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Biomedical subjects

J Graf

Publications and source records attributed to J Graf.

At least 55 records · Page 3Linked to original sources

Gastric tonometry in patients with cardiogenic shock and intra-aortic balloon counterpulsation.

OBJECTIVE: To study the course of gastric regional PCO2 (PrCO2) in patients with cardiogenic shock requiring intra-aortic balloon (IAB) counterpulsation and the prognostic value of PrCO2 in this patient population. DESIGN: A prospective, observational clinical study. SETTING: Medical intensive care unit in a university hospital. PATIENTS: Twenty-six consecutive patients with cardiogenic shock requiring mechanical support with an IAB counterpulsation undergoing mechanical ventilation INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULT: Hemodynamic variables, tonometric variables, arterial blood gases, and arterial lactate were assessed before insertion of IAB (baseline), and 1, 2, 3, 8, 16, 24, and 48 hrs thereafter. A subset of these patients (n = 14) were studied just before and 1, 8, 24, and 32 hrs after IAB removal; 12/26 patients (46.2%) died. Cardiac index increased from baseline to 1 hr after insertion of IAB (1.7 +/- 0.3 to 2.6 +/- 0.8 L/min/m2, p < .05). PrCO2 did not change between admission (47 +/- 13 torr [6.3 +/- 1.7 kPa]) and 8 hrs after placement of IAB but increased to 63 +/- 22 torr (8.4 +/- 2.9 kPa) at 16 hrs (p < .05) without any further alteration until 48 hrs. CO2 gap showed a similar pattern with 15 +/- 11 torr (2.0 +/- 1.5 kPa) at baseline and an increase to 28 +/- 22 torr (3.7 +/- 2.9 kPa) 16 hrs later. PrCO2 and CO2 gap remained at high levels (59 +/- 11 torr [7.7 +/- 1.5 kPa] and 22 +/- 10 torr [2.9 +/- 1.3 kPa], respectively), before IAB removal without further improvement or deterioration thereafter. PrCO2 values showed no difference between survivors and nonsurvivors at any time point. CONCLUSION: Patients with cardiogenic shock developed high PrCO2 within the first 24 hrs, which reflects gastric mucosal ischemia. Persistently high levels of PrCO2 were indicative for prolonged hypoperfusion of the gut. Gastric tonometry failed to discriminate between survivors and nonsurvivors.

Aged↗

Ingested blood contributes to the specificity of the symbiosis of Aeromonas veronii biovar sobria and Hirudo medicinalis, the medicinal leech.

Hirudo medicinalis, the medicinal leech, usually carries in its digestive tract a pure culture of Aeromonas veronii bv. sobria. Such specificity is unusual for digestive tracts that are normally colonized by a complex microbial consortium. Important questions for the symbiotic interaction and for the medical application after microvascular surgery are whether other bacteria can proliferate or at least persist in the digestive tract of H. medicinalis and what factors contribute to the reported specificity. Using a colonization assay, we were able to compare experimentally the ability of clinical isolates and of a symbiotic strain to colonize H. medicinalis. The symbiotic A. veronii bv. sobria strain proliferated well and persisted for at least 7 days inside the digestive tract. In contrast, the proliferation of Pseudomonas aeruginosa and Staphylococcus aureus was inhibited inside the animal compared to growth in the in vitro control, indicating that the ingested blood was modified within the digestive tract. However, both strains were able to persist in the digestive tract for at least 7 days. For an Escherichia coli strain, the viable counts decreased approximately 1, 000-fold within 42 h. The decrease of viable E. coli could be prevented by interfering with the activation of the membrane-attack complex of the complement system that is present in blood. This suggests that the membrane-attack complex remained active inside H. medicinalis and prevented the proliferation of sensitive bacteria. Thus, antimicrobial properties of the ingested vertebrate blood contribute to the specificity of the A. veronii-H. medicinalis symbiosis, in addition to modifications of the blood inside the digestive tract of H. medicinalis.

Aeromonas↗

A new concept in the treatment of anterior knee pain: patellar hypertension syndrome.

This prospective clinical study evaluated 69 patients (136 knees) presenting with anterior knee pain after failure to respond to conservative treatment. All patients agreed to undergo minimally invasive intraosseous pressure measurements of the patella under local anesthesia. Forty patients (50 knees) demonstrated a positive pain provocation test (the typical pain sensation could be reproduced by raising intrapatellar pressure) and were treated with a new method of intraosseous drilling and decompression. Ninety percent of the patients treated experienced pain relief >3 years postoperatively. Repeated intraosseous pressure measurements in 33 knees 1 year postoperatively confirmed objective intraosseous pressure reduction in 88%. Patients with anterior knee pain and a positive pain provocation test were labeled as hypertension syndrome of the patella. These results indicate simple extra-articular patellar decompression may offer a valuable new form of treatment in select patients with anterior knee pain, ie, hypertension syndrome of the patella.

Adolescent↗

Herbal anti-inflammatory agents for skin disease.

Herbs have been used in clinical medicine for thousands of years. However, it is only in recent times that we have been able to employ scientific methods to prove the efficacy of many of these herbs and to give us a better understanding of their mechanisms of action. This article will focus on the use of herbs in various dermatological conditions characterized by inflammation and pruritus. Topical preparations of many of these herbs are more commonplace in Europe. However, their availability is increasing in the US. As this is occurring we are witnessing a growing marriage between alternative and traditional medicines.

Aloe↗

Lower cardiac troponin T and I results in heparin-plasma than in serum.

BACKGROUND: The use of plasma rather than serum for determination of cardiac troponins can improve turnaround time and potentially avoid incomplete serum separation that may produce falsely increased results. We investigated the influence of incomplete serum separation and the effect of heparin-plasma on cardiac troponin concentrations. METHODS: Serum and heparin-plasma samples were drawn simultaneously from 100 patients (50 patients with acute coronary syndrome and 50 patients after open heart surgery) and measured on three different analytical systems, two for determination of cardiac troponin I (cTnI; Abbott AxSYM and Bayer ACS:Centaur) and one for cardiac troponin T (cTnT; Roche Elecsys cTnT STAT). Serum samples were reanalyzed after a second centrifugation to assess the influence of incomplete serum separation. RESULTS: Mean results (+/- 95% confidence interval) in heparin-plasma compared with serum were 101% +/- 2% (AxSYM cTnI), 94% +/- 3% (ACS:Centaur cTnI), and 99% +/- 3% (Elecsys cTnT). Differences >20% were seen in 11% of results on the ACS:Centaur, 9% of results on Elecsys cTnT, and 2% of results on the AxSYM. For the Elecsys cTnT assay, the magnitude of the difference between serum and plasma was independent of the absolute concentration and confined to individual samples, and was reversed by treatment with heparinase. A second centrifugation had no effect on serum results by any of the assays. CONCLUSION: The concentrations of troponins measured in heparin-plasma are markedly lower than in serum in some cases.

Acute Disease↗

Acute troglitazone action in isolated perfused rat liver.

1. The thiazolidinedione compound, troglitazone, enhances insulin action and reduces plasma glucose concentrations when administered chronically to type 2 diabetic patients. 2. To analyse to what extent thiazolidinediones interfere with liver function, we examined the acute actions of troglitazone (0.61 and 3.15 microM) on hepatic glucose and lactate fluxes, bile secretion, and portal pressure under basal, insulin- and/or glucagon-stimulated conditions in isolated perfused rat livers. 3. During BSA-free perfusion, high dose troglitazone increased basal (P < 0.01), but inhibited glucagon-stimulated incremental glucose production by approximately 75% (10.0 +/- 2.5 vs control: 40.0 +/- 7.2 micromol g liver(-1), P < 0.01). In parallel, incremental lactate release rose approximately 6 fold (13.1 +/- 5.9 vs control: 2.2 +/- 0.8 mmol g liver(-1), P < 0.05), while bile secretion declined by approximately 67% [0.23 +/- 0.02 vs control: 0.70 +/- 0.05 mg g liver(-1) min(-1)), P < 0.001]. Low dose troglitazone infusion did not enhance the inhibitory effect of insulin on glucagon-stimulated glucose production, but rapidly increased lactate release (P < 0.0005) and portal venous pressure (+0.17 +/- 0.07 vs +0.54 +/- 0.07 cm buffer height, P < 0.0001). 4. These results indicate that troglitazone exerts both insulin-like and non-insulin-like hepatic effects, which are blunted by addition of albumin, possibly due to troglitazone binding.

Animals↗

Symbiosis of Aeromonas veronii biovar sobria and Hirudo medicinalis, the medicinal leech: a novel model for digestive tract associations.

Hirudo medicinalis, the medicinal leech, is applied postoperatively in modern medicine. Infections by Aeromonas occur in up to 20% of patients unless a preemptive antibiotic treatment is administered. The associated infections demonstrate the need for a better understanding of the digestive tract flora of H. medicinalis. Early studies reported the presence of a single bacterial species in the digestive tract and suggested that these bacteria were endosymbionts contributing to the digestion of blood. In this study, we cultivated bacteria from the digestive tract and characterized them biochemically. The biochemical test results identified the isolates as Aeromonas veronii biovar sobria. This species identification was supported by sequence comparison of a variable region of the genes coding for 16S rRNA. In a colonization assay, a rifampin-resistant derivative of a symbiotic isolate was fed in a blood meal to H. medicinalis. The strain colonized the digestive tract rapidly and reached a concentration similar to that of the native bacterial flora. For the first 12 h, the in vivo doubling time was 1.2 h at 23 degreesC. After 12 h, at a density of 5 x 10(7) CFU/ml, the increase in viable counts ceased, suggesting a dramatic reduction in the bacterial growth rate. Two human fecal isolates, identified as Aeromonas hydrophila and A. veronii biovar sobria, were also able to colonize the digestive tract. These data demonstrate that the main culturable bacterium in the crop of H. medicinalis is A. veronii biovar sobria and that the medicinal leech can be used as a model for digestive tract association of Aeromonas species.

Aeromonas↗

Diverse restriction fragment length polymorphism patterns of the PCR-amplified 16S rRNA genes in Aeromonas veronii strains and possible misidentification of Aeromonas species.

Restriction fragment length polymorphism analysis after PCR amplification (RFLP-PCR) of the 16S rRNA gene has been previously proposed as a rapid method to identify Aeromonas species. In the present study, the precision of RFLP-PCR was evaluated with 62 Aeromonas reference strains. The analysis revealed that Aeromonas veronii biovar sobria strains produce various patterns, possibly leading to its misidentification as an environmental species. For most other Aeromonas species little variation was noted. This study supports the usefulness of RFLP-PCR analysis to separate three clinically important species but also reveals possible misidentifications that necessitate further biochemical tests to validate the preliminary identification.

Aeromonas↗

Electrogenicity of hepatocellular fatty acid uptake.

Sensitivity of cellular fatty acids uptake to the membrane potential difference is still a matter of controversy. For direct evaluation of potential sensitivity the effect of changing membrane potential on uptake of a fluorescent long chain fatty acid derivative, 12-NBD-stearate, in isolated rat hepatocytes, was examined. Changes in membrane potential were achieved by patch clamp procedures. Fatty acid influx was simultaneously determined by recording of cell fluorescence. Hyperpolarization from -30 to -70 mV accelerated fatty acid influx whereas depolarization to +50 mV reduced uptake. After obtaining equilibrium hyperpolarization increased cell fluorescence, whereas depolarization pushed NBD-stearate out of cells. Potential sensitivity of uptake was dependent on the fatty acid concentrations in the medium with most prominent effects at low unbound concentrations. These data show that, at low fatty acid concentrations, uptake is, in part, driven by an intracellular negative electric membrane potential.

4-Chloro-7-nitrobenzofurazan↗

Host-derived amino acids support the proliferation of symbiotic bacteria.

Animals are typically colonized by diverse bacterial symbionts, many of which are commensal and, in numerous cases, even essential for their host's proper development and growth. In exchange, the host must supply a sufficient array and quantity of nutrients to support the proliferation and persistence of its microbial community. In this investigation, we have examined such a nutritional environment by determining the symbiotic competence of auxotrophic mutants of the bioluminescent bacterium Vibrio fischeri, and have demonstrated that the host squid Euprymna scolopes provides at least 9 aa to the growing culture of symbiotic V. fischeri present in its light-emitting organ. We also collected and analyzed the extracellular fluid from this organ, in which the symbionts reside, and confirmed that it contained significant amounts of amino acids. The combined results suggested that host-derived free amino acids, as well as peptides or proteins, are a source of the amino acids that support the growth of the symbionts. This work describes a technique to sample the symbionts and their surrounding environment without contamination by host tissue components and, in combination with molecular genetic studies, allows the characterization of the nutritional conditions that support a cooperative animal-bacterial symbiosis.

Amino Acids↗

Regulation of ion channels in rat hepatocytes.

Patch-clamp studies have been performed to elucidate single ion channels in rat hepatocytes. In rat hepatocytes two types of ion channel have been identified: an inwardly rectifying K+ channel with a mean inward conductance of 55 +/- 6.5 pS (n = 20) and a mean outward conductance of 25 +/- 3.2 pS (n = 20) in the inside-out configuration with 145 mmol/l KCl on either side of the patch as well as an outwardly rectifying Cl- channel with a mean outward conductance of 30 +/- 4.5 pS (n = 8) and a mean inward conductance of 10 +/- 2.3 pS (n = 6) in the inside-out configuration with symmetrical 145 mmol/l KCl. The open probability of these channels is virtually insensitive to Ca2+ activity on the intracellular side. Accordingly, the Ca2+ ionophore ionomycin had no effect on cell membrane potential. Dibutyryl-cAMP (db-cAMP) hyperpolarizes the cell membrane and increases the activity of the 55-pS inwardly rectifying K+ channel by reducing the duration of closure between bursts. Forskolin similarly hyperpolarizes the cell membrane. The inwardly rectifying K+ channel is inhibited by progesterone, while the outwardly rectifying Cl- channel is insensitive to progesterone.

Animals↗

Metabolism of the anticancer drug flavopiridol, a new inhibitor of cyclin dependent kinases, in rat liver.

Flavopiridol (FLAP) is a promising novel chemotherapeutic agent currently undergoing clinical phase I trials. To examine hepatic metabolism and biliary disposition of FLAP we applied the isolated perfused rat liver system. Besides FLAP two metabolites were detected by high performance liquid chromatography in bile and perfusate. Twenty-five min after FLAP (30 microM) addition to the perfusion medium, biliary secretion of metabolite 1 and 2 reached a maximum of 1.04 +/- 0.52 and 11.34 +/- 4.72 nmol/g.liver.min, respectively. Biliary excretion of parent FLAP, however, continuously increased for 60 min up to 406 +/- 134 pmol/g liver.min. In the perfusate, metabolite 1 was below detection limit and release of metabolite 2 was low (2.8 +/- 0.7 pmol/g liver.min after 60 min). Enzymatic hydrolysis with beta-glucuronidase, mass spectroscopy and electron absorption spectroscopy revealed that both metabolites are monoglucuronides with the glucuronide in position 5 and 7 of the flavonoid core, respectively. The amount of FLAP, metabolite 1 and metabolite 2 excreted into bile during the 60 min of perfusion was 1.94 +/- 0.91, 5.15 +/- 1.95 and 57.29 +/- 23.60% of FLAP cleared from the perfusate during 60 min, respectively. In contrast to the structurally similar flavonoids genistein and daidzein, no inhibition of UDP-glucuronyltransferase with methylumbelliferone as a substrate was observed indicating that different UDP-glucuronyltransferase isoforms are involved in FLAP metabolism. In conclusion, we find that glucuronidation is the major mechanism of hepatic FLAP biotransformation. Metabolites are mainly excreted into bile but also released into systemic circulation. The pharmacological and toxicological effects of these metabolites remain to be elucidated.

Animals↗

Three-dimensional echocardiographic determination of left ventricular volumes and function by multiplane transesophageal transducer: dynamic in vitro validation and in vivo comparison with angiography and thermodilution.

The goal of this study was to validate 3-dimensional echocardiography by multiplane transesophageal transducer for the determination of left ventricular volumes and ejection fraction in an in vitro experiment and to compare the method in vivo with biplane angiography and the continuous thermodilution method. In the dynamic in vitro experiment, we scanned rubber balloons in a water tank by using a pulsatile flow model. Twenty-nine measurements of volumes and ejection fractions were performed at increasing heart rates. Three-dimensional echocardiography showed a very high accuracy for volume measurements and ejection fraction calculation (correlation coefficient, standard error of estimate, and mean difference for end-diastolic volume 0.998, 2.3 mL, and 0.1 mL; for end-systolic volume 0.996, 2.7 mL, and 0.5 mL; and for ejection fraction 0.995, 1.0%, and -0.4%, respectively). However, with increasing heart rate there was progressive underestimation of ejection fraction calculation (percent error for heart rate below and above 100 bpm 0.59% and -8.6%, P < .001). In the in vivo study, left ventricular volumes and ejection fraction of 24 patients with symmetric and distorted left ventricular shape were compared with angiography results. There was good agreement for the subgroup of patients with normal left ventricular shape (mean difference +/-95% confidence interval for end-diastolic volume 5.2+/-6.7 mL, P < .05; for end-systolic volume -0.5+/-8.4 mL, P = not significant; for ejection fraction 2.4%+/-7.2%, P = not significant) and significantly more variability in the patients with left ventricular aneurysms (end-diastolic volume 23.1+/-56.4 mL, P < .01; end-systolic volume 5.6+/-41.0 mL, P = not significant; ejection fraction 4.9%+/-16.0%, P < .05). Additionally, in 20 critically ill, ventilated patients, stroke volume and cardiac output measurements were compared with measurement from continuous thermodilution. Stroke volume as well as cardiac output correlated well to thermodilution (r = 0.89 and 0.84, respectively, P < .001), although both parameters were significantly underestimated by 3-dimensional echocardiography (mean difference +/-95% confidence interval = -6.4+/-16.0 mL and -0.6+/-1.6 L/min, respectively, P < .005).

Adult↗

Gastric tonometry: in vivo comparison of saline and air tonometry in patients with cardiogenic shock.

Measurement of gastric intramucosal pH (pHi) has been advocated to assess gastric perfusion. Regional PCO2 (rPCO2) values are measured using saline tonometry (rsPCO2) and more recently using air tonometry (raPCO2). We compared 237 measurements of saline and air tonometry in 19 consecutive, severely ill patients (mean age 59 (range 31-76) yr, 19 males, APACHE II 22 +/- 7) with cardiogenic shock. Equilibration period was set to 90 min. Nineteen independent paired samples of mean raPCO2 and mean rsPCO2 of each patient showed good correlation (r = 0.93, P < 0.001). Mean raPCO2 was 6.5 (1.8) kPa and mean rsPCO2 6.8 (2.4) kPa. PCO2 measured by saline was significantly higher than that measured by air (P < 0.05). Bland and Altman analysis showed a bias (mean rsPCO2-mean raPCO2) of 0.3 kPa and a precision of 1.2 kPa. Agreement between the two methods decreased with increasing rPCO2 concentrations. Although air tonometry of rPCO2 is a promising technique, a systematic disagreement with saline tonometry at high rPCO2 values requires further investigation and cautious interpretation of these values.

Adult↗

Hot spices influence permeability of human intestinal epithelial monolayers.

Indirect evidence suggests that hot spices may interact with epithelial cells of the gastrointestinal tract to modulate their transport properties. Using HCT-8 cells, a cell line from a human ileocoecal carcinoma, we studied the effects of spices on transepithelial electrical resistance (TER), permeability for fluorescein isothiocyanate (FITC)-labeled dextrans with graded molecular weight, and morphological alterations of tight junctions by immunofluorescence using an anti-ZO-1 antibody, a marker for tight junction integrity. Two different reactivity patterns were observed: paprika and cayenne pepper significantly decreased the TER and increased permeability for 10-, 20- and 40-kDa dextrans but not for -70 kDa dextrans. Simultaneously, tight junctions exhibited a discontinuous pattern. Applying extracts from black or green pepper, bay leaf or nutmeg increased the TER and macromolecular permeability remained low. Immunofluorescence ZO-1 staining was preserved. In accordance with the above findings, capsaicin transiently reduced resistance and piperine increased resistance, making them candidates for causing the effects seen with crude spice extracts. The observation that Solanaceae spices (paprika, cayenne pepper) increase permeability for ions and macromolecules might be of pathophysiological importance, particularly with respect to food allergy and intolerance.

Cells, Cultured↗

Vitamin D increases tight-junction conductance and paracellular Ca2+ transport in Caco-2 cell cultures.

We investigated the effects of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] on paracellular intestinal Ca2+ absorption by determination of transepithelial electric resistance (TEER), as a measure of tight-junction ion permeability and bidirectional transepithelial 45Ca2+ fluxes in confluent Caco-2 cell cultures. The rise of TEER to steady-state levels of approximately 2,000 omega.cm2 was significantly attenuated by 1,25(OH)2D3 (by up to 50%) in a dose-dependent fashion between 10(-11) and 10(-8) M. Synthetic analogs of 1,25(OH)2D3, namely, 1 alpha,25-dihydroxy-16-ene,23-yne-vitamin D3 and 1 alpha,25-dihydroxy-26,27-hexafluoro-16-ene,23-yne-vitamin D3, exhibited similar biopotency, whereas their genomically inactive 1-deoxy congeners were only marginally effective. Enhancement of transepithelial conductance of Caco-2 cell monolayers by vitamin D was accompanied by a significant increase in bidirectional transepithelial 45Ca2+ fluxes. Although 1,25(OH)2D3 also induced cellular 45Ca2+ uptake from the apical aspect of Caco-2 cell layers and upregulated the expression of calbindin-9kDa mRNA, no significant contribution of the Ca(2+)-adenosinetriphosphatase-mediated transcellular pathway to transepithelial Ca2+ transport could be detected. Therefore stimulation of Ca2+ fluxes across confluent Caco-2 cells very likely results from a genomic effect of vitamin D sterols on assembly and permeability of tight-junctional complexes.

Biological Transport↗

Modulation of liver canalicular transport processes by the tyrosine-kinase inhibitor genistein: implications of genistein metabolism in the rat.

Rat liver cells express the multispecific organic anion transporter (cmoat, cmrp, mrp2) and P-glycoprotein (Pgp) in their canalicular membranes, proteins that are homologous to the multidrug-resistance related protein (MRP) and multidrug resistance (MDR) gene products in multidrug resistant tumor cells. We tested whether genistein, a modulator of drug resistance in tumor cells, affects biliary secretion of substrates of canalicular multispecific organic anion transporter (cmoat) (glucuronides of bilirubin and rhodamine, glutathione conjugate of bromsulphthalein) and of P-glycoprotein (Pgp) (rhodamine), respectively. Using the isolated perfused rat liver of control Wistar rats (TR+) and of a mutant strain (TR-) that expresses Pgp but not cmoat, we show that genistein effectively inhibits the secretion of anionic substrates of cmoat in Wistar rats but stimulates secretion of cationic rhodamine in TR- rats. Genistein is subject to glucuronidation and sulfatation and secretion of genistein and its metabolites stimulates bile flow in Wistar rats, but secretion is nearly absent in TR- rats. Because genistein and its metabolites are substrates for cmoat, inhibition of anion secretion by genistein is partially explained by competition for this transporter. Genistein is also a substrate of uridindiphosphate (UDP)-glucuronyltransferase isoenzyme(s). Inhibition of glucuronidation reduces the availability of bilirubin and rhodamine glucuronates for transport via cmoat, but unconjugated cationic rhodamine becomes available for transport via Pgp at an increased cellular concentration. Daidzein, a genistein analogue with no effect on protein tyrosine kinase (PTK) shows Similar effects on secretion of organic anions and cations supporting the conclusion that genistein affects transport in liver mainly through competition with other substrates at the sites of glucuronidation and transport via cmoat.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Influence of isokinetic and ergometric exercises on oxygen partial pressure measurement in the human knee joint.

We conducted the first in vivo investigation on the influence of joint movement on intraarticular oxygen partial pressure. The development of a special flexible microcatheter allowed measurements of intraarticular oxygen partial pressure under both physiological and pathological conditions. The aim of this study was to evaluate the influence of different knee joint stresses on intraarticular oxygen partial pressure under physiological (healthy patients) and pathological (patients with osteoarthritis) conditions. The results show that the different exercise patterns influence the intraarticular oxygen partial pressure. Patients with osteoarthritis showed a lower increase of intraarticular oxygen partial pressure compared with healthy patients. This phenomenon is directly correlated to the degree velocity of the isokinetic exercises. We found the same results under ergometric conditions. This method allows functional, intraarticular in vivo measurements under different exercise patterns. For the first time, we were able to measure the influence of joint movement on the intraarticular process of nutrition under physiological and pathological conditions. Also, to evaluate for the first time in vivo different concepts for osteoarthritis therapy.

Adult↗