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Biomedical subjects

D Uebelhart

Publications and source records attributed to D Uebelhart.

At least 37 records · Page 2Linked to original sources
PubMed1998

Protective effect of exogenous chondroitin 4,6-sulfate in the acute degradation of articular cartilage in the rabbit.

The injection of 2.0 mg chymopapain into the adolescent rabbit knee causes severe loss of articular cartilage proteoglycans (PG). Although chondrocytes attempt to restore lost PG, failure to repair ensues. Pure chondroitin 4,6-sulfate (Condrosulf, IBSA Lugano, Switzerland) has been used in clinical studies of human osteoarthritis (OA) as a slow-acting drug for OA (SYSADOA). Using our model of articular cartilage injury, we examined the effects of oral and intramuscular administration of Condrosulf after chymopapain-induced cartilage injury. In this study, animals received an injection of 2.0 mg chymopapain (Chymodiactin, Boots Pharmaceuticals) into the left knee and were sacrificed after 84 days. The contralateral right knee served as a noninjected control. Some animals received oral Condrosulf while others received intramuscular injections of Condrosulf. Serum keratan sulfate (KS) levels were monitored to ensure degradation of the cartilage PG. Those animals not exhibiting at least a 100% increase of serum KS following chymopapain injection were excluded from the study. At sacrifice, cartilage PG contents were markedly reduced in animals receiving an injection of 2.0 mg chymopapain with no further treatment. In contrast, oral administration of Condrosulf beginning 11 days prior to chymopapain injury resulted in significantly higher (P = 0.0036) cartilage PG contents. Intramuscular administration of Condrosulf resulted in higher, but less significantly so (P = 0.0457), cartilage PG contents. These results suggest that daily Condrosulf treatment prior to and continuing after chymopapain injury may have a protective effect on the damaged cartilage, allowing it to continue to re-synthesize matrix PG after the treatment is discontinued.

Administration, Oral↗
PubMed1998

Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study.

The aim of this study was to assess the clinical, radiological and biological efficacy and tolerability of the SYSADOA, chondroitin 4- and 6-sulfate (CS, Condrosulf, IBSA, Lugano, Switzerland), in patients suffering from knee osteoarthritis. This was a 1-year, randomized, double-blind, controlled pilot study which included 42 patients of both sexes, aged 35-78 years with symptomatic knee OA. Patients were treated orally with 800 mg chondroitin sulfate (CS) per day or with a placebo (PBO) administered in identical sachets. The main outcome criteria were the degree of spontaneous joint pain and the overall mobility capacity. Secondary outcome criteria included the actual joint space measurement and the levels of biochemical markers of bone and joint metabolism. This limited study confirmed that chondroitin sulfate was well-tolerated and both significantly reduced pain and increased overall mobility capacity. Treatment with CS was also associated in a limited group of patients with a stabilization of the medial femoro-tibial joint width, measured with a digitized automatic image analyzer, whereas joint space narrowing did occur in placebo-treated patients. In addition, the metabolism of bone and joint assessed by various biochemical markers also stabilized in the CS patients whereas it was still abnormal in the PBO patients. These results confirm that oral chondroitin 4- and 6-sulfate is an effective and safe symptomatic slow-acting drug for the treatment of knee OA. In addition, CS might be able to stabilize the joint space width and to modulate bone and joint metabolism. This is the first preliminary demonstration that a SYSADOA might influence the natural course of OA in humans.

Administration, Oral↗
PubMed1998

Biochemical markers of bone metabolism in draught and warmblood horses.

Concentrations of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and osteocalcin (OC) have been determined in the serum of one hundred clinically healthy adult Draught or Warmblood horses. The correlation between these two markers has been evaluated and the influence of gender, age and type of horse described. No significant variations were observed between animals of different sex, but a significant inverse correlation (P < 0.0001) with age was observed for both measured parameters. After correction for age, serum levels of OC were found to be lower in Draught [adjusted least square mean (LSM) = 6.612 micrograms.L-1] than in Warmblood horses (adjusted LSM = 8.596 micrograms.L-1), whereas levels of ICTP were higher in Draughts (adjusted LSM = 8.035 micrograms.L-1) than in Warmbloods (adjusted LSM = 6.643 micrograms.L-1). A significant correlation (P < 0.0001) was observed between OC and ICTP. This correlation was stronger if the type of horse was taken into account in the statistical model. The ratio OC:ICTP was independent of gender and age. A higher OC:ICTP ratio in Warmbloods compared to the Draught horses might reflect a higher bone remodelling level of horses submitted to regular daily work. It was concluded that ICTP and OC are influenced by the type of horse, and probably reflect a physiological difference in bone remodelling between these animals.

Age Factors↗
PubMed1998

Percutaneous endoscopic gastrostomy in neurological rehabilitation: a report of six cases.

PURPOSE: This study reports the cases of six patients with severe chronic neurological disability and swallowing difficulties due to traumatic brain injury (TBI), anoxia and multiple sclerosis (MS). METHOD: The patients required nutritional supplement through percutaneous endoscopic gastrostomy (PEG). RESULTS: Their clinical follow-up showed a decrease of intercurrent medical complications, especially pressure sores. In addition, an improvement of oropharyngeal function was observed in some patients, also accompanied by slightly better basic psychomotor functions such as vigilance, sustained attention and tone or motor control. However, not every patient did improve with this procedure. The two MS patients benefited most, while the improvement was less homogenous in the three TBI patients. CONCLUSIONS: The advantages of PEG over nasogastric tube on oropharyngeal function can be related to the absence of pharyngeal irritation and its role in overall recovery could be due to an increase in social activities, a control of infections, a better rehabilitation schedule and a long-term effect on brain function due to better nutritional support.

Adult↗
PubMed1997

Effects of 1- and 6-month spaceflight on bone mass and biochemistry in two humans.

The bone mineral density and the biochemical parameters exploring bone cell activities were analyzed in two cosmonauts who spent 1 and 6 months, respectively, in the Russian MIR station. Measurements were performed before the flight, after the flight, and after a recovery period. At the end of the first month, peripheral QCT measurements indicated a slight decrease of trabecular bone mass in the distal tibial metaphysis. However, after 6 months of spaceflight, a more marked loss of trabecular and cortical bones was observed in the tibia, and was still significant after 6 month recovery in the trabecular compartment, whereas a decrease was no longer observed in the cortical envelope. No change was observed in either compartment of the distal radius at any time. Ultrasound BUA of the calcaneus was greatly reduced by the first month, followed by a more dramatic decrease after month 6. Ultrasound SOS detected no change. Parameters reflecting bone formation activity appeared to be depressed after both missions. In contrast, no dramatic change in resorption parameters was observed, except for a trend toward an increase in pyridinoline. In conclusion, the lower weight-bearing bones appeared more sensitive than the upper ones in terms of spaceflight-induced bone loss. This probably explained the absence of marked systemic biochemical data changes. This study further suggests that recovery in the tibial trabecular compartment 6 months after landing was not completed after a 6 month mission.

Adult↗
PubMed1996

Characterization of crosslinked collagens synthesized by mature articular chondrocytes cultured in alginate beads: comparison of two distinct matrix compartments.

We have characterized immunohistochemically and biochemically the collagens accumulating in two compartments of the matrix formed by mature bovine articular chondrocytes in alginate beads. At all times of the 28-day culture period, more than 90% of the collagen molecules were recovered from the rim of cell-associated matrix (CM) which encapsulates individual chondrocytes and chondrocyte clusters. Both the total amount and concentration of collagens in this matrix compartment rose progressively with time. The ratio of collagen/proteoglycan remained relatively constant with time and was always five to seven times higher in the CM than in the interterritorial matrix compartment further removed from the cells. In the CM, collagen types II, IX and XI were present on Day 28 in relative proportions (95/l/3) similar to those in adult cartilage. A higher proportion of newly synthesized collagen type XI than types II or IX molecules did not become incorporated into the pericellular rim of matrix but accumulated in the further removed matrix. Although collagen type I was synthesized in small amounts by flattened cells at the surface of the beads, it did not become incorporated as heterotrimers or homotrimers in the matrix. Mature pyridinium crosslinks, principally pyridinoline, were detected as early as Day 7 of culture but became much more abundant between Days 15 and 28, especially in the CM which contained at all times more than 90% of the crosslinks formed. The codistribution of collagen types II, IX and XI and mature collagen-specific crosslinks support the contention that mature chondrocytes cultured in alginate matrix surround themselves with a protective shell whose composition is very similar to that which encapsulated the cells in vivo.

Alginates↗
PubMed1996

Assessment of urinary hydroxypyridinium cross-links measurement in osteoarthritis.

The aim of this study is to re-evaluate urinary collagen cross-links, previously proposed as markers of osteoarthritis (OA). The urinary excretion of collagen cross-links, pyridinoline (PYD) and deoxypyridinoline (DPD), was measured using high-performance liquid chromatography (HPLC) in 114 patients with OA, 19 patients with rheumatoid arthritis (RA) and 40 healthy subjects. An increase in PYD and DPD, expressed per millimole of creatinine, was confirmed in RA. However, PYD and DPD in patients with hip OA, knee OA and polyOA were similar, and did not differ from controls. In patients with radiographic end-stage OA, PYD and DPD were significantly higher than in patients with an early OA, but not significantly higher than in controls. The PYD/DPD ratio did not vary with the OA stage. Thus, urinary collagen cross-links are not elevated in OA, but could reflect bone sclerosis and/or erosion in late OA.

Adult↗
PubMed1996

Alteration and recovery of the spatial orientation of the collagen network of articular cartilage in adolescent rabbits following intra-articular chymopapain injection.

We have used polarized light (POL) to monitor changes in the organization of the articular cartilage collagen network and matrix proteoglycans (PGs) after intra-articular injection of chymopapain (CP). POL viewing of sirius red stained sections revealed a loss of normal birefringence suggesting an apparent collapse of the collagen network following intra-articular CP. After 21 days, knees injected with 2.0 mg CP showed no return of normal birefringence, however, normal birefringence was noted in knees injected with only 0.2 mg CP. POL viewing of toluidine blue stained sections revealed a severe loss of matrix PGs followed by PG restoration in animals injected with 0.2 mg CP. The most important inference from the data is that articular cartilage can recover from enzyme-induced alterations in the spatial collapse of its fibrillar network. This is an important finding since it has often been inferred that damage to the collagen network leads invariably to progressive articular cartilage destruction.

Animals↗
PubMed1995

Bone metabolism in spinal cord injured individuals and in others who have prolonged immobilisation. A review.

Immobilisation or disuse is a condition known to be associated with a decrease in bone mass, osteopenia and in some people leading to osteoporosis with an increased risk of fractures. In this condition, previous histomorphometric and biochemical reports have shown an uncoupling between bone formation and resorption, but the exact sequence of the events resulting in bone loss is still not fully understood. In spinal cord injury for instance, the main finding soon after the onset is decreased osteoblastic activity associated with a dramatic increase in bone degradation. The overall consequence of these metabolic events is the development of a rapid and severe osteoporosis only observed in the paralysed part of the body associated with the loss of biomechanical strength and the biosynthesis of a structurally modified matrix which is unable to sustain normal mechanical stress. This situation dramatically increases the risk of fractures. The same uncoupling phenomenon has been described in healthy individuals who have been submitted to long duration bedrest and also in astronauts during spaceflight; but the timing, intensity and the metabolic subset may be different as these people do recover after cessation of the disuse period, which does not occur in paralysed patients. As new accurate and sensitive non-invasive techniques have become available recently to assess bone and connective tissue metabolism, more information is now available regarding bone loss in paralysed and/or immobilised individuals. These techniques should be definitely helpful in orientating new therapeutic trials with drugs and/or procedures intended to correct the musculoskeletal deleterious effects of disuse. This paper is therefore aimed at a review of bone metabolism in those with a severe spinal cord injury, or with a long duration of bedrest, or with loss of biomechanical function, or with actual or simulated spaceflight, in all instances using non-invasive techniques.

Bed Rest↗
PubMed1995

Detectable levels of pyridinoline are present in synovial fluid from various patients with knee effusion: preliminary results.

There is a major interest for using biochemical markers of bone metabolism as a non-invasive tool for diagnostic purposes in the field of bone and joint diseases. Based upon the fact that the pyridinium cross-links of collagen are markers of bone and cartilage degradation, this study was designed to assess the presence of pyridinoline in synovial fluid samples originating from various arthritic and non-arthritic knee joints. Using a sample pooling method, significant levels of pyridinoline could be measured in synovial fluid by high performance liquid chromatography. Pyridinoline levels ranged from 19.3 +/- 5.8 pmol mL-1 (mean +/- SD) in osteoarthritic knee joints up to 32.4 +/- 14.6 pmol mL-1 in rheumatoid arthritis joints. Pyridinoline levels in synovial fluid were not significantly correlated to disease duration and synovial fluid cell count, but were correlated to erythrocyte sedimentation rate in osteoarthritic patients (r = 0.99, P = 0.002). This study demonstrates that synovial fluid originating from knee effusion contains significant levels of pyridinoline which can be quantified by high performance liquid chromatography and could, therefore, be a tool to investigate the metabolism of a single joint.

Adult↗
PubMed1994

Early modifications of biochemical markers of bone metabolism in spinal cord injury patients. A preliminary study.

Spinal cord injury is associated with the development of a rapid and severe osteoporosis which might reflect uncoupling between bone formation and resorption. A prospective study was made in 6 spinal cord injury patients followed up to 2-3 months after onset with various markers of a) bone formation: osteocalcin and C-terminal peptide of type I procollagen, b) bone resorption: pyridinolines and C-terminal telopeptide of type I collagen, c) connective tissue metabolism: amino-terminal propeptide of type III collagen (PIIINP). Preliminary results show that early after onset, bone formation was depressed as compared to dramatically increased bone resorption. Low bone formation rate lasted two weeks before it began to raise, while bone resorption showed a continuous tendency to increase. The dramatic increase in PIIINP levels might represent some attempt of bone to repair. This paper describes the evolution of various biochemical markers of bone and connective tissue metabolism after onset of paralysis and critically reviews the use of those markers in patients with spinal cord injury.

Adult↗
PubMed1993

Elevation in urinary levels of pyridinium cross-links of collagen following chymopapain-induced degradation of articular cartilage in the rabbit knee provides evidence of metabolic changes in bone.

To measure urinary levels of two pyridinium cross-links of collagens at various times, rabbits were injected in the left knee with 0.2 mg (N = 11) or 2.0 mg chymopapain (N = 11). Urinary levels of the bone-specific deoxy-pyridinoline cross-link and of the hydroxylysyl pyridinoline cross-link, found in large amounts in articular cartilage and bone, were measured by high performance liquid chromatography (HPLC). The urinary levels were correlated with histological evidence of progressive articular cartilage destruction in animals injected with 2.0 mg chymopapain and of successful repair in rabbits injected with the lower dose. Rabbits injected with 2.0 mg chymopapain showed a very large increase in urinary levels of deoxy-pyridinoline during the first 30 days after the injection. This rise was not seen in animals injected with the lower dose. A rise in urinary level of the hydroxylysyl pyridonline cross-link was observed in all rabbits but was more pronounced and lasted longer in animals receiving the higher dose. The failure of rabbits injected with 2.0 mg chymopapain to repair the damaged articular cartilage was strongly associated with a marked increase in the catabolism of the bone-specific deoxy-pyridinoline cross-link and to a lesser extent with the catabolism of the hydroxylysyl pyridinoline found in bone and in articular cartilage.

Aging↗
PubMed1993

[Assay of cross-linking molecules of collagen (pyridinolines) in the study of the degradation of bone tissue and articular cartilage].

Recent studies aimed at studying the degradation of the fibrillar collagens of bone and articular cartilage have lead to the discovery of naturally fluorescent crosslinking compounds derived from lysine and hydroxylysine. These small molecules characterized by an aromatic 3-hydroxypyridinium ring are present in significant amounts only in bone (pyridinoline and deoxy-pyridinoline) and cartilage (pyridinoline). Diseases characterized by an increased degradation of the fibrillar collagenous network are associated with an increased urinary excretion of both compounds: Pyridinoline and deoxypyridinoline are currently the most sensitive and specific markers of bone resorption. The purpose of this paper is to review current knowledge in the area of collagen crosslinking molecules with special emphasis on the pyridinium crosslinking amino acids and their potential clinical application as a marker of bone and cartilage degradation.

Adolescent↗
PubMed1991

Effect of menopause and hormone replacement therapy on the urinary excretion of pyridinium cross-links.

Pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) are two cross-links of collagen molecules that are present in the extracellular matrix and released during its degradation. In contrast to the wide distribution of collagen, Pyr is present in bone and cartilage, but not in significant amounts in other connective tissues, and D-Pyr appears to be specific for bone tissue. Therefore, the urinary excretion of Pyr and D-Pyr might be a sensitive marker of bone matrix degradation. Using a specific high pressure liquid chromatography assay we have measured Pyr and D-Pyr cross-links in a 24-h and a fasting urine sample in 60 early postmenopausal women and 19 premenopausal women matched for age. Menopause induced a 62% increase in Fu Pyr (49.8 +/- 18.7 vs. 30.8 +/- 8.0 pmol/mumol creatinine; P less than 0.001) and an 82% increase in Fu D-Pyr (8.2 +/- 3.4 vs. 4.5 +/- 1.4 pmol/mumol creatinine; P less than 0.001). In 20 postmenopausal women on hormone replacement therapy, urinary Pyr and D-Pyr returned to premenopausal levels within 6 months, contrasting with unchanged levels during placebo treatment. The 24-h excretion of Pyr and D-Pyr was significantly lower than the fasting excretion, but was similarly decreased after hormone replacement therapy. Pyr and D-Pyr excretion measured in the same urinary sample were highly correlated (r = 0.85 for fasting and 0.83 for 24-h sampling), but correlations between fasting and 24-h values were weak (D-Pyr, r = 0.30; Pyr, r = 0.29; P less than 0.05 for both). Correlations between urinary cross-links and other markers of bone turnover (Fu hydroxyproline/creatinine and plasma osteocalcin) were significant but low (Pyr vs. osteocalcin, r = 0.29, P less than 0.05; Pyr vs. hydroxyproline, r = 0/.34; P less than 0.01; D-Pyr vs. osteocalcin, r = 0.39; P less than 0.01), except for D-Pyr vs. hydroxyproline (r = 0.24; P = 0.07), suggesting that these markers reflect different events of bone metabolism. Finally, a single measurement of the fasting excretion, but not of the 24-h excretion, of cross-links was significantly correlated (Pyr, r = 0.34; P less than 0.05; D-Pyr, r = -0.46; P less than 0.01), with the subsequent spontaneous rate of bone loss assessed by repeated measurements of the radial bone mineral content in 37 postmenopausal women.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed1990

Lateral dual-photon absorptiometry: a new technique to measure the bone mineral density at the lumbar spine.

Bone mineral density (BMD) measurement of the lumbar spine by dual-photon absorptiometry (DPA) using a radioactive source and more recently an x-ray tube (DEXA) is a useful noninvasive technique to assess bone loss in vertebral osteoporosis. Because an anteroposterior (AP) projection is used, DPA measures not only the mainly trabecular bone of the vertebral body but also the cortical bone of the posterior processes, which does not contribute to the development of crushed fractures. Using a DPA apparatus equipped with a 153 Gd source coupled with an 18-detector system that provides better collection efficiency for the narrow beam of 153 Gd radiation, we have developed a technique measuring the BMD of the vertebral body of L2, L3, and L4 on a lateral projection based on previous studies using radiographic photodensitometry for lateral spine. The precision of the method-1.7% in vivo and 0.88% in vitro-is similar to that obtained with the AP projection (respectively, 1.7 and 1.0%). Lateral BMD decreased with age in 143 normal women and was best accounted for by a cubic curve (r = -0.51, p less than 0.001). The age-related bone loss between 30 and 80 years of age was much higher with the lateral (-44%) than with the AP (-22%) projection, a pattern consistent with the greater trabecular than cortical age-related bone loss. When osteoporotics (OP) were compared to age-matched normal women, the decreased in BMD was larger with the lateral (-30%) than with the AP projection (-23%), but in terms of Z scores, no difference could be found between both projections.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1990

Comparison between radial bone mineral density measured by single photon absorptiometry and histomorphometric bone mass parameters measured on iliac crest biopsies.

Bone mineral density (BMD) measured by single photon absorptiometry (SPA) with a Moolsgard 1100 device on the distal and proximal part of the radius was compared with histomorphometric parameters measured on iliac crest biopsies in 37 patients suffering from various bone disorders. In the whole population, a good correlation was observed between the cancellous bone volume (Cn-BV/TV) measured on iliac crest biopsies and BMD from both the proximal part of the radius (r = 0.76, p less than 0.001) and the distal part of the radius (r = 0.73, p less than 0.001). Significant, although weaker correlations, were also found between the cortical width and the BMD from the distal part (r = 0.37, p less than 0.001) and the proximal part (r = 0.44, p less than 0.001) of the radius. In the 14 untreated osteoporotic patients, only a significant Spearman correlation was observed between the iliac Cn-BV/TV and the proximal radial BMD (r' = 0.69, p less than 0.05). It is thus not clear, whether radial proximal BMD correctly indicates cortical bone density in osteoporotic patients or not. The large internal variability of each of the two investigated methods and the small group of osteoporotic patients might explain the lack of correlation between the two methods in this group.

Absorptiometry, Photon↗