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ID PMID Title PublicationDate abstract
30051293 Are the 2016 EULAR/ACR/PRINTO classification criteria for macrophage activation syndrome a 2019 Jan The objectives of this study are to determine whether the 2016 European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organization classification criteria for macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (SJIA) can be used to identify MAS in patients with adult-onset Still's disease (AOSD). Using laboratory data from 76 AOSD patients with and without MAS, we analyzed the ability of the collective and individual constitutive elements of the 2016 MAS in SJIA criteria and additional laboratory measures to discriminate between AOSD patients with (n = 16) and without (n = 60) MAS. Cutoff values to determine the sensitivity, specificity, and predictive values were calculated from receiver operating characteristic curves, and modified classification criteria for MAS in AOSD were evaluated. The 2016 MAS in SJIA classification criteria had an overall sensitivity of 100%, specificity of 70.0%, positive predictive value of 47.1%, and negative predictive value of 100% to discriminate between AOSD patients with and without MAS based on laboratory data. Among the individual criteria, the sensitivity of triglycerides (46.7%) and the specificity of ferritin (15.0%) for MAS in AOSD were particularly low. The sensitivity and specificity for classifying MAS in AOSD patients were increased to 100 and 93%, respectively, by excluding triglycerides and changing the cutoff values for other criteria in the 2016 MAS in SJIA classification. The 2016 classification criteria for MAS in SJIA had higher sensitivity but lower specificity to identify MAS in AOSD patients compared with SJIA patients.
30047435 Less common rheumatologic disorders: Current concepts of skin and systemic manifestations. 2018 Jul The cutaneous manifestations of the common rheumatologic disorders, such as systemic lupus erythematosus, dermatomyositis, and systemic sclerosis, are well known. In contrast, the dermatologic findings of less common rheumatologic disorders, including Sjögren syndrome, mixed connective tissue disease, and relapsing polychondritis, are less widely known. The cutaneous manifestations of these connective tissue disorders are reviewed.
30030617 Salivary adiponectin, but not adenosine deaminase, correlates with clinical signs in women 2019 Mar OBJECTIVES: To evaluate salivary adiponectin and adenosine deaminase (ADA) in women suffering from Sjögren's syndrome (SS). METHODS: Salivary adiponectin and ADA were measured in patients with SS (n = 17) and compared to their values in healthy controls (n = 13) and patients suffering from drug-induced xerostomia (non-SS sicca group; n = 19). A clinical history was made for each patient, patients were examined clinically, and xerostomia inventory (XI) was performed. RESULTS: Salivary adiponectin corrected by total protein was higher in patients with SS than in healthy individuals (P < 0.05) or patients with non-SS sicca (P < 0.01) and correlated with XI (r = 0.555; P < 0.05). Salivary ADA was higher in patients with SS and non-SS sicca compared to controls (P < 0.05 in both cases). CONCLUSION: The results of the present study indicate that adiponectin and ADA are increased in the saliva of patients with SS. CLINICAL RELEVANCE: Salivary adiponectin corrected by total protein can be a potential biomarker of SS. TRIAL REGISTRATION: NCT03156569.
30671484 Current and Emerging Evidence for Toll-Like Receptor Activation in Sjögren's Syndrome. 2018 While the importance of Toll-like receptor (TLR) signaling is well established in many autoimmune diseases, the role of TLR activation in Sjögren's syndrome (SS) is poorly understood. Studies in mice and humans reveal that TLRs are potent mediators of inflammation in SS. TLRs are expressed and functional in salivary tissue, and TLRs in peripheral blood cells of SS patients are also upregulated and hyperresponsive to ligation. In this review, we will detail observations in mouse models regarding the importance of TLR activation in both local and systemic disease. We will then discuss studies in SS patients that provide evidence of the importance of TLR-mediated signaling in disease. While the ligands that activate TLRs in the context of SS are unknown, emerging data suggest that damage-associated molecular patterns (DAMPs) may be significant drivers of the chronic and unremitting inflammation that is characteristic of SS. We will discuss putative DAMPs that may be of clinical significance in disease. Therapies that target TLR signaling cascades will likely reduce both exocrine-specific and systemic manifestations of SS.
30481822 Potential Role of Oxidative Stress in Ocular Surface Inflammation and Dry Eye Disease. 2018 Nov 1 Reactive oxygen species (ROS) are produced as a by-product during the mitochondrial respiration of the oxygen and potentially able to damage the tissues. Oxidative stress occurs as a result of the disruption of the balance between the anti-oxidant system and the pro-oxidant system found in cells. It has been accepted that overexpression of ROS can be induced in the ocular surface as a result of many acute and chronic diseases and even in normal aging. Recent studies demonstrated that oxidative stress damages the ocular surface and plays an important role in the mechanism of dry eye disease. There is a need to investigate the therapeutic modalities employing topical/systemic use of antioxidants in dry eye disease. This review will summarize the recent studies showing the important relationship between oxidative stress and dry eye disease.
29486915 Rescue of autophagy and lysosome defects in salivary glands of MRL/lpr mice by a therapeut 2018 Jun Sjögren's syndrome is a multifactorial systemic autoimmune disorder characterized by lymphocytic infiltrates in exocrine organs. Patients present with sicca symptoms, such as extensive dry eyes and dry mouth, and parotid enlargement. Other serious complications include profound fatigue, chronic pain, major organ involvement, neuropathies and lymphomas. Current treatments only focus on relieving symptoms and do not target the origin of the disease, which is largely unknown. The question we addressed here was whether some defects exist in autophagy processes in Sjögren's syndrome and if they can be corrected or minimized using an appropriate mechanism-driven treatment targeting this central survival pathway. Using a recognized murine model of secondary Sjögren's syndrome, we identified molecular alterations of autophagy occurring in the salivary glands of MRL/lpr mice, and discovered that opposite (up- or down-regulated) autophagy events can arise in distinct organs of the same mouse strain, here in lymphoid organs and salivary glands. We showed further that the therapeutic P140 peptide, known to directly act on chaperone-mediated autophagy, rescued MRL/lpr mice from cellular infiltration and autophagy defects occurring in salivary glands. Our findings provide a proof-of-concept that targeting autophagy might represent a promising therapeutic strategy for treating patients with Sjögren's syndrome.
30256702 Elevation of Serum IL-35 in Patients with Primary Sjögren's Syndrome. 2018 Oct Interleukin-35 (IL-35) is a critical anti-inflammatory cytokine in autoimmune disease. In the current study, we aimed to investigate the serum IL-35 levels and its clinical association in patients with primary Sjögren's syndrome (pSS) and to investigate whether or not IL-35 participates in the pathogenesis of pSS. One hundred seventy-six pSS patients and 60 healthy controls (HCs) were recruited. Disease activity was assessed according to EULAR SS disease activity index. Serum IL-35 levels were quantified by enzyme-linked immunosorbent assay. The correlations between the serum IL-35 levels with the clinical parameters were analyzed by a Spearman's correlation test. The serum IL-35 levels in the patients with pSS were significantly increased compared with the HCs. The serum IL-35 levels were elevated in the patients with pSS. Strikingly, the serum IL-35 levels in pSS patients with short disease duration (<1 year) were significantly lower compared with HCs. However, the serum IL-35 levels in pSS patients with medium (1-2 year) and long disease duration (>2 years) were higher compared with HCs. We also found a positive correlation between expression of IL-35 and erythrocyte sedimentation rate, disease activity, and immunoglobulin G. Furthermore, the pSS patients with RF-positive showed high serum IL-35 levels. These findings suggest that IL-35 could play a key role in pSS pathogenesis. In addition, our results highlight the potential exploitation of IL-35 as a biomarker of disease activity and may represent a novel therapeutic agent for pSS.
29784018 Adding colchicine to immunosuppressive treatments; a potential option for biologics-refrac 2018 May 21 BACKGROUND: Adult-onset Still's disease (AOSD) is a rare inflammatory disorder characterized by the classical triad of daily spiking fever, arthritis, and typical salmon-colored rash. Resistance to first-line corticosteroids and second-line disease modified anti-rheumatic-drugs defines refractory AOSD, which mostly includes the polycyclic or chronic courses of the disease. Anti-cytokine therapies are recommended in AOSD patients who are refractory to traditional treatments. This is the first report on the efficacy of colchicine in a patient with AOSD which was refractory to immunosuppressive treatments including biologics. CASE PRESENTATION: A 24-years Japanese female patient was referred to our hospital for the flare-up of AOSD under the combined treatments with steroid, immunosuppressants, and biologics. She was diagnosed with AOSD according to the Yamaguchi criteria, based on the presence of spiking fever, polyarthralgia, skin rash, and hyperferritinemia. Interleukin-6 or tumor necrosis factor-α blockade treatments were not effective, the oral administration of colchicine was stared under the immunosuppressive treatments with steroid and cyclosporine A (CyA). Colchicine treatment silenced the disease activity of AOSD. The dose of prednisolone was successfully tapered, and the elevated levels of C-reactive protein were normalized. Remission has been maintained for 13 months with the start of oral administration of colchicine. CONCLUSION: We concluded that colchicine is an alternative treatment in patients with refractory AOSD, particularly in those with impaired therapeutic effects against anti-cytokines therapies.
30224614 Implant-supported Prostheses in Patient with Sjögren's Syndrome: Clinical Report with 3-y 2018 Sjögren's syndrome (SS), an autoimmune disorder, affects the exocrine glands, including the lacrimal and salivary glands. It is characterized by symptoms of dry eye and dry mouth. As secretion of saliva decreases, patients with SS experience rampant caries, pain in the oral mucosa, inflammation and hardening of the salivary glands, abnormal taste, dysphagia, and loss of teeth earlier than healthy individuals. A removable partial denture is often used as a prosthesis after tooth loss. Compromised salivary lubrication, however, can produce traumatic ulceration of the mucosa, making use of a removable prosthesis in SS patients painful. In such cases, a dental implant is likely to be requested as an alternative. This report describes dental implant treatment in an SS patient, a 50-year-old woman who presented with the chief complaint of masticatory dysfunction and pain due to a removable partial denture. Eight implants were placed in the maxillary and mandibular first molar tooth and second molar tooth regions. Following a 4-month non-loading period, second-stage surgery and provisional restoration with a screwretained implant temporary crown were performed. Screw-retained superstructures were fitted by means of a customized titanium abutment and zirconia crown as the final restoration. No complications, including inflammation of peri-implant soft tissue or resorption of peri-implant bone, were observed at 3 years following placement of the superstructures.
30070035 Novel parotid sialo-cone-beam computerized tomography features in patients with suspected 2019 Jan OBJECTIVE: Sjogren's syndrome (SjS) causes salivary gland impairment leading to oral dryness. Parotid sialo-cone-beam computerized tomography (sialo-CBCT) demonstrates ductal architecture and to a lesser extent gland activity. This study characterizes radiographic features of patients suspected for SjS and looks for a possible correlation with the diagnosis of SjS. METHODS: The clinical and radiographic data of suspected SjS/dry mouth patients referred for sialo-CBCT in 2011-2014 were reviewed retrospectively. Two observers studied the scans for various radiographic features including duct morphology, level of branching, ductopenia and sialectasia. These features were analysed taking the specific clinical data and two sets of SjS criteria: The 2002 American-European Consensus Group (AECG) and the 2012 American College of Rheumatology (ACR) Group. RESULTS: Sialo-CBCT scans of 67-referred patients suffering from dry mouth (115 parotid glands) were included. Intraradiographic association was found between ductopenia and all other radiographic parameters. Minimal, yet important, radiographic differences were found between left and right parotid glands. AECG-confirmed-SjS patients showed strong correlation with radiographic features, whereas ACR 2012-confirmed-SjS patients did not. CONCLUSION: Sialo-CBCT demonstrates novel radiographic features which may clarify the diagnosis of SjS. Further studies are needed to determine the role of sialo-CBCT in diagnosis of SjS.
29689477 Ultrasound elastography in assessment of salivary glands involvement in primary Sjögren's 2018 Jul OBJECTIVE: Our study aimed to assess the pathological sonoelastographic changes in the major salivary glands and to demonstrate the diagnostic effectiveness of Sonoelastography as an additional method to US in Sjögren's syndrome. METHODS: Fifty eight patients with primary Sjögren's syndrome (pSS) were selected according to the American-European Consensus Group Classification criteria. Twenty five healthy volunteers involved in this study. All patients were evaluated with B-mode and elastography by using Hitachi EUB 7500 digital ultrasound equipment. All subjects were female. The sonoelastography examination, which allowed us to assess the elasticity of the parenchyma, was performed and strain ratios were measured by comparing with the adjacent tissues. RESULTS: Statistically significant differences were found between the pSS and control groups for the elastographic scores and strain ratios (p < 0.001). The highest sensitivity and specificity levels were obtained when the strain ratio cut-off value was taken as 1.55 for the submandibular gland and 2.45 for the parotid gland (sensitivity and specificity were 83% and 88% respectively for the submandibular gland and 83% and 92% respectively for the parotid gland). However, no statistically significant differences were found between the disease duration and the elasticity scores or strain ratios in pSS group (p > 0.05). CONCLUSION: US examination is an efficient method to assess major salivary gland involvement in the diagnosis of pSS. Sonoelastography is a modality which can contribute to the diagnosis by improving specificity in the differential diagnosis of pSS. Strain ratio measurement, which is a semi-quantitative method, increases the diagnostic effectiveness by providing high sensitivity, specificity, and negative predictive values.
29573557 The correlation between the Childhood Health Assessment Questionnaire and disease activity 2018 Sep BACKGROUND: The Childhood Health Assessment Questionnaire (CHAQ) has been adapted from the Stanford Health Assessment Questionnaire for assessing functional ability in children. The present study aimed to determine the correlation between CHAQ and disease activity in juvenile idiopathic arthritis (JIA) during active and inactive disease. METHODS: JIA patients in the Pediatric Department, Ramathibodi Hospital, between January 2011 and December 2013, were included in the study. The CHAQ disability index (DI) and disease activity variables, including active and limited joint count, erythrocyte sedimentation rate, patient's global assessment (PtGA), physician's global assessment (PGA) and 27-joint Juvenile Arthritis Disease Activity Score (JADAS27), were collected from medical records for each patient over six visits. At each visit, each patient was classified as having either active or inactive disease. The correlations between CHAQ-DI and disease activity variables were analysed using Spearman's correlation. RESULTS: The classification of 139 JIA patients consisted of enthesitis-related arthritis (30.9%), systemic JIA (28.1%), oligoarthritis (16.5%), rheumatoid factor (RF)-negative polyarthritis (15.1%), RF-positive polyarthritis (6.5%) and undifferentiated arthritis (2.9%). Out of 812 patient visits, 606 were in active disease and 206 were in inactive disease. RF-negative polyarthritis had the highest CHAQ-DI (0.39 ± 0.66), while oligoarthritis had the lowest (0.20 ± 0.32). There was a good correlation between CHAQ-DI and JADAS27, PGA and PtGA in all JIA subtypes (p < 0.05) during active disease, but a poor correlation between CHAQ-DI and disease activity variables during inactive disease. CONCLUSIONS: CHAQ-DI had a good correlation with disease activity during active disease but a poor correlation during inactive disease. Therefore, CHAQ is only useful for assessing functional ability during active disease.
30111237 Psychometric validation of the Arthritis Helplessness Index in systemic lupus erythematosu 2018 Oct Objective Helplessness is a relevant construct in systemic lupus erythematosus (SLE), an unpredictable chronic illness with no known cure characterized by relapsing and remitting features. However, no measure of helplessness has been validated in this population. The present study examined the structural validity, reliability, and convergent validity of the Arthritis Helplessness Index, a measure initially developed for rheumatoid arthritis populations, in a sample of patients with SLE. Methods Patients with SLE ( N = 136) receiving medical care at a private hospital completed the Arthritis Helplessness Index and other self-report measures. The structural validity of the Arthritis Helplessness Index was examined using confirmatory factor analysis. Internal consistency reliability was evaluated with Cronbach's coefficient alpha. Pearson product-moment correlations were used to examine convergent validity with measures of depression, anxiety and mastery. Results The five-item Arthritis Helplessness Index-Helplessness measure demonstrated a tenable factor structure (comparative fit index 0.98, root mean square error of approximation 0.06, standardized root mean residual 0.04). Internal consistency reliability was fair (α = 0.69). Convergent validity was evidenced by significant correlations with measures of depression, anxiety and mastery. Conclusion The five-item Arthritis Helplessness Index-Helplessness scale can confidently be used as a measure of helplessness in SLE.
29920358 Ephedra gerardiana aqueous ethanolic extract and fractions attenuate Freund Complete Adjuv 2018 Oct 5 ETHNOPHARMACOLOGICAL RELEVANCE: The whole plant, roots and stems of Ephedra gerardiana (Family Ephedraceae) have long been used as a folk remedy to treat rheumatism and painful joints in Northern Areas of Pakistan. AIM OF THE STUDY: The purpose of study was to observe the preventive efficacy of Ephedra gerardiana (EG) aerial parts in treating rheumatoid arthritis using Freund's complete adjuvant (FCA) induced arthritis in rat model and to determine its possible mechanism of action. MATERIAL AND METHODS: Arthritis was induced in Sprague Dawley rats by immunization with 0.1 ml FCA in left footpad. EG aqueous ethanolic extract (30:70) and its aqueous, n-butanol and ethyl acetate fractions at 200 mg/kg were orally administered from day 0, 30 min prior to adjuvant injection and sustained for 28 days. Paw volume/diameter, arthritic score, body weight, and hematological (WBC, RBC, ESR, Hb and Platelet count) and biochemical (AST, ALT, ALP, urea, creatinine, CRP and RF) parameters were observed. The mRNA expression levels of COX-2, IL-1β, IL-6, NF-kB, TNF-α, IL-4 and IL-10 were measured by real time reverse transcription polymerase chain reaction (RT-PCR) while, PGE2 and TNF-α levels in serum samples were measured by Enzyme linked immunosorbent assay (ELISA). Moreover, radiographs of hind paws and histological changes in ankle joint were analyzed in adjuvant injected rats. In addition, anti-oxidant activity of plant extract and fractions was also evaluated using DPPH and reducing power assays. Also, preliminary phytochemistry and total phenolic and flavonoid contents were investigated in most active fraction (aqueous fraction). RESULTS: EG extract and fractions (notably aqueous fraction) significantly suppressed paw swelling and arthritic score, prevented cachexia and remarkably ameliorated hematological and biochemical changes. Furthermore, the overproduction of PGE2, COX-2, IL-1β, IL-6, NF-kB and TNF-α were remarkably attenuated in all EG treated rats, however, IL-4 and 10 were markedly increased. The radiographic and histopathologic improvement in joint architecture was also observed in EG treated rats. Piroxicam, used as reference drug, also significantly suppressed arthritis. Additionally, plant exhibited notable anti-oxidant activity and phytochemical analysis revealed the presence of alkaloids, flavonoids, phenols, tannins, saponins and glycosides. CONCLUSION: These results indicate that EG extract and fractions significantly attenuated adjuvant arthritis in rats by decreasing the levels of aforementioned pro-inflammatory and increasing the levels of anti-inflammatory mediators. This suggests that Ephedra gerardiana aerial parts might be used as a therapeutic agent for treating human arthritis.
30078898 Patellar Resurfacing versus Nonresurfacing with Patellaplasty in Total Knee Arthroplasty. 2018 Jul BACKGROUND: Anterior knee pain following total knee arthroplasty (TKA) remains one of the important reasons for patient dissatisfaction. The management of patellofemoral joint is controversial and a decision whether to resurface the patella or not, is important. The present study compares the clinical and radiological outcomes between patellar resurfacing and nonresurfacing in patients undergoing bilateral TKA. MATERIALS AND METHODS: This is a prospective comparative study with 60 patients undergoing bilateral simultaneous TKA (120 knees) with posterior stabilized Hi flex fixed bearing knee (Zimmer, Warsaw, Indiana), by two surgeons. The patients were allocated to the two groups of resurfacing versus nonresurfacing of patella. In nonresurfacing group, patellaplasty was done. Patients with clinicoradiological signs of tricompartmental arthritis were included in the study. Exclusion criteria included unilateral TKA, rheumatoid arthritis, postseptic arthritis, previous high tibial osteotomy, or unicondylar knee arthroplasty cases. Patients were assessed using Knee Society Score (KSS), Modified Samsung Medical Centre Score (MSMCS), Feller patellar score. Radiological evaluation was performed at 1 year using congruence angle and patellar tilt angle. RESULTS: Mean followup was 19 months (range 12-25 months). Mean KSS, MSMCS, Feller patellar scores in resurfacing group were 82.67, 10.68, and 25.97, respectively and in nonresurfacing group were 82.93, 10.48, and 24.90, respectively. Mean congruence angle in resurfacing group was -12.83° and in nonresurfacing group was -12.383° (P = 0.917) and mean patellar tilt angle in resurfacing is 8.07 and nonresurfacing group is 7.97 (P = 0.873). CONCLUSION: There was no statistically significant difference in short-term clinical, functional, and radiological outcomes in the two groups and therefore, routine patellar resurfacing for patient undergoing TKA is not advantageous.
30408582 Guidelines for biomarkers in autoimmune rheumatic diseases - evidence based analysis. 2019 Jan Autoimmune rheumatic diseases are characterised by an abnormal immune system response, complement activation, cytokines dysregulation and inflammation. In last years, despite many progresses in managing these patients, it has been shown that clinical remission is reached in less than 50% of patients and a personalised and tailored therapeutic approach is still lacking resulting in a significant gap between guidelines and real-world practice. In this context, the need for biomarkers facilitating early diagnosis and profiling those individuals at the highest risk for a poor outcome has become of crucial interest. A biomarker generally refers to a measured characteristic which may be used as an indicator of some biological state or condition. Three different types of medical biomarkers has been suggested: i. mechanistic markers; ii. clinical disease markers; iii. therapeutic markers. A combination of biomarkers from these different groups could be used for an ideal more accurate diagnosis and treatment. However, although a growing body of evidence is focused on improving biomarkers, a significant amount of this information is not integrated on standard clinical care. The overarching aim of this work was to clarify the meaning of specific biomarkers during autoimmune diseases; their possible role in confirming diagnosis, predicting outcome and suggesting specific treatments.
29866668 Case of primary Sjogren's syndrome preceded by dystonia. 2018 Jun 4 There are only six cases in literature that describe development of dystonia with Sjogren's syndrome (SS). We describe a case of a 43-year-old woman who presented with symptoms including movement disorder, sensory neurogenic bladder, sensory loss and neuropathic pain, migraine like headaches, musculoskeletal pain, Raynaud's phenomenon and dysautonomia. Symptoms started in 2000, with weakness that progressed to dystonia in 2003. Diagnostic work-up was inconclusive with negative inflammatory serologies, cerebrospinal fluid and MRI for many years. After patient developed sicca syndrome with dry eyes and mouth in 2009, her rheumatoid factor titre was elevated (550 IU/mL), erythrocyte sedimentation rate, anti-Sjogrens syndrome-related antigen A (anti-Ro/SSA) and anti-SSB/La: anti-Sjogrens syndrome-related antigen B (anti-La/SSB) became positive. Lip biopsy confirmed diagnosis of SS. She was diagnosed with primary SS with neurological involvement. Her symptoms responded well to intravenous methylprednisolone. Symptoms stabilised with trials of immune-suppressive therapy. This is a case that demonstrates the delay of diagnosing SS with preceding unique neurological association.
29522782 Cortical stimulation in conscious rats controls joint inflammation. 2018 Jun 8 The neuronal control of the immune system is fundamental to the development of new therapeutic strategies for inflammatory disorders. Recent studies reported that afferent vagal stimulation attenuates peripheral inflammation by activating specific sympathetic central and peripheral networks, but only few subcortical brain areas were investigated. In the present study, we report that afferent vagal stimulation also activates specific cortical areas, as the parietal and cingulate cortex. Since these cortical structures innervate sympathetic-related areas, we investigate whether electrical stimulation of parietal cortex can attenuate knee joint inflammation in non-anesthetized rats. Our results show that cortical stimulation in rats increased sympathetic activity and improved joint inflammatory parameters, such as local neutrophil infiltration and pro-inflammatory cytokine levels, without causing behavioral disturbance, brain epileptiform activity or neural damage. In addition, we superposed the areas activated by afferent vagal or cortical stimulation to map common central structures to depict a brain immunological homunculus that can allow novel therapeutic approaches against inflammatory joint diseases, such as rheumatoid arthritis.
30336303 Diarylheptanoid, a constituent isolated from methanol extract of Alpinia officinarum atten 2019 Jan 30 ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease that affects the worldwide population. Alpinia officinarum Hance (Zingiberaceae), rhizomes are widely used ethnobotanically as an anti-inflammatory, analgesic, and antioxidant agent in traditional medicine. AIM: To investigate the efficacy and possible mechanism of isolated phytoconstituent from the methanol extract of A. officinarum (MEAO) rhizomes against Freund's complete adjuvant (FCA)-induced arthritis in rats. Furthermore, molecular docking was performed to study the binding mode of this compound into the active site of TNF-α. MATERIALS AND METHODS: Diarylheptanoid was isolated from MEAO, well characterized (HPTLC, (1)H NMR, (13)C NMR, and ESI-MS) and evaluated for its antiarthritic activity in female Wistar rats (170-200 g). Diarylheptanoid (5, 10 and 20 mg/kg, p.o.) was administered starting from day 12. Various behavioral, biochemical, molecular and histopathology parameters were evaluated. Molecular docking study was performed using Glide module integrated into Schrodinger molecular modeling software. RESULTS: The structure and molecular weight of the isolated compound (diarylheptanoid) were confirmed by 1D and mass spectral data and characterized as 1-phenyl-5-hydroxy-7- (4''-hydroxy-3''-methoxyphenyl) heptane-3-one (i.e., 5-HPH) with molecular formula C(20)H(24)O(4). Administration of 5-HPH (10 and 20 mg/kg) significantly inhibited (p < 0.05) FCA induced increases in paw volume, joint diameter, thermal hyperalgesia and tactile allodynia. It also significantly decreased oxido-inflammatory markers (SOD, GSH, MDA, and TNF-α). FCA induced a histological alteration in ankle joint also attenuated by 5-HPH. Its Glide docking score was found to be -9.702 with binding energy (Glide energy) of -37.033 kcal/mol. CONCLUSION: 5-HPH may exhibit its anti-arthritic potential via inhibition of elevated oxido-inflammatory markers thus restoring the elevated hyperalgesia, allodynia and reducing destruction in synovial membrane and cartilage. Therefore, 5-HPH is a potential moiety bearing antioxidant and with anti-inflammatory properties to inhibit FCA-induced arthritis in rats. The results of the present investigation should enable the design of potent small-molecule inhibitors that inactivate TNF-α with high affinity and specificity.
29992636 Association of CD28 and CTLA4 haplotypes with susceptibility to primary Sjögren's syndrom 2019 Jan BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by destruction of exocrine glands as a result of T and B cells infiltrated in glandular tissue. CD28 and CTLA-4 play a crucial role in T cell activation and inhibition. The aim of this study was to associate CD28 and CTLA4 haplotypes with susceptibility to pSS in patients from western Mexico. METHODS: Polymerase chain reaction and restriction fragment length polymorphism were performed to identify CD28 and CTLA4 genotypes in 111 patients with pSS and 138 control subjects (CS). Haplotype analysis was carried out by SHEsis program. Soluble serum levels of CD28 (sCD28) and CTLA-4 (sCTLA-4) were quantified by ELISA kit. RESULTS: The CD28 GC haplotype was associated with low risk to pSS (2.5-folds, P < 0.001). CTLA4 CAG and CGA were identified as genetic risk factor (P < 0.001;OR = 3.82[CI95%:2.022-7.296] and P < 0.001; OR = 11.38[CI95%:3.282-37.69] respectively). No difference in sCD28 and sCTLA-4 were found between patients and CS. However, pSS patients carriers of CD28 IVS3 + 17TC genotype showed high sCD28 (P = 0.039 vs TT carriers in CS). In regard to sCTLA-4, patient who carry CTLA4-319C>T, +49 A>G, and +6230 G>A, or their haplotypes did not show any difference. CONCLUSION: Our findings suggest that CD28 GC, CTLA4 CAG, and CGA haplotypes are associated with susceptibility to pSS in patients from western Mexico. It seems that genetic control of CD28 and CTLA4 as well as local immune response in glandular tissue may regulate the impact of the gene expression in pSS. It is necessary to confirm this hypothesis in an integrative study.