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PubMed2000

The hydroxyproline content of amnion and prelabour rupture of the membranes.

OBJECTIVE: To determine whether prelabour rupture of the membranes is caused by a generalised reduction in amniotic collagen. SETTING: Leeds General Infirmary, UK. STUDY DESIGN: The hydroxyproline content of amnion from 55 women with prelabour rupture of the membranes was compared with that from 50 women whose membranes ruptured during labour and 28 women who were delivered by elective caesarean section. RESULTS: No association was found between hydroxyproline content and the timing of membrane rupture. Hydroxyproline content was inversely correlated with gestation. The hydroxyproline content per cm(2) amnion was significantly increased in cases which had laboured. There was a strong correlation between the mechanical properties and the hydroxyproline content of amnion. CONCLUSIONS: PROM is not associated with a generalised reduction in the hydroxyproline content of amnion.

Amnion↗
PubMed1976

Relevance of hydroxyproline excretion to bone metastasis in breast cancer.

In 181 consecutive patients with breast cancer, urinary hydroxyproline excretion has been critically evaluated in conjunction with clinical, biochemical, radiological and scintigraphic parameters. The urinary hydroxyproline/creatinine ratio is a sensitive index of the presence of bone metastases. Urinary hydroxyproline excretion is a reliable method of selecting those patients whose elevated serum alkaline phosphatase is secondary to bone disease rather than liver idsease. The estimation of hydroxyproline excretion furthermore gives information on the activity of bone metastasis, and its response to treatment, which cannot be given by radiological or scintigraphic methods. It is doubtful whether urinary hydroxyproline estimation will help to detect bone metastases before they are apparent on scintigrams. When the bone scan is doubtful, as often occurs in older subjects, hydroxyproline excretion has been found to be helpful in classifying the patient. When scintigraphy is not available, an elevation of hydroxyproline excretion, together with an elevation of Ca/cr ratio or alkaline phosphatase activity, may pre-date by several months the radiological demonstration of osseous metastases.

Adult↗
PubMed2006

Hydroxyproline ingestion and urinary oxalate and glycolate excretion.

Endogenous synthesis of oxalate is an important contributor to calcium oxalate stone formation and renal impairment associated with primary hyperoxaluria. Although the principal precursor of oxalate is believed to be glyoxylate, pathways in humans resulting in glyoxylate synthesis are not well defined. Hydroxyproline, a component amino acid of collagen, is a potential glyoxylate precursor. We have investigated the contribution of dietary hydroxyproline derived from gelatin to urinary oxalate and glycolate excretion. Responses to the ingestion of 30 g of gelatin or whey protein were compared on controlled oxalate diets. The time course of metabolism of a 10 g gelatin load was determined as well as the response to varying gelatin loads. Urinary glycolate excretion was 5.3-fold higher on the gelatin diet compared to the whey diet and urinary oxalate excretion was 43% higher. Significant changes in plasma hydroxyproline and urinary oxalate and glycolate were observed with 5 and 10 g gelatin loads, but not 1 and 2 g loads. Extrapolation of these results to daily anticipated collagen turnover and hydroxyproline intake suggests that hydroxyproline metabolism contributes 20-50% of glycolate excreted in urine and 5-20% of urinary oxalate derived from endogenous synthesis. Our results also revealed that the kidney absorbs significant quantities of hydroxyproline and glycolate, and their metabolism to oxalate in this tissue warrants further consideration.

Adult↗
PubMed1985

Clinical significance of free plasma hydroxyproline measurement in metabolic bone disease.

Free hydroxyproline was measured in plasma of 67 normal subjects and in 70 patients with bone disease including primary hyperparathyroidism (n = 19), osteoporosis (n = 18), Paget's disease (n = 14), cancer involving bone (n = 8), chronic renal failure (n = 6), and osteomalacia (n = 6), and osteomalacia (n = 5). A good correlation was found between plasma and urinary values of the amino acid in normal subjects (r = 0.66; p less than 0.001). In patients with skeletal disorders a highly significant direct correlation was observed between free plasma hydroxyproline on the one hand and urinary hydroxyproline (r = 0.92; p less than 0.001) and serum alkaline phosphatase activity (r = 0.86; p less than 0.001) on the other, even though there were a few examples of dissociations among these parameters. Free plasma hydroxyproline decreased in the patients with Paget's disease following chronic administration of salmon calcitonin. Following successful parathyroidectomy, free plasma levels of hydroxyproline decreased in all the cases studied. Measurement of free plasma hydroxyproline thus appears to provide a specific index of bone metabolism that may be usefully employed as an alternative to the assay of other markers of bone turnover.

Adult↗
PubMed1978

Urinary hydroxyproline excretion in acromegaly.

The urinary hydroxyproline excretion of 8 acromegalics kept on a collagen free diet has been studied. Urinary hydroxyproline showed a circadian rhythm with maximum excretion rates at night and early morning and minimum excretion rates in the late afternoon and evening. When mean values are compared, there is a significant correlation between fasting GH-levels and 24 h urinary hydroxyproline excretion (Rs = 0.74 and between GH and fasting hydroxyproline:creatinine ratios (Rs = 0.76). No significant correlation could be demonstrated between collagen content of bone biopsies and GH-levels or urinary hydroxyproline excretion. It is suggested that a practical assessment of disease activity in acromegaly can be achieved through a simplified hydroxyproline assay.

Acromegaly↗
PubMed1975

Determination of hydroxyproline content in human heart muscle.

Hydroxyproline content was chemically determined on 45 human hearts obtained at autopsy in order to study whether hydroxyproline contents vary in proportion to heart weight or not. There were no significant differences in the mean hydroxyproline content between the epicardium and the endocardium, between the left ventricle and the right ventricle, or among cardiovascular and renal disease group, malignant disease group and miscellaneous disease group. Total hydroxyproline content per mg dry weight of the left ventricle increased proportionally with heart weight. Hydroxyproline content in neutral salt soluble fraction increased more proportionally than that in acid soluble fraction. This tendency was more evident in the endocardium than in the epicardium of the left ventricle. These results seem to be well consistent with those of histometrical estimation of scar tissue in human heart muscle. Hydroxyproline content in acid soluble fraction of the right ventricle was increased proportionally with heart weight.

Adolescent↗
PubMed2004

Assessment of the effects of age and joint disease on hydroxyproline and glycosaminoglycan concentrations in synovial fluid from the metacarpophalangeal joint of horses.

OBJECTIVE: To assess the effects of age and joint disease on hydroxyproline and glycosaminoglycan (GAG) concentrations in synovial fluid from the metacarpophalangeal joint of horses and evaluate the association of those concentrations with severity of osteoarthritis and general matrix metalloproteinase (MMP) activity. SAMPLE POPULATION: Synovial fluid was collected from the metacarpophalangeal joints of foals at birth (n = 10), 5-month-old foals (10), 11-month-old foals (5), and adult horses (73). PROCEDURE: Hydroxyproline and GAG concentrations were determined in synovial fluid samples. The severity of osteoarthritis in adult joints was quantified by use of a cartilage degeneration index (CDI) and assessment of general MMP-activity via a fluorogenic assay. RESULTS: Hydroxyproline and GAG concentrations in synovial fluid were highest in neonates and decreased with age. Concentrations reached a plateau in adults by 4 years and remained constant in healthy joints. In synovial fluid from osteoarthritic joints, hydroxyproline and GAG concentrations were not increased, compared with unaffected joints, but hydroxyproline were significantly correlated with the CDI and general MMP activity. There was no significant correlation between GAG concentration and CDI value or MMP activity. CONCLUSIONS AND CLINICAL RELEVANCE: Changes in hydroxyproline concentration in synovial fluid appeared to indicate damage to collagen of the articular cartilage. In joints with osteoarthritis, the lack of high GAG concentration in synovial fluid and the absence of a significant correlation between GAG concentration and CDI values or MMP activity may severely limit the usefulness of this marker for monitoring equine joint disease.

Age Factors↗
PubMed1983

Peplomycin sulfate and pulmonary fibrosis: hydroxyproline, uronic acid, proline hydroxylase and glucosamine 6-phosphate synthetase in lungs of hamsters treated with peplomycin.

Effect of peplomycin sulfate (PLM) on pulmonary fibrosis was examined. Hydroxyproline, uronic acid, proline hydroxylase (EC 1.14.11.2) and glucosamine 6-phosphate synthetase (EC 2.6.1.16) in lungs of hamsters treated with PLM were studied and compared with those of hamsters treated with bleomycin (BLM). PLM, when administered intraperitoneally, one injection daily for 10 consecutive days, at either a high- (5 mg/kg) or low- (2.8 mg/kg) dosage-level, caused no significant increase of lung hydroxyproline and uronic acid as compared with controls. BLM on the other hand effected a significant increase in lung hydroxyproline on the high-dosage level (5 mg/kg) but not on the low-dosage level (2.8 mg/kg). In contrast, when administering PLM intratracheally, the concentrations of hydroxyproline in lungs increased 20% over the control levels. A transient increase of proline hydroxylase and glucosamine 6-phosphate synthetase also occurred shortly after the instillation. These increases were also observed in the corresponding groups treated with BLM, which confirmed the previous observations by other investigators. However, the magnitude of the increase was relatively lower in those values of PLM as compared with those of BLM. These data suggested that (1) PLM, when administered with multiple dosages intraperitoneally, showed no significant effect on the elevation of lung hydroxyproline; (2) PLM, when administered with a dose intratracheally, induced pulmonary fibrosis similar to that caused by BLM. However, the hydroxyproline accumulation in lungs of PLM-treated hamsters was less than in those of the BLM-treated; (3) The fibrotic effect on the lungs caused by either PLM or BLM was probably attributed to acceleration of the syntheses of collagen and acidic glycosaminoglycans.

Animals↗
PubMed1991

[Concentration of total and protein-bound hydroxyproline in serum and urine in patients with laryngeal neoplasms].

The concentration of total and protein-bound hydroxyproline in the serum and total hydroxyproline in the urine was measured in the group of 52 patients with larynx carcinoma by means of Prockop's and Udenfriend's colorimetric method modified by Tomaszewski. The mean level of total and protein-bound serum hydroxyproline in the group of clinical patients was statistically significantly raised when compared with control group. The mean level of total hydroxyproline in the urine of patients with larynx carcinoma was statistically insignificantly raised when compared with control group. The degree of clinical or organic progress of larynx carcinoma was not found to influence essentially the level of hydroxyproline in the serum of the examined patients. It was shown however, that statistically essential increase in the total hydroxyproline level in the urine depends on the degree of organic progress of larynx carcinoma.

Adult↗
PubMed1979

Urinary hydroxyproline in healthy patients and in prostate patients with and without bone metastases.

An essential part of the classification of prostate carcinoma is the diagnosis of bone metastases. This was done with 70 patients using x-ray analysis, scintography, determination of the acid and alkaline phosphatase, and pelvic crest biopsy, as well as aspiration of the pelvic and sternal bone marrow. In addition, the hydroxyproline concentration was determined in the 24-hour-urine. The study, which was initially undertaken on a sample group (n = 145), yielded a high correlation between age and sex and hydroxyproline values. Women before menopause show significantly lower values than do men of the same age. The data on patients with prostata cancer (n = 70) showed that patients with and without bone metastases, who had been treated with estrogens, had a significantly lower quantity of hydroxyproline than did patients who had not received estrogen therapy. Patients with skeletal metastases (n = 24) showed significantly higher hydroxyproline excretion in the urine than did those with prostate cancer without metastases, or healthy men of the same age (n = 35). Comparison of the results of hydroxyproline determination with the other diagnostic methods for demonstrating bone metastases showed that hydroxyproline determination was diagnostically on par with the scintigram. Pelvic crest biopsy, pelvic and sternal marrow aspiration can be considered valuable supplementary diagnostic procedures.

Bone Neoplasms↗
PubMed1979

Changes in connective tissue metabolism due to bone fractures in children aged 10--14 years. III. Urinary hydroxyproline and glycosaminoglycan excretion following bone fractures treated in different ways.

Urinary hydroxyproline and glycosaminoglycan excretion was studied in the course of fracture healing in twenty 10--14-year-old children with fracture of the femur or of the tibia and fibula. In 11 children reduction and plaster cast were used, in 5 osteosynthesis, and in 4 extension of 6--21 days duration combined with immobilization by plaster cast. In the state of resorption, an increase was observed in the urinary excretion of hydroxyproline and total glycosaminoglycans and in the six glycosaminoglycan fractions studied. As a result of the soft tissue damage accompanying the fracture, the excretion of hyaluronic acid, heparan sulphate, and dermatan sulphate showed the most marked increase. No statistically significant relationship could be demonstrated between the mode of treatment and the amounts of urinary hydroxyproline and glycosaminoglycan, but the stage of resorption was prolonged in the case of treatment with traction. At the beginning of regeneration, a decrease in hydroxyproline excretion and then an increase corresponding to the intensive synthesis of collagen were demonstrated. Glycosaminoglycan excretion during the development of fibrous callus was considerably below the control value. Excretion of the metabolites decreased markedly in the five operated patients. in the case of extension, the stage of regeneration prolonged by 4 to 10 days. In the stage of calcification, urinary hydroxyproline excretion was increased while the excretion of glycosaminoglycan and its fractions was the same as in the controls except in the patients treated with traction. No statistically significant relationship was found between the urinary amounts of hydroxyproline and glycosaminoglycan and the mode of treatment. In the case of traction, fracture repair and the formation of connective tissue callus were prolonged.

Adolescent↗
PubMed1981

Synovial fluid hydroxyproline fractions before and after osmic acid treatment in rheumatoid arthritis.

Synovial fluid total, dialysable and non-dialysable hydroxyproline were determined in patients with Rheumatoid Arthritis before intra-articular osmic acid injection and on days 2 and 4 after this local treatment. On day 2 the increase in dialysable hydroxyproline paralleled the increase in non-dialysable hydroxyproline. Patients with the highest pre-treatment dialysable hydroxyproline levels also had the highest levels of this fraction on day 2 suggesting that articular damage proceeds after osmic acid injection. However, on day 4 dialysable hydroxyproline levels were consistently lower than before the treatment; the same pattern was observed with non-dialysable hydroxyproline, except for all the joints but one, where effusion recurred 6-12 months after osmic acid treatment. This study suggests that the determination of synovial fluid non-dialysable levels 4 days after osmic acid injection may provide a clue to the prediction of recurrent joint effusion and possibly justify a complementary injection either with osmic acid or with a beta-emitting isotope.

Adult↗
PubMed1976

[Plasma hydroxyproline in chronic renal failure (author's transl)].

The plasma concentration of hydroxyproline fractions were determined in 50 adult patients with renal insufficiency and 19 patients receiving maintenance hemodialysis treatment. Free and peptide bound hydroxyproline fractions (total hydroxyproline) were elevated, the protein bound hydroxyproline (hypro-protein) was only slightly increased without significant correlation to the degree of renal insufficiency. The total hydroxyproline correlated only with the level of the alkaline phosphatase. The validity of the single fractions of hydroxyproline in plasma as parameter of the renal osteodystrophy is discussed.

Alkaline Phosphatase↗
PubMed1994

Measurement of free and total hydroxyproline by automated flow injection of serum or urine samples from maintenance hemodialysis patients with renal osteodystrophy.

An automated measurement of total and free hydroxyproline in serum or urine is presented that uses flow injection analysis. After exclusion of nonspecific substances, hydroxyproline was oxidized by chloramine-T and L-cysteine with Ehrlich's reagent. The linearity obtained was from 3.8 mumole/L to 1.22 mmole/L with good precision (CV < 3%). Comparison of the proposed method with HPLC yielded r = 0.939 as the correlation coefficient. Reference intervals of free and total hydroxyproline are 1.4-9.7 mumole/L, 3.8-27.2 mumole/L for serum, and 10.0-72.5 mumole/L, 25.2-303.6 mumole/L for urine, respectively. Serum free and total hydroxyproline levels in renal osteodystrophy patients on maintenance hemodialysis (N = 71) were significantly higher than in controls (P < 0.0001). This method is superior to the use of HPLC with regard to stability of the color reaction. The measurement of serum free and total hydroxyproline is a useful marker for therapeutic observation of renal osteodystrophy patients.

Chronic Kidney Disease-Mineral and Bone Disorder↗
PubMed1993

Coulometric electrochemical detection of hydroxyproline using 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole.

A new method for detection of hydroxyproline has been developed. Hydroxyproline was derivatized using 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole; separation and detection were accomplished using HPLC with coulometric electrochemical detection. Derivatized hydroxyproline was initially detected using a 16 channel coulometric electrochemical array system. The assay was slightly modified for use with a simpler 2-channel coulometric electrochemical detector. Both detectors are sensitive into the upper fmol range. Derivatization of hydroxyproline occurs in 5 min and the derivative is stable for several hours at 0 degrees C. The techniques were used to quantitate hydroxyproline in purified type I collagen and other biological samples.

4-Chloro-7-nitrobenzofurazan↗
PubMed2003

Transport of proline and hydroxyproline by the neutral amino-acid exchanger ASCT1.

ASCT1 is a member of the glutamate transporter superfamily cloned from human brain and characterized as a Na(+)-dependent neutral amino-acid exchanger, which displays substrate-induced chloride-channel activity and mediates concentrative transport of alanine. Initial studies in ASCT1-expressing Xenopus laevis oocytes showed that proline did not elicit measurable currents, in contrast to what occurred with alanine, serine or cysteine, suggesting that proline was not an ASCT1 substrate, although it induced the release of alanine from preloaded oocytes. Here, we have studied the uptake of proline and hydroxyproline by ASCT1-expressing oocytes in order to investigate the ability of ASCT1 to translocate these imino acids. The results demonstrate ASCT1-mediated proline transport that is Na(+)-dependent, saturable, inhibited by the reported ASCT1 substrates as well as by hydroxyproline and can drive the imino acid against its concentration gradient. The apparent kinetic constants for the transport of alanine and the imino acids, obtained with oocytes from the same batch, showed maximal transport rate for proline and hydroxyproline to be half of that for alanine. However, K(0.5) for proline was 704 +/- 86 microM, about three times higher than alanine K(0.5) (203.3 +/- 36.4 microM), whereas hydroxyproline K(0.5) was 33.2 +/- 4.3 microM, indicating that the hydroxylation on carbon 4 of proline strongly increases the affinity of ASCT1 for this proline derivative. In summary, the present work demonstrates for the first time the ability of ASCT1 to transport proline and hydroxyproline.

Adaptation, Biological↗
PubMed1991

Urinary hydroxyproline and serum alkaline phosphatase in sickle cell disease.

Serum alkaline phosphatase, alkaline phosphatase isoenzymes, and urinary hydroxyproline excretion were studied in 20 young adult sickle cell patients and 58 matching normal controls. Total alkaline phosphatase was significantly higher in the sickle cell patients than in controls. Heat inactivation test and isoenzyme electrophoresis indicated that bone is the predominant isoenzyme in patients. Hydroxyproline excretion was significantly higher in the sickle cell patients than in controls. Serum total alkaline phosphatase correlated well with urinary hydroxyproline excretion in sickle cell patients (r = 0.73). Both alkaline phosphatase and hydroxyproline increased with age in the sickle cell patients. This study suggests that delayed growth and/or bone destruction may contribute to the elevated levels of alkaline phosphatase and urinary hydroxyproline.

Adolescent↗
PubMed1996

Carrier-mediated transport controls hydroxyproline catabolism in heart mitochondria from spontaneously hypertensive rat.

In this study we have investigated hydroxyproline transport in rat heart mitochondria and, in particular, in heart left ventricle mitochondria isolated from both spontaneously hypertensive and Wistar-Kyoto rats. Hydroxyproline uptake by mitochondria, where its catabolism takes place, occurs via a carrier-mediated process as demonstrated by the occurrence of both saturation kinetics and the inhibition shown by phenylsuccinate and the thiol reagent mersalyl. In any case, hydroxyproline transport was found to limit the rate of mitochondrial hydroxyproline catabolism. A significant change in Vmax and Km values was found in mitochondria from hypertensive/hypertrophied rats in which the Km value decreases and the Vmax value increases with respect to normotensive rats, thus accounting for the increase of hydroxyproline metabolism due to its increased concentration in a hypertrophic/hypertensive state.

Animals↗