Comparison of the Antibacterial Activity of Australian Terminalia Spp. Extracts Against Klebsiella Pneumoniae: Novel Treatment for Ankylosing Spondylitis

Traditional medicines prepared using Terminalia species have been used globally to treat inflammation and pathogenic infections. Recent studies have demonstrated that multiple Asian and African Terminalia spp. inhibit bacterial triggers of some autoimmune inflammatory disease, including ankylosing spondylitis. Despite this, the effects of Australian Terminalia spp. on a bacterial trigger of ankylosing spondylitis (K. pneumoniae) remain unexplored. Fifty-five extracts from five Australian Terminalia spp. were investigated for K. pneumoniae growth inhibitory activity. Methanolic, aqueous and ethyl acetate extracts of most species and plant parts inhibited K. pneumoniae growth, with varying potencies. Methanolic leaf extracts were generally the most potent bacterial growth inhibitors, with MIC values of 66 µg/mL (T. ferdinandiana), 128 µg/mL (T. carpenteriae) and 83 µg/mL (T. petiolares). However, the aqueous leaf extract was the most potent T. grandiflora extract (MIC = 87 µg/mL). All T. catappa extracts displayed low growth inhibitory activity. The Terminalia spp. methanolic leaf extracts were examined by LC-MS and GC-MS. All contained a relative abundance of simple gallotannins (particularly gallic and chebulic acids), the flavonoid luteolin, as well as the monoterpenoids cineole and terpineol. Notably, all Terminalia spp. were non-toxic or of low toxicity in ALA and HDF toxicity assays, highlighting their potential for preventing the onset of ankylosing spondylitis and treating its symptoms once the disease is established.

Astroglial and Microglial Purinergic P2X7 Receptor as a Major Contributor to Neuroinflammation during the Course of Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system that leads to the progressive disability of patients. A characteristic feature of the disease is the presence of focal demyelinating lesions accompanied by an inflammatory reaction. Interactions between autoreactive immune cells and glia cells are considered as a central mechanism underlying the pathology of MS. A glia-mediated inflammatory reaction followed by overproduction of free radicals and generation of glutamate-induced excitotoxicity promotes oligodendrocyte injury, contributing to demyelination and subsequent neurodegeneration. Activation of purinergic signaling, in particular P2X7 receptor-mediated signaling, in astrocytes and microglia is an important causative factor in these pathological processes. This review discusses the role of astroglial and microglial cells, and in particular glial P2X7 receptors, in inducing MS-related neuroinflammatory events, highlighting the importance of P2X7R-mediated molecular pathways in MS pathology and identifying these receptors as a potential therapeutic target.

Quality of referrals to a rheumatology service before and after implementation of a triage system with telemedicine support

Purpose To evaluate the quality of referrals for a first Rheumatology consultation at a tertiary care center in a southern Brazilian capital (Porto Alegre, RS), having as background findings from a similar survey performed in 2007/2008. Since then, our state has implemented referral protocols and a triage system with teleconsulting support exclusively for referrals from locations outside the capital, permitting a comparison between patients screened and not screened by the new system. Methods Physicians of the Rheumatology Service at Hospital Nossa Senhora da Conceição prospectively collected information regarding first visits over a 6-month period (Oct 2017 to March 2018). We recorded demographic characteristics, diagnostic hypotheses, date of referral, and the municipality of origin (within the state of Rio Grande do Sul). We considered adequate referrals from primary health care when a systemic autoimmune inflammatory disease (SIRD) was suspected at first evaluation by the attending rheumatologist. Results Three hundred fifty-seven patients/appointments were eligible for analysis (193 from the capital and 164 from small and medium towns). In 2007/2008, suspected SIRD occurred in 76/260 (29.2%) and 73/222 (32.9%) among patients from the capital and outside counties, respectively (P = 0.387). In 2017/2018, suspected SIRD occurred in 75/193 (38.9%) and 111/164 (67.7%) in patients from the capital and outside counties, respectively (difference: 28.8, 95% CI: 19.0 to 38.9, P < 0.001), indicating a marked improvement in referrals submitted to the new triage system. Conclusion The quality of Rheumatology referrals in our state improved over the 10-year interval under study, particularly among patients from locations submitted to referral protocols and teleconsulting support.

Autoimmune Hypophysitis with Late Renal Involvement: A Case Report

We report a case of a 50-year-old male admitted to the Endocrinology Unit because of persistent headaches, nausea, feeling tired, sudden weight loss, cold intolerance, decreased appetite, and lack of sex interest. Diagnostic workup showed a 6-millimeter pituitary tumor without signs of compression, and a condition of progressive panhypopituitarism. After 12 months of hormone replacement therapy, the patient was hospitalized because of sudden weight gain, periorbital-peripheral edema, severe dyslipidemia, hypertension, and proteinuria. Corticosteroid therapy was shifted from oral to continuous intravenous infusion, and once the diagnosis of “immune complex-mediated glomerulonephritis with mesangial deposits suggestive for membranoproliferative glomerulonephritis type IIIIgG4-positive” was made, the immunosuppressant mycophenolate (1500 mg/day) was started. After a 6-month follow-up, the complete resolution of renal symptoms was accompanied by the disappearance of a pituitary lesion and the patient was back to prior hormone replacement therapy. Autoimmune hypophysitis (AH) is a rare autoimmune inflammatory disease of the pituitary gland that can impair hormone secretion and function. IgG4-hypophysitis is rare and is usually associated with other IgG4-related diseases. Herein, we describe a rare case of AH associated with late renal disease, and without any other organ involvement.

Ulcerative Paraneoplastic Dermatomyositis in the Setting of Positive Transcriptional Intermediary Factor 1-γ Antibody

Dermatomyositis (DM) is an autoimmune inflammatory disease of the skin with or without muscle involvement1. One-third of patients present with malignant disease within 3 years2.

Anti-CD20 Therapy Alters the Protein Signature in Experimental Murine AIH, but Not Exclusively Towards Regeneration

Background: Autoimmune hepatitis (AIH) is a chronic autoimmune inflammatory disease that usually requires lifelong immunosuppression. Frequent recurrences after the discontinuation of therapy indicate that intrahepatic immune regulation is not restored by current treatments. Studies of other autoimmune diseases suggest that temporary depletion of B cells can improve disease progression in the long term. Methods: We tested a single administration of anti-CD20 antibodies to reduce B cells and the amount of IgG to induce intrahepatic immune tolerance. We used our experimental murine AIH (emAIH) model and treated the mice with anti-CD20 during the late stage of the disease. Results: After treatment, the mice showed the expected reductions in B cells and serum IgGs, but no improvements in pathology. However, all treated animals showed a highly altered serum protein expression pattern, which was a balance between inflammation and regeneration. Conclusions: In conclusion, anti-CD20 therapy did not produce clinically measurable results because it triggered inflammation, as well as regeneration, at the proteomic level. This finding suggests that anti-CD20 is ineffective as a sole treatment for AIH or emAIH.

Hearing Loss and Teprotumumab

Thyroid eye disease (TED) is an unpredictable autoimmune inflammatory disease which can be sight-threatening, debilitating, and disfiguring. Teprotumumab (IV infusion every 3 weeks x 8 doses) was recently approved as the first and only FDA-approved drug for TED in 2020. Phase 2 and 3 studies showed significant improvement in proptosis, double vision, soft tissue inflammation and quality of life for patients with active moderate to severe TED. Side effects were experienced by 85% of patients on teprotumumab. Hearing loss symptoms were reported in 10% of patients and were reported to be reversible upon stopping the drug. Objective: To explore the incidence of hearing loss symptoms and sensorineural hearing loss in patients treated with teprotumumab. Methods: All patients, followed at one institution, treated with at least 4 infusions of teprotumumab were evaluated. Charts were evaluated for baseline hearing symptoms and hearing symptoms during or after therapy with teprotumumab. Those patients with hearing symptoms were referred for audiogram testing and patulous eustachian tube (PET) testing. Results: Twenty-eight patients were included in this analysis. Thirteen patients (46%) complained of hearing symptoms. The most common symptoms were autophony or an ear plugging sensation and hearing loss or muffled hearing. Hearing symptoms developed after a mean of 3.6 infusions. Of the patients with hearing symptoms, three patients (23%) had sensorineural hearing loss documented on audiogram (n=2) or patulous eustachian tube (n=1) documented on PET testing. To date, the patient with PET has experienced some improvement, but not resolution, of her symptoms. The two patients with documented sensorineural hearing loss have not experienced a significant improvement in hearing, on audiogram, on average 3 months after stopping teprotumumab. Conclusion: Teprotumumab is a promising new therapy for active moderate to severe thyroid eye disease. Providers should consider performing a baseline audiogram with PET testing and performing audiograms with PET testing for patients that develop hearing symptoms during or after therapy. Hearing loss is a concerning adverse event and its mechanism and reversibility should be further studied.

Salivary Cytokines as Potential Diagnostic Biomarkers for Systemic Lupus Erythematosus Disease

Systemic lupus erythematosus (SLE) is a complex autoimmune inflammatory disease characterized by an unknown etiology and a highly variable clinical presentation. This clinical heterogeneity might be explained by dysregulation of tolerance to self and apoptotic mechanisms, overproduction of autoantibodies, and abnormal cytokine levels. Cytokine imbalance levels have been associated with disease activity and severity in SLE patients. In the last years, salivary cytokines related to SLE have gained significant attention and researchers have begun to focus on the identification of cytokines in the saliva of SLE patients using it as a diagnostic fluid for the inflammatory process underlying SLE. This review highlights and summarizes recent studies revealing the cytokines that have been identified in the saliva of individuals with SLE. Data reported and discussed in this report may provide useful additional information to better understand the mechanisms associated with the disease.

EFFECTIVENESS OF ORAL AND TOPICAL UNANI FORMULATIONS IN TAQASHSHUR AL-JILD (PSORIASIS): A CASE STUDY

Taqashshur al-Jild (Psoriasis) is an Autoimmune Inflammatory disease with a worldwide prevalence of about 1.5 -2%. A 27 years old male patient, approached the outpatient department of the N ational Research Institute of Unani Medicine for Skin Disorder (NRIUMSD), Hyderabad, with complaints of itching, scaling like dandruff, bleeding, burning of the scalp for one month. The examination of the skin revealed Psoriasis of the scalp. The patient was treated with the Unani regimen comprising of compound formulations Itrifal Shahetra (oral) 5gm, Habb-i-Musaffi Khoon (oral) 2 tablets, Marham Safed Kafoori (Topical), and Roghan Kamela (Topical) over scalp twice daily for 8 weeks days. The patient did not report any adverse effects during and after the treatment. After 8 weeks days of treatment, the whole scalp showed absence of the sign and symptoms of the disease. There was no recurrence of the disease during the next 2 months of post-treatment follow-up. This case report documented the successful treatment and prevention of recurrence of scalp psoriasis through Unani medicines. It concluded that the Unani regimen is effective and safe in the management of scalp psoriasis.