Intraarticular injection of platelet‐rich plasma reduces inflammation in a pig model of rheumatoid arthritis of the knee joint

Objective

Treatment options for rheumatoid arthritis range from symptomatic approaches to modern molecular interventions such as inhibition of inflammatory mediators. Inhibition of inflammation by platelet‐rich plasma (PRP) has been proposed as a treatment for tendinitis and osteoarthritis. The present study was undertaken to investigate the effect of PRP on antigen‐induced arthritis (AIA) of the knee joint in a large animal model.

Methods

Six‐month‐old pigs (n = 10) were systemically immunized by bovine serum albumin (BSA) injection, and arthritis was induced by intraarticular BSA injection. PRP was injected into the knee joints of 5 of the animals after 2 weeks. An additional 5 animals received no systemic immunization (controls). Signs of arthritis were documented by plain histologic analysis, Safranin O staining, and immunohistochemistry analysis for type II collagen (CII), interleukin‐6 (IL‐6), and vascular endothelial growth factor (VEGF). Interleukin‐1β (IL‐1β), IL‐6, tumor necrosis factor α (TNFα), VEGF, and insulin‐like growth factor 1 (IGF‐1) protein content was measured by Luminex assay.

Results

In the pigs with AIA, plain histologic analysis revealed severe arthritic changes in the synovium. Safranin O and CII staining showed decreased proteoglycan and CII content in cartilage. Immunohistochemistry analysis revealed increased levels of IL‐6 and VEGF in synovium and cartilage, and protein concentrations of IL‐6, VEGF, IL‐1β, and IGF‐1 in synovium and cartilage were elevated as well; in addition, TNFα protein was increased in cartilage. Treatment with PRP led to attenuation of these arthritic changes in the synovium and cartilage.

Conclusion

We have described a porcine model of AIA. Experiments using this model demonstrated that PRP can attenuate arthritic changes as assessed histologically and based on protein synthesis of typical inflammatory mediators in the synovial membrane and cartilage.

     

VEGF expression in adult permanent thyroid cartilage: implications for lack of cartilage ossification

Vascular endothelial growth factor (VEGF) has been shown to play an important role during endochondral bone formation in hypertrophic cartilage remodeling, ossification, and angiogenesis, but it is not expressed in normal adult articular cartilage. Thyroid cartilage undergoes only partial ossification beginning at the age of about 20. Because it never completely ossifies, we investigated a possible role of VEGF and its receptors (VEGFRs) as well as the angiogenetic inhibitor endostatin in this permanent cartilage. In analysis of cartilage samples from all specimens evaluated, VEGF121 and VEGF165 were identified as the only VEGF splice forms expressed. In addition to VEGF, VEGFR-2 (kinase domain region/fetal liver kinase 1), but not VEGFR-1 (fms-like tyrosine kinase 1), was detectable by RT-PCR in cartilage. However, VEGFR-2 expression was only detectable up to the age of 19 years. Deposition of VEGF and VEGFR was confirmed by immunohistochemistry. VEGF concentrations measured by ELISA in thyroid cartilage increased with age in males but decreased in females. Endostatin concentrations measured by ELISA in thyroid cartilage were three times lower than in articular cartilage and showed no change with age, either in females or males. VEGF was immunostained within the intra- and pericellular matrices of some but not all chondrocytes. Thus, apart from its production in hypertrophic chondrocytes of growth plates, VEGF is also produced in single chondrocytes of thyroid cartilage. The data allow us to speculate that thyroid cartilage persists in an embryological state until it has reached its final size. After reaching its final size at the end of the second decade, VEGFR-2 is downregulated and ossification starts in the posterior part of the thyroid cartilage, proceeding ventrally. Both proteins, VEGF121 and VEGF165, should contribute to this process. VEGF concentration is high and changes in an age-related and sex-specific manner. Therefore, we postulate that VEGF is at least one of the key factors that is important for the lifelong ossification in thyroid cartilage.     

Exact focusing of extracorporeal shock wave therapy for calcifying tendinopathy

A controlled prospective randomized study was designed to analyze the effect of extracorporeal shock wave therapy on calcifying tendinopathy of the shoulder focused on the calcified area or the origin of the supraspinatus tendon. Fifty patients were included in the study and were treated with a Storz Minilith Sl-1 shock wave generator. The first group of patients received 4000 impulses (positive energy flux density, 0.78 mJ/mm2) in two treatment sessions after receiving local anesthesia at the origin of the supraspinatus tendon. Patients in the second group received extracorporeal shock wave therapy at the calcified area. Follow-ups were done 12 weeks and 1 year after treatment by an independent observer. An increase of function and a reduction of pain occurred in both groups. Statistical analyses showed a significant superiority of extracorporeal shock wave application at the calcified area in the primary end point (Constant and Murley score). Therefore, exact fluoroscopic focusing of extracorporeal shock wave therapy at the calcific deposit for treatment of calcifying tendinopathy of the supraspinatus muscle is recommended. Based on these results, extracorporeal shock wave application should be focused fluoroscopically with appropriate shock wave generators.     

Pulmonary mycetomas in immunocompetent patients: diagnosis by fine-needle aspiration.

Mycetomas usually grow within preexisting cavities and frequently lead to pulmonary hemorrhage. We describe four males, aged 38 to 72 years, in whom myceotomas were diagnosed by FNA. Preexisting cavitary lesions resulted from tuberculosis, anaerobic abscess, and bullous lung disease (two cases). Fine needle aspiration yielded tangled mats of fungal hyphae (large and grossly visible in three cases) and acute inflammatory cells. The atypical cells often seen in the walls of such lesions were not identified. Cultures showed Aspergillus (3 cases) Pseudoallescheria boydii (1 case). The diagnosis was surgically confirmed in two cases. Two patients were too ill for surgery and the fourth refused. At 7 and 10 months, the two remaining individuals have pulmonary hemorrhage but no evidence of progression or malignancy. In poor surgical candidates, conservative management of mycetomas diagnosed by fine needle aspiration is appropriate. Excluding mycetoma secondary to cavitary lung carcinoma requires careful correlation of historical, clinical, radiographic, cytologic, and follow-up data.     

Effect of adipocyte-derived IGF-I on adipose tissue mass and glucose metabolism in the Berlin Fat Mouse

Besides liver, IGF-I is expressed in adipose tissue. However, the effects of this local IGF-I on adipose tissue and metabolism are unclear. We generated adipocyte-specific knock-out mice on the background of the Berlin Fat Mouse Inbred (BFMI) line to evaluate the contribution of adipocyte-IGF-I on glucose metabolism and adipose tissue development. BFMI mice are obese, non-diabetic with elevated plasma insulin and IGF-I concentration. The knock-out in adipocytes led to a total white adipose tissue expression of 50–60% due to unaltered Igf-1 expression in stromavascular cells. The lack of IGF-I from adipocytes did not alter plasma IGF-I concentration. BFMI^Chr3-Igf-I-KO^Q-AT mice had reduced adipose tissue mass in most depots. During oral glucose tolerance tests, BFMI^Chr3-Igf-I-KO^Q-AT mice showed an impaired glucose clearance (p?=?.03). Interestingly, insulin action was enhanced during insulin tolerance tests (p?=?.05). In conclusion, adipocyte-specific IGF-I ablation in obese BFMI mice results in reduced adipose tissue mass and thereby alters glucose metabolism.     

The Treatment of Intra-articular Calcaneus Fractures with Severe Soft Tissue Damage with a Hinged External Fixator or Internal Stabilization: Long-term Results

We developed a hinged external fixator for the treatment of dislocated intra-articular calcaneus fractures with severe soft tissue damage. The external fixation was performed with a known external fixator system. The screw insertion points were biomechanically tested by defining a virtual rotation axis through the center of the talus to allow early active motion in the ankle joint. Long-term follow-up was performed after an average of 7.3 years. Results were graded with the American Orthopaedic Foot and Ankle Society (AOFAS) score. Radiographs were reviewed according to Sanders classification. Four open fractures and 33 cases with extremely swollen soft tissue, blisters, or compartment syndromes were treated. In 24 cases (64.9%), the hinged fixator was the final method of treatment (group I). A change to open reduction with internal fixation was performed in 13 fractures (35.1%) when soft tissue problems were minimal (group II). There were no late amputations, osteomyelitis, or malunions. According to Sanders classification, group I consisted of 14 type II, 8 type III, and 2 type IV fractures. Pin loosening or pin infection was seen in 4 cases, but there was no redislocation. The Böhler's angle improved in 43%, gaps in the posterior facet were closed in 41%, and any shortening or deviation of the axis was corrected in 82% of the cases. The AOFAS score for the group averaged 66.5. According to Sanders classification, group II consisted of 8 type II and 5 type III fractures. The Böhler's angle improved in 88%, and gaps in the posterior facet were closed in 87%. Any shortening or deviation of the axis was corrected in 95%, and the AOFAS score averaged 61.3. Significant differences in patient outcome scores between open reduction with internal fixation and hinged fixator were not found. P value was > .05. The hinged external fixator frame can be used in all calcaneus fracture types without soft tissue limitation. The hinged fixator allows early movement in the ankle joint, the risk of infection is minimized, and secondary plate fixation remains possible.