EXPERIMENTAL RICKETS IN RATS : IV. THE EFFECT OF VARYING THE INORGANIC CONSTITUENTS OF A RICKETS-PRODUCING DIET.

1. Rachitic bone lesions may be produced in rats by a diet containing an excess of calcium, but deficient in phosphates. 2. Similar lesions follow a diet deficient in calcium, but containing an excess of phosphates. The endochondral lesions, however, are less pronounced. 3. A diet deficient in both calcium and phosphate induces atypical rickets. 4. Inorganic salts other than calcium or phosphate seem to be without influence upon the development or prevention of rachitic lesions. 5. The minimal amount of phosphate (calculated as P) required for normal calcification in young growing rats (30 to 50 gm.) on the diets used in these experiments is approximately 160 mg. per 100 gm. of diet. At 135 mg. individual variations come into play; at 110 mg., or less, rickets invariably follows. 6. An excess of calcium is not necessary to the production of the rachitic lesions. A reduction of the calcium lactate of Diet 84 to 0.6 per cent (111 mg. of Ca per 100 gm. of diet) still results in the development of typical rickets. 7. Adult rats react to a deficiency of phosphate in the diet by the production of calcium-free osteoid in abnormal amount about the spongiosa and cortex. There is not produced any alteration of the epiphyseal cartilage, as in growing animals.     

EXPERIMENTAL RICKETS IN RATS : I. A DIET PRODUCING RICKETS IN WHITE RATS,AND ITS PREVENTION BY THE ADDITION OF AN INORGANIC SALT.

1. A simple diet is presented which regularly induced rickets in young rats. 2. The substitution of 0.4 per cent secondary potassium phosphate for a small part of calcium lactate in this diet completely inhibited the development of rickets. 3. Quantitative determinations of calcium in the bodies of parallel rats showed a marked increase of calcium content in the rats receiving the added phosphate over those which developed rickets. 4. While it is thus shown by x-rays and by histological examinations and by quantitative chemical analysis that added potassium phosphate increased the assimilation and normal deposition of calcium, it may be the quantitative relationship between the inorganic ions rather than actual deficiency of any one of them which was here the determining factor in the cause or prevention of rickets. Our experiments and conclusions do not exclude the possibility of other causes of rickets than those here discussed.     

EXPERIMENTAL RICKETS IN RATS : VI. THE ANATOMICAL CHANGES WHICH ACCOMPANY HEALING OF EXPERIMENTAL RAT RICKETS,UNDER THE INFLUENCE OF COD LIVER OIL OR ITS ACTIVE DERIVATIVES.

Rats which had developed rickets were treated with cod liver oil or an active fraction of cod liver oil, and the various changes which occur in the healing of the bone lesions were studied. Several phases are described, from the early deposit of calcium salts in the zone of preparatory calcification to the return to normal bone. These stages correspond closely to those found in the healing of human rickets.     

EXPERIMENTAL RICKETS IN RATS : VII. THE PREVENTION OF RICKETS BY SUNLIGHT,BY THE RAYS OF THE MERCURY VAPOR LAMP,AND BY THE CARBON ARC LAMP.

Young rats on a diet low in phosphorus can be protected from rickets by irradiations with sunlight for about 15 minutes daily. In the winter months, however, this degree of light was found insufficient. The effective rays of the sun, in the intensities studied, did not penetrate window glass. They manifested some protective value after reflection from a smooth white surface. Irradiation of a few minutes with the rays of the mercury vapor lamp suffices to protect rats against rickets. This is true likewise of the rays from the carbon arc lamp. A standard protective dose of radiation can be formulated for rats on a standard diet. Light is able to prevent the occurrence of rickets in rats fed a rickets-producing diet characterized either by a low phosphorus and high calcium content, or a high phosphorus and low calcium content. Moderate variations in temperature do not alter the effective action of light rays. Pigmentation of the skin markedly lessens their effect, as demonstrated by the failure of a standard dose to protect black rats.     

DIET AND TISSUE GROWTH : V. THE EFFECT OF DIETARY PROTEIN ON THE REMAINING KIDNEY OF ADULT WHITE RATS FOLLOWING A UNILATERAL NEPHRECTOMY.

The effects of the ingestion of diets containing different concentrations of protein on the remaining kidney in adult white rats after a unilateral nephrectomy has been studied. In the animals on the high protein diet (85 per cent casein), actual glomerular and tubular lesions were observed in the kidneys of animals maintained for 90, 120 and 150 days after nephrectomy. In the animals on the standard ration, 18 per cent casein, no significant renal lesions were observed within the experimental period. Spontaneous focal lesions in the kidneys of rats maintained on Sherman''s diets "A" and "B" were inconspicuous at the age of 350 days but became progressively more frequent and were commonly observed after 500 days. The animals on the high protein and standard rations were all under 350 days old at the completion of the experiment. It is suggested that the age factor is of importance in that young animals may have greater powers of adaptation in withstanding the injurious effect of high protein rations. The animals on the high protein ration excreted definitely larger quantities of protein in the urine, and showed a higher incidence of casts in periods roughly corresponding to those in which anatomic lesions were observed than did the rats on the standard diet.     

STUDIES ON EXPERIMENTAL RICKETS : I. THE OCCURRENCE OF RICKETS IN YOUNG RABBITS BORN OF MOTHERS INFECTED WITH SCHISTOSOMUM JAPONICUM.

Our observations show that young rabbits born of mothers afflicted with Schistosomum japonicum develop typical rickets. Rickets can also be produced if we infect the young, healthy rabbits with the same parasite. It is natural to suppose that the rachitic changes are caused by the parasite itself. Since, however, a similar disease can be produced in the offspring, when the mother is fed on egg yolk, the causation is not limited to the action of this parasitic toxin alone. The toxin of Schistosoma may disturb the calcium and phosphorus metabolism of bone in young animals, especially in the period of vigorous growth; that is, 20 to 40 days after birth of the rabbits. Or it may exhaust some element important in the calcium and phosphorus metabolism such as vitamin A or D. The fact that exhaustion of the antirachitic factor in the mother causes rickets in the young, as Grant (1924) showed, and that certain low grade infections can exhaust vitamin B as shown by Wedgewood (1924), is in line with this conception. It may be added here that most investigations on rickets have been carried out on rats and dogs. We have found a simple and excellent way of producing rickets in rabbits by dietary deficiency. Concerning this method, we shall report elsewhere.     

LESIONS OF THE NERVOUS SYSTEM IN VITAMIN DEFICIENCY : I. RATS ON A DIET LOW IN VITAMIN A

Under the conditions of these experiments, which consisted essentially of maintaining rats on a ration adequate in all dietary essentials as far as is known except vitamin A, the following changes were produced in the nervous system. 1. Degeneration of the medullary sheaths of the brachial plexuses and sciatic nerves, and less often of the vagus nerves. Such lesions were not found in the optic nerves. 2. Degeneration of the medullary sheaths of the sensory tracts on the periphery of the spinal cord and in the posterior columns. Much less frequently similar lesions were found in both the crossed and uncrossed pyramidal tracts. 3. Changes of the same nature in the posterior nerve roots and less frequently in the anterior nerve roots of the spinal cord. Evidence was adduced to indicate that the changes in the sensory tracts of the spinal cord followed those in the posterior nerve roots. With the onset of muscular weakness and incoordination in these animals anatomic changes like those just described were found at necropsy, but they were not present for any appreciable period preceding the onset of these clinical signs. For a short but undetermined period following clinical signs of recovery from the nervous disease, marked lesions were still present in the nervous system at necropsy. These lesions in the nervous system were produced by a ration containing no cereals which might have contributed a "toxic" substance to account for the degeneration of the myelin sheaths. Neither does a deficiency in unsaturated fatty acids appear to have played a rôle in their development.     

THE ANEMIA OF SCURVY : EFFECT OF VITAMIN C DIET ON BLOOD FORMATION IN EXPERIMENTAL SCURVY OF GUINEA PIGS

1. Weight loss, progressive anemia, and a moderate increase in reticulated red blood cells occurred in seventeen guinea pigs on a diet deficient in vitamin C. 2. The histological changes of the bone marrow removed from guinea pigs with scurvy showed large numbers of erythrogenic cells, but scant evidence of active maturation to the adult erythrocyte. 3. A reticulocyte response was induced in guinea pigs with scurvy when fed orange juice daily. 4. The histological changes of the bone marrow removed from guinea pigs during the reticulocyte response showed large numbers of mitotic figures and relatively more adult red blood cells than in the bone marrow from guinea pigs with scurvy that had not been treated with orange juice. 5. It is concluded from this study that the anemia of experimentally induced scurvy in the guinea pig is largely dependent upon vitamin C deficiency resulting in retarded maturation of the red blood cell.     

MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN PARATYPHOID-ENTERITIDIS INFECTION OF WHITE MICE : V. THE EFFECT OF DIET ON HOST RESISTANCE.

White mice from the Rockefeller Institute breeding room fed on a McCollum complete diet, consisting of whole wheat (67.5 per cent), casein (15 per cent), milk powder (10 per cent), NaCl (1 per cent), CaCO₃(1.5 per cent), and butter fat (5 per cent) are more resistant to mouse typhoid infection, mercury bichloride intoxication, and botulinus toxin than are similar mice fed on bread and pasteurized milk supplemented by an oatmeal and buckwheat mixture and dog biscuit.     

百令胶囊对实验性糖尿病大鼠肾脏的保护作用

目的观察百令胶囊对实验性糖尿病大鼠肾脏的影响并探讨其作用机制。方法 45只大鼠随机分为对照组、模型组及百令胶囊组,其中模型组及百令胶囊组大鼠采用腹腔注射链脲菌素（25mg/kg）建立糖尿病模型,对照组仅注射0.5mL枸橼酸缓冲液,1周后百令胶囊组以10mg/kg百令胶囊灌胃,每天1次;对照组及模型组以10mL/kg生理盐水灌胃,每天1次,3组大鼠连续灌胃49d。于第7、28、49天各组分别处死大鼠5只,测量肾脏质量并计算肾指数;第7、28、49天大鼠尾静脉取血测定血糖、血清肌酐及尿素氮水平;同时收集24h尿液测定尿微量清蛋白的水平。结果第7、28、49天百令胶囊组肾脏质量、肾指数、血清肌酐、尿素氮及尿微量清蛋白水平明显低于模型组,差异均有显著性（F=13.32~85.36,q=3.58~92.39,P〈0.05）。百令胶囊组血糖与模型组比较,差异无显著性（P〉0.05）。结论百令胶囊对实验性糖尿病大鼠肾脏具有一定的保护作用,其作用机制可能与其阻止肾间质病变、纠正蛋白质及脂质代谢、延缓肾功能减退,进而改善肾功能有关。     

AN EXPERIMENTAL STUDY OF DIATHERMY : V. THE ELEVATION OF TEMPERATURE IN THE PNEUMONIC LUNG.

1. An experimental pneumonia with more or less lobar distribution has been produced in dogs by the method of intrabronchial insufflation of B. friedlænderi, Type B, and Pneumococcus, Type I. 2. Such dogs as showed evidences of a pulmonary lesion when photographed by x-ray were selected for lung temperature measurements. 3. Measurements of lung temperature were made by means of thermocouples before and during diathermy. 4. The thermocouples which recorded the temperature in the consolidated lobes showed in most instances a more rapid rate of heating during diathermy than those in the normal lobes. The final increase in temperature in the pathological lobes over the normal lobes amounted to slightly more than 1°C. 5. When local heating occurred during diathermy it was of the order of magnitude found in a lung in which the branch of the pulmonary artery supplying it had been clamped. 6. Histological examination of the lungs showed the pathological reaction to consist of intraalveolar exudate composed of polymorphonuclear leucocytes and desquamated alveolar epithelium. In some sections the exudate was sufficient to cause compression and emptying of the alveolar capillaries. 7. The local heating, we believe, depends upon this ischemic state of the smaller vessels. 8. Further evidence for an imparied circulation in the pneumonic lung is furnished by injection preparations in which the uninjected area corresponded exactly to the gross pathological lesion.     

抑肝健脾复方抗Wistar大鼠肝纤维化的研究

目的 :研究抑肝健脾复方预防和治疗肝纤维化的作用。方法 :采用 40 %CCl4制备大鼠肝纤维化模型 ,以秋水仙碱为对照 ,观察抑肝健脾复方对大鼠肝纤维化各项指标的影响。结果 :抑肝健脾复方能显著降低大鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶 (AST)、透明质酸 (HA)和肝组织中羟脯氨酸 (HyP)的水平 ,并能显著减轻肝脏胶原纤维增生程度。结论 :抑肝健脾复方具有抗肝纤维化作用     

EFFECT OF JEJUNOSTOMY IN EXPERIMENTAL OBSTRUCTION OF THE JEJUNUM OF THE DOG

1. Jejunostomy does not prevent the development of the chemical changes of the blood characteristic of obstruction of the jejunum in the dog. 2. Jejunostomy following experimental obstruction of the jejunum has no beneficial effect upon the duration of life. There is some evidence that life may be shortened by early jejunostomy. 3. Treatment of jejunal obstruction with sodium chloride solution tends to prolong the life of animals regardless of jejunostomy.     

CONSTITUENTS OF ELEMENTARY BODIES OF VACCINIA : V. A FLAVIN ASSOCIATED WITH THE PURIFIED VIRUS

Suspensions of purified elementary bodies of vaccinia exhibit fluorescence in the presence of ultraviolet light. This fluorescent constituent can be separated by chromatographic methods provided the virus is first denatured by acid and heat. By means of the specific protein of d-amino acid oxidase it has been possible to identify the flavin constituent as flavin-adenine-dinucleotide and show that it can participate in the oxidative deamination of d-alanine. By means of microbiological assay the flavin component has been quantitatively measured and shown to compare favorably in concentration with that observed in animal cells and in some bacteria; its concentration in virus is lower than that observed in yeast. The demonstration that it exists as an integral portion of the virus is not conclusive. So far, however, it has been separated from the elementary bodies only by means which in themselves inactivate the virus.     

THE INFLUENCE OF THE ADRENAL GLANDS ON RESISTANCE : II. THE TOXIC EFFECT OF KILLED BACTERIA IN ADRENALECTOMIZED RATS.

1. The resistance of rats to bacterial intoxication is greatly decreased after double adrenalectomy. 2. This decreased resistance is dependent upon a functional insufficiency of the adrenal cortex. 3. A dose of killed streptococci or staphylococci can be obtained that is invariably fatal to adrenalectomized rats, before hypertrophy of cortical accessories, but never kills control rats.     

THE EPIDEMIOLOGY OF A RABBIT RESPIRATORY INFECTION : V. EXPERIMENTAL SNUFFLES.

1. Data are presented which show that anhydremia does not play a leading rôle in the causation of symptoms in intestinal obstruction. 2. Chemical changes in the blood corresponding with those noted by previous investigators were observed. 3. Additional data regarding the chemistry of the toxin found in the obstructed intestine of dogs were obtained.     

FURTHER STUDIES ON T. LEWISI INFECTION IN ALBINO RATS : I. THE EFFECT OF SPLENECTOMY ON T. LEWISI INFECTION IN ALBINO RATS AND THE PROTECTIVE ACTION OF SPLENIC AUTOTRANSPLANTS II. THE EFFECT OF THYMECTOMY AND BILATERAL GONADECTOMY ON T. LEWISI INFECTION IN ALBINO RATS

T. lewisi infection in normal adult 3 month old albino rats raised from a single stock and maintained under identical conditions was studied. Daily quantitative estimates of the trypanosomes in the circulating blood were made and the course of the infection was studied. Bilateral suprarenalectomy in rats lowers the resistance to a subsequent infection with T. lewisi. About 70 per cent of these rats die in an average period of 5.8 days after injection. The multiplication of the parasites, in the circulating stream, however, is not more considerable in the suprarenalectomized than in the previously normal rats, nor is the duration of the disease in the surviving rats any longer than in the normal group. The removal of the suprarenal glands does not alter the immune reaction to the parasite, but lowers the natural resistance of the animal to the toxic effects of the protozoan infection. Bilateral suprarenalectomy does not lessen the immunity of rats recovered from T. lewisi infection to subsequent infection. Unilateral nephrectomy does not influence the course of a subsequent infection with T. lewisi infection. The mortality of splenectomized rats from Bartonella muris anemia increases from 30 to 100 per cent following the injection of T. lewisi at the height of the anemia 7 days after splenectomy. T. lewisi infection 48 days after splenectomy that is to say at a time when the Bartonella anemia is no longer present produces a more severe infection than in normal rats. The number of trypanosomes at the height of infection averages 3 times the ordinary and the infection endures twice as long. Both the immune substance that inhibits the reproduction of the parasite and the lytic factor are markedly depressed. Splenic autotransplantation performed 4 weeks prior to splenectomy raises the resistance of rats to a subsequent T. lewisi infection. Thymectomy in 6 week old rats diminishes the severity of a subsequent trypanosome infection and shortens its course. Both the formation of the immune substance which inhibits reproduction of the trypanosomes and formation of trypanolytic antibodies are stimulated by this procedure. In the adult rat thymectomy shortens the course of the infection but the severity is only slightly diminished. Bilateral gonadectomy in the adult increases the severity of the infection. The number of trypanosomes at the height of the infection is almost three times the normal. However, the duration of the infection is the same as in the normal rats. The reproduction-inhibiting factor is depressed by bilateral gonadectomy but not the trypanocidal factor. Unilateral gonadectomy does not influence the infection.