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1.
Dis Markers ; 35(3): 141-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24167359

RESUMO

BACKGROUND: Sulfhydryl groups (SH) are considered a key factor in redox sensitive reaction of plasma, and their modification could be considered an expression of abnormal generation of oxygen free radicals. METHODS: Fifty consecutive patients with acute brain stroke were enclosed in this study. The plasma concentrations of SH groups were correlated to cytokines (IL-1b, IL-6, IL-8, TNF- α ), plasma chitotriosidase (Chit), metalloprotease (MMP2-9), intercellular adhesion molecule-1 (ICAM-1). RESULTS: The results demonstrated a significant reduction of SH groups within 24 hours from the onset of an acute ischemic stroke, a reduction of plasma IL-1b, IL-6, and IL-8, and an increase of Chit and TNF- α in relation to the stroke severity. CONCLUSION: The observation of an intense microenvironment activation that follows the stroke and the correlation between SH levels and markers of immune response suggest that, especially in stroke, is necessary to maintain the redox function to prevent the brain damage. The reduced SH levels represent an attempt to neutralize the abnormal generation of free radicals. Since the reperfusion of brain after ischemic event represents a severe oxidative stress, which must be corrected by regeneration of redox sensitive function, pharmacological intervention could be beneficial in this setting.


Assuntos
Citocinas/sangue , Acidente Vascular Cerebral/sangue , Compostos de Sulfidrila/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Hexosaminidases/sangue , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Metaloproteinases da Matriz/sangue , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/imunologia
2.
J Neuroimmunol ; 185(1-2): 201-7, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17336397

RESUMO

Several epidemiological investigations conducted in Sardinia, insular Italy, indicate that the strong selective pressure of malaria along the centuries may have concurred to the elevated genetic MS-risk in this region. To test such hypothesis in an experimental setting, we have compared the immune response to P. falciparum (the causative agent of malaria) in Sardinian MS patients relative to their ethnic healthy controls and control MS patients of different ethnicity. To this purpose, the P. falciparum-driven peripheral mononuclear cell proliferation, the production of pro-inflammatory cytokines of the innate immunity such as TNF-alpha, IL-6 and IL-12 and the ability to inhibit the parasite growth have been tested in relation to HLA-DR alleles and TNF promoter polymorphisms known of being associated to MS. We found that P. falciparum-induced proliferation, cytokine production and parasite killing are significantly augmented in Sardinian MS patients as compared to controls (p<0.01). Additionally, a correlation is found with genes associated to Sardinian MS, namely the TNF(-376A) promoter polymorphism and the class II HLA-DRB1*0405 allele. In conclusion, we have found evidences that some genetic traits formerly selected to confer a protective responses to P. falciparum now partially contribute to the elevated MS susceptibility amongst Sardinians.


Assuntos
Imunidade Inata , Malária/imunologia , Esclerose Múltipla/microbiologia , Plasmodium falciparum/imunologia , Adulto , Animais , Proliferação de Células , Ensaio de Imunoadsorção Enzimática , Feminino , Predisposição Genética para Doença , Antígenos HLA-DR , Humanos , Subunidade p40 da Interleucina-12/biossíntese , Interleucina-6/biossíntese , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Esclerose Múltipla/imunologia , Polimorfismo Genético , Fator de Necrose Tumoral alfa/biossíntese
3.
Int J Biomed Sci ; 3(4): 292-7, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23675056

RESUMO

We designed a large multicentric study to analyse the presence of MSRV particles in blood and CSF of a large cohort of patients and controls from different European areas. 149 MS patients and 153 neurological and healthy controls were selected from Sardinia, Spain, Northern-Italy and Sweden. To avoid biological and inter-assay variability MSRV was detected within a single laboratory through nested and real-time PCR assays specific for pol and env genes. MSRV detection in blood and CSF of MS patients and controls in populations of different ethnicity gave significant differences (p<0.05 compared to neurological controls and <0.001 compared to healthy controls). The presence and viral load of MSRV are significantly associated with MS as compared to neurological and healthy controls in all ethnic groups.

4.
Hum Immunol ; 67(1-2): 108-17, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16698432

RESUMO

Autism spectrum disorders (ASD) are characterized by a broad range in clinical presentation. Although a definite genetic cause has not yet been fully demonstrated, family based studies suggest that a multigenic pattern may be responsible for susceptibility, but most results are conflicting and have yet to be replicated. The purpose of this investigation was to analyze the linkage of the human leukocyte antigen (HLA) and the human serotonin transporter coding (5-HTTLPR) genes with ASD in a group of 37 families of Sardinian ethnicity in insular Italy. In 50% of these families, ASD is linked to HLA, and in the other 50% it is linked to 5-HTTLPR polymorphic genes; in other words, linkage to one or the other was evident in all cases. Despite a very homogenous genetic pattern being generally reported for Sardinians, the linkage observed with HLA and 5-HTTLPR genetic regions indicated a statistically defined heterogeneity (p=0.002). No allelic HLA or 5-HTTLPR polymorphisms were specifically associated with ASD, suggesting these loci as markers of other genes mapped in their close proximity that may be more directly involved and thus may merit further analytical studies.


Assuntos
Transtorno Autístico/epidemiologia , Transtorno Autístico/genética , Grupos Étnicos/genética , Antígenos HLA-DR/genética , Polimorfismo Genético , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adolescente , Criança , Pré-Escolar , Feminino , Ligação Genética , Cadeias HLA-DRB1 , Humanos , Itália/epidemiologia , Itália/etnologia , Masculino , Epidemiologia Molecular
5.
Neurobiol Dis ; 20(3): 961-8, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16023861

RESUMO

Several nuclear hormone receptors have been associated with inflammatory reactions. Particularly, liver X receptors (LXRs) have recently been identified as key transcriptional regulators of genes involved in lipid homeostasis and inflammation. LXRs are negative regulators of macrophage inflammatory gene expression. Multiple sclerosis (MS), a demyelinating disease of the central nervous system of unknown cause, is characterized by recurrent inflammation involving macrophages and their inflammatory mediators. Sweden belongs to the countries with a high MS incidence. In Italy, the MS incidence is lower, except on the island of Sardinia where the incidence is even higher than in Sweden. Subjects from Sardinia are ethnically more homogeneous, and differ from Swedes also regarding genetic background and environment. We studied mRNA expression of several nuclear hormone receptors in blood mononuclear cells (MNC) from female patients with untreated relapsing-remitting MS from Sassari, Sardinia, and Stockholm, Sweden. Sex- and age-matched healthy controls (HC) were from both areas. mRNA expression was evaluated by quantitative real-time PCR. We found altered mRNA expression of LXRs, estrogen receptors (ERs), and androgen receptor (AR) in MS. mRNA expression of both LXRalpha and LXRbeta is lower in MS from Stockholm but not from Sassari. In particular, LXRalpha mRNA expression was significantly lower in MS from Stockholm as compared with all groups in the study including MS from Sassari. Low levels of ERalpha mRNA are seen in MS from both Stockholm and Sassari. The splice variant ERbetacx showed significantly higher mRNA expression in MS from Sassari and Stockholm as compared with corresponding HC. In particular, ERbetacx mRNA in MS from Sassari was remarkably higher as compared with all other groups in the study. Higher levels of AR mRNA are present in HC from Sassari. The findings indicate that the expression levels of anti-inflammatory nuclear receptor superfamily genes in MS appear to reflect both ethnic and environmental influences.


Assuntos
Proteínas de Ligação a DNA/genética , Macrófagos/metabolismo , Esclerose Múltipla/sangue , Esclerose Múltipla/genética , Receptores Androgênicos/genética , Receptores Citoplasmáticos e Nucleares/genética , Receptores Estrogênicos/genética , Adulto , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Grupos Étnicos/genética , Feminino , Predisposição Genética para Doença/genética , Geografia , Humanos , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Itália/epidemiologia , Itália/etnologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Receptores X do Fígado , Macrófagos/imunologia , Pessoa de Meia-Idade , Esclerose Múltipla/etnologia , Receptores Nucleares Órfãos , RNA Mensageiro/metabolismo , Suécia/epidemiologia , Suécia/etnologia
6.
Mult Scler ; 11(1): 16-23, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15732262

RESUMO

Subjects from Sardinia, Italy, are relatively homogeneous compared to Swedes. Although ethnically distant, both populations have similarly high multiple sclerosis (MS) incidence rates. Pro- and anti-inflammatory cytokines and their receptors, signalling molecules and other immune response-associated factors might influence MS pathogenesis, though definite proof is missing. The study of populations with similar MS incidence but different genetic and environmental background could make possible the definition of factors that relate to such background differences. We selected untreated female MS patients from Sassari, Sardinia, and Stockholm, Sweden, and corresponding sex- and age-matched healthy controls (HC), to study blood mononuclear cells (MNC) for mRNA expression of 20 immune response-related genes considered relevant in MS, employing real-time PCR. Higher expression of IL-12p40 mRNA was confined to MS from both Sassari and Stockholm, compared to corresponding HC. MS patients from Sassari, but not Stockholm, expressed higher TNF-alpha compared to corresponding HC. MS patients from Stockholm, but not Sassari, expressed higher IL-6. Indoleamine 2,3 dioxygenase (IDO), a molecule necessary in tolerance induction, was lower in MS from Stockholm compared to corresponding HC. This was not observed in Sassari. No differences were detected for other members of the IL-12 family, other Th1 and Th2 cytokines, and the signalling molecules Stat 4 and 6. The results corroborate a pro-inflammatory state in MS as reflected by high expression of IL-12, TNF-alpha and IL-6, although the extent of expression of TNF-alpha, IL-6 and IDO differs between strictly matched MS patients from different high-incidence areas. This might result from genetic and/or environmental differences. They may account for some of the discrepancies regarding immune response-related molecules previously reported in MS. In conclusion, a pro-inflammatory state exists in MS patients from Sassari as well as Stockholm. The changes of pro-inflammatory and other immune response-related variables differ however between the two MS populations. This may be attributed to the genetic and/or environmental background.


Assuntos
Citocinas/genética , Heterogeneidade Genética , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Receptores de Citocinas/genética , Adulto , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase , Interleucina-10/genética , Interleucina-12/genética , Interleucina-18/genética , Subunidade alfa de Receptor de Interleucina-18 , Interleucina-4/genética , Interleucina-6/genética , Itália , Pessoa de Meia-Idade , Receptores de Interleucina/genética , Receptores de Interleucina-10 , Receptores de Interleucina-12 , Receptores de Interleucina-18 , Receptores de Interleucina-6/genética , Receptores do Fator de Necrose Tumoral/genética , Fator de Transcrição STAT4 , Fator de Transcrição STAT6 , Suécia , Transativadores/genética , Fator de Crescimento Transformador beta/genética , Triptofano Oxigenase/genética , Fator de Necrose Tumoral alfa/genética
7.
Neurobiol Dis ; 17(2): 131-43, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15474351

RESUMO

Multiple sclerosis (MS) is a chronic disease of the central nervous system affecting young adults and thus representing a major burden also for their families and communities. The etiology of MS is obscure and its pathogenesis is yet incompletely depicted. Increased evidences indicate a strong genetic contribution to MS susceptibility, although others support the view that it is also influenced by environmental factors, possibly related to still unidentified pathogens. MS appears to be more heterogeneous than previously believed at the immunological level, and new pathological studies indicate a series of subset of conditions under the common denominator MS. The use of genetically homogeneous and geographically isolated populations at high MS risk, such as that of Sardinia, insular Italy, becomes in principle a vital requirement to reduce biological variables and the intrinsic complexity of the disease. This review will focus on recent findings on the peculiarity of Sardinian MS concerning epidemiological, genetic, and environmental aspects. Epidemiological studies reveal a clear heterogeneous distribution of MS cases in the Northern province of Sassari which may not be uniquely assigned to genetic variations. Furthermore, a different immunogenetic profile, including the association with other immunomediated diseases, and a progressive change in clinical phenotype, including age at onset, are present in this island which gives us unexpected variations at the level of patients' cohort and territorial distribution, especially when the northern province is compared to the southern one. This renders MS etiopathogenesis more complex than formerly thought even in this selected and genetically stable population.


Assuntos
Meio Ambiente , Predisposição Genética para Doença , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/etiologia , Suscetibilidade a Doenças , Humanos , Incidência , Itália/epidemiologia , Esclerose Múltipla/genética , Filogenia , Prevalência
8.
J Neurol ; 250(5): 607-11, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12736743

RESUMO

Interleukin-6 (IL-6) plays an important role in the regulation of the inflammatory response in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Previous reports indicated that the C allele of a variable number tandem repeat (vntr) polymorphism located in the 3'flanking region of the IL-6 gene ( IL-6) is associated with reduced activity of IL-6 in vivo. Since disease-modifying genes are likely to contribute to phenotypic differences in MS patients, we tested the hypothesis that the IL-6 C allele is associated with the clinical course of MS. The IL-6 C allele was equally distributed between 217 MS patients of German Caucasian origin and 111 age-mached healthy controls. Stratification of patients according to the course of disease revealed no significant difference of IL-6 C allele distribution between patients with primary progressive and those with either relapsing-remitting or secondary progressive MS although IL-6 C allele was more frequent in patients with RR-MS. Since IL-6 C allele has been associated with a benign course in Sardinian MS patients, we further analysed an independent sample of 125 Sardinian MS patients revealing that IL-6 C allele was much more frequent than in German MS patients. Taken together, a disease-modifying effect of IL-6 C allele could not be demonstrated in MS patients of German Caucasian descent.


Assuntos
Variação Genética/genética , Interleucina-6/genética , Repetições Minissatélites/genética , Esclerose Múltipla/genética , Polimorfismo Genético/genética , Adulto , Alelos , Análise de Variância , Distribuição de Qui-Quadrado , Citosina , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
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