SERUM CHANGES AND THE CAUSE OF DEATH IN EXPERIMENTAL PANCREATITIS : STUDIES ON FERMENT ACTION. XXX.

1. The serum changes observed during acute experimental pancreatitis indicate that the shock and death are due to an intoxication from protein split products, and not to an intoxication from pure tryptic ferment. 2. When the pancreatitis is produced by the injection of an anti-proteolytic substance (sodium oleate), the degree of intoxication bears no relation to the degree of tissue destruction. 3. The increase in serum antiferment apparently favors the recovery of the animal.     

THE EFFECT OF PROTEIN SPLIT PRODUCTS ON THE SERUM FERMENTS AND ANTIFERMENT : STUDIES ON FERMENT ACTION. XXVI.

1. In dogs the toxic effect of primary proteoses is usually associated with the following serum changes: (a) an increase in serum antiferment, with a following fall in titer; (b) some increase in serum protease; (c) an increase in serum lipase; (d) a decrease in serum proteoses and amino nitrogen. 2. Secondary proteoses produce (a) less marked changes in the antiferment titer; (b) a marked increase in serum protease; (c) an increase in serum proteoses; (d) only a slight change in serum lipase; (e) a primary decrease in amino nitrogen. 3. The peptone which we have used (prepared from dog muscle) caused (a) a change in antiferment titer similar to that produced by the primary proteoses; (b) a marked increase in serum protease; (c) only a slight increase in serum lipase; (d) a primary decrease in proteoses, followed by an increase later; (e) an increase in amino-acids. 4. A very small dose of peptone resulted in a decrease in antiferment titer, together with a primary decrease in serum protease. 5. The peptone preparation was non-toxic when introduced into the stomach or rectum, while the intestinal injection was followed by an immediate intoxication.     

THE MECHANISM OF ANAPHYLACTIC SHOCK : STUDIES ON FERMENT ACTION. XXIII.

1. The serum ferments are practically unaltered by a primary injection of foreign protein. 2. During the course of sensitization the injection of the antigen is followed by the mobilization of a non-specific protease which increases in rapidity and intensity as the maximum period of sensitization is reached. 3. Acute shock is accompanied by: (a) The instantaneous mobilization of a large amount of non-specific protease; (b) a decrease in antiferment; (c) an increase in non-coagulable nitrogen of the serum; (d) an increase in amino-acids; (e) a primary decrease in serum proteoses. 4. Later there is a progressive increase in the non-coagulable nitrogen, in proteoses, and in serum lipase. 5. The acute intoxication is brought about by the cleavage of serum proteins (and proteoses) through the peptone stage by a non-specific protease. 6. The specific elements lie in the rapid, mobilization of this ferment and the colloidal serum changes which bring about the change in antiferment titer.     

SERUM FERMENTS AND ANTIFERMENT DURING TRYPSIN SHOCK : STUDIES ON FERMENT ACTION. XXII.

1. The intravenous injection of trypsin in dogs results in a shock similar in many respects to anaphylactic and peptone shock. 2. The injection is followed by a marked rise of serum protease and lipase. 3. The antiferment usually shows a distinct drop in titer, with a recovery following in from four to twenty-four hours. 4. The non-coagulable nitrogen shows no constant alteration, but is never greatly changed in amount. 5. Inactivated preparations were in some respects followed by symptoms similar to those following the injection of the active preparation. 6. Subcutaneous and gastric absorption was practically without effect. 7. Intestinal absorption was followed by an increase in serum protease without evidence of intoxication, or by typical symptoms of acute poisoning. 8. The leucocyte curve bears no constant relation to the serum protease or lipase.     

SERUM PROTEASES AND THE MECHANISM OF THE ABDERHALDEN REACTION : STUDIES ON FERMENT ACTION. XX.

1. Normal serum protease is not specific; it is active in both dilute acid as well as alkaline media. It is destroyed by heating to 70° C. for thirty minutes. It is markedly impaired when heated at 56° C. for thirty minutes. It is inhibited by the unsaturated soaps and lipoids. 2. Guinea pig and rabbit serum contain relatively much protease; the leucocytes are without proteolytic ferments. 3. Normal human and dog serum contain little or no protease; the leucocytes are strongly proteolytic. 4. Serum complement and protease are not identical. 5. During various pathological conditions the non-specific protease is increased in both human and dog serum. 6. An increase in antiferment is in many instances coincident. 7. During the Abderhalden reaction the placental tissue becomes more resistant to enzyme action, because of the adsorption of the antiferment from the serum. 8. The dialyzed serum loses antiferment because of adsorption by the placental tissue or other adsorbing substances, including probably the dialyzing membrane. 9. The digestive substrate is the serum protein made available for protease action by the adsorption of the antiferment. 10. The proteases in pathological conditions investigated by us (pregnancy, tuberculosis, and pneumonia) are non-specific.     

THE SERUM FERMENTS AND ANTIFERMENT DURING PNEUMONIA : STUDIES ON FERMENT ACTION. XXIV.

1. The crisis in pneumonia is usually accompanied by (a) decrease in the serum antiferment; (b) the mobilization of a non-specific protease in the serum; (c) an increase in serum lipase; (d) a decrease in the non-coagulable nitrogen, and of the proteoses in the serum. 2. The crisis is associated with the beginning of an active autolysis, the latter depending on an altered relation between the ferment-antiferment balance. 3. The fibrin and leucocytic debris must be considered as one of the potential sources of toxic substances. With rapid autolysis proceeding, only non-toxic materials are absorbed.     

A COMPARATIVE STUDY OF LYMPH AND SERUM FERMENTS DURING PROTEIN SHOCK REACTIONS

The relation of two phenomena involved in the mechanism of recovery following protein shock therapy is shown in these experiments to be due to changes that concern the lymph rather than the serum. The first of these, the increase in the rate of flow of the lymph, has been suggested by Teague and McWilliams as a possible factor in recovery from infection when due to bacteria proliferating in the lymph spaces and inaccessible to the antibodies of the serum (typhoid). By means of the protein shock, antibody-rich fluids (serum) are forced into the lymph channels. That the antibodies of the serum are augmented following the shock has been demonstrated by Culver (4). With this possibility in mind it is to be expected that bacterial infection not confined to the lymph spaces will not be influenced by shock therapy to the same extent. How far this holds true we are unable to state, although von Decastello (5) has called attention to the fact that while he was able to cause rapid lysis or a crisis in typhoid patients following the shock reaction, the injection of a similar amount of vaccine in typhus fever was without effect. The second factor, the great increase in the antiferment, is clearly due to the amount of the antiferment entering the general circulation through the lymph stream. This accounts for the marked fluctuations observed in the titer of the serum antiferment in patients following protein shock. If, for instance, the original titer of the lymph is less than that of the blood, the first flushing of the lymphatic current into the blood channel will tend to lower the titer of the serum, but with the increased amount in the lymph after the shock the titer of the serum will also increase. Bacteria proliferate best where the antiferment is absent, as Wright (6) has noted in his studies on war wounds, a fact that is also commonly applied in bacteriological technique when we employ ascitic fluids, containing relatively little antiferment, preferably to serum, in culture media. The increased lymph flow that follows the shock reaction would have value then, not only in forcing specific antibodies into the lymph channels, but ''in increasing the antiferment there as well, which would aid in checking the growth of bacteria.     

SERUM FERMENTS AND ANTIFERMENT AFTER FEEDING : STUDIES ON FERMENT ACTION. XXI.

1. After feeding, an increase in non-coagulable nitrogen of the serum can be determined, reaching a maximum in about six hours. 2. This increase is greatest in the portal blood and is partially due to an increase in amino-acids. There is no increase in proteoses. 3. There is usually a progressive decrease in serum protease, reaching a minimum after from five to seven hours. 4. The portal blood may show an unaltered or an increased amount of protease. 5. The serum antiferment shows a slight increase, but is subject to considerable fluctuation. 6. The serum lipase (esterase) shows a slight increase, reaching a maximum after three hours. The hepatic blood usually contains the lowest concentration of lipase.     

STUDIES ON FERMENT ACTION : IX. A NOTE ON THE RELATION BETWEEN LYSIS AND PROTEOLYSIS OF PNEUMOCOCCI.

Bürgers, Schermann, and Schreiber (1) studied "Auflösungserscheinungen von Bakterien," and concluded that ferments were probably not the main factor in such lysis. Kantorowicz (2) in studying antiferment and bacteriolysis came to the opinion that there was an antiferment in the bodies of bacteria which prevented digestion. This antiferment was likewise an antibody to serum bacteriolysins. But Kantorowicz used as a standard of ferment action merely the clearing up of the bacterial suspension. Our report shows that lysis of pneumococci may be independent of ferment action, and that it is not correct to assume that clearing up of a bacterial suspension even in the presence of a proteolytic ferment indicates proteolysis.     

THE EFFECT OF KILLED BACTERIA ON THE SERUM FERMENTS AND ANTIFERMENT : STUDIES ON FERMENT ACTION. XXVII.

1. The intravenous injection of killed organisms is followed by the mobilization of a non-specific protease and lipase; the rapidity and extent of this reaction depend upon the toxicity of the organism and on the resistance of the organism to proteolysis. 2. The temperature and leucocytic curve bear no relation to the ferment changes. 3. The serum antiferment is usually increased after the injection. 4. Of the organisms studied, the typhoid bacilli produced the most marked ferment changes, and the tubercle bacilli the least. 5. The toxicity of the dried organisms cannot depend wholly upon proteolysis in vivo, but must depend in part on the preformed toxic substances liberated on lysis. 6. Serum protease should not be considered as the sole exciter of intoxication through the production of protein split products; it seems possible that its function may in part be one of detoxication.     

BACTERIAL ANTIFERMENTS : STUDIES ON FERMENT ACTION. XVII.

1. Intact bacteria probably resist tryptic digestion because of the absence of an exposed protein substrate. 2. Dried organisms resist digestion in a degree proportional to their content of unsaturated lipoids. 3. Lipoidal extractives reduce the resistance to tryptic digestion. 4. The extracted lipoids (saponified) are antitryptic in a degree proportional to their unsaturation. 5. The inactivation of the antiferment in Gram-negative organisms is probably due to changes in the degree of lipoidal dispersion. 6. Bacteria adsorb lipoids from the serum when incubated at 37° C. Such organisms when dried are found to be more resistant to tryptic digestion than untreated organisms.     

Beta-N-acetylhexosaminidase in the urine, kidney and serum of bromobenzene-intoxicated mice.

beta-N-Acetylhexosaminidase isoenzymes were separated from the kidney, serum and urine of normal mice and mice intoxicated with bromobenzene, using DEAE-cellulose chromatography. Both mouse serum and urine showed hexosaminidase profiles similar to the human counterparts with the presence of B (basic), I (intermediate) and A (acidic) isoenzymes. A notable feature was the presence of a high proportion of an intermediate form in mouse urine which is not always present in human urine. Hexosaminidase activity increased significantly in urine of mice intoxicated with bromobenzene. Its increase was time-dependent and due to kidney damage with a release in the urine of hexosaminidase A, I and, in higher proportion, B. No significant differences were observed in mouse kidney and serum profiles following intoxication with bromobenzene. The total activity of hexosaminidase, using 4-methylumbelliferyl-2-acetamido-2-deoxy-beta-D-glucopyranoside as substrate, did not increase in the serum of mice intoxicated with bromobenzene. Both hexosaminidase activity and the isoenzyme pattern in urine can be used as indicators of kidney damage by bromobenzene intoxication.     

STUDIES ON THE BLOOD PROTEINS : II. THE ALBUMIN-GLOBULIN RATIO IN EXPERIMENTAL INTOXICATIONS AND INFECTIONS.

The intoxication which develops as the result of a simple obstruction or a closed intestinal loop is accompanied by definite changes in the coagulable proteins of the blood serum. These changes consist essentially in an alteration in the normal albumin-globulin ratio; the globulin fraction is greatly increased and at times the normal relation of the two fractions may show a complete inversion. The increase in the globulin content of the blood serum is most marked in the animals which show some of the complications met with in loop animals,—rupture of the loop and peritonitis. In the latter conditions especially, the globulin increase is rapid and large. We believe this reaction to be of diagnostic value in acute infections attended by the sudden liberation and absorption of a toxic exudate. Infections and intoxications produced by inflammatory irritants are also accompanied by a rise in the blood globulins. This observation suggests that tissue disintegration with absorption of toxic products is responsible for the changes noted, and that bacterial invasion is important only in as far as it gives rise to toxic substances. Animals which have developed a tolerance to proteose intoxication following the periodic injection of small doses of proteose do not show a globulin increase. These experiments do not support the view that the rise in globulins observed in these experimental conditions is an expression of a resistance or tolerance developed by the animal. From the experimental evidence it seems more probable that the alteration in the partition of the blood protein fractions is one of the results of the metabolic disturbance which has been shown to occur in these conditions.     

THE NATURE OF SERUM ANTITRYPSIN : STUDIES ON FERMENT ACTION. XIII.

1. The ferment-inhibiting action of the serum is due to the presence of compounds of the unsaturated fatty acids. 2. These fatty acid compounds may be removed from the serum by means of chloroform or ether. 3. Soaps prepared by saponifying the chloroform or ether extracts inhibit the action of trypsin. 4. The anti-enzyme action of the serum can be removed by filtering acid serum through kaolin, and can in part be restored by extracting the kaolin. 5. The decrease in strength of anti-enzyme in old sera is probably due to the action of the serum lipase. 6. Iodin, potassium iodide, or hydrogen peroxide remove the inhibiting action of the serum. 7. Soaps of the unsaturated fatty acids lose their ferment-inhibiting action when heated with serum at 70° C.     

THE MECHANISM OF ANAPHYLATOXIN FORMATION : STUDIES ON FERMENT ACTION. XV.

1. The unsaturated lipoids (serum antitrypsin) can be adsorbed from guinea pig serum, rabbit serum, and horse serum by kaolin, starch, agar, and bacteria. 2. Diphtheria toxin and cobra venom also reduce the serum antitrypsin, possibly because of their affinity for lipoids. 3. Anaphylatoxins represent sera rendered toxic by partial removal of serum antitrypsin. 4. The matrix of the protein split products lies in the serum proteins so exposed. 5. The amount of removal of serum antitrypsin depends on definite quantitative relations; very large amounts and very small amounts of adsorbing substances are least effective (kaolin, starch, and bacteria). 6. Bacteria previously treated with serum or with oils do not adsorb serum antitrypsin. 7. Bacteria treated with serum become more resistant to the action of trypsin.     

THE R?LE OF THE RETICULO-ENDOTHELIAL SYSTEM IN IMMUNITY : V. PHENOMENA OF PASSIVE IMMUNITY IN BLOCKED AND SPLENECTOMIZED MICE.

1. Blockade of the reticulo-endothelial system by means of one intravenous injection of India ink as well as splenectomy did not alter the course of either Pneumococcus Type I infection or tetanus intoxication in mice. 2. The protective action of Antipneumococcus Type I serum against the corresponding infection, as determined by the injection of in vitro prepared mixtures of serum and culture, was definitely lower in mice which had received one blocking injection of India ink shortly before the test. 3. Titration of tetanus toxin and antitoxin in blocked and splenectomized mice gave results identical with those obtained in normal mice, if in vitro prepared and incubated toxin-antitoxin mixtures were injected. The degree of protection, however, conferred by a preceding dose of antitoxin against subsequent intoxication, was markedly lower in blocked mice than in normal control animals, this difference becoming more pronounced with the increase of the time interval.     

The use of lithium levels in the emergency department.

Most patients on chronic maintenance lithium therapy become toxic at some point during their therapy. Lithium intoxication portends morbidity and mortality. The serum lithium concentration can be used as an adjunct to a physician's clinical acumen in diagnosing and managing the patient with lithium intoxication.     

急性有机磷农药中毒患者血胆碱酯酶和肌酸磷酸激酶的变化与临床意义

目的：探讨血胆碱酯酶（ChE)及血清肌酸磷酸激酶（CPK）在急性有机磷农药中毒（AOPI)工时 的变化特点及其临床意义。方法：对50例采用中西医结合方法治疗的AOPI患者,根据中毒的程度分为轻度中毒组、中度中毒组和重度中毒组,并以25例健康体检者作对照组。采用试纸法和速率法分别检验ChE和CPK活性,并观察患者心脏功能改变。结果：与健康对照组比较,AOPI患者血清CPK均有不同程度升高（P均＜0．01）,且与中毒程度呈平行关系。血ChE活性均有不同程度降低,下降程度有时与中毒程度不相平行。结论：AOPI患者血清CPK升高越显著,提示中毒程度越重,其预后不良,对明确诊断有重要意义。     

PROTEOSE INTOXICATIONS AND INJURY OF BODY PROTEIN : III. TOXIC PROTEIN CATABOLISM AND ITS INFLUENCE UPON THE NON-PROTEIN NITROGEN PARTITION OF THE BLOOD.

The acute intoxication following an injection of a toxic proteose is usually associated with a large increase (40 per cent or more) in the non-protein nitrogen of the blood. This increase is found chiefly in the blood urea nitrogen, but the amino and peptide nitrogens also may show small increases. The changes observed in the blood non-protein nitrogen are identical with those which follow the feeding of large amounts of meat (8). These facts indicate that the proteose intoxication causes an abnormally rapid autodigestion of tissue proteins, but that the nitrogenous end-products are, in chief part at least, the same that result from normal catabolism of food proteins. There is no evidence that the autolytic products play any part in causing the intoxication. The possibility of such a part and a resultant vicious circle is not excluded, but from the available facts the autolysis appears more as a result rather than cause of the intoxication. It appears possible that in disease or intoxication tissue catabolism may be enormously accelerated and yet yield the end-products of normal protein metabolism.     

AN EXPERIMENTAL STUDY OF BLOOD GLYCOLYSIS. THE EFFECTS OF THYROID AND ADRENAL EXTRACTS AND PHLORHIZIN ON GLYCOLYSIS IN VITRO

1. Blood glycolysis in vitro during a period of three hours'' incubation proceeds at practically the same rate under sterile conditions and when no effort is made to prevent contamination. 2. Fresh thyroid extract, adrenalin, and phlorhizin do not contain any substances which have a constant effect upon the rate of blood glycolysis outside of the body. No evidence of the presence of an antiferment was found.