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1.
Can Vet J ; 65(6): 587-593, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38827589

RESUMO

Background: Strongylus vulgaris is one of the most pathogenic nematodes affecting equids. Larval migration through the cranial mesenteric artery (CMA) with attendant arteritis and thromboembolism can result in fatal non-strangulating intestinal infarction. Once considered a historical disease, recent studies have described the reemergence of this pathogen in several European countries; however, little is known of the current prevalence of S. vulgaris in the Canadian horse population. Objective: To determine the prevalence of active S. vulgaris cranial mesenteric arteritis in horses submitted for postmortem examination to the Diagnostic Services Unit (DSU) at the University of Calgary Faculty of Veterinary Medicine. Animals and procedure: We conducted a retrospective review of all equine postmortem cases submitted to the DSU between July 1, 2010 and June 30, 2022. Over 12 y, 510 horses > 2 mo of age from Alberta were submitted to the DSU for necropsy. Active cases were defined as those with endarteritis and thrombosis in the CMA or its branches. Those cases with only intimal scarring of the CMA were classified as historical. Results: The prevalence of all CMA lesions (both historical and active) over the study period was 17.3% (88/510). Active S. vulgaris cranial mesenteric arteritis was documented in 6.1% (31/510) of equine postmortems and the sequelae of verminous arteritis were the cause of euthanasia or death in 1.5% (8/510) of the cases submitted. Conclusion and clinical relevance: Even after historically intense efforts to eradicate this parasite, the continued effects of S. vulgaris are demonstrated by the results of this study. Strongylus vulgaris should not be regarded as a parasite of the past and verminous arteritis remains an important differential diagnosis for horses in western Canada presenting with mild colic or dull demeanor and anorexia of duration > 24 h. Furthermore, S. vulgaris should be taken into careful consideration when implementing antiparasitic control strategies. Practitioners should remain current on prevention, diagnosis, and treatment of this potentially reemerging and fatal equine disease.


Étude rétrospective de la prévalence lors d'autopsies équines de l'artérite mésentérique crâniale causée par Strongylus vulgaris en Alberta (2010 à 2022). Contexte: Strongylus vulgaris est l'un des nématodes les plus pathogènes affectant les équidés. La migration des larves à travers l'artère mésentérique crâniale (CMA), accompagnée d'artérite et de thromboembolie, peut entraîner un infarctus intestinal non étranglant mortel. Autrefois considérée comme une maladie historique, des études récentes ont décrit la réémergence de cet agent pathogène dans plusieurs pays européens; cependant, on sait peu de choses sur la prévalence actuelle de S. vulgaris dans la population équine canadienne. Objectif: Déterminer la prévalence de l'artérite mésentérique crâniale active à S. vulgaris chez les chevaux soumis pour examen post mortem au Diagnostic Service Unit (DSU), College of Veterinary Medicine, University of Calgary. Animaux et procédure: Nous avons effectué un examen rétrospectif de tous les cas post-mortem d'équidés soumis au DSU entre le 1er juillet 2010 et le 30 juin 2022. Sur 12 ans, 510 chevaux âgés de plus de 2 mois de l'Alberta ont été soumis au DSU pour autopsie. Les cas actifs ont été définis comme ceux présentant une endartérite et une thrombose dans la CMA ou ses branches. Les cas présentant uniquement des cicatrices à l'intima de la CMA ont été classés comme anciens. Résultats: La prévalence de toutes les lésions de CMA (anciennes et actives) au cours de la période d'étude était de 17,3 % (88/510). Une artérite mésentérique crâniale active à S. vulgaris a été documentée dans 6,1 % (31/510) des autopsies équines et les séquelles de l'artérite vermineuse ont été la cause de l'euthanasie ou du décès dans 1,5 % (8/510) des cas soumis. Conclusion et pertinence clinique: Malgré des efforts historiquement intenses pour éradiquer ce parasite, les effets continus de S. vulgaris sont démontrés par les résultats de cette étude. Strongylus vulgaris ne doit pas être considéré comme un parasite du passé et l'artérite vermineuse demeure un diagnostic différentiel important pour les chevaux de l'ouest du Canada présentant des coliques légères ou un comportement abattu et une anorexie de durée > 24 h. De plus, S. vulgaris doit être attentivement pris en compte lors de la mise en œuvre de stratégies de contrôle antiparasitaire. Les praticiens doivent rester informés de la prévention, du diagnostic et du traitement de cette maladie équine potentiellement ré-émergente et mortelle.(Traduit par Dr Serge Messier).


Assuntos
Arterite , Doenças dos Cavalos , Strongylus , Animais , Cavalos , Estudos Retrospectivos , Prevalência , Feminino , Masculino , Alberta/epidemiologia , Doenças dos Cavalos/parasitologia , Doenças dos Cavalos/epidemiologia , Doenças dos Cavalos/patologia , Arterite/veterinária , Arterite/epidemiologia , Artérias Mesentéricas/patologia , Infecções Equinas por Strongyloidea/epidemiologia , Infecções Equinas por Strongyloidea/parasitologia
3.
J Neonatal Perinatal Med ; 17(2): 265-268, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38669486

RESUMO

 Streptococcus gallolyticus subspecies pasteurianus is a subtype of Streptococcus bovis (S. bovis) that has become increasingly recognized as a sepsis-causing pathogen in neonates. It is well documented that S. bovis species have a predilection to both cardiac and gastrointestinal tissue, and in adult populations, isolating these organisms in the bloodstream often triggers further evaluation for co-morbid complications such as colon cancer or endocarditis. However, no such guidance currently exists in neonatal literature. We present a case of a preterm infant with S. gallolyticus subsp. pasteurianus bacteremia presenting as necrotizing enterocolitis (NEC) not previously described in the literature. Furthermore, through a complete diagnostic evaluation, including an echocardiogram, our patient was found to have the rare complication of endocarditis.


Assuntos
Enterocolite Necrosante , Recém-Nascido Prematuro , Infecções Estreptocócicas , Humanos , Enterocolite Necrosante/microbiologia , Recém-Nascido , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/microbiologia , Arterite/microbiologia , Streptococcus gallolyticus subspecies gallolyticus , Masculino , Bacteriemia/microbiologia , Doenças do Prematuro/microbiologia , Feminino , Antibacterianos/uso terapêutico
4.
J Clin Immunol ; 44(3): 77, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38451335

RESUMO

PURPOSE: To assess the role of the interleukin (IL)-17 A/IL-17 receptor A (IL-17RA) in Kawasaki disease (KD)-related coronary arteritis (CA). METHODS: In human study, the plasma levels of IL-17 A and coronary arteries were concurrently examined in acute KD patients. In vitro responses of human coronary endothelial cells to plasma stimulation were investigated with and without IL-17RA neutralization. A murine model of Lactobacillus casei cell-wall extract (LCWE)-induced CA using wild-type Balb/c and Il17ra-deficient mice were also inspected. RESULTS: The plasma levels of IL-17 A were significantly higher in KD patients before intravenous immunoglobulin therapy, especially in those with coronary artery lesion. The pre-IVIG IL-17 A levels positively correlated with maximal z scores of coronary diameters and plasma-induced endothelial mRNA levels of chemokine (C-X-C motif) ligand-1, IL-8, and IL-17RA. IL-17RA blockade significantly reduced such endothelial upregulations of aforementioned three genes and inducible nitric oxide synthase, and neutrophil transmigration. IL-17RA expression was enhanced on peripheral blood mononuclear cells in pre-IVIG KD patients, and in the aortic rings and spleens of the LCWE-stimulated mice. LCWE-induced CA composed of dual-positive Ly6G- and IL-17 A-stained infiltrates. Il17ra-deficient mice showed reduced CA severity with the fewer number of neutrophils and lower early inducible nitric oxide synthase and chemokine (C-X-C motif) ligand-1 mRNA expressions than Il17ra+/+ littermates, and absent IL-17RA upregulation at aortic roots. CONCLUSION: IL-17 A/IL-17RA axis may play a role in mediating aortic neutrophil chemoattraction, thus contributory to the severity of CA in both humans and mice. These findings may help to develop a new therapeutic strategy toward ameliorating KD-related CA.


Assuntos
Arterite , Síndrome de Linfonodos Mucocutâneos , Humanos , Animais , Camundongos , Infiltração de Neutrófilos , Óxido Nítrico Sintase Tipo II , Receptores de Interleucina-17/genética , Células Endoteliais , Imunoglobulinas Intravenosas , Interleucina-17 , Leucócitos Mononucleares , Ligantes , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Quimiocinas , RNA Mensageiro
5.
BMC Cardiovasc Disord ; 24(1): 162, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491429

RESUMO

BACKGROUND: All-cause mortality and cardiovascular disease are increased in subjects with metabolic syndrome (MetS). Risk scores are used to predict individual risk of heart disease. We performed a long-term follow-up study to investigate whether risk scores and cardiovascular risk factors such as arterial stiffness, high-sensitive C-reactive protein (hs-CRP) and oxidized LDL (OxLDL) can be used to predict cardiovascular events in Finnish men with MetS. METHODS: After baseline measurements we followed 105 Finnish men aged 30 to 65 years with MetS for a mean period of 16.4 years. The primary outcome of the study was a composite of myocardial infarction, stroke, symptomatic vascular disease diagnosed with invasive angiography, coronary or peripheral revascularization, amputation due to peripheral vascular disease, cardiovascular death and non-cardiovascular death. The endpoints were retrieved from electronic medical records. RESULTS: The number of acute myocardial infarctions and strokes during the first 10 years was lower than estimated by FINRISK score but SCORE predicted cardiovascular death correctly. During the whole follow-up period, 27 of 105 participants (25.8%) had 30 endpoint events. The incidence of the primary composite outcome was significantly lower in subjects with hs-CRP < 1.0 mg/L than in subjects with hs-CRP ≥ 1.0 mg/L (6 of 41 subjects [14.6%] vs. 21 of 64 subjects [32.8%]; p = 0.036). The incidence of the primary composite outcome was higher among subjects with large artery elasticity classified as borderline compared to subjects with normal large artery elasticity (5 of 10 subjects [50%] vs. 22 of 93 subjects [24%]; p = 0.05). There was no difference in the incidence of primary composite outcome in groups with different degrees of small artery elasticity or different level of oxLDL. CONCLUSIONS: Men with MetS who had hs-CRP ≥ 1.0 mg/L had higher risk for CVD and all-cause mortality than those with hs-CRP of < 1.0 mg/L. This also applies to subjects with borderline decreased large artery elasticity. The amount of OxLDL had no predictive value on the incidence of CVD and all-cause mortality. Men with MetS participating in the Hämeenlinna Metabolic Syndrome Research Program without lifestyle or drug intervention had better outcome for myocardial infarction or stroke than estimated by the FINRISK score. TRIAL REGISTRATION: ClinicalTrials.gov NCT01119404 retrospectively registered 07/05/2010.


Assuntos
Arterite , Doenças Cardiovasculares , Lipoproteínas LDL , Síndrome Metabólica , Infarto do Miocárdio , Acidente Vascular Cerebral , Rigidez Vascular , Masculino , Humanos , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Doenças Cardiovasculares/epidemiologia , Seguimentos , Proteína C-Reativa/análise , Finlândia/epidemiologia , Fatores de Risco , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/complicações , Inflamação/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/complicações , Arterite/complicações
6.
Molecules ; 29(6)2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38542959

RESUMO

Previous studies have revealed the microbial metabolism of dietary choline in the gut, leading to its conversion into trimethylamine (TMA). Polymethoxyflavones (PMFs), exemplified by tangeretin, have shown efficacy in mitigating choline-induced cardiovascular inflammation. However, the specific mechanism by which these compounds exert their effects, particularly in modulating the gut microbiota, remains uncertain. This investigation focused on tangeretin, a representative PMFs, to explore its influence on the gut microbiota and the choline-TMA conversion process. Experimental results showed that tangeretin treatment significantly attenuated the population of CutC-active bacteria, particularly Clostridiaceae and Lactobacillus, induced by choline chloride in rat models. This inhibition led to a decreased efficiency in choline conversion to TMA, thereby ameliorating cardiovascular inflammation resulting from prolonged choline consumption. In conclusion, tangeretin's preventive effect against cardiovascular inflammation is intricately linked to its targeted modulation of TMA-producing bacterial activity.


Assuntos
Arterite , Flavonas , Microbioma Gastrointestinal , Ratos , Animais , Colina/metabolismo , Metilaminas/farmacologia , Metilaminas/metabolismo , Bactérias/metabolismo , Inflamação/tratamento farmacológico
7.
Top Companion Anim Med ; 60: 100863, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38513795

RESUMO

OBJECTIVE: To describe an unusual case of spontaneous hemothorax resulting from thymic involution in a dog with suspected acquired bleeding dyscrasia associated with steroid-responsive meningitis-arteritis (SRMA). CASE DESCRIPTION: A 6-month-old spayed female Golden Retriever was referred due to the sudden onset of lethargy, fever (pyrexia), loss of appetite (anorexia), and moderate neck pain. These symptoms emerged six days after an ovariohysterectomy performed by the primary veterinarian. Upon admission, the patient exhibited pale mucous membranes, tachycardia (180 bpm), bilateral muffled heart sounds and tachypnea. Abdominal and thoracic point-of-care ultrasound (POCUS) were performed and revealed bilateral pleural effusion. Due to the patient's unstable condition, emergent thoracocentesis and transfusion of packed red blood cells was required. The initial work-up performed included a complete blood cell count (CBC), biochemistry profile, venous blood gas and coagulation panel (PT, APTT, fibrinogen). Pleural effusion analysis was compatible with hemothorax. Bloodwork was unremarkable including the initial coagulation panel. Further coagulation test was performed including buccal mucosal bleeding time, viscoelastic-based clot detection tests (TEG) and Von Willebrand factor antigen measurement. TEG revealed marked hyperfibrinolysis. Angiostrongylus vasorum and 4DX snap test were performed and yielded a negative result. Thoracic CT scan revealed the presence of a soft tissue-attenuating mass in the ventral mediastinum, thymic involution, and enlargement of the sternal and mediastinal lymph nodes. Therapy with tranexamic acid and corticosteroids at anti-inflammatory doses was initiated. Marked clinical improvement was observed within 24 hours, and after three days of hospitalization the patient was discharged. One month later, the dog was referred again for acute pyrexia, hyporexia, and neck pain which progressed to non-ambulatory tetraparesis. Neurological examination was compatible with C6-T2 lesion. MRI and cerebrospinal fluid analysis were performed and revealed a final diagnosis of steroid-responsive meningitis-arteritis (SRMA) with associated intramedullary hemorrhage. Corticosteroids were started again, and the patient showed a dramatic improvement over the next 24 hours. Three weeks after the diagnosis, the dog returned to a clinically normal state. The treatment was gradually tapered over the following months, guided by regular neurological and clinical examinations and CRP measurements, without any relapses. NEW OR UNIQUE INFORMATION: To the best of the author's knowledge, this is the first documented case of a dog experiencing spontaneous hemothorax as a result of thymic hemorrhage/involution which, in the absence of other identifiable diseases, was attributed to a hyperfibrinolytic state induced by a severe inflammatory disease such as SRMA.


Assuntos
Arterite , Doenças do Cão , Hemotórax , Meningite , Animais , Cães , Feminino , Doenças do Cão/tratamento farmacológico , Meningite/veterinária , Meningite/complicações , Meningite/tratamento farmacológico , Arterite/veterinária , Arterite/complicações , Hemotórax/veterinária , Hemotórax/etiologia , Timo
8.
Sci Rep ; 14(1): 2930, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316950

RESUMO

This study aimed to investigate the association between nonarteritic anterior ischemic optic neuropathy (NAION) and Parkinson's disease (PD) using a retrospective, nationwide, population-based cohort in South Korea. This study utilized data from the Korean National Health Insurance database, including 43,960 NAION patients and 219,800 age- and sex-matched controls. Cox proportional hazards regression models were used to assess the risk of developing PD in the NAION group compared to the control group after adjusting for various confounding factors. Subgroup analyses were conducted based on sex, age, and comorbidities. The incidence rate of PD was higher in the NAION group (1.326 per 1000 person-years) than in the control group (0.859 per 1000 person-years). After adjusting for confounding factors, the risk of developing PD was significantly higher in the NAION group (adjusted hazard ratio [aHR] 1.516, 95% confidence interval [CI] 1.300-1.769). Subgroup analyses did not reveal a significant difference in the risk of PD development based on sex, age, or comorbidities. This retrospective, nationwide, population-based cohort study revealed a significant association between NAION and an increased risk of developing PD in a South Korean population. The incidence rate of PD was observed to be higher in individuals diagnosed with NAION than in age- and sex-matched controls even after adjusting for potential confounding variables, with the risk being approximately 51.6% higher in the NAION group. Further research is necessary to elucidate the underlying pathophysiological mechanisms linking NAION to PD and to determine whether similar associations exist in other ethnic and geographical populations.


Assuntos
Arterite , Neuropatia Óptica Isquêmica , Doença de Parkinson , Humanos , Estudos de Coortes , Estudos Retrospectivos , Neuropatia Óptica Isquêmica/epidemiologia , Neuropatia Óptica Isquêmica/etiologia , Neuropatia Óptica Isquêmica/diagnóstico , Incidência , Doença de Parkinson/epidemiologia , Doença de Parkinson/complicações , Fatores de Risco , Arterite/complicações , Arterite/diagnóstico , Arterite/epidemiologia
11.
J Am Heart Assoc ; 13(5): e032095, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38416140

RESUMO

Cardiovascular disease remains an important comorbidity in patients with rheumatoid arthritis (RA), but traditional models do not accurately predict cardiovascular risk in patients with RA. The addition of biomarkers could improve prediction. METHODS AND RESULTS: The TARGET (Treatments Against RA and Effect on FDG PET/CT) trial assessed whether different treatment strategies in RA differentially impact cardiovascular risk as measured by the change in arterial inflammation on arterial target to background ratio on fluorodeoxyglucose positron emission tomography/computed tomography scans conducted 24 weeks apart. A group of 24 candidate biomarkers supported by prior literature was assessed at baseline and 24 weeks later. Longitudinal analyses examined the association between baseline biomarker values, measured in plasma EDTA, and the change in arterial inflammation target to background ratio. Model fit was assessed for the candidate biomarkers only, clinical variables only, and models combining both. One hundred nine patients with median (interquartile range) age 58 years (53-65 years), RA duration 1.4 years (0.5-6.6 years), and 82% women had biomarkers assessed at baseline and follow-up. Because the main trial analyses demonstrated significant target to background ratio decreases with both treatment strategies but no difference across treatment groups, we analyzed all patients together. Baseline values of serum amyloid A, C-reactive protein, soluble tumor necrosis factor receptor 1, adiponectin, YKL-40, and osteoprotegerin were associated with significant change in target to background ratio. When selected candidate biomarkers were added to the clinical variables, the adjusted R2 improved from 0.20 to 0.33 (likelihood ratio P=0.0005). CONCLUSIONS: A candidate biomarker approach identified several promising biomarkers that associate with baseline and treatment-associated changes in arterial inflammation in patients with RA. These will now be tested in an external validation cohort.


Assuntos
Arterite , Artrite Reumatoide , Doenças Cardiovasculares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Arterite/complicações , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Biomarcadores , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco de Doenças Cardíacas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fatores de Risco , Idoso
13.
Diagn Interv Imaging ; 105(4): 137-143, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38284342

RESUMO

PURPOSE: The purpose of this in vivo animal study was to compare the acute histological effects on the arterial vessel wall of free-flow vs. blocked-flow embolization with metacryloxysulfolane-n­butyl cyanoacrylate (MS-NBCA) in several concentrations. MATERIALS AND METHODS: A total of 42 rabbit renal arteries were embolized using MS-NBCA mixed with ethiodized oil. The MS-NBCA concentration was 12.5%, 25%, or 50%. All mixtures were injected under both free-flow and blocked-flow conditions. The rabbits were euthanised 30 min after arterial embolization. Arterial-lumen distension, intimal inflammation and necrosis, peri­arterial edema, and distality of MS-NBCA penetration were assessed histologically. Multivariable regression analyses were performed using a manual backward procedure, with linear, ordinal and logistic regression to search for factors associated with these outcomes RESULTS: Marked or severe dilatation was observed in 36 out of 42 arteries (86%) and marked or transmural intimal arteritis in all 42 arteries (42/42; 100%). Lumen dilatation caused focal vessel-wall flattening, which resulted in intimal necrosis. Multifocal necrosis extending from the intima to the media occurred in 23 out of 42 kidneys (55%) and peri­arterial edema with multifocal vascular leakage in 19 out of 42 kidneys (45%). At multivariable analysis, blocked-flow MS-NBCA injection was associated with greater severity of vessel-wall lesions, including intimal arteritis (P = 0.003) and intimal necrosis (P = 0.014), compared to free-flow injection. Blocked-flow injection was also associated with peri­arterial edema (P = 0.008) and greater distality of MS-NBCA penetration (P = 0.001). CONCLUSION: Blocked-flow MS-NBCA injection during renal artery embolization is significantly associated with more acute arterial-wall damage and greater distality of glue penetration compared to free-flow injection in a rabbit model. These preliminary findings may have clinical implications, as blocked-flow injection is routinely used to treat specific vascular diseases or malformations in human.


Assuntos
Arterite , Embolização Terapêutica , Embucrilato , Animais , Humanos , Coelhos , Cianoacrilatos , Artéria Renal , Embolização Terapêutica/métodos , Arterite/tratamento farmacológico , Edema , Necrose , Resultado do Tratamento
15.
J Am Vet Med Assoc ; 262(4): 481-488, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38266391

RESUMO

OBJECTIVES: To evaluate blood and cerebrospinal fluid (CSF) concentrations of C-reactive protein (CRP) in dogs with meningoencephalitis of unknown origin (MUO); to evaluate whether blood CRP concentration is associated with epidemiological, clinicopathologic, and MRI findings; and to investigate blood CRP predictive power in survival. ANIMALS: 30 client-owned dogs with MUO, 15 client-owned dogs with steroid-responsive meningitis arteritis (SRMA; positive control group), and 15 healthy dogs (negative control group). METHODS: Blood CRP concentration was measured in each group, while it was performed in CSF only in the MUO and SRMA groups. The analysis of epidemiological data included breed, age, sex, duration of clinical signs, and history of seizures. Blinded analysis of MRI was performed based on a classification grid, and traditional CSF analysis parameters were assessed. The predictive power of blood CRP concentration regarding survival at 6 months was investigated. RESULTS: Of the 30 dogs with MUO, 9 (30%) had an increased CRP concentration in blood, and 3 (10%) showed a measurable CRP in CSF. Median blood CRP concentration in dogs with MUO was 0.1 mg/L (range, 0.1 to 102 mg/L), which was not statistically different from the healthy dog group but significantly lower than the SRMA control group. Only the duration of clinical signs was positively associated with an increased blood CRP level. Blood CRP concentration was not associated with survival at 6 months. CLINICAL RELEVANCE: Blood CRP concentration is of limited value for the diagnosis and prognosis of dogs with MUO. Chronicity of the disease may be associated with an increased concentration of blood CRP.


Assuntos
Arterite , Doenças do Cão , Meningite , Meningoencefalite , Humanos , Cães , Animais , Proteína C-Reativa , Meningoencefalite/diagnóstico , Meningoencefalite/veterinária , Meningite/líquido cefalorraquidiano , Meningite/diagnóstico , Meningite/veterinária , Arterite/diagnóstico , Arterite/veterinária , Arterite/líquido cefalorraquidiano
16.
PLoS One ; 19(1): e0295268, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38241272

RESUMO

In steroid-responsive meningitis-arteritis (SRMA), inflammatory dysregulation is driven by neutrophilic granulocytes resulting in purulent leptomeningitis. Neutrophils can generate neutrophil extracellular traps (NET). Uncontrolled NET-formation or impaired NET-clearance evidently cause tissue and organ damage resulting in immune-mediated diseases. The aim of the study was to verify that NET-formation is detectable in ex vivo samples of acute diseased dogs with SRMA by visualizing and measuring NET-markers in serum and cerebrospinal fluid (CSF) samples. CSF-samples of dogs with acute SRMA (n = 5) and in remission (n = 4) were examined using immunofluorescence (IF)-staining of DNA-histone-1-complexes, myeloperoxidase and citrullinated Histone H3 (H3Cit). Immunogold-labeling of H3Cit and neutrophil elastase followed by transmission electron microscopy (TEM) were used to determine ultrastructural NET-formation in the CSF of one exemplary dog. H3Cit-levels and DNase-activity were measured in CSF and serum samples using an H3Cit-ELISA and a DNase-activity-assay, respectively in patients with the following diseases: acute SRMA (n = 34), SRMA in remission (n = 4), bacterial encephalitis (n = 3), meningioma with neutrophilic inflammation (n = 4), healthy dogs (n = 6). NET-formation was detectable with IF-staining in n = 3/5 CSF samples of dogs with acute SRMA but were not detectable during remission. Vesicular NET-formation was detectable in one exemplary dog using TEM. DNase-activity was significantly reduced in dogs suffering from acute SRMA compared to healthy control group (p < 0.0001). There were no statistical differences of H3Cit levels in CSF or serum samples of acute diseased dogs compared to dogs under treatment, dogs suffering from meningioma or bacterial encephalitis or the healthy control group. Our findings demonstrate that NET-formation and insufficient NET-clearance possibly drive the immunologic dysregulation and complement the pathogenesis of SRMA. The detection of NETs in SRMA offers many possibilities to explore the aetiopathogenetic influence of this defence mechanism of the innate immune system in infectious and non-infectious canine neuropathies.


Assuntos
Arterite , Doenças do Cão , Encefalite , Armadilhas Extracelulares , Neoplasias Meníngeas , Meningioma , Meningite , Humanos , Cães , Animais , Meningite/tratamento farmacológico , Meningite/veterinária , Arterite/tratamento farmacológico , Arterite/veterinária , Esteroides , Desoxirribonucleases
20.
JAMA Cardiol ; 9(2): 189-194, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38090987

RESUMO

Importance: The risk for atherosclerotic disease is increased 1.5- to 2.0-fold among persons with HIV (PWH). Increased activation of the renin-angiotensin-aldosterone system may contribute to increased arterial inflammation in this population. Objective: To determine the effects of eplerenone on arterial inflammation among well-treated PWH without known cardiovascular disease (CVD). Design, Setting, and Participants: Well-treated PWH who participated in the double-blinded, placebo-controlled, Mineralocorticoid Receptor Antagonism for Cardiovascular Health in HIV (MIRACLE HIV) study between February 2017 and March 2022 assessing the effects of eplerenone on myocardial perfusion were invited to participate in the Mineralocorticoid Receptor Antagonism By Eplerenone to Lower Arterial Inflammation in HIV (MIRABELLA) substudy if there was no current statin use. Participants were enrolled in the MIRABELLA study and underwent additional 18F-fludeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) imaging of the aorta and carotid arteries to assess arterial inflammation over 12 months of treatment with eplerenone vs placebo. Interventions: Eplerenone, 50 mg, twice a day vs identical placebo. Main Outcomes and Measures: The primary outcome was change in target to background ratio (TBR), a measure of arterial wall inflammation, in the index vessel after 12 months of treatment. The index vessel was defined as the vessel (aorta, left carotid artery, or right carotid artery) with the highest TBR at baseline in each participant. Results: A total of 26 participants (mean [SD] age, 54 [7] years; 18 male [69%]) were enrolled in the study. Treatment groups (eplerenone, 13 vs placebo, 13) were of similar age, sex, and body mass index. Eplerenone was associated with a reduction in TBR of the primary end point, the index vessel (eplerenone vs placebo: model treatment effect, -0.31; 95% CI, -0.50 to -0.11; P = .006; percentage change, -12.4% [IQR, -21.9% to -2.6%] vs 5.1% [IQR, -1.6% to 11.0%]; P = .003). We further observed a significant reduction of the TBR of the most diseased segment (MDS) of the index vessel (eplerenone vs placebo: -19.1% [IQR, -27.0% to -11.9%] vs 6.8% [IQR, -9.1% to 12.1%]; P = .007). A similar result was seen assessing the index vessel of the carotids (eplerenone vs placebo: -10.0% [IQR, -21.8% to 3.6%] vs 9.7% [IQR, -9.8% to 15.9%]; P = .046). Reduction in the TBR of MDS of the index vessel on 18F-FDG PET/CT correlated with improvement in the stress myocardial blood flow on cardiac magnetic resonance imaging (Spearman ρ = -0.67; P = .01). Conclusion and Relevance: In this small randomized clinical trial, eplerenone was associated with reduction in arterial inflammation among well-treated PWH without known CVD. In addition, reductions in arterial inflammation as measured by 18F-FDG PET/CT were related to improvements in stress myocardial perfusion. Further larger studies should explore whether eplerenone is a potential treatment strategy for inflammatory-mediated CVD in PWH. Trial Registration: ClinicalTrials.gov Identifier: NCT02740179.


Assuntos
Arterite , Aterosclerose , Infecções por HIV , Humanos , Masculino , Pessoa de Meia-Idade , Aterosclerose/tratamento farmacológico , Aterosclerose/complicações , Eplerenona/uso terapêutico , Fluordesoxiglucose F18 , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptores de Mineralocorticoides/uso terapêutico , Resultado do Tratamento , Feminino
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