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1.
J Endocrinol Invest ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683498

RESUMO

PURPOSE: To evaluate the variables influencing the therapeutic choice toward oral versus subcutaneous semaglutide in a cohort of diabetic subjects. METHODS: We retrospectively collected data of 292 patients followed at the Diabetes Unit of the University Hospital of Siena and the Hospital of Grosseto, who were prescribed oral (n = 115) or subcutaneous (n = 177) semaglutide between October 2021 and October 2022. RESULTS: Oral semaglutide was preferentially prescribed in older subjects with longer disease duration in replacement of other antidiabetic drugs, while subcutaneous semaglutide was preferentially prescribed in add-on to metformin in subjects with higher body weight and BMI. After 6 months, both formulations significantly improved glycemic control and body weight, however injectable semaglutide showed a greater efficacy on A1c levels, weight loss, BMI and waist circumference reduction. No differences were found in terms of adverse events. CONCLUSION: In our experience, injectable semaglutide is preferred in patients with excess weight and shorter disease duration, while the oral formulation was used later and especially after therapeutic failure of previous therapies. Follow-up data indicate similar tolerability and efficacy of both formulations, despite subcutaneous semaglutide demonstrated greater efficacy.

2.
Ann Oncol ; 31(2): 266-273, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31959343

RESUMO

BACKGROUND: The mouse strains usually used to generate patient-derived xenografts (PDXs) are immunocompromised, rendering them unsuitable for immunotherapy studies. Here we assessed the value of immune-PDX mouse models for predicting responses to anti-PD-1 checkpoint inhibitor therapy in patients. PATIENTS AND METHODS: Melanoma biopsies contained in a retrospective biobank were transplanted into NOG mice or NOG mice expressing interleukin 2 (hIL2-NOG mice). Tumor growth was monitored, and comparisons were made with clinical data, sequencing data, and current in silico predictive tools. RESULTS: Biopsies grew readily in NOG mice but growth was heterogeneous in hIL2-NOG mice. IL2 appears to activate T-cell immunity in the biopsies to block tumor growth. Biopsy growth in hIL2-NOG mice was negatively associated with survival in patients previously treated with PD-1 checkpoint blockade. In two cases, the prospective clinical decisions of anti-PD-1 therapy or targeted BRAF/MEK inhibitors were supported by the observed responses in mice. CONCLUSIONS: Immune-PDX models represent a promising addition to future biomarker discovery studies and for clinical decision making in patients receiving immunotherapy.


Assuntos
Melanoma , Animais , Tomada de Decisão Clínica , Xenoenxertos , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Estudos Prospectivos , Estudos Retrospectivos , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Curr Heart Fail Rep ; 17(2): 28-33, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32130642

RESUMO

PURPOSE OF REVIEW: This review attempts to summarize the role of standard and advanced echocardiographic techniques together with CMR in the evaluation of the RV in HF, providing an outlook on the recent evidence. RECENT FINDINGS: In the last decade, there has been growing interest in the study of the RV, and it is now widely established that RV function is a strong predictor of mortality, in several cardiovascular diseases, in particular in the setting of heart failure (HF). The evaluation of RV function might be particularly challenging, which justifies the necessity of multi-modality imaging. The echocardiographic assessment remains the mainstay technique even though it might be complex, due to RV crescent shape and its position in the chest, requiring both qualitative and quantitative parameters. Cardiac magnetic resonance (CMR) represents a complementary exam which is particularly useful when precise structural and functional assessment are needed, considering the most recently developed sequences. Despite the technological improvement attested over the last years, there is still no universally accepted parameter that univocally defines RV function, hence the necessity to evaluate several parameters, combining different imaging techniques.


Assuntos
Ecocardiografia/métodos , Insuficiência Cardíaca/diagnóstico , Ventrículos do Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Volume Sistólico/fisiologia , Função Ventricular Direita/fisiologia , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Humanos
4.
Acta Psychiatr Scand ; 133(2): 122-132, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26139469

RESUMO

OBJECTIVE: To investigate the association between peripheral biomarkers and child psychopathology in a large community sample. METHOD: A total of 625 aged 6- to 13-year old subjects were recruited from a community school-based study. Psychopathology was assessed using the Child Behaviour Checklist (CBCL). Psychiatric diagnosis was evaluated using the Development and Well-Being Assessment. The following biomarkers were examined in peripheral blood: brain-derived neurotrophic factor, cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-g, and TNF-α), chemokines (eotaxin/CCL11, IP-10, MCP-1), cytokine receptors (sTNFR1 and sTNFR2), and the oxidative stress marker TBARS. RESULTS: We found significant associations between sTNFR2, eotaxin/CCL11 and CBCL total score, as well as with specific dimensions of psychopathology. There were different patterns of association between these biomarkers and psychological and behavioural symptoms in children with and without a mental disorder. TBARS, IL-6 and MCP-1 were more specific to some clusters of symptoms in children with a psychiatric diagnosis. CONCLUSION: Our data support the potential use of biomarkers, especially those involved in immune-inflammatory pathways, in investigating neurodevelopmental psychopathology. Their association with different dimensions of symptoms might be of useful when analyzing illness severity and clusters of symptoms within specific disorders.

6.
Eur J Vasc Endovasc Surg ; 48(5): 514-20, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25245165

RESUMO

OBJECTIVES: The eversion carotid endartectomy (E-CEA), mainly performed by means of Vanmaele technique, has been associated with loss of the baroreceptor reflex and postoperative hypertension. The purpose of this paper is to determine whether the eversion endarterectomy performed by means of Chevalier technique (C-CEA) modifies the function and the efficiency of baroreceptors, leading to lower postoperative hemodynamic change. METHODS: A retrospective review of 380 patients who underwent carotid endarterectomy (120 Chevalier-CEA; 260 Standard-CEA) from December 2002 to November 2012 has been performed. The changes of blood pressure baseline during the postoperative course in C-CEA and S-CEA group were analysed and compared. Postoperative hypertension was defined as an elevation of systolic pressure >180 mm Hg or >40% rise above baseline. RESULTS: The patients with Chevalier eversion technique did not develop a significantly higher blood pressure in the postoperative course compared to those operated with the standard technique. In the recovery room, the mean systolic blood pressure was 134 ± 21.9 mm Hg in C-CEA group versus 132 ± 24.6 mm Hg in S-CEA group. In the first postoperative day it was 132 ± 17.2 mm Hg in C-CEA versus 133 ± 17.4 mm Hg in S-CEA group. During the first six hours in the recovery room, the need for intravenous antihypertensive drugs was similar in the two groups. Fourteen patients in C-CEA group (11%) and thirty patients (11.5%) in the S-CEA group required vasodilators, without any significant difference (p = 1). The dosage of current preoperative antihypertensive therapy was increased in six patients (4.9%) of C-CEA group and in twelve patients (4.9%) of S-CEA group, without significant difference (p = 1). CONCLUSIONS: C-CEA has the same rate of postoperative hypertension of standard-CEA, which is probably related to the sparing of baroreceptor apparatus, compared to standard E-CEA. The Chevalier procedure could represent an E-CEA technique with its inherent advantages, without penalties related to postoperative hypertension, commonly observed after E-CEA.


Assuntos
Barorreflexo/fisiologia , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/efeitos adversos , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Feminino , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/métodos
7.
Mycoses ; 57(7): 419-28, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24621407

RESUMO

The genus Spiromastix consists of several fungal species that have been isolated from soil and animal dung in various parts of the world. However, these species are considered to be of low pathogenic potential, as no cases of infections caused by these fungi have been reported. Here, we describe the clinical course of discospondylitis in a dog from which a fungus was cultured from a biopsy and identified as a Spiromastix species by morphologic characteristics and sequencing. Phylogenetic analysis determined this to be a new species, Spiromastix asexualis, which is described, and a new order, Spiromastixales, is proposed.


Assuntos
Ascomicetos/classificação , Ascomicetos/isolamento & purificação , Doenças do Cão/microbiologia , Micoses/veterinária , Animais , Ascomicetos/genética , DNA Fúngico/genética , Cães , Feminino , Dados de Sequência Molecular , Micoses/microbiologia , Filogenia
8.
Clin Exp Immunol ; 173(2): 242-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23607333

RESUMO

Genetic polymorphism studies of cytokines may provide an insight into the understanding of acute kidney injury (AKI) and death in intensive care unit (ICU) patients. The aim of this study was to investigate whether the genetic polymorphisms of -308 G < A tumour necrosis factor (TNF)-α, -174 G > C interleukin (IL)-6 and -1082 G > A IL-10 may predispose ICU patients to the development of AKI and/or death. In a prospective nested case-control study, 303 ICU patients and 244 healthy individuals were evaluated. The study group included ICU patients who developed AKI (n = 139) and 164 ICU patients without AKI. The GG genotype of TNF-α (low producer phenotype) was significantly lower in the with AKI than without AKI groups and healthy individuals (55 versus 62 versus 73%, respectively; P = 0·01). When genotypes were stratified into four categories of TNF-α/IL-10 combinations, it was observed that low TNF-α plus low IL-10 producer phenotypes were more prevalent in patients with AKI, renal replacement therapy and death (P < 0·05). In logistic regression analysis, low TNF-α producer plus low IL-10 producer phenotypes remained as independent risk factors for AKI and/or death [odds ratio (OR) = 2·37, 95% confidence interval (CI): 1·16-4·84; P = 0·02] and for renal replacement therapy (RRT) and/or death (OR = 3·82, 95% CI: 1·19-12·23; P = 0·02). In this study, the combination of low TNF-α plus low IL-10 producer phenotypes was an independent risk factor to AKI and/or death and RRT and/or death in critically ill patients. Our results should be validated in a larger prospective study with long-term follow-up to emphasize the combination of these genotypes as potential risk factors to AKI in critically ill patients.


Assuntos
Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/imunologia , Interleucina-10/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Injúria Renal Aguda/genética , Injúria Renal Aguda/mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Humanos , Unidades de Terapia Intensiva , Interleucina-10/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Fator de Necrose Tumoral alfa/genética
9.
Eur Rev Med Pharmacol Sci ; 16(11): 1596-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23111977

RESUMO

ARFI (Acoustic Radiation Force Impulse) is a novel method based on the use of shear acoustic waves remotely induced by the radiation force of a focused ultrasonic beam. Recently, ARFI has been investigated as a non-invasive method for the assessment of liver fibrosis. The reproducibility of ARFI technology was proved in determining liver fibrosis: in detail, for cirrhosis Fibroscan had its best cut-off at >/= 11 kPa (AUROC of 0.80) whereas ARFI >/= 2.0 m/s (AUROC of 0.89). By pair-wise comparison of AUROC, ARFI was significantly more accurate than TE for a diagnosis of significant and severe fibrosis. Due to the low amount of collagen deposition within hepatocellular carcinoma (HCC) nodules in a context of "hard" cirrhotic parenchyma, ARFI propose itself also as a novel, specific method for an early identification of primitive neoplastic nodules during the follow up of cirrhotic patients. The diagnostic accuracy can be demonstrated either versus the surrounding liver tissue or versus dysplastic or metastatic nodules. Further studies are required to confirm ARFI as a useful tool for HCC follow-up.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Técnicas de Imagem por Elasticidade , Neoplasias Hepáticas/diagnóstico , Humanos
10.
Int J Cardiovasc Imaging ; 38(3): 561-570, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34661853

RESUMO

Right ventricular failure (RVF) after left ventricular assist device (LVAD) implant is associated with increasing morbidity and mortality. The aim of this study was to identify the best predictors of RVF post LVAD-implant among biochemical, haemodynamic and echocardiographic parameters. From 2009 to 2019, 38 patients who underwent LVAD implantation at our centre were prospectively enrolled. Preoperative clinical, laboratory, echocardiographic and haemodynamic parameters were reported. Overall, eight patients (21%) developed RVF over time, which revealed to be strongly related to overall mortality. Pulmonary artery pulsatility index (PAPi) resulted to be the most significant right heart catheterization index in discriminating RVF vs no RVF patients [(1.32 ± 0.26 vs. 3.95 ± 3.39 respectively) p = 0.0036]. Regarding transthoracic echocardiography, RVF was associated with reduced free wall right ventricular longitudinal strain (fw-RVLS) (- 7.9 ± 1.29 vs. - 16.14 ± 5.83) (p < 0.009), which was superior to other echocardiographic determinants of RVF. Among laboratory values, N-terminal pro-brain natriuretic peptide (NT-proBNP) was strongly increased in RVF patients [(10,496.13 pg/ml ± 5272.96 pg/ml vs. 2865, 5 pg/ml ± 2595.61 pg/ml) p = 0.006]. PAPi, NT-proBNP and fwRVLS were the best pre-operative predictors of RVF, a post-LVAD implant complication which was confirmed to have a great impact on survival. In particular, fwRVLS has been proven to be the strongest independent predictor.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Disfunção Ventricular Direita , Ecocardiografia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Coração Auxiliar/efeitos adversos , Hemodinâmica , Humanos , Valor Preditivo dos Testes , Estudos Retrospectivos , Disfunção Ventricular Direita/complicações , Disfunção Ventricular Direita/etiologia
11.
Am J Gastroenterol ; 106(12): 2112-20, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21971536

RESUMO

OBJECTIVES: Transient elastography (TE) is adequate for a diagnosis of cirrhosis, but its accuracy for milder stages of fibrosis is much less satisfactory. The objective of this study was to compare the performance and the discordance rate of acoustic radiation force impulse (ARFI) and TE with liver biopsy in a cohort of chronic hepatitis C (CHC) patients. METHODS: One hundred thirty-nine consecutive patients with CHC were enrolled in two tertiary centers, and evaluated for histological (Metavir score) and biochemical features. All patients underwent TE and ARFI. RESULTS: TE was unreliable in nine patients (6.5%), while in no cases (0%) were ARFI invalid measurements recorded (P=0.029). By area under receiver operating characteristic curve (AUROC), the best cutoff values for TE and ARFI for significant fibrosis (≥F2) were ≥6.5 kPa (AUROC: 0.78) and ≥1.3 m/s (AUROC: 0.86), respectively. For severe fibrosis (F3-F4), these cutoff values were 8.8 kPa (AUROC: 0.83) for TE and 1.7 m/s (AUROC: 0.94) for ARFI. For cirrhosis, TE had its best cutoff at ≥11 kPa (AUROC: 0.80) and ARFI at ≥2.0 m/s (AUROC: 0.89). By pairwise comparison of AUROC, ARFI was significantly more accurate than TE for a diagnosis of significant and severe fibrosis (P=0.024 and P=0.002, respectively), while this difference was only marginal for cirrhosis (P=0.09). By partial AUROC analysis, ARFI performance results significantly higher for all three stages of fibrosis. The average concordance rates of TE and ARFI vs. liver biopsy were 45.4 and 54.7%, respectively. By multivariate analysis, ARFI was not associated with alanine aminotransferase (ALT), body mass index, Metavir grade, and liver steatosis, while TE was significantly correlated with the ALT value (P=0.027). CONCLUSIONS: In a cohort of patients with CHC, ARFI imaging was more accurate than TE for the non-invasive staging of both significant and severe classes of liver fibrosis.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Hepatite C Crônica/classificação , Cirrose Hepática/classificação , Adulto , Idoso , Biópsia , Estudos de Coortes , Feminino , Hepacivirus/genética , Hepatite C Crônica/patologia , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/sangue , Curva ROC , Reprodutibilidade dos Testes
12.
Minerva Cardioangiol ; 59(1): 101-8, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21285935

RESUMO

Diabetic complications in the lower extremities, especially those secondary to diabetic macroangiopathy, have increasingly become a clinical emergency, given the high prevalence and progression of the disease. Until recently, the only approach to treating advanced stage disease was medical therapy and major amputation; however, the advent of revascularization procedures has radically improved the prognosis of patients with critical lower limb ischemia. In this setting, iloprost holds a dual position: as first-choice therapy in patients ineligible for revascularization and as complementary therapy in candidates for surgical or endovascular revascularization.


Assuntos
Angiopatias Diabéticas/tratamento farmacológico , Iloprosta/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Interações Medicamentosas , Humanos , Prostaglandinas/uso terapêutico
13.
Sci Total Environ ; 801: 149763, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34438135

RESUMO

Solar driven advanced oxidation processes (AOPs) (an alternative solar photo Fenton like process (SPF), sunlight/H2O2 (SHP) and sunlight/chlorine (SCL)) and respective dark conditions, were compared for the first time to conventional (chlorination and UV-C radiation) disinfection processes, in the inactivation of E. coli and Entero strains inoculated in real roof-harvested rainwater (RHRW), to evaluate their possible safe use for crop irrigation. In this regard, bacterial regrowth was also evaluated 6, 12, 24 and 48 h after disinfection treatment. The SPF, using iminodisuccinic acid (IDS)-Cu complex as catalyst, was optimized (H2O2/IDS-Cu 55/1 best molar ratio) under mild conditions (spontaneous pH) and sunlight. The faster inactivation kinetics were observed for the SCL process (k = 1.473 min-1, t1/2 = 0.47 min for E. coli and k = 1.193 min-1, t1/2 = 0.57 min for Entero), while the most effective processes in controlling bacterial regrowth were SPF and SCL. Although UV-C radiation (0-1.3 × 104 µW s cm-2 dose range) was the second faster disinfection process (k = 1.242 min-1, t1/2 = 0.55 min for E. coli and k = 1.150 min-1, t1/2 = 0.60 min for Entero), it was the less effective process in controlling bacterial regrowth (>10 CFU 100 mL-1 already after 6 h post-treatment incubation). According to the bacterial inactivation and regrowth tests carried out in this work, SPF and SCL are interesting options for RHRW disinfection, in case of effluent use for crop irrigation.


Assuntos
Desinfecção , Purificação da Água , Enterococcus , Escherichia coli , Peróxido de Hidrogênio , Luz Solar , Águas Residuárias
14.
J Exp Med ; 189(2): 219-30, 1999 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-9892605

RESUMO

Pathogenic effector T cells in experimental autoimmune uveitis (EAU) are T helper type 1-like, and interleukin (IL)-12 is required for their generation and function. Therefore, we expected that IL-12 administration would have disease-enhancing effects. Mice were immunized with a uveitogenic regimen of the retinal antigen interphotoreceptor retinoid-binding protein, treated with IL-12 (100 ng/d for 5 d), and EAU was assessed by histopathology. Unexpectedly, IL-12 treatment failed to enhance EAU in resistant strains and downregulated disease in susceptible strains. Only treatment during the first, but not during the second, week after immunization was consistently protective. High levels of interferon gamma (IFN-gamma) were present in the serum during IL-12 treatment, but subsequent antigen-specific IFN-gamma production in protected mice was diminished, as were IL-5 production, lymph node cell proliferation, and serum antibody levels. Treated mice had fewer cells and evidence of enhanced apoptosis in the draining lymph nodes. Unlike wild-type mice, IFN-gamma-deficient, inducible nitric oxide synthase (iNOS)-deficient, and Bcl-2(lck) transgenic mice were poorly protected by IL-12, whereas IL-10-deficient mice were protected. We conclude that administration of IL-12 aborts disease by curtailing development of uveitogenic effector T cells. The data are compatible with the interpretation that IL-12 induces systemic hyperinduction of IFN-gamma, causing activation of iNOS and production of NO, which mediates protection at least in part by triggering Bcl-2 regulated apoptotic deletion of the antigen-specific T cells as they are being primed.


Assuntos
Apoptose/imunologia , Doenças Autoimunes/imunologia , Proteínas do Olho , Interferon gama/deficiência , Interleucina-12/uso terapêutico , Óxido Nítrico/imunologia , Proteínas de Ligação ao Retinol/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Uveíte/imunologia , Animais , Hipersensibilidade Tardia/imunologia , Imunoglobulina G/sangue , Marcação In Situ das Extremidades Cortadas , Interleucina-12/farmacologia , Interleucina-5/imunologia , Linfonodos/patologia , Linfócitos/imunologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Proteínas Proto-Oncogênicas c-bcl-2/imunologia
15.
J Exp Med ; 184(5): 1651-61, 1996 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-8920855

RESUMO

Immunoglobulin (Ig) class switching in B cells is regulated by stimuli transduced by cytokines and cell-cell contact. Among these stimuli, interleukin (IL)-4 has been considered an absolute prerequisite for class switching to IgE in the mouse. Here we report that IL-4-deficient (IL-4-/-) and wildtype mice had comparably elevated serum IgE levels during the course of a murine retrovirus-induced immunodeficiency syndrome, MAIDS. IgE switching in IL-4-/- mice was also induced by injection of anti-IgD antibody. Treatment with anti-IgD induced germline epsilon (g epsilon) transcripts with comparable efficiency in IL-4-/- mice and controls, but the levels of productive epsilon transcripts (p epsilon) were lower by a factor of 200 and serum IgE levels were lower by a factor of 300 in IL-4-/- mice as compared with controls. Induction of g epsilon after anti-IgD treatment of IL-4-/- mice was unaffected by simultaneous treatment with monoclonal antibodies to IL-4 and IL-4 receptor alpha chain. Infection of IL-4-/- mice with Nippostrongylus brasiliensis, a potent stimulus for IgE production, resulted in induction of g epsilon transcripts; however, p epsilon transcripts were barely detectable and serum IgE was not detected. These findings establish a novel IL-4-independent pathway for IgE switching in the mouse that is strongly activated in retroviral infection but weakly in nematode infection. This pathway appears to be dependent on distinct factors that separately control induction of g epsilon transcription and switch recombination to p epsilon.


Assuntos
Switching de Imunoglobulina , Imunoglobulina E/biossíntese , Interleucina-4/deficiência , Síndrome de Imunodeficiência Adquirida Murina/imunologia , Animais , Dinoprostona/biossíntese , Imunoglobulina D/imunologia , Imunoglobulina E/genética , Interferon gama/biossíntese , Interleucina-4/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , RNA Mensageiro/biossíntese , Recombinação Genética , Infecções por Strongylida/imunologia
16.
Scand J Immunol ; 72(1): 31-7, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20591073

RESUMO

The pro-inflammatory cytokines play a critical role in the initiation and propagation of ocular autoimmune diseases. Regulation of these cytokines is generally mediated by the immunoregulatory cytokine such as IL-10 or TGF-beta. In this study, we investigated the immunoregulatory cytokine profile and frequency of natural regulatory T cells (nTregs) in patients with Vogt-Koyanagi-Harada (VKH). We obtained the peripheral blood mononuclear cells (PBMC) from patients with VKH and healthy controls. The cytokine profile from supernatants of PBMC cultured with or without phytohaemagglutinin (PHA) was measured by ELISA, the percentage of CD4(+) Foxp3(+) and CD25(high)Foxp3(+) T regulatory cells were analysed by flow cytometry, and the transcriptional level of Foxp3 expression was analysed by real-time quantitative PCR. The immunoregulatory cytokines, TGF-beta and IL-10, increased in patients with VKH in the inactive stage of the disease. We observed no significant difference in the CD4(+) Foxp3(+) and CD25(high)Foxp3(+) T cells as well as no reduction in FOXP3 mRNA expression in the patients with VKH when compared to healthy controls. We showed in our work, an increase in IFN-gamma secretion by PBMC of patients with VKH in the active stage of the disease when compared to healthy controls and patients in the inactive stage. Our data suggest that IL-10 and TGF-beta cytokines, rather than nTregs are associated with the resolution phase of the disease and may have a more relevant role in controlling this disease.


Assuntos
Fatores de Transcrição Forkhead/imunologia , Interleucina-10/imunologia , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta/imunologia , Síndrome Uveomeningoencefálica/imunologia , Adulto , Antígenos CD4/imunologia , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/genética , Humanos , Subunidade alfa de Receptor de Interleucina-2/imunologia , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , RNA/química , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
17.
Allergy ; 65(4): 510-5, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19839975

RESUMO

BACKGROUND: Many patients with common variable immunodeficiency (CVID) have a clinical history suggestive of allergic respiratory disease. However, in such individuals, the prevalence of asthma and the role of atopy have not been well established. The objective of this study was to evaluate pulmonary function and identify asthma in patients with CVID. We also investigated the role of IgE as a trigger of asthma in these patients. METHODS: Sixty-two patients diagnosed with CVID underwent spirometry, as well as skin prick testing and in vitro determination of serum-specific IgE levels for aeroallergens, together with bronchial provocation with histamine and allergen. RESULTS: The most common alteration identified through spirometry was obstructive lung disease, which was observed in 29 (47.5%) of the 62 patients evaluated. Eighteen (29.0%) of the 62 patients had a clinical history suggestive of allergic asthma. By the end of the study, asthma had been diagnosed in nine (14.5%) patients and atopy had been identified in six (9.7%). In addition, allergic asthma had been diagnosed in four patients (6.5% of the sample as a whole; 22.2% of the 18 patients with a clinical history suggestive of the diagnosis). CONCLUSION: In this study, CVID patients testing negative for specific IgE antibodies and suspected of having allergic asthma presented a positive response to bronchial provocation tests with allergens. To our knowledge, this is the first such study. When CVID patients with a history suggestive of allergic asthma test negative on traditional tests, additional tests designed to identify allergic asthma might be conducted.


Assuntos
Asma/complicações , Asma/imunologia , Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/imunologia , Adolescente , Adulto , Idoso , Asma/epidemiologia , Imunodeficiência de Variável Comum/epidemiologia , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Testes de Função Respiratória , Testes Cutâneos , Adulto Jovem
18.
Eur J Vasc Endovasc Surg ; 39(3): 252-7, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19945315

RESUMO

BACKGROUND: Filter-protected transcervical carotid artery stenting (CAS) has been suggested to reduce the intraoperative cerebral embolisation observed during transfemoral CAS. We therefore evaluated clinical outcome and incidence of ischaemic lesions at diffusion-weighted magnetic resonance imaging (DW-MRI) after transcervical and transfemoral CAS. METHODS: From March 2007 to May 2009, we performed filter-protected CAS in 135 patients with symptomatic (30%) or asymptomatic (70%) carotid stenosis above 70% and below 95%. In 44 patients with risky femoral access or unfavourable aortic arch anatomy, access to common carotid artery was achieved by a small cervical incision. In another 91 procedures we used a classic percutaneous femoral access. Preoperative and postoperative DW-MRI scans were obtained after 111 procedures (82%) - 35 transcervical and 76 transfemoral. RESULTS: The incidence of clinical events (transient ischaemic attack (TIA) and stroke) was 2.3% after transcervical CAS and 19.8% after transfemoral CAS (P<0.01), without any deaths. DW-MRI disclosed new ischaemic lesions in five patients (5/35, 14.3%) after transcervical CAS and in 28 patients (28/76, 36.8%) after transfemoral CAS (P=0.015). All ischaemic lesions depicted after transcervical procedures were ipsilateral to the treated artery. CONCLUSIONS: Transcervical filter-protected CAS, compared with classic percutaneous procedures, seems to reduce clinical events and DW-MRI ischaemic damage and may be useful in selected patients.


Assuntos
Angioplastia/instrumentação , Isquemia Encefálica/prevenção & controle , Estenose Coronária/terapia , Filtração/instrumentação , Embolia Intracraniana/prevenção & controle , Stents , Idoso , Idoso de 80 Anos ou mais , Angioplastia/efeitos adversos , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Estenose Coronária/diagnóstico , Imagem de Difusão por Ressonância Magnética , Desenho de Equipamento , Feminino , Humanos , Embolia Intracraniana/diagnóstico , Embolia Intracraniana/etiologia , Ataque Isquêmico Transitório/etiologia , Ataque Isquêmico Transitório/prevenção & controle , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
19.
Int J Immunopathol Pharmacol ; 23(1): 383-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20394708

RESUMO

The main problem associated with artificial vascular devices is the risk of bacterial infections, mostly sustained by coagulase negative Staphylococci or Staphylococcus aureus. Many efforts have been made to identify materials refractory to bacterial adhesion. The aim of our study is to verify the antimicrobial properties of two kinds of vascular prosthesis to prevent early onset infections and the efficacy of the concomitant action of a systemic antibiotic treatment. Adult male Wistar rats were used. We subcutaneously implanted in four groups a silver-coated prosthesis fragment, and a rifampicin-soaked prosthesis fragment in the remaining four groups. We inoculated in the site of implant a high bacterial burden of S. aureus in four groups and a low burden in the remaining groups. Systemic levofloxacin was administered for seven days in four groups representing the two kinds of prosthesis; after 21 days the rats were sacrificed, prosthesis fragments were sonicated and the corresponding supernatants were plated for bacterial counts. The rifampicin-soaked prostheses explanted from rats treated with levofloxacin were sterile, regardless of the bacterial inoculum. In other groups some prostheses were colonized. In the experimental rat model used, the action of local and systemic antibiotic treatment was able to reduce colonisation of artificial prostheses.


Assuntos
Antibioticoprofilaxia , Prótese Vascular/efeitos adversos , Levofloxacino , Ofloxacino/uso terapêutico , Rifampina/farmacologia , Prata/farmacologia , Animais , Masculino , Infecções Relacionadas à Prótese/prevenção & controle , Ratos , Ratos Wistar , Infecções Estafilocócicas/tratamento farmacológico
20.
Radiol Med ; 115(2): 313-25, 2010 Mar.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-20091136

RESUMO

PURPOSE: It is often difficult to diagnose cerebral venous thrombosis (CVT), an uncommon condition that more frequently affects young subjects, is responsible for 1%-2% of strokes in adults and has a subtle clinic onset. The aim of this study was to evaluate the role of computed tomography (CT), magnetic resonance imaging (MRI) and MR venography in the emergency setting and to discuss the risk factors, clinical presentation, outcome and follow-up of this disease. MATERIALS AND METHODS: We retrospectively studied 40 patients with CVT admitted to the emergency department between 1996 and 2006 and examined with unenhanced CT, MRI and MR venography. Fourteen patients also underwent digital subtraction angiography (DSA). RESULTS: Headache was the most common presenting feature (60%). Unenhanced CT showed typical signs (cord or empty delta sign) in 11 cases and nonspecific signs in the other cases. The diagnosis was achieved with MRI and MR venography in 38/40 cases (95%) and with DSA in 2/40 cases. All patients were treated with heparin. Five patients died, and only one of the remaining patients developed serious disability. CONCLUSIONS: Knowledge of the CT, MRI and MR-venography signs of CVT is crucial and enables an early diagnosis and timely treatment with heparin in the majority of cases. DSA should be reserved for doubtful cases only.


Assuntos
Serviço Hospitalar de Emergência , Trombose Intracraniana/diagnóstico , Angiografia por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Trombose Venosa/diagnóstico , Adolescente , Adulto , Idoso , Angiografia Digital , Anticoagulantes/uso terapêutico , Angiografia Cerebral , Meios de Contraste , Diagnóstico Diferencial , Feminino , Heparina/uso terapêutico , Humanos , Trombose Intracraniana/diagnóstico por imagem , Trombose Intracraniana/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/terapia
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