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1.
Intern Emerg Med ; 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32172459

RESUMO

The majority of patients hospitalized for heart failure (HF) are admitted to internal medicine (IM) rather than to cardiology (CA) units, but to date few studies have analyzed the characteristics of these two populations. In this snapshot survey, we compared consecutive patients admitted for HF in six IM units vs. one non-intensive CA unit. During the 6-month survey period, 467 patients were enrolled (127 in CA, 27.2% vs. 340 in IM, 72.8%). IM patients were almost 10 years older (CA 75 ± 10, IM 82 ± 8 years; p < 0.001), more frequently female (CA 39%, IM 55%; p = 0.002) and living at home alone (CA 12%, IM 21%; p = 0.017). The leading cause of hospitalization in both groups was acute worsening of HF (CA 42%, IM 53%; p = 0.031), followed by atrial fibrillation (CA 29%, IM 12%; p < 0.001) and infections (CA 24%, IM 27%; p = 0.563). Ischemic (CA 43%, IM 30%; p = 0.008) and dilated cardiomyopathy patients (CA 21%, IM 12%; p < 0.001) were primarily admitted to CA unit, whereas those with hypertensive heart disease to IM (CA 3%, IM 39%; p < 0.001). Left ventricular ejection fraction (LVEF) was available in 96% of CA patients, but only in 60% of IM patients (p = 0.001). Among patients with LVEF measured, those with LVEF < 40% were predominantly admitted to CA (CA 60%, IM 14%; p < 0.001), whereas those with LVEF ≥ 50% were admitted to IM (CA 21%, IM 33%; p = 0.019); 26% of IM patients were discharged without a known LVEF. Medical treatments also significantly differed, according to patients' clinical and instrumental characteristics in each unit. This study demonstrates important differences between HF patients hospitalized in CA vs. IM, and the need for a greater interaction between these two medical specialties for a better care of HF patients.

2.
Hum Immunol ; 81(4): 162-167, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31848026

RESUMO

Human leucocyte antigen-G (HLA-G) is a nonclassical class I major histocompatibility complex (MHC) molecule characterized by complex immunoregulatory and tolerogenic functions. Membrane-bound HLA-G is expressed on the surface of different cell populations in both physiological and pathological conditions. Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by widespread tissue fibrosis, vascular lesions and immunological alterations. Systemic lupus erythematosus is the prototypic systemic autoimmune disease affecting virtually any organ system, such as skin, joints, central nervous system, or kidneys. In SSc and SLE patients, the membrane expression of HLA-G on monocytes (0.88 ± 1.54 and 0.43 ± 0.75, respectively), CD4+ (0.42 ± 0.78 and 0.63 ± 0.48, respectively), CD8+ (2.65 ± 3.47 and 1.29 ± 1.34, respectively) and CD4+ CD8+ double-positive cells (13.87 ± 15.97 and 3.79 ± 3.11, respectively) was significantly higher than in healthy controls (0.12 ± 0.07; 0.01 ± 0.01; 0.14 ± 0.20 and 0.32 ± 0.38, respectively) (p < 0.0001). Our results show that in SSc and SLE the membrane expression of HLA-G by different subpopulations of peripheral blood mononuclear cells (PBMC) is increased, suggesting a potential role of HLA-G molecules in the complex immunological pathogenesis of these two autoimmune disorders.

3.
Int J Mol Sci ; 20(23)2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31766607

RESUMO

Several allergic and immunologic diseases including asthma, food allergy (FA), chronic spontaneous urticaria (CSU), atopic dermatitis (AD), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), and Behçet's disease (BD) are characterized by the involvement of Th2 immunity. Several mediators lead to immunoglobulin (Ig)E production, thus including key cytokines such as interleukin (IL)-4, IL-5, and IL-13. Among them, IL-31 and IL-33 have been recently studied as novel biomarkers and future therapeutic targets for allergic and immunological disorders. IL-31 is a proinflammatory cytokine-it regulates cell proliferation and is involved in tissue remodeling. IL-33, acting through its receptor suppression of tumorigenity (ST2L), is an alarmin cytokine from the IL-1 family, whose expression is mediated by tissue damage. The latter has a pleiotropic effect, as it may modulate specific and innate immune cells functions. To date, several researchers have investigated the involvement of IL-31 and IL-33 in several allergic and immune-mediated diseases. Further studies are needed to understand the future applications of these molecules as novel therapeutic agents. This paper aims to give the readers a complete and updated review of IL-31 and IL-33 involvement among the most common autoimmune and allergic disorders.

4.
Int J Mol Sci ; 20(16)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412612

RESUMO

INTRODUCTION: MiRNAs have been shown to play a crucial role among lung cancer, pulmonary fibrosis, tuberculosis (TBC) infection, and bronchial hypersensitivity, thus including chronic obstructive pulmonary disease (COPD) and asthma. The oncogenic effect of several miRNAs has been recently ruled out. In order to act on miRNAs turnover, antagomiRs have been developed. MATERIALS AND METHODS: The systematic review was conducted under the PRISMA guidelines (registration number is: CRD42019134173). The PubMed database was searched between 1 January 2000 and 30 April 2019 under the following search strategy: (((antagomiR) OR (mirna antagonists) OR (mirna antagonist)) AND ((lung[MeSH Terms]) OR ("lung diseases"[MeSH Terms]))). We included original articles, published in English, whereas exclusion criteria included reviews, meta-analyses, single case reports, and studies published in a language other than English. RESULTS AND CONCLUSIONS: A total of 68 articles matching the inclusion criteria were retrieved. Overall, the use of antagomiR was seen to be efficient in downregulating the specific miRNA they are conceived for. The usefulness of antagomiRs was demonstrated in humans, animal models, and cell lines. To our best knowledge, this is the first article to encompass evidence regarding miRNAs and their respective antagomiRs in the lung, in order to provide readers a comprehensive review upon major lung disorders.


Assuntos
Antagomirs/genética , Regulação da Expressão Gênica , Pneumopatias/genética , Interferência de RNA , Animais , Antagomirs/administração & dosagem , Biomarcadores , Linhagem Celular , Células Cultivadas , Humanos , Pneumopatias/diagnóstico , Pneumopatias/metabolismo , Pneumopatias/terapia , MicroRNAs/genética , Modelos Animais
5.
Autoimmun Rev ; 18(9): 102350, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31323357

RESUMO

Vitamin D plays a key role in in calcium homeostasis and, thus, provides an important support in bone growth by aiding in the mineralization of the collagen matrix. However, vitamin D performs various immunomodulatory, anti-inflammatory, antioxidant and anti-fibrotic actions. Autoimmune diseases result from an aberrant activation of the immune system, whereby the immune response is directed against harmless self-antigens. Does vitamin D play a role in the pathophysiology of autoimmune diseases? And, if so, what is its role? In the last decade, researchers' interest in vitamin D and its correlations with autoimmune diseases has considerably increased. We conducted a literature review, covering the period January 1, 2009 through March 30, 2019, in PubMed. We analyzed more than 130 studies in order to find a correlation between vitamin D levels and its effect upon several autoimmune diseases. The analysis demonstrated an inverse association between vitamin D and the development of several autoimmune diseases, such as SLE, thyrotoxicosis, type 1 DM, MS, iridocyclitis, Crohn's disease, ulcerative colitis, psoriasis vulgaris, seropositive RA, polymyalgia rheumatica. International multicenter study could allow us to confirm the data already present in the literature in the single clinical studies and to evaluate when to effectively supplement vitamin D in patients who do not take corticosteroids.


Assuntos
Doenças Autoimunes/etiologia , Doenças Autoimunes/terapia , Vitamina D/fisiologia , Doenças Autoimunes/sangue , Doenças Autoimunes/epidemiologia , Comorbidade , Suplementos Nutricionais , Prática Clínica Baseada em Evidências/tendências , Humanos , Sistema Imunitário/efeitos dos fármacos , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/imunologia
8.
Clin Exp Med ; 19(3): 357-366, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30989453

RESUMO

Vasculopathy is a crucial feature of systemic sclerosis (SSc), and Raynaud's phenomenon (RP) and digital ulcers (DU) have a deep impact on the quality of patients' life. The management of vascular disease can be challenging for the clinician because of the suboptimal tolerability of the treatments and lack of consensus on the best therapeutic approach. Intravenous iloprost, a synthetic analogue of prostacyclin, is broadly used for the treatment of RP and ischemic ulcers secondary to SSc. However, no standardized protocol on iloprost use is currently available and, consequently, the management of this treatment is largely based on the experience of each single center. The PROSIT project is an observational, multicenter study aiming to investigate the current treatments for SSc vasculopathy, the use of prostanoids, with special regard to iloprost, and the perception of the treatment from a patient's perspective. The study was conducted on a cohort of 346 patients from eight Italian centers and included a structured survey addressed to physicians, data collected from patient's medical records and two patient-administered questionnaires assessing the level of satisfaction, tolerability and perception of the efficacy of Iloprost. PROSIT data confirmed that in the contest of SSc iloprost represents the first-line choice for the management of severe RP and DU. Moreover, it is a well-tolerated treatment as reported by patients' experience. Although a standard protocol for the treatment of SSc-related vasculopathy is lacking, PROSIT study identified different therapeutic approaches largely supported by tertiary Italian centers. Further studies are needed in order to optimize the best treatment for SSc vascular diseases, in particular to improve the best iloprost schedule management.


Assuntos
Gerenciamento Clínico , Iloprosta/uso terapêutico , Doenças Vasculares Periféricas/tratamento farmacológico , Doenças Vasculares Periféricas/patologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Vasodilatadores/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária , Resultado do Tratamento , Adulto Jovem
10.
Expert Opin Drug Saf ; 18(3): 219-229, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30704314

RESUMO

INTRODUCTION: TNF-α inhibitors can be administered either as monotherapy or in combination with other anti-inflammatory drugs or DMARDs in the treatment of chronic immune-mediated diseases. AREAS COVERED: Patients receiving TNF-α inhibitors are at high risk of infections. An update is made on the risk of infection in patients receiving TNF-α inhibitors and the strategies for mitigating against the development of these serious adverse events. EXPERT OPINION: Infliximab than etanercept appears to be responsible for the increased risk of infections. Re-activation of latent tuberculosis infection and the overall risk of opportunistic infections should be considered before beginning a course of TNF-α inhibitors. A careful medical history, Mantoux test/quantiferon-TB Gold In-tube Test and chest-X-ray should always be performed before starting TNF-α inhibitors. Particular attention should be paid to risk factors for Pneumocystis jirovecii infection. Hepatitis B and C virological follow-up should be considered during TNF-α inhibitors treatment. Finally, appropriate vaccinations for influenza, S. pneumoniae, and HBV should be administered to decrease the risk of infection, and patients who are at high risk of herpes zoster reactivation would benefit from a second vaccination in adulthood.


Assuntos
Doenças do Sistema Imunitário/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Etanercepte/administração & dosagem , Etanercepte/efeitos adversos , Humanos , Doenças do Sistema Imunitário/imunologia , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/etiologia , Fatores de Risco
11.
Virchows Arch ; 473(4): 425-433, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29845360

RESUMO

To analyze expression of human leukocyte antigen-G (HLA-G) in gastric adenocarcinoma and correlate its expression with histological and clinical variables. A continuous series of 94 unselected patients with gastric adenocarcinoma (stage I to III) were selected. All histological and clinical variables were collected including the intensity of intra- and peri-tumor lymphocytic infiltration. HLA-G expression was investigated using immunohistochemistry. All histological samples analyzed for HLA-G expression were taken from the primary gastric lesion and included non-neoplastic mucosa. Evaluation of HLA-G expression was performed on the transition zone between tumor and non-neoplastic mucosa, and the invasive front of the tumor and assessment was performed as follows: percentage of positive (strong expression vs weak) cells. A variable amount of HLA-G-positive tumor cells was found in 24 out of 94 cases (25.5%). No significant correlation was found between HLA-G expression and other clinicopathological variables (sex, age, stage, grade, histotype). The overall median survival was worse in patients with HLA-G-positive adenocarcinoma (24.3 months, CI95% 7.7-41.0) compared to those with HLA-G-negative tumors (66.3 months, CI95% 53.0-79.7; p < 0.0001). Two- and 5-year survival rates of HLA-G-negative patients were 88 and 44%, respectively, while were 42 and 11% in those HLA-G-positive. This trend was observed in all stages but was more marked in stage III. HLA-G expression is associated with poor survival in stage III gastric cancer patients and represents a possible immunoescape mechanism of cancer cells.


Assuntos
Adenocarcinoma/imunologia , Biomarcadores Tumorais/análise , Antígenos HLA-G/análise , Neoplasias Gástricas/imunologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Fatores de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Fatores de Tempo , Resultado do Tratamento , Evasão Tumoral
12.
Mod Rheumatol ; 28(3): 417-431, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28837372

RESUMO

TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases such as rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis (AS), psoriasis (Ps) and/or psoriatic arthritis (PsA) and may be administered off-label to treat disseminated granuloma annulare, systemic lupus erythematosus and systemic sclerosis. There are several TNF-α inhibitors available for clinical use including infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. In this article, we discuss the efficacy and safety of etanercept in the treatment of spondyloarthritis and juvenile idiopathic arthritis (JIA). Etanercept is effective in the treatment of PsA, AS, JIA and uveitis. Independent predictors of achieving a sustained clinical improvement or MDA in children with JIA include shorter disease duration, no concurrent oral corticosteroid use, history of chronic anterior uveitis and age <9 years. IBD incidence was lower in patients receiving etanercept plus MTX. Intra-articular administration of etanercept seems to favor a prompt target joint improvement without serious adverse events. Etanercept improve endothelial function reducing the risk of acute cardiovascular and/or cerebrovascular events. The most commonly reported adverse events were nasopharyngitis, epidermal and dermal conditions, upper respiratory tract infection, cough, headache and fatigue.


Assuntos
Antirreumáticos/efeitos adversos , Artrite Juvenil/tratamento farmacológico , Etanercepte/efeitos adversos , Espondilite Anquilosante/tratamento farmacológico , Adolescente , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Criança , Etanercepte/administração & dosagem , Etanercepte/uso terapêutico , Humanos
13.
Semin Arthritis Rheum ; 47(4): 569-574, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28870413

RESUMO

INTRODUCTION: Distal esophageal baseline impedance (BI) levels reflect the esophageal mucosal integrity in reflux disease. Systemic sclerosis (SSc) could potentially affect the integrity of esophageal mucosa and consequently impair distal and proximal BI levels, but data in this regard are lacking. AIM AND METHODS: We aimed to prospectively investigate and compare BI levels among non-erosive reflux disease (NERD), SSc patients, and healthy controls (HCs). Consecutive patients with reflux symptoms and well-defined diagnosis of SSc underwent upper endoscopy and, in case of no lesions encountered, manometry and impedance-pH testing off-therapy. In addition to traditional impedance-pH parameters, BI values at 3, 5, 7, and 17cm above the lower esophageal sphincter were calculated. RESULTS: Fifty-two patients with NERD, 50 with SSc, and 50 HCs were enrolled. Nineteen (38%) SSc patients and 22 (42%) NERD patients had abnormal acid exposure. In patients with SSc, median BI values were significantly lower than in NERD patients and HCs (p < 0.0001) at 3, 5, and 7cm; there was no difference between HCs and NERD patients at 17cm in the proximal esophagus, whereas a significant difference was observed at 17cm between SSc and NERD as well as HCs (p < 0.01). CONCLUSION: Distal and proximal BI values in SSc patients were lower than in NERD and HCs, thus we speculated that these findings may be related to the deposition of collagen in the connective tissue. Measurement of BI may be used as an indirect, but simple and accurate marker of esophageal involvement in patients with SSc.


Assuntos
Esôfago/fisiopatologia , Refluxo Gastroesofágico/diagnóstico , Escleroderma Sistêmico/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Impedância Elétrica , Feminino , Refluxo Gastroesofágico/etiologia , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Adulto Jovem
14.
Expert Opin Drug Saf ; 16(10): 1173-1179, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28750567

RESUMO

INTRODUCTION: TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases. Etanercept is a decoy receptor" for TNF-α and it is composed of two p75 TNF-α receptors fused to human IgG1. Areas covered: We discuss the potential role of pharmacogenetics in predicting the response to etanercept in patients with Ps and PsA. Expert opinion: Pharmacogenetics represents the new frontier for the discovery of potential genetic markers of biological response to TNF-α inhibitors. Clinical studies showed that TNF-α -308 G/G, +489 GG and the +489 GA, TNF-α -857C (rs1799724), TNFRSF1B 676T (rs1061622), TNFAIP3 G SNP (rs610604), FcγRIIIA-V158F, HLA-C*06, IL-17 A (rs2275913 and rs10484879), IL-17F (rs763780) and IL17RA (rs4819554) SNPs favor the response to etanercept. However, most of these studies are often small and not sufficiently powered to detect an effect and markers tend to be more prognostic than predictive of therapeutic response. Furthermore, studies often examines only the effects of a single SNP, while it would be more useful to analyze more haplotypes in contemporary in the same patients. Appropriately designed clinical trials are needed before a pharmacogenetic approach may be applicable in daily clinical therapeutic practice.


Assuntos
Artrite Psoriásica/tratamento farmacológico , Etanercepte/uso terapêutico , Psoríase/tratamento farmacológico , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artrite Psoriásica/genética , Etanercepte/farmacologia , Humanos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Farmacogenética , Polimorfismo de Nucleotídeo Único , Psoríase/genética , Projetos de Pesquisa , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética
15.
Clin Exp Med ; 17(3): 257-267, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27334977

RESUMO

Antiphospholipid antibody syndrome (APS) is an autoimmune acquired thrombophilia characterized by recurrent thrombosis and pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). APS can be primary, if it occurs in the absence of any underlying disease, or secondary, if it is associated with another autoimmune disorder, most commonly systemic lupus erythematosus. The exact pathogenetic mechanism of APS is unknown, but different, not mutually exclusive, models have been proposed to explain how anti-PL autoantibodies might lead to thrombosis and pregnancy morbidity. Diagnosis of APS requires that a patient has both a clinical manifestation (arterial or venous thrombosis and/or pregnancy morbidity) and persistently positive aPL, but the clinical spectrum of the disease encompasses additional manifestations which may affect every organ and cannot be explained exclusively by a prothrombotic state. Treatment for aPL-positive patients is based on the patient's clinical status, presence of an underlying autoimmune disease, and history of thrombotic events. In case of aPL positivity without previous thrombotic events, the treatment is mainly focused on reduction of additional vascular risk factors, while treatment of patients with definite APS is based on long-term anticoagulation. Pregnancy complications are usually managed with low-dose aspirin in association with low molecular weight heparin. Refractory forms of APS could benefit from adding hydroxychloroquine and/or intravenous immunoglobulin to anticoagulation therapy. Promising novel treatments include anti-B cell monoclonal antibodies, new-generation anticoagulants, and complement cascade inhibitors. The objective of this review paper is to summarize the recent literature on APS from pathogenesis to current therapeutic options.


Assuntos
Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/fisiopatologia , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/fisiopatologia , Síndrome Antifosfolipídica/epidemiologia , Feminino , Humanos , Masculino , Gravidez , Complicações na Gravidez/epidemiologia , Fatores Sexuais
16.
Clin Exp Med ; 17(1): 93-100, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26567007

RESUMO

The serum levels of soluble HLA class I antigens (sHLA-A, -B, -C and sHLA-G) were determined in 40 HCV genotype 1-infected patients before (T 0), after 3, 6, and 12 months (T 3, T 6, and T 12) of pegylated-IFN-α plus ribavirin therapy and 6 months (T 18) after the end of treatment. Twenty patients were sustained virological responders (SVR), and 20 were non-responders (NR). sHLA-A, -B, -C levels at T 0 were significantly higher in both SVR (mean 10.48 µg/ml) and NR (mean 11.87 µg/ml) patients as compared to healthy controls (mean 0.34 µg/ml, p < 0.0001) and HIV-infected subjects (mean 1.22 µg/ml, p < 0.0001). sHLA-G levels at T 0 were significantly higher in SVR (mean 24.78 ng/ml) and NR (mean 24.93 ng/ml) patients as compared to healthy controls (mean 10.34 ng/ml, p = 0.015 and p = 0.014, respectively) but were lower as compared to HIV-infected subjects (mean 48.00 ng/ml, p < 0.0001). The levels of sHLA-A, -B, -C and sHLA-G significantly decreased in SVR from T 0 to T 18 (mean 1.64 and 1.43 ng/ml, respectively, p < 0.0001) and correlated with HCV-RNA, AST, ALT, γGT, and ALP levels. The determination of soluble HLA class I levels could be proposed as a surrogate marker to discriminate SVR and NR HCV-infected patients during PEG-IFN-α plus ribavirin therapy.


Assuntos
Antivirais/uso terapêutico , Biomarcadores Farmacológicos/sangue , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , RNA Viral/antagonistas & inibidores , Ribavirina/uso terapêutico , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Coinfecção , Quimioterapia Combinada , Feminino , Expressão Gênica , HIV/efeitos dos fármacos , HIV/fisiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/virologia , Antígenos HLA-A/sangue , Antígenos HLA-A/genética , Antígenos HLA-A/imunologia , Antígenos HLA-B/sangue , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Antígenos HLA-C/sangue , Antígenos HLA-C/genética , Antígenos HLA-C/imunologia , Antígenos HLA-G/sangue , Antígenos HLA-G/genética , Antígenos HLA-G/imunologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/fisiologia , Hepatite C Crônica/genética , Hepatite C Crônica/imunologia , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , RNA Viral/biossíntese , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento
17.
J Int Med Res ; 44(1 suppl): 85-89, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27683147

RESUMO

OBJECTIVE: To investigate the effects of long-term treatment with bosentan on pulmonary arterial hypertension (PAH) in patients with systemic sclerosis. METHODS: Patients with systemic sclerosis were followed between 2003 and 2014; those who developed digital ulcers were treated with standard regimens of bosentan. Patients were assessed at baseline and every 12 months using transthoracic Doppler echocardiography, 6-min walking distance test, Borg dyspnoea index and monitoring of plasma levels of 76-amino-acid N-terminal probrain natriuretic peptide. Patients who developed PAH underwent right heart catheterization to confirm the diagnosis. RESULTS: Sixty-nine patients with systemic sclerosis were enrolled in the study. Of these, 25 developed digital ulcers and received treatment with bosentan; the remaining 44 comprised the control group. None of the patients treated with bosentan developed PAH during the follow-up period. Furthermore, in these patients the mean ± SD systolic pulmonary arterial pressure significantly decreased from 33.64 ± 2.91 mmHg at baseline to 26.20 ± 1.78 mmHg at the end of the follow-up period. In contrast, in the control group, seven patients developed PAH during the follow-up period, with the mean ± SD systolic pulmonary arterial pressure significantly increasing from 33.57 ± 2.75 mmHg at baseline to 39.41 ± 4.11 mmHg at the end of the follow-up period. CONCLUSION: Long-term treatment with bosentan reduces the risk of developing PAH in patients with systemic sclerosis.

18.
Hum Immunol ; 77(12): 1172-1178, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27527921

RESUMO

BACKGROUND: It has been reported that soluble HLA-G serum levels are increased in patients with pollen-induced allergic rhinitis and decrease after immunotherapy. However, no functional study has been conducted so far. The aim of this study was to evaluate the membrane expression and secretion of HLA-G molecules in peripheral blood mononuclear cells from allergic rhinitis patients after in vitro incubation with the causal allergen. METHODS AND RESULTS: Twenty-two allergic rhinitis patients and ten healthy subjects were enrolled. Membrane HLA-G expression was determined by flow cytometry and soluble HLA-G in culture supernatant was determined by immunoenzymatic assay. HLA-G expression was detected in CD4+ (T-helper-2) cells and monocytes after in vitro stimulation with the causal allergen but not with non specific stimuli and non causal allergens. Accordingly, the release of soluble HLA-G in culture supernatant occurred only after the stimulation with the causal allergen. Collectively, these results were confirmed by Western blot analysis. CONCLUSIONS: The present study provides the first in vitro evidence that in allergic patients HLA-G expression and secretion is specifically induced by the causal allergen. These data may add new insights into the pathogenetic mechanisms underlying allergic inflammation and allergen specific immunotherapy.


Assuntos
Leucócitos Mononucleares/imunologia , Rinite Alérgica/imunologia , Células Th2/imunologia , Adulto , Alérgenos/imunologia , Células Cultivadas , Grupos Étnicos , Feminino , Antígenos HLA-G/genética , Humanos , Índia , Masculino
19.
J Immunol Res ; 2016: 6865758, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27413762

RESUMO

Allergic diseases are sustained by a T-helper 2 polarization leading to interleukin-4 secretion, IgE-dependent inflammation, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, play a central role in modulation of immune responses. Elevated levels of soluble HLA-G (sHLA-G) molecules are detected in serum of patients with allergic rhinitis to seasonal and perennial allergens and correlate with allergen-specific IgE levels, clinical severity, drug consumption, and response to allergen-specific immunotherapy. sHLA-G molecules are also found in airway epithelium of patients with allergic asthma and high levels of sHLA-G molecules are detectable in plasma and bronchoalveolar lavage of asthmatic patients correlating with allergen-specific IgE levels. Finally, HLA-G molecules are expressed by T cells, monocytes-macrophages, and Langerhans cells infiltrating the dermis of atopic dermatitis patients. Collectively, although at present it is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation.


Assuntos
Alérgenos/imunologia , Antígenos HLA-G/genética , Antígenos HLA-G/imunologia , Hipersensibilidade/genética , Hipersensibilidade/imunologia , Imunomodulação , Alelos , Asma/genética , Asma/imunologia , Asma/metabolismo , Asma/terapia , Dermatite Atópica/genética , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Dermatite Atópica/terapia , Feminino , Antígenos HLA-G/química , Humanos , Hipersensibilidade/metabolismo , Hipersensibilidade/terapia , Gravidez , Isoformas de Proteínas , Rinite Alérgica/genética , Rinite Alérgica/imunologia , Rinite Alérgica/metabolismo , Rinite Alérgica/terapia
20.
Hum Vaccin Immunother ; 12(3): 632-43, 2016 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-26750996

RESUMO

Systemic Lupus Erythematosus (SLE) is characterized by abnormal autoantibody production and clearance. Infections are among the most important causes of morbidity and mortality in SLE patients; they have an increased frequency of severe bacterial and viral infections possibly due to inherited genetic and immunologic defects and to immunosuppressive therapies. In addition, infectious agents can switch on lupus disease expression and activity. Among the strategies to reduce the risk of infection, vaccination can be considered the most reliable option. Most vaccines are effective and safe in SLE patients, although in certain cases immunogenicity may be sub-optimal and vaccination can trigger a flare. Although these issues are currently unresolved, the risk benefit balance is in favor for vaccination to reduce the risk of infection in SLE patients. In the present review we discuss the preventive strategies currently recommended to reduce bacterial and viral infections in SLE.


Assuntos
Infecções Bacterianas/epidemiologia , Infecções Bacterianas/prevenção & controle , Lúpus Eritematoso Sistêmico/complicações , Vacinas/administração & dosagem , Vacinas/imunologia , Viroses/epidemiologia , Viroses/prevenção & controle , Humanos
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