scholarly journals GELATIN—ITS USEFULNESS AND TOXICITY

1944 ◽  
Vol 80 (2) ◽  
pp. 145-164 ◽  
Author(s):  
F. S. Robscheit-Robbins ◽  
L. L. Miller ◽  
G. H. Whipple
Keyword(s):  
Amino Acids ◽  
Plasma Protein ◽  
Protein Production ◽  
Blood Protein ◽  
Plasma Substitutes ◽  
Toxic Response ◽  
Histological Evidence ◽  
Anaphylactoid Reactions ◽  
Sensitive Testing ◽  
Significant Disturbance

Gelatin given by vein to doubly depleted dogs (anemic and hypoproteinemic) gives no immediate toxic response, no anaphylactoid reactions, and may contribute something to the building of new hemoglobin and plasma protein. Gelatin given by vein during 1 to 2 weeks (total 3 to 17 gm. per kilo) usually causes serious disturbances—inhibition of blood protein production, signs of intoxication, much weight loss, and even death. Gelatin given by vein for 2 to 3 days (total 1 to 3 gm. per kilo) may not cause any recognizable abnormalities, but dogs vary greatly in their response to gelatin by vein. Some dogs may tolerate a total of 7 gm. per kilo without significant disturbance and other dogs may be seriously intoxicated by 2 to 3 gm. per kilo. No one can predict which animal will be least tolerant. Some experiments with gelatin by vein for 2 to 3 days (total gelatin 1 to 2 gm. per kilo) given with and followed by amino acids or casein digests do show absence of intoxication and ample production of new hemoglobin and plasma protein during the weeks following the injection of gelatin. This may suggest possible usefulness of gelatin with amino acids or casein digests in acute emergencies (shock, hemorrhage). These doubly depleted dogs are very susceptible to various injurious agents as compared to normal dogs. They may serve as sensitive testing machines for evaluating plasma substitutes. Where the gelatin by vein inflicts its damage is not clear and there is little if any significant histological evidence but the disturbance of blood protein production implicates the liver. Gelatin of smaller molecular weight (degraded by autoclaving) is no less toxic than the standard gelatin. Gelatin by mouth may contribute to but cannot alone support the production of new hemoglobin and plasma protein. Gelatin by vein has definite limitations in dogs and, by implication, when used in human cases the amount given should be very carefully watched.

scholarly journals DIETARY EFFECTS ON ANEMIA PLUS HYPOPROTEINEMIA IN DOGS

1949 ◽  
Vol 89 (3) ◽  
pp. 359-368 ◽  
Author(s):  
F. S. Robscheit-Robbins ◽  
G. H. Whipple
Keyword(s):  
Weight Loss ◽  
Plasma Protein ◽  
Protein Production ◽  
Wheat Gluten ◽  
Peanut Flour ◽  
Blood Protein ◽  
Base Line ◽  
Total Blood ◽  
Dietary Effects ◽  
Hemoglobin Production

Casein (purified or commercial) in this type of experiment falls in the top bracket as a protein consistently favorable for maximal new hemoglobin and plasma protein production in doubly depleted dogs (anemic and hypo-proteinemic). Lactalbumin is less favorable for total blood protein production and the ratio of plasma protein to hemoglobin is high—that is lactalbumin favors plasma protein production as compared with casein, or is less favorable for hemoglobin production. Peanut flour (purified or commercial) is less than half as effective as casein in promoting new blood protein production. The ratio of plasma protein to hemoglobin is about the same as casein. Wheat gluten as tested is distasteful to dogs. It is neither very good nor very poor for blood protein production when it is eaten. There is nothing unusual about the response. Weight loss usually confuses the picture. Liver stands as a control base line for the above experiments. Its capacity to further hemoglobin and plasma protein production is well established. The production of hemoglobin was about 3 times that of plasma protein in the experiments.

scholarly journals Adverse Effects of Plasma Volume Expanders

1980 ◽  
Vol 8 (2) ◽  
pp. 145-151 ◽  
Author(s):  
James P. Isbister ◽  
Malcolm Mcd. Fisher
Keyword(s):  
Side Effects ◽  
Plasma Protein ◽  
Plasma Volume ◽  
Clinical Medicine ◽  
Prolonged Storage ◽  
Plasma Substitutes ◽  
Significant Incidence ◽  
Release Histamine ◽  
Anaphylactoid Reactions ◽  
Conscious Patient

Plasma protein solutions and synthetic plasma substitutes have an established role in therapy in many areas of clinical medicine. Although there have been many advances in the field of plasma volume expanders, an effective, stable, readily available and economical solution, free from side effects remains elusive. In particular, all plasma volume expanders may be associated with a small, but significant incidence of side effects. Allergic and anaphylactoid reactions are the most feared, but questions about prolonged storage and effects on haemostasis and renal function should be considered. Plasma protein fraction may be associated with hypotension, probably due to kinin activation. In the fully conscious patient, features of vasodilatation including flushing, fullness in the head, nasal stuffiness, may also be noted. There have also been reports of true anaphylactic type reactions occurring in atopic subjects after the infusion of small amounts of plasma protein solution. Modified fluid gelatins are well known to release histamine when infused rapidly. The reactions are usually confined to the skin and present clinically as pruritis, urticaria or flushing. There are also reports of anaphylactic reactions not related to dosage which are probably immune in origin. The dextrans are well recognised to cause such anaphylactoid reactions. Accepting that anaphylactoid and anaphylactic reactions may occur in association with plasma volume expanders, anticipation, diagnosis and rapid institution of therapy determine the outcome of these reactions.

scholarly journals HEMOGLOBIN AND PLASMA PROTEIN PRODUCTION

1946 ◽  
Vol 83 (6) ◽  
pp. 463-475 ◽  
Author(s):  
F. S. Robscheit-Robbins ◽  
L. L. Miller ◽  
G. H. Whipple
Keyword(s):  
Plasma Protein ◽  
Protein Production ◽  
Protein Supplementation ◽  
Blood Protein ◽  
Supporting Evidence ◽  
Food Proteins ◽  
Low Protein ◽  
Loss Of Appetite ◽  
Protein Diets ◽  
Protein Output

Given healthy dogs, fed abundant iron and protein-free or low protein diets, with sustained anemia and hypoproteinemia due to bleeding, we can study the capacity of these animals to produce simultaneousiy new hemoglobin and plasma protein. The reserve stores of blood protein-producing materials in this way are largely depleted, and levels of 6 to 8 gm. per cent for hemoglobin and 4 to 5 gm. per cent for plasma protein can be maintained for considerable periods of time. These dogs are very susceptible to infection and to injury by many poisons. Dogs tire of these diets and loss of appetite terminates many experiments. These incomplete experiments are not recorded in the present paper but give supporting evidence in harmony with those tabulated. Under these conditions (double depletion) the dogs use effectively the proteins listed above—egg, lactalbumin, meat, beef plasma, and digests of various food proteins and hemoglobin. Egg protein at times seems to favor slightly the production of plasma protein when compared with the average response (Tables 1 and 2). Various digests and concentrates compare favorably with good food proteins in the production of new hemoglobin and plasma protein in these doubly depleted dogs. Whole beef plasma by mouth is well utilized and the production of new hemoglobin is, if anything, above the average—certainly plasma protein production is not especially favored. "Modified" beef plasma by vein causes fatal anaphylaxis (Table 4). Hemoglobin digests are well used by mouth to form both hemoglobin and plasma protein. Supplementation by amino acids is recorded. Methionine in one experiment may have been responsible for a better protein output and digest utilization (Table 7).

scholarly journals AMINO ACID MIXTURES EFFECTIVE PARENTERALLY FOR LONG CONTINUED PLASMA PROTEIN PRODUCTION. CASEIN DIGESTS COMPARED

1944 ◽  
Vol 79 (6) ◽  
pp. 607-624 ◽  
Author(s):  
S. C. Madden ◽  
R. R. Woods ◽  
F. W. Shull ◽  
G. H. Whipple
Keyword(s):  
Amino Acids ◽  
Intravenous Injection ◽  
Plasma Protein ◽  
Nitrogen Balance ◽  
Protein Production ◽  
Nitrogen Retention ◽  
Essential Amino Acids ◽  
Skin Lesions ◽  
Good Utilization ◽  
Rapid Injection

When blood plasma proteins are depleted by bleeding with return of red cells suspended in saline (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet nitrogen intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and to certain intoxications. The ten growth essential amino acids of Rose plus glycine will maintain nitrogen balance and produce as much new plasma protein as will good diet proteins. This good utilization is demonstrated over periods of several months when the amino acids are given either orally or parenterally. There is no evidence of toxicity in general nor to unnatural forms of these synthetic amino acids in particular. Given parenterally appropriate mixtures of these amino acids are well tolerated even upon rapid injection. The minimal daily requirements for a 10 kilo dog may be given intravenously in 10 minutes without reaction. Subcutaneously a 10 per cent solution may be given rapidly without reaction. Among various mixtures tested Vt approximates a minimum for a 10 kilo dog. It contains in grams (dl-threonine 0.7, dl-valine 1.5, l-(-) leucine 1.5, dl-isoleucine 1.4, dl-lysine hydrochloride 1.5, l(-) tryptophane 0.4, dl-phenylalanine 1.0, dl-methionine 0.6, l(+)-histidine hydrochloride 0.5, l(+)-arginine hydrochloride 0.5, and glycine 1.0. The presence of glycine improves tolerance to rapid intravenous injection, but excess glycine does not improve utilization of the mixture. Over a long period this mixture appears suboptimal in quantity. Doubled it is more than ample. Of two casein digests tested the one prepared by enzymatic hydrolysis provided good nitrogen retention and fairly good plasma protein production but was much less tolerable upon intravenous injection than certain mixtures of pure amino acids. The other one prepared by acid hydrolysis and tryptophane fortification afforded bare nitrogen equilibrium and produced virtually no plasma protein. Skin lesions observed after 10 to 20 weeks of synthetic diet probably reflect a deficiency of some member or members of the vitamin B2 group. A persistent slight weight loss in the face of a strongly positive nitrogen balance may accompany this deficiency.

scholarly journals TEN AMINO ACIDS ESSENTIAL FOR PLASMA PROTEIN PRODUCTION EFFECTIVE ORALLY OR INTRAVENOUSLY

1943 ◽  
Vol 77 (3) ◽  
pp. 277-295 ◽  
Author(s):  
S. C. Madden ◽  
J. R. Carter ◽  
A. A. Kattus ◽  
L. L. Miller ◽  
G. H. Whipple
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Protein ◽  
Nitrogen Balance ◽  
Protein Intake ◽  
Protein Production ◽  
The Body ◽  
Acid Mixture ◽  
Negative Nitrogen Balance ◽  
Growth Mixture

When blood plasma proteins are depleted by bleeding with return of the washed red cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet protein intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and to certain intoxications. When the protein intake of such dogs is completely replaced by the growth mixture (Rose) of crystalline amino acids, plasma protein production is excellent, weight and nitrogen balance are maintained. This growth mixture consists of ten amino acids, threonine, valine, leucine, isoleucine, tryptophane, lysine, phenylalanine, methionine, histidine, arginine, and is as effective as most diet proteins in plasma protein production. The above amino acid mixture in aqueous solution may be given by vein with equally good plasma protein production and no apparent clinical disturbance even when given rapidly. Cystine may replace methionine in the above mixture with equally good plasma protein production for 7 to 10 days but at the expense of the body tissues, that is, with weight loss and a negative nitrogen balance. The addition of cystine to the protein-free, otherwise adequate diet may result in the production of considerable new plasma protein during a period as long as 1 week (cystine effect). This reaction may depend upon the amino acid constitution of the preceding diet protein in that it occurred following a liver feeding but did not occur after pancreas feeding. Arginine is required in the diet of the protein depleted dog for fabrication of plasma protein. It is apparently not needed for nitrogen balance for as long as 1 or 2 weeks. The omission of either threonine or valine from the growth mixture is quickly followed by a sharp decline in plasma protein formation and by a negative nitrogen balance. When histidine, arginine, and most of the lysine are omitted from the growth mixture, nitrogen balance and weight may be maintained for as long as 1 week but plasma protein production falls off markedly. The findings indicate that the growth mixture of amino acids should be a valuable addition to transfusion and infusion therapy in disease states associated with deficient nitrogen intake or tissue injury and accelerated nitrogen loss, including shock, burns, and major operative procedures.

scholarly journals PLASMA PROTEIN PRODUCTION INFLUENCED BY AMINO ACID MIXTURES AND LACK OF ESSENTIAL AMINO ACIDS

1945 ◽  
Vol 82 (2) ◽  
pp. 77-92 ◽  
Author(s):  
S. C. Madden ◽  
F. W. Anderson ◽  
J. C. Donovan ◽  
G. H. Whipple
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Protein ◽  
Protein Production ◽  
Daily Intake ◽  
Essential Amino Acids ◽  
Nitrogen Excretion ◽  
Acid Mixture ◽  
Rapid Weight Loss ◽  
Urinary Nitrogen

When blood plasma proteins are depleted by bleeding with return of red cells suspended in saline (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet nitrogen intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and intoxication and probably to vitamin deficiency. When the diet nitrogen is provided by certain mixtures of the ten growth essential amino acids plus glycine, given intravenously at a rapid rate, plasma protein production is good. The same mixture absorbed subcutaneously at a slower rate may be slightly better utilized. Fed orally the same mixture is better utilized and associated with a lower urinary nitrogen excretion. An ample amino acid mixture for the daily intake of a 10 kilo dog may contain in grams dl-threonine 1.4, dl-valine 3, dl-leucine 3, dl-isoleucine 2, l(+)-lysine·HCl·H2O 2.2, dl-tryptophane 0.3, dl-phenylalanine 2, dl-methionine 1.2, l(+)-histidine·HCl·H2O 1, l(+)-arginine·HCl 1, and glycine 2. Half this quantity is inadequate and not improved by addition of a mixture of alanine, serine, norleucine, proline, hydroxyproline, and tyrosine totalling 1.4 gm. Aspartic acid appears to induce vomiting when added to a mixture of amino acids. The same response has been reported for glutamic acid (8). Omission from the intake of leucine or of leucine and isoleucine results in negative nitrogen balance and rapid weight loss but plasma protein production may be temporarily maintained. It is possible that leucine may be captured from red blood cell destruction. Tryptophane deficiency causes an abrupt decline in plasma protein production. No decline occurred during 2 weeks of histidine deficiency but the urinary nitrogen increased to negative balance. Plasma protein production may be impaired during conditions of dietary deficiency not related to the protein or amino acid intake. Skin lesions and liver function impairment are described. Unidentified factors present in liver and yeast appear to be involved.

scholarly journals PLASMA PROTEIN AND HEMOGLOBIN PRODUCTION

1947 ◽  
Vol 85 (3) ◽  
pp. 243-265 ◽  
Author(s):  
F. S. Robscheit-Robbins ◽  
L. L. Miller ◽  
G. H. Whipple
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Protein ◽  
Nitrogen Balance ◽  
Essential Amino Acids ◽  
Amino Acid Mixture ◽  
Blood Protein ◽  
Acid Mixture ◽  
Amino Acid Mixtures ◽  
Urinary Nitrogen

Given healthy dogs fed abundant iron and protein-free or low protein diets with sustained anemia and hypoproteinemia, we can study the capacity of these animals to produce simultaneously new hemoglobin and plasma protein. Reserve stores of blood protein-building materials are measurably depleted and levels of 6 to 8 gm. per cent for hemoglobin and 4 to 5 gm. per cent for plasma protein can be maintained for weeks or months depending upon the intake of food proteins or amino acid mixtures. These dogs are very susceptible to infection and various poisons. Dogs tire of these diets and loss of appetite terminates many experiments. Under these conditions (double depletion) standard growth mixtures of essential amino acids are tested to show the response in blood protein output and urinary nitrogen balance. As a part of each tabulated experiment one of the essential amino acids is deleted from the complete growth mixture to compare such response with that of the whole mixture. Methionine, threonine, phenylalanine, and tryptophane when singly eliminated from the complete amino acid mixture do effect a sharp rise in urinary nitrogen. This loss of urinary nitrogen is corrected when the individual amino acid is replaced in the mixture. Histidine, lysine, and valine have a moderate influence upon urinary nitrogen balance toward nitrogen conservation. Leucine, isoleucine, and arginine have minimal or no effect upon urinary nitrogen balance when these individual amino acids are deleted from the complete growth mixture of amino acids during 3 to 4 week periods. Tryptophane and to a less extent phenylalanine and threonine when returned to the amino acid mixture are associated with a conspicuous preponderance of plasma protein output over the hemoglobin output (Table 4). Arginine, lysine, and histidine when returned to the amino acid mixture are associated with a large preponderance of hemoglobin output. Various amino acid mixtures under these conditions may give a positive urinary nitrogen balance and a liberal output of blood proteins but there is always weight loss, however we may choose to explain this loss. These experiments touch on the complex problems of parenteral nutrition, experimental and clinical.

scholarly journals MAXIMAL HEMOGLOBIN AND PLASMA PROTEIN PRODUCTION UNDER THE STIMULUS OF DEPLETION

1945 ◽  
Vol 82 (5) ◽  
pp. 311-316 ◽  
Author(s):  
F. S. Robscheit-Robbins ◽  
L. L. Miller ◽  
G. H. Whipple
Keyword(s):  
Plasma Protein ◽  
Protein Production ◽  
Intravenous Iron ◽  
Protein Diet ◽  
Blood Protein ◽  
Limiting Factor ◽  
The Face ◽  
Maximal Output ◽  
Maximal Plasma ◽  
Diet Intake

The maximal output ceiling for hemoglobin in anemia due to blood loss is about 60 gm. per week—the dog receiving a rich protein diet plus high iron intake. Ferrous and ferric salts are equally effective. Iron intravenously plus a rich protein diet may push this level up to 90 to 100 gm. per week. Evidently iron absorption is a limiting factor. Maximal output for hemoglobin plus plasma protein in doubly depleted dogs may reach 120 to 130 gm. per week and using intravenous iron may reach 140 to 160 gm. per week. Maximal output for plasma protein alone in hypoproteinemia due to plasmapheresis reaches 60 to 70 gm. per week but this is not the true ceiling. Technically we cannot remove the new plasma protein as fast as it is formed and the hypoproteinemia is not maintained in the face of a rich protein diet intake. Furthermore the evidence points to the protein circulating pool contributing to the accretion of tissue protein in such dogs with a strong positive nitrogen balance and weight gain. Maximal figures for hemoglobin production in anemia run close to 1 gm. hemoglobin per kilo per day. Maximal figures for new hemoglobin plus plasma protein production in anemia and hypoproteinemia using iron given intravenously, may reach 1.5 gm. blood protein per kilo per day. The actual maximal plasma protein production equals about 1 gm. per kilo per day but the true production ceiling cannot be reached by this technique, for reasons given above.

Purification of Antihemophilic Factor (Factor VIII) by Amino Acid Precipitation*

1964 ◽  
Vol 11 (01) ◽  
pp. 064-074 ◽  
Author(s):  
Robert H Wagner ◽  
William D McLester ◽  
Marion Smith ◽  
K. M Brinkhous
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Factor Viii ◽  
Plasma Protein ◽  
Acid Precipitation ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Specific Procedure ◽  
Beta Alanine ◽  
Antihemophilic Factor

Summary1. The use of several amino acids, glycine, alpha-aminobutyric acid, alanine, beta-alanine, and gamma-aminobutyric acid, as plasma protein precipitants is described.2. A specific procedure is detailed for the preparation of canine antihemophilic factor (AHF, Factor VIII) in which glycine, beta-alanine, and gammaaminobutyric acid serve as the protein precipitants.3. Preliminary results are reported for the precipitation of bovine and human AHF with amino acids.

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