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PubMed1977

Bone necrosis and urinary hydroxyproline excretion in rabbits.

1. Aseptic necrosis of bone is a serious chronic complication of deep-sea diving and compressed-air work. 2. The changes to the bone which occur in this condition take time to develop to the stage where they cause the radiographic signs of bone necrosis, and consequently there is a delay of some months between the causal incident and the first diagnosis by radiography. 3. As a possible method for the earlier detection of bone necrosis the 24 h urinary excretion of hydroxyproline was measured over a period before and after experimental production of bone necrosis in rabbits by the intra-arterial injection of glass microspheres. 4. Total hydroxyproline excretion rose significantly within a few days of the injection in those rabbits in which there was later shown to be historical evidence of bone necrosis. This rise occurred long before there was any radiographic changes. 5. It is suggested that measurements of urinary hydroxyproline might be used to give an early indication of bone necrosis in man.

Animals↗
PubMed2002

Conformation and anion binding properties of cyclic hexapeptides containing L-4-hydroxyproline and 6-aminopicolinic acid subunits.

Two cyclic hexapeptides containing alternating all R and all S configured Ll-(4R/S)-hydroxyproline and 6-aminopicolinic acid subunits are presented, and the influence of the hydroxyl groups on the solubility, conformation, and receptor properties is investigated. Cyclopeptide 2, containing the natural 4R configured hydroxyproline, adopts a conformation similar to that of the unsubstituted peptide 1, which is able to bind anions such as halides and sulfate in aqueous solution. 2 also interacts with these anions, but whereas 1 forms sandwich type 2:1 complexes, in which the anion is bound by two cyclopeptide moieties, 2 forms 1:1 complexes. The stabilities of the halide and sulfate complexes of 2 range between 10(0) and 10(2) M(-1) in 80% D(2)O/CD(3)OD. Complex formation is detectable even in water, but with slightly smaller stability constants. Using this information a quantitative evaluation of the stability of the 2:1 complexes of 1, for which overall stability constants in the order 10(4) to 10(5) M(-2) in 80% D(2)O/CD(3)OD were observed, was made. In contrast to 2, the conformation of 3, containing the non-natural 4S configured hydroxyproline, is strongly affected by the presence of the hydroxyl groups. In d(6)-DMSO and methanol/water mixtures a slow conformational equilibrium between two C(3)-symmetrical conformers is observed, and 3 is thus much less preorganized for anion binding than either 1 or 2.

Anions↗
PubMedDate not supplied

Increased urinary excretion of hydroxyproline in runners training in urban areas.

In this study, the authors investigated urinary excretion of hydroxyproline in 120 subjects to test the hypothesis that physical activity is associated with increased exposure to pollution derived from traffic exhaust. The study population comprised active noncompetitive runners (i.e., 21.1% trained < 2.5 hr/wk, 20% trained for 2.5-5.0 hr/wk, and 54.4% trained > 5 hr/wk) who lived in Genoa, an urban area of Northern Italy. The mean hydroxyproline value (24.39 +/- 8.38 standard deviation] mg/24 hr x m2) in a group of 69 runners who trained in tracks and streets located in downtown Genoa was higher (p < .05) than the mean value recorded in a group of 21 runners (13.33 +/- 2.51 mg/24 hr x m2) who trained mainly in a rural environment of Genoa. The difference was even greater (p < .01) when a third comparable group of 30 nonrunners was considered (mean = 12.54 +/- 3.41 [standard deviation] mg/24 hr x m2). In the urban environment, urinary levels of hydroxyproline were correlated significantly with intensity and frequency of running, but they were unrelated to smoking status.

Adult↗
PubMedDate not supplied

Nitrogen dioxide exposure and urinary excretion of hydroxyproline and desmosine.

The relationship between average and peak personal exposure to nitrogen dioxide and urinary excretion of hydroxyproline and desmosine was investigated in a population of preschool children and their mothers. Weekly average personal nitrogen dioxide exposures for subjects who resided in homes with one or more potential nitrogen dioxide source (e.g., a kerosene space heater, gas stove, or tobacco smoke) ranged between 16.3 and 50.6 ppb (30.6 and 95.1 micrograms/m3) for children and between 16.9 and 44.1 ppb (12.8 and 82.9 micrograms/m3) for mothers. In these individuals, the hydroxyproline-to-creatinine and desmosine-to-creatinine ratios were unrelated to personal nitrogen dioxide exposure--even though continuous monitoring documented home nitrogen dioxide concentration peaks of 100-475 ppb lasting up to 100 h in duration. Significantly higher hydroxyproline-to-creatinine and desmosine-to-creatinine ratios were observed in children, compared with mothers (p < .001 and .003, respectively).

Adult↗
PubMed1957

Studies on the biosynthesis of collagen. II. The conversion of 14C-L-proline to 14C-hydroxyproline by fowl osteoblasts in tissue culture.

1. Fowl osteoblasts grown in bulk tissue cultures in the presence of (14)C-(L)-proline incorporated this amino acid into peptide linkage. A significant amount of the incorporated radioactivity was found in the hydroxyproline, glutamic acid, and aspartic acid fractions of the cultures. 2. The rate of formation of protein-bound (14)C-hydroxyproline from (14)C-(L)-proline was maximal in cultures grown for 15 hours and fell exponentially with the increasing age of the cultures. 3. (14)C-(L)-glutamic acid was incorporated by the osteoblast cultures, but no significant amount was converted to hydroxyproline.

Amino Acids↗
PubMed1997

A new procedure for the specific high-performance liquid chromatographic determination of hydroxyproline.

A procedure suitable for a selective high-performance liquid chromatographic (HPLC) analysis of the imino acid hydroxyproline in the presence of a large excess of amino acids is proposed. To deaminate the amino acids, the well-known reaction with nitrous acid is exploited. The N-nitroso derivatives of imino acids obtained are extracted in ethyl acetate, denitrosated by hydrobromic acid, and treated with dabsyl-chloride. The final HPLC separations are carried out on a reversed-phase column in a rapid isocratic run. The use of the cis isomer of hydroxyproline as an internal standard allows good reproducibility. As an application of the described method, the hydroxyproline content in samples containing collagen and an excess of bovine serum albumine (up to 20:1) is determined.

Animals↗
PubMed1986

Effects of NaCl on calcium balance, parathyroid function and hydroxyproline excretion in prednisolone-treated rats consuming low calcium diet.

The short-term effects of dietary sodium chloride supplementation on calcium balance were examined in an animal model of corticosteroid-mediated osteoporosis. Changes in calcium and phosphate balance, parathyroid function and bone resorption elicited by salt supplements alone (8 g/100 g diet), prednisolone alone (2.2 mg/kg body wt per day) and both salt and prednisolone in combination were measured in rats consuming a low calcium diet (0.1% calcium) for 10 d. Parathyroid function was monitored by measuring urinary cyclic AMP excretion. Bone resorption was monitored by measuring urinary hydroxyproline excretion. Salt alone raised urinary calcium, cyclic AMP and hydroxyproline; prednisolone alone depressed net calcium absorption and urinary hydroxyproline but had no effect on urinary calcium. Salt and prednisolone each depressed calcium retention independently and together produced an additive adverse effect on calcium balance. Thus high dietary salt intakes augment urinary calcium loss, raise parathyroid activity, increase bone resorption and adversely affect calcium balance in prednisolone-treated growing rats with a restricted dietary calcium intake. These findings support the view that high salt intakes may exaggerate bone loss during chronic glucocorticoid therapy. Because people also develop osteoporosis during glucocorticoid therapy and respond to dietary salt supplements by increasing urinary calcium excretion and parathyroid hormone, high salt intakes may accelerate bone loss in patients receiving chronic glucocorticoid therapy. The beneficial effects of dietary salt restriction on the conservation of bone mass warrant investigation in these patients.

Absorption↗
PubMed1989

Dietary guar gum effects on postprandial blood glucose, insulin and hydroxyproline in humans.

Meals (425 kcal) containing various doses of guar gum (0, 2.5, 7.5 or 12.5 g) were ingested by nine healthy male subjects after a 12-h fast. The rise in blood glucose was higher after the control meal without guar gum than after the guar gum-containing meals, which all gave a similar rise in glucose. In contrast, increased doses of guar gum led to a greater reduction in the postprandial rise in insulin. The postprandial increase in serum hydroxyproline, an amino acid added to all meals, was decreased in a similar manner by all of the guar gum doses. Gastric emptying was measured after the control meal without guar gum and the meal containing 12.5 g of guar gum by monitoring 51Cr, which was added to the meals. Guar gum was found to reduce the variation between individuals, as well as the initial rate of gastric emptying, which correlated with changes in both serum hydroxyproline (rs = 0.93, P less than 0.01) and blood glucose (rs = 0.83, P less than 0.01). The effectiveness of guar gum in reducing postprandial response was lost after heating and homogenization for canning. A threshold in the reduction in rise of glucose or hydroxyproline was reached with the lowest dose (2.5 g) of viscous guar gum; larger doses had no additional effects. The reduced absorption seems to be an effect of a slower gastric emptying rate.

Adult↗
PubMed1991

Hydroxyproline in the oesophageal mucosa of patients with progressive systemic sclerosis during omeprazole-induced healing of reflux oesophagitis.

Hydroxyproline concentration in oesophageal mucosal biopsies was used as an index of collagen in an attempt to evaluate the potential for stricture formation in patients with progressive systemic sclerosis. Eight patients suffering from progressive systemic sclerosis with complicating gastro-oesophageal reflux, 8 patients with idiopathic gastro-oesophageal reflux, and 7 normal controls were compared. Acid gastro-oesophageal reflux was assessed with 24-h pH-metry; degree of oesophagitis was evaluated both endoscopically and histopathologically. The patients with progressive systemic sclerosis were investigated at the start of the study and later when healing of oesophagitis was accomplished with omeprazole therapy. The hydroxyproline concentration was significantly increased (P less than 0.01) in the oesophageal mucosa from patients with progressive systemic sclerosis (median 21.8 nmol/mg) as compared to patients with idiopathic gastro-oesophageal reflux (median 6.4 nmol/mg) and normal controls (median 8.1 nmol/mg). Hydroxyproline concentration in oesophageal mucosa from patients with progressive systemic sclerosis decreased significantly and to a normal level (median 6.5 nmol/pg; P = 0.014) when healing of oesophagitis was achieved.

Adult↗
PubMed1995

Hydroxyproline excretion is increased in diabetes mellitus and related to the presence of microalbuminuria.

Increased fracture frequency and low bone mass have each been reported in patients with diabetes. To see if these were related to increased bone resorption we have measured the urinary excretion of hydroxyproline in 73 patients with Type 1 (insulin-dependent) diabetes, 67 patients with Type 2 (non-insulin-dependent) diabetes, and 75 control subjects. Hydroxyproline excretion was increased in both types of diabetes: Type 1: 21 (10-36) (median (IQR) mumol mmol creatinine-1; Type 2: 25 (13-43) mumol mmol creatinine-1; control: 10 (6-22) mumol mmol creatinine-1 (p < 0.0001 and < 0.0002, respectively). Hydroxyproline excretion was not related to age, duration of diabetes or blood glucose control. Neither was it different in patients with or without retinopathy, neuropathy and macrovascular disease. However it was higher in patients with microalbuminuria at 35 (20-53) mumol mmol creatinine-1 than in those with normal protein excretion (25(13-37) mumol mmol creatinine-1 p = 0.03) or those with established proteinuria (18(8-26) mumol mmol creatinine-1 p = 0.001). We conclude that there is evidence of increased bone resorption in diabetes and that this is related to alterations in renal function.

Adult↗
PubMed1972

Hydroxyproline heterooligosaccharides in Chlamydomonas.

Most of the hydroxyproline in Chlamydomonas reinhardtii is glycosidically linked to oligosaccharides and a monosaccharide that are different from the arabinosides found in hydroxyproline-containing plant cell walls previously examined. Of particular interest is the presence of hydroxyproline-O-galactose. These differences may be common to the volvocalean green algae and may be related to lower tensile strength of the cell walls of this group of plants.

Arabinose↗
PubMed1980

One year's study of growth and total hydroxyproline excretion in scoliotic children.

21 children with scoliosis were studied for a year during which time 24-hour urinary total hydroxyproline levels are estimated and anthropometric measurements were made on 4 occasions. The total hydroxyproline levels (using hydroxyproline centiles) and the uncorrected heights of the children were all normal. The sitting heights of the children were below average, but, although the sample was small, the findings indicate that the children's 'uncoiled' height would be greater than average.

Adolescent↗
PubMed1975

Hydroxyproline excretion in patients with breast cancer and response to treatment.

The urinary excretion of hydroxyproline, measured as the hydroxyproline: creatinine ratio, was useful in monitoring the progression of metastatic cancer of the breast. After new treatment was started changes in the hydroxyproline excretion occurred earlier than other clinically observable responses. The test could therefore be used for predicting the response to treatment and early detection of the sensitivity of the tumour to hormone therapy.

Antineoplastic Agents↗
PubMed1982

Measurement of the fasting urinary hydroxyproline: creatinine ratio in normal adults and its variation with age and sex.

Conditions for the determination of the fasting urinary hydroxyproline: creatinine ratio (OHPr: Cr ratio) have been examined, using a resin-catalysed hydrolysis and automated colorimetric procedure for the determination of hydroxyproline. Feeding experiments with gelatin showed that hydroxyproline is rapidly absorbed and excreted in the urine and that a 12-hour (overnight) fast is sufficient to ensure correct and reproducible fasting OHPr: Cr ratios. The mean fasting OHPr: Cr ratio decreased slightly with increasing age in both men and premenopausal women but there was no significant difference between the sexes. There was, however, a significant increase in the mean ratio in postmenopausal women. The normal range of fasting OHPr: Cr ratios for men and premenopausal women was found to be 0.003--0.015.

Adolescent↗
PubMed1982

Urinary excretion of hydroxyproline in workers occupationally exposed to vibration.

Urinary hydroxyproline excretion was measured in 130 chain saw operators aged 28-59 and in 31 normal control subjects aged 26-59 with no occupational exposure to vibration. The results measured were expressed as a ratio of hydroxyproline to creatinine. (1) No significant correlation between hydroxyproline/creatinine ratio and age was observed among normal subjects. (2) In chain saw operators grip and pinch strength decreased gradually with an increase of the total chain saw operating time, while the prevalence of pain in the hands or motility disturbance in the elbow joints showed a tendency to become greater as total operating time increased. Hydroxyproline/creatinine ratio in the group with over 9000 hours' experience was significantly higher than that in the group with under 3000 hours (p less than 0.05). By comparison with controls, the ratio in the group with over 3000 hours was significantly higher at the 5% level. (3) Hydroxyproline/creatinine ratio in the group with pain in the hands or with motility disturbance in the elbow joints was significantly higher than that in the group without them (p less than 0.05). (4) Hydroxyproline/creatinine ratio was inversely correlated with grip and pinch strength in operators ranging in age from 40 to 49 (p less than 0.01). (5) All individual ratios for operators with lower grip strength showed a higher increment than the mean values obtained from controls. These results indicate that increased urinary hydroxyproline excretion in chain saw operators may occur in association with damage to the musculoskeletal system caused by the prolonged use of vibrating tools.

Adult↗
PubMed1992

Effects of histamine H2-receptor antagonists and a proton pump inhibitor on the mucosal hydroxyproline content of ethanol-HCl-induced gastric lesions in rats.

We evaluated the effects of different antisecretory agents (H2-receptor antagonists and a proton pump inhibitor) on collagen regeneration in rat gastric lesions induced by intragastric administration of 50% ethanol +0.15 N HCl (EtOH-HCl). The lesion indices showed the highest value 30 min after administration of EtOH-HCl and a significantly decreased value 15 h later. The mucosal hydroxyproline concentration was significantly increased 30 min after EtOH-HCl administration, reached a maximum 6 h later and subsequently decreased as time passed. Intraperitoneal administration of cimetidine at a dose of 100 mg/kg or famotidine at a dose of 5 mg/kg 30 min after EtOH-HCl administration could not reduce the lesion indices in less than 24 h and suppressed the increase in mucosal hydroxyproline concentrations significantly compared with the control group. On the other hand, treatment with 10 mg/kg of E-3810, a proton pump inhibitor, had no effects on the lesion healing nor on the fluctuation of mucosal hydroxyproline concentrations. These facts suggest that H2-receptor antagonists might delay the healing of EtOH-HCl-induced gastric lesions through the suppression of collagen regeneration under the condition of exclusion of gastric acid secretion.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1989

Reduction of hydroxyproline content in the vessels of the human umbilical cord in premature rupture.

The hydroxyproline content of the amnion and the umbilical vessels obtained from cases in which the fetal membranes were instrumentally or prematurely ruptured was assayed. Hydroxyproline concentration (in micrograms/mg) in the latter group was 23.76, 16.79 and 17.86 in the amnion, artery and vein, whereas in the former the corresponding values were 42.20, 26.61 and 32.48. These results show that, in addition to a decrease in the amnion, hydroxyproline is lowered also in the umbilical vessels, suggesting that the reduction in the collagen in the fetal membranes is probably a particular manifestation of a general metabolic deficiency.

Amnion↗
PubMed1979

Genetic evidence for a common enzyme catalyzing the second step in the degradation of proline and hydroxyproline.

The initial step in the degradation pathways of proline and hydroxyproline is catalyzed by proline oxidase and hydroxyproline oxidase, yielding delta 1-pyrroline-5-carboxylate and delta 1-pyrroline-3-hydroxy-5-carboxylate, respectively. The second step is the oxidation of delta 1-pyrroline-5-carboxylate to glutamate and delta 1-pyrroline-3-hydroxy-5-carboxylate to gamma-hydroxy-glutamate. To determine if this second step in the degradation of proline and hydroxyproline is catalyzed by a common or by separate enzyme(s), we developed a radioisotopic assay for delta 1-pyrroline-3-hydroxy-5-carboxylate dehydrogenase activity. We then compared delta1-pyrroline-3-hydroxy-5-carboxylate dehydrogenase activity with that of delta 1-pyrroline-5-carboxylate dehydrogenase in fibroblasts and leukocytes from type II hyperprolinemia patients, heterozygotes, and controls. We found that cells from type II hyperprolinemia patients were deficient in both dehydrogenase activities. Furthermore, these activities were highly correlated over the range found in the normals, heterozygotes, and patients. We conclude from these data that a common delta 1-pyrroline-5-carboxylate dehydrogenase catalyzes the oxidation of both delta 1-pyrroline-5-carboxylate and delta 1-pyrroline-3-hydroxy-5-carboxylate, and that this activity is deficient in type II hyperprolinemia.

1-Pyrroline-5-Carboxylate Dehydrogenase↗