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1.
Immun Ageing ; 18(1): 24, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016150

RESUMO

BACKGROUND: One hundred fifty million contagions, more than 3 million deaths and little more than 1 year of COVID-19 have changed our lives and our health management systems forever. Ageing is known to be one of the significant determinants for COVID-19 severity. Two main reasons underlie this: immunosenescence and age correlation with main COVID-19 comorbidities such as hypertension or dyslipidaemia. This study has two aims. The first is to obtain cut-off points for laboratory parameters that can help us in clinical decision-making. The second one is to analyse the effect of pandemic lockdown on epidemiological, clinical, and laboratory parameters concerning the severity of the COVID-19. For these purposes, 257 of SARSCoV2 inpatients during pandemic confinement were included in this study. Moreover, 584 case records from a previously analysed series, were compared with the present study data. RESULTS: Concerning the characteristics of lockdown series, mild cases accounted for 14.4, 54.1% were moderate and 31.5%, severe. There were 32.5% of home contagions, 26.3% community transmissions, 22.5% nursing home contagions, and 8.8% corresponding to frontline worker contagions regarding epidemiological features. Age > 60 and male sex are hereby confirmed as severity determinants. Equally, higher severity was significantly associated with higher IL6, CRP, ferritin, LDH, and leukocyte counts, and a lower percentage of lymphocyte, CD4 and CD8 count. Comparing this cohort with a previous 584-cases series, mild cases were less than those analysed in the first moment of the pandemic and dyslipidaemia became more frequent than before. IL-6, CRP and LDH values above 69 pg/mL, 97 mg/L and 328 U/L respectively, as well as a CD4 T-cell count below 535 cells/µL, were the best cut-offs predicting severity since these parameters offered reliable areas under the curve. CONCLUSION: Age and sex together with selected laboratory parameters on admission can help us predict COVID-19 severity and, therefore, make clinical and resource management decisions. Demographic features associated with lockdown might affect the homogeneity of the data and the robustness of the results.

2.
Immun Ageing ; 17: 22, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802142

RESUMO

BACKGROUND: The SARS-CoV-2 infection has widely spread to become the greatest public health challenge to date, the COVID-19 pandemic. Different fatality rates among countries are probably due to non-standardized records being carried out by local health authorities. The Spanish case-fatality rate is 11.22%, far higher than those reported in Asia or by other European countries. A multicentre retrospective study of demographic, clinical, laboratory and immunological features of 584 Spanish COVID-19 hospitalized patients and their outcomes was performed. The use of renin-angiotensin system blockers was also analysed as a risk factor. RESULTS: In this study, 27.4% of cases presented a mild course, 42.1% a moderate one and for 30.5% of cases, the course was severe. Ages ranged from 18 to 98 (average 63). Almost 60 % (59.8%) of patients were male. Interleukin 6 was higher as severity increased. On the other hand, CD8 lymphocyte count was significantly lower as severity grew and subpopulations CD4, CD8, CD19, and NK showed concordant lowering trends. Severity-related natural killer percent descents were evidenced just within aged cases. A significant severity-related decrease of CD4 lymphocytes was found in males. The use of angiotensin-converting enzyme inhibitors was associated with a better prognosis. The angiotensin II receptor blocker use was associated with a more severe course. CONCLUSIONS: Age and age-related comorbidities, such as dyslipidaemia, hypertension or diabetes, determined more frequent severe forms of the disease in this study than in previous literature cohorts. Our cases are older than those so far reported and the clinical course of the disease is found to be impaired by age. Immunosenescence might be therefore a suitable explanation for the hampering of immune system effectors. The adaptive immunity would become exhausted and a strong but ineffective and almost deleterious innate response would account for COVID-19 severity. Angiotensin-converting enzyme inhibitors used by hypertensive patients have a protective effect in regards to COVID-19 severity in our series. Conversely, patients on angiotensin II receptor blockers showed a severer disease.

3.
J Neuroinflammation ; 15(1): 296, 2018 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-30367633

RESUMO

BACKGROUND: Recent studies in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS), suggest an involvement of the histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) in important processes such as cell adhesion and migration. METHODS: Here, we aimed to expand these initial observations by investigating the role of EZH2 in MS. mRNA expression levels for EZH2 were measured by real-time PCR in peripheral blood mononuclear cells (PBMC) from 121 MS patients (62 untreated and 59 receiving treatment) and 24 healthy controls. RESULTS: EZH2 expression levels were decreased in PBMC from untreated patients compared to that from controls, and treatment significantly upregulated EZH2 expression. Expression of miR-124 was increased in MS patients compared to controls. Blood immunophenotyping revealed EZH2 expression mostly restricted to CD4+ and CD8+ T cells, and circulating EZH2+ CD4+ and CD8+ T cells were decreased in untreated MS patients compared to controls. CD8+ T cells expressing EZH2 exhibited a predominant central memory phenotype, whereas EZH2+ CD4+ T cells were of effector memory nature, and both T cell subsets produced TNF-α. EZH2+ T cells were enriched in the cerebrospinal fluid compartment compared to blood and were found in chronic active lesions from MS patients. EZH2 inhibition and microarray analysis in PBMC was associated with significant downregulation of key T cell adhesion molecules. CONCLUSION: These findings suggest a role of EZH2 in the migration of T cells in MS patients. The observation of TNF-α expression by CD4+ and CD8+ T cells expressing EZH2 warrants additional studies to explore more in depth the pathogenic potential of EZH2+-positive cells in MS.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Leucócitos Mononucleares/metabolismo , Esclerose Múltipla Crônica Progressiva/patologia , Esclerose Múltipla Recidivante-Remitente/patologia , Adulto , Animais , Estudos de Coortes , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/etiologia , Encefalomielite Autoimune Experimental/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Feminino , Adjuvante de Freund/toxicidade , Humanos , Leucócitos Mononucleares/classificação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/imunologia , Esclerose Múltipla Recidivante-Remitente/imunologia , Glicoproteína Mielina-Oligodendrócito/toxicidade , Fragmentos de Peptídeos/toxicidade , Proteínas Proto-Oncogênicas c-vav/genética , Proteínas Proto-Oncogênicas c-vav/metabolismo , Subpopulações de Linfócitos T , Talina/genética , Talina/metabolismo , Adulto Jovem
4.
Mult Scler ; 24(10): 1317-1327, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-28653862

RESUMO

BACKGROUND: The precise mechanism of action of dimethyl fumarate (DMF) treatment in MS remains unknown. OBJECTIVE: To identify the changes in the blood lymphocyte profile of MS patients predicting no evidence of disease activity (NEDA) status after DMF treatment. METHODS: We studied blood lymphocyte subsets of 64 MS patients treated with DMF at baseline and after 6 months of treatment by flow cytometry. NEDA (41 patients) or ongoing disease activity (ODA, 23 patients) were monitored after a year of follow-up. RESULTS: During treatment, all patients experienced an increase in the naive T cells and a decrease in effector memory ones. However, only NEDA patients showed a significant reduction in central memory CD4+ and CD8+ T cells, memory B cells, CD4+ T cells producing interferon (IFN)-gamma, CD8+ T cells producing tumor necrosis factor-alpha (TNF-alpha), and IFN-gamma and B cells producing TNF-alpha. Additionally, they had an increase in regulatory CD56bright cells not observed in ODA group. After treatment, there was a negative correlation between CD56bright cells and CD8+ T cells producing IFN-gamma and TNF-alpha. CONCLUSION: A pro-tolerogenic shift in the blood leukocyte profile associates with an optimal response to DMF in MS.


Assuntos
Subpopulações de Linfócitos B/imunologia , Fumarato de Dimetilo/uso terapêutico , Imunossupressores/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Subpopulações de Linfócitos B/efeitos dos fármacos , Feminino , Humanos , Tolerância Imunológica/efeitos dos fármacos , Tolerância Imunológica/imunologia , Inflamação/imunologia , Masculino , Subpopulações de Linfócitos T/efeitos dos fármacos , Adulto Jovem
5.
J Vitreoretin Dis ; 8(5): 593-596, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39318982

RESUMO

Purpose: To describe the structural features of the autologous retinal transplant donor tissue area seen on optical coherence tomography (OCT). Methods: This observational prospective study included patients who had vitrectomy and autologous retinal graft surgery for a macular hole. OCT of the donor area was performed in the postoperative period after gas reabsorption (mean, 16.2 days ±9.8 [SD] after surgery; range, 7 to 28 days), and structural findings in the harvest area were recorded and analyzed. Results: Of the 12 eyes included in the series, most showed glial tissue or some migration of the inner nuclear layer (INL) in the donor area. Hyperreflective dots and epiretinal membranes were present in a few cases; 2 eyes showed denuded retinal epithelial pigment. Conclusions: OCT revealed changes in the donor area, predominantly filled with glial tissue, INL migration, and inflammatory signs, that mostly resolved during follow-up.

6.
Clin Ophthalmol ; 18: 2473-2480, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246553

RESUMO

Introduction: Maculopathy secondary to pathologic myopia (PM) is increasingly causing visual impairment and blindness worldwide. PM is associated with tractional maculopathy that ranges from macular foveoschisis to macular hole. These disorders are treated with different options that offer variable results, reflecting the need for new techniques that address myopic maculopathy with consistent outcomes. Methods: Since human amniotic membrane (HAM) has been reported to be safe for intraocular use and to promote retinal healing, it was incorporated as an adjuvant in pars plana vitrectomy in patients with different tractional disorders related to myopia. This work presents a prospective, consecutive case series of seven patients with high myopia who underwent a 25-gauge vitrectomy with ILM peeling and HAM transplantation. Results and Discussion: Our six-month results show that this novel technique delivers functional success related to tissue permanence without recurrence of traction that translates into visual acuity gain and maintenance that are superior to other techniques.

7.
Access Microbiol ; 6(6)2024.
Artigo em Inglês | MEDLINE | ID: mdl-39045243

RESUMO

Infectious endophthalmitis is a severe ophthalmic emergency. This infection can be caused by bacteria and fungi. For efficient treatment, the administration of antimicrobial drugs to which the microbes are susceptible is essential. The aim of this study was to identify micro-organisms in biopsies of Mexican endophthalmitis patients using metagenomic next-generation sequencing and determine which antibiotic resistance genes were present in the biopsy samples. In this prospective case study, 19 endophthalmitis patients were recruited. Samples of vitreous or aqueous humour were extracted for DNA extraction for metagenomic next-generation sequencing. Analysis of the sequencing results revealed the presence of a wide variety of bacteria in the biopsies. Resistome analysis showed that homologues of antibiotic resistance genes were present in several biopsy samples. Genes possibly conferring resistance to ceftazidime and vancomycin were detected in addition to various genes encoding efflux pumps. Our findings contrast with the widespread opinion that only one or a few bacterial strains are present in the infected tissues of endophthalmitis patients. These diverse communities might host many of the resistance genes that were detected, which can further complicate the infections.

8.
Int J Retina Vitreous ; 8(1): 3, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983678

RESUMO

BACKGROUND: To describe the epidemiological traits, clinical characteristics, diagnostic procedures, therapeutic interventions and evolution in a large series of patients with diagnosis of Eales' disease. METHODS: A clinical retrospective review of patients with Eales' disease, evaluated and treated between April 2009 and April 2018, with a 1-year minimum follow-up. Thirty patients (59 eyes), were included. Age, sex, laboratory results (CBC, glycemia, protein electrophoresis, ACE levels) immunological profile and a Quantiferon-TB Gold Plus test were recorded. The patients were divided into groups according to their evolution, medical or surgical treatment, and visual outcomes. RESULTS: Seventeen male patients and 13 female patients were included, and their ages ranged from 14 to 35 years. The Quantiferon-TB Gold Plus test was positive in 25 patients. Twenty-eight patients had unilateral vitreous hemorrhage, 10 of whom presented with vasculitis and non-perfusion areas in the contralateral eye, 9 presented contralateral peripheral neovascularization and 9 had contralateral fibrovascular proliferation. The remaining 2 patients presented with a rhegmatogenous retinal detachment. In 6 patients, conservative treatment with intravitreal anti-VEGF injections and photocoagulation was performed after the hemorrhage cleared. Twenty-two patients, required vitrectomy, with good visual outcomes. Macular edema was found in 16 eyes, which responded to periocular and/or systemic corticosteroid therapy, except for 9 eyes that required intravitreal bevacizumab, with complete resolution in 7 eyes and partial resolution in 2 eyes. CONCLUSIONS: Eales' disease is a pathology of significant prevalence in our country. The distribution according to sex, tends to be equivalent. The etiology, even when it is not specifically determined, according to laboratory tests, confirms the probable immunologic response in the presence of Mycobacterium tuberculosis antigens. This is still a diagnosis of exclusion, and therefore, it is advisable to perform a complete laboratory work-up in each case. Timely application of laser and other medical treatments, help to avoid progression to more advanced stages and their complications. The surgical treatment of vitrectomy for vitreous hemorrhage, and/or tractional vitreous detachment yields good primary anatomical and functional outcomes. Secondary macular edema responds to periocular and intravitreal corticosteroids, and in refractory cases, the use of anti-VEGF therapy leads to an effective resolution.

9.
Case Rep Ophthalmol ; 13(3): 783-788, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36845456

RESUMO

This case report describes a novel surgical technique for the treatment of macular hole and focal macular detachment associated with high myopia and posterior staphyloma. A 65-year-old female presented with a stage 3C myopic traction maculopathy and VA of 20/600. OCT examination confirmed a macular hole of 958 µm diameter, posterior staphyloma, and macular detachment. We performed combined phacoemulsification surgery with 23G pars plana vitrectomy; the anterior capsule was preserved and divided into two equal circular laminar flaps. We proceeded with central and peripheral vitrectomy, brilliant blue staining, and partial ILM peeling; capsular sheets were introduced sequentially in the vitreous chamber, the first one was implanted below the hole and attached to pigment epithelium, the second lamina was inserted into the hole, and the remaining portion of ILM was implanted crosswise below the edges of the hole. Macular-hole closure and progressive reapplication of the macular detachment were obtained, with a final VA of 20/80. Treatment of macular holes and focal macular detachment in high myopic eyes is complex, even for experienced surgeons. We propose a new technique with additional mechanisms based on anterior lens capsule and internal limiting membrane tissue properties that showed functional and anatomical improvement and could be considered an alternative treatment.

10.
Case Rep Ophthalmol ; 13(2): 504-510, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35950021

RESUMO

A 16-year-old boy with elevated hyperopia presented to the office with a 24-h history of bilateral blurred vision, mainly of the left eye, and bilateral central serous chorioretinopathy. He showed a clinically recognizable bacillary layer detachment in one eye and excellent multimodal diagnostic image correlation, with the best-corrected visual acuity as 20/400. He had bilateral serous retinal detachment, as confirmed by optical coherence tomography. Laser photocoagulation was performed with good results, and reestablishment of the foveal anatomical structure was documented 16 days after treatment.

11.
Sci Rep ; 11(1): 9299, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33927255

RESUMO

Serum neurofilament light chains (sNfL) are biomarkers of disease activity in multiple sclerosis (MS), but their value to predict response to treatment, and their association with patient immunological profile, need to be further explored. We studied 80 relapsing-remitting MS patients initiating dimethyl fumarate (DMF) treatment. sNfL levels were explored at baseline and at 3, 6 and 12 months by single molecule array. Blood lymphocyte subsets were measured at baseline and at 6 months by flow cytometry. Patients were followed a year and classified as NEDA (no evidence of disease activity) or ODA (ongoing disease activity). NEDA patients had lower sNfL levels at baseline (p = 0.0001), and after three (p = 0.004) and six (p = 0.03) months of DMF treatment. Consequently, low baseline sNfL values (≤ 12 pg/ml) increased the probability of NEDA (OR 5.8; CI 1.82-15.6; p = 0.002, after correcting by disease activity in the previous year), and associated with significant reductions of central memory CD4+ T lymphocytes, interferon-gamma+ CD8+ T lymphocytes, Natural Killer T cells, and memory B cells upon DMF treatment, being the highest differences in memory B cells (p < 0.0001). This shows that low baseline sNfL values identify MS patients with higher probability of optimal response to DMF and of a reduction in effector immune cells.


Assuntos
Fumarato de Dimetilo/uso terapêutico , Imunossupressores/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/dietoterapia , Proteínas de Neurofilamentos/sangue , Adulto , Linfócitos B/imunologia , Biomarcadores/sangue , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/imunologia , Estudos Prospectivos , Linfócitos T/imunologia , Resultado do Tratamento
12.
Sci Rep ; 11(1): 8441, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33875702

RESUMO

Epstein-Barr virus (EBV), human herpesvirus 6A/B (HHV-6A/B) and multiple sclerosis (MS)-associated retrovirus (MSRV) have been described as possible MS triggers. We analysed antibody titres against EBV and HHV-6, and MSRV envelope (env) mRNA expression, in the serum of pregnant multiple sclerosis patients (P-MS) to study their possible link to the clinical activity of MS during pregnancy and postpartum and their possible role as relapse predictors. For that purpose, serum samples were collected from 71 pregnant women (50 pregnant MS and 21 pregnant healthy controls-P-HC) during pregnancy and postpartum. Relating to antibody titres, IgM antibody titres against HHV-6A/B were significantly higher in P-MS than in P-HC both in each pregnancy trimester and in the postpartum period. Moreover, IgM antibody titres against HHV-6A/B were higher in P-MS who suffered a relapse during the postpartum. Regarding MSRV env mRNA expression, the prevalence in the first trimester of pregnancy was significantly higher in P-MS who suffered relapses during pregnancy. Summing it up, high IgM antibody titres against HHV-6A/B and MSRV env mRNA expression during the first trimester of pregnancy could act as relapse predictors for the gestation/postpartum periods.


Assuntos
Herpesvirus Cercopitecino 1/imunologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 6/imunologia , Esclerose Múltipla , Viroses/diagnóstico , Adulto , Anticorpos Antivirais/sangue , Biomarcadores , Retrovirus Endógenos/isolamento & purificação , Retrovirus Endógenos/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Feminino , Herpes Zoster , Humanos , Imunoglobulina M/sangue , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/etiologia , Esclerose Múltipla/virologia , Gravidez , RNA Mensageiro/sangue , RNA Viral/sangue , Proteínas do Envelope Viral/sangue , Proteínas do Envelope Viral/genética , Viroses/complicações , Viroses/imunologia
13.
Front Immunol ; 12: 760546, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34691084

RESUMO

Objective: To explore if baseline blood lymphocyte profile could identify relapsing remitting multiple sclerosis (RRMS) patients at higher risk of developing secondary autoimmune adverse events (AIAEs) after alemtuzumab treatment. Methods: Multicenter prospective study including 57 RRMS patients treated with alemtuzumab followed for 3.25 [3.5-4.21] years, (median [interquartile range]). Blood samples were collected at baseline, and leukocyte subsets determined by flow cytometry. We had additional samples one year after the first cycle of alemtuzumab treatment in 39 cases. Results: Twenty-two patients (38.6%) developed AIAEs during follow-up. They had higher B-cell percentages at baseline (p=0.0014), being differences mainly due to plasmablasts/plasma cells (PB/PC, p=0.0011). Those with no AIAEs had higher percentages of CD4+ T cells (p=0.013), mainly due to terminally differentiated (TD) (p=0.034) and effector memory (EM) (p=0.031) phenotypes. AIAEs- patients also showed higher values of TNF-alpha-producing CD8+ T cells (p=0.029). The percentage of PB/PC was the best variable to differentiate both groups of patients. Baseline values >0.10% closely associated with higher AIAE risk (Odds ratio [OR]: 5.91, 95% CI: 1.83-19.10, p=0.004). When excluding the 12 patients with natalizumab, which decreases blood PB/PC percentages, being the last treatment before alemtuzumab, baseline PB/PC >0.1% even predicted more accurately the risk of AIAEs (OR: 11.67, 95% CI: 2.62-51.89, p=0.0007). The AIAEs+ group continued having high percentages of PB/PC after a year of alemtuzumab treatment (p=0.0058). Conclusions: A PB/PC percentage <0.1% at baseline identifies MS patients at low risk of secondary autoimmunity during alemtuzumab treatment.​.


Assuntos
Alemtuzumab/efeitos adversos , Autoimunidade/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Imunossupressores/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto , Linfócitos B/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
14.
Front Immunol ; 12: 685139, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34322119

RESUMO

Patients with multiple sclerosis (MS) suffer with age an early immunosenescence process, which influence the treatment response and increase the risk of infections. We explored whether lipid-specific oligoclonal IgM bands (LS-OCMB) associated with highly inflammatory MS modify the immunological profile induced by age in MS. This cross-sectional study included 263 MS patients who were classified according to the presence (M+, n=72) and absence (M-, n=191) of LS-OCMB. CSF cellular subsets and molecules implicated in immunosenescence were explored. In M- patients, aging induced remarkable decreases in absolute CSF counts of CD4+ and CD8+ T lymphocytes, including Th1 and Th17 cells, and of B cells, including those secreting TNF-alpha. It also increased serum anti-CMV IgG antibody titers (indicative of immunosenescence) and CSF CHI3L1 levels (related to astrocyte activation). In contrast, M+ patients showed an age-associated increase of TIM-3 (a biomarker of T cell exhaustion) and increased values of CHI3L1, independently of age. Finally, in both groups, age induced an increase in CSF levels of PD-L1 (an inductor of T cell tolerance) and activin A (part of the senescence-associated secretome and related to inflammaging). These changes were independent of the disease duration. Finally, this resulted in augmented disability. In summary, all MS patients experience with age a modest induction of T-cell tolerance and an activation of the innate immunity, resulting in increased disability. Additionally, M- patients show clear decreases in CSF lymphocyte numbers, which could increase the risk of infections. Thus, age and immunological status are important for tailoring effective therapies in MS.


Assuntos
Imunossenescência/imunologia , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Bandas Oligoclonais/imunologia , Ativinas/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Linfócitos B/imunologia , Antígeno B7-H1/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Proteína 1 Semelhante à Quitinase-3/líquido cefalorraquidiano , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Linfócitos T/imunologia , Adulto Jovem
15.
PeerJ ; 8: e10220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240608

RESUMO

BACKGROUND: Gut microbiota has been related to multiple sclerosis (MS) etiopathogenesis. Short-chain fatty acids (SCFA) are compounds derived from microbial metabolism that have a role in gut-brain axis. OBJECTIVES: To analyse SCFA levels in plasma of MS patients and healthy donors (HD), and the possible link between these levels and both clinical data and immune cell populations. METHODS: Ninety-five MS patients and 54 HD were recruited. Patients were selected according to their score in the Expanded Disability Status Scale (EDSS) (49 EDSS ≤ 1.5, 46 EDSS ≥ 5.0). SCFA were studied in plasma samples by liquid chromatography-mass spectrometry. Peripheral blood mononuclear cells were studied by flow cytometry. Gender, age, treatments, EDSS and Multiple Sclerosis Severity Score (MSSS) were evaluated at the recruitment. RESULTS: Plasma acetate levels were higher in patients than in HD (p = 0.003). Patients with EDSS ≥ 5.0 had higher acetate levels than those with EDSS≤ 1.5 (p = 0.029), and HD (p = 2.97e-4). Acetate levels correlated with EDSS (r = 0.387; p = 1.08e-4) and MSSS (r = 0.265; p = 0.011). In untreated MS patients, acetate levels correlated inversely with CD4+ naïve T cells (r =  - 0.550, p = 0.001) and directly with CD8+ IL-17+ cells (r = 0.557; p = 0.001). CONCLUSIONS: Plasma acetate levels are higher in MS patients than in HD. In MS there exists a correlation between plasma acetate levels, EDSS and increased IL-17+ T cells. Future studies will elucidate the role of SCFA in the disease.

17.
J Neurol Sci ; 398: 4-8, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30658226

RESUMO

BACKGROUND: Lymphopenia is a major concern in MS patients treated with dimethyl-fumarate (DMF) as it increases the risk of progressive multifocal leukoencephalopathy. OBJECTIVE: To identify factors associated with lymphopenia in DMF-treated patients and explore changes in blood lymphocyte subsets associated with DMF-induced lymphopenia. METHODS: Prospective longitudinal study including 106 patients initiating DMF treatment followed for a median time of 24.67 months. Blood lymphocyte subsets were studied in 64 patients by flow cytometry at baseline and 6 months after. RESULTS: Mean absolute lymphocyte counts (ALCs) decreased by 29% during the first year of DMF-treatment. Patients developing lymphopenia showed a faster decline within the three first months. A reduction of ALCs higher than 38% at this time was associated to subsequent development of grade 2-3 lymphopenia (OR = 5.93, 95% CI: 1.9-18.6, p = 0.002). All patients showed a significant decrease in different T and B lymphocyte subsets upon DMF therapy. In addition, lymphopenic patients experienced a selective decrease in natural killer T (NKT) cell percentages (p = 0.01), and a high drop in NKT total counts (p < 0.0001). CONCLUSIONS: Patients who experience a drop in ALCs by >38% at three months of DMF-treatment are about 6-times more likely to develop significant lymphopenia. This decrease is clearly associated with a considerable loss of NKT cells.


Assuntos
Fumarato de Dimetilo/efeitos adversos , Imunossupressores/efeitos adversos , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Linfopenia/sangue , Linfopenia/induzido quimicamente , Adulto , Feminino , Humanos , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Estudos Longitudinais , Contagem de Linfócitos/métodos , Linfopenia/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
18.
Ann Clin Transl Neurol ; 6(2): 355-363, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30847367

RESUMO

Objectives: Teriflunomide, a disease-modifying treatment approved for multiple sclerosis (MS), inhibits reversibly dihydroorotate dehydrogenase, an enzyme involved in de novo pyrimidine biosynthesis and down-regulates proliferation of activated lymphocytes. We aimed to study the impact of this drug in the lymphocyte profiles of MS patients. Methods: Fifty-five patients with relapsing-remitting MS who initiated teriflunomide treatment were included in the study. We studied peripheral blood mononuclear cells obtained before and 6 months after treatment initiation and explored effector, memory, and regulatory cells by flow cytometry. Wilcoxon matched pair tests were used to assess differences between basal and 6 months after treatment results. P-values were corrected with Bonferroni test. Results: When explored T and B cell subsets, we observed a decrease in the percentages of terminally differentiated CD4+ T cells (P = 0.001) and plasmablasts (P < 0.0001) after 6 months of treatment. These results were confirmed with the total cell number. When studied immunomodulatory cells, we observed a clear increase of monocytes expressing programmed death-ligand 1 (PD-L1) (P = 0.005), which correlated negatively with all effector CD8+ T cell subsets. We also observed an increase in the percentage of CD8+ T cells (P = 0.028) and monocytes (P = 0.04) producing IL-10. Conclusions: Teriflunomide induces a specific reduction in effector T and B cells that have shown to play a role in MS course and an increase in immunomodulatory cells. Particularly, this drug induces the expression of PD-L1, a molecule involved in tolerance to autoantigens, which can contribute to inhibit the abnormal immune response taking place in MS.


Assuntos
Antígeno B7-H1/metabolismo , Crotonatos/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Esclerose Múltipla/tratamento farmacológico , Toluidinas/farmacologia , Adulto , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Antígeno B7-H1/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Feminino , Humanos , Hidroxibutiratos , Leucócitos Mononucleares/imunologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Nitrilas , Receptor de Morte Celular Programada 1/efeitos dos fármacos , Receptor de Morte Celular Programada 1/metabolismo , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia
19.
Rev Esp Salud Publica ; 79(2): 297-308, 2005.
Artigo em Espanhol | MEDLINE | ID: mdl-15913062

RESUMO

BACKGROUND: The health effects of air pollution have been analyzed in numerous studies over recent years, thus having made it possible to quantify the relationship between the two. This study is aimed at analyzing the theoretical benefits which would be achieved by meeting the air quality objectives set forth under EC Directive 1999/30/EC with regard to suspended particles. METHODS: The exposure measurement was taken for Black Smoke (Barcelona, Bilbao, Valencia) and suspended particles under 10 microm (PM10) (Bilbao, Madrid y Sevilla). The health indicators calculated were the mortality due to all causes and respiratory and cardiovascular causes, and emergency hospital admissions and mortality due to respiratory and cardiovascular causes. In the case of PM10 the impact has been calculated because its effects to short-term, within a period of up to 40 days following exposure, and to long-term. For Black Smoke the effects only has been calculated to short-term. RESULTS: The daily levels of PM10 from exceeding 50 microg/m3 in Bilbao, Madrid and Sevilla cause the earlier death of 1.4/100,000 individuals per year because its effects. The effect within a period of up to 40 days following exposure is of 2.8 deaths/100,000. The total number of deaths per year which may be later due to long-term exposure if the yearly average is lowered to 20 microg/m3 is 68/100,000. CONCLUSIONS: The health impact of the current air pollution levels is quantifiable and is not insignificant. APHEIS and the impact evaluations may be of aid in healthcare planning and environmental policies.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/análise , Cidades , Exposição Ambiental , Estudos Epidemiológicos , Humanos , Saúde Pública , Espanha
20.
Rev. colomb. cardiol ; 14(4): 246-252, jul.-ago. 2007. ilus, tab, graf
Artigo em Espanhol | LILACS | ID: lil-469045

RESUMO

El parche de pericardio bovino se ha utilizado como una alternativa para diferentes patologías quirúrgicas, entre las que se incluyen las malformaciones cardiacas congénitas. Pese a ello, hay pocos artículos que reportan la experiencia con este tipo parche. El objetivo de este estudio es evaluar la experiencia con el uso de pericardio bovino para la reconstrucción de cardiopatías en la Clínica Cardiovascular Santa María, desde 1994.Materiales y métodos: se sometieron 520 pacientes a un procedimiento quirúrgico correctivo o paliativo de alguna cardiopatía congénita en la que se utilizó el parche de pericardio bovino. De éstos, 163 tenían un seguimiento de por lo menos dos años. Se evaluó la localización del parche, el tipo de procedimientos, la supervivencia, las calcificaciones, los aneurismas y las fugas. Así mismo, se evaluó la clase funcional y se comparó la supervivencia de los pacientes de acuerdo con la localización y el tipo de parche.


Bovine pericardial patch has been utilized as an alternative for different surgical pathologies, including congenital heart malformations. Nevertheless, there are only few articles that report the experience with this kind of patch. The objective of this study is to evaluate the experience with the use of bovine pericardium for the reconstruction of cardiopathies in the Santa Maria Cardiovascular Clinic Medellín since 1994. Materials and methods: 520 patients underwent a corrective or palliative surgical procedure of a congenital heart disease in which the bovine pericardial patch was utilized. 163 of these patients had at least two years follow-up. The localization of the patch, as well as the kind of procedures, the survival, calcifications, aneurysms and leaks, were evaluated. The functional class was evaluated as well and the patients’ survival was compared according to the localization and the kind of patch. Results: 520 procedures were realized using the bovine pericardial patch. Prevalent malformations were septal defects (58%) followed by the tetralogy of Fallot (16%).The patch was also used in total or partial anomalous venous connections, and pulmonary atresia among others. 50.9% was localized in a systemic way and 49.7% in the pulmonary circulation. According to the localization, 50.3% were intracardiac and 49.7% extracardiac. Two leaks, two bleedings and three re-interventions were reported during the implantation. During the follow-up only three leaks were reported. Global survival was 95%. There were no significant differences in survival with intra or extracardiac patches or in those that supported pulmonary or systemic circulation. No calcifications were reported. 95% of patients were in functional class I or II, and the rest in III and IV.Conclusions: bovine pericardial patch is a useful tool for the correction of congenital heart diseases. Tissue characteristics offer advantages to the surgeon, such as the easy molding...


Assuntos
Anormalidades Cardiovasculares , Cirurgia Geral , Pericárdio , Transplante Heterólogo
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