Platelet-rich plasma enhances the initial mobilization of circulation-derived cells for tendon healing

Circulation-derived cells play a crucial role in the healing processes of tissue. In early phases of tendon healing processes, circulation-derived cells temporarily exist in the wounded area to initiate the healing process and decrease in number with time. We assumed that a delay of time-dependent decrease in circulation-derived cells could improve the healing of tendons. In this study, we injected platelet-rich plasma (PRP) containing various kinds of growth factors into the wounded area of the patellar tendon, and compared the effects on activation of circulation-derived cells and enhancement of tendon healing with a control group (no PRP injection). To follow the circulation-derived cells, we used a green fluorescent protein (GFP) chimeric rat expressing GFP in the circulating cells and bone marrow cells. In the PRP group, the numbers of GFP-positive cells and heat-shock protein (HSP47; collagen-specific molecular chaperone)-positive cells were significantly higher than in the control group at 3 and 7 days after injury. At the same time, the immunoreactivity for types I and III collagen was higher in the PRP group than in the control group at early phase of tendon healing. These findings suggest that locally injected PRP is useful as an activator of circulation-derived cells for enhancement of the initial tendon healing process.     

Growth factor-enriched autologous plasma improves wound healing after surgical debridement in odontogenic necrotizing fasciitis: a case report

Introduction

Intracranial tuberculomas are a rare complication of tuberculosis occurring through hematogenous spread from an extracranial source, most often of pulmonary origin. Testicular tuberculosis with only intracranial spread is an even rarer finding and to the best of our knowledge, has not been reported in the literature. Clinical suspicion or recognition and prompt diagnosis are important because early treatment can prevent patient deterioration and lead to clinical improvement.

Case presentation

We present the case of a 51-year-old African man with testicular tuberculosis and multiple intracranial tuberculomas who was initially managed for testicular cancer with intracranial metastasis. He had undergone left radical orchidectomy, but subsequently developed hemiparesis and lost consciousness. Following histopathological confirmation of the postoperative sample as chronic granulomatous infection due to tuberculosis, he sustained significant clinical improvement with antituberculous therapy, recovered fully and was discharged at two weeks post-treatment.

Conclusion

The clinical presentation of intracranial tuberculomas from an extracranial source is protean, and delayed diagnosis could have devastating consequences. The need to have a high index of suspicion is important, since neuroimaging features may not be pathognomonic.     

New recurrent chromosome alterations in patients with multiple myeloma and plasma cell leukemia

Chromosome abnormalities detected in metaphases from multiple myeloma (MM) cells have a clear impact on prognosis and response to therapy. Thirteen out of 50 (26%) patients with plasma cell disorders and abnormal karyotypes (11 with MM and 2 with plasma cell leukemia (PCL)) were selected for inclusion in the present report based on the presence of karyotypes with new and/or infrequent structural aberrations. Thirty-three new rearrangements, including a novel recurrent aberration: psu dic(5;1)(q35;q10), were detected. Chromosome 1 was the most frequently involved. Gains of genetic material (57%) were noted more frequently than losses (43%). Three rearrangements that were observed only once in the literature appear to be recurrent from our data: del(16)(q13), del(5)(p13) and i(3)(q10), the latter being a single structural aberration in the karyotype. Clinical parameters from our series were compared with 2 control groups: 20 MM cases with recurrent aberrations in MM/PCL with a similar distribution of abnormalities associated with poor prognosis (group 1), and 40 with normal karyotypes and fluorescence in situ hybridization analysis (group 2). Significantly increased serum calcium levels (p = 0.022) in patients with new and/or infrequent chromosome changes with respect to both control groups, and a higher percentage of bone marrow plasma cell infiltration (p = 0.005), β(2) microglobulin, and lactate dehydrogenase levels (p < 0.0001) compared to group 2 were observed. Our results suggest that some of these novel rearrangements may be capable to deregulate genetic mechanisms related to the development and/or progression of the disease. The finding of new recurrent aberrations supports this hypothesis.     

Bisphosphonate-associated osteonecrosis of the jaw: the rheumatologist's role

Several recent reports have described osteonecrosis of the jaws (ONJ) associated with the use of bisphosphonates. Rheumatologists treating bone diseases with bisphosphonate need, therefore, to be aware of this potential risk and plan the prophylaxis, early diagnosis and prevention of potential consequences. We review the literature on this newly described complication, with particular focus on systemic and local predisposing pathologies, preventive measures suggested before and during therapy with bisphosphonates, and the most frequent clinical presentation of the oral lesions. The expert panel recommendations for the management of care of patients who develop ONJ are summarized.     

A novel therapeutic phosphate-based glass improves full-thickness wound healing in a rat model

Wound healing is a highly dynamic process and innovative therapeutic approaches are currently developed to address challenges of providing optimal wound care. In this study, phosphate-based glasses in the (CuO)_x·(KPO₃)_79.5-x·(ZnO)₂₀·(Ag₂O)_0.5 system (CuKPO₃ZnAg), with different CuO/ KPO₃ ratios were prepared by melt-quenching technique. Constant Cu concentrations were released from the samples during immersion in Simulated Body Fluid (SBF), while Zn concentrations were slightly decreased over time. Glass surface phosphatation leading to formation of Zn crystalline salts was revealed through spectroscopic techniques. This finding was supported by SEM images that illustrated new compound formation. Subsequent cytotoxicity evaluation on HaCaT Keratinocytes using the indirect MTT cell viability assay revealed a CuO concentration-dependent cytotoxicity profile and excellent biocompatibility at low CuO concentrations, in all CuKPO₃ZnAg glasses. Furthermore, the (CuO)₅·(KPO₃)_74.5·(ZnO)₂₀·(Ag₂O)_0.5 sample (5CuKPO₃ZnAg)_, demonstrated superior antibacterial potency against S. aureus (ATCC 25923) strain compared to amoxicillin and ciprofloxacin. In vivo full-thickness wound healing evaluation showed a significantly higher regenerative effect of the 5CuKPO₃ZnAg sample, in terms of angiogenesis, collagen synthesis and re-epithelialization compared to non-treated wounds. These findings advance our understanding of the therapeutic perspectives of phosphate-based glasses, showing promising potential for wound-healing applications.     

Early plasma cell recruitment in multiple myeloma following chemotherapy

Therapy-induced modifications of bone marrow plasma cell kinetics were studied in three patients with myelomatosis. The investigation was performed prior to and 15 d after termination of a course of aggressive chemotherapy. An increase in the labelling index (40-212% of pretreatment values) with a corresponding reduction of Ts (5-34%) was observed in all cases. As a consequence of this combined variation, the fractional turnover rate (which represents the percentage of cells produced per unit time) was the parameter with the highest increment (54-276%). These results indicate that plasma cell recruitment occurs soon after chemotherapy and is characterized by a shorter S phase and a higher number of DNA-synthesizing cells.     

Topical application of plasma fibronectin in full-thickness skin wound healing in rats

Fibronectin (Fn) has been shown to play an important role in wound healing because it appears to be the stimulus for migration of fibroblasts and epidermal cells. The purpose of this study was to investigate whether topical application of plasma Fn (pFn) improves healing of full-thickness skin wounds in rats. A round section of full-thickness skin (diameter of approximately 15 mm) was resected in rats. Animals were then divided into two groups, and wounds were treated topically with a single application of human plasma albumin (control group) or human pFn (FN group). Wound closure rate, hydroxyproline concentration, and histologic features (immunohistochemical staining) were evaluated. The FN group had a significantly higher wound closure rate and hydroxyproline level in the skin than the control group. Histologic analysis of macrophage and fibroblast migration, collagen regeneration, and epithelialization were significantly increased in the FN group compared with the control group. A single topical application of pFn increased the migration of macrophages, myofibroblasts, and fibroblasts. Moreover, further release of transforming growth factor-beta1 from activated fibroblasts, keratinocytes, and epithelial cells may also contribute to the beneficial effect of pFn on wound healing.     

Connexins in wound healing; perspectives in diabetic patients

Skin lesions are common events and we have evolved to rapidly heal them in order to maintain homeostasis and prevent infection and sepsis. Most acute wounds heal without issue, but as we get older our bodies become compromised by poor blood circulation and conditions such as diabetes, leading to slower healing. This can result in stalled or hard-to-heal chronic wounds. Currently about 2% of the Western population develop a chronic wound and this figure will rise as the population ages and diabetes becomes more prevalent [1]. Patient morbidity and quality of life are profoundly altered by chronic wounds [2]. Unfortunately a significant proportion of these chronic wounds fail to respond to conventional treatment and can result in amputation of the lower limb. Life quality and expectancy following amputation is severely reduced. These hard to heal wounds also represent a growing economic burden on Western society with published estimates of costs to healthcare services in the region of $25B annually [3]. There exists a growing need for specific and effective therapeutic agents to improve healing in these wounds. In recent years the gap junction protein Cx43 has been shown to play a pivotal role early on in the acute wound healing process at a number of different levels [4-7]. Conversely, abnormal expression of Cx43 in wound edge keratinocytes was shown to underlie the poor rate of healing in diabetic rats, and targeting its expression with an antisense gel restored normal healing rates [8]. The presence of Cx43 in the wound edge keratinocytes of human chronic wounds has also been reported [9]. Abnormal Cx43 biology may underlie the poor healing of human chronic wounds and be amenable therapeutic intervention [7]. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.     

Steroid-carrier proteins in patients with multiple myeloma

Patients with multiple myeloma have transcortin levels lower than normal. This is due in essence to a subgroup of patients producing IGG heavy chains with lambda light chains. Patients producing IGG with predominantly kappa light chains have almost normal transcortin levels. On the other hand, the binding activity of the steroid binding beta globulin (SB beta G) of the kappa type of multiple myeloma is significantly higher than the steroid binding of the lambda type of multiple myeloma. The serum levels of vitamin D binding protein (DBP) fall in the normal range.     

Endocytosis-dependent coordination of multiple actin regulators is required for wound healing

The ability to heal wounds efficiently is essential for life. After wounding of an epithelium, the cells bordering the wound form dynamic actin protrusions and/or a contractile actomyosin cable, and these actin structures drive wound closure. Despite their importance in wound healing, the molecular mechanisms that regulate the assembly of these actin structures at wound edges are not well understood. In this paper, using Drosophila melanogaster embryos, we demonstrate that Diaphanous, SCAR, and WASp play distinct but overlapping roles in regulating actin assembly during wound healing. Moreover, we show that endocytosis is essential for wound edge actin assembly and wound closure. We identify adherens junctions (AJs) as a key target of endocytosis during wound healing and propose that endocytic remodeling of AJs is required to form “signaling centers” along the wound edge that control actin assembly. We conclude that coordination of actin assembly, AJ remodeling, and membrane traffic is required for the construction of a motile leading edge during wound healing.     

Whole body MR in patients with multiple myeloma

BackgroundMultiple myeloma is a cancer of plasma cells which leads to bone marrow infiltration.AimWhole-body MR is the most sensitive imaging method available to detect multiple myeloma lesions.Material and MethodsMR scans were performed in 100 patients with multiple myeloma who were receiving treatment in the Haematology Clinic in Poznań in the years 2005–2006. Whole-body MR scans were performed with general coil 1.0 T in STIR sequences and T1 sequences, in coronal and sagittal planes with scanning area covering the head, neck, trunk and the limbs (FOV for specific regions was 36–48 cm). The bone lesions were classified as focal (monofocal/multifocal lesions), in-filtrative, mixed and “salt and pepper” type. Depending on the size of the lesions the patients were included in one of three groups according to Salmon-Durie Plus classification.ResultsFour main types of multiple myeloma were distinguished based on MR scans: focal (48 patients; monofocal in 10 patients), infiltrative (17 patients), mixed type (19 patients) and “salt and pepper” type (4 patients). The remaining 12 patients had no multiple myeloma lesions in the bone marrow. Additionally, in 18% of patients a soft tissue mass could be observed. According to Salmon-Durie Plus categorisation 27 subjects were classified as having stage I, 16 patients stage and 57 patients stage III disease. In 12% of patients MR data changed the disease staging.ConclusionsWB MR is a sensitive and effective diagnostic method with an important impact on staging and further treatment of multiple myeloma.     

Immobilizing Cu,Zn-superoxide dismutase in hydrogels of carboxymethylcellulose improves its stability and wound healing properties

Hydrogels of carboxymethylcellulose (CMC) with 50 and 90% cross-linking degree (CMC50% and CMC90%, respectively) were prepared and loaded with bovine erythrocyte Cu,Zn-superoxide dismutase (SOD) to obtain two drug delivery systems: SOD-CMC50% and SOD-CMC90%. Resistance of native SOD to inactivation by H₂O₂ and the effect of applying SOD-CMC hydrogels to open wounds of rats’ back skin were examined and compared to that of SOD trapped into CMC50% and CMC90% hydrogels. Also, the effect of CMC50% and SOD-CMC90% on human fibroblasts proliferation was evaluated at different times. It was found that SOD in the hydrogel was more resistant to H₂O₂ inactivation than the native enzyme and at the same time it reduced the time necessary for wound healing. Furthermore, the highest cell proliferation value was found for the CMC50% hydrogels, which had a three-dimensional structure suitable for gas and nutrient exchanges and improving cell life conditions. Published in Russian in Biokhimiya, 2006, Vol. 71, No. 12, pp. 1627–1632.