a toxic substance produced elsewhere in the body, possibly in the muscular system. Oliver and Schaefer, and, about the same time, Cybulski and Szymonowicz,3 have given reasons for believing that this organ forms a peculiar substance that has a very definite physiological action especially upon the circulatory system. They find that aqueous extracts of the medulla of the gland when injected into the blood of a living animal have a remarkable influence upon the heart and blood-vessels. If the vagi are intact, the adrenal extracts cause a very marked slowing of the heart 'together with a rise of blood-pressure. When the inhibiting fibre vagus are thrown out of action by section or by the use of atropin

extracts.

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rate is accelerated, while the blood-pressure is increased sometimes to an extraordinary extent. These facts are obtained with very small doses of the extracts. Schaefer states that as little as 51⁄2 milligrams of the dried gland may produce a maximal effect upon a dog weighing 10 kilograms. The effects produced by such extracts are quite temporary in character. In the course of a few minutes the blood-pressure returns to normal, as also the heart-beat, showing that the substance has been destroyed in some way in the body, although where or how this destruction occurs is not known. According to Schaefer, the kidneys and the adrenals themselves are not responsible for this prompt elimination or destruction of the injurious substance. The constriction of the blood-vessels seems to be due to a direct effect on the muscles in the walls of the vessels, in part at least, since it is present after destruction of the vaso-motor centre and most or, indeed, all of the spinal cord. Several observers have shown satisfactorily that the material producing this effect is present in perceptible quantities in the blood of the adrenal vein, so that there can be but little doubt that it is a distinct internal secretion of the adrenal. Dreyer has shown, moreover, that the amount of this substance in the adrenal blood is increased, judging from the physiological effects of its injection, by stimulation of the splanchnic nerve. Since this result was obtained independently of the amount of blood-flow through the gland, Dreyer makes the justifiable assumption that the adrenals possess secretory nerve fibres. Abel has succeeded in isolating the substance that produces the effect on blood-pressure and heart-rate, and proposes for it the name. epinephrin. He assigns to it the formula C,HNO, and describes it as a peculiar unstable basic body. Salts of epinephrin were obtained which when injected into the circulation caused the typical effects produced by injection of extracts of the gland. It is possible that the substance in question may be continually secreted under normal conditions by the adrenal bodies and play a very important part with reference to the functional activity of the muscular tissues.

2

Pituitary Body.-This body is usually described as consisting of two parts, a large anterior lobe of distinct glandular structure, and a much smaller posterior lobe, whose structure is not clearly known, although it contains nerve-cells and also apparently some glandular cells. Embryologically the two lobes are entirely distinct. The anterior lobe, which it is preferable to call the hypophysis cerebri, arises from the epithelium of the mouth, while the posterior lobe, or the infundibular body, develops as an outgrowth from the infundibulum of the brain, and in the adult remains connected with this portion of the brain by a long stalk. Howell and others have shown that extracts of the hypophysis when injected intravenously have little or no physiological effect, while extracts of the infundibular body, on the contrary,

2

American Journal of Physiology, 1899, vol. ii. p. 203.

Zeitschrift für physiologische Chemie, 1899, Bd. xxviii. S. 318.

Journal of Experimental Medicine, 1898, vol. iii. p. 245; also Schaefer and Vincent: Journal of Physiology, 1899, vol. xxv. p. 87.

cause a marked rise of blood-pressure and slowing of the heart-beat. These effects resemble in general those obtained from adrenal extracts, but differ in some details. They seem to warrant the conclusion that the infundibular body is not a mere rudimentary organ, as has been generally assumed, but produces a peculiar substance, an internal secretion, that may have a distinct physiological value. A number of observers, especially Vassale and Sacchi, have succeeded in removing the entire pituitary body. They report that the operation results eventually in the death of the animal with a certain group of symptoms, such as muscular tremors and spasms, apathy and dyspnœa, that resemble the results of thyroidectomy. It has been suggested therefore that the pituitary body may be related in function to the thyroids and may be able to assume vicariously the functions of the latter after thyroidectomy. There is no satisfactory evidence, however, in support of this view. On the pathological side it has been shown that usually lesions of the pituitary body, particularly of the hypophysis, are associated with a peculiar disease known as acromegaly, the most prominent symptom of which is a marked hypertrophy of the bones of the extremities and of the face. The conclusion sometimes drawn from this fact that acromegaly is caused by a disturbance of the functions of the pituitary body is, however, very uncertain, and is not supported by any definite clinical or experimental facts.

Testis and Ovary.-Some of the earliest work upon the effect of the internal secretions of the glands was done upon the reproductive glands, especially the testis, by Brown-Séquard. According to this observer, extracts of the fresh testis when injected under the skin or into the blood may have a remarkable influence upon the nervous system. The general mental and physical vigor, and especially the activity of the spinal centres, are greatly improved, not only in cases of general prostration and neurasthenia, but also in the case of the aged. Brown-Séquard maintained that this general dynamogenic effect is due to some unknown substance formed in the testis and subsequently passed into the blood, although he admitted that some of the same substance may be found in the external secretion of the testis-i. e., the spermatic liquid. More recently Poehl 2 asserts that he has prepared a substance, spermin, to which he gives the formula C,H,N2, which has a very beneficial effect upon the metabolism of the body. He believes that this spermin is the substance that gives to the testicular extracts prepared by Brown-Séquard their stimulating effect. He claims for this substance an extraordinary action as a physiological tonic. The precise scientific value of the results of experiments with the testicular extracts cannot be estimated at present, in spite of the large literature upon the subject; we must wait for more detailed and exact experiments, which doubtless will soon be made. Zoth3 and also Pregel seem to have obtained exact objective proof, by means

1 Archives de Physiologie normale et pathologique, 1889-92.

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3

Pflüger's Archiv für die gesammte Physiologie, 1896, Bd. Ixii. S. 335; also 1897,

4

S. 386.

♦ Ibid.,

VOL. I.-18

of ergographic records, of the stimulating action of the testicular extracts upon the neuro-muscular apparatus in man. They find that injections of the testicular extracts cause not only a diminution in the muscular and nervous fatigue resulting from muscular work, but also lessen the subjective fatigue sensations. The fact that the internal secretion of the testis, if it exists at all, is not absolutely essential to the life of the body as a whole, as in the case of the thyroids, adrenals, and pancreas, naturally makes the satisfactory determination of its existence and action a more difficult task.

Similar ideas in general prevail as to the possibility of the ovaries furnishing an internal secretion that plays an important part in general nutrition. In gynecological practice it has been observed that complete ovariotomy with its resulting premature menopause is often followed by distressing symptoms, mental and physical. In such cases many observers have reported that these symptoms may be alleviated by the use of ovarian extracts. So also in the natural, as well as in the premature menopause following operations, it is a frequent, though not invariable, result for the individual to gain noticeably in weight. The probability of an effect of the ovaries on general nutrition is indicated also by the interesting fact that in cases of osteomalacia, a disease characterized by softening of the bones, removal of the ovaries may exert a very favorable influence upon the course of the disease. These indications have found some experimental verification recently in a research by Loewy and Richter' made upon dogs. These observers found that complete removal of the ovaries, although at first apparently without effect, resulted in the course of two to three months in a marked diminution in the consumption of oxygen by the animal, measured per kilo. of body-weight. If now the animal in this condition was given ovarian extracts (oöphorin tablets) the amount of oxygen consumed was not only brought to its former normal, but considerably increased beyond it. A similar result was obtained when the extracts were used upon castrated males. The authors believe that their experiments show that the ovaries form a specific substance which is capable of increasing the oxidation of the body.

2

Kidney. Tiegerstedt and Bergman state that a substance may be extracted from the kidneys of rabbits which when injected into the body of a living animal causes a rise of blood-pressure. They get the same effect from the blood of the renal vein. They conclude, therefore, that a substance, for which they suggest the name "rennin," is normally secreted by the kidney into the renal blood, and that this substance causes a vaso-constriction.

1 Archiv für Physiologie, 1899, Suppl. Bd. S. 174.

2 Skandinavisches Archiv für Physiologie, 1898, Bd. viii. S. 223; see also Bradford: Proceedings of the Royal Society, 1892.

V. CHEMISTRY OF DIGESTION AND NUTRITION.

A. DEFINITION AND COMPOSITION OF FOODS; NATURE OF ENZYMES.

SPEAKING broadly, what we eat and drink for the purpose of nourishing the body constitutes our food. A person in adult life who has reached his maximum growth, and whose weight remains practically constant from year to year, must eat and digest a certain average quantity of food daily to keep himself in a condition of health and to prevent loss of weight. In such a case we may say that the food is utilized to repair the wastes of the body —that is, the destruction of body-material which goes on at all times, even during sleep, but which is increased by the physical and psychical activities of the waking hours-and in addition it serves as the source of heat, mechanical work, and other forms of energy liberated in the body. In a person who is growing-one who is, as we say, laying on flesh or increasing in stature—a certain portion of the food is used to furnish the energy and to cover the wastes of the body, while a part is converted into the new tissues formed during growth. The material that we eat or drink as food is for the most part in an insoluble form, or has a composition differing very widely from that of the tissues which it is intended to form or to repair. The object of the processes of digestion carried on in the alimentary tract is to change this food so that it may be absorbed into the blood, and at the same time so to alter its composition that it can be utilized by the tissues of the body. For we shall find, later on, that certain foods-eggs, for example-which are very nutritious when taken into the alimentary canal and digested cannot be used at all by the tissues if injected at once, unchanged, into the blood. The food of mankind is most varied in character. At different times of the year and in different parts of the world the diet is changed to suit the necessities of the environment. When, however, we come to analyze the various animal and vegetable foods made use of by mankind it is found that they are all composed of one or more of five or six different classes of substances to which the name food-stuffs or alimentary principles has been given. To ascertain the nutritive value of any food, it must be analyzed and the percentage amounts of the different food-stuffs contained in it must be determined. The classification of food-stuffs usually given is as follows:

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