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The paraneoplastic Ma antigen (PNMA) proteins are associated with cancer-induced paraneoplastic syndromes that present with an autoimmune response and neurological symptoms. Why PNMA proteins are associated with this severe autoimmune disease is unclear. PNMA genes are predominantly expressed in the central nervous system and are ectopically expressed in some tumors. We show that PNMA2, which has been co-opted from a Ty3 retrotransposon, encodes a protein that is released from cells as non-enveloped virus-like capsids. Recombinant PNMA2 capsids injected into mice induce autoantibodies that preferentially bind external "spike" PNMA2 capsid epitopes, whereas a capsid-assembly-defective PNMA2 protein is not immunogenic. PNMA2 autoantibodies in cerebrospinal fluid of patients with anti-Ma2 paraneoplastic disease show similar preferential binding to spike capsid epitopes. PNMA2 capsid-injected mice develop learning and memory deficits. These observations suggest that PNMA2 capsids act as an extracellular antigen, capable of generating an autoimmune response that results in neurological deficits.
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Antígenos de Neoplasias , Neoplasias , Proteínas do Tecido Nervoso , Síndromes Paraneoplásicas do Sistema Nervoso , Animais , Humanos , Camundongos , Autoanticorpos , Capsídeo/metabolismo , Epitopos , Neoplasias/complicações , Síndromes Paraneoplásicas do Sistema Nervoso/metabolismo , Síndromes Paraneoplásicas do Sistema Nervoso/patologia , Antígenos de Neoplasias/metabolismo , Proteínas do Tecido Nervoso/metabolismoRESUMO
OBJECTIVE: The aim is to determine the pattern of initial clinical presentations of systemic lupus erythematous (SLE) in patients in a Pakistani lupus cohort. METHODS: This is a multi-centric, retrospective, descriptive study that was done through the analysis of electronic records of patients registered with outdoor clinics of the Arthritis Care Foundation (ACF) from November 2021 to March 2023. Follow-up records of all patients diagnosed and labeled as SLE as per ACR/EULAR criteria 2019 were reviewed and only those patients whose initial presentation of SLE was documented at their incident visit (after verifying the signs and symptoms from record of their GP/referring physicians' visits) were included in the study. A total of 388 patients diagnosed with SLE were included in the study. Their data was then entered and analyzed by using SPSS 23. The qualitative data was expressed as percentages and numbers while the quantitative variables were expressed as mean and standard deviation. Data correlation was calculated by Chi-Square test, and a p-value of less than 0.05 was considered statistically significant. RESULTS: Of our 388 patients, 360 (92.8%) were females and 28 (7.2%) were males giving a female-to-male ratio of 12:1. The mean age of our patients was 32.8 + 9.8 years. Mucocutaneous manifestations were most commonly reported in our patient group by 336 (86.7%) patients. Musculoskeletal complaints were the next most common presenting feature reported by 246 (61.9%) patients followed by constitutional symptoms in 78 (20.1%) patients, and renal involvement in 42 (10.8%) patients. CONCLUSION: In our study, a majority of patients presented with mucocutaneous symptoms. It is therefore of paramount importance to suspect autoimmune diseases in patients with these system involvements.
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Artrite , Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Lúpus Eritematoso Sistêmico/diagnóstico , Estudos Retrospectivos , PaquistãoRESUMO
Rheumatoid Arthritis (RA) is a chronic, symmetrical inflammatory autoimmune disorder characterized by painful, swollen synovitis and joint erosions, which can cause damage to bone and cartilage and be associated with progressive disability. Despite expanded treatment options, some patients still experience inadequate response or intolerable adverse effects. Consequently, the treatment options for RA remain quite limited. The enzyme AKT1 is crucial in designing drugs for various human diseases, supporting cellular functions like proliferation, survival, metabolism, and angiogenesis in both normal and malignant cells. Therefore, AKT serine/threonine kinase 1 is considered crucial for targeting therapeutic strategies aimed at mitigating RA mechanisms. In this context, directing efforts toward AKT1 represents an innovative approach to developing new anti-arthritis medications. The primary objective of this research is to prioritize AKT1 inhibitors using computational techniques such as molecular modeling and dynamics simulation (MDS) and shape-based virtual screening (SBVS). A combined SBVS approach was employed to predict potent inhibitors against AKT1 by screening a pool of compounds sourced from the ChemDiv and IMPPAT databases. From the SBVS results, only the top three compounds, ChemDiv_7266, ChemDiv_2796, and ChemDiv_9468, were subjected to stability analysis based on their high binding affinity and favorable ADME/Tox properties. The SBVS findings have revealed that critical residues, including Glu17, Gly37, Glu85, and Arg273, significantly contribute to the successful binding of the highest-ranked lead compounds at the active site of AKT1. This insight helps to understand the specific binding mechanism of these leads in inhibiting RA, facilitating the rational design of more effective therapeutic agents.
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CONTEXT: IgM-dominant immune complex-mediated glomerulonephritis (IgM-dominant ICMGN) is a rare renal entity, characterized by a membranoproliferative pattern by light microscopy, dominant IgM staining by immunofluorescent staining, and subendothelial deposits by electron microscopy. This study was to investigate if some of IgM-ICMGN were associated with autoimmune disorders induced by hydralazine. DESIGN: Seven IgM-dominant ICMGN cases were identified over 8 years. Their pathologic phenotypes and clinical scenarios were analyzed in detail. RESULTS: Patients' ages ranged from 47 to 87 years old with 5 women and two men. Six of seven patients had drug-induced autoimmune phenomenon (hydralazine-induced positive ANCA and ANA). All of them had renal dysfunction and some proteinuria. Most pathologic features showed a membranoproliferative pattern of glomerulonephritis with dominant IgM deposits at subendothelial spaces. IgM nephropathy (a variant of focal segmental glomerulosclerosis), chronic thrombotic microangiopathy, and cryoglobulinemic glomerulopathy were ruled out in the cases. CONCLUSION: The hydralazine-induced autoimmune phenomenon can be seen in IgM-dominant ICMGN, which should be classified as a subtype of membranoproliferative glomerulonephritis.
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Hidralazina , Imunoglobulina M , Humanos , Pessoa de Meia-Idade , Feminino , Hidralazina/efeitos adversos , Masculino , Idoso de 80 Anos ou mais , Idoso , Glomerulonefrite Membranoproliferativa/imunologia , Glomerulonefrite Membranoproliferativa/patologia , Glomerulonefrite Membranoproliferativa/induzido quimicamente , Anti-Hipertensivos/efeitos adversos , Glomerulonefrite/imunologia , Glomerulonefrite/induzido quimicamente , Glomerulonefrite/patologia , Complexo Antígeno-AnticorpoRESUMO
Immune thrombocytopenia (ITP) is a complex clinical and pathophysiological autoimmune disorder and in the past decade, thousands of papers have been published on this topic. To shed light on the global scientific output, Ou et al. performed a comprehensive bibliometric analysis of the ITP literature to clarify the major hotspots and future research directions. Commentary on: Ou et al. A bibliometric analysis of primary immune thrombocytopenia from 2011 to 2021. Br J Haematol 2023;201:954-970.
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Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , LeituraRESUMO
The platelet antibodies that cause pseudothrombocytopenia (PTCP) act only in vitro and do not produce clinical bleeding. Most studies on PTCP have focused on improving differential diagnosis with true thrombocytopenia but studies on the characteristics of patients with PTCP are limited. In this study, we aimed to evaluate the clinical and biological characteristics of 192 patients with PTCP. In addition to general variables, we evaluated automated and microscopic platelet counts, platelet clumps, platelet diameters, immature platelet fraction (IPF), and platelet antibodies. Adult women accounted for the largest subgroup of patients (n=82; 42.7%) and 67 patients (34.9%) were grouped into families. Forty-four patients (22.9%) had one or more associated autoimmune disorders (ADs); 39 relatives of these patients (19.8%) had ADs and 45 relatives (23.4%) had immune thrombocytopenia (ITP) or unspecified thrombocytopenia. Platelet cryptantibodies and/or autoantibodies were positive in 56 patients (30.1%). Most patients (n=169; 80%) had automated platelet counts >80×109/L. In all patients, microscopic platelet counts were ≥150×109/L. The platelet clump index (% increase in microscopic platelet count compared to automatic count) ranged from 30 to >7000%. Platelet diameters and IPF parameters were significantly greater in the PTCP versus healthy controls (p<0.001). A total of 17 patients (8.8%) had had previous ITP or the PTCP evolved into ITP. Our data suggest that PTCP should be considered a situation of autoimmunity; the assessment of platelet clumps has a high diagnostic value; the close association between ITP and PTCP suggests that these conditions could be different phases of the same process.
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Púrpura Trombocitopênica Idiopática , Trombocitopenia , Adulto , Humanos , Feminino , Ácido Edético , Trombocitopenia/diagnóstico , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia , Contagem de Plaquetas , Autoanticorpos , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/complicaçõesRESUMO
OBJECTIVE: To evaluate the relationship between postural orthostatic tachycardia syndrome (POTS) and pregnancy. DESIGN: Cross-sectional survey. SETTING: International. SAMPLE: A total of 8941 female patients with a diagnosis of POTS. METHODS: Data from the survey were analysed using descriptive measures and stratified for comparisons. MAIN OUTCOME MEASURES: Symptom course of POTS during pregnancy. Secondary outcomes included pregnancy loss, POTS onset during pregnancy and the impacts of a comorbid diagnosis of Ehlers-Danlos syndrome or an autoimmune disorder on symptoms during pregnancy. RESULTS: Overall, 40.8% (n = 3652) of participants reported one or more pregnancies. Most participants experienced worsening of symptoms in the first (62.6%) and third (58.9%) trimesters and 3 months after pregnancy (58.7%), and 81.1% experienced worsening symptoms at any point in their pregnancy. Most participants with worsening symptoms in the first trimester also experienced worsening symptoms in the second (61.6%) and third (68.1%) trimesters, but if they improved in the first trimester then this improvement persisted in the second and third trimesters. Of participants who reported that POTS was triggered by a specific event (41.3%), 8.1% reported pregnancy as the trigger for the onset. CONCLUSIONS: Postural orthostatic tachycardia syndrome symptoms in the first trimester of pregnancy may help predict symptom course throughout the duration of pregnancy. Some individuals may experience an initial onset of POTS during pregnancy. This novel information may guide clinicians in counselling patients with POTS who are planning pregnancy.
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Aborto Espontâneo , Síndrome de Ehlers-Danlos , Síndrome da Taquicardia Postural Ortostática , Gravidez , Humanos , Feminino , Síndrome da Taquicardia Postural Ortostática/diagnóstico , Síndrome da Taquicardia Postural Ortostática/epidemiologia , Estudos Transversais , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/epidemiologia , ComorbidadeRESUMO
BACKGROUND: Primary Sjögren's syndrome (pSS) is a common chronic systemic autoimmune disorder which primarily affects the exocrine glands. Patients may have extraglandular disease involving multiple organs, including the kidneys. This study aimed at investigating the clinical data and laboratory markers which were associated with renal function damage or renal involvement. METHOD: One thousand two hundred eighty-eight adult pSS patients from the Department of Rheumatology and Clinical Immunology were enrolled in this retrospective cohort study. And there were 334 patients of them followed up for more than two years for analyzing demographic, clinical data and laboratory markers. Statistical analysis was performed by R software (Version 3.6.2). RESULT: Nearly 95% of 1288 pSS patients were women, and the positive rates of anti-SSA (Sjögren's syndrome A) and anti-SSB were 63% and 27% respectively. 12% of the pSS patients presented renal involvement with eGFR < 60 mL/min/1.73 m2, and the mean age of hospital presentation, serum creatinine and urea were the highest (P < 0.001), and ANA (antinuclear antibody)-positive, anti-SSB-positive and anti-scl-70-positive were more prevalent in this group. Multivariate analyses showed that age, urea, chlorine and anti-SSA indicate a significant association with renal dysfunction. Potassium, sodium and Jo-1 were also confirmed to be related with decreased renal function. The receiver operating characteristic (ROC) analysis including the above factors showed a good performance on the evaluation of renal injury including eGFR < 60 mL/min/1.73 m2 and eGFR 60 -90 mL/min/1.73 m2 in pSS, with area under curve (AUC) values of 0.957 and 0.821, and high sensitivity (71.1% and 84.4%) and specificity (95.5% and 70.5%). After a more than two years follow-up of anti-SSA positive patients, 34.14% of them developed decreased renal function, and 13.58% of them experienced a progression of renal injury with a 23.64% decrease in eGFR. CONCLUSION: Age, urea, chlorine, and anti-SSA were highly associated with renal injury in pSS. Early screening for autoantibodies would be meaningful for evaluation and prevention of renal injury in pSS.
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The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a significant role in health and disease. In this pathway, cGAS, one of the major cytosolic DNA sensors in mammalian cells, regulates innate immunity and the STING-dependent production of pro-inflammatory cytokines, including type-I interferon. Moreover, the cGAS-STING pathway is integral to other cellular processes, such as cell death, cell senescence, and autophagy. Activation of the cGAS-STING pathway by "self" DNA is also attributed to various infectious diseases and autoimmune or inflammatory conditions. In addition, the cGAS-STING pathway activation functions as a link between innate and adaptive immunity, leading to the inhibition or facilitation of tumorigenesis; therefore, research targeting this pathway can provide novel clues for clinical applications to treat infectious, inflammatory, and autoimmune diseases and even cancer. In this review, we focus on the cGAS-STING pathway and its corresponding cellular and molecular mechanisms in health and disease.
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Doenças Autoimunes , Interferon Tipo I , Animais , Imunidade Adaptativa , Autofagia , Mamíferos , NucleotidiltransferasesRESUMO
Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome was first described by McCarty in 1985 and is characterized by pitting oedema and an acute symmetrical synovitis of small joints. Self-directed inflammation in autoimmune disorders is caused by an abnormal activation of the adaptive immune system, while in autoinflammatory disorders, it is due to aberrant activation of the innate immune system without autoantibodies or autoreactive T cells. The role of autoimmunity in the pathogenesis of RS3PE syndrome is suggested by possible associations with some autoimmune diseases and human leukocyte antigen (HLA) haplotypes. However, several other features point to a possible role of autoinflammation in RS3PE syndrome. In this review, the relative contributions of both innate and adaptive immune systems to the pathogenesis of RS3PE syndrome are discussed.
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Artrite Reumatoide , Doenças Autoimunes , Sinovite , Humanos , Sinovite/complicações , Síndrome , Artrite Reumatoide/complicações , Edema , Doenças Autoimunes/complicaçõesRESUMO
Background: Though epileptic seizures are common in posterior reversible encephalopathy syndrome (PRES), status epilepticus (SE) as the presenting feature is rare. Objective: To study the clinical spectrum and outcome of patients with SE as presenting feature of PRES. Methods: This is a retrospective study. PRES was diagnosed based on the clinical features and imaging findings on brain MRI (n = 40) which became normal after 6 months follow-up imaging. Patients with SE as the initial manifestation of PRES were identified. Baseline information regarding the clinical presentation, etiology, past history of illness, treatment history, imaging findings, EEG and long-term clinical outcome. Result: Seizure was the most common presentation seen in 31 patients (77.5%). The etiologies in PRES were preeclampsia, or eclampsia [n = 33 (82.5%)], hypertensive encephalopathy [n = 3 (7.5%)], systemic lupus erythematosus (SLE), AIP, and chronic renal failure (CRF) in one patient each [n = 01 (2.5%)]. Brain MRI showed the involvement of parieto-occipital lobes (n = 33 [82.5%]) mostly. Status epilepticus (generalized convulsive) was the presenting feature in eight cases (20%). Among them, five cases (0.5%) had a history of chronic epilepsy. In the remaining three patients, SLE and acute intermittent porphyria, CRF precipitated the SE. Conclusion: The study highlights the clinico-etiological spectrum of PRES and the identification of SE within its context leading to the early diagnosis and management if treated early. The role of antenatal care is important for the identification and treatment of etiologies, blood pressure, proper antiepileptic drug compliance and appropriate counseling. How to cite this article: Prasad P. Status Epilepticus as a Presenting Feature in Posterior Reversible Encephalopathy Syndrome: Tertiary Care Center Experience. Indian J Crit Care Med 2023;27(7):488-492.
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Multiple neurobiological pathways have been implicated in the pathobiology of major depressive disorder (MDD). The identification of reliable biological substrates across the entire MDD spectrum, however, is hampered by a vast heterogeneity in the clinical presentation, presumably as a consequence of heterogeneous pathobiology. One way to overcome this limitation could be to explore disease subtypes based on biological similarity such as "inflammatory depression". As such a subtype may be particularly enriched in depressed patients with an underlying inflammatory condition, multiple sclerosis (MS) could provide an informative disease context for this approach. Few studies have explored immune markers of MS-associated depression and replications are missing. To address this, we analyzed data from two independent case-control studies on immune signatures of MS-associated depression, conducted at two different academic MS centers (overall sample size of n = 132). Using a stepwise data-driven approach, we identified CD4+CCR7lowTCM cell frequencies as a robust correlate of depression in MS. This signature was associated with core symptoms of depression and depression severity (but not MS severity per se) and linked to neuroinflammation as determined by magnetic resonance imaging (MRI). Furthermore, exploratory analyses of T cell polarization revealed this was largely driven by cells with a TH1-like phenotype. Our findings suggest (neuro)immune pathways linked to affective symptoms of autoimmune disorders such as MS, with potential relevance for the understanding of "inflammatory" subtypes of depression.
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Transtorno Depressivo Maior , Esclerose Múltipla , Biomarcadores , Estudos de Casos e Controles , Depressão/metabolismo , Transtorno Depressivo Maior/complicações , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/metabolismoRESUMO
BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is a major regulator of immune response and chronic inflammatory conditions acting through regulation of B cells, T-helper 17 (Th17) cells, and IL-17 production. Previous studies have demonstrated that dysregulation of STAT3 is crucial for SLE pathogenesis and disease severity. It is believed that single nucleotide polymorphisms (SNPs) located at the 3'-UTR sequence of the target genes could dysregulate their expression by disrupting the binding site of miRNAs. In the present study, we assessed the possible association between rs1053005 and rs1053023 SNPs at miRNA binding sites in the STAT3 gene and the risk of SLE in the Iranian population for the first time. METHODS: 112 SLE cases and 120 healthy controls were genotyped for rs1053005 (A>G) and rs1053023 (A>G) polymorphisms in STAT3 using real-time PCR high resolution melting method (HRM). RESULTS: Our results revealed substantial associations between GG genotype and G allele of rs1053023 with enhanced risk of SLE (OR for GG genotype= 3.13; 95%CI [1.61-6.1], OR for G allele = 2.22; 95%CI [1.51-3.25]). However, no important correlations have been found between rs1053005 polymorphism and SLE susceptibility in this population (p>0.05). Moreover, stratification analysis showed that these polymorphisms are correlated with parameters indicating disease activity and more severe course of the disease. These factors include some laboratory test results and clinical manifestations such as renal involvements. CONCLUSION: The current study suggests a significant association between STAT3 polymorphisms and augmented risk of SLE, clinical symptoms, disease activity, and severity.
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Lúpus Eritematoso Sistêmico , MicroRNAs , Sítios de Ligação , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Irã (Geográfico) , Lúpus Eritematoso Sistêmico/diagnóstico , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único/genética , Fator de Transcrição STAT3/genéticaRESUMO
BACKGROUND: SARS-CoV-2 vaccination is associated with an increased risk for Bell's palsy and some other neurological disorders assumed to be of autoimmune origin. While facial nerve palsy is frequent and usually idiopathic, hypoglossal nerve palsy is rare, and a specific cause is almost always found. We firstly report two patients who developed isolated hypoglossal nerve palsy shortly after SARS-CoV-2 vaccination. CASE PRESENTATION: Two otherwise healthy patients, a 49-year-old man and a 39-year-old woman, developed unilateral hypoglossal nerve palsy 10 and 7 days after the second SARS-CoV-2-vaccination (AstraZeneca and BioNTech/Pfizer), respectively. In both subjects, needle electromyography showed denervation and rarefication of motor units. CT, MRI, examination of blood and CSF as well as ENT exam were unremarkable. In both subjects symptoms gradually improved. CONCLUSION: Due to close temporal relationship, the absence of other etiologies, and spontaneous improvement we suspect the vaccination as the cause for hypoglossal nerve palsy in both patients. This is further supported by the rarity of isolated hypoglossal nerve palsies, especially in idiopathic cases. We suggest the addition of hypoglossal nerve palsy to the list of neurological injuries potentially caused by SARS-CoV-2 vaccination.
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Paralisia de Bell , Vacinas contra COVID-19 , COVID-19 , Paralisia Facial , Doenças do Nervo Hipoglosso , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paralisia de Bell/diagnóstico , COVID-19/complicações , Vacinas contra COVID-19/efeitos adversos , Doenças do Nervo Hipoglosso/etiologia , SARS-CoV-2 , Vacinação/efeitos adversosRESUMO
Bruton's tyrosine kinase (BTK) is a promising target in the treatment of B cell malignancies and autoimmune disorders. Developing selective non-covalent BTK inhibitors is an important strategy to overcome the side effects and drug resistance induced by covalent BTK inhibitors. In this article, we designed and synthesized pyrrolo[1,2-a]quinoxalin-4(5H)-one and imidazo[1,2-a]quinoxalin-4(5H)-one based selective noncovalent BTK inhibitors via scaffold hopping from BMS-986142 and investigated their biological activities. Among the synthesized compounds, pyrrolo[1,2-a]quinoxalin-4(5H)-one derivatives 2 and 4 showed great BTK inhibition potency with IC50 value at 7.41 nM and 11.4 nM, respectively. Besides, they showed equivalent or even better potency in U937 and Ramos cells than BMS-986142. The kinase selectivity profiling study illustrated the excellent selectivity of compound 2 against a panel of 468 kinases. In U937 xenograft models, compound 2 could significantly inhibit tumor growth with TGI = 65.61%. In all, we provided a new scaffold as non-covalent selective BTK inhibitors and the representative compounds exhibited potency both in vitro and in vivo.
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Inibidores de Proteínas Quinases , Quinoxalinas , Tirosina Quinase da Agamaglobulinemia , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Quinoxalinas/farmacologia , Relação Estrutura-AtividadeRESUMO
Rare cases of membranous glomerulopathy (MGN) with subepithelial deposits consisting of microspherular structures identified by electron microscopy have been described in the literature as either MGN with spherules or podocyte infolding glomerulopathy (PIG). The paucity of available studies shows a strong association with underlying autoimmune disease. To further understand the significance of subepithelial microspherular deposits, we retrospectively identified native kidney biopsies from 10 patients diagnosed as MGN with subepithelial microspherular structures identified by ultrastructural examination at the University of Rochester Medical Center (URMC) during an 11-year period. The majority were Caucasian (80%) with a mean age of 51.3 (±12.9) years. 50% had an autoimmune disorder, of which 80% were SLE. Two SLE cases had concomitant rheumatoid arthritis and Sjogren's syndrome. One additional case had antiphospholipid syndrome and showed lupus-like features on biopsy. 40% were idiopathic and negative for PLA2R, NELL1, and THSD7A. MGN with subepithelial microspherular structures is frequently associated with an underlying autoimmune disease. The majority are negative for markers of primary MGN (PLA2R, THSD7A, and NELL1) and show features suggestive of secondary MGN.
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Glomerulonefrite Membranosa , Lúpus Eritematoso Sistêmico , Biópsia , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/patologia , Humanos , Microscopia Eletrônica , Estudos RetrospectivosRESUMO
The 'Focal Infection Era in Dentistry' in the late 19th and early 20th century resulted in widespread implementation of tooth extraction and limited the progress of endodontics. The theory proposed that bacteria and toxins entrapped in dentinal tubules could disseminate systemically to remote body parts, resulting in many types of degenerative systemic diseases. This theory was eventually refuted due to anecdotal evidence. However, lately there has been increased interest in investigating whether endodontic disease could have an impact on general health. There are reviews that have previously been carried out on this subject, but as new data have emerged since then, this review aims to appraise the available literature investigating the dynamic associations between apical periodontitis, endodontic treatment, and systemic health. The available evidence regarding focal infection theory, bacteraemia and inflammatory markers was appraised. The review also collated the available research arguing the associations of apical periodontitis with cardiovascular diseases, diabetes mellitus, adverse pregnancy outcome and autoimmune disorders, along with the effect of statins and immunomodulators on apical periodontitis prevalence and endodontic treatment prognosis. There is emerging evidence that bacteraemia and low-grade systemic inflammation associated with apical periodontitis may negatively impact systemic health, e.g., development of cardiovascular diseases, adverse pregnancy outcomes, and diabetic metabolic dyscontrol. However, there is limited information supporting the effect of diabetes mellitus or autoimmune disorders on the prevalence and prognosis post endodontic treatment. Furthermore, convincing evidence supports that successful root canal treatment has a beneficial impact on systemic health by reducing the inflammatory burden, thereby dismissing the misconceptions of focal infection theory. Although compelling evidence regarding the association between apical periodontitis and systemic health is present, further high-quality research is required to support and establish the benefits of endodontic treatment on systemic health.
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Doenças Autoimunes , Bacteriemia , Doenças Cardiovasculares , Diabetes Mellitus , Infecção Focal , Periodontite Periapical , Doenças Autoimunes/complicações , Doenças Cardiovasculares/complicações , Feminino , Infecção Focal/complicações , Humanos , Periodontite Periapical/complicações , Periodontite Periapical/microbiologia , Periodontite Periapical/terapia , GravidezRESUMO
Artemisinins are a family of sesquiterpene lactones originally derived from the sweet wormwood (Artemisia annua). Beyond their well-characterized role as frontline antimalarial drugs, artemisinins have also received increased attention for other potential pharmaceutical effects, which include antiviral, antiparsitic, antifungal, anti-inflammatory, and anticancer activities. With concerted efforts in further preclinical and clinical studies, artemisinin-based drugs have the potential to be viable treatments for a great variety of human diseases. Here, we provide a comprehensive update on recent reports of pharmacological actions and applications of artemisinins outside of their better-known antimalarial role and highlight their potential therapeutic viability for various diseases.
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Antimaláricos , Artemisia annua , Artemisininas , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Reposicionamento de Medicamentos , HumanosRESUMO
Acquired idiopathic generalized anhidrosis (AIGA) is a rare disorder in which systemic anhidrosis/hypohidrosis occurs without causative dermatological, metabolic or neurological disorder. Most cases of AIGA have been reported in Asia, especially in Japan, but there have been only a few reports in Europe and the United States. Severe AIGA may result in heatstroke and can reduce quality of life due to restriction of exercise and outdoor works. AIGA is often accompanied by cholinergic urticaria (CholU), and it is thought that AIGA and CholU with anhidrosis/hypohidrosis belong to the same spectrum of the disease. However, the pathophysiology of AIGA has not yet been clarified. Decreased expression of cholinergic receptor M3 on the epithelial cells of eccrine sweat glands is often accompanied by T cell infiltration around eccrine apparatus, suggesting an immunological mechanism of disordered perspiration. AIGA is occasionally associated with various complications indicative of autoimmune disorders. The association of autoimmune complications further suggests that AIGA is an autoimmune disorder. Studies on complications may lead to a better understanding of the pathophysiology of AIGA.
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Doenças Autoimunes/patologia , Hipo-Hidrose/patologia , Animais , Doenças Autoimunes/complicações , Doenças Autoimunes/imunologia , Humanos , Hipo-Hidrose/complicações , Hipo-Hidrose/imunologia , Receptor Muscarínico M3/análise , Receptor Muscarínico M3/imunologia , Receptores Colinérgicos/análise , Receptores Colinérgicos/imunologia , Urticária/etiologia , Urticária/imunologia , Urticária/patologiaRESUMO
Parry-Romberg syndrome, also known as progressive hemifacial atrophy, is a rare, slowly progressive disorder characterized by unilateral, painless atrophy of the skin and subcutaneous tissue of the face. Neurological manifestations such as epilepsy, migraine and trigeminal neuralgia are relatively common and accompany in 15-20% of cases. Various etiologies such as infection, trauma, embryonic developmental dysfunction, sympathetic dysfunction and autoimmune disorders have been suggested as possible causes. Here we describe a 37-year-old woman whose disease manifested with dynamic contrast enhanced white matter changes over a period of two years, suggesting a "relapsing-remitting" course. Besides the inflammatory activity, positive serum-autoantibodies, inflammatory findings in cerebrospinal fluid, and an overlapping systemic autoimmune disorder may further support the hypothesis of autoimmune-inflammatory mediated pathogenesis.