20 December 2016, Volume 30 Issue 4(S1)

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  • A Gigante, L Senesi, S Manzotti, A Palmieri, E Skrami, V Sollazzo
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 1-6.
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    Nerve growth factor (NGF) is involved in several joint diseases. It participates in nociception and neurogenic inflammation and its concentrations increase in synovial fluid and tissue from arthritis. However, data about its role in articular cartilage are scant and conflicting. This study analysed effects of different NGF concentrations on cultured human chondrocytes by evaluating cell proliferation, cell phenotype, and gene expression. The MTT test excluded an influence on cell viability. Alcian blue and S100 staining demonstrated that NGF may induce de-differentiation of the chondrocyte phenotype. Real-time PCR showed that NGF did not influence gene expression of type I, II and XI collagen, TGF-β, IGF-1 and metalloproteinase (MMP)-13, while it reduced the expression of MMP-3. These findings show that NGF may have uncertain effects in human chondrocytes. Further investigations by wider gene expression and protein synthesis analyses are required to determine how chondrocytes may be influenced by NGF.

  • A Stellavato, F De Novellis, S Reale, M De Rosa, C Schiraldi
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 7-16.
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    Hyaluronan (HA) is central in joint and cartilage functions and to restore synovial fluid viscosity. In patients with osteoarthritis (OA), molecular weight (MW) and concentration of hyaluronic acid (HA) are reduced, diminishing joint lubrication. IL-1β treatment was used to mimic osteoarthritis in a chondrocytes based in vitro model. The aim of our research, using this model and human chondrocytes was to assess the anti-inflammatory effect of H/L-HA hybrid complexes (SINOVIAL-HL®) in comparison with HA at high (H-HA) and low molecular weight (L-HA) separately used, through the evaluation of specific biomarkers involved in cartilage degradation and correlated to osteoarthritis. Specifically, TNF-α and IL-6 mRNA were evaluated by qRT-PCR. Cytokines levels were measured using Bio-plex assays and COMP-2 through immunofluorescence staining and western blot. H/L-HA significantly reduced inflammation biomarkers respect to both L-HA or H-HA separately considered at transcriptional and protein level.

  • R Papalia, B Zampogna, F Russo, S Vasta, M C Tirindelli, C Nobile, A C Di Martino, G Vadalà, V Denaro
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 17-23.
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    Cartilage lesions are very common causes of chronic knee pain in athletes. Current treatment options consist in conservative strategies, such as viscosupplementation and platelet-rich plasma injections. This randomized controlled trial aims to investigate the effect of intra-articular Hybrid Hyaluronic Acid injections compared to PRP for the treatment of cartilage lesions among athletes at the end of their career. Since March 2015, 48 professional soccer players were randomized into two groups: 24 patients received 3 injections of HHA and 23 patients received 3 intra-articular injections of PRP. All patients achieved a statistically significant clinical improvement from preoperative to postoperative time in both groups. Patients in the HHA group showed a significant superiority compared to PRP group at 3 and 6 months. Intergroup differences decrease gradually until loss of significance at 12 months follow-up. Athletes with chronic degenerative cartilage lesions of the knee responded positively both to HHA and PRP until last follow up.

  • F Gervaso, L Mangiavini, A Di Giancamillo, F Boschetti, D Izzo, D D Zani, M Di Giancamillo, I Tessaro, M Domenicucci, F Scalera, C Domeneghini, A M Crovace, A Sannino, G M Peretti
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 25-31.
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    In the last years, several tissue engineering techniques have been applied to develop different kinds of osteochondral substitutes to overcome the scarce reparative properties of this tissue. The aim of this study was to generate and compare three biphasic scaffolds in an osteochondral lesion in a large-animal model. A critical osteochondral defect was generated in the medial femoral condyle of 18 skeletally mature sheep. Three defects were left untreated, the remaining lesions were divided into three groups: 5 lesions were treated with a biphasic scaffold made of collagen type I and small cylinders of Magnesium Hydroxyapatite; 5 lesions were treated with a biphasic substituted formed by collagen type I and Wollastonite, 5 lesions were treated with a scaffold made of collagen type I and small cylinders of Wollastonite/Hydroxyapatite. Animals were sacrificed after 3 months and samples were analyzed by CT and MRI, macroscopic evaluation and histology. Our study demonstrated that one of these novel biphasic scaffolds possesses the potential for being applied for one-stage procedures for osteochondral defects.

  • A Marmotti, S Mattia, L Mangiavini, D E Bonasia, M Bruzzone, F Dettoni, F Rosso, D Blonna, R Rossi, F Castoldi, G M Peretti
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 33-40.
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    The possible toxic effects of intra-articular tranexamic acid (TA) are still debated. The aim of this study was to evaluate TA effects on human cartilage fragments and synovial biopsies. Explant culture of minced articular cartilage underwent prolonged TA exposure. Histological analysis, immunofluorescence and colorimetric assay for quantification of s-GAG and DNA were performed at the end term. Synoviocytes were cultured for 48h in presence of TA. Light microscopy and flow cytometry analysis were performed at the end of the exposure to TA and one week after the treatment. TA exposure did not influence i) the chondrocyte outgrowth and migration, ii) the expression of chondrogenic and proliferative markers and iii) the s-GAG/DNA ratio. TA treatment did not affect synoviocytes’ morphology and treated cells were phenotypically similar to control cells. This study demonstrated that TA does not negatively affect chondrocytes and synoviocytes cultured in vitro. Thus, our findings may be clinically relevant in order to validate the intra-articular TA administration during orthopedic procedures.

  • R Papalia, L Diaz Balzani, G Torre, M C Tirindelli, C Nobile, N Maffulli, V Denaro
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 41-49.
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    Cartilage lesions are the most common cause of chronic knee pain. Micro-fracturing is reliable, effective, easy to perform and inexpensive. We propose a novel approach to cartilage lesions where microfractures are performed contextually to intra-operative or post-operative administration of platelet concentrates. We retrospectively evaluate 48 patients divided in 3 groups. Group 1: 15 patients underwent microfractures and intraoperative administration of PRF (PRF group); group 2: 16 microfractures and postoperative injections of PRP (PRP group); group 3: 17 patients with isolated microfractures (Microfractures group). Clinical scores (IKDC, VAS pain) were administered at 2 and 5 years postoperative and MRI was performed to evaluate the lesions of patients according to the MOCART criteria (2006). Patients treated with platelet concentrates achieved better clinical results compared to patients treated with microfracture only. The PRF group showed better results than the PRP group at 2 years, with loss of significance at 5 years. At MOCART score, PRF group obtained better results earlier than the other two groups.

  • J P Araújo, L Silva, R Andrade, M Paços, H Moreira, N Migueis, R Pereira, A Sarmento, H Pereira, N Loureiro, J Espregueira-Mendes
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 51-62.
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    The scientific literature has shown positive results regarding intra-articular injections of hyaluronic acid in osteoarthritic joints. When injecting in the hip joint, the guidance of ultrasound can provide higher injection accuracy and repeatability. However, due to the methodological limitations in the current available literature, its recommendation in the current practice is still controversial. This study shows that ultrasound-guided intra-articular injections of triamcinolone hexacetonide and hyaluronic acid can improve pain, function and quality of life in patients with symptomatic and radiographic hip osteoarthritis. In addition, the administration of triamcinolone hexacetonide and hyaluronic acid to the hip joint in these patients can delay the need for interventional surgery.

  • C Bottegoni, L Farinelli, A Aquili, E Chiurazzi, A Gigante
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 63-67.
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    Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by dry eyes, dry mouth, and other clinical manifestations. The most common extraglandular manifestation of pSS is articular involvement and to date their management is unclear. The aims of the current pilot study were to assess the safety and the outcomes of homologous platelet-rich plasma (HPRP) injections in pSS cohort affected by knee arthralgia/arthritis at short-term follow up. This pilot study provides the first evidence that HPRP injections are a safe treatment and induce a short-term clinical improvement. Although the lack of a control group, randomization and long-term follow up prevents the assessment of the real effectiveness of this treatment, further studies are needed to confirm these findings and to determine the mechanism of action, biological changes and disease-modifying properties of PRP.

  • G Vadalà, R Papalia, L La Verde, F Russo, V Denaro, M A Rosa
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 69-76.
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    The aim of this systematic review is to examine current clinical evidences supporting the intraarticular injection of bone marrow concentrate cells (BMC) and adipose-derived stromal vascular fraction cells (SVF) for the treatment of osteoarthritis (OA). The research was performed on PubMed (Medline), EMBASE and Cochrane Library considering the English literature. Only clinical trials have been included. The systematic research identified twelve clinical trials. Articles included in the study, were one of level II, four of level III, six of level IV and one level V. Among clinical trials, none were randomized, four were comparative, seven were case series, and one was a case report. Seven studies were focused on the use of SVF (1332 patients) and five on the use of BMC (963 patients), with preliminary interesting findings in the OA treatment. Despite the growing interest in this biological approach for OA, knowledge on this topic is still preliminary. Randomized controlled trials are needed to support the potential of BMC and SVF injections and to evaluate advantages and disadvantages with respect to the available treatments.

  • R Papalia, G Vadalà, G Torre, M Perna, L Saccone, F Cannata, V Denaro
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 77-83.
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    At present, diagnosis and progression monitoring of osteoarthritis (OA) is made through radiological and clinical assessment. Several studies investigated the role of synovial fluid analysis, to find out whether joint disease could be characterized by the pattern of cytokines, which acts during the pathogenic process or in specific stages of it. Online PubMed-Medline search was performed in order to retrieve evidence concerning synovial fluid analysis of cytokines involved in OA degenerative process. Concerning pro-inflammatory cytokines, it has been shown that interleukin (IL)-6, TNF-α and IL-17 are mainly over-expressed in the synovial fluid of OA joints, as well as anti-inflammatory cytokine IL-10. Variations of cytokines levels occur with radiological and clinical progression. It was also reported that metalloproteinases are involved. Synovial fluid analysis may be helpful in defining stage and type of OA, but more research is needed, especially focusing on the variation of sets of cytokines during OA stages and correlating these patterns with clinical features.

  • A Di Giancamillo, L Mangiavini, I Tessaro, A Marmotti, R Scurati, G M Peretti
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 85-90.
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    Meniscal lesions still represent an unsolved problem in clinical practice. Like the articular cartilage, meniscus has a scarce healing potential. Thus, when this tissue is damaged, the joint biomechanics is completely altered, leading to the development and progression of premature osteoarthritis. Therefore, in the last years, several tissue-engineering strategies have been developed to regenerate the meniscus with debated results. The comprehension of complex processes underlying meniscus maturation and structure is essential for a correct approach for the generation of a biomimetic meniscal substitute. In this chapter, we will first review the morphology of the meniscus during growth, focusing on the unique pattern of vascularization, and then we will discuss the most common tissue engineering strategies for meniscus repair.

  • R Simonetta, G Di Vico, R Papalia, S Vasta, V Denaro
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 91-97.
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    Athletes whose knees are subjected to sudden changes of direction and high jumps such as martial arts athletes, dancers, wrestlers and football players are at higher risk of injuring popliteomeniscal fascicles. Painful squatting and mechanical symptoms such as locking sensation are common. Current available treatments includes open or arthroscopic in repair. Arthroscopic repair with all-inside device can relieve symptoms and restore knee function. Six patients from two surgical centers with isolated popliteomeniscal fascicles tears were treated with arthroscopic all-inside repair. The surgical technique is thoroughly described. All patients showed consistent symptoms and MRI findings, as well as meniscal hypermobility during arthroscopic probing. Moreover, four out of six showed a chondral lesion of the lateral femoral condyle. All of them had their lateral meniscus sutured with one or more sutures. Symptoms were relieved and all but one were able to return to play at the pre-injury level. No postoperative complications were encountered. The diagnosis of the disruption of popliteomeniscal fascicles is challenging and often seen in athletes that play sports which involve repetitive twisting. However, patients complaints are consistent. Arthroscopic repair with an all-inside device showed to be a reliable and easy technique for addressing the condition, although some issues still need to be investigated, such as how much constraint the repair should provide. Arthroscopic all-inside repair of popliteomeniscal tears prove to be safe and effective in the short-term follow-up, allowing for sport activity resumption.

  • R Papalia, R Simonetta, G Di Vico, G Torre, L Saccone, J Espregueira-Mendes, V Denaro
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 99-106.
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    Postero-lateral corner of the knee is composed of several structures including the popliteo-meniscal fascicles (PMFs). These fibrous structures form a stable ligamentous complex around the popliteus tendon, which stabilize the lateral meniscus, increasing the strength of postero-lateral corner. Studies were retrieved through an electronic search of CINAHL, EMBASE, and Pub-Med, until May 2016. Studies in English, Italian, French, and Spanish were considered for inclusion. Randomized controlled trials, prospective and retrospective comparative studies, case series, and case reports were included. Studies eligible for inclusion concerned PMFs anatomy, biomechanics, diagnostic assessment of PMFs tears and clinical options for tears management. Thirteen studies were included in this review. There were: 7 case series, 4 case reports and 3 anatomical studies. Through anatomic dissection, two or three PMFs (antero-inferior fascicle, aiPMF; postero-superior fascicle, psPMF; postero-inferior fascicle, piPMF) can be indentified and isolated. Evaluation through MRI can be a useful diagnostic tool in detecting PMFs tears, especially using proton density (PD) sequences. The biomechanical analysis assessed that lateral meniscus (LM) motion is directly related with PMFs integrity and increased with section of one or both the fascicles. The clinical studies clearly state that a snapping syndrome, associated with lateral knee pain, can develop when one or both PMFs are torn. The three PMFs described are considered as relevant components of the popliteal hiatus, in the posterolateral aspect of the knee. MRI evaluation can detect these fibrous fascicles with good sensitivity. More studies with larger samples would be needed for a clear comprehension of PMFs function and clinical management of PMFs tears, especially with large case series and modern biomechanical testing.

  • P Sabatelli, F Sardone, F Traina, L Merlini, S Santi, R Wagener, C Faldini
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 107-113.
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    Collagen VI is a microfibrillar collagen with a potential regulatory role in tendon repair mechanism. We studied the expression of collagen VI α5 and α6 chains in normal human tendon fibroblast cultures, both under basal condition and in response to TGF-β1, a potent regulator of tendon healing. Under basal condition, we found that the α5 chain was expressed, although to a lesser extent with respect to the α3 chain; in contrast, the α6 chain was absent. The treatment with TGFβ1 induced an opposite effect on the expression of the α5 and α6 chains; in fact, while the α5 chain was dramatically reduced, the α6 chain was induced and released in the culture medium. These data indicate that collagen VI α5 and α6 chains are differentially involved in tendon matrix homeostasis. The α6 chain may represent a new potential biomarker for monitoring TGFβ1-related events in tendon, as healing and fibrotic scar formation.

  • A D'Addona, D Somma, S Formisano, D Rosa, S L Di Donato, N Maffulli
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 115-122.
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    The aim of our study is to investigate the behaviour of healthy and tendinopathic human tenocytes after a heat shock. After we harvested tendinopathic and healthy human tendon samples, we split tenocytes into 4 groups: 3 groups were submitted to heat shock, followed by different periods of post-heating (2, 4 and 20 h). The other group represents our negative control. The target genes were analysed using Real Time PCR. IL-1β and IL-6 expression were significantly increased in tendinopathic samples after heat shock. COL1 and COL3 expression were increased in non-stimulated tendinopathic tenocytes, but their levels significantly decreased after heat shock (p less than 0.01). COL3 levels increase in healthy samples after 20 h post-heating (p less than 0.01). COL1 and COL3 decreased after heat shock as a sign of the failure of repair mechanisms in tendinopathic tendons. Heat shock in in vitro models was insufficient to trigger pro-inflammatory cytokines in healthy human tenocytes.

  • D Cucchi, A Menon, F M Feroldi, A Kwapisz, F Randelli, F Cabitza, A Tassi, P Randelli
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 123-129.
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    The aim of this study was to document the incidence of postoperative shoulder stiffness (SS) after arthroscopic rotator cuff repair and evaluate the role of risk factors for its development. Seventy-five consecutive patients that underwent arthroscopic rotator cuff repair were included. The incidence of postoperative SS was prospectively investigated and the presence of 20 potential risk factors was documented retrospectively. The incidence of post-operative SS was 10.4%. All patients were women, and sex was significantly associated to pathology development (p=0.0067). The presence of gastroesophageal diseases was found to be significantly associated with post-operative SS development (p=0.0046). A significant association between the occurrence of post-operative SS and the presence of gastroesophageal diseases was identified. This finding, not yet reported in literature, deserves further investigation. The incidence of postoperative SS fell among previously reported ranges, with females significantly more affected than men.

  • F Traina, F Perna, A Ruffilli, A Mazzotti, R Meliconi, L Berti, C Faldini
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 131-138.
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    Insertional Achilles tendinopathy is a frequent cause of pain and performance impairment of the ankle. It is more common in runners, but may also affect general population. Conservative treatment is the gold standard in the early phases but 10% to 30% of patients require surgery. The aim of this study is to review the current literature in order to evaluate current surgical strategies for Insertional Achilles tendinopathy and to analyze the effectiveness of the available techniques. We performed a systematic review of the literature, to identify studies reporting clinical outcome after surgical treatment for Insertional Achilles tendinopathy in any population group with at least 6 months follow-up. The quality of the articles included was evaluated by the Coleman Methodology Score and correlated with the reported outcome and year of publication. We identified 16 studies reporting on 465 surgically treated Insertional Achilles tendinopathy with a mean follow-up of 29.8 months. Average age at the time of surgery was 53 years. Two different categories of surgical treatment were distinct: debridement alone or debridement with augmentation in case of excessive tendon loss. Results were excellent or good in 89.6% of cases and fair or poor in 10.4%. Average complications rate was 18.3%, with 15.7% of minor and 2.6% of major complications with no difference in the two groups. Negative correlation was found between Coleman Methodology Score and the reported outcome and positive correlation was found between Coleman Methodology Score and year of publication. Good or excellent outcome can be expected after surgical treatment for Insertional Achilles tendinopathy whatever the adopted procedure, but there is no specific evidence regarding which surgical technique provides a better outcome or a lower rate of complications. Research with higher levels of evidence and methodology that is more rigorous are needed in order to evaluate the optimal surgical strategy for patients with IAT.

  • A Notarnicola, G Vicenti, G Maccagnano, F Silvestris, P Cafforio, B Moretti
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 139-144.
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    The effects of treatment with shock waves (SW) on osteoblastic cells have already been described. Furthermore, the effects of treatment with SW are also determined by the contextual stimulation of other cell lines, in particular of mesenchymal cells. This is the first experimental study of stimulation of a human mesenchymal stem cell line, taken from bone marrow, using SW (electromagnetic device), with two energy levels. The results showed a significant increase in expression of the main osteoblastic differentiation genes: BMP2, alkaline phosphatase, osteocalcin, COL1A1, RUNX2. The monitoring within 96 hours demonstrated a progressive increase of cell adhesion and an intense cell proliferation at 48 h. The differentiation response and proliferation of stem cells after treatment with SW shows that this therapy is an effective method of regenerative medicine.

  • D Granchi, R Caudarella, C Ripamonti, P Spinnato, A Bazzocchi, E Torreggiani, A Massa, N Baldini
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 145-151.
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    In this study, we explored if urinary lithogenic risk parameters could have some application for monitoring bone health status. We recruited 20 women with postmenopausal osteopenia and a negative medical history for nephrolithiasis. Markers of lithogenic risk were evaluated on 24-h urine and fastingmorning urine. Serum levels of bone turnover markers (BTM) were measured in fasting-blood samples. We found that cross-linked telopeptide of type I collagen (CTX) was significantly correlated with 24-h calcium excretion. N-terminal propeptide of type I procollagen (PINP) correlated with 24-h excretion of potassium, calcium and citrate. CTX had considerably increased in patients with pH less than 5.5. Low citrate levels (less than 3.3 mmol/24 h) were associated with lower levels of CTX and PINP. Our findings suggest that a low-grade acidosis and some lithogenic risk factors are detectable in a proportion of patients with postmenopausal osteopenia. Further studies are necessary to confirm that this evaluation could be clinically relevant.

  • E Pola, D Colangelo, L A Nasto, V Pambianco, G Autore, V M Formica, G Maccauro
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 153-158.
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    PAO is an uncommon condition affecting pregnant women during last trimester or early post-delivery period; it is often asymptomatic or presents with pain related to some acute fragility fractures. The diagnosis is often delayed or missed, the etiology remains unknown and no guidelines about treatment have been published. We present one case of PAO in a 33-year-old primigravid woman presenting acute worsening back pain. Our patient was treated with a TLSO brace, oral 25 (OH)-vitamin D supplementation and Teriparatide for 6 months. A short review of the literature has been included and useful advice about how to suspect and diagnose this uncommon disease were given in order to recognize and treat such a debilitating and severe condition for young mothers as best as possible, based on the available scientific evidences.

  • C Perisano, M A Rosa, F Donati, C Barone, G Maccauro
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 159-164.
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    The solitary bone cyst is a typical tumor-like lesion of the immature skeleton, whose etio-pathogenesis is still unclear. The purpose of this work is to perform a review of the literature about the different surgical approaches focusing on the role of bone substitutes and growth factors. Literature analysis shows injection techniques of substances such as methylprednisolone, autologous bone marrow, demineralized bone matrix, calcium sulphate and surgical techniques that involve the resection and curettage associated with bone graft and/or intramedullary nailing. Although there are good results currently associated to these techniques and the different ways of treatment, the only evidence-based treatment is given by injections of steroids. However, given the high rate of failure, autologous bone marrow and platelet gel represent a viable therapeutic option.

  • G Vadalà, A Di Martino, F Russo, M C Tirindelli, L De Felice, F Agostini, R Papalia, V Denaro
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 165-172.
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    Bone marrow cells concentrate (BMCs) is a source of osteoprogenitor cells and platelet-rich plasma (PRP) is a source of growth factors. The objective of the study was to determine whether BMC and PRP could increase the potential of bone allograft to induce posterolateral-lumbar spinal fusion compared to the bone allograft alone. A prospective nonrandomized radiographic study has been conduced on 10 patients with posterolateral instrumented fusion for degenerative lumbar disease with 1-year follow-up using CT scan. A fresh frozen bone allograft alone and bone allograft with a mixture of autologous BMC and PRP blended with thrombin were apposed in the right and left posterolateral side, respectively. CT showed good right fusion masses (allograft alone) in 4 patients and poor in 6; good left masses (BMC and PRP plus allograft) in 9 patients and poor in 1. The differences detected between right-side and left-side masses show an advantage in adding BMC and PRP to the bone allograft to increase spinal fusion rate.

  • G Vadalà, F Russo, L Ambrosio, R Papalia, V Denaro
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 173-179.
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    Low back pain (LBP) is one of the most common disabling symptoms affecting the adult population throughout the industrialized world. The main cause underlying this condition is intervertebral disc degeneration (IDD), which is characterized by progressive decrease of the proteoglycan content within the nucleus pulposus (NP), leading to disc dehydration and loss of its morpho-functional and biomechanical properties. To date, LBP treatment is based upon conservative and invasive procedures which are not capable of restoring the degenerative alterations of the disc, as they only help relieve the symptoms and/or slow down disc degeneration and are, nonetheless, characterized by significant comorbidities, costs and secondary risks. The potential use of different mesenchymal stem/stromal cells (MSCs) for treating IDD has been promisingly tested in vitro and in vivo. The combination of different cell types, preconditioning culture conditions, engineered scaffolds and delivery systems have yielded proof of disc matrix reconstitution, increased cell viability and tissue regeneration in several experimental settings. This article reviews the current literature on stem cell-based therapy for IDD and the outcomes that diverse approaches have achieved.

  • C Faldini, F Perna, M Chehrassan, R Borghi, K Martikos, A Mazzotti, N Stefanini, L Cristofolini, F Traina
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 181-186.
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    Adolescent idiopathic scoliosis (AIS) is a triplanar deformity associated with rib hump, especially when a principle thoracic curve is present. The aim of this study is to evaluate the results of AIS correction retrospectively, using simultaneous double rod derotation manoeuvre technique followed by en-bloc direct vertebral rotation (DVR). Fourteen patients were included in this study. Coronal and sagittal thoracic Cobb angle, global coronal balance, sagittal balance, rib hump prominence, Scoliosis Research Society outcome instrument score (SRS-22) and Walter Reed visual assessment scale (WR-VAS) values were recorded pre- and postoperatively and evaluated. Results were evaluated at a mean follow-up of 2 years. Good to excellent radiographic and clinical results were obtained in all patients. No major perioperative complications occurred. This technique has proved to be effective for surgical correction of the deformity in Lenke type 1 AIS with good clinical and radiological results and low rate of complications.

  • F Niccolai, P D Parchi, A Vigorito, G Pasqualetti, F Monzani, M Lisanti
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 187-191.
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    A femoral neck fracture in an elderly patient often represents a major challenge for the orthopaedic surgeon who has to face not only the fracture, but also all the multiple issues related to age. Among others, malnutrition has been recognised as an important factor associated with severe aggravation in these patients. One-hundred-and-forty-seven patients were enrolled to investigate the use of two markers of patient nutritional status, i.e. serum albumin level and total leukocyte count (TLC), as predictors of mortality in the elderly patient suffering from proximal femur fracture. We found that low preoperative values of serum albumin and TLC proved to be directly related to worse outcomes. Therefore, these exams can be useful to identify patients with a femoral neck fracture that have higher risk of malnutrition and consequent higher mortality and that can benefit from some measures, such as albumin or protein nutritional supplement.

  • C Faldini, F Perna, F Pilla, N Stefanini, C Pungetti, V Persiani, F Traina
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 193-199.
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    Minimally invasive approach to the hip is a blood preserving surgery, with rapid rehabilitation, and low dislocation rate. Intuitively, these characteristics render this approach extremely suitable in the elderly patient. The aim of this study was to analyze the early clinical and radiographic results in the first 30 consecutive patients above 70 years of age undergoing THR through a minimally invasive anterior approach. Clinical evaluations showed an improvement of the Harris Hip Score and WOMAC score after surgery. Radiographic assessment showed cup orientation averaging 47° (range 40°-59°) and no valgus stem aligned. Allogeneic blood transfusion was required in only 6 patients (19.8%). One patient experienced an intraoperative fracture of the greater trochanter. No early implant dislocation was observed in the study population. In conclusion we advise a minimally invasive anterior approach for THR in older patients when a careful patient selection has been done.

  • C Faldini, F Pilla, D Fenga, F Perna, L Berti, N Stefanini, C Pungetti, A Mazzotti, F Traina
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 201-206.
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    Direct anterior approach to the hip allows perfect exposure of the acetabulum and an easy proximal and medial extension that makes it eligible for isolate acetabular cup revision although it is seldom used and there are only few published studies. On 23 consecutive acetabular revision (16 cases Paprosky grade 1 or 2, 5 cases 3A, 1 case 3B and 1 case 4) at an average 28-month follow up, we did not record failures or major complications. Early complications included prolonged wound healing in 4 cases and transient femoral cutaneous nerve palsy in 2 cases, the mean postoperative Harris Hip Score was 82.2 with 82.5% of excellent and good results. Our results are consistent with those reported in the literature with similar techniques. The direct anterior approach has shown excellent results for isolated cup revision, though is probably better suited for surgeons that have some experience with the same approach for primary cases.

  • G Vicenti, G Solarino, A Spinarelli, M Carrozzo, G Picca, R Maddalena, F Rifino, B Moretti
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 207-212.
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    The use of modular stems is still debated and controversial. Some authors have highlighted a number of disadvantages of modular prostheses including high costs, the tendency to fracture, the fretting and corrosion and the increased production of debris. Other authors have emphasized several advantages to adapt the prosthesis to the morphometric differences of patients, to allow better accuracy in restoring the anatomy and biomechanics of hip joint. The advantages of the modular devices appear to be more evident in patients with developmental dysplasia of the hip (DDH). In our study we compared 96 patients, operated for arthritis of the hip with 55 modular neck prostheses (PROFEMUR®, Wright® Arlington, Tennesse, USA) and 41 standard femoral stems (SYMAX®, Striker® Kalamazoo, Michigan, USA). The precision of restoring the natural offset during surgery was correlated with the clinical outcome and the radiological early migration of each stem measured using the computer-assisted EBRA-FCA method. The average preoperative HHS (Harris Hip Score) was 44 (23-66); the postoperative 86.56 in the 55 patients operated with modular prostheses and 81.70 in the 41 patients with monoblock stem. The worst HH Scores were seen in patients in whom the offset was not restored properly. On the contrary, the best scores have been reached in patients in which that value is closer to the "target" value (offset value of the contralateral hip). Restoring the proper offset seems to determine an appropriate tension of the abductor muscles of the hip and implies a better functioning of the joint and a better primary stability of the implant, with less early migration. This has to be a primary objective of THA surgery.

  • M Carnovali, M Mariotti, G Banfi
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 213-218.
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    In the last decade, several examples have been produced by scientific literature about zebrafish as a model to study human bone diseases. In fish, bone turnover, reparation and remodeling of the adult bone tissue cannot be studied in embryonic or juvenile stages. In addition, fins and scales represent unique anatomical features useful to study adult bone metabolism and diseases. For these reasons, the adult zebrafish represents an innovative and readily available resource for studying the bone metabolism at cellular and molecular level. Although the adult fish is less used than the embryo, several applications have been found in the last years with the production of innovative pathological models in adult zebrafish, helpful to understand the mechanisms of bone physiopathology. The use of mutants, regenerating organs, transgenic fish and scales have increased the power of this model in the last years.

  • R Sahemey, P Malliaras, J S Lewis, G J Michael, P Shortland, D Morrissey, N Maffulli
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 219-227.
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    We wanted to observe and compare the appearance of neurovascular tissue from tendon ex vivo, in patients with and without painful rotator cuff tendinopathy. Supraspinatus tendons were biopsied from 5 participants with painful tendinopathy and normal tendon from a young male. Slides were stained with haematoxylin and eosin and toluidine blue for histological assessment. Immunohistochemical markers for general nerves (protein gene-product 9.5 and synaptophysin), sensory nerves (calcitonin gene-related peptide; substance-P) and vascularisation (vascular endothelial growth factor) were used. PGP9.5 and CGRP-immunoreactive fibres were associated with vessels in cases and control. Synaptophysinlabelled fibres were observed in close relation to vessels in tendinopathy. PGP9.5, CGRP, SP and VEGF-immunoreaction also labelled tenocyte-like cells in degenerative areas and fibres in regions of fat and collagen. Sensory innervation and vascularity are increased in tendinopathy. The evidence for innervation and vascularity of symptomatic rotator cuff tendon may aid the development of novel investigations and therapies in the management of patients with this ailment.

  • D Fenga, M Currò, M Rosi, D J Ortolà, A Cantivalli, R Ientile, M A Rosa
    Journal of Biological Regulators and Homeostatic Agents. 2016, 30(4(S1)): 229-235.
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    The purpose of this study is to investigate the best preparation method of the cement powder mixture, solvent and antibiotic in order to obtain the greatest amount of antibiotic in the joint for the longest time as possible. At time T0 the three samples, packed in a sterile environment in different formulations, were placed in sterile tubes, adding to each one 5 ml of saline phosphate buffer solution (PBS) and put in a stove at 37°C for 24 h. A sample of PBS without cement (T control) was also created. Qualitative and quantitative assessment of the incubated liquid with cement was performed along with biochemical analysis with High Performance Liquid Chromatography (HPLC). The analysis of the raw data demonstrated that at T1 there was a prevalence of antibiotic release from sample , compared to sample 2 and 3. This difference was maintained until the T20; from T21 the antibiotic release gradually leveled in 3 samples. The elution of the antibiotic remained detectable up to T60. Our work shows that the sample preparation is decisive on the quantity of released antibiotic. These results are confirmed by microbiological tests. It is useful to know the actual kinetics of antibiotics in articulation. Further studies are necessary to determine the effectiveness of antibiotic against micro-organisms and how long it acts.