PRP as a modulator of inflammation in FLS of RA patients by regulation of galectins and TGF-ß1.

An autoimmune and inflammatory condition known as rheumatoid arthritis is characterized by joint inflammation and an aggressive fibroblast-like synoviocytes. (FLS) One of the most significant immunological regulators are the galectins. Platelet-rich plasma are probably effective in immunomodulation. The aim of the present work is to investigate the role of platelet rich plasma (PRP) as a modulation of inflammation, which affects the expression of galectins and TGF-ß in FLS from Rheumatoid arthritis (RA) patients. Methods: Human FLS cells from RA patients' synovial fluid were cultured in DMEM-F12 medium, characterized by flowcytometry, treated with PRP alone, TNF-α+PRP, SF + PRP, TNF-α alone, and untreated control groups. Expression of Galectin-1, Galectin-3, Galectin-9, and TGF-ß1 genes was assessed by Real-Time PCR. Results: In SF + PRP, TNF + PRP, and PRP groups, the gene expression of Galectin-3 was considerably reduced (P > 0.05). Galectin-1 and TGF-ß1 expression levels were also lowered (P > 0.05) in the TNF + PRP groups. Galectin-9 expression increased significantly in the PRP group (P > 0.05). Galectin-3 expression was markedly and extensively reduced in multiple study groups after treatment of FLS cells with 10 % PRP. Galectin-3 expression was considerably reduced when FLS were exposed to TNF- and synovial fluid in conjunction with PRP to simulate localized body inflammation. Conclusion: Our results showed that PRP may be useful in lowering FLS-induced inflammation in RA patients' joints, particularly when Galectin-3 is involved. In the future, inflammatory illnesses like RA may be treated locally using PRP or its derivatives, which will have a larger immune modulation role and more likely pathways.

Pernicious Anemia Following COVID-19 Vaccination: A Report of Two Cases.

Since December 2019 and the global epidemic of COVID-19 different countries have focused on vaccines, and one of the inactivated produced vaccines was the Sinopharm COVID-19 vaccine. Some side effects of this vaccine were reported previously, including pain at the vaccination site, fatigue, lethargy, headache, and tenderness, which were more prevalent among individuals <49 years old. Herein, we reported two patients aged 45 and 51 years old. Both patients have different signs and symptoms after receiving the second dose of the vaccine. None had a history of chronic disease. On examination and following labs and other diagnostic investigations, we found megaloblastic anemia due to atrophic gastritis and low intrinsic factor. These cases showed an autoimmune side effect of the Sinopharm COVID-19 vaccine that was previously reported with an exact mechanism but other features called Covid Arm, Guillain-Barré syndrome, and thrombocytopenia. The mechanism of this reaction is unclear yet.

COVID-19 infection: a possible induction factor for development of autoimmune diseases?

Following the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the importance of investigation of the pathogenesis and immunological characteristics of COVID-19 became quite clear. Currently, there are reports indicating that COVID-19 is able to induce autoimmune responses. Abnormal immune reactions are a cornerstone in the pathogenicity of both conditions. Detection of autoantibodies in COVID-19 patients may suggest a link between COVID-19 and autoimmunity. In this study, we focused on the similarities and possible differences between COVID-19 and autoimmune disorders to explore the relationship between them. Comparing the pathogenicity of SARS-CoV-2 infection with autoimmune conditions revealed significant immunological properties of COVID-19 including the presence of several autoantibodies, autoimmunity-related cytokines, and cellular activities that could be useful in future clinical studies aiming at managing this pandemic.

Effects of crystalline penicillin G sodium on human T-cells differentiation.

BACKGROUND: Although antibiotics are well-known for their anti-bacterial effects, their inaugurated immunomodulatory roles in chronic inflammatory diseases have not elucidated yet. Anecdotal reports support the beneficial effects of parenteral penicillin in arthritis suggesting an immunomodulatory other than antibacterial effects for penicillin. The present study was designed to address the possible effects of penicillin G sodium (PCN-G) on different T-helper cells differentiation. MATERIALS AND METHODS: In this experimental study, peripheral blood mononuclear cells (PBMCs) of 10 healthy donors were isolated using Ficoll density gradient. The stimulated PBMCs by anti-CD3, anti-CD28, and anti-CD69 were cultured in the presence of 120 µg/ml of PCN-G. Foxp3, T-bet, RORγT, GATA3 as well as interferon-gamma (IFN-γ) and interleukin (IL)-17A mRNA in stimulated cells were measured by the real-time polymerase chain reaction. Mann-Whitney U-test was used for determining differences between the medium of gene expression levels of stimulated cell population and unstimulated cells by PCN. Correlations between the related genes were determined using the Spearman test. RESULTS: Based on the results, T-bet gene expression levels were similar in stimulated cells by PCN G after 24 and 48 h while significant reduction was observed after 72 incubation with PCN G (difference = 3; 0.09-0.34; P = 0.031). Meanwhile, treated cells with PCN G expressed decreased levels of IFN-γ (difference = 8.0; 0.49-1.07; P = 0.001) and IL-17A (difference = 2.2; 0.05-0.75; P ≤ 0.05) genes comparing to unstimulated cell by PCN-G. GATA3 genes expression levels downregulated by PCN G after 72 h of incubation by PBMCs (difference = 1.1; 0.77-0.88; P = 0.035). CONCLUSION: Our results confirmed the immunomodulatory role of PCN G by affecting the expression of different cytokines genes in PBMCs.

Penicillin in oral aphthosis, new insight for an old drug: A randomized, double-blind, controlled clinical trial.

BACKGROUND: Oral aphthosis is a painful ulceration of mucus membranes characterized by round or oval lesions with central necrosis and erythematous haloes. Due to unknown etiology, treatment is highly controversial and based mainly on individual experience. The aim of this study was to investigate the safety and efficacy of topical penicillin 6.3.3 for the treatment of recurrent aphthous stomatitis. MATERIALS AND METHODS: This randomized, double-blind, controlled clinical trial was done in Shahid Sadoughi Hospital Clinic in Yazd (2011-2012). Fifty patients aged 15-45 with recurrent oral aphthosis were randomly divided into two groups. After obtaining informed consents, patients in the case and control groups were treated (four times/day for a week), respectively, by topical penicillin 6.3.3 powder and placebo in similar vial. The patients who had acute-onset oral aphthae (≤48 h of appearance) with diameter ≥5 mm were included. History of sensitivity to ß-lactam antibiotics and cephalosporin; spontaneous recovery during <5 days in previous episodes; concurrent systemic, infectious, or any autoimmune disorders; history of taking drugs (local or systemic) from 2 weeks prior to presentation; alcohol or drug abuse; smoking cigarette or tobacco; and poor compliance were exclusion criteria. Patients were examined in days 0, 3, 6, and 8. The main outcome measure was reduction in the median pain. Burning, pain, erythema, and inflammation were recorded as complications. RESULTS: Of 25 patients receiving penicillin, 13 were female and 12 were male. Regarding the pain score (mean difference = 1.6 vs. 0.88, P = 0.012) and size of aphthus (mean difference = 9.43 vs. 1.24, P = 0.008), patients who received penicillin had significantly better results than the placebo group on day 8 after the treatment. The mean duration to healing was 3 days for penicillin group and 6 days for placebo group (P = 0.016). No topical or systemic adverse effects were observed. CONCLUSION: Our study showed a dramatic response to topical penicillin with respect to placebo. Hence, it seems that penicillin could be a safe and effective option in managing oral aphthosis.

Evaluation of sodium valproate low dose efficacy in radicular pain management and it's relation with pharmacokinetics parameters.

BACKGROUND: Radiculopathy due to lumbar or cervical disc disease is the most common chronic neuropathic pain in adults. The aim of present study was evaluation of low dose of sodium valproate (VPA) on radicular pain and determining VPA pharmacokinetics. MATERIALS AND METHODS: In this double blind randomized placebo control clinical study, 80 patients with established lumbar or cervical radicular pain, have been randomly allocated into two study groups: 40 have received sodium valproate 200 mg/day and Celecoxib 100 mg/day and acetaminophen 500 mg PRN as rescue medication, and second group has received placebo, Celecoxib and acetaminophen. Quantitative assessment of pain was done by visual analogue scale (VAS) prior to perform the intervention and after ten days (treatment duration). Blood sample has been taken for determining mean through concentration after five half-lives. Evaluation of plasma concentration of VPA and that of efficacy on pain score relationship by comparing VAS before and after the therapy was done. RESULTS: Group A and B have demonstrated significant alleviation in mean VAS score; -21.97 ± 25.41, -14.39 ± 23.03 respectively (P < 0.001). The mean plasma concentration of VPA in group A was: 26.9 ± 13.5 mg/L. Moreover, no significant correlation was seen between pain score with age, gender, and weight (p > 0.05). CONCLUSION: Low dose of sodium valproate especially together with NSAIDs demonstrated good efficacy in lumbar and cervical radicular pain management.

Corrigendum to "Rheumatological Findings in Candidates for Valvular Heart Surgery".

[This corrects the article DOI: 10.5402/2012/927923.].

Review of Anti-Inflammatory Herbal Medicines.

Medicinal plants and their secondary metabolites are progressively used in the treatment of diseases as a complementary medicine. Inflammation is a pathologic condition that includes a wide range of diseases such as rheumatic and immune-mediated conditions, diabetes, cardiovascular accident, and etcetera. We introduce some herbs which their anti-inflammatory effects have been evaluated in clinical and experimental studies. Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, evening primrose, and Devil's claw are some of the introduced medicinal herbs in this review. Since the treatment of inflammation is not a one-dimensional remedy, this review tries to reach a multidimensional therapeutic approach to inflammation with the help of herbal medicine and modification in lifestyle.

Frequency of sacroiliitis among patients with low back pain.

INTRODUCTION: Sacroiliitis is one of the important symptoms in patients attending infectious diseases and rheumatology clinics. Some patients with sacroiliitis are asymptomatic, and some have unspecific symptoms. The aim of this study was to determine the frequency of sacroiliitis causes among patients attending Shahid Sadoughi's infectious disease and rheumatology clinics. METHODS: In this study, we evaluated patients attending Shahid Sadoughi rheumatology and infectious diseases clinic in 2014. Patients who had positive findings in favor of sacroiliitis were evaluated by history, physical exam, laboratory tests, and imaging. The patients were divided into infectious, inflammatory non-infectious, and degenerative causes. The data were analyzed by IBM SPSS version 20 using the independent samples t-test, ANOVA, the chi-squared test, and the Fisher's exact test. RESULTS: We studied 136 patients. Among them 64 (47.1%) were male, and 72 (52.9%) were female. The mean age of the participants was 34.28 ± 10.36 years. Among the patients, 12 (8.8%) had infectious causes, 120 (88.2%) had inflammatory non-infectious causes, and four (2.9%) had degenerative causes. CONCLUSION: Based on our results, inflammatory non-infectious causes are at the top of the list of sacroiliitis causes, but we should always consider infectious causes, including brucellosis.

Thromboangiitis obliterans with cryoglobulinemia.

Thromboangiitis obliterans (TAO), or Buerger's disease, is a vascular occlusive disease associated with cigarette smoking. It typically affects medium sized vessels of extremities. Basic pathology of TAO is described to be endothelial activation with highly inflammatory intraluminal thrombosis preserving internal elastic membrane. Cryoglobulins are immunoglobulins that precipitate in the cold and dissolve on re-warming. Cryoglobulinemic vasculitis is a typical small vessel disease associated with cryoglobulinemia commonly bearing typical purpuric skin lesions. An association of TAO with cryoglobulinemia is not reported yet. We report a 34-year-old male heavy cigarette smoker seen for extremity pain and cyanosis of left little finger along with skin rashes characteristic of small vessel disease. Initial presentation of his symptoms at winter and unusual purpuric skin lesions led to search for cold-agglutinating globulins in his plasma. He had severe cryoglobulinemia while the other laboratory tests were normal. TAO associated with cryoglobulinemia merges as a possibility.

Systemic aspects of soft tissue rheumatic disorders (STRDs).

OBJECTIVE: To determine the markers of systemic inflammation in soft tissue rheumatic disorders (STRDs). STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Rheumatology Clinic, Yazd, Iran, from November 2010 to December 2011. METHODOLOGY: Patients aged 20 years or above with known diagnosis of STRD according to clinical criteria and/ or paraclinical investigations for at least 3 weeks duration were longitudinally followed. Patients with diagnosis of rheumatoid arthritis, hypothyroidism, or any other known systemic conditions (other than diabetes mellitus) were excluded. After careful and detailed history taking, laboratory tests indicating systemic inflammation including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and routine screening rheumatologic tests were assessed. RESULTS: Of the 90 patients, 75% were female and 25% were male and 28 (31.1%) of patients had diabetes mellitus. Fifty six (62%) and 49 (54%) of all studies cases had some degrees of morning stiffness and remarkable fatigue respectively. Twenty two (24%) had elevated CRP and 5 (5.5%) had abnormal ESR. Rheumatoid factor (RF) and anti-CCP was positive in 5 (5.5%) and 12 (13.3%) of patients accordingly. Three (3.3%) patients suffered from anemia of chronic disease. Mean ESR was 48 ± 7.34 (hl) and mean CRP was 10.06 ± 1.96 mg/dl. Mean RF was 10.8 ± 1.64 U/ml and mean anti- CCP was 18.5 ± 2.71 U/ml. Mean hemoglobin was between 10.4 ± 1.01 g/dl. CONCLUSION: Features of subtle systemic inflammation are positive in some cases of soft tissue rheumatism.

Visual problem and low back pain as initial manifestation of multiple myeloma complicating pre-existing systemic sclerosis.

Some connective tissue diseases are associated with an increased risk of developing neoplastic disorders. Association of rheumatoid arthritis and systemic lupus erythematosus with lymphoma, and of dermatomyositis with different malignancies including ovarian and lung cancer has been reported in the literature. Here, we describe a 58 years old man with systemic sclerosis (SSc) for 15 years who developed severe lumbar pain when he was admitted for intravenous infusion of prostaglandin E1 for his fingertip ulcers. He was found to have abnormal skeletal imaging. Laboratory tests including bone marrow aspiration and biopsy determined multiple myeloma causing extensive bony infiltration. The patient expired after two cycles of VAD and Bortezomide chemotherapy.

Felty's Syndrome, Insights and Updates.

Felty's syndrome (FS) is characterized by the triad of seropositive rheumatoid arthritis (RA) with destructive joint involvement, splenomegaly and neutropenia. Current data shows that 1-3 % of RA patients are complicated with FS with an estimated prevalence of 10 per 100,000 populations. The complete triad is not an absolute requirement, but persistent neutropenia with an absolute neutrophil count (ANC) generally less than 1500/mm3 is necessary for establishing the diagnosis. Felty's syndrome may be asymptomatic but serious local or systemic infections may be the first clue to the diagnosis. FS is easily overlooked by parallel diagnoses of SjÓ§gren syndrome or systemic lupus erythematosus or lymphohematopoietic malignancies. The role of genetic (HLA DR4) is more prominent in FS in comparison to classic rheumatoid arthritis. There is large body of evidence that in FS patients, both cellular and humoral immune systems participate in neutrophil activation, and apoptosis and its adherence to endothelial cells in the spleen. It has been demonstrated that proinflammatory cytokines may have inhibitory effects on bone marrow granulopoiesis. Binding of IgGs to neutrophil extracellular chromatin traps (NET) leading to neutrophil death plays a crucial role in its pathophysiology. In turn, "Netting" neutrophils may activate auto-reactive B cells leading to further antibody and immune complex formation. In this review we discuss on basic pathophysiology, epidemiology, genetics, clinical, laboratory and treatment updates of Felty's syndrome.

Digital panoramic radiography as a useful tool for detection of bone loss: a comparative study.

This study was aimed to investigate the use of panoramic radiography in patients with low bone mineral density (BMD) in order to diagnose and prevent osteoporotic fractures. Panoramic radiographs of 60 patients  (20 men and 40 women) aged from 40 to 70 years with cortical thicknesses of less than 3 mm in the mandibular angle were selected from patients referred to a dentomaxillofacial radiology clinic and were then examined for mandibular cortical angles. These were measured using Computed Radiography (CR) software. The bone densitometry was carried out using Dual Energy X-ray Absorptiometry (DEXA). Cortical thicknesses at the lower border of the mandibles were also measured by panoramic radiographs. Statistics analyses were then undertaken using Fisher's exact test, Chi-square, t-test, ANOVA and receiver operating characteristic (ROC) curve. In most cases, no significant difference in mandibular angle cortical thickness was found between those patients with a normal BMD and those patients with a lowered BMD (P=0.621). There was a relationship between the cortical thicknesses of the mandibular lower border, and vertebral and femoral BMD (P<0.0001), and there was a significant difference between the thickness of the mandibular lower border and BMD. The results of this study also revealed a new marker of osteoporosis on the mandibular lower border under the third molar. A thickness of 2.80 mm of the mandibular lower border was detected as a threshold for the measurement of bone densitometry in the chosen Iranian population. Panoramic radiography is effective for screening patients who are at risk of having decreased bone mineral density. Patients with a threshold of 2.80 mm thickness of the mandibular lower border should be considered as individuals likely to have osteoporosis associated low bone density.

Management of immune cytopenias in patients with systemic lupus erythematosus - Old and new.

There are various immune cytopenias associated with systemic lupus erythematosus (SLE). The most common one is anemia; however, there are different etiologies for the anemia caused by SLE. Anemia could be due to chronic disease, secondary to renal insufficiency, blood loss, drug induced or autoimmune hemolysis. There are other very rare causes of anemia secondary to SLE which include red cell aplasia, aplastic anemia, and microangiopathic hemolytic anemia. Treatment of the anemia would be according to the cause. Leukopenia, neutropenia, and lymphopenia are hematologic complications associated with SLE, and in majority of cases no treatment is required. Thrombocytopenia is one of the complications of SLE and is usually treated by steroids. However, there are significant numbers of patients which will either not respond to or relapse after treatment. This article summarizes immune cytopenias seen in patients with SLE, and it also discusses management of these cytopenias.

Cardiac manifestations of rheumatological conditions: a narrative review.

Cardiovascular diseases are common in systemic rheumatologic diseases. They can be presented at the time of diagnosis or after diagnosis. The cardiac involvements can be the first presentation of rheumatologic conditions. It means that a patient with rheumatologic disease may go to a cardiologist when attacked by this disease at first. These manifestations are very different and involve different structures of the heart, and they can cause mortality and morbidity of patients with rheumatologic diseases. Cardiac involvements in these patients vary from subclinical to severe manifestations. They may need aggressive immunosuppressive therapy. The diagnosis of these conditions is very important for choosing the best treatment. Premature atherosclerosis and ischemic heart disease are increased in rheumatoid arthritis and systemic lupus erythematosus, and may be causes of mortality among them. The aggressive control of systemic inflammation in these diseases can reduce the risk of cardiovascular disease especially ischemic heart disease. Although aggressive treatment of primary rheumatologic diseases can decrease mortality rate and improve them, at this time, there are no specific guidelines and recommendations, to include aggressive control and prevention of traditional risk factors, for them.

The effect of garlic tablet on pro-inflammatory cytokines in postmenopausal osteoporotic women: a randomized controlled clinical trial.

INTRODUCTION: Menopause is one of the important causes of osteoporosis which results from estrogen deficiency. In addition, some clinical and experimental evidence indicates that there is an association between increasing pro-inflammatory cytokine activity and postmenopausal bone loss. The purpose of this study was to determine the effect of garlic tablet on pro-inflammatory cytokines in postmenopausal osteoporotic women. METHODS: The present study was a double-blind randomized controlled clinical trial in Yazd conducted during November 2009 until July 2010. The sample included 44 postmenopausal osteoporotic women who were randomly assigned into two groups: the garlic group (GG) and the placebo group (PG). Participants in GG took two garlic tablets daily for 1 month and the participants in PG took placebo tablets in the same manner. Serum interlukin-1, interlukin-6, and tumor necrosis factor alpha (TNF-α) were measured using the ELISA method before and after the intervention. Also, 24-hour dietary recall was recorded for estimation of daily intake of some nutrients. Data were analyzed using SPSS software. RESULTS: There was no statistically significant difference between interlukin-1 and interlukin-6 in the two groups before and after the intervention. The mean of TNF-α did not show any statistically significant difference between the two groups before and after the intervention, but it was significantly reduced by about 47% (from 31.14±50.53 to 19.33±22.19 ng/ml, P-value = 0.05) in GG after the intervention, However, no significant difference was seen in PG. CONCLUSIONS: The present study produced some evidence for an immunomodulatory effect of garlic, as well as the modulation of cytokine production.

Dermatomyositis sine myositis with membranoproliferative glomerulonephritis.

Dermatomyositis (DM) is an autoimmune disease that is characterized by involvement of proximal musculature and skin. We report a 52-year-old woman with a 6-year history of dermatomyositis sine myositis, who developed lower extremity edema and proteinuria. Pathological examination of renal biopsy showed membranoproliferative glomerulonephritis. She received steroid, cyclophosphamide, and mycophenolate mofetil. Over the 9 to 10 months after the beginning of treatment, the proteinuria was improved.