Bone Marrow Changes Research Articles

Selective Inhibition of SIRT2 Improves Outcomes in a Lethal Septic Model

Background: Seven isoforms of histone deacetylase Class III have been reported - Sirtuin (SIRT) 1-7. We recently demonstrated that EX-527, an inhibitor of SIRT1, reduces mortality in a mouse model of lethal-cecal-ligation-and-puncture (CLP)-induced septic shock. Our present study was aimed at determining whether selective inhibition of SIRT2, with AGK2, would decrease animal death and attenuate the inflammatory response in a septic model. Methods: Experiment I: C57BL/6J mice were intraperitoneally given either AGK2 (82 mg/kg) in dimethyl sulfoxide (DMSO) or DMSO alone, and 2 h later subjected to CLP. Survival was monitored for 240 hours. Experiment II: mice treated the same way as Experiment I, were grouped into (i) DMSO vehicle, and (ii) AGK2, with sham mice (operating but without any treatment) serving as controls. Peritoneal fluid and peripheral blood were examined at 24 and 48 hours for cytokine production. Samples of blood at 48 h were also allocated to assess coagulability using Thrombelastography (TEG). Morphological changes of bone marrow were evaluated from long bones (femurs and tibias) with hematoxylin and eosin (H&E) staining. Bone marrow atrophy was quantified by a blinded pathologist. Experiment III: cytokines in supernatant of the cultured normal primary splenocytes were measured after the cells were stimulated by lipopolysaccharide and treated with or without AGK2 (10 μM) for 6 hours. Results: AGK2 significantly reduced mortality and decreased levels of cytokines in blood (TNF-α: 298.3±24.6 vs 26.8±2.8 pg/ml, p=0.0034; IL-6: 633.4±82.8 vs 232.6±133.0 pg/ml, p=0.0344) and peritoneal fluid (IL-6: 704.8±67.7 vs 391.4±98.5 pg/ml, p=0.033) compared to vehicle control. Also, AGK2 suppressed the TNF-α and IL-6 production in the cultured splenocytes (TNF-α: 68.1±6.4 vs 23.9±2.8 pg/ml, p=0.0009; IL-6: 73.1±4.2 vs 49.6±3.0 pg/ml; p=0.0051). The TEG data showed that the mice subjected to CLP displayed prolonged fibrin formation and fibrin cross-linkage time, slower clot formation, decreased platelet function, and clot rigidity. AGK2 treatment was associated with dramatic improvements in fibrin cross-linkage and clot formation times, without a significant impact on the clot initiation parameters or platelet function. Additionally, AGK2 significantly attenuated the bone marrow atrophy (58.3±6.5 vs 30.0±8.2%, p=0.0262). Conclusion: Selective inhibition of SIRT2 significantly improves survival, and attenuates sepsis-associated “cytokine storm”, coagulopathy, and bone marrow atrophy in a mouse model of lethal septic shock.

Abnormal perfusion in patellofemoral subchondral bone marrow in the rat anterior cruciate ligament transection model of post-traumatic osteoarthritis: a dynamic contrast-enhanced magnetic resonance imaging study

Although anterior cruciate ligament (ACL) injury is a well-recognized risk factor for developing knee post-traumatic osteoarthritis (PTOA), the process in the patellofemoral (PF) joint after ACL injury is still under-researched. Our aim was to investigate the perfusion changes in PF subchondral bone marrow in the rat ACL transection (ACLX) model of PTOA using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Eighteen male Sprague Dawley rats were randomly separated into three groups (n = 6 each group): a normal control group and groups receiving ACLX and sham-surgery, respectively, in the right knee. Perfusion parameters in the patellar and femoral subchondral bone marrows of all rats were measured on DCE-MRI at 0, 4, 8, and 16 weeks after respective treatment. After the last MRI at week 16, the rats were sacrificed and their right knees were harvested for histologic examination. In addition, to observe the long-term histologic change in PF joints, 9 additional rats (n = 3 in each group) were included and sacrificed at week 32 for histologic examination. In the ACLX group vs the sham and control groups, the perfusion parameters were significantly changed in both patellar and femoral subchondral bone marrows at week 16. Histologic examination revealed cartilage defects in ACLX rats at 32 weeks after surgery. These data point to a possible functional relationship between subchondral bone marrow perfusion abnormalities and cartilage breakdown in PTOA. Moreover, the perfusion parameters derived from DCE-MRI can potentially serve as biomarkers of early OA.

Apparent Diffusion Coefficient of Normal Abdominal Organs and Bone Marrow From Whole-Body DWI at 1.5 T: The Effect of Sex and Age.

The objectives of this study were to define the range of apparent diffusion coefficients (ADCs) from whole-body DWI in normal abdominal organs and bone marrow, to identify ADC differences between sexes and changes occurring with age, and to evaluate the effect of the fat fraction (FF) on the ADC of normal liver parenchyma and bone marrow. Fifty-one healthy volunteers (mean age = 38 years; age range = 23-68 years) underwent whole-body DWI using single-shot echo-planar imaging (b = 0, 150, 400, 750, and 1000 s/mm(2)). A two-point Dixon technique was used to evaluate the FF. Perfusion-sensitive ADCs, which we refer to as "ADCALL," and perfusion-insensitive ADCs, which we refer to as "ADCHIGH," of the liver and renal parenchyma, spleen, pancreatic tail, and red and yellow bone marrow were calculated. The relationships between ADC and sex, age, and FF were examined. ADCALL and ADCHIGH were significantly higher in female volunteers for the pancreatic tail (p = 0.046 and 0.008, respectively), red bone marrow (p = 0.029 and 0.001), and yellow bone marrow (p < 0.001 for both) but with considerable overlap. There were significant negative correlations between ADCALL and ADCHIGH and age in the liver parenchyma (p = 0.008 and 0.01, respectively) and in the yellow bone marrow (p = 0.013 and 0.039) for all subjects. ADCALL and ADCHIGH were also negatively correlated with FF in the liver parenchyma (p = 0.006 and 0.008, respectively) and in yellow bone marrow (p < 0.001 and p = 0.001) in all subjects. The ADCs of normal liver parenchyma and bone marrow change significantly with age. The ADCs of bone marrow in women are significantly higher than those of men and correlate strongly with FF. These effects may have an impact on image interpretation when using whole-body DWI to assess disease burden and treatment response.

Quantitative Analysis of MR Imaging to Assess Treatment Response for Patients with Multiple Myeloma by Using Dynamic Intensity Entropy Transformation: A Preliminary Study.

To develop a quantitative measure of bone marrow changes in magnetic resonance (MR) images and investigate its capability for assessment of treatment response for patients with multiple myeloma (MM). This study was retrospective, institutional review board approved, and HIPAA compliant. Informed consent was waived. Patients (n = 64; mean age, 58.8 years [age range, 27-75 years]) who were diagnosed with MM and underwent autologous bone marrow stem cell transplantation (BMT) were evaluated. A pair of spinal MR examinations performed before and after BMT was collected from each patient's records. A three-dimensional dynamic intensity entropy transformation (DIET) method was developed to transform MR T1-weighted signal voxel by voxel to a quantitative entropy enhancement value (qEEV), from which predictor variables were derived to train a linear discriminant analysis classifier by using a leave-one-out method. The output of the linear discriminant analysis provided a qEEV-based response index for quantitative assessment of treatment response. The performance of quantitative response index for the discrimination of responder and nonresponder patients was evaluated by receiver operating characteristic curve analysis. Among the 46 and 18 clinically diagnosed responder and nonresponder patients, the quantitative response index at a chosen decision threshold correctly identified 42 responder and 17 nonresponder patients. The agreement between the DIET method and the clinical outcome reached 0.922 (59 of 64; κ = 0.816; area under the receiver operating characteristic curve, 0.886 ± 0.042). This study demonstrated the feasibility of quantitative response index to differentiate responder and nonresponder patients and had substantial agreement with clinical outcomes, which indicated that this quantitative measure has the potential to be an image biomarker to assess MM treatment response.

Microenvironmental remodeling as a parameter and prognostic factor of heterogeneous leukemogenesis in acute myelogenous leukemia.

Acute myelogenous leukemia (AML) is a heterogeneous disorder characterized by clonal proliferation of stem cell-like blasts in bone marrow (BM); however, their unique cellular interaction within the BM microenvironment and its functional significance remain unclear. Here, we assessed the BM microenvironment of AML patients and demonstrate that the leukemia stem cells induce a change in the transcriptional programming of the normal mesenchymal stromal cells (MSC). The modified leukemic niche alters the expressions of cross-talk molecules (i.e., CXCL12 and JAG1) in MSCs to provide a distinct cross-talk between normal and leukemia cells, selectively suppressing normal primitive hematopoietic cells while supporting leukemogenesis and chemoresistance. Of note, AML patients exhibited distinct heterogeneity in the alteration of mesenchymal stroma in BM. The distinct pattern of stromal changes in leukemic BM at initial diagnosis was associated with a heterogeneous posttreatment clinical course with respect to the maintenance of complete remission for 5 to 8 years and early or late relapse. Thus, remodeling of mesenchymal niche by leukemia cells is an intrinsic self-reinforcing process of leukemogenesis that can be a parameter for the heterogeneity in the clinical course of leukemia and hence serve as a potential prognostic factor.

Evaluation of bone marrow in cowpox virus infection in cynomolgus macaques (VIR1P.1127)

Abstract Evaluation of countermeasures against variola virus, the causative agent of smallpox, must be performed through extrapolation from suitable animal models of human smallpox. In previous studies, the gross and histopathological findings of nonhuman primates intravenously (IV) infected with Cowpox Brighton Red (CPXV) included the presence of necrotic areas of bone marrow that were orthopox-viral antigen positive by immunohistochemistry (IHC). Here, we describe changes in bone marrow in regards to cellular composition, orthopox-viral antigen positivity, viral load, and histological findings during a serial disease progression study of cynomolgus macaques following IV inoculation of CPXV. Our results demonstrate infectious CPXV as early as day 3 post inoculation in the bone marrow. Flow cytometry and histological analysis indicate changes in bone marrow composition. Furthermore, flow cytometry analysis indicates many cell populations including monocytes, CD34+ stem cells, and neutrophils were orthopox-viral antigen positive, while mesenchymal stromal cells were not. We have previously shown immunopositivity in the bone marrow by IHC. Flow cytometry revealed no significant differences in early or late apoptosis between CPXV- and mock-infected NHPs. These data indicate an important role for bone marrow function during the progression of disease in the CPXV- nonhuman primate model of smallpox.

Abstract 272: Chronic Hyperlipidemia Alters the Population of Endothelial Progenitor Cells in Bone Marrow and Peripheral Circulation via Both ROS-dependent and Independent Mechanisms

Background/Aims: Bone marrow (BM)-derived endothelial progenitor cells (EPCs) make significant contribution to the function and integrity of vasculature. The number of EPCs is significantly decreased in hyperlipidemic patients. Reactive oxygen species (ROS) and oxidative stress were considered an important mechanism for the development of atherosclerosis in hyperlipidemia. The present study was to determine the role of ROS production in the changes of EPC population in chronic hyperlipidemia. Methods and Results: EPC numbers and ROS formation in BM and blood were determined in wild-type (WT) male C57BL/6 mice and hyperlipidemic LDL receptor knockout (LDLR-/-) mice with high fat diet for 4 months. Intracellular blood, extracellular BM and blood ROS production was significantly increased in hyperlipidemic LDLR-/- mice that was effectively blocked with N-acetylcysteine treatment. Hyperlipidemia produced complex changes in EPC populations in BM and blood. The c-Kit+/CD31+ cell number was significantly decreased in BM and blood, and the numbers of CD34+/CD133+ cells and Sca-1+/Flk-1+ cells were significantly decreased in blood without change in BM, which were not affected by inhibition of ROS production. Interestingly, blood CD34+/Flk-1+ cell number was significantly increased in hyperlipidemic mice that was prevented when ROS formation was inhibited. Conclusions: Chronic hyperlipidemia produced significant and complex changes in EPC populations in both BM and circulation through both ROS-dependent and ROS-independent mechanisms in mice.

Aseptic Spondylodiscitis after Lumbar Discectomy: Case Report and Literature Review

Introduction Aseptic inflammatory changes in the vertebral bone marrow, end plates and intervertebral discs have been described as part of different entities such as Modic changes (MCs). MCs are classified in three types according to the formation of vascularized fibrous, fatty, or cicatricial bone tissue. Radiologically, each type is distinguished by particular magnetic resonance imaging (MRI) findings. MCs can be seen as part of normal spinal degeneration or secondary to spine surgical procedures such as lumbar discectomy. Even though their prevalence varies between studies, in clinical practice they generally are infrequent radiological findings. Patient and Methods: A case report of a 26-year-old man with 10 days of postoperative intense low back pain refractory to oral analgesia after L4–L5 lumbar discectomy is presented. A nonsystematic literature review about postoperative MCs was conducted. Results The patient evolved with difficult pain management needing to be hospitalized and studied with laboratory examinations and spinal images. Elevation of inflammatory parameters and lumbar spine MRI with T1-weighted image hypointensity, T2-weighted image hyperintensity, and increased signal with gadolinium at vertebral bone marrow and end plates adjacent to L4–L5 disc were the main findings. Septic spondylodiscitis was suspected as differential diagnosis, but conservative treatment was followed by clinical observation and evaluation of inflammatory parameters. The patient evolved with a progressive decrease of back pain and slight elevation of control inflammatory parameters but neither antibiotic treatment nor surgery was needed. At 9th day of hospitalization, the patient was discharged given positive clinical response with no pain at rest and slight pain with movement. Ambulatory follow-up with laboratory and imaging study exhibited normalization of inflammatory parameters and resolution of vertebral bone marrow and end plates changes accompanied by remission of patient's pain. Conclusion MCs are infrequent radiological findings. Type 1 MCs show similar MRI findings to those seen in the infectious process of the spine, which turns septic discitis/spondylodiscitis the main differential diagnosis to discard. When MCs are present, laboratory and imaging evaluation has to be performed to rule out an infectious etiology. Evaluation of inflammatory parameters, diffusion-enhanced MRI, and analysis of MRI contrast enhancement patterns are useful tools for this purpose. Because of the significant association between MCs and low back pain, symptomatic MCs must be treated with a first-line conservative treatment of analgesia and physical activity restriction.

In situ analysis of interleukin-6 expression at different sites of zygapophyseal joints from patients with ankylosing spondylitis in comparison to controls

Objectives: Analysis of interleukin (IL)-6 serum levels in patients with ankylosing spondylitis (AS) has indicated that IL-6 might be a pro-inflammatory cytokine involved in AS. However, two placebo-controlled trials with monoclonal antibodies directed against the IL-6 receptor have failed to demonstrate the efficacy of the monoclonal humanized anti-human IL-6 receptor antibody over placebo for the treatment of symptoms of AS. In this study we conducted an in situ analysis of IL-6 expression at different sites of inflammation in zygapophyseal joints of patients with AS in comparison to osteoarthritis autopsy controls (CO).Method: Our immunohistochemical analysis involved 14 patients with AS, 12 autopsy controls (CO), and 11 patients with osteoarthritis (OA). Immunohistochemistry was performed to detect IL-6+ cells at five different sites: within subchondral bone marrow, fibrous tissue replacing subchondral bone marrow, hyaline cartilage, and the subchondral bone plate, and at entheseal sites.Results: Apart from changes in subchondral bone marrow, no significant differences were observed at the sites analysed when comparing AS patients and controls. A significantly lower frequency of IL-6+ cells was evident in AS patients compared to controls (p = 0.0043). In addition, AS patients tended to have even lower percentages of IL-6+ cells than controls at subchondral bone plates and entheseal sites. A significantly lower number of IL-6 expressing cells was also seen within the fibrous tissue of AS compared to OA patients (p = 0.0237).Conclusions: This in situ analysis confirms that IL-6 is not a key player in the pathogenesis of inflammatory processes in spondyloarthritides (SpA). The relevance of pro-inflammatory agents in axial SpA might be studied better in situ in bony specimens at the primary site of inflammation.

The associations between disc degeneration and co-existent structural abnormalities in the lumbosacral spine – A 3.0T MRI study of community-based adults

The associations between disc degeneration and co-existent structural abnormalities in the lumbosacral spine – A 3.0T MRI study of community-based adults

Gelatinous Transformation of Bone Marrow: A Prospective Tertiary Center Study, Indicating Varying Trends in Epidemiology and Pathogenesis.

Gelatinous bone marrow transformation (GTBM) also known as serous atrophy is a degenerative change in the hematopoietic bone marrow and is a rare well recognized pathological entity. It was earlier described mainly in association with anorexia nervosa and psychiatric eating disorders, but recently it has been reported in ulcerative colitis, tuberculosis, chronic renal diseases, immuno suppressed states (mainly HIV infection), malignancies and Kala azar. Treatment is based on treating the underlying disease. Our objective was to study the epidemiology and pathogenesis of diseases causing gelatinous transformation of bone marrow, at a tertiary center level. A prospective study was conducted on 732 samples of bone marrow aspirate with the aim of identifying gelatinous transformation in bone marrow aspirates which was confirmed by Alcian blue stain at pH 2.5. The presence of this material was correlated with the hematological profile of the patient, the presenting signs and symptoms and provisional clinical diagnosis at initial visit. Incidence of gelatinous transformation was calculated to be nearly 4.8% and the condition was more common in males (23) as compared to females (12) (Male:Female=2:1). Forty percent of the cases were seen in children followed by 37% in adolescents and young adults. The older individuals comprised only 23% of the cases. The bone marrow was hypocellular in 21 (60%), normocellular in 10 (28.5%) and hypercellular in four cases (11.5%). Five cases with GTBM progressed to aplastic anaemia of which three were in children.

A novel modulation of structural and functional changes of mouse bone marrow derived dendritic cells (BMDCs) by interleukin-2(IL-2)

IL-2 is a pleiotropic cytokine produced by T cell after antigen activation of T cell and it is so called T cell growth factor. A large number of documents suggest that Il-2 plays pivotal roles in the immune response and now Il-2 is an approved drug being used for various kinds of diseases such as cancer and dermatitis.1 The aim of present exploration was to look at effect of IL-2 on structural, phenotypic and functional maturation of murine BMDCs. The structural and phenotypic maturation of BMDCs under influence of IL-2 were evaluated by light microscope and flow cytometry (FCM). The functional maturation of BMDCs was confirmed by cytochemistry assay, FITC-dextran, acid phosphatase (ACP) activity, bio-assay and enzyme linked immunosorbent assay (ELISA).We elucidated that IL-2 up-regulated the expression of key surface markers such as: CD80, CD83, CD86, CD40 and MHC II molecules on BMDCs, down-regulated phagocytosis activity, induced more production of IL-12 and TNF-α secreted by BMDCs. Therefore it can be concluded that IL-2 effectively enhance the maturation of BMDCs. Our results provide direct evidence to support IL-2 would be used as a potent adjuvant in preparation of DC-based vaccines, as well as an immune remedy for cancer situation.

Magnetic resonance imaging and BMB score in the evaluation of bone involvement in Gaucher's disease patients.

ObjectiveTo evaluate by magnetic resonance imaging changes in bone marrow of patients undergoing treatment for type I Gaucher’s disease.Materials and MethodsDescriptive, cross-sectional study of Gaucher’s disease patients submitted to 3 T magnetic resonance imaging of femurs and lumbar spine. The images were blindly reviewed and the findings were classified according to the semiquantitative bone marrow burden (BMB) scoring system.ResultsAll of the seven evaluated patients (three men and four women) presented signs of bone marrow infiltration. Osteonecrosis of the femoral head was found in three patients, Erlenmeyer flask deformity in five, and no patient had vertebral body collapse. The mean BMB score was 11, ranging from 9 to 14.ConclusionMagnetic resonance imaging is currently the method of choice for assessing bone involvement in Gaucher’s disease in adults due to its high sensitivity to detect both focal and diffuse bone marrow changes, and the BMB score is a simplified method for semiquantitative analysis, without depending on advanced sequences or sophisticated hardware, allowing for the classification of the disease extent and assisting in the treatment monitoring.

A case with ZNF198-FGFR1 gene rearrangement presenting as acute eosinophil myeloid leukemia.

A previously healthy 47-year-old Chinese man presented in January 2009 with extreme fatigue, fever, and night sweats. Hepatomegaly (palpable, 2 cm in the right hypochondrium) and splenomegaly (palpable, 2 cm in the left hypochondrium) were identified, and axillary lymph nodes were swollen. A laboratory investigation showed a white blood cell (WBC) count of 39.8 × 109/L with eosinophils 52% (absolute eosinophil count of 20.7 × 109/L), hemoglobin level of 14.9 g/dl and platelet count of 50.0 × 109/L. Bone marrow (BM) aspirate revealed hypercellular and occupied by approximately 22.0% blasts; eosinophils comprised 23.5% of total cellularity [Figure 1a]. Flow cytometry of these blast cells demonstrated expression of CD13, CD33, CD34, CD117, CD14, CD15, and human leukocyte antigen-DR indicating that myeloblasts were presented. Cytogenetic studies on BM showed a 46, XY, t (8;13)(p11.2;q12.1)[15]/46, idem,-7, der (14), +Mar[5] karyotype [Figure 1c]. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to detect gene rearrangements of BCR/ABL, FIPIL1/PDGFRA, TEL/PDGFRB were all negative as well as c-KIT and JAK2V617F mutations. Fluorescence in situ hybridization using a dual-fusion probe confirmed FGFR1 gene rearrangement [Figure 1b], the ZNF198-FGFR1 fusion test was done by RT-PCR using ZNF198-and FGFR1-specific primers (5′-TCCCTGTGCCTGTG TATATCCC-3′ and 5′-CGGGAAGCTCATACTCAGAGAC-3′, respectively) and showed a specific amplification product of 195 bp [Figure 1d]. Sequencing identified an in-frame fusion of exon 17 of ZNF198 to exon 9 of FGFR1 [Figure 1e], which was indicative of 8p11 myeloproliferative syndrome (EMS, World Health Organization [WHO] 2008, myeloid and lymphoid neoplasms with FGFR1 abnormalities[1]). Treatment was started with imatinib (400 mg once daily) plus urbason (40 mg once daily) at day 5, about 2 weeks after initiating treatment, WBC count (30.43 × 109/L) did not achieve a significant decrease and the level of hemoglobin and platelet count gradually reduced to 8.6 g/dl and 10.0 × 109/L, respectively. Therefore, imatinib and urbason therapy was stopped. Subsequently, the patient received AA (aclacinomycin plus cytarabine) regimen and had a marked initial response to the first cycle of chemotherapy: The WBC and platelet count returned to normal. However, 25 days later, the patient again developed worse, his WBC rose to 52.7 × 109/L. BM study revealed inadequate aspirate due to dry tap. At the time, a bone biopsy was performed and revealed a hypercellular with marked hypereosinophilia. High-dose cytarabine therapy was recommended and completed. Nonetheless, the patient failed to respond to aggressive chemotherapy and supportive treatment. He died in May 2009, 5 months after the initial diagnosis. Figure 1 (a) Morphologic changes of bone marrow (BM) smear (Wrighte Giemsa, 1 000) showed markedly increased abnormal myeloblasts with eosinophils. (b) Fluorescence in situ hybridization analysis of BM cells with an FGFR1 break-apart DNA probe revealing FGFR1 ...

Imaging Patterns in MRI in Recent Bone Injuries Following Negative or Inconclusive Plain Radiographs.

Few bony injuries and most soft tissue injuries cannot be detected on plain radiography. Magnetic resonance imaging (MRI) can detect such occult bony injuries due to signal changes in bone marrow. In addition to excluding serious bony injuries, it can also identify tendon, ligament, cartilage and other soft tissue injuries and thus help in localizing the cause of morbidity. To determine the MRI imaging patterns in recent bone injuries (less than 4 weeks) following negative or inconclusive plain radiographs. To determine the role of MRI in recent fractures. Out of the 75 individuals with history of recent injury of less than 4 weeks duration, fracture line was demonstrated in 16 patients (21%) who had no obvious evidence of bone injury on plain radiographs. Bone contusion or bruising of the bone was demonstrated in 39 (52%) patients. This was the commonest abnormality detected in MRI. The remaining 20 patients did not show any obvious injury to the bone on MR imaging however, soft tissue injury could be demonstrated in 12 (16%) patients which show that the extent of soft tissue injury was relatively well demonstrated by MR imaging. The present study showed that occult injuries commonly occur at the Knee followed by Ankle, Wrist, Foot, Elbow, Leg, Hands, Hips & Spine. The study showed that MR is efficient in the detection of occult bone injuries which are missed on radiography. Compared to radiographs, MRI clearly depicted the extent of injuries and associated soft tissue involvement. MRI demonstrates both acute and chronic injuries and also differentiates both, whereas radiography has poor sensitivity for acute injuries. Also, the soft tissue injuries like tendionous and ligamentous injuries cannot be identified on radiographs.

Influence of Light Emitting Diode on Bone Marrow and Healing of Dermatome Wounds

The irradiation of large surfaces or whole body with light emitting diode LED λ-470 nm and λ-940 nm (LED shower) causes structural changes in bone marrow and stimulates healing of experimental dermatome wounds. The increase of migration of the bone marrow cells in derma and epithelial layers of skin indicates that LED-shower intensifies intercellular interactions and cells migration between tissues.

Oxidized low-density lipoprotein alters endothelial progenitor cell populations

Oxidized low-density lipoprotein (ox-LDL) is critical to atherosclerosis in hyperlipidemia. Bone marrow (BM)-derived endothelial progenitor cells (EPCs) are important to preventing atherosclerosis, and significantly decreased in hyperlipidemia. This study was to demonstrate ox-LDL and hyperlipidemia could exhibit similar effect on EPC population and the role of reactive oxygen species (ROS). ROS production in BM and blood was significantly increased in male C57BL/6 mice with intravenous ox-LDL treatment, and in hyperlipidemic LDL receptor knockout mice with 4-month high-fat diet. ROS formation was effectively blocked with overexpression of antioxidant enzymes or N-acetylcysteine treatment. In hyperlipidemic and ox-LDL-treated mice, c-Kit(+)/CD31(+) cell number in BM and blood, and Sca-1(+)/Flk-1(+) cell number in blood, not in BM, were significantly decreased, which were not affected by inhibiting ROS production, while blood CD34(+)/Flk-1(+) cell number was significantly increased that was prevented with reduced ROS formation. However, blood CD34(+)/CD133(+) cell number increased in ox-LDL-treated mice, while decreased in hyperlipidemic mice. These data suggested that ox-LDL produced significant changes in BM and blood EPC populations similar (but not identical) to chronic hyperlipidemia with predominantly ROS-independent mechanism(s).

Magnetic resonance imaging of the spinal marrow: Basic understanding of the normal marrow pattern and its variant

For now, magnetic resonance (MR) is the best noninvasive imaging modality to evaluate vertebral bone marrow thanks to its inherent soft-tissue contrast and non-ionizing nature. A daily challenging scenario for every radiologist interpreting MR of the vertebral column is discerning the diseased from normal marrow. This requires the radiologist to be acquainted with the used MR techniques to judge the spinal marrow as well as its normal MR variants. Conventional sequences used basically to image marrow include T1W, fat-suppressed T2W and short tau inversion recovery (STIR) imaging provides gross morphological data. Interestingly, using non-routine MR sequences; such as opposed phase, diffusion weighted, MR spectroscopy and contrasted-enhanced imaging; may elucidate the nature of bone marrow heterogeneities; by inferring cellular and chemical composition; and adding new functional prospects. Recalling the normal composition of bone marrow elements and the physiologic processes of spinal marrow conversion and reconversion eases basic understanding of spinal marrow imaging. Additionally, orientation with some common variants seen during spinal marrow MR imaging as hemangiomas and bone islands is a must. Moreover, awareness of the age-associated bone marrow changes as well as changes accompanying different variations of the subject's health state is essential for radiologists to avoid overrating normal MR marrow patterns as pathologic states and metigate unnecessary further work-up.

The role of imaging in diagnosis and management of femoral head avascular necrosis.

The aim of this paper is to critically review the literature documenting the imaging approach in adult Femoral Head Avascular Necrosis (FHAVN). For this purpose we described and evaluated different radiological techniques, such as X-ray, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Nuclear Medicine. Plain films are considered the first line imaging technique due to its ability to depict femoral head morphological changes, to its low costs and high availability. CT is not a routinely performed technique, but is useful to rule out the presence of a subchondral fracture when MRI is doubtful or contraindicated. MRI is unanimously considered the gold standard technique in the early stages, being capable to detect bone marrow changes such as edema and sclerosis. It may be useful also to guide treatment and, as CT, it is a validated technique in follow-up of patients with FHAVN. Nuclear medicine imaging is mostly applied in post-operative period to detect graft viability or infective complications. More advanced techniques may be useful in particular conditions but still need to be validated; thus new research trials are desirable. In conclusion, X-ray examination is the first line approach, but lacks of sensitivity in early stage whereas MRI is indicated. CT easily depicts late stage deformation and may decrease MRI false positive results in detecting the subchondral fracture. However, the role of both Nuclear Medicine Imaging and advanced MR techniques in FHAVN still need to be investigated.

Bone marrow fibrosis may be an effective independent predictor of the ‘TKI drug response level’ in chronic myeloid leukemia

ObjectivesThe aim of this study was to assess bone marrow (BM) fibrosis and dysplasia in chronic myeloid leukemia (CML) patients receiving the first-generation tyrosine kinase inhibitor (TKI), imatinib, or second-generation TKIs, dasatinib, and nilotinib. We further investigated whether CML under TKI is associated with dysplastic BM changes during the clinicopathological course of the disease.MethodsIn total, pre-treatment BM paraffin blocks of biopsy specimens were available for 41 adult patients diagnosed with chronic phase CML. Post-treatment BM aspirate clot and core biopsy samples were reviewed for fibrosis and dyshematopoiesis.ResultsOverall, 13 (31.7%) patients achieved a complete cytogenetic response with imatinib treatment, with no events. In 25 patients, imatinib was discontinued owing to primary or secondary resistance. In patients with initial dysmyelopoiesis, the rate of BM fibrosis was 82.4 versus 47.6% for other patient groups (P = 0.02). Overall, 24 patients with newly diagnosed CML showed marrow fibrosis, among which 19 (79.1%) had imatinib resistance. However, only 5 out of 15 patients (33.5%) without marrow fibrosis had imatinib resistance (P = 0.08).DiscussionOur findings indicate that BM fibrosis is an independent predictor of the ‘TKI drug response level’ in CML and support its inclusion as a critical pathobiological parameter for decision-making with regard to TKI drug selection de novo, calculation of prognosis at the onset of disease, and monitoring response to TKI in the long-term disease course of CML.