Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
24332476 Transient sternoclavicular joint arthropathy, a self-limited disease. 2014 Apr BACKGROUND: The sternoclavicular joint (SCJ) is a true diarthrodial synovial joint and therefore vulnerable to the same disease processes as in other synovial joints. We identified a group of patients with monarticular arthritis of the SCJ that had a benign process and a self-limited disease course. METHODS: This retrospective study included 25 female patients who presented with pain or swelling of the SCJ between January 2000 and December 2010. Their mean age was 59 years, and the average follow-up was 44 months. All patients underwent baseline radiographic imaging, technetium bone scan, computed tomography, and magnetic resonance imaging. Blood profiles were negative for rheumatoid factor in all patients. Functional outcome was assessed with the Rockwood SCJ score. RESULTS: The patients presented with complaints of pain (72%), local swelling (88%), and redness (8%) that progressed during 4 weeks. The physical examination revealed tenderness (84%), swelling (88%), and limited range of motion (16%). These findings persisted for a median of 5 months. Plain radiographs showed arthritic changes in 5 patients (20%). Increased uptake was observed in all 9 patients who underwent a bone scan. Soft tissue swelling was demonstrated on computed tomography in 5 patients (20%) and on magnetic resonance imaging in 5 patients (20%). One patient had osteoarthritic changes on magnetic resonance imaging. Pain resolved spontaneously in all patients, leaving only swelling in 9 patients and tenderness in 1 patient. CONCLUSION: Our experience is that SCJ arthropathy may often be a self-limited disease. After being treated solely with nonsteroidal anti-inflammatory medication, 24 of the 25 study patients showed complete regression of pain and return to full function without recurrence of symptoms. Basic blood tests and radiographs are sufficient to rule out a septic joint.
25627230 [Multicentric Castleman disease not associated with HHV-8 and HIV viruses]. 2014 Jul Castleman's disease (CD) is a polyclonal lymphoproliferative disorder also known as giant nodular hyperplasia or angiofollicular lymph node hyperplasia. It is a rare disease often associated to human immunodeficiency virus (HIV) and human herpes virus 8 (HHV-8). Histopathological findings in Castleman's disease suggest an exaggerated response to antigenic stimuli seen in other diseases associated with immune activation, such as rheumatoid arthritis. An important aspect of its pathogenesis is the autonomous production of interleukin-6 (IL-6). In this disease, the clinical manifestations are associated to IL-6 serum levels, and surgical removal of the compromised lymph nodes or use of anti-IL-6 antibodies can slow down the symptoms. We describe a multicentric Castleman's disease in a young woman not associated to HHV-8 virus infection or immunosuppression. A short review of the literature follows the description of this clinical case.
25579431 Risk of infections of biological therapies with accent on inflammatory bowel disease. 2014 BACKGROUND: Biological therapies using anti-tumor necrosis factor (TNF)-α agents have an important impact in the treatment of inflammatory bowel disease, rheumatoid arthritis, psoriasis, and other inflammatory conditions. However, a significant number of patients lose their response to these medications over time. Clinical trials have demonstrated that antibodies against anti-TNF agents may impact treatment response and increase the risk of infusion reactions. Of concern is also the possibility of developing adverse events induced by anti-TNF agents. The purpose of the present systematic review is to describe the current knowledge on the risk of infections associated with anti-TNF agents antagonists, as well as integrin antagonists. We also intend to describe case reports of these adverse events in inflammatory bowel disease patients. METHODS: Currently approved anti-TNF biologicals in IBD include the monoclonal antibodies infliximab, adalimumab, certolizumab pegol and golimumab. Integrin antagonists include natalizumab, etrolizumab and vedolizumab. RESULTS: The most frequently-reported adverse events of these biologicals were infections, and these are described in detail in this study. DISCUSSION: Most adverse events are due to the failure of host immunological control, which involves de novo infection, or reactivation of latent bacterial or viral infection, often with a different expression of disease. CONCLUSION: Risk assessment in individuals undergoing treatment with biologicals represents a step towards achieving treatment personalization to identify those patients that will safely benefit from this therapeutic approach. Patients and physicians must be alert for anti-TNF agents and anti-integrin medication as potential causes of drug-induced infections and monitor the therapies. Personalizing therapeutic vigilance promises to optimize benefits while minimizing infections.
25575769 Risk factors for periprosthetic joint infection after total joint arthroplasty: a systemat 2015 Feb Many of the mooted risk factors associated with periprosthetic joint infection (PJI) after total joint arthroplasty (TJA) remain controversial and are not well characterized. Online and manual searches were performed using Medline, Embase, Chinese National Knowledge Infrastructure and the Cochrane Central Database from January 1980 to March 2014). For inclusion, studies had to meet the quality assessment criteria of the CONSORT statement, and be concerned with evaluation of risk factors for PJI after TJA. Two reviewers extracted the relevant data independently and any disagreements were resolved by consensus. Fourteen studies were included in this meta-analysis. The following significant risk factors for PJI were identified: body mass index (both continuous and dichotomous variables); diabetes mellitus; corticosteroid therapy; hypoalbuminaemia; history of rheumatoid arthritis; blood transfusion; presence of a wound drain; wound dehiscence; superficial surgical site infection; coagulopathy; malignancy, immunodepression; National Nosocomial Infections Surveillance Score ≥2; other nosocomial infection; prolonged operative time; and previous surgery. Factors that were not significantly associated with PJI were: cirrhosis; hypothyroidism; urinary tract infection; illicit drug abuse; alcohol abuse; hypercholesterolaemia; hypertension, ischaemic heart disease; peptic ulcer disease; hemiplegia or paraplegia; dementia; and operation performed by a staff surgeon (vs a trainee). Strategies to prevent PJI after TJA should focus, in particular, on those patients at greatest risk of infection according to their individual risk factors.
25483364 Inhibition of 5-lipoxygenase triggers apoptosis in pancreatic cancer cells. 2015 Feb The 5-lipoxygenase (5-LOX) pathway has been associated with a variety of inflammatory diseases including asthma, atherosclerosis, rheumatoid arthritis, cancer and liver fibrosis. Several classes of 5-LOX inhibitors have been identified, but only one drug, zileuton, a redox inhibitor of 5-LOX, has been approved for clinical use. In the present study, 5-LOX was found to be overexpressed not only in pancreatic cancer cell lines but also in tissue samples of patients suffering from pancreatic adenocarcinoma. There was a close correlation between the tumor expression levels of 5-LOX mRNA and protein and the clinicopathological patient characteristics including lymph node metastasis and TNM stage. Zileuton suppressed the proliferation of SW1990 cells in a concentration- and time‑dependent manner. In addition, zileuton induced SW1990 cells to undergo apoptosis and significantly decreased 5-LOX expression. The number of apoptotic cells, estimated by flow cytometry, Annexin V/PI assay, TUNEL staining and sub‑diploid population was significantly higher than that of the control. These results suggest that the level of 5-LOX expression was increased in pancreatic cancer tissues and may be related to lymph node metastasis and TNM stage.
25440383 Components and reporting of yoga interventions for musculoskeletal conditions: a systemati 2014 Oct OBJECTIVES: To identify the content and reporting details of randomised controlled trials of yoga for musculoskeletal conditions through a systematic review of the literature. DESIGN: Twenty electronic databases were searched to identify randomised controlled trials (RCTs) of yoga interventions for musculoskeletal conditions. Eligibility criteria were full-text, peer reviewed articles, of RCTs with yoga as a primary intervention, on a population aged 18 years and over, with a clinical diagnosis of a musculoskeletal condition. Data relating to study characteristics, yoga styles, yoga practices, home practice, and reporting were extracted and summarised. RESULTS: Seventeen articles met inclusion criteria, representing five musculoskeletal conditions: low back pain, osteoarthritis, rheumatoid arthritis, kyphosis, and fibromyalgia. 15 studies were non-residential, and two were residential. Study duration ranged from 1 to 24 weeks; weekly dosage of yoga ranged from 1 to 56h. Five styles of posture-based Hatha yoga were specified. Intervention content included seven yoga practises: postures, breathing, relaxation, meditation, philosophy, chanting, and cleansing practises. Ten studies either encouraged or requested home practice. Reporting details included class plans, posture lists, and diagrams. Due to insufficient detail regarding delivery of the yoga intervention only eight of the 17 interventions were considered replicable as reported. CONCLUSIONS: Evaluation of study characteristics and yoga components indicated several areas of homogeneity across studies, suggesting an existing degree of standardisation. However, heterogeneity related to intervention content and reporting impeded determination of intervention content and delivery. Standardisation of content, nomenclature, and reporting details is recommended to enhance protocol transparency, replication, and comparison of intervention effectiveness.
25398491 Role of IL-17 and IL-22 in autoimmunity and cancer. 2014 Oct The dysregulation of inflammatory cytokines can cause a variety of diseases, such as autoimmunity and cancer. Since their identification in 2005, Th17 cells and its signature cytokine IL-17, have been implicated in the pathogenesis of autoimmune diseases such as psoriasis and rheumatoid arthritis (RA), and inflammatory associated cancers such as colorectal carcinoma (CRC). Recently, IL-22 a Th17 related cytokine has been shown to be pathogenic in psoriasis and RA. In this review, we will summarize the biological functions of IL-17 and IL-22, their role in autoimmune diseases and briefly review results from clinical trials targeting IL-17 or its receptor for the treatment of autoimmune diseases. Next, we will discuss pre-clinical and clinical data supporting the rationale of targeting other cytokines implicated in the Th17/IL-17 pathway, such as IL-22 and IL-23. Finally, we discuss the role of IL-17, and in particularly IL-22 in tumour immunity and possible therapeutic interventions.
25294623 Establishment of a quantitative PCR system for discriminating chitinase-like proteins: cat 2014 Oct 8 BACKGROUND: Mice and humans produce chitinase-like proteins (CLPs), which are highly homologous to chitinases but lack chitinolytic activity. Mice express primarily three CLPs, including breast regression protein-39 (BRP-39) [chitinase 3-like-1 (Chi3l1) or 38-kDa glycoprotein (gp38k)], Ym1 (Chi3l3) and Ym2 (Chi3l4). Recently, CLPs have attracted considerable attention due to their increased expression in a number of pathological conditions, including asthma, allergies, rheumatoid arthritis and malignant tumors. Although the exact functions of CLPs are largely unknown, the significance of their increased expression levels during pathophysiological states needs to be determined. The quantification of BRP-39, Ym1 and Ym2 is an important step in gaining insight into the in vivo regulation of the CLPs. METHODS: We constructed a standard DNA for quantitative real-time PCR (qPCR) by containing three CLPs target fragments and five reference genes cDNA in a one-to-one ratio. We evaluated this system by analyzing the eight target cDNA sequences. Tissue cDNAs obtained by reverse transcription from total RNA from four embryonic stages and eight adult tissues were analyzed using the qPCR system with the standard DNA. RESULTS: We established a qPCR system detecting CLPs and comparing their expression levels with those of five reference genes using the same scale in mouse tissues. We found that BRP-39 and Ym1 were abundant in the mouse lung, whereas Ym2 mRNA was abundant in the stomach, followed by lung. The expression levels of BRP-39 and Ym1 in the mouse lung were higher than those of two active chitinases and were comparable to glyceraldehyde-3-phosphate dehydrogenase, a housekeeping gene which is constitutively expressed in all tissues. CONCLUSION: Our results indicate that catalytically inactive BRP-39 and Ym1 are constitutive genes in normal mouse lung.
25260368 Interpreting trial results following use of different intention-to-treat approaches for pr 2014 Sep 26 INTRODUCTION: When participants drop out of randomised clinical trials, as frequently happens, the intention-to-treat (ITT) principle does not apply, potentially leading to attrition bias. Data lost from patient dropout/lack of follow-up are statistically addressed by imputing, a procedure prone to bias. Deviations from the original definition of ITT are referred to as modified intention-to-treat (mITT). As yet, the impact of the potential bias associated with mITT has not been assessed. Our objective is to investigate potential bias and disadvantages of performing mITT and evaluate possible concerns when executing different mITT approaches in meta-analyses. METHODS AND ANALYSIS: Using meta-epidemiology on randomised trials considered less prone to bias (ie, good internal validity) and assessing biological or targeted agents in patients with rheumatoid arthritis, we will meta-analyse data from 10 biological and targeted drugs based on collections of trials that would correspond to 10 individual meta-analyses. ETHICS AND DISSEMINATION: This study will enhance transparency for evaluating mITT treatment effects described in meta-analyses. The intended audience will include healthcare researchers, policymakers and clinicians. Results of the study will be disseminated by peer-review publication. PROTOCOL REGISTRATION: In PROSPERO CRD42013006702, 11. December 2013.
25180614 CCAAT/enhancer binding protein α (C/EBPα)(+) M2 macrophages contribute to fibrosis in Ig 2015 May IgG4-related disease (IgG4-RD) is a new disease entity characterized by type 2 helper T (Th2)-dominant inflammation and progressive fibrosis. We found the infiltration of strange cell populations in the fibrotic lesions of submandibular gland specimens obtained from 15 patients with IgG4-RD. These cells expressed CCAAT/enhancer binding protein a (C/EBPα). Many of the cell populations were identified with M2 macrophages. The degrees of infiltration of C/EBPα(+)M2 macrophages and the ratio of fibrotic lesions in the specimens were correlated (r(2) = 0.83, p < 0.01). We also analyzed the expression of C/EBPα in other chronic inflammatory disorders: synovium in rheumatoid arthritis (RA), liver tissue in chronic viral hepatitis, and mucosa in ulcerative colitis. The specimens from RA and chronic viral hepatitis showed infiltration of C/EBPα(+) cells, but there were few C/EBPα-positive cells in ulcerative colitis. Fibrosis is not a major issue in ulcerative colitis. In conclusion, we found the remarkable infiltration of C/EBPα(+)M2 macrophages in cases of chronic inflammation with fibrosis, including IgG4-RD. This primitive study also disclosed that most of C/EBPα(+)M2 macrophages localized in fibrotic lesions, and the degree of the infiltration and the ratio of fibrotic area were correlated.
25098219 [Tumor necrosis factor alpha (TNF-α) in autoimmune diseases (AIDs): molecular biology and 2014 Jul It has been estimated that autoimmune diseases (AIDs) affect 5-8% of the US population. AIDs are a serious public health problem worldwide. These diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. AIDs cause various clinical consequences ranging from mild to severe, affecting one or more target organs and repeatedly causing the patient's death. Five of the most common AIDs are rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Graves´ disease (GD), insulin-dependent diabetes mellitus or type I (T1DM), and multiple sclerosis (MS). The TNF-α gene and its protein product, the cytokine TNF-α, play an important role in the pathogenesis of EAs. The anti-TNF-α therapies using monoclonal antibodies directed against TNF-α have shown good results in diseases such as RA, JRA, but not in other EA such as SLE and MS. This review focuses on presenting to the reader the biological role of TNF-α under normal conditions and the initiation, development, susceptibility, severity, and treatment response of the most common AIDs.
24909318 Effects of laser treatment on the expression of cytosolic proteins in the synovium of pati 2014 Oct BACKGROUND AND OBJECTIVE: Low level laser therapy (LLLT) has been developed for non-invasive treatment of joint diseases. We have previously shown that LLLT influenced synovial protein expression in rheumatoid arthritis (RA). The aim of this study was to assess the effects of laser irradiation on osteoarthritic (OA) synovial protein expression. STUDY DESIGN/MATERIALS AND METHODS: The synovial membrane samples removed from the knees of 6 OA patients were irradiated ex vivo using near infrared diode laser (807-811 nm; 25 J/cm(2) ). An untreated sample taken from the same patient served as control. Synovial protein separation and identification were performed by two-dimensional differential gel electrophoresis and mass spectrometry, respectively. RESULTS: Eleven proteins showing altered expression due to laser irradiation were identified. There were three patients whose tissue samples demonstrated a significant increase (P < 0.05) in mitochondrial heat shock 60 kD protein 1 variant 1. The expression of the other proteins (calpain small subunit 1, tubulin alpha-1C and beta 2, vimentin variant 3, annexin A1, annexin A5, cofilin 1, transgelin, and collagen type VI alpha 2 chain precursor) significantly decreased (P < 0.05) compared to the control samples. CONCLUSIONS: A single diode laser irradiation of the synovial samples of patients with osteoarthritis can statistically significantly alter the expression of some proteins in vitro. These findings provide some more evidence for biological efficacy of LLLT treatment, used for osteoarthritis.
24655039 E-pharmacophore and molecular dynamics study of flavonols and dihydroflavonols as inhibito 2014 DiHydroOrotate DeHydrogenase [huDHODH] is a therapeutic target for Rheumatoid arthritis [RA]. Leflunomide [A771726] is a widely used synthetic inhibitor against huDHODH. We to find more efficient lead like compounds. A four featured E-Pharmacophore A1D4H6R7 was built based on the inhibitor A771726. This pharmacophore was validated by checking its ability to identify known highly active inhibitors of huDHODH and assigning higher fitness scores to them. A reverse validation was also performed where random 4 featured pharmacophores were built and its efficiency in identifying actives was compared with our E-Pharmacophore. Our Epharmacophore was very efficient, since it passed both validations by picking the known active molecules with high fitness scores. This validated E- pharmacophore was searched against the KEGG phytochemicals subset database. This search resulted in 18 molecules which were subjected to docking with huDHODH. The molecules with docking score greater than that of A771726 were selected. The docking results were further validated using MM/GBSA which gave similar ranking with high binding free energy values. The four molecules 6-Methoxytaxifolin, Rhamnetin, Rhamnazin and Pinoquercetin were taken for explicit 3ns simulation and it was observed that all four molecules had acceptable RMSD values and stable interactions. Thus our study, suggests four phytomolecules that might inhibit huDHODH more efficiently than A771726. Interestingly, some of the obtained hits have already been proven in vitro anti-inflammatory activity which confirms that, the developed E-pharmacophore can be used to identify novel small molecules against inflammatory target, huDHODH.
24479644 Living with the unexplained: coping, distress, and depression among women with chronic fat 2014 Chronic fatigue syndrome (CFS) and fibromyalgia are disabling conditions without objective diagnostic tests, clear-cut treatments, or established etiologies. Those with the disorders are viewed suspiciously, and claims of malingering are common, thus promoting further distress. It was hypothesized in the current study that levels of unsupportive social interactions and the coping styles used among those with CFS/fibromyalgia would be associated with perceived distress and depressive symptoms. Women with CFS/fibromyalgia (n=39), in fact, reported higher depression scores, greater perceived distress and more frequent unsupportive relationships than healthy women (n=55), whereas those with a chronic, but medically accepted illness comprising an autoimmune disorder (lupus erythematosus, multiple sclerosis, rheumatoid arthritis; n=28), displayed intermediate scores. High problem-focused coping was associated with low levels of depression and perceived distress in those with an autoimmune condition. In contrast, although CFS/fibromyalgia was also accompanied by higher depression scores and higher perceived distress, this occurred irrespective of problem-focused coping. It is suggested that because the veracity of ambiguous illnesses is often questioned, this might represent a potent stressor in women with such illnesses, and even coping methods typically thought to be useful in other conditions, are not associated with diminished distress among those with CFS/fibromyalgia.
24450503 Liposome bupivacaine for postsurgical pain in an obese woman with chronic pain undergoing 2014 Jan 22 INTRODUCTION: To reduce incidence and severity of postsurgical pain and minimize the effect of its clinical and economic correlates, multimodal therapy for surgical patients is recommended. In this report, we discuss the use of liposome bupivacaine, a novel multivesicular formulation of bupivacaine indicated for single-dose infiltration into the surgical site to produce postsurgical analgesia, as part of a multimodal analgesic regimen in a patient with a history of chronic pain scheduled to undergo laparoscopic sleeve gastrectomy. To the best of our knowledge, this is the first published report of liposome bupivacaine in the setting of laparoscopic sleeve gastrectomy. CASE PRESENTATION: A 35-year-old white woman with morbid obesity was admitted for laparoscopic sleeve gastrectomy to lose weight prior to hip replacement surgery. Because of a complicated medical history that included rheumatoid arthritis, fibromyalgia, diabetes mellitus, hypertension, and chronic pain, for which she was receiving high doses of opioid analgesics, postsurgical pain management was a concern and she was considered a candidate for multimodal analgesia. At initiation of surgery, 50mL of lidocaine and epinephrine was infiltrated around the port sites. At the conclusion, 25mL of normal sterile saline was added to a 20mL vial of liposome bupivacaine (266mg) and injected around the port sites and at the site of liver retraction. Laparoscopic sleeve gastrectomy was successfully completed. Our patient was discharged to the postanesthesia care unit for approximately four hours before discharge to the surgical floor with a pain score of 5 (11-point scale; 0 = no pain, 10 = worst possible pain). Her postoperative course was uneventful; no adverse events were recorded during surgery or during the remainder of her hospital stay. Our patient was discharged on the same opioid regimen used previously for control of her preexisting chronic pain. CONCLUSIONS: Liposome bupivacaine use in this morbidly obese patient undergoing laparoscopic sleeve gastrectomy provided analgesic efficacy and limited postsurgical opioids to a level comparable with her baseline opioid regimen for chronic pain. Given her complex medical history and previous issues with acute and chronic pain, we consider these results highly successful and continue to use liposome bupivacaine as part of a multimodal analgesic regimen in an effort to optimize postsurgical pain management.
24440854 Stabilized Interleukin-6 receptor binding RNA aptamers. 2014 Interleukin-6 (IL-6) is a multifunctional cytokine that is involved in the progression of various inflammatory diseases, such as rheumatoid arthritis and certain cancers; for example, multiple myeloma or hepatocellular carcinoma. To interfere with IL-6-dependent diseases, targeting IL-6 receptor (IL-6R)-presenting tumor cells using aptamers might be a valuable strategy to broaden established IL-6- or IL-6R-directed treatment regimens. Recently, we reported on the in vitro selection of RNA aptamers binding to the human IL-6 receptor (IL-6R) with nanomolar affinity. One aptamer, namely AIR-3A, was 19 nt in size and able to deliver bulky cargos into IL-6R-presenting cells. As AIR-3A is a natural RNA molecule, its use for in vivo applications might be limited due to its susceptibility to ubiquitous ribonucleases. Aiming at more robust RNA aptamers targeting IL-6R, we now report on the generation of stabilized RNA aptamers for potential in vivo applications. The new 2'-F-modified RNA aptamers bind to IL-6R via its extracellular portion with low nanomolar affinity comparable to the previously identified unmodified counterpart. Aptamers do not interfere with the IL-6 receptor complex formation. The work described here represents one further step to potentially apply stabilized IL-6R-binding RNA aptamers in IL-6R-connected diseases, like multiple myeloma and hepatocellular carcinoma.
24389211 The role of PGRN in musculoskeletal development and disease. 2014 Jan 1 Progranulin (PGRN) is a growth factor that has been implicated in wound healing, inflammation, infection, tumorigenesis, and is most known for its neuroprotective and proliferative properties in neurodegenerative disease. This pleiotropic growth factor has been found to be a key player and regulator of a diverse spectrum of multi-systemic functions. Its critical anti-inflammatory role in rheumatoid arthritis and other inflammatory disease models has allowed for the propulsion of research to establish its significance in musculoskeletal diseases, including inflammatory conditions involving bone and cartilage pathology. In this review, we aim to elaborate on the emerging role of PGRN in the musculoskeletal system, reviewing its particular mechanisms described in various musculoskeletal diseases, with special focus on osteoarthritis and inflammatory joint disease patho-mechanisms and potential therapeutic applications of PGRN and its derivatives in these and other musculoskeletal diseases.
24375868 Proliferation rate of stem cells derived from human dental pulp and identification of diff 2014 May Stem cells from human exfoliated deciduous teeth (SHED) and dental pulp stem cells (DPSCs) obtained from the dental pulp of human extracted tooth were cultured and characterized to confirm that these were mesenchymal stem cells. The proliferation rate was assessed using AlamarBlue® cell assay. The differentially expressed genes in SHED and DPSCs were identified using the GeneFishing™ technique. The proliferation rate of SHED (P < 0.05) was significantly higher than DPSCs while SHED had a lower multiplication rate and shorter population doubling time (0.01429, 60.57 h) than DPSCs (0.00286, 472.43 h). Two bands were highly expressed in SHED and three bands in DPSCs. Sequencing analysis showed these to be TIMP metallopeptidase inhibitor 1 (TIMP1), and ribosomal protein s8, (RPS8) in SHED and collagen, type I, alpha 1, (COL1A1), follistatin-like 1 (FSTL1), lectin, galactoside-binding, soluble, 1, (LGALS1) in DPSCs. TIMP1 is involved in degradation of the extracellular matrix, cell proliferation and anti-apoptotic function and RPS8 is involved as a rate-limiting factor in translational regulation; COL1A1 is involved in the resistance and elasticity of the tissues; FSTL1 is an autoantigen associated with rheumatoid arthritis; LGALS1 is involved in cell growth, differentiation, adhesion, RNA processing, apoptosis and malignant transformation. This, along with further protein expression analysis, holds promise in tissue engineering and regenerative medicine.
24346838 A retrospective comparison of cost and efficiency of the medial double and dual incision t 2014 Feb While the medial double arthrodesis has gained significant popularity for hindfoot arthrodesis in recent years, much has been touted about the efficiency and cost savings of the procedure in comparison to its triple counterpart without any literature to reinforce this claim. The purpose of this retrospective study was to compare the hardware costs and operative time between the medial double and triple arthrodeses. A total of 276 patients (277 feet) were identified via CPT codes with 47 hindfoot cases (47 feet) meeting the inclusion criteria consisting of 21 medial double (6 males, 15 females) and 26 triple (8 males, 18 females) arthrodeses. No significant difference was noted in age, body mass index, gender, chronic steroid use, preoperative osteopenia/osteoporosis, tobacco abuse, surgical side, presence of diabetes, immune compromised state, kidney disease, rheumatoid arthritis, or liver disease. Mean medial double operative (OR) time 106 ± 31 minutes (range = 73-201 minutes) with a procedure time of 84 ± 29 minutes (range = 44-163 minutes) was identified versus an OR time of 127 ± 23 minutes (range = 91-200 minutes) and procedure time of 104 ± 23 minutes (range = 50-169 minutes) for the triple arthrodesis group. The mean fixation cost for the triple arthrodesis was found to be higher with the mean triple hardware cost $2932.75 ± $736.60 (range = $1434.00 to $3980.00) against the medial double's $1197.59 ± $635.57 (range = $463.20 to $2019.00). Both efficiency and cost were found to favor the medial double for hindfoot arthrodesis at a level of statistical significance level (P = .0028 for OR time, P = .0033 for procedure time, and P < .0001 for cost).
24328571 Radical acylation of L-lysine derivatives and L-lysine-containing peptides by peroxynitrit 2014 Mar Highly electrophilic α-dicarbonyls such as diacetyl, methylglyoxal, 3-deoxyglucosone, and4,5-dioxovaleric acid have been characterized as secondary catabolites that can aggregate proteins and form DNA nucleobase adducts in several human maladies, including Alzheimer's disease, rheumatoid arthritis, diabetes, sepsis, renal failure, and respiratory distress syndrome. In vitro, diacetyl and methylglyoxal have also been shown to rapidly add up the peroxynitrite anion (k2 ~ 10(4)-10(5) M(-1) s(-1)), a potent biological nucleophile, oxidant and nitrosating agent, followed by carbon chain cleavage to carboxylic acids via acetyl radical intermediate that can modify amino acids. In this study, we used the amino acid derivatives Ac-Lys-OMe and Z-Lys-OMe and synthesized the tetrapeptides H-KALA-OH, Ac-KALA-OH, and H-K(Boc)ALA-OH to reveal the preferential Lys amino group targeted by acyl radical generated by the α-dicarbonyl/peroxynitrite system. The pH profiles of the reactions are bell-shaped, peaking at approximately 7.5; hence, they are close to the pKa values of ONOOH and of the catalytic H2PO4(-) anion. RP-HPLC and ESI-MS analyses of reaction products confirmed (α)N- and (ϵ)N-acetylation of Lys by diacetyl as well as acetylation and formylation by methylglyoxal, with preference for the α-amino group. These data suggest the possibility of radical acylation of proteins in epigenetic processes, where enzymatic acetylation of these biomolecules is a well-documented event, recently reported to be as critical to the cell cycle as phosphorylation. Also noteworthy is the observed formylation of L-Lys containing peptides by methylglyoxal never reported to occur in amino acid residues of peptides and proteins.