scholarly journals THE RELATIVE REACTION WITHIN LIVING MAMMALIAN-TISSUES

1925 ◽  
Vol 41 (3) ◽  
pp. 399-411 ◽  
Author(s):  
Peyton Rous

The acidity of the macrophage granules in which litmus comes to be stored during life is considerable. It has proved possible to stain these granules in vivo with some of the phthalein indicators and the results, had they been obtained under controlled conditions, would indicate a pH of 3.0 or less. The amount of acid material which may accumulate within the cells of animals stained with litmus is great, sufficient in the case of the elements of a peritoneal exudate for the acid reaction to prevail when they are gathered together and crushed. The material is derived, not from the dye, but from living elements responding characteristically to a stimulus far from unique. Such responses may well play a rôle in normal physiological activities and in the cellular defense against microorganisms. Vital staining with litmus demonstrates anew that the intracellular reaction during life is independent of that of the body fluids. By means of color changes in the stored indicator one can distinguish sick as well as dead cells of certain sorts and follow their distribution and fate within the organism. There are data to suggest that with the aid of the indicator the normal period of survival of certain elements at least can be determined. By the indicator method, of which the foregoing observations afford a crude illustration, much should be learnt in the future about body processes. The present paper is the second of a series upon the theme.

1925 ◽  
Vol 41 (3) ◽  
pp. 379-397 ◽  
Author(s):  
Peyton Rous

The present paper is the first of a series of reports on the relative reaction of living tissues as determined by vital staining with indicators. It is possible to bring about a localized and a general coloration of living rats and mice with litmus. The animals remain in good health and the coloration of some of the tissues persists for months. Much of the dye is stored in cell granules, especially in those of the reticulo-endothelial elements, but a diffuse staining of certain tissues occurs, notably of bone, epidermis, cartilage, and connective tissue everywhere. In the intensity and localization of the bony coloration litmus has resemblances to madder. Diffuse staining with it renders blue most, if not all, of the tissues affected, while a granular staining causes others to become notably pink, owing to the fact that the indicator, though introduced into the organism in the blue form and circulating as such in the body fluids, is ordinarily red when stored in cells. The polymorphonuclear elements and macrophages of a peritoneal exudate, may become so laden with material colored red by litmus that the blue color of the fluid constituent is masked and the exudate appears a deep, turbid red. The phenomenon is but one manifestation of a notable acidity within cell granules throughout the organism. Like many another in the stained animals it would appear to be of physiological import. Some of the questions suggested by the work will be dealt with in the paper immediately following.


MRS Bulletin ◽  
1991 ◽  
Vol 16 (9) ◽  
pp. 75-77 ◽  
Author(s):  
James M. Anderson ◽  
Q. H. Zhao

The living body is an aggressive environment for almost all types of foreign materials, devices, prostheses, and artificial organs which are in contact with the tissues or body fluids of the living body. This aggressive environment can potentially produce changes in the chemical, physical, mechanical, and structural properties of biomaterials, i.e., biodegradation. The vast majority of biomedical polymers used today as biomaterials or in prostheses, devices, or artificial organs are considered biostable and are expected to resist the influence of the in vivo environment for the lifetime of the device or patient while retaining the necessary properties that fulfill the intended functions. In contrast, biodegradable or bioresorbable biomedical polymers are designed to be degraded and eliminated from the body by normal metabolic and physiological processes without adversely affecting body fluids, tissues, and organs.The term “biostability” commonly refers to the relative stability of biomedical polymers in the physiological environment as a function of time. It is advantageous to discuss biostability and biodegradation of biomedical polymers together. In vivo physiological mechanisms leading to changes in the properties of biomedical polymers are considered to be biodegradation phenomena, while biostable materials are considered to be those materials where physiological interactions do not lead to material property changes and loss of function during the service life of the biomedical polymer.


Attempts to achieve “internal disinfection,” that is to say, to kill organisms in the body of infected animals by means of drugs, have hitherto afforded little promise of success in the case of the common pathogenic bacteria, the only exception being the action of ethyl-hydrocuprein in pneumococcus infections, discovered by Morgenroth with his co-workers, Levy and others. The reasons for the failure are probably to be attributed mainly to two facts; in the first place, antiseptics in general enter into combination with proteins of the tissues and body fluids, either by a process of physical adsorption or by the formation of chemical compounds. In either case, the usual result is that the bactericidal action of a substance, as determined in a watery medium, is greatly reduced by protein-solutions, e. g. , serum. Secondly, the majority of chemical antiseptics are general protoplasm poisons, and exert on mammalian tissues a degree of toxic action equal to, or greater than, that which they exhibit towards micro-organisms; hence these substances prove lethal for animals in doses which are insufficient to confer bactericidal properties on the body fluids. The classical example of such failures was afforded by mercuric chloride, which Koch employed in the hope of treating effectively anthrax septicæmia in animals. Ehrlich and Bechhold investigated compounds which were more potent antiseptics than any hitherto known, among the most active being tetrabrom- (and chlor-) ortho-biphenol; they found, however, that the bactericidal properties of these substances were also greatly reduced when the organisms were suspended in a serum medium. Thus, tetrachlor-orthobiphenol in a concentration of 1 : 320,000 prevented the growth of diphtheria bacilli in bouillon, whereas in serum growth occurred in the presence of 1 : 10,000 of this reagent. Similarly we have found that the dose of perchloride of mercury which is required to inhibit completely the growth of Staphylococcus aureus or B. coli in serum is 100 times greater than that which produces this effect in watery medium containing a small amount of nutrient peptone (0·7 per cent.).


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.


1996 ◽  
Vol 320 (1) ◽  
pp. 315-319 ◽  
Author(s):  
Thomas HARI ◽  
Hans KUNZE ◽  
Ernst BOHN ◽  
Urs BRODBECK ◽  
Peter BÜTIKOFER

Glycosylphosphatidylinositol (GPI)-hydrolysing enzymes have been described in many mammalian tissues and body fluids; however, their site(s) of action and in vivo functions have remained unclear. In order to identify a possible intracellular site of GPI hydrolysis, we studied the subcellular distribution of GPI-hydrolysing activity in rat liver. We found that purified fractions from rat liver hydrolysed the GPI moieties of two GPI-anchored proteins with the specificity of a phospholipase D. This GPI-specific phospholipase D (GPI-PLD) activity was found to be highly enriched in a lysosomal fraction and showed a similar intracellular distribution to that of typical lysosomal enzymes. Our results indicate that lysosomes may represent a possible intracellular site of GPI-PLD action.


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.


1925 ◽  
Vol 41 (4) ◽  
pp. 451-470 ◽  
Author(s):  
Peyton Rous

Mice can be vitally stained with many of the phthalein indicators. The staining is diffuse, appearing to interfere not at all with health in the case of the majority of the dyes. The color phenomena show that these retain the character of indicators. A special technique has been evolved for the determination of the hues of the various organs, which are readily modified by extraneous influences. The ability to recognize that the pH has thus been altered is a signal advantage of the indicator method. Phthaleins of slightly alkaline range or one that trenches slightly on acidity have been employed for the work here reported. Cresol red, phenol red, and brom phenol red have proved especially useful. The observations with the three agree closely in pointing to the existence of notable differences between the reaction of the blood and that within the tissues generally. The hue of blood plasma from the right heart is such as to suggest that its reaction lies at about pH 7.38 ordinarily, whereas that of the most alkaline of the tissues, judging from its color, the connective tissue, would appear to have a pH of 7.2 or slightly less. The tendons seem to be nearly but not quite so alkaline. The other stained tissues without exception, are of a hue which would indicate that the reaction lies beyond the range of phenol red on the acid side, that is to say is at least as acid as pH 6.6. In a subsequent paper observations which accord with these findings, carried out with indicators of frankly acid range, will be described. On the exposure of tissues to air, without disturbance of the circulation, some of them become alkaline. In the case of connective tissue, at least, the change is a consequence of the escape of carbon dioxide. The gas passes readily in and out, exerting a practically immediate influence on the color of the tissue bared by eversion of a skin flap; and so much may be absorbed on exposure to pure carbon dioxide, when the surface is large, that a general acidosis results. The precise interpretation of the color changes in terms of pH waits necessarily upon further work.


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.


Author(s):  
А.А. Раецкая ◽  
С.В. Калиш ◽  
С.В. Лямина ◽  
Е.В. Малышева ◽  
О.П. Буданова ◽  
...  

Цель исследования. Доказательство гипотезы, что репрограммированные in vitro на М3 фенотип макрофаги при введении в организм будут существенно ограничивать развитие солидной карциномы in vivo . Методика. Рост солидной опухоли инициировали у мышей in vivo путем подкожной инъекции клеток карциномы Эрлиха (КЭ). Инъекцию макрофагов с нативным М0 фенотипом и с репрограммированным M3 фенотипом проводили в область формирования солидной КЭ. Репрограммирование проводили с помощью низких доз сыворотки, блокаторов факторов транскрипции STAT3/6 и SMAD3 и липополисахарида. Использовали две схемы введения макрофагов: раннее и позднее. При раннем введении макрофаги вводили на 1-е, 5-е, 10-е и 15-е сут. после инъекции клеток КЭ путем обкалывания макрофагами с четырех сторон область развития опухоли. При позднем введении, макрофаги вводили на 10-е, 15-е, 20-е и 25-е сут. Через 15 и 30 сут. после введения клеток КЭ солидную опухоль иссекали и измеряли ее объем. Эффект введения макрофагов оценивали качественно по визуальной и пальпаторной характеристикам солидной опухоли и количественно по изменению ее объема по сравнению с группой без введения макрофагов (контроль). Результаты. Установлено, что M3 макрофаги при раннем введении от начала развития опухоли оказывают выраженный антиопухолевый эффект in vivo , который был существенно более выражен, чем при позднем введении макрофагов. Заключение. Установлено, что введение репрограммированных макрофагов M3 ограничивает развитие солидной карциномы в экспериментах in vivo . Противоопухолевый эффект более выражен при раннем введении М3 макрофагов. Обнаруженные в работе факты делают перспективным разработку клинической версии биотехнологии ограничения роста опухоли, путем предварительного программирования антиопухолевого врожденного иммунного ответа «в пробирке». Aim. To verify a hypothesis that macrophages reprogrammed in vitro to the M3 phenotype and injected into the body substantially restrict the development of solid carcinoma in vivo . Methods. Growth of a solid tumor was initiated in mice in vivo with a subcutaneous injection of Ehrlich carcinoma (EC) cells. Macrophages with a native M0 phenotype or reprogrammed towards the M3 phenotype were injected into the region of developing solid EC. Reprogramming was performed using low doses of serum, STAT3/6 and SMAD3 transcription factor blockers, and lipopolysaccharide. Two schemes of macrophage administration were used: early and late. With the early administration, macrophages were injected on days 1, 5, 10, and 15 following the injection of EC cells at four sides of the tumor development area. With the late administration, macrophages were injected on days 10, 15, 20, and 25. At 15 and 30 days after the EC cell injection, the solid tumor was excised and its volume was measured. The effect of macrophage administration was assessed both qualitatively by visual and palpation characteristics of solid tumor and quantitatively by changes in the tumor volume compared with the group without the macrophage treatment. Results. M3 macrophages administered early after the onset of tumor development exerted a pronounced antitumor effect in vivo , which was significantly greater than the antitumor effect of the late administration of M3 macrophages. Conclusion. The observed significant inhibition of in vivo growth of solid carcinoma by M3 macrophages makes promising the development of a clinical version of the biotechnology for restriction of tumor growth by in vitro pre-programming of the antitumor, innate immune response.


2020 ◽  
Author(s):  
Johannes Karges ◽  
Shi Kuang ◽  
Federica Maschietto ◽  
Olivier Blacque ◽  
Ilaria Ciofini ◽  
...  

<div>The use of photodynamic therapy (PDT) against cancer has received increasing attention overthe recent years. However, the application of the currently approved photosensitizers (PSs) is somehow limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E’)-4,4´-bisstyryl 2,2´-bipyridine ligands showed impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While non-toxic in the dark, these compounds were found phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and be able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2 Photon excitation.</div>


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