Publications by authors named "Arman Ahmadzadeh"

29 Publications

  • Page 1 of 1

TEN/SJS-like lupus erythematosus presentation complicated by COVID-19.

Dermatol Ther 2021 Jan 10;34(1):e14612. Epub 2020 Dec 10.

Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.1111/dth.14612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744967PMC
January 2021

Coexistence of Parathyroid Adenoma, Sarcoidosis, and Hypercalcemia.

J Clin Rheumatol 2020 Aug 17. Epub 2020 Aug 17.

Pathology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.1097/RHU.0000000000001514DOI Listing
August 2020

Frequency and outcome of olfactory impairment and sinonasal involvement in hospitalized patients with COVID-19.

Neurol Sci 2020 Sep 12;41(9):2331-2338. Epub 2020 Jul 12.

ENT and Head & Neck Research center and Department, The Five Senses Institute, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.

Background: Olfactory dysfunction has shown to accompany COVID-19. There are varying data regarding the exact frequency in the various study population. The outcome of the olfactory impairment is also not clearly defined.

Objective: To find the frequency of olfactory impairment and its outcome in hospitalized patients with positive swab test for COVID-19.

Methods: This is a prospective descriptive study of 100 hospitalized COVID-19 patients, randomly sampled, from February to March 2020. Demographics, comorbidities, and laboratory findings were analyzed according to the olfactory loss or sinonasal symptoms. The olfactory impairment and sinonasal symptoms were evaluated by 9 Likert scale questions asked from the patients.

Results: Ninety-two patients completed the follow-up (means 20.1 (± 7.42) days). Twenty-two (23.91%) patients complained of olfactory loss and in 6 (6.52%) patients olfactory loss was the first symptom of the disease. The olfactory loss was reported to be completely resolved in all but one patient. Thirty-nine (42.39%) patients had notable sinonasal symptoms while rhinorrhea was the first symptom in 3 (3.26%). Fifteen patients (16.3%) had a taste impairment. Patients with sinonasal symptoms had a lower age (p = 0.01). There was no significant relation between olfactory loss and sinonasal symptoms (p = 0.07).

Conclusions: Sudden olfactory dysfunction and sinonasal symptoms have a considerable prevalence in patients with COVID-19. No significant association was noted between the sinonasal symptoms and the olfactory loss, which may suggest that other mechanisms beyond upper respiratory tract involvement are responsible for the olfactory loss.
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http://dx.doi.org/10.1007/s10072-020-04590-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354355PMC
September 2020

Effect of Guluronic Acid (G2013), As a New Anti-inflammatory Drug on Gene Expression of Pro-inflammatory and Anti-inflammatory Cytokines and Their Transcription Factors in Rheumatoid Arthritis Patients.

Iran J Allergy Asthma Immunol 2019 Nov 11;18(6):639-648. Epub 2019 Nov 11.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran AND Research Center for Immunodeficiencies, Children's Medical Centre, Tehran University of Medical Sciences, Tehran, Iran.

Rheumatoid arthritis (RA) as a long-term autoimmune disease is characterized by pain, swelling and joints destruction. The therapeutic efficacy of Guluronic acid (G2013) (patented, DEU: 102016113017.6) was reported in phase I/II clinical trial in RA patients. In this study, we aimed to evaluate the effect of G2013 as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive property on genes expression of anti-inflammatory and pro-inflammatory cytokines and their transcription factors in the blood sample of RA patients. This study was performed on 12 patients with RA who had an inadequate response to conventional treatments which were disease-modifying anti-rheumatic drugs (DMARDs), NSAID, and biologics. G2013 was administered orally at a dose of 500 mg twice daily for 12 weeks. Before and after the treatment of patients with drug G2013, the peripheral blood mononuclear cells (PBMCs) were isolated for evaluating the gene expression level of interleukin 10 (IL10), interleukin 22 (IL22), interferon γ (IFNγ), and transcription factors specific to the T helper cell lineages, forkhead box P3 (Fox-P3), Aryl hydrocarbon receptor (AHR) and T-box-containing protein expressed in T cells (T-bet) using the real-time PCR method. Since these cytokines have a key role in the progression of RA and disease condition expected induction of IFNγ, AHR, IL22, T-bet, and reduction of IL10, Fox-P3. Results indicated a significant reduction in the level of IFNγ, AHR and a significant induction in IL10, Fox-P3 gene expression in comparison with the control group. In conclusion; the results of this investigation showed a part of the immunological mechanism of G2013 as a novel anti-inflammatory that could reduce pro-inflammatory cytokine and their transcription factors. Furthermore, it increased the anti-inflammatory cytokine and its transcription factor (clinical trial identifier: IRCT2016092813739N5).
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http://dx.doi.org/10.18502/ijaai.v18i6.2176DOI Listing
November 2019

The role of β-d-mannuronic acid, as a new non-steroidal anti-inflammatory drug on expression of miR-146a, IRAK1, TRAF6, NF-κB and pro-inflammatory cytokines following a clinical trial in rheumatoid arthritis patients.

Immunopharmacol Immunotoxicol 2020 Jun 29;42(3):228-236. Epub 2020 Mar 29.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

miR-146a, its targets (IRAK1, TRAF6) and NF-κB transcription factor play a fundamental role in rheumatoid arthritis (RA). Positive effects of drug β-d-mannuronic acid (M2000) were proven on their expression in the HEK-Blue hTLR2 cell line, and results of its phase III clinical trial on RA patients were encouraging. This research aimed to investigate the effects of M2000 on expression of these genes and serum levels of IL-6 and TNF-α as pro-inflammatory cytokines in RA patients. In this study (Trial Registration Number: IRCT2017100213739N10), 12 RA patients (according to the American College of Rheumatology criteria) and 12 healthy subjects (as control group) were selected. The gene expression of miR-146a, IRAK1, TRAF6, and NF-κB were measured at the baseline and after 12 weeks M2000 therapy, using quantitative real-time PCR method. Moreover, the serum levels of IL-6 and TNF-α were evaluated at the similar times by ELISA method. Our findings showed that the gene expression of miR-146a, IRAK1, TRAF6, and NF-κB significantly decreased after 12 weeks M2000 therapy in RA patients (0.81-, 0.68-, 0.79-, 0.82-fold, with  < .05,  < .01,  < .01,  < .05, respectively). Furthermore, the serum levels of IL-6 and TNF-α significantly reduced in these patients after 12 weeks M2000 therapy (both with  < .05). The present research results determined the part of molecular mechanisms of drug M2000 in RA treatment, based on the expression and function modification of miR-146a, IRAK1, TRAF6, NF-κB, IL-6 and TNF-α.
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http://dx.doi.org/10.1080/08923973.2020.1742734DOI Listing
June 2020

The Situation of Chemokine Ligands and Receptors Gene Expression, Following the Oral Administration of Drug Mannuronic Acid in Rheumatoid Arthritis Patients.

Recent Pat Inflamm Allergy Drug Discov 2020 ;14(1):69-77

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: Regarding the leukocytes infiltration into the synovium of Rheumatoid Arthritis (RA) patients is mostly mediated by chemokine ligands and receptors, and following the efficient and motivating results of international Phase III clinical trial of β-D-Mannuronic acid (M2000) patented EP067919 (2017), as a novel anti-inflammatory drug, in patients with RA, the present research was designed.

Objectives: This study aimed to assess the oral administration effects of this new drug on gene expression of some chemokine receptors and ligands, including CXCR4, CXCR3, CCR2, CCR5 and CCL2/MCP-1 in PBMCs of patients with active form of RA.

Methods: Twelve patients suffering from RA, with inadequate response to conventional drugs were selected (Clinical trial identifier IRCT2017100213739N10) and 1000mg/day of M2000 was orally administrated to them for 12 weeks. The mRNA expression of target molecules was then evaluated in PBMCs of the patients before and after treatment with M2000 using real-time PCR and was compared to healthy controls. Patents related to this study were also reviewed.

Results: The results showed that M2000 was able to significantly down-regulate the mRNA expression of CXCR4, CCR2 and CCL2/MCP-1 in the PBMCs of the RA patients. It should be noted that the gene expression situation of the target molecules was in coordinate with the clinical and paraclinical assessments in the patients.

Conclusion: Taken together, the results of this investigation revealed the part of molecular and immunological mechanisms of drug Mannuronic acid (M2000) in the treatment of RA, based on chemokine ligands and receptors mediated processes.
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http://dx.doi.org/10.2174/1872213X13666191114111822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509734PMC
December 2020

Immunopharmacological effect of β-d-mannuronic acid (M2000), as a new immunosuppressive drug, on gene expression of miR-155 and its target molecules (SOCS1, SHIP1) in a clinical trial on rheumatoid arthritis patients.

Drug Dev Res 2020 05 1;81(3):295-304. Epub 2019 Nov 1.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

The positive impacts of β-d-mannuronic acid (M2000) on the gene expression of miR-155, its target molecules (SOCS1 and SHIP1), and NF-κB transcription factor were demonstrated in a study using the HEK293-TLR2 cell line. This new drug has been approved as a safe and effective medication by a randomized, multinational, phase III clinical trial on RA patients. The present study aimed to evaluate the oral administration effect of M2000 on the expression levels of the mentioned genes in RA patients. This research was conducted on 12 RA patients and 12 healthy individuals. After extraction of total RNA from PBMCs of patients and synthesis of cDNA, the expression levels of miR-155, SOCS1, SHIP1, and NF-κB genes were measured through quantitative Real-time PCR at baseline and after 12 weeks of M2000 therapy. Our findings showed that the miR-155 gene expression level significantly decreased in the M2000-treated patients compared with the baseline (0.76-fold, with p < .05). The expression levels of SOCS1 and SHIP1 genes significantly increased in the patients treated with M2000 compared with the before treatment (1.46-, 1.54-fold, with p < .01, p < .05, respectively). In addition, it was found that the gene expression level of the NF-κB transcription factor significantly reduced in M2000-treated patients compared with the baseline (0.81-fold, with p < .05). This study showed that the oral administration of M2000 was able to reduce the expression of the miR-155, increase the expression of SOCS1 and SHIP1, and decrease the NF-κB gene expression (Trial Registration Number: IRCT2017100213739N10).
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http://dx.doi.org/10.1002/ddr.21619DOI Listing
May 2020

Influence of β-D-mannuronic Acid, as a New Member of Non-steroidal Anti- Inflammatory Drugs Family, on the Expression Pattern of Chemokines and their Receptors in Rheumatoid Arthritis.

Curr Drug Discov Technol 2021 ;18(1):65-74

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: Based on the encouraging results of phase III clinical trial of β-Dmannuronic acid (M2000) (as a new anti-inflammatory drug) in patients with RA, in this study, we aimed to evaluate the effects of this drug on the expression of chemokines and their receptors in PBMCs of RA patients.

Methods: PBMCs of RA patients and healthy controls were separated and the patients' cells were treated with low, moderate and high doses (5, 25 and 50 μg/mL) of M2000 and optimum dose (1 μg/mL) of diclofenac, as a control in RPMI-1640 medium. Real-time PCR was used for evaluating the mRNA expression of CXCR3, CXCR4, CCR2, CCR5 and CCL2/MCP-1. Cell surface expression of CCR2 was investigated using flow cytometry.

Results: CCR5 mRNA expression reduced significantly, after treatment of the patients' cells with all three doses of M2000 and optimum dose of diclofenac. CXCR3 mRNA expression was downregulated significantly followed by the treatment of these cells with moderate and high doses of M2000 and optimum dose of diclofenac. CXCR4 mRNA expression declined significantly after the treatment of these cells with moderate and high doses of M2000. CCL2 mRNA expression significantly reduced only followed by the treatment of these cells with a high dose of M2000, whereas, mRNA and cell surface expressions of CCR2 diminished significantly followed by the treatment of these cells with a high dose of M2000 and optimum dose of diclofenac.

Conclusion: According to our results, M2000 through the down-regulation of chemokines and their receptors may restrict the infiltration of immune cells into the synovium.
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http://dx.doi.org/10.2174/1570163816666191023103118DOI Listing
January 2021

Acute versus chronic methotrexate poisoning; a cross-sectional study.

BMC Pharmacol Toxicol 2019 07 3;20(1):39. Epub 2019 Jul 3.

School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Data is limited on comparison of acute and chronic methotrexate (MTX) poisoning. Methotrexate is an anti-folate drug that may be prescribed in some malignant or chronic inflammatory conditions. The aim of the current study was to compare signs and symptoms, complications, treatment and final outcome of acute and chronic MTX toxicity.

Method: In a retrospective study in a referral center between March 2010 and March 2018, all patients who had been referred with the history of MTX poisoning and hospitalized due to acute or chronic poisoning were evaluated and compared.

Results: Of the total 27 patients admitted during the study period, 13 had referred with acute (group 1; consumption of MTX for less than 7 days) and 14 had referred with chronic toxicity (group 2; consumption of MTX for more than 7 days). Mean age was significantly higher in the second group (P < 0.001). Median total dose of MTX was similar between the groups (P = 0.90). Mucosal ulcers and skin lesions (P < 0.001 and 0.02, respectively) were the only symptoms significantly different between the two groups. Leukopenia (P < 0.001), thrombocytopenia (P < 0.001), and anemia (P = 0.04) were significantly more common in the second group. Blood urea nitrogen and creatinine were also significantly higher in the second group of the patients (P < 0.001 and P = 0.048). Median leucovorin administered dose was 200 mg [14, 480] versus 150 mg [75, 187] (P = 0.69) in groups 1 and 2, respectively.

Conclusions: Chronic MTX poisoning is more serious than acute toxicity and accompanies higher dermatologic, hematologic, and hepatic complications necessitating more aggressive treatments including administration of higher doses of leucovorin or bone marrow stimulants such as G-CSF. This may be attributable to the underlying diseases and features (including older ages) which predispose these patients to complications.
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http://dx.doi.org/10.1186/s40360-019-0316-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609338PMC
July 2019

Magnetic Nanoparticle-Based Molecular Communication in Microfluidic Environments.

IEEE Trans Nanobioscience 2019 04 25;18(2):156-169. Epub 2019 Jan 25.

The possibility to guide and control magnetic nanoparticles in a non-invasive manner has spawned various applications in biotechnology, such as targeted drug delivery and sensing of biological substances. These applications are facilitated by the engineering of the size, selective chemical reactivity, and general chemical composition of the employed particles. Motivated by their widespread use and favorable properties, in this paper, we provide a theoretical study of the potential benefits of magnetic nanoparticles for the design of molecular communication systems. In particular, we consider a magnetic nanoparticle-based communication in a microfluidic channel where an external magnetic field is employed to attract the information-carrying particles to the receiver. We show that the particle transport affected by the Brownian motion, fluid flow, and an external magnetic field can be mathematically modeled as diffusion with drift. Thereby, we reveal that the key parameters determining the magnetic force are the particle size and the magnetic field gradient. Moreover, we derive an analytical expression for the channel impulse response, which is used to evaluate the potential gain in the expected number of observed nanoparticles due to the magnetic field. Furthermore, adopting the symbol error rate as performance metric, we show that using magnetic nanoparticles can enable a reliable communication in the presence of disruptive fluid flow. The numerical results obtained by the particle-based simulation validate the accuracy of the derived analytical expressions.
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http://dx.doi.org/10.1109/TNB.2019.2895244DOI Listing
April 2019

International multicenter randomized, placebo-controlled phase III clinical trial of β-D-mannuronic acid in rheumatoid arthritis patients.

Inflammopharmacology 2019 Oct 2;27(5):911-921. Epub 2019 Jan 2.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Box: 14155-6446, Tehran, Iran.

Background: The oral administration of drug β-D-mannuronic acid (M2000) showed a potent therapeutic effect in phase I/II study in rheumatoid arthritis (RA) patients. Here, our aim is to assess the efficacy and safety of this new drug in RA patients under a multinational, randomized placebo-controlled phase III clinical trial.

Method: Patients (n = 288) with active disease at baseline and inadequate response to conventional drugs were randomly allocated to three groups; (1) receiving mannuronic acid at a dose of two capsules (500 mg) per day orally for 12 weeks, (2) placebo-controlled, and (3) conventional. The primary endpoints were the America College of Rheumatology 20 response (ACR20), 28-joint disease activity score (DAS28) and Modified Health Assessment Questionnaire-Disability Index (M-HAQ-DI). In addition, the participants were followed-up for safety assessment.

Results: In this phase III trial, after 12 weeks of treatment, there was a significant reduction in ACR20 between mannuronic-treated patients compared to placebo and conventional groups. Moreover, there was a similar significant improvement for DAS28 following mannuronic therapy. The statistical analysis showed a significant reduction in the swollen and tender joint count in mannuronic-treated patients compared with the placebo group. On the other side, mannuronic acid showed no-to-very low adverse events in comparison to placebo.

Conclusion: The results of this multinational, phase III clinical trial provided a potent evidence base for the use of β-D-mannuronic acid as a new highly safe and efficient drug in the treatment of RA.
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http://dx.doi.org/10.1007/s10787-018-00557-2DOI Listing
October 2019

Early Cancer Detection in Blood Vessels Using Mobile Nanosensors.

IEEE Trans Nanobioscience 2019 04 7;18(2):103-116. Epub 2018 Dec 7.

In this paper, we propose using mobile nanosensors (MNSs) for early stage anomaly detection. For concreteness, we focus on the detection of cancer cells located in a particular region of a blood vessel. These cancer cells produce and emit special molecules, so-called biomarkers, which are symptomatic for the presence of anomaly, into the cardiovascular system. Detection of cancer biomarkers with conventional blood tests is difficult in the early stages of a cancer due to the very low concentration of the biomarkers in the samples taken. However, close to the cancer cells, the concentration of the cancer biomarkers is high. Hence, detection is possible if a sensor with the ability to detect these biomarkers is placed in the vicinity of the cancer cells. Therefore, in this paper, we study the use of MNSs that are injected at a suitable injection site and can move through the blood vessels of the cardiovascular system, which potentially contain cancer cells. These MNSs can be activated by the biomarkers close to the cancer cells, where the biomarker concentration is sufficiently high. Eventually, the MNSs are collected by a fusion center (FC), where their activation levels are read and exploited to declare the presence of anomaly. We analytically derive the biomarker concentration in a network of interconnected blood vessels as well as the probability mass function of the MNSs' activation levels and validate the obtained results via particle-based simulations. Then, we derive the optimal decision rule for the FC regarding the presence of anomaly assuming that the entire network is known at the FC. Finally, for the FC, we propose a simple sum detector that does not require knowledge of the network topology. Our simulations reveal that while the optimal detector achieves a higher performance than the sum detector, both proposed detectors significantly outperform a benchmark scheme that uses fixed nanosensors at the FC.
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http://dx.doi.org/10.1109/TNB.2018.2885463DOI Listing
April 2019

Biological Optical-to-Chemical Signal Conversion Interface: A Small-Scale Modulator for Molecular Communications.

IEEE Trans Nanobioscience 2019 01 18;18(1):31-42. Epub 2018 Sep 18.

Although many exciting applications of molecular communication (MC) systems are envisioned to be at microscale, the MC testbeds reported in the literature so far are mostly at macroscale. This may partially be due to the fact that controlling an MC system at microscale is challenging. To link the macroworld to the microworld, we propose and demonstrate a biological signal conversion interface that can also be seen as a microscale modulator. In particular, the proposed interface transduces an optical signal, which is controlled using a light-emitting diode, into a chemical signal by changing the pH of the environment. The modulator is realized using Escherichia coli bacteria as microscale entity expressing the light-driven proton pump gloeorhodopsin from Gloeobacter violaceus. Upon inducing external light stimuli, these bacteria locally change their surrounding pH level by exporting protons into the environment. To verify the effectiveness of the proposed optical-to-chemical signal converter, we analyze the pH signal measured by a pH sensor, which serves as a receiver. We develop an analytical parametric model for the induced chemical signal as a function of the applied optical signal. Using this model, we derive a training-based channel estimator that estimates the parameters of the proposed model to fit the measurement data based on a least square error approach. We further derive the optimal maximum likelihood detector and a suboptimal low-complexity detector to recover the transmitted data from the measured received signal. It is shown that the proposed parametric model is in good agreement with the measurement data. Moreover, for an example scenario, we show that the proposed setup is able to successfully convert an optical signal representing a sequence of binary symbols into a chemical signal with a bit rate of 1 bit/min and recover the transmitted data from the chemical signal using the proposed estimation and detection schemes. The proposed modulator may form the basis for future MC testbeds and applications at microscale.
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http://dx.doi.org/10.1109/TNB.2018.2870910DOI Listing
January 2019

Autologous Fat Grafting in the Treatment of Facial Scleroderma.

Dermatol Res Pract 2018 1;2018:6568016. Epub 2018 Aug 1.

Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Systemic sclerosis (SSc) is a rare systemic autoimmune disease, characterized by progressive cutaneous and internal organ fibrosis. Orofacial manifestations of systemic sclerosis are extremely disabling and treatment options are limited. In this study, we aimed to assess the safety and efficacy of autologous fat grafting in the face of patients with systemic sclerosis. We enrolled 16 SSc patients suffering from facial sclerosis and limited mouth opening capacity. Autologous fat injection ranging from 15 to 40 ml was administered per patient, based on their face morphology. The patients were evaluated at baseline and 3 months after fat injection. Evaluations included mouth opening capacity, mouth handicap in systemic sclerosis (MHISS), Rodnan skin sclerosis score, skin biophysical properties using a sensitive biometrologic device with the assessment of cutaneous resonance running time (CRRT), volumizing and aesthetic effects based on pre- and posttreatment photographs, possible side effects, and global patient satisfaction. Clinical assessment showed autologous fat transfer significantly improved mouth opening capacity and the MHISS and Rodnan score of patients with facial scleroderma (p value <.001). The aesthetic and/or functional results of fat injection were satisfying to about 80% of the patients. The changes in CRRT values were not significant. Our findings support the possible therapeutic role of autologous fat grafting in improving facial scleroderma both in aesthetic and in functional aspects. This trial is registered with IRCT20180209038677N1.
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http://dx.doi.org/10.1155/2018/6568016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6093005PMC
August 2018

Association of CD26/dipeptidyl peptidase IV mRNA level in peripheral blood mononuclear cells with disease activity and bone erosion in rheumatoid arthritis.

Clin Rheumatol 2018 Dec 22;37(12):3183-3190. Epub 2018 Aug 22.

Department of Radiology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Dipeptidyl peptidase IV (DPP-IV, CD26) plays many roles in the pathogenesis of several autoimmune and inflammatory diseases. The current study evaluated the association of DPP-IV enzymatic activity and its gene expression with disease activity and bone erosion in rheumatoid arthritis. Blood samples were collected from 20 rheumatoid arthritis patients and 40 healthy volunteers. Patients were divided into four subgroups using DAS28 index. CD26 gene expression levels were analyzed in peripheral blood mononuclear cells by quantitative reverse transcription-polymerase chain reaction. Additionally, the enzymatic activity of this molecule in serum was determined using Gly-Pro-p-nitroanilide as substrate. Digital radiography was applied to obtain images for bone erosion assessment. No significant difference in serum DPP-IV activity level was seen between patients and controls (p = 0.140). However, patients exhibited an increase in CD26 mRNA expression (1.68 times) when compared to controls (p = 0.001). Moreover, a strong positive correlation between CD26 gene expression and DAS28 index as well as bone erosion in the hands was observed (r = 0.71, p = 0.002 and r = 0.61, p = 0.049, respectively). This study demonstrated that CD26 mRNA expression in rheumatoid arthritis patients is associated with disease activity and bone erosion, suggesting a potential role for this molecule in the immunopathology of rheumatoid arthritis and bone erosion.
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http://dx.doi.org/10.1007/s10067-018-4268-yDOI Listing
December 2018

Symbol Synchronization for Diffusion-Based Molecular Communications.

IEEE Trans Nanobioscience 2017 12;16(8):873-887

Symbol synchronization refers to the estimation of the start of a symbol interval and is needed for reliable detection. In this paper, we develop several symbol synchronization schemes for molecular communication (MC) systems where we consider some practical challenges, which have not been addressed in the literature yet. In particular, we take into account that in MC systems, the transmitter may not be equipped with an internal clock and may not be able to emit molecules with a fixed release frequency. Such restrictions hold for practical nanotransmitters, e.g., modified cells, where the lengths of the symbol intervals may vary due to the inherent randomness in the availability of food and energy for molecule generation, the process for molecule production, and the release process. To address this issue, we develop two synchronization-detection frameworks which both employ two types of molecule. In the first framework, one type of molecule is used for symbol synchronization and the other one is used for data detection, whereas in the second framework, both types of molecule are used for joint symbol synchronization and data detection. For both frameworks, we first derive the optimal maximum likelihood (ML) symbol synchronization schemes as performance upper bounds. Since ML synchronization entails high complexity, for each framework, we also propose three low-complexity suboptimal schemes, namely a linear filter-based scheme, a peak observation-based scheme, and a threshold-trigger scheme, which are suitable for MC systems with limited computational capabilities. Furthermore, we study the relative complexity and the constraints associated with the proposed schemes and the impact of the insertion and deletion errors that arise due to imperfect synchronization. Our simulation results reveal the effectiveness of the proposed synchronization schemes and suggest that the end-to-end performance of MC systems significantly depends on the accuracy of the symbol synchronization.
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http://dx.doi.org/10.1109/TNB.2017.2782761DOI Listing
December 2017

A phase III, randomized, two-armed, double-blind, parallel, active controlled, and non-inferiority clinical trial to compare efficacy and safety of biosimilar adalimumab (CinnoRA®) to the reference product (Humira®) in patients with active rheumatoid arthritis.

Arthritis Res Ther 2017 07 20;19(1):168. Epub 2017 Jul 20.

Tehran University of Medical Sciences, Faculty of Pharmacy, Tehran, Iran.

Background: This study aimed to compare efficacy and safety of test-adalimumab (CinnoRA®, CinnaGen, Iran) to the innovator product (Humira®, AbbVie, USA) in adult patients with active rheumatoid arthritis (RA).

Methods: In this randomized, double-blind, active-controlled, non-inferiority trial, a total of 136 patients with active RA were randomized to receive 40 mg subcutaneous injections of either CinnoRA® or Humira® every other week, while receiving methotrexate (15 mg/week), folic acid (1 mg/day), and prednisolone (7.5 mg/day) over a period of 24 weeks. Physical examinations, vital sign evaluations, and laboratory tests were conducted in patients at baseline and at 12-week and 24-week visits. The primary endpoint in this study was the proportion of patients achieving moderate and good disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR)-based European League Against Rheumatism (EULAR) response. The secondary endpoints were the proportion of patients achieving American College of Rheumatology (ACR) criteria for 20% (ACR20), 50% (ACR50), and 70% (ACR70) responses along with the disability index of health assessment questionnaire (HAQ), and safety.

Results: Patients who were randomized to CinnoRA® or Humira® arms had comparable demographic information, laboratory results, and disease characteristics at baseline. The proportion of patients achieving good and moderate EULAR responses in the CinnoRA® group was non-inferior to the Humira® group at 12 and 24 weeks based on both intention-to-treat (ITT) and per-protocol (PP) populations (all p values >0.05). No significant difference was noted in the proportion of patients attaining ACR20, ACR50, and ACR70 responses in the CinnoRA® and Humira® groups (all p values >0.05). Further, the difference in HAQ scores and safety outcome measures between treatment arms was not statistically significant.

Conclusion: CinnoRA® was shown to be non-inferior to Humira® in terms of efficacy at week 24 with a comparable safety profile to the reference product.

Trial Registration: IRCT.ir, IRCT2015030321315N1 . Registered on 5 April 2015.
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http://dx.doi.org/10.1186/s13075-017-1371-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520357PMC
July 2017

CD13/aminopeptidase N mRNA expression and enzyme activity in Systemic Lupus Erythematosus.

Acta Reumatol Port 2017 Apr-Jun;42(2):162-167

Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aims: To determine the significance of CD13/aminopeptidase N (APN) in systemic Lupus Erythromatus (SLE), we examined its catalytic activity and mRNA expression level in sera and peripheral whole blood cells of patients with SLE.

Methods: In this study, 47 SLE patients and 44 age, sex matched healthy controls were included. The SLE disease activity index score and clinical finding including renal involvement and blood pressure were recorded. Catalytic activities of CD13/APN were measured in serum samples. In addition, CD13 mRNA level in peripheral whole blood cells was analyzed by quantitative real-time PCR.

Results: A Significant higher aminopeptidase activity was observed in serum from patients with SLE than serum from controls. In addition, CD13/APN mRNA expression was 6.12 times higher in SLE patients than in healthy controls. However, CD13/APN mRNA level, or its activity in serum, did not correlate with the score determined according to SLE disease activity index. Additionally, there was not any significant correlation between the complication in organs, including, kidney, and CD13/APN gene expression level or CD13/APN enzyme activity.

Conclusion: CD13/APN enzyme activity and mRNA expression level were higher in SLE patients regardless of their disease activity. More studies are needed to better clarify the role of CD13/APN in the pathogenesis of SLE.
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October 2018

Does Regular Use of a Complementary Medicine of and Have Adverse Effects on Lipid Profile and Fasting Blood Glucose of Rheumatoid Arthritis (RA) Patients Under Treatment with DMARD Regimens Containing Methotrexate?

Iran J Pharm Res 2016 ;15(4):933-940

Food Safety Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ; Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Rheumatoid arthritis (RA) patients are vulnerable to cardiovascular morbidity and mortality in which atherosclerosis plays a major role. In this study, the lipid profile and fasting blood sugar (FBS) of RA patients receiving a complementary medicine of olive and fig, as add-on therapy for routine disease-modifying antirheumatic drugs (DMARDs) regimen containing low dose methotrexate (MTX), were studied. A randomized controlled clinical trial was designed. Adult RA patients were randomly allocated in two groups receiving routine DMARDs regimen (control group) and routine DMARDs regimen plus the herbal supplementary formulation of olive oil, fig and olive fruits (intervention group). Patients were followed every 4 weeks for total study period of 16 weeks. In addition to demographic and medical history of the patients, the total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), the atherogenic index of plasma (AIP) defined as log(TG/HDL-C), and the fasting blood sugar (FBS) were determined and recorded. 56 patients (control = 27 and intervention = 29), with mean ± sd age of 50.9 ± 12.3 years completed the study. Average MTX dose received by intervention and control groups were 24.30 ± 18.39 and 17.61 ± 15.53 mg/week, respectively (p = 0.11). Repeated measures analysis of variance (ANOVA) revealed that differences between lipid profile indicators and FBS in the two study groups were not statistically significant (P>0.05). No additional substantial adverse reaction was seen in the study groups. Our findings are more reassuring for patients and their doctors to trust on the safety of the investigated complementary preparation to be used as add-on therapy to manage rheumatoid arthritis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316274PMC
January 2016

Study of the Effect of an Oral Formulation of Fig and Olive on Rheumatoid Arthritis (RA) Remission Indicators: A Randomized Clinical Trial.

Iran J Pharm Res 2016 ;15(3):537-545

Department of Rheumatology, Loghman-e Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

This study was designed to explore the complementary effects of a combination formulation of olive oil, olive and fig fruits on RA remission indicators. A randomized controlled clinical trial was designed. Adult RA patients were randomly divided into two groups receiving routine Disease-modifying antirheumatic drugs (DMARDs) regimen (control group) and routine DMARDs regimen plus the herbal supplementary formulation of olive oil, fig and olive fruits (intervention group). Patients were followed every 4 weeks for total study period of 16 weeks. In addition to demographic and medical history of the patients, the Disease Activity Score with 28-joint counts based on Erythrocyte Sedimentation Rate (DAS28_ESR) were recorded. SPSS (version 22.0) software was used to analyze data, assuming p<0.05 as significance level. 56 patients (control = 27 and intervention = 29), with mean ± sd age of 50.91 ± 12.26 years completed the study. Repeated measures analysis revealed that differences between remission indicators in the two study groups were not statistically significant, however, there was a p = 0.03 for the within-subjects contrast test of the Patient Global Assessment (PtGA), approving a nonlinear change for PtGA with respect to time. No between groups differences in adjunct drug therapy pattern for disease flares were seen. In conclusion, although, non-significant changes in the study variable of DAS28_ESR is in agreement with few previous reports, nevertheless, trends in its reduction in the intervention group along with the significant delayed PtGA score improvements occurred in the intervention group convince us to suggest further investigations on the supplementary olive and fig products, with a longer follow up periods.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5149042PMC
January 2016

The Effect of Quercetin on Inflammatory Factors and Clinical Symptoms in Women with Rheumatoid Arthritis: A Double-Blind, Randomized Controlled Trial.

J Am Coll Nutr 2017 01 6;36(1):9-15. Epub 2016 Oct 6.

c Department of Nutrition , School of Public Health, Iran University of Medical Sciences , Tehran , IRAN.

Objective: Previous studies have shown that the bioflavonoid quercetin has anti-inflammatory and anti-nociceptive effects. We investigated the effect of quercetin supplementation on inflammation, disease severity, and clinical symptoms in women with rheumatoid arthritis (RA).

Methods: The present study was a randomized, double-blind, placebo-controlled clinical trial in which 50 women with RA were allocated into a quercetin (500 mg/day) or placebo group for 8 weeks. Plasma levels of high-sensitivity tumor necrosis factor-α (hs-TNFα), erythrocyte sedimentation rate (ESR), clinical symptoms including early morning stiffness (EMS), morning and after-activity pain, and tender (TSC) and swollen joint counts (SJC) were determined. Disease activity and functional disability were assessed by Disease Activity Score 28 (DAS-28), physician global assessment (PGA), and a health assessment questionnaire (HAQ) at the beginning and end of the study.

Results: Quercetin supplementation for 8 weeks significantly reduced EMS, morning pain, and after-activity pain (p < 0.05). DAS-28 and HAQ scores decreased in the quercetin group compared to placebo and the number of patients with active disease significantly decreased in the quercetin group. Plasma hs-TNFα level was significantly reduced in the quercetin group compared to placebo (p < 0.05). There were no significant differences in TJC and SJC between groups but TJC significantly decreased in the quercetin group after the intervention. Supplementation had an effect on ESR but it was not significant (p > 0.05).

Conclusions: Five hundred milligrams per day quercetin supplementation for 8 weeks resulted in significant improvements in clinical symptoms, disease activity, hs-TNFα, and HAQ in women with RA.
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http://dx.doi.org/10.1080/07315724.2016.1140093DOI Listing
January 2017

Comprehensive Reactive Receiver Modeling for Diffusive Molecular Communication Systems: Reversible Binding, Molecule Degradation, and Finite Number of Receptors.

IEEE Trans Nanobioscience 2016 10 14;15(7):713-727. Epub 2016 Sep 14.

This paper studies the problem of receiver modeling in molecular communication systems. We consider the diffusive molecular communication channel between a transmitter nano-machine and a receiver nano-machine in a fluid environment. The information molecules released by the transmitter nano-machine into the environment can degrade in the channel via a first-order degradation reaction and those that reach the receiver nano-machine can participate in a reversible bimolecular reaction with receiver receptor proteins. Thereby, we distinguish between two scenarios. In the first scenario, we assume that the entire surface of the receiver is covered by receptor molecules. We derive a closed-form analytical expression for the expected received signal at the receiver, i.e., the expected number of activated receptors on the surface of the receiver. Then, in the second scenario, we consider the case where the number of receptor molecules is finite and the uniformly distributed receptor molecules cover the receiver surface only partially. We show that the expected received signal for this scenario can be accurately approximated by the expected received signal for the first scenario after appropriately modifying the forward reaction rate constant. The accuracy of the derived analytical results is verified by Brownian motion particle-based simulations of the considered environment, where we also show the impact of the effect of receptor occupancy on the derived analytical results.
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http://dx.doi.org/10.1109/TNB.2016.2609600DOI Listing
October 2016

Correlating Whole-Body Bone Mineral Densitometry Measurements to Those From Local Anatomical Sites.

Iran J Radiol 2016 Jan 27;13(1):e25609. Epub 2016 Jan 27.

Clinical Research and Development Center, Imam Hossein Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Using the same cutoff points for whole-body measurements as for site-specific measurements will result in underestimation of osteoporosis.

Objectives: We assessed the correlation between densitometry measurements for the whole body with those for the femur, lumbar spine, and forearm to evaluate the possibility of replacing site-specific values with whole-body measurements.

Patients And Methods: In this cross-sectional study, we evaluated all patients referred to a single rheumatology clinic for bone mineral density measurements from 2009 to 2010. All patients who had bone mineral density measurements taken from the hip, lumbar spine, forearm, and whole body were enrolled in the study. Standard bone mineral density measurements were performed using a dual energy X-ray absorptiometry device (Hologic Delphi A; Hologic, Bedford, MA, USA). Bone mineral density, Z-score, and T-score were measured for all patients and all body regions.

Results: The mean age of the 152 participating patients was 56.7 ± 12.6 years, and 97.4% were female. Pearson correlation coefficients of the whole-body bone mineral density values compared with site-specific values in patients over age 50 were 0.66 - 0.75. Using T-score cutoff points of -1 and -2.5 for osteopenia and osteoporosis, whole-body measurements underestimated the percentage of abnormal patients compared with the site-specific measurements (all P < 0.001). Using receiver operating characteristic (ROC) analysis, the whole-body bone mineral density showed respective areas under the curve of 0.96 and 0.84 for the diagnosis of abnormal hip bone mineral density and osteoporosis.

Conclusion: Using the same cutoff points for whole-body measurements as for site-specific measurements will result in overestimation or especially underestimation of osteopenia and osteoporosis diagnosis. Choosing new and appropriate cutoff points for whole-body densitometric measurements when we want to substitutes this assessment instead of site specific measurements seems mandatory and will decrease the rate of false diagnoses of densitometric deficiencies in these anatomical sites.
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http://dx.doi.org/10.5812/iranjradiol.25609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841932PMC
January 2016

Ion Channel Based Bio-Synthetic Modulator for Diffusive Molecular Communication.

IEEE Trans Nanobioscience 2016 07 21;15(5):418-432. Epub 2016 Apr 21.

In diffusion-based molecular communication (DMC), a transmitter nanomachine is responsible for signal modulation. Thereby, the transmitter has to be able to control the release of the signaling molecules employed for representing the transmitted information. In nature, an important class of control mechanisms for releasing molecules from cells utilizes ion channels which are pore-forming proteins across the cell membrane. The opening and closing of the ion channels is controlled by a gating parameter. In this paper, an ion channel based modulator for DMC is proposed which controls the rate of molecule release from the transmitter by modulating a gating parameter signal. Exploiting the capabilities of the proposed modulator, an on-off keying modulation technique is introduced and the corresponding average modulated signal, i.e., the average release rate of the molecules from the transmitter, is analyzed. However, since the modulated signal is random in nature, it may deviate from its average. Therefore, the concept of modulator noise is introduced and the statistics of the modulated signal are investigated. Finally, by assuming a simple transparent receiver, the performance of the proposed on-off keying modulation format is studied. The derived analytical expressions for the average modulated signal are confirmed with particle based simulations. Our numerical results reveal that performance estimates of DMC systems obtained based on the assumption of instantaneous molecule release at the transmitter may substantially deviate from the performance achieved with practical modulators.
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http://dx.doi.org/10.1109/TNB.2016.2557350DOI Listing
July 2016

Evaluation of safety, efficacy and post-cessation efficacy durability of tocilizumab in patients with active rheumatoid arthritis.

Int J Rheum Dis 2017 Feb 19;20(2):231-237. Epub 2015 Sep 19.

Loghman Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aim: To evaluate safety and efficacy of tocilizumab (TCZ) in a post-approval pilot study among selected Iranian patients with moderate to severe rheumatoid arthritis (RA) and inadequate responses to disease-modifying antirheumatic drugs (DMARDs).

Methods: Twenty-four weeks monitoring of adverse events and efficacy of TCZ plus previously used DMARD(s) and steroids, as well as investigating durability of TCZ effects within a year after the drug cessation. The efficacy end-points included 28-joint Disease Activity Score (DAS28) and an annual change in radiographic Sharp-van der Heijde score (SHS).

Results: With no withdrawal from the study due to adverse events (AE) or unsatisfactory responses in the 21 treated patients, the most common drug-related AEs were dermatologic and the most common serious AEs were infectious in origin (all of the latter occurring after the last drug dose). The only case of TCZ dose alteration was due to increased transaminase levels. Changes in lipid and hemoglobin levels were within the expected ranges. At week 24, cumulative frequencies for significant clinical response, low disease activity and remission were 100%, 90.5% and 76.2%, respectively. The mean SHS in both hands showed no significant change a year after the first TCZ dose. Mean DAS28 levels gradually increased through 1 year post-cessation follow-up, with a somewhat slower rate compared to the initial mean DAS28 reduction.

Conclusion: In our DMARD-resistant RA patients, TCZ plus DMARD provided a predicted rapid clinical improvement and inhibited structural joint damage, but with some unexpected safety concerns and an expected vanishing of post-cessation efficacy.
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http://dx.doi.org/10.1111/1756-185X.12686DOI Listing
February 2017

Safety, Tolerability, and Efficacy of Tocilizumab in Rheumatoid Arthritis: An Open-Label Phase 4 Study in Patients from the Middle East.

Int J Rheumatol 2015 19;2015:975028. Epub 2015 May 19.

Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

This open-label study investigated the safety and efficacy of tocilizumab in Middle Eastern patients with rheumatoid arthritis (RA). Patients whose Disease Activity Score based on 28 joints (DAS28) was >3.2 received tocilizumab 8 mg/kg intravenously every 4 weeks for 24 weeks. Patients receiving aTNF ± nonbiologic disease-modifying antirheumatic drug(s) (DMARD(s)) switched to tocilizumab; patients receiving nonbiologic DMARD monotherapy added tocilizumab. Primary end points were adverse events (AEs), serious AEs (SAEs), and laboratory parameters; secondary end points were DAS28, Health Assessment Questionnaire-Disability Index, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Eighty-eight of 95 patients completed 24 weeks. Overall, 125 AEs were reported in 43 (45%) patients; the most common were increased hepatic enzymes (16%) and cholesterol (11%). Eight patients experienced SAEs. Significant changes from baseline to week 24 occurred for hemoglobin, neutrophils, platelets, total cholesterol, and liver enzymes (P < 0.05). DAS28, CRP, and ESR decreased significantly from baseline at each visit (P < 0.0001). At week 24, the proportions of patients reporting DAS28 clinically meaningful improvement (decrease ≥1.2), low disease activity (DAS28 ≥2.6 to ≤3.2), and remission (DAS28 <2.6) were 92%, 23%, and 64%, respectively. Safety and efficacy of tocilizumab were consistent with values reported in Western patients.
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http://dx.doi.org/10.1155/2015/975028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452319PMC
June 2015

Comparison of three different osteoporosis risk assessment tools: ORAI (osteoporosis risk assessment instrument), SCORE (simple calculated osteoporosis risk estimation) and OST (osteoporosis self-assessment tool).

Med J Islam Repub Iran 2014 15;28:94. Epub 2014 Sep 15.

5. Assistant Professor of ENT-Head and Neck Surgery, Endoscopic Pituitary and Skull Base Surgery Unit, ENT-Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: SCORE, OST and ORAI risk assessment tools could reduce the cost burden of BMD tests by selecting the high risk patients to osteoporosis. In this study we compared the ability of these risk assessment measures to assess probability of the osteoporosis among post-menopausal women.

Methods: 211 post-menopausal women aged 45-88 years enrolled into the study. All of the patients underwent BMD test and divided into two groups according to T-Score level. 43 patients (20.4%) had T-Score ≤-2.5 (osteoporotic) (group-1) and 168 (70.6%) patients had T-Score of > -2.5 (non-osteoporotic). Among 168 nonosteoporotic cases, 88 had -2.5≤T-Score≤-2 in at least one bony area. These 88 cases in addition to the 43 cases with -2.5≤T-Score considered as high risk group to osteoporosis (group 2). Afterward, SCORE, OST and ORAI risk scores were calculated and sensitivity, specificity, likelihood ratio, accuracy index and area under the curve of each tool were determined in both groups and then compared with each other.

Results: SCORE had the highest sensitivity compared with others in both groups (95% and 88.2% respectively). Moreover, it had the highest diagnostic odds ratio and negative predictive value between the three methods. OST had the highest likelihood ratio and specificity in both groups (71.4% and 75.4%). There was significant difference between the sensitivity and specificity of the tests (p= 0.004 and 0.027).

Conclusion: OST with the highest specificity and positive LR had a special role in determining the osteoporotic patients and SCORE with the highest sensitivity and negative predictive value had an exceptional role in exclusion of the non- osteoporotic individuals. However, considering the area under the curve, there was no significant difference among these three methods in determining osteoporosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301225PMC
February 2015

The effect of quercetin on plasma oxidative status, C-reactive protein and blood pressure in women with rheumatoid arthritis.

Int J Prev Med 2014 Mar;5(3):293-301

Department of Nutrition and Biochemistry, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran ; Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Iran.

Background: Considering the increased production of free radicals and inflammatory factors in rheumatoid arthritis (RA) and the effects of bioflavonoid quercetin on reducing oxidative stress, inflammation and blood pressure, the present study examined the effects of bioflavonoid quercetin on total antioxidant capacity (TAC) of plasma, lipid peroxidation and blood pressure in women with RA.

Methods: The current study was a randomized double-blind clinical trial in which 51 women with RA aged 19-70 years, were participated. Patients were assigned into quercetin (500 mg/day) or placebo groups for 8 weeks. Dietary intake was recorded using 24-h dietary recall questionnaire and the physical activity was assessed through an international short questionnaire of physical activity at the beginning and end of the study. Plasma TAC and malondialdehyde (MDA) using colorimetric method, oxidized low density lipoprotein (ox-LDL) and high sensitivity C-reactive protein (hs-CRP) using enzyme-linked immunosorbent assay method and also blood pressure were measured at the beginning and end of intervention.

Results: After 8 weeks there were no significant differences in TAC of plasma, ox-LDL, MDA, hs-CRP, systolic and diastolic blood pressure between quercetin and placebo groups and in each group comparing before and after.

Conclusions: In this study, quercetin had no effect on oxidative and inflammatory status of plasma and blood pressure in patients with RA. Further studies are needed to ensure the effect of quercetin on oxidative stress and inflammation in human.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018638PMC
March 2014

Assessing rheumatologists and radiologists agreement rate regarding the diagnosis of focal bone erosions and osteopenic changes using hand X-rays radiography in patients with rheumatoid arthritis.

Rheumatol Int 2013 Aug 5;33(8):2019-23. Epub 2013 Feb 5.

Rheumatology Research Department, Loghman Hakim Hospital, Shaheed Beheshti University of Medical Sciences, South Kargar Street, 13336-31151 Tehran, Iran.

In rheumatoid arthritis, diagnosis of bone erosions and osteopenic changes in earlier stages is extremely important to the initiation of specific and more aggressive treatment to subsidize the disease, decrease morbidities, and increase patients' quality of life. In the present study, we assessed consensus rate of rheumatologists and radiologists regarding the detection of radiographic changes of hand in rheumatoid arthritis. Ninety-six adult patients with documented rheumatoid arthritis referring to our outpatient rheumatology clinic during March 2009-2010, enrolled into this cross-sectional study. Hands and wrists X-ray obtained for all patients. The films were observed by a rheumatologist and a radiologist separately, to detect focal bone erosions, periarticular osteopenic changes, and joint space losses. Agreement rates between the two specialists were assessed using the kappa test ratio. A total of 96 patients comprising 86 (89.5%) female and 10 (10.41%) male with a mean age of 48.5 ± 1.2 years (range 22-76 years old) were studied. The proportion agreement between the radiologist and rheumatologist regarding bone erosions and juxta-articular osteopenic changes was 69.7 and 84.3%, respectively. The kappa agreement coefficient for the diagnosis of bone erosions was 36% which showed significant poor agreement between two specialist (p < 0.001, proportion agreement = 69.7%). As well, the kappa of 20% for the detection of juxta-articular osteopenic changes revealed significant poor agreement between the two specialist (p < 0.047, proportion agreement = 84.3%). The results of the present study demonstrate that there is a minimal agreement between the two radiology and rheumatology specialists regarding simultaneous diagnosis of bone erosions and periarticular osteopenic changes in rheumatoid arthritis patients that emphasis requiring both specialists' X-ray report at the time of diagnosis.
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http://dx.doi.org/10.1007/s00296-012-2645-4DOI Listing
August 2013