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Biomedical subjects

A Veihelmann

Publications and source records attributed to A Veihelmann.

At least 19 recordsLinked to original sources

Percutaneous cryodenervation of lumbar facet joints: a prospective clinical trial.

Facet joint pain is an important aspect of degenerative lumbar spine disease, and radiofrequency medial branch neurotomy remains an established therapy, while cryodenervation has still been poorly examined. This study was undertaken to examine the effects of medial branch cryodenervation in the treatment of lumbar facet joint pain. This was a prospective clinical case series. Patient selection was based on the history, physical examination and positive medial branch blocks. Percutaneous medial branch cryodenervation was performed using a Lloyd Neurostat 2000. Target parameters were low back pain (VAS), limitation of activity (McNab) and overall satisfaction. Fifty patients were recruited, and 46 completed the study. The follow-up time was 1 year. At 6 weeks, 33 patients (72%) were pain free or had major improvement of low back pain; 13 (28%) had no or little improvement. Including failures, mean low back pain decreased significantly from 7.7 preoperatively to 3.2 at 6 weeks, 3.3 at 3 months, 3.0 at 6 months and 4.2 at 12 months (P<0.0001). Limitation of the activities of daily living improved parallel to reduced pain. Our results suggest that medial branch cryodenervation is a safe and effective treatment for lumbar facet joint pain.

Adult↗

Platelet-endothelial cell interactions in murine antigen-induced arthritis.

OBJECTIVES: Growing evidence supports the substantial pathophysiological impact of platelets on the development of rheumatoid arthritis. At present there are no methods for studying these cellular mechanisms in vivo. The aim of this study was to visualize and investigate platelet-endothelial cell interaction in the knee joint of mice with antigen-induced arthritis (AiA) by means of intravital microscopy. METHODS: In 14 mice (Balbc) intravital microscopic assessment was performed on day 8 after AiA induction in two groups (controls, AiA). The severity of AiA was assessed by measuring knee joint swelling and by histological scoring. Ex vivo fluorescently labelled rolling and adherent platelets and leucocyte-endothelium interactions were investigated by intravital fluorescence microscopy. RESULTS: Swelling of the knee joint as well as histological score was significantly enhanced in arthritic animals compared with controls. In control mice intravital microscopy revealed low baseline rolling and sticking of leucocytes and fluorescently labelled platelets. AiA induced a significant increase in the fraction of rolling leucocytes (3 times) and rolling platelets (6 times) compared to the control group. Furthermore, AiA induction resulted in a significantly enhanced number of adherent leucocytes (3-fold) and adherent platelets (12-fold) in comparison with control animals. CONCLUSIONS: Platelet kinetics were directly analysed using intravital microscopy in the arthritic microcirculation in vivo for the first time. We provide the first evidence that platelets accumulate in arthritic vessels, indicating platelet activation due to AiA. Platelet recruitment and subsequent activation might play an important role in the pathogenesis of rheumatoid arthritis.

Animals↗

[Chronic radiculopathy. Use of minimally invasive percutaneous epidural neurolysis according to Racz].

Treatment of chronic low back pain exhibiting radicular symptoms poses a clinical problem that has not yet been solved. The technique of percutaneous minimally invasive neurolysis described by Racz is being performed increasingly to treat chronic radiculopathy. A total of 61 patients with corresponding symptomatology after screening for inclusion and exclusion criteria in the region of the lumbar spinal nerve were treated with the Racz catheter technique. Distinct clinical improvement was observed at the 3- and 6-month follow-ups after percutaneous minimally invasive epidural neurolysis. Subjective pain perception, quantified by the McNab score, clearly improved after 3 as well as 6 months. With the exception of partial catheter shearing in two cases and one occurrence of infection, no relevant side effects were noted. The Racz catheter technique for treatment of chronic radiculopathy following disk surgery is suitable with minimal side effects.

Analgesics↗

Particles of all sizes provoke inflammatory responses in vivo.

The aim of this study was to investigate whether all sizes of wear particles are capable of provoking inflammatory responses and whether there are different responses among different particle sizes. The knees of 40 female Balb/c mice were injected with polystyrene particles of three different diameters, 0.5 microm, 2.0 microm, and 75 microm, using a 0.1% vol/vol concentration. Seven days after particle injection, assessment of the synovial microcirculation using intravital microscopy, and histologic examination, were done. All the mice injected with polystyrene particles had enhanced leukocyte-endothelial cell interactions and histologic scores regardless of particle size when compared with control animals injected with sterile phosphate buffered saline. Polystyrene particles 0.5 microm in size provoked stronger membrane thickening and increased leukocyte-endothelial cell interactions than 75-microm particles. The fraction of rolling leukocytes was enhanced in the 2.0-microm particle group when compared with the 75-microm particle group. These results indicate that polystyrene particles of all sizes (0.5 microm, 2.0 microm, and 75 microm) are capable of inducing an inflammatory response. Small particles (0.5 microm, 2.0 microm) seem to provoke a stronger inflammatory response than larger particles (75 microm) in conditions with equal particle volume.

Animals↗

Quantitative assessment of angiogenesis in murine antigen-induced arthritis by intravital fluorescence microscopy.

Inhibition of angiogenesis might be a therapeutic approach to prevent joint destruction caused by the overgrowing synovial tissue during chronic joint inflammation. The aim of this study was to investigate angiogenesis in the knee joint of mice with antigen-induced arthritis (AIA) by means of intravital microscopy. In 14 mice (C57BL6/129Sv) intravital microscopic assessment was performed on day 8 after AIA induction in two groups (controls, AIA). Synovial tissue was investigated by intravital fluorescence microscopy using FITC-dextran (150 kD). Quantitative assessment of vessel density was performed according to the following categories: functional capillary density (FCD, vessels <10 microm in diameter), functional vessel density (FVD, vessels >10 microm) and FVD of vessels with angiogenic criteria (convoluted vessels, abrupt changes of diameter, vessels which are generated by sprouting and progressively pruned and remodelled). Microvessel count was performed using immunohistochemistry. There was no significant difference in FCD between the control group (337 +/- 9 cm/cm2; mean +/- SEM) and the AIA group (359 +/- 13 cm/cm2). The density of vessels larger than 10 microm diameter was significantly increased in animals with AIA (135 +/- 10 vs. 61 +/- 5 cm/cm2 in control). The density of blood vessels with angiogenic criteria was enhanced in arthritic animals (79 +/- 17 vs. 12 +/- 2 cm/cm2 in control). There was a significant increase in the microvessel count in arthritic animals (297 +/- 25 vs. 133 +/- 16 mm(-2) in control). These findings demonstrate that angiogenesis in murine AIA can be assessed quantitatively using intravital microscopy. Further studies will address antiangiogenic strategies in AIA.

Animals↗

Tunnel enlargement and changes in synovial fluid cytokine profile following anterior cruciate ligament reconstruction with patellar tendon and hamstring tendon autografts.

There is growing evidence that cytokines such as tumor necrosis factor (TNF) alpha, interleukin (IL) 1beta, IL-6, bone morphogenetic proteins (BMP), and nitric oxide (NO) play an important role in the pathogenesis of bone tunnel enlargement following anterior cruciate ligament (ACL) reconstruction. Furthermore, the release of these mediators has been considered a possible reason for the higher incidence of bone tunnel enlargement following hamstring tendon (HST) than following patellar tendon (PT) ACL reconstruction observed in several studies. In this investigation synovial fluid samples from 13 patients were collected immediately before (24+/-7 days after ACL rupture) and 7 days after ACL surgery and values of TNF-alpha, IL-1beta, IL-6, NO, and BMP-2 were analyzed. Furthermore, the incidence of bone tunnel enlargement was assessed using radiographs 38+/-7 weeks after surgery. Six patients underwent autologous HST ACL reconstruction, and in seven patients an PT autograft was used. In the overall patient population there were significantly higher synovial fluid concentrations of IL-6 and BMP-2 postoperatively than preoperatively; TNF-alpha showed a trend towards lower postoperative levels while IL-1beta and NO remained unchanged. The concentrations of NO, TNF-alpha, and IL-6 found in the present study were clearly higher than normal values given in the literature. Assessment of bone tunnel enlargement revealed an average increase in tibial tunnel width of 28.4+/-3.1% with comparable values for HST and PT ACL reconstructions. There was no significant correlation between bone tunnel enlargement and postoperative synovial fluid concentrations of TNF-alpha, IL-1beta, IL-6, NO, and BMP-2. However, all patients with bone tunnel enlargement had higher postoperative concentrations of TNF-alpha, IL-6, and NO in the synovial fluid. There were no significant differences in concentrations between HST and PT groups. In conclusion, we observed an association between tibial bone tunnel enlargement and elevated synovial fluid concentrations of IL-6, TNF-alpha, and NO 7 days after ACL surgery indicating the potential involvement of these biological mediators in the pathogenesis of bone tunnel enlargement. However, there was no difference between HST and PT ACL reconstructions regarding synovial fluid contents of IL-6, TNF-alpha, IL-1beta, NO, and BMP-2, suggesting a comparable biological response between these autografts following their use in ACL reconstruction.

Adult↗

Effects of ibandronate on inflammation in mouse antigen-induced arthritis.

OBJECTIVE: To investigate the effects of ibandronate, a novel aminobisphosphonate, on inflammation as well as leukocyte-endothelial cell interaction in mouse antigen-induced arthritis (AiA). MATERIAL AND TREATMENT: 36 Balb/c mice were subcutaneously injected with 160 microg/kg of ibandronate once per day beginning at day 7 until day 13 after induction of AiA. METHODS: The severity of arthritis was assessed by changes of the transverse knee joint diameter. For the intravital fluorescence microscopy measurements on day 14 after AiA induction, the patella tendon was partly resected to visualize the intraarticular synovial tissue of the knee joint. The number of rolling and adherent leukocytes as well as red blood cell (RBC) velocity and functional capillary density (FCD) were quantified in synovial microvessels. Furthermore, leukocyte infiltration in the synovium was determined in histological sections with an established score. RESULTS: Both fractions of rolling leukocytes (p = 0.016) as well as number of extravasated leukocytes (p = 0.004) were enhanced in control animals treated with ibandronate in comparison to animals which received saline. Arthritic animals with and without ibandronate treatment revealed an increased FCD (p = 0.006, p = 0.008), enhanced number of rolling ( p = 0.002, p = 0.001) and adherent leukocytes (p = 0.009, p = 0.007) and greater swelling of the left knee joint (p = 0.002, p = 0.001) when compared to control animals. No significant differences between arthritic animals and arthritic animals treated with ibandronate were found in any of the parameters assessed including leukocyte adherence, FCD, histology, and knee joint swelling. CONCLUSION: Ibandronate treatment of healthy mice was associated with an enhanced fraction of rolling leukocytes and increased numbers of extravasated leukocytes indicating a proinflammatory effect on the synovial microcirculation. In animals with a preexisting antigen-induced arthritis, however, ibandronate did not induce an exacerbation of joint inflammation and leukocyte adherence.

Animals↗

[Chronic recurrent multifocal osteomyelitis].

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, inflammatory, skeletal disease of unknown origin, which mainly affects children and adolescents in terms of cleido-spondylo-metaphysal skeletal inflammation. Only 10% of the patients are older than 20 years. To date, only about 200 cases have been reported in the literature. In the course of the disease, the initial radiological signs are osteolysis followed by sclerosis and hyperostosis in the end stage. The histological investigations reveal chronic inflammatory infiltrates with lymphocytes and hyperostosis. Although the prognosis of CRMO, to our current understanding, is self limiting, serious complications have been reported such as pathological fractures and compression fractures of the spine. A recently recommended therapy scheme is based on the administration of azithromycin combined with calcitonin. We present the case of a 25 year old female patient who has suffered from CRMO for 1.5 years with the cervical spine and the manubrium sterni being affected. The current state of diagnosis, therapy, and prognostic outlook of this rare disease are discussed.

Adult↗

[The significance of immunology in orthopaedics today].

Within the last years, basic science in immunology has been able to extensively increase the knowledge about the pathogenesis of many diseases. Although much hesitation persists, it has been possible to develop new immunomodulatory strategies which have proven their efficiency and safety in a number of clinical studies. Prior to that, a large number of in vitro and in vivo investigations have established a knowledge base for the development of drugs used in clinical settings. In orthopedic diseases, these immunomodulatory strategies are directed mainly towards the treatment of rheumatoid arthritis and osteoarthritis. Furthermore, immunotherapeutic approaches to bone and soft tissue tumor/metastasis has been improved and we expect first clinical results soon. Moreover, improvement of our understanding of the pathogenesis of inflammation occurring in various diseases, such as aseptic loosening of endoprostheses might help identify a whole field of orthopedic problems as a target for immunomodulatory therapies. In this review, recent developments and applications of immunomodulation in orthopedics will be discussed and a view into the future of such therapies will be given.

Adjuvants, Immunologic↗

[Metal-on-metal pairs for hip prostheses].

Due to engineering deficiencies as well as problems in the basic material, the first generation of metal-on-metal hip prostheses was not up to standard.Furthermore, unsatisfying clinical results led to a decrease in the use of these prostheses.Nevertheless, there were several cases which demonstrated good results in long-term clinical outcome. After distinct improvements in manufacturing and materials, metal-on-metal prostheses have made a come back. This second generation, which are known mainly under the names METASUL and SIKOMET,have been in clinical use for up to 10 years and the good results found in biomechanical set ups seem to be confirmed in clinical trials. However, a possible disadvantage of this second generation of metal-on-metal hip prostheses might be the production of large amounts of particulate wear debris in the nanometer size range. Whether the great number of small size particles with an extended metal surface and the possible distribution of these particles in the body have biological effects on the cells and tissues (such as allergic or toxic reactions) remains unknown. Among the tribological problems, there is currently a discussion on the possible inflammatory effect of these metal particles, which might play a crucial role in longterm, systemic reactions of the body to metal particles.

Biomechanical Phenomena↗

[Inflammatory responses to wear particles in vivo: a novel model in the murine knee joint].

Although it is now widely recognized that the inflammatory response to implant wear particles plays an important role in aseptic loosening of total joint replacements, the precise mechanisms of this process remain unclear. The aim of this study was to establish an animal model for the study of the adverse response to particulate wear debris and the effects on the synovial microcirculation as well as the leukocyte-endothelial cell interaction in the murine knee joint in vivo. Balb/c mice were injected with 50 microl of a 0.5-microm polystyrene particle suspension (0.1% v/v) into the knee joint. The severity of the inflammatory response was evaluated at days 1, 2, 3, 5, 7 (acute), 21 (intermediate), and 63 (chronic) after particle injection. Histological examination as well as assessment of the synovial microcirculation using intravital microscopy was performed. For the intravital microscopy measurements, the patella tendon was partially resected for visualization of the synovial tissue of the knee joint and the fluorescent markers FITC-dextran and rhodamine 6G were injected intravenously. There was a significantly enhanced leukocyte-endothelial cell interaction beginning at day 3 after particle injection with a maximum in the acute phase (days 5-7) and a subsequent decline in the intermediate (day 21) and chronic (day 63) phases. Functional capillary density was significantly increased from day 3 until day 21 after particle application. The histological examination showed an inflammatory reaction that complied widely with the temporal course of the microvascular parameters and resembled the histological appearance of the synovial-like membrane around loose joint prostheses. A novel model was established for the qualitative and quantitative investigation of the particle-induced inflammatory response in the joint environment. It was shown for the first time that there is a significantly enhanced leukocyte-endothelial cell interaction in the synovial tissue after intra-articular particle injection. This model seems to be suitable for further investigations, e.g., dealing with the biocompatibility of different particle materials.

Animals↗

Differential function of nitric oxide in murine antigen-induced arthritis.

BACKGROUND: The aim of our study was to investigate the role of inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) production in different stages of murine antigen-induced arthritis (AiA). METHODS: Clinical, histological and microcirculatory parameters (measured by intravital fluorescence microscopy) were assessed in the knee joint during acute and chronic AiA after inhibition of iNOS with L-N(6)-(1-iminoethyl)lysine (L-NIL). Plasma concentrations of and were evaluated by the Griess reaction and the expression of iNOS, P- and E-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) by immunohistochemistry. RESULTS: In both stages of the disease, plasma concentrations of and were increased and iNOS was expressed. In the acute phase, swelling, leucocyte adhesion, leucocyte infiltration and expression of adhesion molecules were increased in arthritic animals treated with L-NIL in comparison with untreated arthritic animals. In the chronic phase, no change in the disease parameters could be detected after L-NIL treatment. CONCLUSION: Increased NO production induced by iNOS during the acute phase of AiA can be regarded as a protective response in the prevention of further leucocytic infiltration and joint destruction, whereas it seems to play a subordinate role in chronic AiA.

Acute Disease↗

Heparin protects local skin microcirculation in 210 minutes-long intravital microscopy observations under general anaesthesia.

UNLABELLED: Prolonged immobilization of severely ill, bed-ridden patients results in formation of pressure ulcers following inappropriate tissue blood perfusion, and local activation of leukocyte - endothelial cell interactions (L/EC). Various treatment modalities were implemented to improve local microcirculation with controversial results. The aim of our study was to investigate the influence of heparin and buflomedil, drugs improving the microcirculation, on local skin blood perfusion using intravital fluorescent microscopy (IVM) technique. MATERIAL AND METHODS: Experiments were carried out on 24 male hairless mice under inhalatory isofluran anaesthesia. Intravenous injection of FITC-dextran (150 kD, 5%) allowed to visualize capillaries during IVM, after immobilisation of hind limb, in an observation chamber. Observations were performed after i.v. injection of heparin (66 IU/kg b.w., n = 8) or buflomedil (6 mg/kg b.w., n = 8) 30, 120 and 210 minutes after chamber installation. Observations were recorded in 30 sec sequences on S-VHS tapes and evaluated using special software. Functional capillary density (FCD), defined as a total length of red cells perfused capillaries per observation field (expressed in cm/cm(2)), postcapillary venule diameters, and number of sticking leukocytes per 0.2 mm vessel length during 30 sec observation time, served as parameters of skin blood perfusion and activation of L/EC interactions. RESULTS: A statistically significant decrease of FCD from 152.7 +/- 38.5 to 100.7 +/- 36.7 cm/cm (2) (p<0.05) was observed in control animals during 210 min lasting observation. Administration of heparin prevented decrease in FCD occurring in control animals during intravital microscopy, whereas buflomedil was found ineffective. Both drugs induced a nonsignificant reduction in the number of sticking leukocytes, whereas no changes in postcapillary venule diameters could be observed. CONCLUSION: The results suggest a protective effect of heparin in clinical therapeutic doses against impairment of skin perfusion during IVM. This observation may justify a trial on the effects of heparin in prevention of development of pressure ulcers.

Animals↗

Exacerbation of antigen-induced arthritis in inducible nitric oxide synthase-deficient mice.

OBJECTIVE: Inhibition of nitric oxide (NO) produced by inducible NO synthase (iNOS) is suggested to be beneficial in experimental arthritis. Although NO is important for the integrity of the microcirculation, the effects of inhibition of iNOS on the synovial microcirculation are not currently known. This study investigated the synovial microcirculation and leukocyte-endothelial cell interactions in iNOS-deficient mice with antigen-induced arthritis (AIA) and compared these findings with disease severity. METHODS: Fourteen homozygous iNOS-/- and 14 iNOS+/+ mice were used. The severity of AIA was assessed by measuring knee joint swelling and by histologic scoring. The number of rolling and adherent leukocytes was quantitatively analyzed in synovial microvessels using intravital microscopy of intraarticular synovial tissue. Nitrite/nitrate concentrations were measured, and the expression of iNOS, E- and P-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 (VCAM-1) was assessed by immunohistochemistry. RESULTS: In iNOS+/+ animals with AIA, the plasma concentration of nitrite/nitrate was increased 3-fold and iNOS expression was detected in cells of the joint. Swelling of the knee joint as well as leukocyte infiltration were enhanced in the iNOS-/- arthritic animals compared with iNOS+/+ mice with AIA. AIA-associated leukocyte-endothelial cell interaction in synovial postcapillary venules was more pronounced in iNOS-/-, compared with iNOS+/+, arthritic mice. A strong expression of P-selectin and VCAM-1 was observed in the iNOS-/- arthritic mice only. CONCLUSION: These data suggest that NO production by iNOS in vivo has antiinflammatory effects in experimental arthritis, by mediating a reduction in leukocyte adhesion and infiltration.

Animals↗

The value of desoxypyridinoline in the diagnostics of loosened arthroplasty.

According to several reports in the last few years, desoxypyridinoline (Dpd) in urine increases significantly in cases of loosened arthroplasty. Therefore, this marker was suggested as useful in the diagnostics of implant loosening. In this study, the level of Dpd was determined in 69 patients with arthroplasty of the hip or the knee joint. Thirty-four of these patients received revision surgery following implant loosening. In 35 of these 69 patients, there were no clinical or radiological signs of loosening (control group). The mean age of the patients with loosened implants (22 women, 13 men) was 67.9 years and of the control group (22 women, 12 men) 66.9 years. In the group with arthroplastic loosening, as well as in the control group, 14 patients had increased levels of Dpd. There were 20 patients in the group with loosened arthroplasty and 19 patients in the control group that had normal levels of Dpd. The female patients had a mean Dpd level of 8.6 nmol/mmol creatinine (4.3-24 nmol/mmol creatinine) in the urine in cases of loosening and 10.1 nmol/mmol creatinine (2-33 nmol/mmol creatinine) in the control group. The male patients had a mean Dpd level of 7.8 nmol/mmol creatinine (3.2-19.2 nmol/mmol creatinine) in the urine in cases of loosening and 5.8 nmol/mmol creatinine (0.3-11.7 nmol/mmol creatinine) in the control group. In conclusion there was no significant increase in Dpd in patients with implant loosening compared with the control group. Furthermore, older patients often suffer from diseases causing increased bone resorption that may falsify the test results. We cannot confirm that Dpd is helpful in the diagnostics and screening of implant loosening.

Adult↗

Extracorporeal shock-wave therapy for chronic lateral tennis elbow--prediction of outcome by imaging.

Today the clinical use of extracorporeal shockwave application (ESWA) for the treatment of lateral tennis elbow is hampered by the lack of results from randomized controlled trials and of predictive parameters of clinical outcome. The present prospective study aimed to provide the latter by means of magnetic resonance imaging (MRI). Twenty-three female and 19 male patients with unilateral chronic tennis elbow of the dominant site were clinically examined before and after repetitive low-energy ESWA. MRI was performed before ESWA to evaluate signal intensity changes or contrast enhancement of the common extensor tendon and the lateral epicondyle. After ESWA (mean follow-up period 18.6 months for all patients), clinical evaluation showed a significantly better mean clinical performance after ESWA than before treatment. Interestingly, male patients showed a significantly better mean clinical performance after ESWA than female patients, and male and female patients differed significantly in the signal intensity of the common extension tendon cross-section and tendon thickening on MRI. For female patients, MRI scans could be applied for predicting a positive clinical outcome of ESWA. This study reports the first indication of predictability of positive clinical outcome of the treatment of chronic lateral tennis elbow by ESWA using imaging prior to treatment. This may serve as an important step towards overcoming the therapeutic nihilism with respect to the non-operative management of this condition recently in the literature.

Adult↗

[Case report: emergency surgery of a giant scrotal hernia].

We present the case of a 61-year-old patient, who had developed a giant scrotal hernia during the course of 30 years. The patient was transferred to our service after stabilization of hemorrhagic shock due to bleeding from varicosis of the giant scrotal sack. The urgent operation was performed by resection of parts of small intestine, colon ascendens, transversum, and the left testis. After 9 days on our intensive care unit and 18 days on our ward the patient was discharged to further ambulatory care. At one year follow up the patient complained about only discrete abdominal problems which could be successfully treated by diet. The operative treatment modalities of so called "giant hernias" as well as possible complication management are discussed.

Aortography↗

Oxaceprol, an atypical inhibitor of inflammation, reduces leukocyte adherence in mouse antigen-induced arthritis.

Oxaceprol (N-acetyl-L-hydroxyproline), an atypical inhibitor of inflammation, is an established drug forjoint disease without serious side-effects. Recent studies have emphasized that oxaceprol has an effect on the microcirculation. Since the exact mechanism of action remains unclear, the aim of our study was to investigate the leukocyte-endothelial cell interactions in oxaceprol-treated mice with antigen-induced arthritis (AiA) using intravital microscopy. In our study, Balb/c mice were allocated to 4 groups (n 7, 8, 8, 8): 2 control groups with saline or oxaceprol and 2 groups of arthritic animals which received saline or oxaceprol (100 mg/kg twice a day intraperitoneally). The severity of arthritis was quantified by the transverse knee joint diameter. For the intravital fluorescence microscopy measurements on day 10 after inducing arthritis, the patella tendon was partily resected to visualize the intraarticular synovial tissue of the knee joint. The number of rolling and adherent leukocytes as well as RBC velocity and functional capillary density (FCD) were quantified in synovial microvessels. Furthermore, leukocyte infiltration was determined in the histological sections with an established score. No significant changes in mean arterial blood pressure or functional capillary density were found in any of the groups. However, the leukocyte rolling fraction and number of leukocytes adherent to the endothelium were increased in postcapillary venules of the synovium in arthritic animals (0.16 to 0.31, 78 cells/mm2 to 220 cells/mm2). In animals with AiA treated with oxaceprol, leukocyte adherence and swelling were significantly reduced in comparison to the arthritic animals treated with saline. Furthermore, the histological score showed less leukocyte infiltration in the oxaceprol treated arthritic animals. Thus, oxaceprol reduces leukocyte adherence in vivo and leukocyte infiltration in mouse AiA, indicating an effect on synovial microcirculation.

Animals↗