scholarly journals THE FATE OF TYPHOID BACILLI WHEN INJECTED INTRAVENOUSLY INTO NORMAL RABBITS

1915 ◽  
Vol 22 (4) ◽  
pp. 475-483 ◽  
Author(s):  
Carroll G. Bull

Typhoid bacilli are agglutinated promptly in the circulating blood of normal rabbits and quickly removed from the blood stream. The clumped bacilli accumulate in the organs and are taken up by assembled polymorphonuclear leucocytes in the liver, spleen, and possibly other organs. The phagocyted clumps of bacilli are digested and destroyed by the phagocytes. Hence, destruction of typhoid bacilli intra vitam is brought about by an entirely different process than is the destruction by serum and whole blood in vitro. While the latter is caused by bacteriolysis, the former results from agglutination and intraphagocytic digestion. Lysis by fresh blood serum is not appreciably affected by spleen or kidney pulp, but it is inhibited by liver pulp. The action of the liver is referable to its biliary constituents, which exert anticomplementary action. Probably in certain examples of typhoid fever in man the typhoid bacilli in the circulating blood being inagglutinable cannot be removed by the organs and hence are not phagocyted and destroyed. The observed disparity between the ready destruction of typhoid bacilli by serum and shed blood and the resistance sometimes offered by the bacilli in the infected body is explained by the essential differences in the destructive processes in operation within and without the body.

1953 ◽  
Vol 97 (2) ◽  
pp. 297-314 ◽  
Author(s):  
Lucien A. Gregg ◽  
O. H. Robertson

With the purpose of ascertaining the influence exerted by the pneumococcidal activity of the blood on the course of bacteremia occurring in experimental canine pneumococcal pneumonia, a study was made of the rates at which intravenously injected pneumococci disappeared from the circulation and the shed blood of diseased dogs. Preliminary studies on normal animals showed that blood containing hundreds of thousands of pneumococci per cc. immediately after injection usually became sterile or nearly so within an hour's time. Simultaneous observations carried out on the blood in vitro showed an analogous rapid disappearance of the microorganisms, although the effect was not quite as marked. Similar tests on non-bacteremic dogs with pneumonia revealed essentially the same ability of the body to dispose of large numbers of circulating pneumococci. The shed blood likewise exhibited marked bactericidal power. The occurrence of bacteremia during pneumonia did not retard greatly the rate at which injected pneumococci disappeared from the circulation, as compared with the non-bacteremic state. After several hours the numbers of circulating microorganisms were approximately the same as prior to the intravenous injection. Blood in vitro often cleared as fully as it did in vivo over the same length of time. Studies on the role played by humoral immune substances in the bactericidal action of the blood showed that while their presence was necessary for maximum killing power, and that bacteremic blood lacking humoral immune properties was rarely capable of self-sterilization in vitro, nevertheless such blood often retained considerable bactericidal potency as shown by its ability to reduce materially the numbers of pneumococci added to it. This phenomenon is discussed. The marked pneumococcidal capacity of the blood exhibited by dogs with experimental pneumococcal pneumonia and its persistence during bacteremia suggest that this constitutes the principal mechanism for limiting the degree of blood invasion. The similarity of the findings in canine and human pneumococcal lobar pneumonia is pointed out.


1909 ◽  
Vol 11 (6) ◽  
pp. 786-797 ◽  
Author(s):  
Andrew Watson Sellards

These experiments suggest the following conclusions concerning hemolytic action: 1. It is probably the proteid part of the serum which inhibits the bile salts. 2. The cholalic acid group is the active part of the bile salt molecule. 3. The protection afforded by bile salts against serum is of especial interest from the following considerations: (a) The protective action is a property apparently peculiar to proteids obtained from blood serum. It is not given satisfactorily by egg albumen. (b) The conjugation of cholalic acid with glycocoll in the formation of the bile salts is of some advantage to the organism. Although the toxicity of the cholalate for red corpuscles, when free from serum, is at most only slightly diminished by conjugation, yet the blood serum possesses a greater inhibiting action for the resulting glycocholate than for the original cholalate. 4. As compared with its inhibition of sodium glycocholate, normal serum possesses relatively little inhibiting action against certain foreign hemolytic agents, such as tetanus toxin, sodium benzoate, phenol and ethyl alcohol. 5. Hemolytic experiments afford a fairly general method for studying, in vitro, certain syntheses occurring in the body. They avoid, largely, the complications, such as rapid chemical alteration, which might occur in animal experimentation. Contrary to the results obtained with bile salts, the conjugation of benzoic acid and of phenol results in an effective reduction of their hemolytic action independently of the presence or absence of serum.


1973 ◽  
Vol 51 (6) ◽  
pp. 577-587 ◽  
Author(s):  
N. R. Roller ◽  
S. S. Desser

The rate of initiation of exflagellation of microgametocytes of Leucocytozoon simondi was studied in relation to temperature, age and density of gametocytes, and changes in gas composition. Observations were made in vitro through examination of fresh blood, and thin blood films were prepared at appropriate intervals. An inverse relationship between temperature and the time required for initiation of ex-flagellation was demonstrated. There was a decrease in the time required for initiation of exflagellation as the temperature increased from 15 to 26C. Between 26 and 40C exflagellation usually occurred in 1–1½ min. Exflagellation at 40C, which approximates the body temperature of the host, indicates that a drop in temperature per se is not necessary for the initiation of exflagellation. Gametocytes appear to be capable of exflagellation for about 5 days postmaturity. Differences in density of parasitemia do not affect the time for initiation of exflagellation. The presence of O2 and a decrease in CO2 are important stimuli for exflagellation. The effect of the above factors on the initiation of exflagellation is discussed in relation to the uptake of infected blood by the simuliid vector of the parasite, and compared with the situation in related Haemosporina


1936 ◽  
Vol 64 (2) ◽  
pp. 307-330 ◽  
Author(s):  
John F. Enders ◽  
Morris F. Shaffer ◽  
Chao-Jen Wu

Among the experimental findings reported in this paper to which we wish to give particular emphasis are the following: 1. The results which follow the intravenous injection into rabbits of two strains of Pneumococcus Type III of different degrees of virulence vary with the state of the capsule. Thus when this structure is completely developed both remain in the blood. A culture of either strain begins to become susceptible to the blood-clearing mechanism contemporaneously with the onset of capsular degeneration and the initiation of other concomitant changes at the surface of the organism (cf Paper II), which occur much earlier with the less virulent strain. 2. When, in either case, removal from the blood stream occurs, this is effected by the phagocytic cells of the body. There is no suggestion that a new or unknown mechanism is involved. The greatest share of the burden is borne by the fixed phagocytic cells of the liver and spleen, and to a less extent by those of the lung and bone marrow. Nevertheless, it has been demonstrated that the polymorphonuclear leucocytes may also participate. 3. Phagocytosis by the leucocytes of the normal animal either in intro or in vivo has been observed only at such a time as the capsule has become impaired. Ingestion of the organisms by the fixed tissue cells appears also to be effective only under the same condition and is accordingly observed with much younger cultures of the less virulent strain. 4. Following their removal from the blood and their accumulation within the fixed phagocytes of the organs, destruction of most of the cocci proceeds within 2 to 4 hours. Both strains are destroyed provided they are in the state favorable to phagocytic attack. 5. Evidence has been presented which indicates that just as in vitro, so in a local area of inflammation within the body, aging with attendant capsular loss and increasing susceptibility to phagocytosis may take place. 6. With organisms from either strain a variable period of lag follows their injection into the blood stream, even when they are introduced in a state of active multiplication and complete encapsulation. 7. Differences in virulence for rabbits of two strains of Pneumococcus Type III do not imply that this animal possesses a defensive mechanism which is absent in other species, since it has been possible to demonstrate similar differences when the organisms are injected intravenously into mice. This fact indicates that the factors determining the degree of virulence of these strains are to be sought in the organisms themselves, rather than in the kind of host.


1926 ◽  
Vol 44 (5) ◽  
pp. 625-634
Author(s):  
F. S. Jones

The experiments are of interest in several respects. It is clear that crystallized egg albumen is rapidly eliminated from the circulation and in the experiments cited it could no longer be detected after 18 or 19 hours. A considerable portion of it rapidly passes through the kidney in an apparently unaltered state. Evidently this passage begins almost at once and may continue for a day or two. In an experiment not reported in this paper, egg albumen appeared in naturally voided urine 2 hours following its injection into the peritoneal cavity. In the experiments reported no urine was voided until 5½ and 6½ hours following intravenous administration, but in each instance egg albumen was present in considerable amounts. However, sufficient egg albumen must have been utilized to produce antibody. It is hardly to be expected that such a protein, whose elimination is so rapid, could persist unaltered within the body and reappear within the circulation coincident with its antibody. The behavior of the protein cannot be ascribed to alterations which may have taken place during the process of crystallization since Ascoli showed that the proteins of egg white readily pass from the circulation into the urine. Certain observations of the writer confirm this point. The experience of Alexander, Becke, and Holmes who exposed sensitized guinea pigs to sprays of dilute egg white with the result that 80 per cent of the animals developed symptoms of anaphylaxis, further strengthens the contention that certain of the membranes are readily permeable for the proteins of egg. The conditions following the injection of casein are different. There is no appreciable passage through the kidney. Casein is present within the circulation for a considerable period; it could be detected in the blood serum 12 and 13 days after its introduction into the peritoneal cavity. Antibody appeared on the 7th and 8th days, respectively, so that both antigen and antibody were present in the serum for a period of 3 or 4 days. The phenomenon of antigen and antibody occurring together might be explained on the ground that certain proteins are utilized slowly and that the antibody found in the blood, usually after the 7th day, results from the portion of antigen first utilized. During the next few days a continual supply of antibody enters the circulation and during the period there is a steady utilization of the antigenic substance; it is possible that during this time there is constant union of antigen and antibody within the blood, with the slow utilization of the antigen and a slight utilization of the antibody which is made up by a slow increase from the body cells. Thus there would be a period in which considerable antigen would be present with weak antibody, succeeded by a second period when the amount of antigen would be small with well defined antibody, and finally only antibody. Certain observations tend to support such a view. Bayne-Jones injected rabbits whose serum contained precipitin from egg albumen with this substance and noted the occurrence of both antigen and antibody for a period of 48 hours. Some of his experiments in vitro are equally suggestive. In one instance a rabbit well immunized with egg albumen was injected intravenously with this substance. An hour later it was bled and the stored serum refrigerated for a period. During this time there was a slow spontaneous precipitation with a decline in both precipitin and antigen titer, but even after 6 days both were present. After a longer period only antigen remained. P. A. Lewis and D. Loomis have shown that an injection of sheep red blood cells in guinea pigs results in a well defined hemolysin titer about the 9th day, followed by a definite decline, with a secondary rise in hemolysin until the peak is reached on the 20th day. It becomes evident, then, that the reaction of the rabbit to a single injection of a relatively pure protein will depend on the character of the protein injected. When crystallized egg albumen is administered it is rapidly eliminated from the circulation. The rapid disappearance of the egg albumen from the blood stream is partly accounted for by its prompt elimination through the urine. Antibody appears in the serum from the 7th to the 10th day. Casein behaves differently. It persists in the blood for a considerable period; after the 7th or 8th day both antigen and antibody may be demonstrated in the blood. Casein cannot be detected in the urine following its injection into the body. The behavior of casein within the body affords an analogy with the conditions frequently noted after the administration of foreign serum, in both cases both antigen and antibody may be present in the circulation together.


2019 ◽  
Vol 21 (94) ◽  
pp. 103-108 ◽  
Author(s):  
A. Y. Ostapyuk ◽  
B. V. Gutyj

The article presents the results of studies on the influence of cadmium sulfate in different doses on the organism of poultry. Absorbed cadmium accumulates in the liver as a complex with metallothionein. The purpose of the work was to find out the effect of cadmium sulfate in doses of 2 and 4 mg / kg of body weight on the functional state of the liver of chicken. For research, three groups of birds were formed: control and two experimental. The control group of chickens were in the usual diet, they were fed with forage and were given water without introducing cadmium sulfate. To the drinking water of chickens of experimental groups for 30 days, added cadmium sulfate in doses: the first group – 2 mg/kg, the second group – 4 mg/kg body weight. The conditions for keeping chickens and the microclimate parameters in the room for all bird groups were similar. Blood from the chickens was taken from the subclavian vein in periods: before the dasg was given and on the first, seventh, fourteenth, twenty-first and thirtieth day of the experiment. It was determined that the presentation of cadmium sulfate in doses of 2 and 4 mg/kg of body weight of cows, which contributed to a violation of the functional state of the liver, as evidenced by the increased activity of aminotransferases in their blood serum. The activity of alanine and aspartate aminotransferase was higher in serum of blood of chickens in the second experimental group at 21st and 30th days of the experiment. The high activity of aminotransferases in the blood serum of chickens for cadmium loading indicates destructive processes in the liver that cause an increase in the release of aminotransaminases from cellular organelles in the blood of experimental poultry. Thus, the obtained results indicate an increase in destructive processes in the body of chickens for cadmium loading.


1923 ◽  
Vol 37 (4) ◽  
pp. 511-524 ◽  
Author(s):  
Elizabeth Pauline Wolf

1. None of the salts tested produce a marked inflammation in vivo in concentrations under 10 per cent. Potassium salts and the different citrates produced atypical inflammatory reactions in mice, but not in frogs. There was no true inflammation, however, characterized by blood vessel changes, migration of polymorphonuclear leucocytes and erythrocytes, and fluid exudation. 2. Synergistic action occurs when equal parts of strontium and magnesium salts are employed. There is a change in the appearance of the mesentery without a true inflammation, and this change does not occur with either salt alone. 3. Amino-acids and amines as a class do not produce inflammation, but histamine produces a marked inflammatory reaction in frogs and mice. 4. Tyramine does not cause an inflammatory reaction but has other marked effects; agglutination thrombi occur within the smaller blood vessels, both veins and arteries; in frogs there is a rapid clumping of the white blood cells followed by a true coagulation with strands of fibrin and entanglement of erythrocytes. This is very widespread and often kills the animal within an hour after injection. In mice it is the erythrocytes that clump and coagulation occurs very much later, usually at the end of 24 hours; still later there is complete absorption of the coagulated masses and the mesenteric circulation returns to normal. None of the mice died during the stage of clumping, and the clots never extended up the larger vessels as they did in the frogs. These effects are similar to the phenomena observed in the in vitro work, in which clumping of the cells appeared constantly. 5. Cantharidinum, histamine, and turpentine produced the most rapid and marked inflammation of any substances tried. These substances are all strongly positively chemotactic in vitro. The differences occurring when these substances are used in different species is a quantitative rather than a qualitative one, the body temperature being of some importance. Papain acted only in warmblooded animals; this is consistent with its chemotactic action in vitro. The degree of positive chemotaxis varied markedly with the blood employed and in the in vivo work the inflammation varied with the species of animal used. 6. Certain substances produced inflammation only some time after injection; this is true of scarlet R and croton oil in weak dilutions. These are not strongly positively chemotactic. 7. Parazol produces an inflammation associated with necrosis of the tissues. This is similar to the results obtained in vitro, parazol being positively chemotactic in low concentrations and negative in high concentrations. 8. The exact chemical nature of many of the substances which produce marked inflammation is unknown. This is true of cantharidin, and the active constituents of turpentine and croton oil. 9. All substances which produce marked and rapid inflammation on injection are positively chemotactic, but not all strongly positively chemotactic substances produce inflammation; i.e., calcium compounds, sodium phosphate, etc. 10. Only substances which are positively chemotactic and also soluble in oil seem capable of producing inflammation in animals.


1927 ◽  
Vol 45 (5) ◽  
pp. 807-814 ◽  
Author(s):  
Hobart A. Reimann

It is conceivable that a change from the virulent, non-phagocytable S form of Pneumococcus to the avirulent phagocytable R form may take place in pneumococcus disease, but the experiments here reported do not settle the question whether or not this is an important factor in determining the outcome in natural infection. It has been shown experimentally that the degradation from the S form to the R form actually does take place in cultures of Pneumococcus growing in agar subcutaneously embedded in guinea pigs, in agar enclosed in vials subcutaneously embedded in rabbits, and spontaneously in the blood stream of infected horses. However, it was not possible in any of the experiments here cited to demonstrate the complete change from S to R pneumococci before the bacteria disappeared from the body. When the intermediate or R forms did appear, they were always accompanied and usually exceeded in number by the S forms and all three forms disappeared together. S organisms may disappear entirely without evidence of first going through the intermediate and R stages. On the other hand, contrary to expectations, pure cultures of R forms remained viable in subcutaneous foci for weeks although apparently freely accessible to the action of phagocytes. It seems of some significance that the R forms appeared early in the vials (inoculated with S pneumococci) in immunized and normal rabbits alike, indicating that the presence of demonstrable specific immune bodies was not alone responsible for the variation of the bacteria. Of some importance also is the fact that R forms were never derived from similarly prepared control cultures growing in vitro at the same temperature and immersed in normal serum, although the S forms remained viable and unaltered for 6 weeks. It is likely that variations of pneumococci do not occur readily when S cultures are exposed to normal serum in vitro, especially when growing in closed vials under a diminished oxygen supply, for it has previously been shown (2) that only slight variation occurs even after prolonged (240) transfers in heterologous serum broth in the test-tube. It is possible, therefore, that the variation which occurred among pneumococci growing in agar vials embedded in normal rabbits was actually provoked by unknown influences in the living tissue fluids. Although R forms have been shown to occur in vivo, no positive evidence can be derived from these experiments to prove that recovery from pneumococcus infection depends upon the degradation of the virulent S forms of pneumococci to the avirulent R forms and the subsequent destruction of the latter by phagocytes.


1920 ◽  
Vol 31 (3) ◽  
pp. 233-251 ◽  
Author(s):  
Carroll G. Bull ◽  
Luis Bartual

1. It has been shown that the whole uncoagulated blood of immune animals is not as highly pneumococcidal in vitro, as has been claimed by others. 2. Cultures of pneumococci in the fresh whole blood of immune animals, as compared with cultures in the blood of susceptible animals, show a greatly prolonged latent period, and, in a general way, the relative lengths of the latent periods of the cultures correspond to the relative resistances of the animals to infection by these organisms. 3. The blood of animals artificially immunized, both actively and passively, retards the growth of pneumococci in the same manner as the blood of naturally immune animals. 4. Microscopic examination of cultures of pneumococci in immune blood reveals chain formation, growth in clumps, and phagocytosis of the organisms by the polynuclear cells. It also shows that growth occurs first in the free serum, the clot being invaded later. 5. The retardation of multiplication depends on two factors, opsonization of the pneumococci by the immune serum and phagocytosis of the organisms by the polynuclear cells; growth readily occurs when either agent is absent. 6. Pneumococci multiply in defibrinated immune blood because few phagocytes are present after defibrination. 7. Pneumococci grow in the most potent immune blood after mechanical destruction of the white cells. 8. It has not been shown that immune blood does not kill a certain number of the pneumococci with which it is inoculated, but the tentative conclusion has been arrived at that no killing occurs since none of the tests became sterile during the course of our experiments.


2020 ◽  
Vol 65 (1) ◽  
pp. 37-41
Author(s):  
O. Bragina ◽  
A. Vorobyeva ◽  
V. Tolmachev ◽  
A. Orlova ◽  
V. Chernov ◽  
...  

Purpose: Evaluation of a radiopharmaceutical based on 99mTc-labeled targeted molecules DARPin9_29 for radionuclide diagnostics of malignancies with Her2/neu overexpression. Material and methods: The DARPin9_29 sequence was amplified from the plasmid pET-DARP-6HIS for the DARPin9_29-His6 gene expression in E. coli cells. The eluent of 99mTcO4– (400–500 μl, 4 GBq) was added to the kit and incubated at a temperature of 100 °C for 20 minutes. After incubation, 40 μl of tricarbonyl technetium was added to 168 μg of DARPin9_29 in 100 μl of PBS (sodium phosphate buffer), followed by incubation at 40 °C for 60 minutes. The radiochemical yield and purity were determined by thin layer radiochromatography, the purification was performed using NAP-5 cleansing columns (GE Healthcare). Cell lines with different levels of Her2/neu expression were used: SKOV-3> BT474 >> DU-145 for the determination of the radiopharmaceutical specificity. Her2/neu expressing cell line SKOV-3 was used for in vitro study. The study was conducted 6 hours after the administration of the drug. Results: The radiochemical yield was 72 ± 8 %, the radiochemical purity after purification was 98.7 ± 1.0 %. The stability in PBS (phosphate buffered saline) solution after 1 hour was 99.8 ± 0.2; after 3 hours – 98.2 ± 0.1. In vitro studies showed that the accumulation of explored compound was directly proportional to the level of Her2/neu expression in cells, while blocking the receptors with an excess of unlabeled protein showed a significant reduction in binding in the group of cells. Data on biodistribution and SPECT/CT in the body of the animal BALB/c nu/nu demonstrated rapid removal of the compound from the blood stream and high accumulation in the liver, kidney and bladder 6 hours after the introduction of the radiopharmaceutical. Conclusion: The studies demonstrated high radiochemical yields and purity, as well as stability of the studied compound. The results of in vitro and in vivo analysis showed the specificity and affinity of the radiopharmaceutical to the Her2/neu receptor on the surface of tumor cells. The high accumulation of the drug in the liver and kidneys, detected in in vivo studies, is probably due to the lipophilicity of the 99mTc(CO)3-histidine tag and indicates the limitation of its further clinical use in assessing the condition of the above organs, which will require additional diagnostic methods, as well as possible modification chemical structure.


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