Wound Contraction in Relation to Collagen Formation in Scorbutic Guinea-pigs

Development ◽  
1956 ◽  
Vol 4 (2) ◽  
pp. 167-175
Author(s):  
M. Abercrombie ◽  
M. H. Flint ◽  
D. W. James

A Wound in any mobile part of the skin of a mammal diminishes in area as it heals by a centripetal movement of the undamaged skin surrounding it. This movement, usually called wound contraction, depends on a pull exerted by the material within the wound (Lindquist, 1946; Abercrombie, Flint, & James, 1954; Billingham & Medawar, 1955). It is commonly believed that the effective force is developed by the newly formed collagen fibres. In a previous paper, however (Abercrombie, Flint, & James, 1954), we found that the course of the contraction of skin wounds in rats did not parallel the deposition of new collagen, chemically measured. This result, while certainly in no way conclusive by itself, suggested that the supposed role of collagen in contraction ought to be tested more stringently. This we have now done by measuring wounds made on guinea-pigs receiving a diet devoid of ascorbic acid.

Development ◽  
1954 ◽  
Vol 2 (3) ◽  
pp. 264-274
Author(s):  
M. Abercrombie ◽  
M. H. Flint ◽  
D. W. James

During the healing of an open wound in the loose skin of a mammal there occurs a conspicuous diminution of wound size, the result of a centripetal movement of the whole thickness of the surrounding skin, with a corresponding shrinkage of the wound content. This ‘wound contraction’ is distinct from the process of epithelialization. Many authors (e.g. v. Gaza, 1918; Lindquist, 1946) have supposed that wound contraction is in some way causally related to the process of collagen formation, which is simultaneously occurring in the wounded area. The investigation of this supposed relation requires a more exact quantitative picture of collagen formation in skin wounds than is at present available from histological studies (such as those of Dann, Glücksmann, & Tansley, 1941; Hunt, 1941; Lindquist, 1946) or from investigations of changes in tensile strength (such as those of Howes, Sooy, & Harvey, 1929; Botsford, 1941).


Blood ◽  
1961 ◽  
Vol 18 (3) ◽  
pp. 310-316 ◽  
Author(s):  
NICHOLAS L. PETRAKIS

Abstract Studies were made to evaluate the influence of ascorbic acid upon the differentiation of mononuclear leukocytes to fibroblasts when cultivated in diffusion chambers, in vivo. Ascorbic acid-depleted leukocytes grown in ascorbic acid-deficient host guinea pigs developed into abnormal cellular forms characterized by nuclear enlargement, multipolar mitoses, and giant forms These changes could be reversed by treatment of the host guinea pigs with ascorbic acid. The findings indicate a direct cellular role of ascorbic acid in the differentiation of mononuclear leukocytes to fibroblasts.


1962 ◽  
Vol 12 (3) ◽  
pp. 533-551 ◽  
Author(s):  
Russell Ross ◽  
Earl P. Benditt

The sequence encountered in healing skin wounds in scorbutic guinea pigs has been examined by methods of light and electron microscopy. Linear incisions in the skin of female guinea pigs fed a scorbutigenic diet were allowed to heal. The wounds were removed for examination at 1, 3, 5, 9, and 14 days after wounding. The fibroblasts of the scorbutic wounds differ from those of the controls in three major aspects. First, little collagen is present within the intercellular spaces, although small groups of individual collagen fibrils can be found adjacent to some of the fibroblasts; in addition, large amounts of somewhat fibrillar, poorly structured, dense matter are present throughout the extracellular regions. The second alteration consists of large aggregates of intracytoplasmic lipid deposits present within the majority of the fibroblasts. Third, the endoplasmic reticulum of the fibroblasts is altered in form from that of the controls. The profiles of the cisternae are round, non-continuous within the plane of section, and are less extensively developed than in the controls. An increased macrophagic activity of the histiocytes is also described. These changes are discussed in light of the available biochemical data associated with this abnormality of protein synthesis.


1990 ◽  
Vol 68 (10) ◽  
pp. 1166-1173 ◽  
Author(s):  
Harish Padh

It has long been suspected that ascorbic acid is involved in many cellular reactions. This is evident from the multitude of seemingly unrelated symptoms seen in scurvy. However, until recently, our understanding of its involvement was confined to its role in the synthesis of collagen. Studies in the past few years have unveiled mechanisms of its actions in collagen formation and many other enzymatic reactions. In addition, numerous physiological responses are reportedly affected by ascorbic acid. From the well-characterized enzymatic reactions involving ascorbic acid, it has become clear that in animal cells the ascorbate does not seem to be directly involved in catalytic cycles. Rather its major function seems to keep prosthetic metal ions in their reduced form. The role of ascorbate as a reductant in these enzymatic reactions complements its other antioxidant functions which have been recently appreciated, including that as a scavenger of free radicals. Therefore, it seems that the major function of ascorbate is to protect tissues from harmful oxidative products and to keep certain enzymes in their required reduced forms. However, it remains unclear how the deficiency of ascorbate leads to the pathological symptoms found in scurvy.Key words: ascorbic acid, vitamin C, biochemical functions, antioxidant, recommended dietary allowances, hydroxylation.


Blood ◽  
1956 ◽  
Vol 11 (2) ◽  
pp. 123-142 ◽  
Author(s):  
ROLV K. SLUNGAARD ◽  
GEORGE M. HIGGINS

Abstract Megaloblastosis has been produced in young guinea pigs by feeding them purified diets deficient its pteroylglutamic acid (PGA) or vitamin B12 or both. The withholding of ascorbic acid from the diet did not produce megaloblastosis but it greatly enhanced its development when PGA was also withheld. Spontaneous remission took place in several instances. The possible role of growth of the animal and changes in the bacterial flora of the gastrointestinal tract has been discussed. Bacteriologic studies appeared to indicate a possible interrelationship between the occurrence of Escherichia coli in the stools of guinea pigs consuming deficient diets and the development of megaloblastosis. Diarrhea and infections are considered important in the pathogenesis of megaloblastic anemia but infections were not observed in animals of the present study. However, diarrhea was a prominent feature and appeared to be a factor associated with megaloblastosis. Anemia was usually present in association with megaloblastosis; however, megaloblastosis of a mild degree appearing in some of the animals fed the diets deficient in PGA or vitamin B12 was not accompanied by anemia. When ascorbic acid was withheld in addition, then anemia always developed. A dimorphic picture of macrocytosis and microcytosis was found most commonly in the peripheral blood of animals with megaloblastosis. This has been explained on the basis of regenerative macrocytosis or as a disturbance of the maturation of erythrocytes in such deficiencies. Data obtained from peripheral blood are not a reliable indicator of megaloblastosis, nor is the clinical condition of the animal indicative of the pathologic state. One animal which had been fed a diet deficient in vitamin B12 and PGA and which showed megaloblasts in its bone marrow was given injections of vitamin B12. The megaloblastosis was corrected but the animal died on the sixteenth day of treatment. Two animals fed diets deficient in PGA and ascorbic acid were subsequently given injections of PGA and ascorbic acid. The results demonstrated that administration of ascorbic acid alone did not interrupt the development of severe megaloblastosis in the continuing absence of PGA. When PGA was given, reticuocytosis then ensued and there was a reversal of megaloblastic erythropoiesis.


1977 ◽  
Vol 11 (2) ◽  
pp. 113-117 ◽  
Author(s):  
J. C. S. Kim

Disorganization of muscle structures such as fragmentation of myofilaments with a loss of contrast in the Z bands, swelling of mitochondria and glycogenic infiltration, was seen in ascorbic acid deficient guinea-pigs. Vacuolar degeneration of external and internal endothelial cell membranes with accompanying dystrophic changes of the surrounding muscle and lack of collagen formation were consistent findings. Chondroblasts showed a marked dissolution of the matrix vesicle and a lack of hyaline droplets.


1970 ◽  
Vol 48 (10) ◽  
pp. 1178-1180
Author(s):  
M. C. Nath ◽  
Idrees Bhai

In the livers of the scorbutic guinea pigs the activity of p-hydroxyphenylpyruvic acid oxidase was found to remain unchanged but profoundly reduced after the feeding of extra tyrosine. Glucose cycloacetoacetate hydrolysate, a reducing compound, when ingested simultaneously with tyrosine was found to prevent the reduction in the enzyme activity. This effect was comparable to that of ascorbic acid.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Ioannis V. Yannas ◽  
Dimitrios S. Tzeranis

AbstractTo understand why mammals generally do not regenerate injured organs, we considered the exceptional case of spontaneous skin regeneration in the early lamb fetus. Whereas during the early fetal stage skin wounds heal by regeneration, in the late fetal stage, and after birth, skin wounds close instead by scar formation. We review independent evidence that this switch in wound healing response coincides with the onset of wound contraction, which is also enabled during late fetal gestation. The crucial role of wound contraction in determining the wound healing outcome in adults has been demonstrated in three mammalian models of severe injury (excised guinea pig skin, transected rat sciatic nerve, excised rabbit conjunctival stroma) where grafting the injury with DRT, a contraction-blocking scaffold of highly-specific structure, altered significantly the wound healing outcome. While spontaneous healing resulted in scar formation in these animal models, DRT grafting significantly reduced the extent of wound contraction, prevented scar synthesis, and resulted in partial regeneration. These findings, as well as independent data from species that heal spontaneously via regeneration, point to a striking hypothesis: The process of regeneration lies dormant in mammals until appropriately activated by injury. In spontaneous wound healing of the late fetus and in adult mammals, wound contraction impedes such endogenous regeneration mechanisms. However, engineered treatments, such as DRT, that block wound contraction can cancel its effects and favor wound healing by regeneration instead of scar formation.


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