Transcatheter arterial embolisation in upper gastrointestinal bleeding in a sample of 29 patients in a gastrointestinal referral center in Germany.

OBJECTIVE: This is a retrospective analysis of interventional embolisation performed with catheter angiography in 29 patients with upper gastrointestinal bleeding in the setting of a secondary care hospital. PATIENTS, MATERIALS, AND METHODS: From April 2007 to February 2013, 29 patients with upper gastrointestinal bleeding underwent endovascular diagnostics and treatment. The diagnosis was established by endoscopy, computed tomography or clinically based on a significant decrease in hemoglobin. Transcatheter arterial embolisation was performed with coils, liquid embolic agents, and particles. The technical and clinical outcomes were assessed by postinterventional endoscopy, hemoglobin concentrations, number of necessary transfusions, or surgical interventions, as well as by post-interventional mortality within 28 days after the procedure. RESULTS: Selective angiographic embolisation in upper gastrointestinal bleeding was primarily successful technically and clinically in 22 of 29 patients. In 4/29 cases an angiographic reintervention was performed, which was successful in 3 cases. In 3 cases of primarily technically unsuccessful procedures reintervention was not attempted. No catheterisation-related complications were recorded. Peri-interventional mortality was 31%, but only 2 of these patients died due to uncontrolled massive bleeding, whereas the lethal outcome in the other 7 patients was due to their underlying diseases. CONCLUSION: Transcatheter arterial embolisation is an effective and rapid method in the management of upper gastrointestinal bleeding. Radiological endovascular interventions may considerably contribute to reduced mortality in GI bleeding by avoiding a potential surgical procedure following unsuccessful endoscopic treatment. The study underlines the importance of the combination of interventional endoscopy with interventional radiology in secondary care hospitals for patient outcome in complex and complicated upper gastrointestinal bleeding situations.

[Autoinflammatory syndromes/fever syndromes]. / Autoinflammatorische Syndrome/Fiebersyndrome.

Hereditary periodic (fever) syndromes, also called autoinflammatory syndromes, are characterized by relapsing fever and additional manifestations such as skin rashes, mucosal manifestations, or joint symptoms. Some of these disorders present with organ involvement and serological signs of inflammation without fever. There is a strong serological inflammatory response with an elevation of serum amyloid A (SAA), resulting in an increased risk of secondary amyloidosis. There are monogenic disorders (familial mediterranean fever (FMF), hyper-IgD-syndrome (HIDS), cryopyrin-associated periodic syndromes (CAPS), "pyogenic arthritis, acne, pyoderma gangrenosum" (PAPA), and "pediatric granulomatous arthritis (PGA) where mutations in genes have been described, which in part by influencing the function of the inflammasome, in part by other means, lead to the induction of the production of IL-1ß. In "early-onset of enterocolitis (IBD)", a functional IL-10 receptor is lacking. Therapeutically, above all, the IL-1 receptor antagonist anakinra is used. In case of TRAPS and PGA, TNF-antagonists (etanercept) may also be used; in FMF colchicine is first choice. As additional possible autoinflammatory syndromes, PFAPA syndrome (periodic fever with aphthous stomatitis, pharyngitis and adenitis), Schnitzler syndrome, Still's disease of adult and pediatric onset, Behçet disease, gout, chronic recurrent multifocal osteomyelitis (CRMO) and Crohn's disease also are mentioned.

RAP-PCR fingerprinting reveals time-dependent expression of matrix-related molecules following stem-cell based TGFß1-induced chondrocyte development.

Different approaches of engineering cartilage to treat defects in the articulating surfaces of the joints have been designed, which mainly use mesenchymal stem cells or autologous chondrocytes for in situ transplantation. However, these cells are poorly characterized with respect to viability, degree of differentiation and morphology or production of extracellular matrix. At present, one of the key approaches to generate chondrocytes is the stimulation of stem cells with transforming growth factor (TGF) ß1. To characterize the molecular alterations occurring during the cellular transformation induced by TGF-ß1 exposure, the differentiation process of bone marrow-derived stem cells into chondrocytes was investigated using an in vitro chondrogenesis model and the RNA arbitrarily primed PCR (RAP-PCR) fingerprinting technique. Distinct genes were found to be differentially regulated during chondrocyte development beginning on day 1: collagen type I, non-muscle myosin MYH9, followed by manganese superoxide dismutase and sodium-potassium ATPase on day 7. The results suggest that using RAP-PCR for differential display fingerprinting is a useful tool to investigate the differentiation process of bone marrow-derived stem cells following TGF-ß1-stimulation.

Role of the netrin system of repellent factors on synovial fibroblasts in rheumatoid arthritis and osteoarthritis.

Changes in the expression of repellent factors, i.e., Netrins and their receptors, may be responsible for the invasive behavior of the synovial tissue cells in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). This study was carried out to analyze the expression of Netrins and their receptors in synovial cells of patients with RA, OA, and control subjects without synovial inflammation. Quantitative RT-PCR was performed to measure the expression of Netrin-1, -3, -4, Neogenin, DCC, UNC5A-D. The influence of Netrin-1 on synovial fibroblasts (SF) was analyzed by determining proliferation, migration, and their ability to organize collagen. SF expressed all repellent factors of the Netrin family. When comparing SF of healthy donors to patients with RA and OA, a stronger expression of UNC5B (4 fold) and UNC5C (769 fold) in RA and OA was found, whereas expression of the other molecules revealed no significant differences. Treating the SF-cells with recombinant Netrin-1 resulted in inhibition of migration of RA- and OA-SFs whereas control cells were not affected. The stronger expression of UNC5B and UNC5C receptors might contribute to the disordered phenotype of RA- and OA-SFs. Addition of Netrin-1 reduces the migratory ability of SFs, potentially by repulsion, as seen in neuronal cells in embryonic development. Due to its function, Netrin-1 may constitute a novel target in the treatment of OA and RA.

Long-term effects of chondrospheres on cartilage lesions in an autologous chondrocyte implantation model as investigated in the SCID mouse model.

Microtraumata often lead to articular cartilage lesions. Due to the bradytrophic character of hyaline cartilage, these lesions are hardly repaired by the organism. Autologous chondrocyte implantation (ACI) was established for restoring isolated structural cartilage defects in knee joints. However, results are not always convincing. Human chondrocytes from patients undergoing total knee arthroplasty were cultured in monolayer followed by condensing single chondrocytes to spheroids (chondrospheres). The integrative capacity of chondrospheres was examined by implanting them into lesions in human articular cartilage specimens and co-implanting them into SCID mice. Mice were sacrificed after 4, 12 and 24 weeks. HE and safranin O staining as well as immunohistochemistry using anti-S100, anti-collagen I and II antibodies were performed and analyzed using semiquantitative scores. Integration of the chondrospheres with the (native) cartilage matrix was analyzed by determining the percentage of adhering surface. With respect to long-term stability, the chondrocytes within chondrospheres showed a typical chondrocytic morphology. Immunohistochemically, a high collagen II production was detected. Over a time period of 24 weeks, an increasing content of collagen type II, glycosaminoglycans and collagenous fibers were found. Importantly, the newly synthesized cartilaginous matrix integrated continuously with the native cartilage lesion border. In conclusion, the presented data demonstrate that chondrospheres are able to restore and conserve their phenotype for at least 24 weeks under in vivo conditions. Moreover, chondrospheres adhere to full-thickness cartilage defects and appear to produce a cartilaginous extracellular matrix which fuses with native cartilage thus generating an autologous cartilage-like repair tissue.

Whole-body MRI: a helpful diagnostic tool for juvenile dermatomyositis case report and review of the literature.

Juvenile Dermatomyositis (JDM) is a rare autoimmune disease in childhood. Distinction between muscle inflammation and a residual state can be difficult especially under immunosuppressive therapy and in active disease without correlating muscle enzyme tests or functional muscle scores. Our goal is to demonstrate the benefit of whole-body magnetic resonance imaging (MRI) as a diagnostic modality in the detection and management of JDM. One patient with JDM was monitored using clinical examination, muscle enzyme tests, muscle scores and whole-body MRI. During immunosuppression, the patient presented several times to our department without clear correlation between clinical picture, muscle enzyme tests and muscle scores. Whole-body MRI proved reliable in assessing the true state of the disease, thus providing invaluable information in the management of the inflammatory myopathy. This is of utmost importance for the therapeutic optimization in order to prevent further damage especially in children with active but subclinical disease.

[Periodic fever syndrome/autoinflammatory syndrome]. / Periodische Fiebersyndrome/autoinflammatorische Syndrome.

Hereditary periodic fever syndromes (autoinflammatory syndromes) are characterised by relapsing fevers and additional manifestations such as skin rashes, mucosal manifestations, and joint pain. Some of these disorders only present with organ manifestations and serological signs of inflammation without obvious fever (e.g. PAPA and Blau syndrome). There is a strong serological inflammatory response with an elevation of serum amyloid A (risk of secondary amyloidosis). There are monogenic disorders for which the mode of inheritance and gene mutation are known, but probably also polygenic diseases which present with similar symptoms to the classic autoinflammatory syndromes. Gene mutations have been described for the monogenic disorders (FMF, HIDS, CAPS, PAPA and Blau syndrome), which lead to an induction of the production of IL-1ss. Therapeutically, the IL-1-receptor antagonist anakinra is mainly used. In the case of TRAPS and Blau syndrome, TNF antagonists may also be used. PFAPA syndrome, the Schnitzler syndrome, Still's disease of adult and pediatric onset, Behçet's disaese and Crohn's disease also are mentioned as additional possible autoinflammatory syndromes.

[Autoimmune cholangitis with vasculitic ulcers, rheumatoid arthritis and IgA glomerulonephritis]. / Autoimmuncholangitis mit vaskulitischen Ulzera, rheumatoider Arthritis und IgA-Glomerulonephritis.

HISTORY AND ADMISSION FINDINGS: A 51-year-old woman was admitted because of relapsing episodes of fever and leg ulcers for 14 years. In addition, she had polyserositis, polyarthralgias and polyarthritides, renal failure with proteinuria and elevation of gamma-GT and alkaline phosphatase. The patient was in a reduced general condition and cachectic nutritional state. She had slight scleral icterus, the liver being palpable 5 cm under the costal margin, edema of the lower limbs and two ulcers at the right foot. INVESTIGATIONS: Laboratory examinations revealed leukocytosis, anemia, elevation of cholestasis and inflammation parameters as well as renal failure. During a 24 hour collection period, a significant proteinuria was demonstrated. Immunoserologically, an ANA titer of 1:100 and a positive rheumatoid factor were found, ANCAs and AMAs were negative. On ultrasound, both kidneys exhibited a blurred pelvic parenchymal border. Thyroid ultrasound demonstrated parenchymal changes consistent with Hashimoto's disease. Ultrasound of the wrist revealed extensive arthritis with tendovaginitis. A renal biopsy revealed mesangioproliferative glomerulonephritis. DIAGNOSIS, THERAPY AND CLINICAL COURSE: Due to serologically persistent cholestasis, a liver biopsy was performed which, together with negative AMAs, revealed the diagnosis of an autoimmune cholangitis (AIC; AMA-negative primary-biliary cirrhosis (PBC)). In addition, the patient presented with rheumatoid arthritis, polyserositis, IgA glomerulonephritis, vasculitic leg ulcers and Hashimoto's thyreoiditis which were interpreted as extra-hepatic manifestations of the AIC. After initiation of high dosage corticosteroid therapy, rapid healing of the leg ulcers occurred. Therapy of the AIC consisted in ursodeoxycholic acid. CONCLUSION: The multitude of associated immunological phenomena in this patient resulted in a delay of the diagnosis. A AIC/PBC, however, should, always be considered in case of cholestasis.

Differential adherence of osteoarthritis and rheumatoid arthritis synovial fibroblasts to cartilage and bone matrix proteins and its implication for osteoarthritis pathogenesis.

In osteoarthritis (OA), cartilage and bone fragments have been described within the synovial tissue which are surrounded by synovial cells (i.e. detritus synovitis). These cells appear to attach actively to the cartilage and bone fragments. In rheumatoid arthritis (RA), on the other hand, synovial fibroblasts (SF) have also been shown to be localized at sites of invasion into cartilage and bone and to degrade extracellular matrix (ECM) by secreting proteolytic enzymes. One prerequisite for exerting their aggressive properties is the attachment to cartilage and bone ECM. This attachment appears to be mediated by the expression of different adhesion molecules for which corresponding binding sites on ECM components are known. As it has not been addressed to which ECM proteins SF adhere and with which affinity this process takes place, we investigated the adherence of SF from patients with OA and RA to different cartilage and bone matrix proteins. Synovial tissue samples were obtained during synovectomy or arthroplastic surgery and used for isolating and culturing SF. Synovial cells attaching to cartilage/bone fragments were characterized using immunohistochemistry. The adherence of SF to ECM proteins was examined using an adhesion assay with the following proteins coated on 96-well plates: aggrecan (AGG), bone sialoprotein (BSP), cartilage oligomeric matrix protein (COMP), collagen type I, II and VI, proline arginine-rich, end leucine-rich repeat protein (PRELP), osteopontin (OPN) and recombinant chondroadherin (CHAD). Bovine serum albumin was used as negative control. In addition, adhering fibroblasts were photographed using a phase-contrast microscope. As compared with RA-SF, significantly higher numbers of OA-SF adhering to collagen type II, OPN and CHAD could be detected (P < 0.05). In contrast, RA-SF showed increased attachment to collagen type II, OPN and BSP. Adhesion to AGG, COMP and PRELP appeared not to be significantly increased and differed widely among the SF samples, and, apart from one exception (BSP), OA-SF adhered in higher numbers to the matrix proteins than did RA-SF. Using immunohistochemistry, synovial cells attached to cartilage/bone fragments could be shown to predominantly express CD68 (>/=50%). The CD68-negative population was of the fibroblast phenotype (AS02 positive). The study demonstrates that the binding pattern of OA-SF and RA-SF to ECM proteins differs considerably and therefore provides novel insights into the difficult pathophysiology of OA and RA. In general, it appeared that SF adhere primarily to ECM proteins that contain known binding sites for adhesion molecules (e.g. integrins: collagen/integrin alpha(2)beta(1)) and that higher numbers of OA-SF adhered to the cartilage and bone matrix proteins than did RA-SF.

Discrepancy between mRNA and protein expression of tumour suppressor maspin in synovial tissue may contribute to synovial hyperplasia in rheumatoid arthritis.

OBJECTIVE: To investigate the expression of maspin in RA synovial tissue and compare it with the expression in osteoarthritis (OA) and normal synovial tissue (NS). METHODS: Using specific primers for maspin, a 237 bp fragment was amplified from cDNA obtained from cultured RA, OA, and normal synovial fibroblasts (SF) by RT-PCR. Additionally, mRNA expression levels were determined quantitatively by real time PCR. mRNA expression of maspin was investigated on snap frozen and paraffin embedded synovial tissue sections by in situ hybridisation. Immunohistochemistry was used to identify the cell type expressing maspin. SDS-PAGE and western blotting were performed to evaluate the protein expression in cultured SF. To confirm protein synthesis in situ, immunohistochemistry with specific anti-maspin antibodies was performed in synovial tissue sections of patients with RA. RESULTS: RT-PCR showed expression of maspin in all cDNA samples from cultured SF. Maspin mRNA was found to be decreased in RA SF twofold and 70-fold compared with OA SF and NS SF, respectively. Maspin mRNA was expressed in RA, OA, and normal synovial tissue. Importantly, maspin transcripts were also found at sites of invasion into cartilage and bone. At the protein level, maspin could be detected in RA and, less prominently, OA SF. In RA synovial tissue, maspin protein was detected in only a few synovial lining cells. CONCLUSION: Maspin is expressed intensively in RA SF at the mRNA level, but only slightly at the protein level, possibly owing to down regulation of maspin; this may contribute to the hyperplasia of synovial tissue in RA.

The expression of cyclooxygenase-1, cyclooxygenase-2 and 5-lipoxygenase in inflammatory muscle tissue of patients with polymyositis and dermatomyositis.

OBJECTIVE: To describe cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) expression in muscle tissue in patients with idiopathic inflammatory myopathies (IIM) - dermatomyositis (DM) and polymyositis (PM) and to find out if any differences between affected and non-affected muscles detected by MRI exist. METHODS: Samples of muscle tissue from 7 patients with dermatomyositis (DM) and from 4 with polymyositis (PM) were obtained by needle biopsy from affected and non-affected sites distinguished by magnetic resonance imaging. In situ hybridization with antisense mRNA probes was employed to detect COX-1, COX-2 and 5-LOX mRNA. RESULTS: Expression of COX-1, COX-2, and 5-LOX mRNA was found in all samples - in the muscle cells, inflammatory cells and in vessels. COX-1 mRNA expression predominated in the inflammatory cells and vessels and was higher in affected than in non-affected sites detected by MRI (mean intensity 3.22+/-0.67 vs. 2.0+/-0.87; p = 0.0006). The expression of COX-2 mRNA was high mainly in inflammatory cells and/or vessels and was increased in MRI-detected affected tissues (3.5+/-0.88; 1.9+/-1.1; p = 0.003), as was the expression of COX-2 mRNA in muscle cells (2.1+/-1.0 vs. 1.3+/-1.0; p = 0.021). 5-LOX mRNA was largely expressed in muscle cells from MRI-detected affected sites and the signal intensity was higher in comparison with samples taken from non-affected tissues detected by MRI (3.22+/-0.7 vs. 1.67+/-0.7; p = 0.0007). CONCLUSION: Expression of COX-1, COX-2 and 5-LOX mRNA was observed for the first time in muscle tissues from IIM patients. This expression was increased in affected tissues detected by MRI, which may suggest a role of COX-1, COX-2, and 5-LOX in the pathogenesis of IIM.

Renal clearance and daily excretion of cortisol and adrenal androgens in patients with rheumatoid arthritis and systemic lupus erythematosus.

BACKGROUND: In rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), patients demonstrate low levels of adrenal hormones. OBJECTIVE: To investigate whether increased renal clearance and daily excretion contribute to this phenomenon. METHODS: Thirty patients with RA, 32 with SLE, and 54 healthy subjects (HS) participated. Serum and urinary levels of cortisol, cortisone, 17-hydroxyprogesterone (17OHP), androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulphate (DHEAS) were measured. RESULTS: Clearance of DHEAS and DHEA was lower in patients than in HS, and clearance of androstenedione was somewhat higher in patients than in HS, but daily excretion of this latter hormone was low. Clearance of cortisol, cortisone, and 17OHP was similar between the groups. The total molar amount per hour of excreted DHEA, DHEAS, and androstenedione was lower in patients than HS (but similar for cortisol). Serum DHEAS levels correlated with urinary DHEAS levels in HS and patients, whereby HS excreted 5-10 times more of this hormone than excreted by patients. Low serum levels of adrenal androgens and cortisol in patients as compared with HS were confirmed, and proteinuria was not associated with changes of measured renal parameters. CONCLUSIONS: This study in patients with RA and SLE demonstrates that low serum levels of adrenal androgens and cortisol are not due to increased renal clearance and daily loss of these hormones. Decreased adrenal production or increased conversion or conjugation to downstream hormones are the most likely causes of inadequately low serum levels of adrenal hormones in RA and SLE.

Targeting cathepsin L (CL) by specific ribozymes decreases CL protein synthesis and cartilage destruction in rheumatoid arthritis.

The present study was undertaken to examine whether ribozymes cleaving specifically cathepsin L (CL) mRNA are able to decrease the synthesis of CL protease in rheumatoid arthritis synovial fibroblasts (RA-SF) and thereby reduce the invasiveness into cartilage both in vitro and in the SCID mouse coimplantation model of RA. Two different ribozymes that cleave CL mRNA specifically at positions 533 (RzCL533) and 790 (RzCL790) were generated. Using retroviral gene transfer, RA-SF were transduced with the ribozyme constructs or the empty vector. To examine the effect of the ribozymes on the mRNA level, quantitative analysis for CL mRNA was performed using real-time PCR. For evaluation on the protein level, ELISA using specific anti-CL antibodies was performed. In addition, transduced RA-SF were examined in vitro in a three-dimensional destruction assay evaluating their ability to degrade extracellular matrix produced by human chondrocytes. Matrix destruction was monitored by the release of soluble glycosaminoglycans (sGAG). Using the in vivo SCID mouse coimplantation model of RA, RzCL533-transduced RA-SF and control cells were coimplanted with human cartilage for 60 days. After being killed, invasion of RA-SF into the cartilage was evaluated by using a semiquantitative score. Transduction of RA-SF with RzCL533 and RzCL790 ribozymes decreased significantly the expression of CL mRNA to 44% (range 25-62%) and 20% (range 1-43%), respectively, when compared to mock-transduced cells. The protein concentration of CL in the cell culture supernatants of transduced RA-SF was decreased from 16.0 ng/ml in the mock constructs to 4.1 and 8.2 ng/ml (mean), respectively. Using the in vitro cartilage destruction assay, the release of sGAG decreased to 46 and 60%, respectively, after 14 days when compared to mock-transduced cells. In the SCID mouse coimplantation model of RA, RzCL533-transduced RA-SF revealed a significant lower cartilage invasion when compared to mock and untransduced cells. Using retroviral gene transfer, ribozymes cleaving CL mRNA inhibit specifically the synthesis of this matrix-degrading enzyme and reduce cartilage destruction in in vitro and in vivo models. Our study therefore suggests that ribozymes targeting CL could be a novel and efficient tool to inhibit joint destruction in RA.

Expression of osteopontin messenger RNA and protein in rheumatoid arthritis: effects of osteopontin on the release of collagenase 1 from articular chondrocytes and synovial fibroblasts.

OBJECTIVE: Osteopontin (OPN) is an extracellular matrix protein that has been implicated in the interactions between tumor cells and host matrix, including those involved in invasion and spread of tumor cells. Because joint destruction in rheumatoid arthritis (RA) is mediated by the invasive growth of synovial tissue through its attachment to cartilage, we examined the expression of OPN in the synovia of patients with RA and the effect of OPN on the production of collagenase 1 in rheumatoid synovial fibroblasts and articular chondrocytes. METHODS: The expression of OPN messenger RNA (mRNA) and protein in synovia from 10 RA patients was examined by in situ hybridization and immunohistochemistry. Synovial fibroblasts from RA patients and articular chondrocytes from patients without joint disease were cultured in the presence of various concentrations of OPN, and levels of collagenase 1 in the culture supernatants were measured by enzyme-linked immunosorbent assay. RESULTS: The expression of OPN mRNA and protein was observed in 9 of 10 specimens obtained from patients with RA. OPN was expressed in the synovial lining and sublining layer and at the interface of cartilage and invading synovium. Double labeling revealed that the majority of OPN-expressing cells were positive for the fibroblast-specific enzyme prolyl 4-hydroxylase and negative for the macrophage marker CD68, while only a few, single OPN-expressing cells were positive for CD68 at sites of synovial invasion into cartilage. OPN staining was not observed in lymphocytic infiltrates or leukocyte common antigen (CD45)-positive cells. Three of 3 cultures of human articular chondrocytes secreted detectable basal amounts of collagenase, with a dose-dependent increase upon OPN stimulation, while synovial fibroblast cultures produced much lower levels of collagenase, with only 2 of 4 fibroblast cultures responding in a dose-dependent manner. CONCLUSION: These findings suggest that OPN produced by synovial fibroblasts in the synovial lining layer and at sites of cartilage invasion not only mediates attachment of these cells to cartilage, but also contributes to matrix degradation in RA by stimulating the secretion of collagenase 1 in articular chondrocytes.

The biomechanic origin of sprint performance enhancement after one-week creatine supplementation.

In order to test whether an improvement of maximal sprinting speed after creatine (Cr) supplementation was due to the increase of stride frequency (SF), stride length (SL) or both, 7 subjects ran 4 consecutive sprints after 1 week of placebo or Cr supplementation. SF and SL were assessed by a triaxial accelerometer. Compared to the placebo, Cr induced an increase of running speed (+1.4% p < 0.05) and SF (+1.5%, p < 0.01), but not of SL. The drop in performance following repeated sprints was partially prevented by Cr. In conclusion, exogenous Cr enhanced sprinting performance by increasing SF. This result may be related to the recent findings of shortening in muscular relaxation time after Cr supplementation.

Acute creatine loading enhances human growth hormone secretion.

BACKGROUND: The main objective of this study was to explore the effect of acute creatine (Cr) ingestion on the secretion of human growth hormone (GH). METHODS: In a comparative cross-sectional study, 6 healthy male subjects ingested in resting conditions a single dose of 20 g creatine (Cr-test) vs a control (c-test). During 6 hours the Cr, creatinine and GH concentrations in blood serum were measured after Cr ingestion (Cr-test). RESULTS: During the Cr-test, all subjects showed a significant stimulation of GH (p<0.05), but with a large interindividual variability in the GH response: the difference between Cr-test and c-test averaged 83% (SD 45%). For the majority of subjects the maximum GH concentration occurred between 2 hrs and 6 hrs after the acute Cr ingestion. CONCLUSIONS: In resting conditions and at high dosages Cr enhances GH secretion, mimicking the response of strong exercise which also stimulates GH secretion. Acute body weight gain and strength increase observed after Cr supplementation should consider the indirect anabolic property of Cr.