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ID PMID Title PublicationDate abstract
24939591 Production of anti TNF-α antibodies in eukaryotic cells using different combinations of v 2015 Oct Tumor necrosis factor-α (TNF-α) plays a key role in rheumatoid arthritis and some other autoimmune diseases. Therapy with anti-TNF-α recombinant antibodies (Ab) appears to be highly effective. Production of new hyper-producing eukaryotic cell lines can decrease the treatment cost, which currently is very high. However, due to the complexity of protein transcription, translation, processing, and secretion in mammalian cells, the stages at which antibody expression is affected are still poorly determined. The aim of this work was to compare the productivity of two cell lines developed in CHO DG44 cells, deficient in dihydrofolate reductase, transfected with vectors carrying either heavy (H) or light (L) chains of chimeric antibody under different combinations of selective elements. Both H and L chains were cloned either in pOptiVEC or pcDNA3.3 vectors and different combinations were used to produce HL and LH cell lines. We have shown that Ab production has been low and comparable between HL and LH cells until selection on methotrexate (MTX) when LH but not HL cells have responded with 3.5 times increased productivity. Flow cytometry analysis has demonstrated that intracellular concentration of full size Abs in LH cells was 5.6 times higher than in HL ones due to higher amount of H chain synthesis. No differences in viability between HL and LH cells have been found. We have concluded that the expression of H chain in the pOptiVEC vector, which is responsible for MTX resistance, has led to the suppression of H chain synthesis and limitation in full Ab assembly.
24899377 Inhibition of human pyridoxal kinase by 2-acetyl-4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)i 2015 Apr 2-Acetyl-4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)imidazole (THI) is observed as a minor contaminant in caramel food colourings (E 150c). Feeding experiments with rodents have revealed a significant lymphopenic effect that has been linked to the presence of THI in these food colourings. Pyridoxal kinase inhibition by THI has been suggested, but not demonstrated, as a mode of action as it leads to lowered levels of pyridoxal-5'-phosphate, which are known to cause lymphopenia. Recently, THI was also shown to inhibit sphingosine-1-phosphate lyase causing comparable immunosuppressive effects and derivatives of THI are being developed for the treatment of rheumatoid arthritis in humans. Interestingly, sphingosine-1-phosphate lyase activity depends on pyridoxal-5'-phosphate, which in turn is provided by pyridoxal kinase. This report shows that THI does inhibit pyridoxal kinase with competitive and mixed-type non-competitive behaviour towards its two substrates, pyridoxal and ATP, respectively. The corresponding inhibition constants are in the low millimolar range.
24633464 Absolute bioavailability and metabolism of aceclofenac in rats. 2015 Jan Aceclofenac is one of the most popular analgesic and anti-inflammatory drugs used for the relief of pain, rheumatoid arthritis, and osteoarthritis. To date, no intravenous preparation of aceclofenac has been developed because of its poor water solubility. In this study, to investigate its absolute bioavailability and metabolism in rats, aceclofenac was dissolved in a sterile aqueous solution containing urea (20 %) and trisodium citrate (10 %), and administered via oral (20 mg/kg) and intravenous (10 mg/kg) routes. Blood samples were taken serially, and aceclofenac and its three major metabolites (4'-hydroxydiclofenac, 4'-hydroxyaceclofenac, and diclofenac) were measured by HPLC-MS/MS. The absolute oral bioavailability of aceclofenac was approximately 15 %. Diclofenac and 4'-hydroxydiclofenac were the main metabolites in rats, in contrast to 4'-hydroxyaceclofenac in humans. The low bioavailability of aceclofenac is likely due to extensive metabolism, and bioavailability may be even lower if the drug were administered as a tablet, considering its low water solubility. This study provides complete time profiles of the plasma concentrations of aceclofenac and its metabolites in rats and highlights the difference in drug metabolism between rats and humans.
27829170 Encapsulation of NSAIDs for inflammation management: Overview, progress, challenges and pr 2016 Dec 30 Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed drugs. Debilitating diseases such as rheumatoid arthritis and osteoarthritis are commonly managed by NSAIDs. However, NSAIDs pharmacological mechanism is often associated with the presence of gastrointestinal side effects. NSAIDs encapsulation is performed in order to overcome some of the drawbacks linked to their clinical use. To fulfill this purpose, various vectors like polymer-based nanoparticles, liposomes and solid lipid nanoparticles have been proposed. Such vehicles could have advantages but some limitations as well. This manuscript highlights current NSAIDs encapsulation approaches based on either preformed polymers or lipids. Moreover, properties of the prepared carriers and their applications are also discussed. Many factors are taken into account for selecting carrier type and encapsulation method. It was concluded that different vehicles and preparation methods have been employed for NSAIDs encapsulation. Mostly, vehicles sizes ranged within the nanoscale. Main advantages that have been confirmed by in vitro and in vivo studies include promoted stability, sustained release and bioavailability enhancement.
27761055 Life Stress and Health: A Review of Conceptual Issues and Recent Findings. 2016 Oct Life stress is a central construct in many models of human health and disease. The present article reviews research on stress and health, with a focus on (a) how life stress has been conceptualized and measured over time, (b) recent evidence linking stress and disease, and (c) mechanisms that might underlie these effects. Emerging from this body of work is evidence that stress is involved in the development, maintenance, or exacerbation of several mental and physical health conditions, including asthma, rheumatoid arthritis, anxiety disorders, depression, cardiovascular disease, chronic pain, human immunodeficiency virus/AIDS, stroke, and certain types of cancer. Stress has also been implicated in accelerated biological aging and premature mortality. These effects have been studied most commonly using self-report checklist measures of life stress exposure, although interview-based approaches provide a more comprehensive assessment of individuals' exposure to stress. Most recently, online systems like the Stress and Adversity Inventory (STRAIN) have been developed for assessing lifetime stress exposure, and such systems may provide important new information to help advance our understanding of how stressors occurring over the life course get embedded in the brain and body to affect lifespan health.
27698786 Involvement of macrophage migration inhibitory factor in cancer and novel therapeutic targ 2016 Oct Macrophage migration inhibitory factor (MIF) was originally identified in 1966 by Bloom and Bennett as a pro-inflammatory cytokine involved in the inhibition of macrophage motility. Since then, studies have investigated the functional contribution of this pro-inflammatory cytokine in several immune diseases, including rheumatoid arthritis and lupus erythematous. Recently, MIF has been reported to be involved in a variety of neoplastic diseases. The present review discusses previous cancer research studies that have investigated the involvement of MIF in carcinogenesis, disease prognosis, tumor cell proliferation and invasion, and tumor-induced angiogenesis. Finally, potential therapeutic approaches based on the use of MIF antagonists and neutralizing antibodies are examined. The review concludes that MIF could be a good prognostic biomarker in several types of cancer, but also that the inhibition of MIF could represent a novel therapy against cancer.
27663827 Treatment of Depression in patients with Osteoarthritis: the importance of an early diagno 2016 Sep BACKGROUND: Osteoarthritis (OA) also called degenerative joint disease is the most common chronic condition of the joints that just in 2004, caused moderate to severe disability in 43.4 million of people. OA in Western populations is one of the most frequent causes of joint pain, loss of function and disability in adults. In the U.S. it is the second most common cause of work disability in men over 50 years of age, following ischaemic heart disease, and accounts for a higher number of hospitalizations when compared with rheumatoid arthritis (RA) each year. This condition is associated with chronic pain (which can be severe in many cases) and long term inflammatory processes which all together represent conditions that are known to be associated with depression. Depression is among the most burdensome disorders worldwide having affected just in 2010 15.4 million adults worldwide. Depression is associated with increase of symptom burden, greater level of functional impairment and increased risk of both disease complications and mortality. With this research we wished to put in evidence the importance of an early diagnosis of Depression in patients with osteoarthritis by using PHQ9 and suggest Duloxetine as an antidepressant that can be helpful in the management of not only pain but also depression in OA patients. METHODS: Our study is a literature based research. CONCLUSION: Early Diagnosis of depression of patients with osteoarthritis appears to be crucial for improving the outcomes of patients with OA and that can be easily and efficiently done with PHQ9. Duloxetine presents itself as an ally in the fight against the evolution of depression in patients with OA and should be considered even in mild to moderate states of depression.
27569557 Osteonecrosis of the Jaw in the Absence of Antiresorptive or Antiangiogenic Exposure: A Se 2017 Jan PURPOSE: Medication-related osteonecrosis of the jaws (MRONJ) is a well-described complication of antiresorptive and antiangiogenic medications. Although osteonecrosis can be associated with other inciting events and medications, such as trauma, infection, steroids, chemotherapy, and coagulation disorders, these are rarely reported in the literature. MATERIALS AND METHODS: This is a six case series of MRONJ associated with medications other than antiresorptive or antiangiogenic drugs. RESULTS: Patient demographics, inciting event, location, stage, imaging findings, and outcome are reported. CONCLUSION: With the continued development and clinical use of new biologic medications for diseases such as cancer and rheumatoid arthritis, it is important to continue to evaluate their effects on the oral cavity. The degree of risk for osteonecrosis in patients taking these new classes of drugs is uncertain but warrants awareness and monitoring.
27511498 Serological prevalence of human parvovirus B19 in diseases or disordersrelated to differen 2016 Feb 17 BACKGROUND/AIM: Human parvovirus B19 is a pathogen that affects different parts of the body. We planned this study because of the lack of data on B19 seroprevalence based on different body-system diseases. MATERIALS AND METHODS: The prevalence of parvovirus B19 antibodies was investigated retrospectively in 1239 patients by review of medical records from 2009-2012, according to their diseases classified under general titles in compliance with the International Classification of Diseases (ICD-10). Parvovirus B19-specific antibodies were detected by quantitative enzyme immunoassays. RESULTS: The positivity rate was 27.8% for only IgG, 8.5% for only IgM, and 2.6% for both IgG and IgM. The highest positivity for IgG alone was found in musculoskeletal system and connective tissue diseases (55.9%), while the highest positivity for IgM was found in neoplasms (16.4%). The highest positivity for IgG was seen in rheumatoid arthritis (72.2%) and pregnancy (52.6%), and the highest positivity for total IgM was found in upper respiratory tract disease (21.0%) and hepatic failure (17.1%). CONCLUSION: Parvovirus B19 seroprevalence was relatively low in northeastern Anatolia compared to most serological studies conducted in other regions. We think that this study has provided the first wide-ranging information on the seroprevalence of B19 in diseases and disorders of the major human body systems.
27403120 Duodenal Adenocarcinoma Diagnosed from a Biopsy Specimen of a Depressed Lesion Obtained by 2016 Jan Biopsies are necessary for the management of duodenal tumors. However, the most suitable targets for biopsy are not known. An 82-year-old woman who regularly visited our hospital for rheumatoid arthritis underwent abdominal ultrasonography. This screening revealed a dilated pancreatic duct. Magnetic resonance cholangiopancreatography was performed, and dilatation of the pancreatic duct was confirmed. The patient underwent duodenoscopy to investigate the possibility of obstruction of the papilla of Vater. The examination revealed an elevated lesion around the papilla of Vater. Endoscopic ultrasonography and a 20-MHz mini-probe were used to investigate the depth of the invasion. The common bile and pancreatic ducts were intact. The mucosal and submucosal borders were indistinct; however, the border between the submucosa and muscularis propria was clear, suggesting that the muscularis propria was intact. Magnifying endoscopy was used to examine the surface of the elevated lesion, which revealed a depressed lesion. A biopsy specimen of the depressed lesion was taken, and the tumor was diagnosed as an adenocarcinoma. Another biopsy specimen from a non-depressed lesion was diagnosed as an adenoma. The patient was diagnosed with duodenal adenocarcinoma, and was recommended surgery. She declined surgery and was followed up for 34 months. Because it is possible for depressed lesions of duodenal tumors to be adenocarcinomas, biopsy specimens should be obtained from depressed lesions of duodenal tumors.
27082957 Usefulness of Cyclophosphamide Pulse Therapy in Interstitial Lung Diseases. 2016 BACKGROUND: Interstitial lung diseases (ILDs) are a group of disorders characterised by progressive lung function decline. Stabilisation of lung function under intermittent i.v. cyclophosphamide was shown in patients suffering from systemic sclerosis, yet data in ILD patients are scarce. OBJECTIVES: To retrospectively evaluate the usefulness of cyclophosphamide pulse therapy in ILD. METHODS: We retrospectively analysed all patients who received i.v. cyclophosphamide in our centre from 2002 to 2012. Lung function, survival status, and bronchoalveolar lavage cytology were recorded during a follow-up period of 18 months. RESULTS: Twenty-six patients with idiopathic pulmonary fibrosis, 6 with lymphocytic interstitial pneumonia (LIP), 8 with idiopathic non-specific interstitial pneumonia (NSIP), 7 with rheumatoid arthritis-associated ILD, and 7 with perinuclear anti-neutrophil cytoplasmic antibody-positive ILD (pANCA+ ILD) were included. Patients with LIP and NSIP had the best survival outcome, those with pANCA+ ILD the worst. In the total cohort, we found a significantly higher total lung capacity decline in the year before treatment compared to the year after treatment. CONCLUSIONS: This retrospective analysis of cyclophosphamide treatment shows a stabilisation of lung function in most patients with fibrotic ILDs, yet prospective studies in clearly defined diagnoses are urgently needed.
27048482 Microbial inhibitors of cysteine proteases. 2016 Aug Cysteine proteases are one of the major classes of proteolytic enzymes involved in a number of physiological and pathological processes in plants, animals and microorganisms. When their synthesis, activity and localization in mammalian cells are altered, they may contribute to the development of many diseases, including rheumatoid arthritis, osteoporosis and cancer. Therefore, cysteine proteases have become promising drug targets for the medical treatment of these disorders. Inhibitors of cysteine proteases are also produced by almost every group of living organisms, being responsible for the control of intracellular proteolytic activity. Microorganisms synthesize cysteine protease inhibitors not only to regulate the activity of endogenous, often virulent enzymes, but also to hinder the host's proteolytic defense system and evade its immune responses against infections. Present work describes known to date microbial inhibitors of cysteine proteases in terms of their structure, enzyme binding mechanism, specificity and pathophysiological roles. The overview of both proteinaceous and small-molecule inhibitors produced by all groups of microorganisms (bacteria, archaea, fungi, protists) and viruses is provided. Subsequently, possible applications of microbial inhibitors in science, medicine and biotechnology are also highlighted.
27004932 Three cases of anti-TNF induced myositis and literature review. 2016 Mar 6 Anti-tumor necrosis factor (anti-TNF) drugs are frequently preferred in the treatment of rheumatologic diseases and other inflammatory diseases. The development of myositis after using anti-TNF is a rare clinical condition. Here we aimed to report cases who developed myositis after using anti-TNF and review the current literature. We report two cases of rheumatoid arthritis (RA) and a case of ankylosing spondylitis (AS) developed idiopathic inflammatory myopathy following anti-TNF therapy. In conclusion, myositis could develop during anti-TNF therapy, so these patients should be evaluated carefully initially for myositis and should be closely monitored due to the potential for developing myositis in treatment process.
26992955 Atypical femoral fracture in a 51-year-old woman: Revealing a hypophosphatasia. 2016 May We report a 51-year old woman who suffered 2 atypical subtrochanteric femoral fractures (AFFs). She had a history of several metatarsal fractures. She had a normal bone densitometry. An adult form of hypophosphatasia (HPP) was diagnosed from low serum alkaline phosphatase (ALP), and tissue nonspecific isoenzyme of ALP (TNSALP) mutation analysis revealing 2 heterozygous mutations: c.299C>T (p. T100M) and c.571G>A (p. E191K). Low ALP is the hallmark of the diagnosis of HPP; which is associated in adults with premature loss of deciduous teeth, recurrent metatarsal stress fractures, and joints and tendons disorders. The incidence of AFFs in the population is 5.9 per 100,000 person-years. Physicians and patients with bone fragility must pay attention to prodromal pain, which require urgent radiographic evaluation of both femurs. Rheumatoid arthritis, use of glucocorticoids, and proton pump inhibitors have been associated with an excess risk of AFFs. Healthy subjects carrying a TNSALP mutation with low ALP value may be exposed to develop AFF spontaneously or while receiving potent anti-resorptive drugs. Low ALP must be checked as a cause of bone fragility.
26935519 [Abdominal obesity mediates the association between a low physical activity and a decline 2016 AIM: A low physical activity leads to obesity and a decline in the physical function. The aim of this cross-sectional study was to examine whether the association between a low physical activity and low physical function was mediated by obesity. METHODS: A total of 73 community-dwelling elderly people participated in this study. The analysis included 56 participants without knee and hip osteoarthritis, low cognitive function (the Mini Mental State Examination score <24) and rheumatoid arthritis (mean age±SD: 73.3±4.1, female: 50%). The daily step count was collected as a measure of physical activity by a single axial accelerometer. The physical function was measured by the gait speed. Obesity was measured by the body mass index and waist circumference. To assess whether the association between the physical activity and physical function was mediated by obesity, linear regression models were fitted according to Baron and Kenny procedures for a mediation analysis. A p value <0.05 was considered to be statistically significant. RESULTS: The body mass index did not act as a mediator in the association between the physical activity and gait speed, whereas the waist circumference acted as a full mediator in the association between the physical activity and gait speed. CONCLUSION: An increased waist circumference mediates the association between a low physical activity and a low physical function in community-dwelling elderly people.
26757391 Effect of Circadian Rhythm on Clinical and Pathophysiological Conditions and Inflammation. 2015 Circadian rhythms have long been known to regulate numerous physiological processes that vary across the diurnal cycle. The circadian clock system also controls various parameters of the immune system and its biological defense functions, allowing an organism to anticipate daily changes in activity and feeding and the associated risk of infection. Inflammation is an immune response triggered in living organisms in response to external stimuli. The risk of sepsis, an excessive inflammatory response, has been shown to have a diurnal variation. On the other hand, inflammatory responses are emerging to be induced by endogenous factors. Recent studies have suggested that chronic inflammation causes chronic diseases including rheumatoid arthritis, allergies, and aging-related diseases and that proteins encoded by clock genes affect the development of such chronic inflammatory diseases or increase the severity of their symptoms. Therefore, detailed understanding of circadian rhythm effects on inflammatory responses is expected to lead to new strategies for prevention or treatment of inflammatory diseases.
26697019 Discovery of Innovative Therapies for Rare Immune-Mediated Inflammatory Diseases via Off-L 2015 Biologics have revolutionized the field of clinical immunology and proven to be both effective and safe in common immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, inflammatory bowel diseases, and various hematological disorders. However, in patients with rare, severe IMIDs failing on standard therapies, it is virtually impossible to conduct randomized controlled trials. Therefore, biologics are usually prescribed off-label in these often severely ill patients. Unfortunately, off-label prescription is sometimes hampered in these diseases due to a lack of reimbursement that is often based on a presumed lack of evidence for effectiveness. In the present article, we will discuss that off-label prescription of biologics can be a good way to discover new treatments for rare diseases. This will be illustrated using a case of multicentric Castleman's disease, an immune-mediated lymphoproliferative disorder, in which off-label tocilizumab (humanized anti-IL-6 receptor blocking antibody) treatment resulted in remarkable clinical improvement. Furthermore, we will give recommendations for monitoring efficacy and safety of biologic treatment in rare IMIDs, including the use of registries. In conclusion, we put forward that innovative treatments for rare IMIDs can be discovered via off-label prescription of biologicals, provided that this is based on rational arguments including knowledge of the pathophysiology of the disease.
26536784 [Metabolomics for Biomarker Discovery in Systemic Lupus Erythematosus]. 2015 Apr Metabolomics is the identification and quantification of the metabolome, all low-molecular-weight metabolites in a biological sample. Cell metabolism is known to have a marked impact on the function of various immune cells. We recently examined the differences in the serum metabolome between patients with systemic lupus erythematosus (SLE) and healthy subjects, using gas chromatography/mass spectrometry (GC/MS), and sought to identify candidates for metabolic biomarkers. We found that the levels of 25 metabolites were significantly different in SLE patients compared to healthy controls. A two-dimensional plot of the principal component analysis scores showed distinct clustering for the two subject groups. Multivariate analysis revealed that variations in the levels of glutamic acid, urea, tyrosine, phosphate and glycerol markedly contributed to the observed separation of metabolomic profiles of the SLE patients and healthy controls. A number of metabolites showed different changes between SLE and rheumatoid arthritis. Furthermore, the serum levels of glutamic acid were significantly correlated with the SLE disease activity index score in the patient group. These findings suggest that GC/MS-based serum metabolomics can serve as a novel diagnostic and monitoring tool for autoimmune diseases, and the pattern of variation in metabolite levels may be useful for understanding the pathophysiology of the diseases and developing novel therapeutic strategies.
26488759 Alterations in electrodermal activity and cardiac parasympathetic tone during hypnosis. 2016 Feb Exploring autonomic nervous system (ANS) changes during hypnosis is critical for understanding the nature and extent of the hypnotic phenomenon and for identifying the mechanisms underlying the effects of hypnosis in different medical conditions. To assess ANS changes during hypnosis, electrodermal activity and pulse rate variability (PRV) were measured in 121 young adults. Participants either received hypnotic induction (hypnosis condition) or listened to music (control condition), and both groups were exposed to test suggestions. Blocks of silence and experimental sound stimuli were presented at baseline, after induction, and after de-induction. Skin conductance level (SCL) and high frequency (HF) power of PRV measured at each phase were compared between groups. Hypnosis decreased SCL compared to the control condition; however, there were no group differences in HF power. Furthermore, hypnotic suggestibility did not moderate ANS changes in the hypnosis group. These findings indicate that hypnosis reduces tonic sympathetic nervous system activity, which might explain why hypnosis is effective in the treatment of disorders with strong sympathetic nervous system involvement, such as rheumatoid arthritis, hot flashes, hypertension, and chronic pain. Further studies with different control conditions are required to examine the specificity of the sympathetic effects of hypnosis.
26402614 Autoimmune rheumatic disease and sleep: a review. 2015 Nov PURPOSE OF REVIEW: Sleep has an important role to play in the human immune system and it is critical in the restoration and maintenance of homeostasis. Sleep deprivation and disorders may have a profound impact on health, well being and the ability to resist infection. Autoimmune rheumatic diseases are multisystem disorders that involve complicated hormonal and immunological pathophysiology. Previous studies have suggested that sleep deprivation may lead to immunological disturbance in experimental mouse models. RECENT FINDINGS: Sleep disorders may trigger immune system abnormalities inducing autoantibody production, possibly leading to the development of autoimmune disease such as systemic lupus erythematosus, scleroderma or rheumatoid arthritis. Indeed, in experimental models, it has been suggested that sleep deprivation may induce the onset of autoimmune disease. SUMMARY: Chronic deprivation of sleep is common in modern society and has been seen in various autoimmune inflammatory rheumatic diseases. We have reviewed various aspects of sleep deprivation and sleep apnoea syndrome, and their effects on the immune system and their relevance to autoimmune diseases. We hope that these data will encourage greater awareness of the role that improved sleep hygiene may play in the management of these rheumatic diseases.