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1.
Nat Immunol ; 25(4): 671-681, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38448779

RESUMO

Cognitive impairment is a frequent manifestation of neuropsychiatric systemic lupus erythematosus, present in up to 80% of patients and leading to a diminished quality of life. In the present study, we used a model of lupus-like cognitive impairment that is initiated when antibodies that crossreact with excitatory neuronal receptors penetrate the hippocampus, causing immediate, self-limited, excitotoxic death of hippocampal neurons, which is then followed by a significant loss of dendritic complexity in surviving neurons. This injury creates a maladaptive equilibrium that is sustained in mice for at least 1 year. We identified a feedforward loop of microglial activation and microglia-dependent synapse elimination dependent on neuronal secretion of high mobility group box 1 protein (HMGB1) which binds the receptor for advanced glycation end products (RAGE) and leads to microglial secretion of C1q, upregulation of interleukin-10 with consequent downregulation of leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1), an inhibitory receptor for C1q. Treatment with a centrally acting angiotensin-converting enzyme inhibitor or with an angiotensin-receptor blocker restored a healthy equilibrium, microglial quiescence and intact spatial memory.


Assuntos
Autoanticorpos , Proteína HMGB1 , Animais , Camundongos , Complemento C1q , Proteína HMGB1/metabolismo , Doenças Neuroinflamatórias , Qualidade de Vida , Receptor para Produtos Finais de Glicação Avançada/metabolismo
2.
Semin Arthritis Rheum ; 65: 152347, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38185079

RESUMO

BACKGROUND: Long-term anticoagulant therapy is generally recommended for thrombotic antiphospholipid syndrome (TAPS) patients, however it may be withdrawn or not introduced in routine practice. OBJECTIVES: To prospectively evaluate the risk of thrombosis recurrence and major bleeding in non-anticoagulated TAPS patients, compared to anticoagulated TAPS, and secondly, to identify different features between those two groups. PATIENTS/METHODS: Using an international registry, we identified non-anticoagulated TAPS patients at baseline, and matched them with anticoagulated TAPS patients based on gender, age, type of previous thrombosis, and associated autoimmune disease. Thrombosis recurrence and major bleeding were prospectively analyzed using Kaplan-Meier method and compared using a marginal Cox's regression model. RESULTS: As of June 2022, 94 (14 %) of the 662 TAPS patients were not anticoagulated; and 93 of them were matched with 181 anticoagulated TAPS patients (median follow-up 5 years [interquartile range 3 to 8]). The 5-year thrombosis recurrence and major bleeding rates were 12 % versus 10 %, and 6 % versus 7 %, respectively (hazard ratio [HR] 1.38, 95 % confidence interval [CI] 0.53 to 3.56, p = 0.50 and HR 0.53; 95 % CI 0.15 to 1.86; p = 0.32, respectively). Non-anticoagulated patients were more likely to receive antiplatelet therapy (p < 0.001), and less likely to have more than one previous thrombosis (p < 0.001) and lupus anticoagulant positivity (p = 0.01). CONCLUSION: Fourteen percent of the TAPS patients were not anticoagulated at recruitment. Their recurrent thrombosis risk did not differ compared to matched anticoagulated TAPS patients, supporting the pressing need for risk-stratified secondary thrombosis prevention trials in APS investigating strategies other than anticoagulation.


Assuntos
Síndrome Antifosfolipídica , Trombose , Humanos , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , Hemorragia/etiologia , Estudos Prospectivos , Recidiva , Sistema de Registros , Trombose/complicações , Ensaios Clínicos como Assunto , Masculino , Feminino
3.
Clin Immunol ; 258: 109848, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38036277

RESUMO

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and/or pregnancy complications in the presence of persistently positive antiphospholipid antibodies (aPL). Although long-term anticoagulation with vitamin K antagonists is considered standard of care, there is an unmet need for safe therapeutics as primary thromboprophylaxis or adjuncts to standard of care in APS. APS is driven by oxidative stress, procoagulant, proinflammatory and angiogenic pathways. For these reasons there has been an increased interest into the investigation of antithrombotic, anti-inflammatory and anti-oxidant properties of natural supplements in APS. The objective of this review is to summarize the mechanistic, epidemiologic and clinical evidence behind the use of natural supplements in APS, with a specific focus on vitamin D, omega-3 fatty acids, coenzyme Q10, gingerol, and isoquercetin. This review should serve as a compelling argument for the future study of natural supplements in APS.


Assuntos
Síndrome Antifosfolipídica , Complicações na Gravidez , Tromboembolia Venosa , Feminino , Gravidez , Humanos , Anticoagulantes/uso terapêutico , Tromboembolia Venosa/complicações , Tromboembolia Venosa/tratamento farmacológico , Anticorpos Antifosfolipídeos , Complicações na Gravidez/tratamento farmacológico
4.
Arthritis Rheumatol ; 75(10): 1687-1702, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37635643

RESUMO

OBJECTIVE: To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR. METHODS: This international multidisciplinary initiative included 4 phases: 1) Phase I, criteria generation by surveys and literature review; 2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; 3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and 4) Phase IV, validation using independent adjudicators' consensus as the gold standard. RESULTS: The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into 6 clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and 2 laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti-ß2 -glycoprotein I antibodies). Patients accumulating at least 3 points each from the clinical and laboratory domains are classified as having APS. In the validation cohort, the new APS criteria versus the 2006 revised Sapporo classification criteria had a specificity of 99% versus 86%, and a sensitivity of 84% versus 99%. CONCLUSION: These new ACR/EULAR APS classification criteria were developed using rigorous methodology with multidisciplinary international input. Hierarchically clustered, weighted, and risk-stratified criteria reflect the current thinking about APS, providing high specificity and a strong foundation for future APS research.


Assuntos
Síndrome Antifosfolipídica , Reumatologia , Feminino , Gravidez , Humanos , Estados Unidos , beta 2-Glicoproteína I , Autoanticorpos , Imunoglobulina G , Imunoglobulina M
5.
Ann Rheum Dis ; 82(10): 1258-1270, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37640450

RESUMO

OBJECTIVE: To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR. METHODS: This international multidisciplinary initiative included four phases: (1) Phase I, criteria generation by surveys and literature review; (2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; (3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and (4) Phase IV, validation using independent adjudicators' consensus as the gold standard. RESULTS: The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into six clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and two laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti-ß2-glycoprotein I antibodies). Patients accumulating at least three points each from the clinical and laboratory domains are classified as having APS. In the validation cohort, the new APS criteria vs the 2006 revised Sapporo classification criteria had a specificity of 99% vs 86%, and a sensitivity of 84% vs 99%. CONCLUSION: These new ACR/EULAR APS classification criteria were developed using rigorous methodology with multidisciplinary international input. Hierarchically clustered, weighted, and risk-stratified criteria reflect the current thinking about APS, providing high specificity and a strong foundation for future APS research.


Assuntos
Síndrome Antifosfolipídica , Reumatologia , Feminino , Gravidez , Humanos , Síndrome Antifosfolipídica/diagnóstico , Autoanticorpos , Imunoglobulina G , Imunoglobulina M
6.
Res Sq ; 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37292843

RESUMO

Cognitive impairment is a frequent manifestation of neuropsychiatric systemic lupus erythematosus (NPSLE), present in up to 80% of patients and leading to a diminished quality of life. We have developed a model of lupus-like cognitive impairment which is initiated when anti-DNA, anti-N-methyl D-aspartate receptor (NMDAR) cross- reactive antibodies, which are present in 30% of SLE patients, penetrate the hippocampus1. This leads to immediate, self-limited excitotoxic death of CA1 pyramidal neurons followed by a significant loss of dendritic arborization in the remaining CA1 neurons and impaired spatial memory. Both microglia and C1q are required for dendritic loss1. Here we show that this pattern of hippocampal injury creates a maladaptive equilibrium that is sustained for at least one year. It requires HMGB1 secretion by neurons to bind RAGE, a receptor for HMGB1 expressed on microglia, and leads to decreased expression of microglial LAIR-1, an inhibitory receptor for C1q. The angiotensin converting enzyme (ACE) inhibitor captopril, which can restore a healthy equilibrium, microglial quiescence, and intact spatial memory, leads to upregulation of LAIR-1. This paradigm highlights HMGB1:RAGE and C1q:LAIR-1 interactions as pivotal pathways in the microglial-neuronal interplay that defines a physiologic versus a maladaptive equilibrium.

7.
BMC Musculoskelet Disord ; 24(1): 382, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37189114

RESUMO

BACKGROUND: Giant Cell Arteritis (GCA) is a large vessel vasculitis that most commonly presents with headache, scalp tenderness, jaw claudication, and vision changes. Various other, less common, manifestations have been reported in the literature such as scalp and tongue necrosis. Though most patients respond to corticosteroids, some cases of GCA are refractory to the high doses of corticosteroids. CASE PRESENTATION: We present a 73-year-old female with GCA refractory to corticosteroids presenting with tongue necrosis. This patient significantly improved with a dose of tocilizumab, an IL-6 inhibitor. CONCLUSION: To the best of our knowledge, this is the first case report of a patient with refractory GCA presenting with tongue necrosis that had rapid improvement with tocilizumab. Prompt diagnosis and treatment can prevent severe outcomes such as tongue amputation in GCA patients with tongue necrosis, and tocilizumab may be effective for corticosteroid-refractory cases.


Assuntos
Arterite de Células Gigantes , Feminino , Humanos , Idoso , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Células Gigantes/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Língua , Necrose/tratamento farmacológico
8.
Adv Rheumatol ; 61(1): 64, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711275

RESUMO

BACKGROUND: Antiphospholipid syndrome (APS) is characterized by episodes of thrombosis, obstetric morbidity or both, associated with persistently positive antiphospholipid antibodies (aPL). Studying the profile of a rare disease in an admixed population is important as it can provide new insights for understanding an autoimmune disease. In this sense of miscegenation, Brazil is characterized by one of the most heterogeneous populations in the world, which is the result of five centuries of interethnic crosses of people from three continents. The objective of this study was to compare the clinical and laboratory characteristics of Brazilian vs. non-Brazilian primary antiphospholipid syndrome (PAPS) patients. METHODS: We classified PAPS patients into 2 groups: Brazilian PAPS patients (BPAPS) and PAPS patients from other countries (non-BPAPS). They were compared regarding demographic characteristics, criteria and non-criteria APS manifestations, antiphospholipid antibody (aPL) profile, and the adjusted Global Antiphospholipid Syndrome Score (aGAPSS). RESULTS: We included 415 PAPS patients (88 [21%] BPAPS and 327 [79%] non-BPAPS). Brazilian patients were significantly younger, more frequently female, sedentary, obese, non-white, and had a higher frequency of livedo (25% vs. 10%, p < 0.001), cognitive dysfunction (21% vs. 8%, p = 0.001) and seizures (16% vs. 7%, p = 0.007), and a lower frequency of thrombocytopenia (9% vs. 18%, p = 0.037). Additionally, they were more frequently positive for lupus anticoagulant (87.5% vs. 74.6%, p = 0.01), and less frequently positive to anticardiolipin (46.6% vs. 73.7%, p < 0.001) and anti-ß2-glycoprotein-I (13.6% vs. 62.7%, p < 0.001) antibodies. Triple aPL positivity was also less frequent (8% vs. 41.6%, p < 0.001) in Brazilian patients. Median aGAPSS was lower in the Brazilian group (8 vs. 10, p < 0.0001). In the multivariate analysis, BPAPS patients still presented more frequently with livedo, cognitive dysfunction and sedentary lifestyle, and less frequently with thrombocytopenia and triple positivity to aPL. They were also less often white. CONCLUSIONS: Our study suggests a specific profile of PAPS in Brazil with higher frequency of selected non-criteria manifestations and lupus anticoagulant positivity. Lupus anticoagulant (not triple positivity) was the major aPL predictor of a classification criteria event.


Assuntos
Síndrome Antifosfolipídica , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/diagnóstico , Brasil , Técnicas de Laboratório Clínico , Bases de Dados Factuais , Feminino , Humanos , Inibidor de Coagulação do Lúpus/sangue , Masculino , Fatores de Risco
10.
Adv Rheumatol ; 61: 64, 2021. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1345104

RESUMO

Abstract Background: Antiphospholipid syndrome (APS) is characterized by episodes of thrombosis, obstetric morbidity or both, associated with persistently positive antiphospholipid antibodies (aPL). Studying the profile of a rare disease in an admixed population is important as it can provide new insights for understanding an autoimmune disease. In this sense of miscegenation, Brazil is characterized by one of the most heterogeneous populations in the world, which is the result of five centuries of interethnic crosses of people from three continents. The objective of this study was to compare the clinical and laboratory characteristics of Brazilian vs. non-Brazilian primary antiphospholipid syndrome (PAPS) patients. Methods: We classified PAPS patients into 2 groups: Brazilian PAPS patients (BPAPS) and PAPS patients from other countries (non-BPAPS). They were compared regarding demographic characteristics, criteria and non-criteria APS manifestations, antiphospholipid antibody (aPL) profile, and the adjusted Global Antiphospholipid Syndrome Score (aGAPSS). Results: We included 415 PAPS patients (88 [21%] BPAPS and 327 [79%] non-BPAPS). Brazilian patients were significantly younger, more frequently female, sedentary, obese, non-white, and had a higher frequency of livedo (25% vs. 10%, p < 0.001), cognitive dysfunction (21% vs. 8%, p = 0.001) and seizures (16% vs. 7%, p = 0.007), and a lower frequency of thrombocytopenia (9% vs. 18%, p = 0.037). Additionally, they were more frequently positive for lupus anticoagulant (87.5% vs. 74.6%, p = 0.01), and less frequently positive to anticardiolipin (46.6% vs. 73.7%, p < 0.001) and anti-ß2-glycoprotein-I (13.6% vs. 62.7%, p < 0.001) antibodies. Triple aPL positivity was also less frequent (8% vs. 41.6%, p < 0.001) in Brazilian patients. Median aGAPSS was lower in the Brazilian group (8 vs. 10, p < 0.0001). In the multivariate analysis, BPAPS patients still presented more frequently with livedo, cognitive dysfunction and sedentary lifestyle, and less frequently with thrombocytopenia and triple positivity to aPL. They were also less often white. Conclusions: Our study suggests a specific profile of PAPS in Brazil with higher frequency of selected non-criteria manifestations and lupus anticoagulant positivity. Lupus anticoagulant (not triple positivity) was the major aPL predictor of a classification criteria event.

12.
Arthritis Rheumatol ; 71(9): 1413-1425, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31102496

RESUMO

Cognitive dysfunction (CD) is an insidious and underdiagnosed manifestation of systemic lupus erythematosus (SLE) that has a considerable impact on quality of life, which can be devastating. Given the inconsistencies in the modes of assessment and the difficulties in attribution to SLE, the reported prevalence of CD ranges from 5% to 80%. Although clinical studies of SLE-related CD have been hampered by heterogeneous subject populations and a lack of sensitive and standardized cognitive tests or other validated objective biomarkers for CD, there are, nonetheless, strong data from mouse models and from the clinical arena that show CD is related to known disease mechanisms. Several cytokines, inflammatory molecules, and antibodies have been associated with CD. Proposed mechanisms for antibody- and cytokine-mediated neuronal injury include the abrogation of blood-brain barrier integrity with direct access of soluble molecules in the circulation to the brain and ensuing neurotoxicity and microglial activation. No treatments for SLE-mediated CD exist, but potential candidates include agents that inhibit microglial activation, such as angiotensin-converting enzyme inhibitors, or that protect blood-brain barrier integrity, such as C5a receptor blockers. Structural and functional neuroimaging data have shown a range of regional abnormalities in metabolism and white matter microstructural integrity in SLE patients that correlate with CD and could in the future become diagnostic tools and outcome measures in clinical trials aimed at preserving cognitive function in SLE.


Assuntos
Disfunção Cognitiva/etiologia , Lúpus Eritematoso Sistêmico/psicologia , Anticorpos/sangue , Anticorpos/imunologia , Barreira Hematoencefálica , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Citocinas/sangue , Citocinas/imunologia , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Testes Neuropsicológicos , Prevalência
13.
Arch Gynecol Obstet ; 299(4): 923-931, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30739174

RESUMO

PURPOSE: To summarize and define the most appropriate diagnostic methods and therapeutic options for ruptured renal artery aneurysms in pregnancy based on rarely published data. METHODS: Literature searches of English-, German-, Spanish-, and Italian-language articles were performed in PubMed (1946-2018), PubMed Central (1900-2018) and Google Scholar. The search terms included renal artery aneurysm, renal artery rupture, pregnancy, puerperium, nierenarterienaneurysma, schwangerschaft, wochenbett, aneurisma de la arteria renal, el embarazo, puerperio, aneurisma dell'arteria renale and gravidanza. Additional studies were identified by reviewing reference lists of retrieved studies. RESULTS: Fifty-three cases were collected. The average maternal age was 31 ± 6 years; 71.4% were multiparous and significantly older than primiparas. The majority presented in the third trimester (62.3%), followed by second (20.7%) and the first (5.7%), while 11.3% presented postpartum. All postpartum patients presented during the first week postpartum and 50% during the first 24 h postpartum. Parity was not associated with the trimester of presentation. The left renal artery was affected slightly more frequently (58.5% vs. 41.5%). There were no differences in the affected side according to trimester of presentation, including postpartum. 25 out of 53 cases underwent ipsilateral nephrectomy (47.1%) and 18 underwent aneurysm repair or coil embolization (34.0%). There was no difference in maternal (25.8%) vs. 4 (18.1%) and fetal mortality according to the side of rupture. There were no differences in the distribution of maternal or fetal mortality frequency according to the trimester of presentation. CONCLUSIONS: The clinical presentation is easily confused with more common conditions and time to diagnosis is often delayed. Diagnostic delay is associated with high maternal and fetal mortality. Ruptured renal artery aneurysm should be included in the differential diagnosis for pregnant or peripartum patients presenting with acute and severe flank pain, especially if followed by a drop in blood pressure. Early diagnosis and immediate intervention are important for achieving better maternal and fetal outcomes. There are several methods of managing asymptomatic or ruptured renal artery aneurysm during pregnancy although no established guidelines exist.


Assuntos
Aneurisma/etiologia , Mortalidade Materna/tendências , Período Pós-Parto/fisiologia , Artéria Renal/anormalidades , Adulto , Aneurisma/patologia , Aneurisma Roto/diagnóstico , Feminino , Humanos , Gravidez
14.
Semin Arthritis Rheum ; 49(1): 74-83, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30598332

RESUMO

INTRODUCTION: Thrombotic microangiopathy (TMA) is a life-threatening, albeit infrequent, complication of systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). Recommendations for the treatment of SLE- and APS-related secondary TMA are currently based solely on case reports and expert opinion. Unfortunately, interventions may not yield timely results or effectively halt the progression of TMA. Since complement activation plays a key role in the pathogenesis of secondary TMA due to SLE, APS, a therapy that targets the complement pathway is an attractive intervention. Eculizumab, a recombinant, fully humanized IgG2/IgG4 monoclonal antibody inhibits C5 activation and is FDA-approved for PNH and atypical HUS (aHUS). However, limited case reports are available on its use in treatment of secondary TMA. CASE PRESENTATION AND RESULTS: We present the largest case series to date that includes 9 patients with SLE and/or APS who were successfully treated with eculizumab for refractory secondary TMA. In this case series, we report significant responses in hematology values, renal function and other organs following treatment with eculizumab. At 4 weeks, 75% improvement in platelet counts was observed in 78% of patients. Two-thirds of patients demonstrated >75% improvement of haptoglobin and LDH at four weeks. At 4 weeks, eGFR improved by 25% in half of the patients, and 43% had reductions in proteinuria. Two of 3 patients that required hemodialysis were able to be taken off hemodialysis. CONCLUSION: Based on these observations, we suggest that eculizumab may be a potential treatment option for acutely ill patients with secondary TMA due to SLE and/or APS who have failed standard of care. A collective approach is needed to better elucidate the role and optimal timing of eculizumab use in the management of TMA complicating SLE and/or APS.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Microangiopatias Trombóticas/tratamento farmacológico , Adulto , Síndrome Antifosfolipídica/complicações , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , Microangiopatias Trombóticas/etiologia , Resultado do Tratamento , Adulto Jovem
15.
J Exp Med ; 215(10): 2554-2566, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30185634

RESUMO

Cognitive impairment occurs in 40-90% of patients with systemic lupus erythematosus (SLE), which is characterized by autoantibodies to nuclear antigens, especially DNA. We discovered that a subset of anti-DNA antibodies, termed DNRAbs, cross reacts with the N-methyl-d-aspartate receptor (NMDAR) and enhances NMDAR signaling. In patients, DNRAb presence associates with spatial memory impairment. In a mouse model, DNRAb-mediated brain pathology proceeds through an acute phase of excitotoxic neuron loss, followed by persistent alteration in neuronal integrity and spatial memory impairment. The latter pathology becomes evident only after DNRAbs are no longer detectable in the brain. Here we investigate the mechanism of long-term neuronal dysfunction mediated by transient exposure to antibody. We show that activated microglia and C1q are critical mediators of neuronal damage. We further show that centrally acting inhibitors of angiotensin-converting enzyme (ACE) can prevent microglial activation and preserve neuronal function and cognitive performance. Thus, ACE inhibition represents a strong candidate for clinical trials aimed at mitigating cognitive dysfunction.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anticorpos Antinucleares/imunologia , Autoanticorpos , Encéfalo , Lúpus Eritematoso Sistêmico/imunologia , Transtornos da Memória , Neurônios/imunologia , Animais , Autoanticorpos/imunologia , Autoanticorpos/toxicidade , Encéfalo/imunologia , Encéfalo/patologia , Feminino , Lúpus Eritematoso Sistêmico/patologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/imunologia , Transtornos da Memória/patologia , Camundongos , Camundongos Endogâmicos BALB C , Microglia , Neurônios/patologia , Receptores de N-Metil-D-Aspartato/imunologia
16.
Cureus ; 10(3): e2373, 2018 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-29805942

RESUMO

Myotonic muscular dystrophy (DM) is a multi-system disorder affecting skeletal muscles as well as smooth and cardiac muscles. Patients with DM experience disturbances in gastrointestinal motility; however, pancreatobiliary manifestations have rarely been described. We report the case of a 58-year-old male with MD who presented with a sudden onset of vomiting and abdominal pain. Laboratory and radiological findings were consistent with acute pancreatitis. No identifiable cause of pancreatitis could be identified despite an extensive workup. Sphincter of Oddi dysfunction (SOD) was felt to be the most likely cause of our patient's acute pancreatitis. SOD leading to acute pancreatitis results from spasm of both the distal common biliary duct and the duct of Wirsung. It is a very rarely reported gastrointestinal manifestation of MD, but one that should not be overlooked.

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