scholarly journals Studies in vivo on the biosynthesis of collagen and elastin in ascorbic acid-deficient guinea pigs

1969 ◽  
Vol 113 (2) ◽  
pp. 387-397 ◽  
Author(s):  
M. J. Barnes ◽  
B. J. Constable ◽  
E. Kodicek
Keyword(s):  
Ascorbic Acid ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Specific Radioactivity ◽  
Cross Link ◽  
Control Groups ◽  
Acid Deficiency ◽  
Severe Impairment ◽  
Proline Incorporation

1. After the administration of labelled proline to guinea pigs deprived of ascorbic acid for 15 days, the dorsal skin was examined 5 days later in an attempt to detect the presence of hydroxyproline-deficient collagen (protocollagen). The extent of incorporation of proline into skin collagens indicated a severe impairment of collagen synthesis. 2. A comparison of proline and hydroxyproline specific radioactivities in diffusible peptides obtained by treatment with collagenase of either purified skin collagens or direct hot-trichloroacetic acid extracts of skin failed to indicate the presence of protocollagen. Possible reasons for this are discussed. 3. The incorporation results did not indicate an inability of normal collagen, i.e. collagen hydroxylated to the normal degree, to cross-link in scurvy. 4. Incorporation of labelled proline into aortic elastin isolated from the same animals did not indicate a decrease in elastin biosynthesis in ascorbic acid deficiency, beyond that attributable to the inanition accompanying the vitamin deficiency. The proline/hydroxyproline specific-radioactivity ratio in elastin from scorbutic guinea pigs was about 6:1 in contrast with the 1:1 ratio in control groups. It is concluded that the formation of elastin hydroxyproline was ascorbate-dependent and that a hydroxyproline-deficient elastin is formed and retained in scurvy. The formation of desmosines was unimpaired in scorbutic animals. 5. Studies with chick embryos confirmed the formation of elastin hydroxyproline from free proline. Incorporation of free hydroxyproline into elastin hydroxyproline was negligible. 6. Digestion of solubilized samples with collagenase indicated that the hydroxyproline in guinea-pig aortic elastin preparations was not derived from contamination by collagen. It is suggested that most if not all of the hydroxyproline in the guinea pig elastin preparations investigated can be considered an integral part of the elastin molecule.

scholarly journals Studies in vivo on the biosynthesis of collagen and elastin in ascorbic acid-deficient guinea pigs. Evidence for the formation and degradation of a partially hydroxylated collagen

1970 ◽  
Vol 119 (3) ◽  
pp. 575-585 ◽  
Author(s):  
M. J. Barnes ◽  
B. J. Constable ◽  
L. F. Morton ◽  
E. Kodicek
Keyword(s):  
Molecular Weight ◽  
Ascorbic Acid ◽  
Guinea Pigs ◽  
Specific Radioactivity ◽  
Rapid Decline ◽  
Time Intervals ◽  
Skin Collagen ◽  
Labelled Compound ◽  
Degree Of Degradation

1. After the administration of l-[G-3H]proline to guinea pigs deprived of ascorbic acid for increasing periods of time, the specific radioactivities of proline and hydroxyproline in skin collagen and aortic elastin were determined at various time-intervals after administration of the labelled compound with a view to studying the formation and degradation of collagen and elastin both deficient in hydroxyproline. 2. As judged from the incorporation of radioactivity into elastin proline, elastin synthesis was not decreased in the ascorbic acid-deficient animals. There was however, a rapid decline in the specific radioactivity of elastin hydroxyproline. The proline/hydroxyproline specific-radioactivity ratio was approx. 1.5:1 after 6 days and 20:1 after 12 days of ascorbic acid deprivation, in contrast with the ratio of 1:1 in controls. The results suggested that the effect of ascorbic acid deficiency on elastin biosynthesis could be regarded as simply an elimination of hydroxylation of elastin proline with the formation and retention of a polymer increasingly deficient in hydroxyproline. 3. Collagen proline and hydroxyproline specific radioactivities were derived from material that was soluble in hot trichloroacetic acid, non-diffusible and collagenase-degradable. In contrast with elastin, there was a rapid decline in the specific radioactivity of proline as well as hydroxyproline in collagen from the ascorbic acid-deficient animals. However, the proline/hydroxyproline specific-radioactivity ratio in all samples from scorbutic animals was consistently slightly above 1:1. The results suggest the appearance in place of collagen, but in rapidly diminishing amounts, of a partially hydroxylated collagen in which the degree of hydroxylation may be decreased only by approx. 10%. 4. Incorporation of radioactivity into the diffusible hydroxyproline in skin remained relatively high despite the rapid decline in the incorporation of radioactivity into collagen. This observation is interpreted as indicative of an increasing degree of degradation of partially hydroxylated collagen to diffusible peptides. An alternative explanation might be that partially hydroxylated peptides are released to an increasing extent from ribosomes before they attain a length at least sufficient to render them non-diffusible. In either case it implies the accumulation in scurvy of low-molecular-weight peptides enriched in proline and deficient in hydroxyproline and could explain the failure to accumulate a high-molecular-weight collagen deficient in hydroxyproline. 5. It is thought, however, that, in addition, an inhibition of ribosomal amino acid incorporation leading to decreased synthesis of partially hydroxylated collagen may also occur, perhaps secondarily to impaired hydroxylation.

scholarly journals Bronchial responses to substance P after antigen challenge in the guinea-pig: in vivo and in vitro studies

1992 ◽  
Vol 1 (3) ◽  
pp. 207-212 ◽  
Author(s):  
E. Boichot ◽  
V. Lagente ◽  
G. Le Gall ◽  
C. Carré ◽  
J. M. Mencia-Huerta ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Bronchial Hyperresponsiveness ◽  
Neutral Endopeptidase ◽  
Antigen Challenge ◽  
Control Groups ◽  
Airway Responses

The effect of antigen challenge on the airway responses to substancePand on the epithelial neutral endopeptidase (NEP) activity was investigated in aerosol sensitized guinea-pigs. In vivo, bronchial responses to aerosolized substancePwere similar to the responses observed in antigen-challenged guinea-pigs and in the control groups. In contrast, when the guinea-pigs were pretreated with the NEP inhibitor, phosphoramidon, a significant increase in the airway responses to substancePwas observed after antigen challenge in vivo. However, in vitro, the contractile responses of the tracheal smooth muscle to substancePwere similar between groups of guinea-pigs, in respect to the presence or absence of the epithelium and/or phosphoramidon. Histological studies showed an accumulation of eosinophils in the tracheal submucosa after antigen challenge and intact epithelial cells. These results show that in vivo bronchial hyperresponsiveness to substancePafter antigen challenge in the guinea-pig is not associated with increased responses of the smooth muscle to exogenousSPin vitro. In addition, the results with phosphoramidon suggest that loss of NEP activity cannot account for the in vivo bronchial hyperresponsiveness to substancePpresently observed.

scholarly journals The effect of scurvy on glycosaminoglycans of granulation tissue and costal cartilage

1968 ◽  
Vol 110 (4) ◽  
pp. 609-616 ◽  
Author(s):  
I. Antonowicz ◽  
E. Kodicek
Keyword(s):  
Ascorbic Acid ◽  
Granulation Tissue ◽  
Guinea Pigs ◽  
Costal Cartilage ◽  
Absolute Amount ◽  
Ascorbic Acid Deficiency ◽  
Acid Deficiency ◽  
And Cartilage

1. The effect of ascorbic acid deficiency on glycosaminoglycans of granulation tissue and cartilage of guinea pigs was investigated by determination of the changes in the glucosamine and galactosamine contents 12 days after tendonectomy. 2. In normal granulation tissue, the glucosamine and galactosamine contents rose to a peak at 5 and 10 days respectively, whereas the hydroxyproline and proline contents continued to rise throughout the 20 days after tendonectomy. 3. The galactosamine in scorbutic granulation tissue, but not in that of pair-fed controls, decreased significantly in absolute amount and relatively to glucosamine, which remained practically unchanged; the cartilage galactosamine did not decrease during the 22 days of deficiency owing to the presence of excess of preformed galactosaminoglycans, which masked the small amount of newly formed glycosaminoglycans. 4. The chemical results were confirmed by radioactivity studies in vivo of incorporation of [U−14C]glucose into galactosamine and glucosamine of scorbutic granulation tissue and cartilage. The incorporation of 14C into galactosamine decreased significantly in scurvy in both tissues. 5. The results indicated in both tissues a decreased formation of galactosamine during scurvy, although an increased degradation of polymerized glycosaminoglycans could not be entirely ruled out. It is concluded that, if lack of ascorbic acid causes an impaired galactosamine formation, the most likely position for the block may be in the UDP-N-acetylglucosamine 4-epimerase reaction.

scholarly journals Effect of pharmacological doses of ascorbic acid on the hepatic microsomal haemoproteins in the guinea-pig

1983 ◽  
Vol 49 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Judith L. Sutton ◽  
T. K. Basu ◽  
J. W. T. Dickerson
Keyword(s):  
Ascorbic Acid ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Sucrose Solution ◽  
Significant Rise ◽  
Mixed Function Oxidase ◽  
Ascorbic Acid Deficiency ◽  
Acid Deficiency ◽  
Specific Activities ◽  
Endogenous Substrates

1. Ascorbic acid deficiency results in a reduction in the activity of the hepatic mixed function oxidase systems in the guinea-pig. In this study, male Dunkin-Hartley guinea-pigs were given 0, 50, 100, 200 or 300 mg ascorbic acid/d in two equal doses in buffered sucrose solution (200 g/l) for 4 d. Controls received an equal volume of sucrose solution.2. A dose of 50 mg ascorbic acid/d resulted in a significant rise in the specific activities of both cytochromes P-450 and b5. At doses of 200 and 300 mg ascorbic acid/d the concentration of both haemoproteins was significantly lower than the control values. These effects were mirrored by total microsomal haem concentration.3. These results suggest that when given in large doses, ascorbic acid ceases to act simply as a vitamin and should be considered a drug competing for substrates and cofactors with co-administered drugs and endogenous substrates such as cholesterol.

Ketone body metabolism in ascorbic acid deficiency: in vivo utilization of ketone bodies in guinea pigs

1959 ◽  
Vol 196 (3) ◽  
pp. 607-610 ◽  
Author(s):  
Habeeb Bacchus ◽  
Albert F. Debons ◽  
Sidney Levin ◽  
John W. Wallace
Keyword(s):  
Ascorbic Acid ◽  
Guinea Pigs ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Deficient Animal ◽  
Ascorbic Acid Deficiency ◽  
Acid Deficiency ◽  
Urinary Levels ◽  
Ketone Body Metabolism

Blood and urinary levels of ketone bodies were studied in normal, ascorbic acid-deficient, and pair-fed control, guinea pigs. The resting levels of ketone bodies in the blood and urine throughout the course of ascorbic acid-deficiency do not differ significantly from those of control animals. The ketonemic response to fasting is greater in the control animals than in the ascorbic acid-deficient animals. The disappearance of injected ketone bodies (ß-hydroxybutyrate) is decreased in the ascorbic acid-deficient animal. The data suggest that in ascorbic acid-deficiency there is a decreased utilization of ketone bodies coupled with a decreased spontaneous ketogenesis.

Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu
Keyword(s):  
Guinea Pig ◽  
Acetylsalicylic Acid ◽  
Guinea Pigs ◽  
Glass Bead ◽  
Animal Species ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

scholarly journals EVIDENCE THAT THE L-ASPARAGINASE OF GUINEA PIG SERUM IS RESPONSIBLE FOR ITS ANTILYMPHOMA EFFECTS

1963 ◽  
Vol 118 (1) ◽  
pp. 99-120 ◽  
Author(s):  
J. D. Broome
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Serum Proteins ◽  
Deae Cellulose ◽  
Salt Precipitation ◽  
Asparaginase Activity ◽  
Pig Serum

A number of the properties of the L-asparaginase present in guinea pig serum have been examined and shown to be indistinguishable from those of the agent responsible for inhibiting cells of lymphoma 6C3HED in vivo. The patterns of instability of the enzyme to changes in temperature and pH were found to parallel closely those of the antilymphoma agent. L-Asparaginase activity was essentially absent from the serum of newborn guinea pigs and this failed to inhibit 6C3HED cells. On separating guinea pig serum proteins by salt precipitation, electrophoresis, and chromatography on DEAE cellulose, antilymphoma activity was found only in fractions which contained L-asparaginase.

scholarly journals [3H]proline incorporation and hydroxyproline concentration in articular cartilage during the development of osteoarthritis caused by immobilization. A study in vivo with rabbits

1981 ◽  
Vol 200 (2) ◽  
pp. 435-440 ◽  
Author(s):  
T Videman ◽  
I Eronen ◽  
T Candolin
Keyword(s):  
Total Protein ◽  
Collagen Synthesis ◽  
Weight Bearing ◽  
Specific Radioactivity ◽  
Collagen Content ◽  
Synthetic Activity ◽  
Synthesis Rate ◽  
Hydroxyproline Concentration ◽  
Proline Incorporation

Proline metabolism in vivo was studied during the development of immobilization osteoarthritis in rabbits. Collagen content was measured as the hydroxyproline concentration of the tissue in question. The incorporation of [3H]proline was used as the indicator for total protein synthesis; collagen synthesis rate was estimated from measurements of the specific radioactivity of hydroxyproline. Cartilage samples from knee and hip joints were analysed after 3, 7, 11, 18, 35 and 56 days of immobilization. The total protein and collagen synthesis rates of the immobilized legs increased and reached a maximum after 11-35 days. Although they decreased thereafter, these rates remained elevated to the end of the experiment. A slight increase in the synthetic activity of the non-immobilized contralateral legs was also detected after 7--18 days of immobilization. The isotope incorporation was markedly higher in tibial marginal tissue than in weight-bearing cartilage. In spite of the increased synthesis, no clear changes were found in the collagen content of the tissues studied during the experiment.

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