scholarly journals A CONTRIBUTION TO THE CHEMOTHERAPY OF TUBERCULOSIS

1916 ◽  
Vol 24 (2) ◽  
pp. 107-147 ◽  
Author(s):  
Gensaburo Koga

Judging from the macroscopic and microscopic study of the animals treated with the liquid, its action upon the tubercular lesions seems to be about as follows: The effect of a single injection upon the lesions is either negative or inconspicuous. But after repeated injections of the preparation the congestion and leukocytic infiltration about the lesions are markedly decreased, the cheesy material resulting from degeneration of the lesions and other degeneration products are in process of absorption, and young connective tissue is being actively produced in the periphery. While these changes are taking place the number of the bacilli is also being reduced until finally they can no longer be detected on microscopic examination. Hence it appears that while the preparation may lack bactericidal action in vivo powerful enough to destroy all the bacilli at one injection, yet repeated infusions may nevertheless bring about the destruction of all the bacilli and the modification of the tubercular lesion into that of the suspended stage or even into the healed condition. Whether, therefore, the preparation brings about these results directly by killing the bacilli or indirectly by favoring the healing processes of the body, nevertheless it has power to inhibit the growth of or annihilate entirely the bacilli in vivo. The experiments reported leave no doubt that Liquid D is capable of bringing about the healing of experimental tubercular lesions; but thus far that most important problem in chemotherapeutics, namely, the extent of the cure produced, has not been solved. The experiments indicate that sterility of the tissues as far as microscopic examinations go has been secured; but microscopic examination is not after all an absolute test of sterility. In order to test this point, emulsions were made of the lungs, liver, spleen, and other organs of Treated Animals 134 and 135 (Table VII), and they were inoculated into the abdominal cavity of guinea pigs. Some of the animals receiving the emulsion developed tuberculosis, and therefore absolute sterility of the treated animals had not been obtained in these instances. The problem of the destination and distribution of the preparation in the body of the treated animal, as well as its action against the tubercle bacilli, lesions, and the tubercular organs of the infected guinea pigs, is now being studied further with results to be reported at some future time.

Author(s):  
A. L. Kravtsov ◽  
A. Yu. Goncharova ◽  
S. A. Bugorkova ◽  
Z. L. Devdariani ◽  
V. A. Kozhevnikov

The purpose of the study was to determine the effect of Yersinia pestis EV NIIEG on the process of neutrophil extracellular traps formation in vivo when modeling plague infection and assess their contribution to antiplague protection.Materials and methods. BALB/c mice, which were immunized subcutaneously with the Y. pestis EV NIIEG vaccine strain, were used in the study. Animals were infected with a virulent strain Y. pestis 231 at a dose of 20 LD50 (103 CFU). To evaluate the contribution of neutrophil extracellular traps (NETs) to antibacterial protection, an experimental model was used based on fermenting NETs in the abdominal cavity of mice with nuclease. To calculate the number of NETs in peritoneal exudate (PE) fluorescent microscopy was applied. Phagocytic activity of PE cells was determined by flow cytometry. Bactericidal effect of NETs was recorded using bacteriological method.Results and discussion. In pre-immunized mice, the process of NETs formation in response to the reintroduction of plague microbe living cells was 5 times more intense than in intact animals and was accompanied by a significant increase in the killing of Y. pestis cells in PE. The use of micrococcus nuclease in the experiment for fermentation of the NETs, produced in the body of immunized animals, provided evidence of NET participation in conferring anti-infective protection against plague infection. Thus, the established fact of the NET formation in case of Y. pestis infection of mice immunized with Y. pestis EV NIIEG vaccine strain and the influence of this process on the effectiveness of protection against plague is the basis for further clarifying the immunopathogenetic role of neutrophil granulocytes in plague. 


2019 ◽  
Vol 1 (1) ◽  
pp. 20-31
Author(s):  
Généviève Nguedia ◽  
Emile Miégoué ◽  
Fernand Tendonkeng ◽  
Mouchili Mama ◽  
Et Etienne Tedonkeng Pamo ◽  
...  

The intake and in vivo digestibility of Trypsacumlaxum in guinea pigs according to the graded level of spirulina was evaluated in Cameroon. 20 animals aged of 6 months with an average weight of 450 ± 50 g were randomly divided into 4 equivalent groups. Each group received T. laxum and 40g of compound feed containing 0% (TS0), 2% (TS2), 4% (TS4), and 6% (TS6) of spirulina. Feed intake was the different between the left over and the quantity served. The sample of T. laxum and those of each diet as well as feces were collected and analyzed for the apparent digestibility of each nutrient. Animals were weighed at the beginning and at the end of each period of the test to determine the body weight gain. This study showed that the average daily intake of dry matter (DM) for TS0, TS2, TS4 and TS6 was 74.39 ± 2.98, 78.66 ± 3.14, 83.89 ± 4.28 and 77.76 ± 4.40 g/head/day. The highest apparent digestibility coefficients of different nutrients were obtained with animals fed TS6 group while the lowest were observed in TS0.The apparent digestibility coefficient of dry matter (DM), organic matter (OM) and crude protein (CP) of the supplemented group were statistically higher than those of the control diet. Animals’ weight performances were statistically comparable between treatments. Thus, the combination of T. laxum with concentrated feed containing spirulina can be recommended for guinea-pigs, but the level of incorporation may not exceed 4% of its daily ration.


1994 ◽  
Vol 267 (4) ◽  
pp. R1078-R1088 ◽  
Author(s):  
B. Rubinsky ◽  
J. S. Hong ◽  
K. B. Storey

Two visual techniques were used to analyze the patterns of natural freezing and thawing in freeze-tolerant hatchling painted turtles Chrysemys picta marginata. Directional solidification plus light microscopy of liver, heart, and skeletal muscle slices was used to compare freezing at -4 degrees C (a survivable temperature in vivo) and -20 degrees C (not survivable). At -4 degrees C tissues showed large amounts of ice in expanded extracellular and vascular spaces, occupying 36% (liver) and 61% (muscle) of total tissue volume. Cells at -4 degrees C were shrunken, but intracellular water remained; at -20 degrees C, however, cells showed little evidence of free water. Liver micrographs showed novel spherical shells of water associated with intracellular particles (apparently glycogen granules) suggesting that a noncolligative method of cell water retention was employed. Proton magnetic resonance imaging was used for noninvasive analysis of freezing and thawing in the intact animal. Images showed that freezing propagated in a directional manner through the body with ice formed first in extraorgan spaces (e.g., abdominal cavity, brain ventricles). However, thawing occurred uniformly throughout the body core, and organs melted more rapidly than the extraorgan ice surrounding them.


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.


2020 ◽  
Author(s):  
V. Gauttier ◽  
A. Morello ◽  
I. Girault ◽  
C. Mary ◽  
L. Belarif ◽  
...  

AbstractThe COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) which enters the body principally through the nasal and larynx mucosa and progress to the lungs through the respiratory tract. SARS-CoV-2 replicates efficiently in respiratory epithelial cells motivating the development of alternative and rapidly scalable vaccine inducing mucosal protective and long-lasting immunity. We have previously developed an immunologically optimized multi-neoepitopes-based peptide vaccine platform which has already demonstrated tolerance and efficacy in hundreds of lung cancer patients. Here, we present a multi-target CD8 T cell peptide COVID-19 vaccine design targeting several structural (S, M, N) and non-structural (NSPs) SARS-CoV-2 proteins with selected epitopes in conserved regions of the SARS-CoV-2 genome. We observed that a single subcutaneous injection of a serie of epitopes induces a robust immunogenicity in-vivo as measured by IFNγ ELIspot. Upon tetramer characterization we found that this serie of epitopes induces a strong proportion of virus-specific CD8 T cells expressing CD103, CD44, CXCR3 and CD49a, the specific phenotype of tissue-resident memory T lymphocytes (Trm). Finally, we observed broad cellular responses, as characterized by IFNγ production, upon restimulation with structural and non-structural protein-derived epitopes using blood T cells isolated from convalescent asymptomatic, moderate and severe COVID-19 patients. These data provide insights for further development of a second generation of COVID-19 vaccine focused on inducing lasting Th1-biased memory CD8 T cell sentinels protection using immunodominant epitopes naturally observed after SARS-CoV-2 infection resolution.Statement of SignificanceHumoral and cellular adaptive immunity are different and complementary immune defenses engaged by the body to clear viral infection. While neutralizing antibodies have the capacity to block virus binding to its entry receptor expressed on human cells, memory T lymphocytes have the capacity to eliminate infected cells and are required for viral clearance. However, viruses evolve quickly, and their antigens are prone to mutations to avoid recognition by the antibodies (phenomenon named ‘antigenic drift’). This limitation of the antibody-mediated immunity could be addressed by the T-cell mediated immunity, which is able to recognize conserved viral peptides from any viral proteins presented by virus-infected cells. Thus, by targeting several proteins and conserved regions on the genome of a virus, T-cell epitope-based vaccines are less subjected to mutations and may work effectively on different strains of the virus. We designed a multi-target T cell-based vaccine containing epitope regions optimized for CD8+ T cell stimulation that would drive long-lasting cellular immunity with high specificity, avoiding undesired effects such as antibody-dependent enhancement (ADE) and antibody-induced macrophages hyperinflammation that could be observed in subjects with severe COVID-19. Our in-vivo results showed that a single injection of selected CD8 T cell epitopes induces memory viral-specific T-cell responses with a phenotype of tissue-resident memory T cells (Trm). Trm has attracted a growing interest for developing vaccination strategies since they act as immune sentinels in barrier tissue such as the respiratory tract and the lung. Because of their localization in tissues, they are able to immediately recognize infected cells and, because of their memory phenotypes, they rapidly respond to viral infection by orchestrating local protective immune responses to eliminate pathogens. Lastly, such multiepitope-based vaccination platform uses robust and well-validated synthetic peptide production technologies that can be rapidly manufactured in a distributed manner.


2008 ◽  
Vol 87 (4) ◽  
pp. 378-380 ◽  
Author(s):  
F.X. Reichl ◽  
M. Seiss ◽  
N. Kleinsasser ◽  
K. Kehe ◽  
K.H. Kunzelmann ◽  
...  

Bisphenol-A-glycidyldimethacrylate (BisGMA) is used in many resin-based dental materials. It was shown in vitro that BisGMA was released into the adjacent biophase from such materials during the first days after placement. In this study, the uptake, distribution, and excretion of [14C]BisGMA applied via gastric and intravenous administration (at dose levels well above those encountered in dental care) were examined in vivo in guinea pigs to test the hypothesis that BisGMA reaches cytotoxic levels in mammalian tissues. [14C]BisGMA was taken up rapidly from the stomach and intestine after gastric administration and was widely distributed in the body following administration by each route. Most [14C] was excreted within one day as 14CO2. The peak equivalent BisGMA levels in guinea pig tissues examined were at least 1000-fold less than known toxic levels. The peak urine level in guinea pigs that received well in excess of the body-weight-adjusted dose expected in humans was also below known toxic levels. The study therefore did not support the hypothesis.


Author(s):  
Adriana CHENDE ◽  
Cristian MARTONOS ◽  
Adrian Florin GAL ◽  
Vasile RUS ◽  
Viorel MICLĂUȘ ◽  
...  

In this study, the caecum of five guinea pigs was anatomically, histologically, and histochemically analyzed. From an anatomical point of view, it has been proved that the caecum in guinea pigs occupies the caudal segment of the abdominal cavity and consists of three parts: the ampullary portion, the body of the caecum, and the apex of the caecum, without a caecal appendix. In our histological analysis, we observed that the caecum has a simple structure, and the cecal mucosal glands are rare and contain, in addition to enterocytes, a small number of goblet cells, which are better represented in the deep part of the glands. Histochemically it has been observed that goblet cells are PAS and Alcian blue positive, which shows that they secrete both neutral and acidic mucins. The intensity of these two histochemical reactions is similar to that of goblet cells from other intestinal segments, proving that they are typical goblet cells. The large volume of the caecum suggests that this is an important section for the digestion process, although the relatively simple structure of the caecal mucosa suggests that the digestion here is not preponderant, but only complements the intestinal one.


1939 ◽  
Vol 69 (4) ◽  
pp. 555-578 ◽  
Author(s):  
Max B. Lurie

1. The fate of bacilli of reinfection at the portal of entry and in metastatic foci, and also the associated host responses, are essentially similar in rabbits and guinea pigs. 2. However, in the guinea pig tubercle bacilli of reinfection are more effectively fixed at the portal of entry than in the rabbit. 3. The guinea pig fixes at the site of reinfection unrelated substances, such as trypan blue and agar particles, more effectively than the rabbit. 4. At the site of a local non-specific inflammation precipitins from the circulating blood accumulate in higher concentration in tuberculous guinea pigs than in tuberculous rabbits. 5. These differing fixing capacities of the two species are associated with differences of extracellular character in the inflammation resulting from reinfection. (a) In the guinea pig, whose tissues are highly sensitized and greatly injured by the tubercle bacillus, the lymphatics adjoining the site of reinfection become thrombosed. In the rabbit whose tissues are moderately sensitized and less injured by the tubercle bacillus the corresponding lymphatics remain open. (b) In the guinea pig the fibrinous network at the site of inflammation forms a fine sieve-like structure. In the rabbit this network forms a coarse sieve-like barrier. 6. In rabbits and guinea pigs primarily infected, the destruction of tubercle bacilli takes place first and most extensively at the portal of entry. At this time they are less effectively destroyed in the nearest metastatic foci. Simultaneously they are still growing without hinderance in such foci in remote internal organs. 7. The cell-free body fluids of normal animals support the growth of tubercle bacilli in vivo. The body fluids of tuberculous animals under the same conditions are bacteriostatic for this microorganism. 8. Tubercle bacilli often multiply by preliminary subdivision into non-acid-fast granules, from which the acid-fast rods sprout. This confirms the work of Kahn.


1937 ◽  
Vol 65 (3) ◽  
pp. 339-345 ◽  
Author(s):  
H. E. Fierz ◽  
W. Jadassohn ◽  
W. Stoll
Keyword(s):  
The Body ◽  

Injection of sodium atoxyl-diazoamino-sulfoanthranilate into guinea pigs produces an anaphylactic hypersensitiveness to the corresponding azoprotein (Schultz-Dale test). This leads to the conclusion that the injected sodium atoxyl-diazoamino-sulfoanthranilate first decomposes and then couples in vivo with the body protein to form the corresponding azoprotein and that therefore it is this compound, produced within the organism itself, which sensitizes.


2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.


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