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ID PMID Title PublicationDate abstract
27625480 A randomized, double-blind, placebo-controlled, cross-over study to evaluate analgesic act 2016 Jul BACKGROUND AND AIMS: To evaluate analgesic activity and safety of single oral dose (1000 mg) of Terminalia chebula using a mechanical pain model in healthy human volunteers. MATERIAL AND METHODS: Twelve healthy volunteers were randomized to receive either single oral dose of 2 capsules of T. chebula 500 mg each or identical placebo capsules in a double-blinded manner. Mechanical pain was assessed using Ugo basile analgesy meter (Randall-Selitto test) before and 3 h after administration of test drug. The parameters evaluated were pain threshold force and time; pain tolerance force and time. A washout period of 1-week was given for crossover between active drug and placebo. RESULTS: Terminalia chebula significantly increased the mean percentage change for pain threshold force and time, and pain tolerance force and time compared to placebo (P < 0.001). The mean percentage change for pain threshold force and time (20.8% and 21.0%) was increased more than that of pain tolerance force and time (13.4% and 13.4%). No adverse drug reaction was reported with either of the study medications during the study period. CONCLUSION: T. chebula significantly increased pain threshold and pain tolerance compared to placebo. Both the study medications were well tolerated. Further multiple dose studies may be needed to establish the analgesic efficacy of the drug in patients suffering from osteoarthritis, rheumatoid arthritis and other painful conditions.
27536552 The diagnostic journey of patients with mucopolysaccharidosis I: A real-world survey of pa 2016 Sep Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disease. Affected individuals have disease ranging from attenuated to severe with significant disease burden, disability, and premature death. Early treatment with enzyme replacement therapy and/or stem cell transplantation can reduce disease progression and improve outcomes. However, diagnosis is often delayed, particularly for patients with attenuated phenotypes. We conducted a survey of 168 patients and 582 physicians to explore health care seeking patterns and familiarity of physicians with MPS I symptoms. Patients with attenuated MPS I typically first presented with stiff joints or hernia/bulging abdomen, and patients with severe disease with noisy/difficult breathing, or hernia/bulging abdomen. There was a mean delay from time of symptom presentation to diagnosis of 2.7 years for patients with attenuated disease, with a mean of 5 physicians consulted before receiving a correct diagnosis. MPS I was most commonly misidentified by physicians as rheumatoid arthritis (48-72%), with a wide variety of suspected diseases, including lupus. CONCLUSION: Patient and physician real-world surveys show that MPS I is under-recognized and diagnosis of MPS I remains delayed, particularly in patients with attenuated disease. Across regions and specialties, physicians require differential diagnosis education in order to improve early detection and early treatment initiation of MPS I.
27483231 Computational Approaches to Toll-Like Receptor 4 Modulation. 2016 Jul 30 Toll-like receptor 4 (TLR4), along with its accessory protein myeloid differentiation factor 2 (MD-2), builds a heterodimeric complex that specifically recognizes lipopolysaccharides (LPS), which are present on the cell wall of Gram-negative bacteria, activating the innate immune response. Some TLR4 modulators are undergoing preclinical and clinical evaluation for the treatment of sepsis, inflammatory diseases, cancer and rheumatoid arthritis. Since the relatively recent elucidation of the X-ray crystallographic structure of the extracellular domain of TLR4, research around this fascinating receptor has risen to a new level, and thus, new perspectives have been opened. In particular, diverse computational techniques have been applied to decipher some of the basis at the atomic level regarding the mechanism of functioning and the ligand recognition processes involving the TLR4/MD-2 system at the atomic level. This review summarizes the reported molecular modeling and computational studies that have recently provided insights into the mechanism regulating the activation/inactivation of the TLR4/MD-2 system receptor and the key interactions modulating the molecular recognition process by agonist and antagonist ligands. These studies have contributed to the design and the discovery of novel small molecules with promising activity as TLR4 modulators.
27461996 The Science of Salt: A Regularly Updated Systematic Review of Salt and Health Outcomes (Au 2016 Oct The purpose of this review was to systematically identify, summarize, and critically appraise studies on dietary salt relating to health outcomes that were published from August to November 2015. The search strategy was adapted from a previous systematic review on dietary salt and health. Overall, 15 studies were included in the review: one study assessed cardiovascular events, five studies assessed blood pressure or hypertension incidence, six studies assessed surrogate outcomes for cardiovascular or kidney diseases, and three studies assessed other outcomes (age-related cataracts, rheumatoid arthritis, and bone mineral density, respectively). Four studies were selected for detailed appraisal and commentary.
27357971 Celecoxib Versus Placebo in Tonsillectomy: A Prospective, Randomized, Double-Blind Placebo 2016 Oct OBJECTIVES: Celecoxib is a cyclooxygenase-2-specific inhibitor indicated to treat acute pain and pain secondary to osteoarthritis and rheumatoid arthritis. Surgical models of acute pain have demonstrated superior pain relief to placebo. The objective of this study was to test the safety and efficacy of celecoxib for pain relief after tonsillectomy compared to placebo. METHODS: Adult subjects were randomized to 200 mg celecoxib versus placebo with a loading dose the night before surgery then twice daily for 10 days. Subjects were instructed to supplement the study drug with hydrocodone/acetaminophen liquid or acetaminophen for pain as needed. Subjects completed a daily diary regarding their pain, nausea, vomiting, diet, and activity. RESULTS: Seventeen subjects enrolled. Intraoperative blood loss was similar between groups, and no subject had postoperative bleeding. Three patients returned to the emergency department for treatment, and 2 patients could not complete the diaries, all in the placebo group. Subjects in the placebo group required statistically significant (P < .05) higher doses of narcotic and acetaminophen to control pain. Pain and diet rating scores were slightly better in the celecoxib group compared to placebo. CONCLUSIONS: In this small cohort, celecoxib reduced postoperative narcotic and acetaminophen requirements compared to placebo without complications.
27335701 High prevalence of hypovitaminosis D of patients with autoimmune rheumatic diseases in Chi 2016 We aimed to determine the prevalence of hypovitaminosis D in patients with autoimmune rheumatic diseases (ARDs) in China and its association with demographic characteristics of the patients. We recruited 384 patients in this cross-sectional study including 121 cases of systemic lupus erythematosus (SLE), 131 rheumatoid arthritis (RA), 102 spondyloarthritis (SpA) and 30 other ARDs. For each patient, demographic information was collected and serum concentration of 25OHD3 was measured by electrochemiluminescence immunoassay (ECLIA). The multivariate logistic regression model was used to investigate the association between vitamin D deficiency and patient characteristics. The mean serum vitamin D level of the 384 patients was 18.91 (8.12) ng/mL, and the median age was 37.33 (12.01) yrs. Among these patients, 222 (57.81%) and 127 (33.07%) were found to be vitamin D deficiency and insufficiency, respectively. From the disease perspective, the percentages of insufficiency and deficiency were as follow: 97.52% and 84.30% in SLE, 87.02% and 48.85% in RA, 88.24% and 40.20% in SpA, 90.89% and 57.81% in other ARDs patients. The causative factors for vitamin D deficiency included SLE per se (OR 12.54, P < 0.001) and high body mass index (BMI) (OR 1.88, P < 0.001). However, the seniors were less likely to have vitamin D deficiency (OR 0.95, P = 0.005). No correlation was disclosed between vitamin D deficiency and gender or disease duration. Hypovitaminosis D is highly prevalent among autoimmune rheumatic diseases population in China. The SLE per se and the obesity are the risk factors for vitamin D deficiency. Clinicians are advised to supplement vitamin D in these patients.
27105348 Association of FAM167A-BLK rs2736340 Polymorphism with Susceptibility to Autoimmune Diseas 2016 May OBJECTIVE: The purpose of this study is to evaluate the correlation between family with sequence similarity 167A-B lymphoid tyrosine kinase (FAM167A-BLK) rs2736340 polymorphism and autoimmune diseases. METHODS: Databases including PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature database (CBM) and Chinese database, Wan Fang database were used in searching eligible studies from January 1, 1966 to October 2, 2015. The odds ratios (ORs) and their 95% confidence intervals (CIs) were pooled to estimate the strength of the association. RESULTS: A total of 25 studies with 30,217 patients and 44,754 controls were included in the meta-analysis. The overall results showed FAM167A-BLK rs2736340 T allele was a risk allele for autoimmune diseases (OR 1.36, 95% CI 1.28-1.44, p < 0.001). In the subgroup by ethnicities, the results suggested T allele was an increased risk in North America, Europe, and Asia (OR 1.33, 95% CI 1.10-1.60, p = 0.004; OR 1.26, 95% CI 1.22-1.31, p < 0.001; and OR 1.46, 95% CI 1.40-1563, p < 0.001, respectively), but not in Africa. Subgroup analysis in different genetic models (recessive, dominant, and additive) revealed significant association between rs2736340 and autoimmune diseases in Asia and North America, but not the recessive model in Europe or Africa, or the additive model in Africa. Stratification analysis by diseases suggested FAM167A-BLK rs2736340 had a positive association with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Kawasaki disease, primary Sjogren's syndrome (pSS), primary antiphosholipid syndrome (APS), and myositis. CONCLUSION: The current meta-analysis suggested that FAM167A-BLK rs2736340 polymorphism is associated with several autoimmune diseases.
26993500 Allele-specific transcription factor binding to common and rare variants associated with d 2016 May Genome-wide association studies (GWAS) have identified a large number of disease-associated SNPs, but in few cases the functional variant and the gene it controls have been identified. To systematically identify candidate regulatory variants, we sequenced ENCODE cell lines and used public ChIP-seq data to look for transcription factors binding preferentially to one allele. We found 9962 candidate regulatory SNPs, of which 16 % were rare and showed evidence of larger functional effect than common ones. Functionally rare variants may explain divergent GWAS results between populations and are candidates for a partial explanation of the missing heritability. The majority of allele-specific variants (96 %) were specific to a cell type. Furthermore, by examining GWAS loci we found >400 allele-specific candidate SNPs, 141 of which were highly relevant in our cell types. Functionally validated SNPs support identification of an SNP in SYNGR1 which may expose to the risk of rheumatoid arthritis and primary biliary cirrhosis, as well as an SNP in the last intron of COG6 exposing to the risk of psoriasis. We propose that by repeating the ChIP-seq experiments of 20 selected transcription factors in three to ten people, the most common polymorphisms can be interrogated for allele-specific binding. Our strategy may help to remove the current bottleneck in functional annotation of the genome.
26982101 Probing binding mechanism of interleukin-6 and olokizumab: in silico design of potential l 2016 Dec Computer-aided antibody engineering has been successful in the design of new biologics for disease diagnosis and therapeutic interventions. Interleukin-6 (IL-6), a well-recognized drug target for various autoimmune and inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, and psoriasis, was investigated in silico to design potential lead antibodies. Here, crystal structure of IL-6 along with monoclonal antibody olokizumab was explored to predict antigen-antibody (Ag - Ab)-interacting residues using DiscoTope, Paratome, and PyMOL. Tyr56, Tyr103 in heavy chain and Gly30, Ile31 in light chain of olokizumab were mutated with residues Ser, Thr, Tyr, Trp, and Phe. A set of 899 mutant macromolecules were designed, and binding affinity of these macromolecules to IL-6 was evaluated through Ag - Ab docking (ZDOCK, ClusPro, and Rosetta server), binding free-energy calculations using Molecular Mechanics/Poisson Boltzman Surface Area (MM/PBSA) method, and interaction energy estimation. In comparison to olokizumab, eight newly designed theoretical antibodies demonstrated better result in all assessments. Therefore, these newly designed macromolecules were proposed as potential lead antibodies to serve as a therapeutics option for IL-6-mediated diseases.
26754327 Mesenchymal Stem Cells Ageing: Targeting the "Purinome" to Promote Osteogenic Differentiat 2016 Sep Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into bone forming cells. Such ability is compromised in elderly individuals resulting in bone disorders such as osteoporosis, also limiting their clinical usage for cell transplantation and bone tissue engineering strategies. In bone marrow niches, adenine and uracil nucleotides are important local regulators of osteogenic differentiation of MSCs. Nucleotides can be released to the extracellular milieu under both physiological and pathological conditions via (1) membrane cell damage, (2) vesicle exocytosis, (3) ATP-binding cassette transporters, and/or (4) facilitated diffusion through maxi-anion channels, hemichannels or ligand-gated receptor pores. Nucleotides and their derivatives act via adenosine P1 (A1 , A2A , A2B , and A3 ) and nucleotide-sensitive P2 purinoceptors comprising ionotropic P2X and G-protein-coupled P2Y receptors. Purinoceptors activation is terminated by membrane-bound ecto-nucleotidases and other ecto-phosphatases, which rapidly hydrolyse extracellular nucleotides to their respective nucleoside 5'-di- and mono-phosphates, nucleosides and free phosphates, or pyrophosphates. Current knowledge suggests that different players of the "purinome" cascade, namely nucleotide release sites, ecto-nucleotidases and purinoceptors, orchestrate to fine-tuning regulate the activity of MSCs in the bone microenvironment. Increasing studies, using osteoprogenitor cell lines, animal models and, more recently, non-modified MSCs from postmenopausal women, raised the possibility to target chief components of the purinergic signaling pathway to regenerate the ability of aged MSCs to differentiate into functional osteoblasts. This review summarizes the main findings of those studies, prompting for novel therapeutic strategies to control ageing disorders where bone destruction exceeds bone formation, like osteoporosis, rheumatoid arthritis, and fracture mal-union. J. Cell. Physiol. 231: 1852-1861, 2016. © 2016 Wiley Periodicals, Inc.
26742198 [Achondroplasia: a pilot study on the psychosocial and medical features of a sample in Pue 2015 Jul This study explores the psychological wellbeing of twenty-two (n = 22) adults with achondroplasia. The sample was composed of seven (n = 7) males and fifteen (n = 15) females between the ages of 21 and 75 (mean age = 39.6). Each individual completed four self-administered questionnaires: the Beck Depression Inventory (BDI-l), the Beck Anxiety Inventory (BAI), the Beck Hopelessness Scale (BHS), and Derogatis Symptom Check-list-90-Revisited (SCL-90-R). They also filled out a socio-demographic questionnaire. We found that 31.8% of the sample reported at least one comorbid condition such as, hypertension, diabetes, rheumatoid arthritis, asthma, scoliosis, thyroid problems, neuropathy, psoriasis, gastritis and/or sleep apnea; 32% reported mild to severe depressive symp- toms; 55% reported mild to severe symptoms associated to anxiety and 18% reported mild to severe symptoms associated with hopelessness; 22.7% reported mild to severe symptoms in at least one of the sub-scales in Derogatis Symptom Checklist-90-Revisited (SCL-90-R) particularly the obsessive-compulsive, paranoid and depressive subscales. Chi Square correlations (X2) were made to observe if there was interdependence between the socio-demographic variables and the administered tests. In general, no significant correlations were found between BDI-Il, BAI, BHS, SCL-90-R and civil status, gender, income and age. However, a significant correlation was found between age and the somatization sub-scale of the SCL-90-R (rs = 0.510, p < 0.05). Our findings suggest that this particular sample is at risk for developing psycho-medical conditions. There is a marked lack of research in Puerto Rico associated to achondroplasia. The development of preventive and cultural sensitive interventions is suggested in order to protect and treat individuals with the condition.
26728774 Imaging Patterns of Cardiovascular Involvement in Mixed Connective Tissue Disease Evaluate 2015 BACKGROUND: To clarify the imaging patterns of cardiovascular lesions in patients with mixed connective tissue disease (MCTD) and cardiovascular symptoms with or/ without abnormal routine non-invasive evaluation. PATIENTS-METHODS: Twenty-two MCTD patients (19F/3M), aged 38±4 yrs with cardiovascular symptoms were evaluated using a 1.5 T scanner. Of them, 8/22 had systemic lupus erythematosus (SLE), 5/22 rheumatoid arthritis (RA), 5/22 scleroderma (SSc) and 4/22 myositis (MY) overlap syndromes; 10/22 patients with MCTD presented with Raynaud phenomenon (RP) and all were positive for Anti-RNP antibodies. The cardiovascular magnetic resonance study (CMR) included evaluation of function, inflammation and fibrosis. Myocardial stress perfusion-fibrosis evaluation was performed only in MCTD patients with RP. RESULTS: A positive CMR study was identified in 4/8 with SLE, 1/5 with RA, 4/5 with SSc and in 1/4 with MY like MCTD. The CMR lesions were subendocardial or transmural LGE following the distribution of coronary arteries, intramyocardial LGE and diffuse subendocardial LGE in SLE-RA, MY and SSc like MCTD, respectively. Although no evidence of fibrosis was identified in patients with RP, adenosine stress myocardial perfusion revealed diffuse subendocardial perfusion defects. No correlation between disease duration and/or inflammatory indices and cardiac lesions was identified. CONCLUSION: CMR can reveal myocardial lesions in MCTD patients with cardiac symptoms including myocardial infarction, inflammation, diffuse subendocardial fibrosis and diffuse perfusion defects, necessitating further cardiac investigation and/or treatment.
26563649 Effect of Obesity on Complication Rate After Elbow Arthroscopy in a Medicare Population. 2016 Mar PURPOSE: To use a national insurance database to explore the association of obesity with the incidence of complications after elbow arthroscopy in a Medicare population. METHODS: Using Current Procedural Terminology (CPT) and International Classification of Diseases, 9th Revision (ICD-9) procedure codes, we queried the PearlDiver database for patients undergoing elbow arthroscopy. Patients were divided into obese (body mass index [BMI] >30) and nonobese (BMI <30) cohorts using ICD-9 codes for BMI and obesity. Nonobese patients were matched to obese patients based on age, sex, tobacco use, diabetes, and rheumatoid arthritis. Postoperative complications were assessed with ICD-9 and Current Procedural Terminology codes, including infection, nerve injury, stiffness, and medical complications. RESULTS: A total of 2,785 Medicare patients who underwent elbow arthroscopy were identified from 2005 to 2012; 628 patients (22.5%) were coded as obese or morbidly obese, and 628 matched nonobese patients formed the control group. There were no differences between the obese patients and matched control nonobese patients regarding type of elbow arthroscopy, previous elbow fracture or previous elbow arthroscopy. Obese patients had greater rates of all assessed complications, including infection (odds ratio [OR] 2.8, P = .037), nerve injury (OR 5.4, P = .001), stiffness (OR 1.9, P = .016) and medical complications (OR 6.9, P < .0001). CONCLUSIONS: Obesity is associated with significantly increased rates of all assessed complications after elbow arthroscopy in a Medicare population, including infection, nerve injury, stiffness, and medical complications. LEVEL OF EVIDENCE: Therapeutic Level III, case-control study.
26502871 A case report of successful treatment of pyoderma gangrenosum in a patient with autoimmune 2015 Oct 26 BACKGROUND: Pyoderma Gangrenosum (PG) is a cutaneous condition, its diagnosis suggested by the presence of a painful cutaneous ulcer showing rapid progression. Pyoderma gangrenosum is associated with a concomitant systemic disease in 50 to 70 % of cases, including inflammatory bowel disease (IBD), rheumatoid arthritis, and lymphoproliferative disorders. Although PG has also been reported with viral hepatitis, it is rarely associated with autoimmune hepatitis. CASE PRESENTATION: A 19-year-old Caucasian female, with a prior diagnosis of autoimmune hepatitis (AIH) in remission, presented with bilateral lower limb ulcers 4 years after the diagnosis of AIH. She was diagnosed with PG and treated with high-dose prednisolone, methotrexate and cyclosporine. One year later she was well, the ulcers completely healed, and with the autoimmune hepatitis still in remission. CONCLUSION: We report a case of autoimmune hepatitis and the subsequent, rarely occurring, extra-hepatic onset of pyoderma gangrenosum, with the AIH in remission, strengthening the association between the two conditions. Since both the AIH and the PG can present serious diagnostic challenges, thus delaying vital therapy, it is important that the development of either prompts us to consider the possibility of the other developing in the future or if already present facilitate its diagnosis, such considerations making the case for a systematic follow up.
26352927 Development and Characterization of a New Antipeptide Monoclonal Antibody Directed to Huma 2015 Sep The rapid expansion of immunotherapeutic approaches for treatment of various diseases, including cancers, has been greatly facilitated by the invention of new generation of antibodies. Clinical studies have indicated that anti-CD20 mAb-based therapies represent an effective treatment for various diseases with overexpression of CD20 on their cell surface, such as non-Hodgkin's lymphoma, hemolytic anemia, as well as autoimmune diseases like rheumatoid arthritis. Technically, due to a short extra membrane domain, the recombinant CD20 protein is a difficult antigen to raise immune responses. In search for new monoclonal antibodies, the authors used an antigenic polypeptide, which yielded numbers of new binders that may lead to production of anti-CD20 antibodies, with improved diagnostic or clinical attributes. Mice were immunized with extra membrane loop of human CD20 (exCD20) polypeptide. The exCD20 antigen showed a desired immune response and was able to develop a monoclonal antibody, 3B4C10, which reacted well with peptide antigen as well as native antigen on the surface of Raji B-cell line. The antibody 3B4C10 with a balanced K(on) and K(off) may be applicable in the construction of affinity columns or beads for isolation and purification of CD20-positive cells and cancer stem cells.
26339588 Effect of Dietary ω-3 Polyunsaturated Fatty Acid DHA on Glycolytic Enzymes and Warburg Ph 2015 The omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are a class of lipids that has been shown to have beneficial effects on some chronic degenerative diseases such as cardiovascular diseases, rheumatoid arthritis, inflammatory disorders, diabetes, and cancer. Among ω-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) has received particular attention for its antiproliferative, proapoptotic, antiangiogenetic, anti-invasion, and antimetastatic properties, even though the involved molecular mechanisms are not well understood. Recently, some in vitro studies showed that DHA promotes the inhibition of glycolytic enzymes and the Warburg phenotype. For example, it was shown that in breast cancer cell lines the modulation of bioenergetic functions is due to the capacity of DHA to activate the AMPK signalling and negatively regulate the HIF-1α functions. Taking into account these considerations, this review is focused on current knowledge concerning the role of DHA in interfering with cancer cell metabolism; this could be considered a further mechanism by which DHA inhibits cancer cell survival and progression.
26298810 Constructing an atomic-resolution model of human P2X7 receptor followed by pharmacophore m 2015 Sep The P2X purinoceptor 7 (P2X7R) is a trimeric ATP-activated ion channel gated by extracellular ATP. P2X7R has important role in numerous diseases including pain, neurodegeneration, and inflammatory diseases such as rheumatoid arthritis and osteoarthritis. In this prospective, the discovery of small-molecule inhibitors for P2X7R as a novel therapeutic target has received considerable attention in recent years. At first, 3D structure of P2X7R was built by using homology modeling (HM) and a 50ns molecular dynamics simulation (MDS). Ligand-based quantitative pharmacophore modeling methodology of P2X7R antagonists were developed based on training set of 49 compounds. The best four-feature pharmacophore model, includes two hydrophobic aromatic, one hydrophobic and one aromatic ring features, has the highest correlation coefficient (0.874), cost difference (368.677), low RMSD (2.876), as well as it shows a high goodness of fit and enrichment factor. Consequently, some hit compounds were introduced as final candidates by employing virtual screening and molecular docking procedure simultaneously. Among these compounds, six potential molecule were identified as potential virtual leads which, as such or upon further optimization, can be used to design novel P2X7R inhibitors.
26234512 Chemometrics-assisted Spectrofluorimetric Determination of Two Co-administered Drugs of Ma 2015 Methotrexate (MTX) is widely used to treat rheumatoid arthritis (RA), mostly along with non-steroidal anti-inflammatory drugs (NSAIDs), the most common of which is aspirin or acetyl salicylic acid (ASA). Since NSAIDs impair MTX clearance and increase its toxicity, it was necessary to develop a simple and reliable method for the monitoring of MTX levels in urine samples, when coadministered with ASA. The method was based on the spectrofluorimetric measurement of the acid-induced hydrolysis product of MTX, 4-amino-4-deoxy-10-methylpteroic acid (AMP), along with the strongly fluorescent salicylic acid (SA), a product of acid-induced hydrolysis of aspirin and its metabolites in urine. The overlapping emission spectra were resolved using the derivative method (D method). In addition, the corresponding derivative emission spectra were convoluted using discrete Fourier functions, 8-points sin xi polynomials, (D/FF method) for better elimination of interferences. Validation of the developed methods was carried out according to the ICH guidelines. Moreover, the data obtained using derivative and convoluted derivative spectra were treated using the non-parametric Theil's method (NP), compared with the least-squares parametric regression method (LSP). The results treated with Theil's method were more accurate and precise compared with LSP since the former is less affected by the outliers. This work offers the potential of both derivative and convolution using discrete Fourier functions in addition to the effectiveness of using the NP regression analysis of data. The high sensitivity obtained by the proposed methods was promising for measuring low concentration levels of the two drugs in urine samples. These methods were efficiently used to measure the drugs in human urine samples following their co-administration.
26058889 T Lymphocyte Prestimulation Impairs in a Time-Dependent Manner the Capacity of Adipose Mes 2015 Sep 15 The immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) make them an attractive therapeutic tool to treat chronic inflammatory diseases, such as rheumatoid arthritis or Crohn's disease. These indications are characterized by a chronic activation of immune cells that perpetuates the disease. In vitro, when adipose mesenchymal stem cells (ASCs) are cultured with T lymphocytes at the time of stimulation, their proliferation is inhibited. However, these experimental settings do not necessarily fit with what ASCs will face in inflammatory conditions in vivo, where ASCs will likely encounter and interact with already activated immune cells which might affect their immunomodulatory capacity. In most in vitro studies, MSCs have been cultured with peripheral blood mononuclear cells at the time of lymphocyte stimulation and information about the interaction between MSCs and prestimulated lymphocytes in vitro is scarce. Therefore, a better understanding of the capacity of MSCs to modulate the responses of preactivated immune cells is needed. In this study we focused on the effects of ASCs on prestimulated lymphocytes and systematically investigated the potential mechanisms involved. We report that prestimulation of T lymphocytes 48 h before the coculture with ASCs impairs the capacity of ASCs to inhibit proliferation. Preactivation of ASCs with interferon γ or the toll-like receptor ligand Poly I:C, but not other stimuli tested, enhanced the ability to inhibit the proliferation of 48 h-stimulated T lymphocytes. The inhibitory effect of ASCs was shown to be time dependent and mediated through the actual magnitude of tryptophan degradation by indoleamine 2,3-dioxygenase.
25834171 Simultaneous Determination of 10 Active Components in Hulisan Tablets by a High-Performanc 2015 Oct Hulisan tablets (HLST), a famous classic traditional Chinese prescriptions consisting of four medicinal herbs, have been applied for treating fractures, rheumatoid arthritis, mechanical phlebitis and traumatic bleeding extensively. In this study, a simple and reliable method using high-performance liquid chromatography with diode array detector (HPLC-DAD) was established for the simultaneous determination of 10 active compounds in HLST. The chromatographic analysis was performed on a Symmetry(®)-C18 column (4.6 × 250 mm, i.d., 5 µm; Waters, Wexford, Leinster, Ireland) at 30°C with a gradient elution of 0.1 mol/L ammonium acetate (containing 0.5 mL glacial acetic acid per 1,000 mL) and acetonitrile at a flow rate of 1.0 mL/min. The detection UV wavelengths were set at 232, 254 and 280 nm. The method was validated by linearity, precision, stability and recovery. Calibration curves for the 10 compounds showed good linear regressions (R(2) > 0.9992). The limits of detection and quantification fell in the ranges of 0.03-0.36 and 0.11-1.01 µg/mL, respectively. The results of the recovery test were 97.19-102.04% with a RSD value of 0.65-2.47%. The developed method was subsequently applied to evaluate five batches of HLST and testified to be suitable for the quality control.