Showing papers in "The Journal of Physiology in 1910"

Flexion-reflex of the limb, crossed extension-reflex, and reflex stepping and standing.

Abstract: II. Reflex-movements accessory to the flexion-reflex: crossed extensionreflex: its reflex-figure: principles of coordination exhibited: receptive-field: rebound extension .55 III. Flexion-reflex and its accessory reactions in decerebrate and spinal preparations compared: flexor and extensor reflexes decerebrate and decapitate: rhythm and refractory-phase in decerebrate and spinal reflexes respectively . .-59

Chemical structure and sympathomimetic action of amines.

Abstract: Introductory. The elucidation of the structure of the active principle of the stupra-renal medulla by the work of Abell, v. Fifirth2, Takamine3, Aldrich4, Pauly5, and Jowett6, and its synthesis by Stolz 7 and by Dakin8, almost simultaneously, led to the physiological investigation of substances nearly related to it in chemical structure. Loewi and Meyer9, working with Stolz's preparations, investigated a number of ketones of the general formula (OH)2C5H3 . CO . CH2NR1R2 and the corresponding secondary alcohols (OH)2C.H3.CHOH. CHNR,R2, obtaine(d by reduction of the ketones, among these reduction products

A new mathematical treatment of changes of ionic concentration in muscle and nerve under the action of electric currents, with a theory as to their mode of excitation.

Abstract: A SHORT time ago Nernst' puit forward a physical theory of the electric excitation of living tissues, and subjected it to a mathematical treatment. An electric current passing through a tissue containing membranes impermeable to the dissolved ions will set up differences of concentration at and near the membranes. He supposes that these differences of concentration, when sufficiently large, cause an excitation:

On the ‘heat-coagulation’ of proteins

Abstract: ON heating soltutions of many proteins, as temperature rises, an irreversible change of state occurs-so-called \"heat-coagulation.\" Similarly, in the case of most proteins endowed with active physiological properties (e.g. ferments, toxins, lysins, opsonins, complements, etc.), at or about a particular temperature these properties are destroyed. Up to the present it has been the almost universal practice to regard the temperature at which change of state or loss of activity occurs, as if it were a physical constant characteristic of the particular protein, this temperature being subject to small variations according to the conditions of experiment. This may however be an entirely misleading way of regarding the matter and the well-known fact that the destruction of active properties, or precipitation as the case may be, does not occur instantaneously suggests a time process in which heat merely plays the subsidiary part of accelerator. This view of the coagulation of proteins was indeed advanced by Duclau x (1893) and has since been established by Famulener and Madsen (1908) for the destruction of the active properties in solutions of three antigens, vibriolysin, tetanolysin and goats'-serum-haemolysin, and by Madsen and Streng (1909) for agglutinins. We have occupied ourselves in the first instance with an investigation of the laws governing the precipitation of solutions of pure proteins because such a process lends itself more easily to accurate quantitative methods.

The secretion of urine.

Abstract: THE researches of Sch layer (), his co-workers and others have made it desirable that some further investigation of the metabolism of the kidney during diuresis, should be made. Schlayer recognises two kinds of diuresis, the mechanism of the one is vascular and the other tubular. The action of the vascular diuretics is maintained after the cells of the tubules have been poisoned with salts of the heavy metals. The original intention of our research was to investigate the vascular diuretics for the purpose of finding out whether, or no, their action was associated with increased metabolism of the kidney, and if so whether such had its seat in the glomerular epithelium. Heretofore the onlv diuretics whose action on the mammalian kidney (2) has been studied in this way are urea, sodium sulphate and phloridzin. There is a considerable amount ofevidence culled from various organs in the body-striped (8), and cardiac muscle(4, submaxillary (5) and parotid glands (6), pancreas (7), kidney with certain diuretics (8), intestine (9) which leads us to suppose that activity of the organ is associated with an immediate increase in the oxygen taken up by it, assurming that the oxygen is available, and we have regarded it as a fair assumption that if urine appears without increased oxidation in the kidney itself, the mechanism which accounts for its appearance is a purely physical one, whereas if there is a well marked increase in the metabolism of the kidney a secretory process is called into play. General method of experiment. Our experiments have been performed on cats and rabbits; dogs proved unsuitable, because the large doses of diuretic necessary were retained in the tissues to such an extent that it was found impossible to free the animal from them. The dissections do not differ materially from those described by

On the significance of carbon dioxide for the heart beat

Abstract: THE idea that carbon dioxide was not only a waste product but might play a distinct part in the regulation of the ordinary functions of the body was puit forward by Miescher. Miescher pointed this out in connection with the regulation of the respiratory movemenits, and his views have been amply confirnmed by Haldane and his pupils. So far as we are aware, the importance of the carbon dioxide tension in the blood for functions of the body other than that of respiration was first emphasised by Mosso, who, as is well known, ascribed the symptoms involved in mountain sickness to a diminution of the normal carbon dioxide tension in the blood, a condition named by him acapnia. In a series of recent papers', Yandell Henderson has laid stress on the importance of the normal carbon dioxide tension for a number of the bodily functions and amongst others for the maintenance of the blood pressure and for the beat of the heart. He finds that even a slight reduction in the carbon dioxide content of the arterial blood causes a marked quickening of the heart-rate, and that a certain fuirther reduction causes extreme tachyeardia. A great reduction rapidly effected causes the heart to pass into a state bordering on tetanus which practically abolishes the action of the heart. In a research on the spinal and intact animal lately carried out in this laboratory2 it was observed that although an increased CO2 tension in the blood caused a rise of blood pressure, this rise of pressure could be maintained for almost any length of time and did not tend to come to an end by failure of the heart, as is the case when the rise is due to diminution of oxygen. In the spinal animal, inhalation of C02 caused

The nature of oxyhaemoglobin, with a note on its molecular weight.

Abstract: IN the present paper we propose (1) to set forth some additional evidence for supposing that the union of oxygen with haemoglobin is a chemical one, (2) to press this supposition to its logical conclusion and on thermodynamical principles deduce the heat generated when one molecular weight of haemoglobin unites with oxygen, (3) by actual determinations of the heat produced by the union of one gram of hemoglobin with oxygen, to calculate the molecular weight of haemoglobin. The paper will -therefore divide itself into three portions corresponding to the subjects set forth above'.

The heat produced in contracture and muscular tone.

Abstract: IN some experiments on the efficiency of a muscle as a machine it was noticed that the heat set free by a stimulus was not always produced at one moment but might be evolved continuously during a considerable period. Apparently under some conditions a stimulus. does not cause only an explosive, discharge of energy into heat, but also a continuous breakdown for some seconds following. It was found in allthe cases where this occurred that the muscle showed, after stimulation, that particular form of tone named \" contracture \": in other words it did not reach its original -length for some considerable time after the primary twitch. It might perhaps have been expected that this was due simply to.the viscosity of the muscle, which prevented it from relaxing at once after contraction. That this contracture is always accompanied by a continuous heat production makes it probable however that it is very closely allied to the normal state of contraction. The objects of this paper are, (i) to show that contracture is accompanied by a steady heat production, and to investigate the relations between the two as far as possible, and (ii) to consider the amount of heat production during muscular tone, especially in muscles during incomplete tetanus and in the heart. Method. Blixl has described an apparatus designed by himself for estimating the heat production of working muscles. Prof. Langley some years ago obtained from him one of these instruments, with which the present investigation has been carried out. Various modifications have been applied to it, and it has been made much more sensitive and less easily disturbed than in its original form. Some idea of its sensitivity may be obtained from the statement that it is easily possible,

Observations on the sympathetic and sacral autonomic system of the frog.

Abstract: PAGE Anatomical. Methods .451 The sympathetic innervation of the iris and of the viscera 457 1. The iris. 457 2. The heart .458 3. The cesophagus, stomach, small intestine and upper colon. (a) Vaso-motor nerves. (h) Viscero-motor nerves .460 4. The lower colon .464 5. The generative organs. The kidney and fat body 464 The sympathetic and sacral autonomic innervation of the bladder and rectum . .465 Viscero-motor fibres in the posterior roots 473 Summary of results .. . .478 Comparison of the autonomic system with that of the mammal. 479

The action of beryllium, lanthanum, yttrium and cerium on the frog's heart

Abstract: THE study of the reactions of living tissues towards inorganic salts which in the course of their phylogenetic history they have in all probability never met is of value for several reasons. We have a simplification of knowledge if we can state that some physiological property is characteristic of a group of substances, otherwise defined by their chemical or physical resernblances, rather than of one of its members. In such classification lies a method of attacking the problem of how the normal saline constituents of the tissue fluids exert their action and what is the meaning of their antagonisms and harmonies. Particular interest attaches to any case where a clear parallel exists between the action of salts on a living organ and on a colloid system, such as for instance Hiber (16) has shown in the order of activity of the alkali m6tals. Such discoveries help to bring the mechanism of the cell within range of the methods of physical chemistry. Meltzer and Auer('), in an extended series of researches, have drawn attention to the remarkable effects produced on rabbits by the salts of magnesium. The injection of suitable doses causes anaesthesia and general motor paralysis: the most characteristic and immediate phenomenon is the paralysis of the respiratory centre. The investigations which form the subject of this paper originated in an attempt to compare the physiological activity of beryllium with that of magnesium. Beryllium (Glucinum) is di-valent, possesses an atomic weight of 9-1 and chemically resembles magnesium, which it immediately precedes in the second group of the periodic classification. A few experiments carried out on rabbits, anmesthetised with A.C.E. mixture and urethane, showed that the primary effect of beryllium

The action of tetrahydropapaveroline hydrochloride.

Abstract: TETRAHYDROPAPAVEROLINE hydrochloride is a new alkaloid which was made recently by Pyman(') during his study of the reduction products of papaverine. It presents some features of interest owing to its wellmarked physiological action. The effects it produces on the normal animal are such as hold out the hope of its value as a therapeutic agent and on that account an investigation of its physiological action seemed desirable. Its relationship to papaverine is shown in the following structural formulas:

The diastolic filling of the mammalian heart.

Abstract: During the period of discharge the volume curve of the ventricles shows a sudden and steep descent, beginning with the moment of the opening of the semilunar valves and accounting for 90 per cent. of the total output from the ventricle. At the bottom the volume curve is rounded and comes to a blunt point, at the apex of which the semilunar valves close. For a brief period immediately following the completion of systole all the heart valves are probably closed. Yet during this period, according to Henderson, the volume curve rises sharply, a slight notch in the curve sometimes marking the end of this brief period. He attributes this initial increase in the bulk of the ventricles to the rush of blood from the aorta into the coronary vessels. During the, period of filling of the ventricles the moment of opening of the auriculo-ventricular valves is marked by a rapid movement upwards of the volume curve. The line traced by the lever rises steeply and often nearly straight almost to its summit, then curves quickly and runs for some time parallel to the abscissa. Thus the filling of the ventricles occupies only the early part of diastole and is as rapid a process as the emptying in systole. According to this author, the volume curve during the latter part of diastole runs parallel to the abscissa, indicating that during this period no movement of blood occurs into the ventricles. Henderson suggests the name \" diastasis \" for this period, and states that differences in the rate of the heart beat depend almost entirely on lengthening or shortening of this period. In a very rapidly beating heart the period of diastasis entirely disappears, the volume curve becoming simply a series of sharp up and down strokes. He suggests that the contraction of the auricles increases the ventricular volume at the most to the extent of a few drops.

A contribution to the study of muscle-enzymes.

Abstract: THE following communication contains the results of experiments made with the object of studying the glycolytic ferment in muscle. In the first place it was necessary to obtain a preparation freed from nerves and blood vessels which would present, in a handy form and with as little change as possible, the essential elements of muscle. It must contain the ferments and also retain the power of spontaneously coagulating or passing into rigor so characteristic of muscular tissue. Trials were first made with \"press-juice\" of muscle, but, these not turning out satisfactorily, resource was had to the ordinary method of freezing and extracting, which, with certain precautions described below, was found to answer well. The careful, and on the face of them convincing, experiments of Stoklasa(l) and his co-workers, on glycolytic enzyme, lactacidase, etc., and their preparation from the tissues of plants and animals, have up to the present hardly found universal acceptance. Portier (2) and others were not successful in obtaining the same results. Cohnheim's failure was attributed by Stoklasa(3) to the use of frozen materials. It will be shown later that it is quite possible to extract a solution containing active ferment from muscle which has been frozen, and that a precipitate obtained from this solution is also active. Method. About twelve frogs are pithed, the aorta of each is cut through and, by gently stroking downwards the hind legs of the inverted animal, the muscles of the legs freed, as far as may be, from blood. The skin is then stripped off the legs, the feet removed and the spine and tissues cut through, so as to separate the legs from the rest of the body with as little injury as possible to the leg muscles. Each pair of skinned legs, as soon as it is ready, is laid in a freezing mixture. When the twelve pairs of legs are frozen hard they are passed through a carefully cooled mincing machine and, without giving them time to thaw, replaced in the freezing mixture. When again quite hard they

A reversed action of the vagus on the mammalian heart.

Abstract: Introductory. A cardio-accelerator action of the mammalian vagus has frequently been described, and in several instances has been regarded as indicating the presence in the vagus itself of true accelerator fibres. The earlier observations, such as those of Rutherford(') (who, indeed, explained the phenomenon otherwise), of Boehm (2), or of Sc hi ff(3), and the later experiments of Arloing 4), whether the accelerator action was revealed by the aid of drugs such as atropine or curare, or by degenerative section of the nerve, are alike open to explanation by the existence in the vagus of recurrent sympathetic fibres, arising from the stellate or the inferior cervical ganglion, joining the vagus by one of the communicating branches which unite it with the anterior limbs of the annulus, and looping back to their distribution in the cardiac branches. We have ourselves in one case, which will be mentioned later in more detail, obtained a result by means of degenerative section similar to those of Arloing, and susceptible of the same explanation. The phenomenon which is our main concern in this paper is of a different kind. It can be reproduced with regularity under given conditions, and we shall give evidence that it has no connexion with the true sympathetic system. Whether it is due to the presence in the vagus of fibres which are normally accelerator in function is still open to question.

An investigation of the sino-auricular node of the mammalian heart.

Abstract: IN tracing the form and nature of the muscular connections between the primary divisions of the vertebrate heart, the writer, together with Prof. Arthur Keith', described a remarkable remnant of primitive fibres which persists at the sino-auricular junction in the mammalian heart. Many human hearts, foetal normal and pathological, were examined as well as the hearts of such divergent species as the mole, porpoise, dolphin, kangaroo, wallaby, whale, mouse, shrew-mouse, rat, kitten, ram, pig, cart horse, pony, and foetal gibbon. In all these hearts was this remnant of the sinus of the primitive heart found. It is now known by the name of the \"Keith-Flack node \" or better the \"sinoauricular node.\" In structure it resembles that of the already known auriculo-ventricular node \" (A-V node) or \" node of Tawara2.\" The sino-auricular node lies in the sulcus terminalis just below the fork formed between the junction of the upper surface of the auricular appendix with the superior vena cava. Its position can be seen from the accompanying figure modified from our original paper. As can be seen the sino-auricular node is remarkable for its special arterial supply. In microscopic sections of it the artery is found surrounded by fibrous tissue in which are numerous peculiar muscle fibres, some nerve cells and nerve fibres. Dissection in large hearts shows that the nerve cells and fibres connect with the vagal and sympathetic nerve trunks, which form a rich plexus at this junction. The musculature of the node becomes continuous with that of the superior cava, auricle and auricular canal. In describing the node in the heart of the mole we said: \"Although the mass by its connections

The action of atropine, pilocarpine and physostigmine.

Abstract: SCHMIEDEBERG and Koppe, working on the action of muscarine on the heart, were struck by the absence of effect when atropine had been injected previously, and on the ground that atropine was known to paralyse the vagus they formulated the theory that muscarine stimulates this nerve. Subsequently pilocarpine proved to resemble muscarine so closely in its action that it has generally been descrited as of the same nature. The exact point of action of these alkaloids on the path of the nerve impulse has been located differently by different workers, but the more recent supporters of this view are unanimous in placing it in the \"terminations\" of the post-ganglionic fibres. The later investigations of the behaviour of the heart under these alkaloids have only confirmed more exactly the resemblance between it and that under stimulation of the inhibitory fibres'. The action on the iris and on the salivary and sweat glands also resembles that of stimulation of the motor and secretory fibres, and the antagonism of atropine is so complete that here also the action on the terminations of the post-ganglionic fibres has been generally accepted. It is true that Anderson has shown that pilocarpine continues to contract the pupil after degeneration of the post-ganglionic fibres of the motor oculi, but this merely pushes the seat of action further towards the periphery, indicating that it affects not the anatomical terminations of the nerve fibres but some receptive substance (Langley) interpolated between them and the final contractile substance. The receptive substances for pilocarpine, muscarine and atropine have thus been localised in the extremities of the path of nerve impulse on the same grounds as have applied in the cases of adrenaline, nicotine and curarine.

Quantitative researches on the summation of inadequate stimuli in muscle and nerve, with observations on the time-factor in electric excitation.

Abstract: IN a number of papers published in this Journal during the last few years I have investigated in detail the response of certain excitable tissuies to electric currents of varying duration. From these researches it appears that not only different tissues examined under like conditions, but also like tissues examined under different conditions of temperature and of surrounding medium, show well-defined differences in their response to such currents. All tissues examined behave alike in one matter; in every case the weakest current which will excite becomes progressively smaller as the duration of passage is increased up to a certain limit, and beyond that limit the same strength of current is required whatever the duration. It is in the duration of cuirrent at which this lowest limit of the exciting current is reached that a clear difference is found to exist between unlike tissues examined under like conditions or between like tissues examined under different conditions. There is no need to reproduce here the detailed observations on this matter which have already been published'. It will be enough to recall the broad facts which have beeni established. It has been shown that the current-duration at which the lowest limit of the exciting current is first reached is shorter in the motor nerve-fibres to the toad's gastrocnemius than in the sartorius muscle-fibres of the same animal, is shorter in certain tissues of the frog than in the corresponding tissues of the toad, is shorter both in muscle and in nerve when these tissues

The delay of the electrical response of nerve to a second stimulus.

Abstract: IN a recent paper Keith Lucas has described some peculiarities of the time relations of the electrical response of the sartorius muscle to a second direct stimulus'. These comprise a modification in the time of commencement of the second response when evoked by a stimulus occurring at certain intervals after its predecessor; this time, according to the observations which he has set forth, may be greatly delayed and the second response appears to commence after this prolonged delay at the same moment even when the actual moment of stimulation is shifted through a considerable range of time. It thus appears that in the sartorius muscle the true refractory period is succeeded by one in which the development of the response is latent or at any rate masked and the term \" irresponsive period\" is suggested for the whole of the two periods. My own work in association with Burch on the refractory period in nerve is so directly related to this new feature of the muscular response to a second stimuilus that it seemed inevitable to ascertain how far the conclusions arrived at by Keith Lucas were supported by observations upon nerve2. In this connexion two points seemed especially to demand reinvestigation. First the detailed comparison of the delay of the second electrical response with that of the first response of isolated nerve; and secondly the more extended examination of the time relations of the electrical response of nerve to a second stimulus. I possess a large number of records obtained, with the cooperation of G. J. Burch, by photographing the movements of my sensitive electrometer and among these are many which are suitable for affording information on these two points. These have now been re-examined

On the exhalation of drugs by the lungs

Abstract: THE exhalation of vapours by the lungs has not been the subject of systematic observations hitherto, and no definite statement is to be found in the literature as to the factors involved in it apart from the volatility of the substances eliminated by this passage. As regards individual substances, some results have been recorded; thus MagnusL found that ammonia is not excreted by the living lung and also fails to be absorbed from the air passages, and he considers the living pulmonary epithelium to be impermeable by ammoniia. A number of observers have demonstrated that ethyl alcohol is eliminated by the lungs only in traces even when large quantities have been ingested, while on the other hand it is well known that some of the higher alcohols can be detected in the breath, when comparatively small amounts have been absorbed. Poh 12 has recently shown that in the dog and cat, and to a smaller extent in the rabbit, amylene hydrate and tertiary butyl alcohol injected intravenously are exhaled by the lungs in large part, while isoamyl alcohol and methyl alcohol ingested in the same way appear only in traces in the breath. In one experiment he found isopropyl alcohol also excreted by the lungs in considerable quantity. Pohl seems disposed to consider it a general rule that primary alcohols are excreted only in traces by the lungs, while secondary and tertiary alcohols are mainly eliminated in this way except in so far as they enter into combinations (e.g. with glycuronic acid) and are oxidised in the tissues. This view seems to involve the conception that the exhalation of these bodies is determined by their capacity for undergoing some chemical combinations in the excreting cells rather than by their more

An analysis of changes and differences in the excitatory process of nerves and muscles based on the physical theory of excitation.

Abstract: THE researches on the summation of stimuli which I published in a recent number of this Journal' led me to the conclusion that the main differences observed between the excitatory processes of different tissues, and the changes of excitability produced by various conditions, ought to be expressible, in terms of Nernst's theory of electric excitation, by simple physical constants. I withheld the discussion of this point until a modification of Nernst's theory should be available by which the phenomena in question should be capable of quantitati-ve treatment. The mathematical investigation of Nernst's theory carried out by Mr Hill is published in the present number of this Journal, and I am accordingly able to return to the question. In order that the physical constants to which I shall refer may be fullyunderstood, it is necessary that I should first resume briefly the steps which have led to the recent development of the theory of electric excitation. The word excitation has by somewhat loose usage become applicable to all or any of the successive processes which constitute the connecting links between the application of a stimulus to a nerve or muscle and the appropriate final response. The application of the stimulus is not infrequently spoken of as excitation. The immediate local effect of the stimulus is called by the same name. The disturbance which is conducted away from the seat of application of the stimulus is often called the wave of excitation. A muscle is even said to be excited when it contracts in consequence of a stimulus applied to its motor nerve. It

On the recovery of muscle and nerve after the passage of a propagated disturbance.

Abstract: I. The electric response of the gastrocnemius muscle of the frog to two stimuli applied to the sciatic nerve . .368 11. The electric response of the sartorius muscle to two stimuli applied directly to the muscle-fibres ..379 III. The electric response of cardiac muscle to two stimuli . 381 IV. Discussion of the phenomenon of the delayed second response 386 V. Investigation of the factors concerned in the increased delay of the second response . .391 VI. Remarks on the application of the results obtained . 401 VII. Summary of conclusions ..403 VIII. Appendix showing analyses of electrometer recoirds 404

The determination of the total oxygen capacity and blood volume at different altitudes by the carbon monoxide method

Abstract: THEI precise changes which are undergone by the ha3moglobin of the blood as a reaction to changes of altitude have been a matter of controversy for a considerable time', and it cannot be yet said with certainty whether at high altitudes the lammoglobin shows a real increase in total amount or whether the increase in the percentage value of the hbemoglobin in the blood which is so frequently observed is due to a mere concentration of the blood, or whether both factors come into play. When one looks through the literature it is evident that much of the uncertainty is due to differences of the interpretation of single results obtained on individual animals, some of which have been kept at the low and others at the high altitude, for the method of estimating the total amount of he-moglobin and blood in the animal has hitherto been Welcker's or some modification of that method, each estimation necessitating the death of the animal examined. To solve the problem some intra vitam method of making the required observations, and one which does no harm to the subject, is therefore necessary. For this purpose Haldane and Lorrain Smith's carbonic oxide method2 for determining the total oxygen capacity and blood volume of man was employed during a recent expedition to the Peak of Teneriffe which has been described in greater detail in the preceding paper. In order to render the necessary apparatus easier to transport a modification of the original method of administering the carbonic oxide was adopted. Hill's oxygen bag3 in which the gas is produced

Creatin excretion in the bird and its significance.

Abstract: Introduction. In spite of a large amount of work by many investigators the significance of creatin in the economy is still unexplained. (1) Before 1905 creatin was generally regarded as a catabolite of muscular metabolism which is ultimately excreted in the urine as creatinin. The chief evidence uipon which this view was based is that creatin is a constant constituent of muscle. But even the important investigations of Meissner and of Voit which will presently be considered afford no conclusive proofs that the production of creatin in muscle or the output of creatinin in the urine is increased during increased muscular catabolism as it should be if it is a product of such catabolism. Further, the value of most of the older observations is vitiated by the faulty and defective methods of estimation which were employed. (2) The colorimetric method described by Folin in 1905 undoubtedly gives much more satisfactory results than any of the older methods, although possible fallacies in the results obtained have to be considered'. Using this method, Folin, from the examination of a large number of specimens of urines of individuals kept upon a creatin and creatinin free diet, came to the conclusion that the excretion of creatinin is a measure of the endogenous metabolism of the body2. Somewhat laters he recorded a series of experiments upon the administration of creatin by the mouth to man, which, according to him, show that the substance is not excreted as creatinin, but that it is, to a certain extent at least, retained in the body, a retention which is better marked upon a nitrogenpoor than upon a nitrogen-rich diet.