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1.
Heliyon ; 6(10): e05401, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33163668

RESUMO

Spread of multi-drug resistant (MDR) bacteria in natural environments pose a risk to human and animal health. Wild birds are considered to be reservoirs of human pathogens and vectors of antimicrobial resistance distribution in the environment. The aim of this study is to assess the occurrence of antibiotic resistant bacteria in isolates from bird specimens living in three agro-pastoral areas of the southeastern Sicily. We analyzed the microbiomes of the Eurasian Stone curlew Burhinus oedicnemus (Charadriiformes, Aves) and identified 91 Gram positive and 212 Gram negative strains, whose antimicrobial susceptibility to 11 and 9 antibiotic classes (respectively) was evaluated using agar disk diffusion test. Isolates showed significant levels of antimicrobial resistance, and a high percentage of MDR strains was found both between the Gram positive (49.4%) and the Gram negative (34.9%). Multi-drug resistance levels are higher among strains isolated in the beak and the eye than among enteric (faeces and cloaca) strains. Our results indicate high levels of MDR strains among wild bird populations, with a potential threat to wildlife and human populations.

2.
J Feline Med Surg ; 22(7): 613-622, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31524037

RESUMO

OBJECTIVES: The aim of this study was to determine the antimicrobial susceptibility of Enterobacteriaceae isolated from cats affected by diseases commonly encountered in practice, and to characterise the third-generation cephalosporin (3GC)-resistance molecular mechanisms involved. METHODS: Clinical samples (n = 100) included 58 rectal swabs from cats with diarrhoea, 31 nasal swabs from cats with clinical signs of upper respiratory tract disease, four ear swabs from cats with otitis, three conjunctival swabs from cats with conjunctivitis, two oral swabs from cats with stomatitis, one swab from a skin abscess and one urine sample from a cat with cystitis. A total of 125 Enterobacteriaceae were isolated from 90 cats. Escherichia coli was the most frequently isolated species (n = 65), followed by Enterobacter species (n = 20), Proteus species (n = 13), Citrobacter species (n = 12) and others (n = 15). Bacterial susceptibility testing was performed with respect to eight antimicrobial classes. Beta (ß)-lactamase genes were identified by PCR and nucleotide sequencing. RESULTS: Overall, the higher frequency of resistance was to amoxicillin-clavulanate (61.3%), trimethoprim/sulfamethoxazole (33.6%) and cefotaxime (32.8%). Thirty-six percent of the isolates (n = 45) were resistant to 3GCs. Of these isolates, 34 were tested by PCR and nucleotide sequencing and 23 were confirmed as encoding ß-lactamase genes. Fourteen 3GC-resistant isolates harboured extended-spectrum ß-lactamases (ESBLs) belonging to groups CTX-M-1 (n = 12, two of which were CTX-M-79), CTX-M-2 (n = 1) and CTX-M-9 (n = 1), as well as SHV-12 (n = 1) and TEM-92 (n = 1). Nine isolates had CMY-2 plasmid-mediated AmpC ß-lactamases (pAmpC). Thirty-one percent (n = 39) of the isolates were multidrug resistant (MDR) and were isolated from 34% (n = 31/90) of the cats. CONCLUSIONS AND RELEVANCE: A high frequency of MDR and ESBL/pAmpC ß-lactamase-producing Enterobacteriaceae were detected among bacteria isolated from a feline population in southern Italy with a variety of common clinical conditions, which poses limitations on therapeutic options for companion animals. We describe the first detection of CTX-M-79 and TEM-92 ESBL genes in isolates from cats.

3.
Sci Rep ; 9(1): 18956, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831800

RESUMO

Zoophytophagous insect predators can induce physiological responses in plants by activating defence signalling pathways, but whether plants can respond to facultative phytophagy by recruiting natural enemies remains to be investigated. In Y-tube olfactometer bioassays, using a system including a Vicia faba plant, the zoophytophagous predator Podisus maculiventris and the egg parasitoid Telenomus podisi, we first demonstrated that T. podisi females are attracted by broad bean plants damaged by feeding activity of P. maculiventris and on which host egg masses had been laid, while they are not attracted by undamaged plants or plants damaged by feeding activity alone. In a second experiment, we evaluated the impact of the invasive phytophagous pest Halyomorpha halys on this plant volatile-mediated tritrophic communication. Results showed that the invasive herbivorous adults do not induce plants to recruit the native egg parasitoid, but they can disrupt the local infochemical network. In fact, T. podisi females are not attracted by volatiles emitted by plants damaged by H. halys feeding alone or combined with oviposition activity, nor are they attracted by plants concurrently infested by P. maculiventris and H. halys, indicating the specificity in the parasitoid response and the ability of the invasive herbivore in interrupting the semiochemical communication between plants and native egg parasitoids. To the best of our knowledge, this is the first study showing that zoophytophagous predator attacks induce indirect plant defences similarly to those defence strategies adopted by plants as a consequence of single or concurrent infestations of herbivorous insects.


Assuntos
Heterópteros/fisiologia , Himenópteros/fisiologia , Vicia faba , Compostos Orgânicos Voláteis/metabolismo , Animais , Vicia faba/metabolismo , Vicia faba/parasitologia
4.
Oxid Med Cell Longev ; 2019: 8056904, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485299

RESUMO

Neuroinflammation, a hallmark of chronic neurodegenerative disorders, is characterized by sustained glial activation and the generation of an inflammatory loop, through the release of cytokines and other neurotoxic mediators that cause oxidative stress and limit functional repair of brain parenchyma. Dietary antioxidants may protect against neurodegenerative diseases by counteracting chronic neuroinflammation and reducing oxidative stress. Here, we describe the effects of a number of natural antioxidants (polyphenols, carotenoids, and thiolic molecules) in rescuing astrocytic function and neuronal viability following glial activation by reducing astrocyte proliferation and restoring astrocytic and neuronal survival and basal levels of reactive oxygen species (ROS). All antioxidant molecules are also effective under conditions of oxidative stress and glutamate toxicity, two maladaptive components of neuroinflammatory processes. Moreover, it is remarkable that their antioxidant and anti-inflammatory activity occurs through differential modulation of NF-κB binding activity in neurons and astrocytes. In fact, we show that inflammatory stimuli promote a significant induction of NF-κB binding activity in astrocytes and its concomitant reduction in neurons. These changes are prevented in astrocytes and neurons pretreated with the antioxidant molecules, suggesting that NF-κB plays a key role in the modulation of survival and anti-inflammatory responses. Finally, we newly demonstrate that effective antigliosis and neuroprotective activity is achieved with a defined cocktail of four natural antioxidants at very low concentrations, suggesting a promising strategy to reduce inflammatory and oxidative damage in neurodegenerative diseases with limited side effects.


Assuntos
Antioxidantes/metabolismo , Astrócitos/metabolismo , NF-kappa B/genética , Doenças Neurodegenerativas/genética , Neuroproteção/genética , Estresse Oxidativo/genética , Humanos
5.
Gerontology ; 65(1): 45-56, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30165362

RESUMO

BACKGROUND: Atherosclerosis is the leading cause of death worldwide. The disease development is by and large driven by old age and lifestyle factors, such as diet, physical activity, and smoking. In the present study, we have investigated the effect of exercise and diet on the development of atherosclerosis in young and aged mice. OBJECTIVE: This study aimed at comparing multiple age-dependent factors that may influence atherosclerosis in a transgenic mouse model. METHODS: Young (14 weeks) and aged (49-52 weeks) C57BL/6 wild-type (WT) and atherosclerosis-prone ApoE-/- mice were subjected to physical endurance exercise on a treadmill, with or without a high-fat diet. Five weeks later, the frequencies of regulatory T cells (TREGs) in lymph nodes were assessed by flow cytometry, plasmatic cytokines (interleukin [IL]-1ß, IL-6, IL-10, IL-17, interferon-γ, tumor necrosis factor-α, and transforming growth factor [TGF]-ß1) levels were determined by Luminex assay. Lipids (cholesterol and triglycerides) and anti-heat shock protein 60 (HSP60) autoantibodies were measured by ELISA. Aortic lesion sizes were assessed by en face imaging. Microarray analysis and qPCR of skeletal muscle gene expression were also performed. RESULTS: Exercise leads to a reduction of aortic lesions in young ApoE-/- and aged WT mice independent of diet. In most groups, this reduction was followed by an increased proportion of TREGs and TGF-ß1 levels. Moreover, gene expression analysis showed that exercise seems to affect the AMPK signaling pathway. In particular, PGC-1α1 mRNA was induced in aged WT mice, whereas it was reduced in young ApoE-/- mice. In addition, GSEA analysis showed a marked reduction in the insulin signaling pathway in aged ApoE-/- mice. CONCLUSION: Practicing endurance exercise seems to be enough for reducing early aortic lesion formation, independent of diet. However, this was only true in mice with smaller aortic lesions, since mice with large, advanced, complicated atherosclerotic plaques did not show any reduction in lesion size with exercise training.


Assuntos
Aterosclerose , Dieta Hiperlipídica , Treino Aeróbico/métodos , Resistência Física/fisiologia , Transdução de Sinais/fisiologia , Animais , Aorta/patologia , Apolipoproteínas E/metabolismo , Aterosclerose/diagnóstico por imagem , Aterosclerose/metabolismo , Aterosclerose/terapia , Chaperonina 60/sangue , Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Dieta Hiperlipídica/métodos , Interferon gama , Interleucinas/sangue , Interleucinas/classificação , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Análise em Microsséries/métodos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue
6.
Environ Toxicol Pharmacol ; 63: 69-73, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30172957

RESUMO

Antimicrobial-resistant (AMR) bacteria are a threat to global health. Epidemiological studies are necessary to gain a more detailed understanding of the transmission modality of resistant bacteria to wild animals and their diffusion into the environment to ensure a broader evaluation of the epidemiological role of wildlife. The study aimed to identify little-known epidemiological aspects by focusing on the isolation of Enterobacteriaceae in order to bring knowledge on the bacterial flora of wild mammals living in the National Park of Aspromonte (Calabria, Italy). Two hundred twenty-five faecal samples of wild mammals were collected and submitted to standard bacteriological examination for Enterobacteriaceae detection. Isolates were identified by mass spectrometry MALDI-TOF (matrix assisted laser desorption/ionisation - time of fligt mass spectrometry). The 30 isolates showing the highest number of resistances were screened for Extended Spectrum Beta Lactamase (ESBL) production. Antimicrobial susceptibility testing of the bacterial isolates was performed by the disk diffusion method. Two hundred sixty-three strains were isolated. The most frequently recovered bacterial species were Hafnia alvei, Escherichia coli and Citrobacter spp.. Potentially pathogenic species including Salmonella spp., Yersinia enterocolitica and Serratia marcescens have also been identified. Isolates displayed significant frequencies of antibiotic resistance. The resistance to amoxicillin (71.4%) was the most frequent, followed by amoxicillin/clavulanic acid (55.5%), ampicillin (49.8%), streptomycin (35.7%), doxycycline (16.3%), tobramycin (15.2%), tetracycline (13.3%) and gentamicin (10.6%). Nine strains showed resistance to imipenem and 1 to meropenem. All isolates were negative for the presence of ESBL-encoding genes. Wild animals can be regarded as sentinel species and used as environmental health indicators.


Assuntos
Farmacorresistência Bacteriana , Enterobacteriaceae/isolamento & purificação , Mamíferos/microbiologia , beta-Lactamases/genética , Animais , Animais Selvagens/microbiologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Enterobacteriaceae/classificação , Enterobacteriaceae/enzimologia , Enterobacteriaceae/genética , Fezes/microbiologia , Itália , Testes de Sensibilidade Microbiana , Parques Recreativos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
7.
Autoimmun Rev ; 17(6): 588-600, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29655674

RESUMO

In early-onset Myasthenia Gravis (MG) with anti-acetylcholine receptor antibodies, thymic abnormalities associated with ectopic germinal centers are frequent. miRNAs by acting as post-transcriptional regulators are involved in autoimmunity. To investigate the implication of miRNAs in thymic changes associated with early-onset MG, we performed a miRnome study and data were analyzed with different approaches. miRNAs of interest were further investigated by RT-PCR and transfection experiments for functional tests. First, analyzing specific dysregulated miRNAs, we focused our attention on miR-7-5p and miR-125a-5p, and confirmed by RT-PCR their respective down- and up-regulation in MG thymuses. miR-7 was the most down-regulated thymic miRNA in MG and we observed an inverse correlation between its expression and CCL21 mRNA expression. We next showed that miR-7 down-regulation was due to thymic epithelial cells and by transfecting these cells with miR-7, we demonstrated that it controlled CCL21 release. As CCL21 is essential for germinal center development, we suggested that miR-7 could be involved in thymic changes associated with MG. miR-125a was up-regulated in MG thymuses and is of great interest as it is known to regulate FoxP3 expression, and to modulate the different inflammatory signaling pathways. Thanks to this thymic miRnome study, we also showed the specific dysregulation of miRNA clusters. In particular, we observed that miRNAs localized at the extremity of the X chromosome were down-regulated. This effect seemed linked to their close localization to the fragile X mental retardation 1 gene (FMR1) and the DNA methylation status. Altogether, this miRnome analysis demonstrated that specific thymic miRNAs can be associated with MG and provides novel insights into the pathogenesis of MG.


Assuntos
Pesquisa Biomédica/tendências , MicroRNAs/genética , Miastenia Gravis/genética , Timo/metabolismo , Quimiocina CCL21/genética , Quimiocina CCL21/metabolismo , Regulação da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Miastenia Gravis/imunologia , Transdução de Sinais/genética , Timo/patologia
8.
J Stroke Cerebrovasc Dis ; 27(6): 1666-1672, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29503167

RESUMO

BACKGROUND: Vascular dementia and Alzheimer's disease are the most diffuse forms of dementia. Sometimes, they are difficult to distinguish due to overlaps in symptomatology, pathophysiology, and comorbidity. Visual constructive apraxia is very common in dementia and impairment in these abilities can provide clinical information for differential diagnosis. MATERIALS AND METHODS: All patients underwent Mini Mental State Examination (MMSE) at basal visit (T0) and after 1 year (T1). We analyzed differences in Qualitative Scoring Method for the Pentagon Copying Test and we explored the visual constructive apraxia evolution in these 2 types of dementia. RESULTS: In intragroup analysis, we found a significant difference in each group between T0 and T1 in MMSE score (P < .001) and total qualitative scores (P < .001). In intergroup analysis, at T0, we found significance difference in total qualitative scores (P < .001), in numbers of angles (P = .005), in distance/intersection (P < .001), in closure/opening (P = .01), in rotation (P < .001), and in closing-in (P < .001). At T1, we found significance difference in total qualitative scores (P < .001), in particular, in numbers of angles (P < .001), in distance/intersection (P < .001), in closure/opening (P < .001), in rotation (P < .001), and in closing-in (P < .001). The total score showed the highest classification accuracy (.90, 95%CI = .81-0.96) in differentiating patients with Alzheimer's disease from patients with vascular dementia. The optimal threshold value was k = 5. with .84 (95%CI = .69-0.93) sensitivity and .81 (95%CI = .64-0.93) specificity. CONCLUSION: Patients with vascular dementia showed more accuracy errors and graphic difficulties than patients with Alzheimer's disease. Qualitative analysis of copy provided a sensitive measure of visual constructive abilities in differentiating dementias, underlining a particularly vulnerability of visuoconstructive functions in vascular dementia compared with Alzheimer's disease.


Assuntos
Doença de Alzheimer/diagnóstico , Apraxias/diagnóstico , Demência Vascular/diagnóstico , Testes de Estado Mental e Demência , Testes Neuropsicológicos , Percepção Visual , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Apraxias/psicologia , Área Sob a Curva , Demência Vascular/psicologia , Diagnóstico Diferencial , Feminino , Humanos , Estudos Longitudinais , Masculino , Valor Preditivo dos Testes , Pesquisa Qualitativa , Curva ROC , Reprodutibilidade dos Testes
9.
J Leukoc Biol ; 102(6): 1421-1430, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29021366

RESUMO

NO mediates a variety of physiologic processes and is considered an important intracellular messenger in different cellular systems. Because of its complex regulation and multiple molecular and cellular targets, NO provides both stimulatory and suppressive properties in the immune system. Dendritic cells (DCs) are considered the most potent APCs, whose regulation has important implications in the induction of an effective immune response. In this study, we analyzed the effect of the compound NCX 2057, a new class of NO-releasing derivatives of ferulic acid, on activation and functional properties of DCs. NCX 2057 was able to modulate the inflammatory program, the cytokines production, and the cellular life cycle but not the maturation markers and the T cells stimulatory capacity of DCs in the presence or absence of LPS. The results indicate that NCX 2057 may modulate different aspects of the activation of DCs and suggest novel applications of NO donors in the contest of inflammatory response modulation through the life cycle regulation of DCs.


Assuntos
Anti-Inflamatórios/farmacologia , Células Dendríticas/citologia , Células Dendríticas/metabolismo , Inflamação/patologia , Doadores de Óxido Nítrico/farmacologia , Animais , Apresentação do Antígeno/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Células da Medula Óssea/citologia , Butanos/farmacologia , Citocinas/biossíntese , Células Dendríticas/efeitos dos fármacos , Dinitrato de Isossorbida/análogos & derivados , Dinitrato de Isossorbida/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Nitritos/metabolismo , Nitrocompostos/farmacologia , Proteólise/efeitos dos fármacos
10.
J Pest Sci (2004) ; 90(4): 1079-1085, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28824353

RESUMO

Plants respond to insect attack by emission of volatile organic compounds, which recruit natural enemies of the attacking herbivore, constituting an indirect plant defence strategy. In this context, the egg parasitoid Trissolcus basalis is attracted by oviposition-induced plant volatiles emitted by Vicia faba plants as a consequence of feeding and oviposition by the pentatomid host Nezara viridula. However, this local tritrophic web could be affected by the recent invasion by the alien pentatomid bug Halyomorpha halys, an herbivore that shares the same environments as native pentatomid pests. Therefore, we investigated in laboratory conditions the possible impact of H. halys on the plant volatile-mediated signalling in the local tritrophic web V. faba-N. viridula-T. basalis. We found that T. basalis wasps were not attracted by volatiles induced in the plants by feeding and oviposition activities of H. halys, indicating specificity in the wasps' response. However, the parasitoid attraction towards plant volatiles emitted as a consequence of feeding and oviposition by the associated host was disrupted when host, N. viridula, and non-associated host, H. halys, were concurrently present on the same plant, indicating that invasion by the alien herbivore interferes with established semiochemical webs. These outcomes are discussed in a context of multiple herbivory by evaluating the possible influences of alien insects on local parasitoid foraging behaviour.

11.
J Geriatr Psychiatry Neurol ; 30(2): 109-121, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28073327

RESUMO

Parkinson disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor symptoms. Nonmotor symptoms include cognitive deficits and impairment in emotions recognition ability associated with loss of dopaminergic neurons in the substantia nigra and with alteration in frontostriatal circuits. In this review, we analyzed the studies on social cognition ability in patients with PD. We searched on PubMed and Web of Science databases and screening references of included studied and review articles for additional citations. From initial 260 articles, only 18 met search criteria. A total of 496 patients were compared with 514 health controls, through 16 different tests that assessed some subcomponents of social cognition, such as theory of mind, decision-making, and emotional face recognition. Studies on cognitive function in patients with PD have focused on executive function. Patients with PD showed impairment in social cognition from the earliest stages of disease. This ability seems to not be significantly associated with other cognitive functions.


Assuntos
Sintomas Afetivos/etiologia , Transtornos Cognitivos/etiologia , Cognição/fisiologia , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Comportamento Social , Adulto , Idoso , Transtornos Cognitivos/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
12.
Neurol Sci ; 38(4): 553-562, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28101762

RESUMO

Migraine is considered a disabling disorder with highly prevalence in population. Recent studies report that migraine patients have a cognitive decline associated to structural brain alterations. We search on PubMed and Web of Science databases and screening references of included studies and review articles for additional citations. From 519 studies identified, only 16 met the inclusion criteria. All studies were conducted on 1479 migraineurs (190 non-migraine headache and 11,978 controls subject) and examined the association between migraine and cognitive impairment. The results are discordant. Indeed, while cognitive deficits during the attack of migraine are now recognized, only few studies confirmed the presence of cognitive impairment in migraine patients. Given the prevalence of migraine in the population (especially among women), and the early age of the population, an association between migraine and cognitive impairment could have substantial public health implications. Future studies should determine if specific migraine characteristics, for example, attack frequency, may impact the association between migraine and cognitive decline.


Assuntos
Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/psicologia , Testes Neuropsicológicos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Humanos , Transtornos de Enxaqueca/complicações
13.
Oncotarget ; 8(8): 13652-13665, 2017 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-28099143

RESUMO

Success of dendritic cell (DC) therapy in treating malignancies is depending on the DC capacity to attract immune effector cells, considering their reciprocal crosstalk is partially regulated by cell-contact-dependent mechanisms. Although critical for therapeutic efficacy, immune cell recruitment is a largely overlooked aspect regarding optimization of DC vaccination. In this paper we have made a head-to-head comparison of interleukin (IL)-15-cultured DCs and conventional IL-4-cultured DCs with regard to their proficiency in the recruitment of (innate) immune effector cells. Here, we demonstrate that IL-4 DCs are suboptimal in attracting effector lymphocytes, while IL15 DCs provide a favorable chemokine milieu for recruiting CD8+ T cells, natural killer (NK) cells and gamma delta (γδ) T cells. Gene expression analysis revealed that IL-15 DCs exhibit a high expression of chemokines involved in antitumor immune effector cell attraction, while IL-4 DCs display a more immunoregulatory profile characterized by the expression of Th2 and regulatory T cell-attracting chemokines. This is confirmed by functional data indicating an enhanced recruitment of granzyme B+ effector lymphocytes by IL-15 DCs, as compared to IL-4 DCs, and subsequent superior killing of tumor cells by the migrated lymphocytes. Elevated CCL4 gene expression in IL-15 DCs and lowered CCR5 expression on both migrated γδ T cells and NK cells, led to validation of increased CCL4 secretion by IL15 DCs. Moreover, neutralization of CCR5 prior to migration resulted in an important inhibition of γδ T cell and NK cell recruitment by IL-15 DCs. These findings further underscore the strong immunotherapeutic potential of IL-15 DCs.


Assuntos
Células Dendríticas/imunologia , Imunoterapia Adotiva/métodos , Interleucina-15/imunologia , Células Matadoras Naturais/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Movimento Celular/imunologia , Quimiocinas/genética , Quimiocinas/imunologia , Expressão Gênica , Humanos , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Proteínas de Transporte Vesicular/imunologia
14.
Pharmacogenet Genomics ; 27(2): 51-56, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27922550

RESUMO

OBJECTIVE: We investigated the association of single nucleotide polymorphisms (SNPs) in drug-metabolizing enzymes and transporters (DMETs) with the response to azathioprine (AZA) in patients affected by myasthenia gravis (MG) to determine possible genotype-phenotype correlations. PATIENTS AND METHODS: Genomic DNA from 180 AZA-treated MG patients was screened through the Affymetrix DMET platform, which characterizes 1931 SNPs in 225 genes. The significant SNPs, identified to be involved in AZA response, were subsequently validated by allelic discrimination and direct sequencing. SNP analysis was carried out using the SNPassoc R package and the haploblocks were determined using haploview software. RESULTS: We studied 127 patients in the discovery phase and 53 patients in the validation phase. We showed that two SNPs (rs8058694 and rs8058696) found in ATP-binding cassette subfamily C member 6, a subfamily member of ATP-binding cassette genes, constituted a new haplotype associated with AZA response in MG patients in the discovery cohort (P=0.011; odds ratio: 0.40; 95% confidence interval: 0.20-0.83) and in the combined cohort (P=0.04; odds ratio: 1.58). CONCLUSION: These findings highlight the role that the ATP-binding cassette subfamily C member 6 haplotype may play in AZA drug response. In view of the significant effects and AZA intolerance, these novel SNPs should be taken into consideration in pharmacogenetic profiling for AZA.


Assuntos
Azatioprina/administração & dosagem , Estudos de Associação Genética/métodos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Miastenia Gravis/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Azatioprina/farmacocinética , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/genética , Variantes Farmacogenômicos , Análise de Sequência de DNA
15.
Sci Rep ; 6: 33900, 2016 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-27652524

RESUMO

In vertebrates, microorganisms are recognized by pathogen recognition receptors (PRRs). Exposure of immune cells to the ligands of these receptors activates intracellular signaling cascades that rapidly induce the expression of a variety of genes. Within these genes, the cytokines family plays a crucial function because of its role in adaptive immunity induction and in tissue-specific functional regulation, such as tissue repair and tissue homeostasis during steady state conditions. Within the myeloid compartment, dendritic cells (DCs) release a variety of inflammatory cytokines in response to microbes. In this study, we show that BMDCs release IL-22 directly upon PRRs activation without the need of IL-23 signaling as reported for other IL22-producing cells. Moreover, we demonstrate that cytokine IL-22 is rapidly released in a cell-specific manner as macrophages are not able to produce IL-22 through the same PRRs system. In addition, we characterize the intracellular signaling cascade required for IL-22 release in BMDCs. Myd88, MEK1/2, NFkb and AhR, but not p38, NFAT, and RORgt, were found to be involved in IL-22 regulation in DCs. Our study suggests that BMDCs possess a unique intracellular molecular plasticity which, once activated, directs different BMDCs functions in a cell-specific manner.

16.
Vet Ital ; 52(2): 139-44, 2016 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-27393875

RESUMO

Wild birds have been considered to be reservoirs of enteric human pathogens and vectors of resistance dissemination to the environment. During annual migration, they potentially play a role in the epidemiology of human associated zoonoses. The aim of this study was to investigate the frequency of isolation and antimicrobial susceptibility profiles of Enterobacteriaceae members isolated from cloacal swabs of common European wild birds. Fifty-five cloacal swabs were taken during birds' entrance evaluation in a rescue centre for injured wild birds in the Province of Messina (Sicily, Italy). All samples were examined for the presence of members of the family Enterobacteriaceae using standard methods and on the isolated strains antibiotic susceptibility testing was performed. Eighty three Enterobacteriaceae strains were isolated from raptors, waterbirds and passerines. The bacterial species isolated were: Escherichia coli, Proteus mirabilis, Proteus vulgaris, Citrobacter freundii, Enterobacter cloacae, Klebsiella oxytoca, Salmonella Typhimurium, Escherichia vulneris, Enterobacter amnigenus biogroup 2, Salmonella Duesseldorf and Hafnia alvei. The isolates showed significant frequencies of antibiotic resistance. Multiresistance to three or more groups of antibiotics also occurred. None of them have shown a phenotypic Extended Spectrum Beta Lactamase (ESBL) profile.


Assuntos
Aves/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificação , Animais , Animais Selvagens , Farmacorresistência Bacteriana , Europa (Continente) , Microbioma Gastrointestinal
17.
Front Immunol ; 7: 191, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27252700

RESUMO

Mycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. We show here that both effects are mediated by Toll-like receptor 2 (Tlr2), by exploiting a previously characterized Tlr2 variant (Met82Ile). Tlr2 82ile promoted self-specific proinflammatory polarization as well as expansion of ag-specific FoxP3(+) Tregs, while Tlr2 82met impairs the expansion of Tregs and reduces the production of IFN-γ and IL-17 proinflammatory cytokines. Preferential dimerization with Tlr1 or Tlr6 could not explain these differences. In silico, we showed that Tlr2 variant Met82Ile modified the binding pocket for peptidoglycans and participated directly to a putative binding pocket for sugars and cadherins. The distinct pro- and anti-inflammatory actions impacted severity, extent of remission, and distribution of the lesions within the central nervous system of experimental autoimmune encephalomyelitis. Thus, Tlr2 has a janus function in vivo as mediator of the role of bacterial products in balancing pro- and anti-inflammatory immune responses.

18.
Cancer Res ; 74(6): 1833-44, 2014 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-24599129

RESUMO

The stem cell-determining transcription factor Sox2 is required for the maintenance of normal neural stem cells. In this study, we investigated the requirement for Sox2 in neural cancer stem-like cells using a conditional genetic deletion mutant in a mouse model of platelet-derived growth factor-induced malignant oligodendroglioma. Transplanting wild-type oligodendroglioma cells into the brain generated lethal tumors, but mice transplanted with Sox2-deleted cells remained free of tumors. Loss of the tumor-initiating ability of Sox2-deleted cells was reversed by lentiviral-mediated expression of Sox2. In cell culture, Sox2-deleted tumor cells were highly sensitive to differentiation stimuli, displaying impaired proliferation, increased cell death, and aberrant differentiation. Gene expression analysis revealed an early transcriptional response to Sox2 loss. The observed requirement of oligodendroglioma stem cells for Sox2 suggested its relevance as a target for therapy. In support of this possibility, an immunotherapeutic approach based on immunization of mice with SOX2 peptides delayed tumor development and prolonged survival. Taken together, our results showed that Sox2 is essential for tumor initiation by mouse oligodendroglioma cells, and they illustrated a Sox2-directed strategy of immunotherapy to eradicate tumor-initiating cells.


Assuntos
Neoplasias Encefálicas/metabolismo , Células-Tronco Neoplásicas/fisiologia , Oligodendroglioma/metabolismo , Fatores de Transcrição SOXB1/fisiologia , Animais , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Vacinas Anticâncer , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Imunoterapia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Oligodendroglioma/imunologia , Oligodendroglioma/patologia , Oligodendroglioma/terapia , Fragmentos de Peptídeos/imunologia , Fatores de Transcrição SOXB1/imunologia , Transcriptoma , Células Tumorais Cultivadas
19.
J Autoimmun ; 52: 53-63, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24405842

RESUMO

Myasthenia gravis (MG) is an autoimmune disease in which the thymus frequently presents follicular hyperplasia and signs of inflammation and T cells display a defect in suppressive regulation. Defects in a suppressive assay can indicate either the defective function of Treg cells or the resistance of Tconv cells to suppression by Treg cells. The aim of this study was to determine which cells were responsible for this defect and to address the mechanisms involved. We first performed cross-experiment studies using purified thymic Treg cells and Tconv cells from controls (CTRL) and MG patients. We confirmed that MG Treg cells were defective in suppressing CTRL Tconv proliferation, and we demonstrated for the first time that MG Tconv cells were resistant to Treg cell suppression. The activation of MG Tconv cells triggered a lower upregulation of FoxP3 and a higher upregulation of CD4 and CD25 than CTRL cells. To investigate the factors that could explain these differences, we analyzed the transcriptomes of purified thymic Treg and Tconv cells from MG patients in comparison to CTRL cells. Many of the pathways revealed by this analysis are involved in other autoimmune diseases, and T cells from MG patients exhibit a Th1/Th17/Tfh signature. An increase in IL-17-related genes was only observed in Treg cells, while increases in IFN-γ, IL-21, and TNF-α were observed in both Treg and Tconv cells. These results were confirmed by PCR studies. In addition, the role of TNF-α in the defect in Tconv cells from MG patients was further confirmed by functional studies. Altogether, our results indicate that the immunoregulatory defects observed in MG patients are caused by both Treg cell and Tconv cell impairment and involve several pro-inflammatory cytokines, with TNF-α playing a key role in this process. The chronic inflammation present in the thymus of MG patients could provide an explanation for the escape of thymic T cells from regulation in the MG thymus.


Assuntos
Miastenia Gravis/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Adolescente , Adulto , Antígenos CD4/metabolismo , Células Cultivadas , Criança , Pré-Escolar , Feminino , Fatores de Transcrição Forkhead/metabolismo , Perfilação da Expressão Gênica , Humanos , Tolerância Imunológica , Lactente , Recém-Nascido , Mediadores da Inflamação/metabolismo , Interleucina-17/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
20.
Vet Ophthalmol ; 16(2): 89-92, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22520064

RESUMO

OBJECTIVE: To describe the bacterial flora present in the normal conjunctiva of donkeys from Sicily (Italy). ANIMALS STUDIED: A total of 46 healthy donkeys housed in 3 locations within the territory of Palermo (Sicily, Italy) were studied. Donkeys ranged from 2 to 13 years of age, with a median age of 6 years. PROCEDURES: Forty-six conjunctival swabs were obtained from both eyes of each animal, and specimens were cultured for aerobic bacteria. Furthermore, the antimicrobial activity of methicillin (1 µg) and oxacillin (5 µg) on Staphylococcus spp. isolates was evaluated, and a specific PCR assay, which allows the detection of mecA gene specific for methicillin-resistant Staphylococcus aureus (MRSA) strains, was performed. RESULTS: Forty of 46 (86.9%) donkeys were positive for bacteria. Eighty bacterial isolates, representing 9 bacteria genera, were successfully cultured. The most frequently recovered bacterial genus was Staphylococcus (52/80 isolates; 65%). Several strains (20/80 isolates; 25%) belonging to the Enterobacteriaceae family were also isolated, among which the most frequently isolated genus was Enterobacter (eight isolates). Of the 52 Staphylococcus spp. isolates, 14 (26.9%) strains were oxacillin/methicillin resistant. The mecA gene was detected in 6/52 (11.5%) strains. CONCLUSIONS: This study contributes to the knowledge about normal ocular flora and MRSA occurrence in donkey farms in Sicily.


Assuntos
Antibacterianos/farmacologia , Túnica Conjuntiva/microbiologia , Equidae , Resistência a Meticilina , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Meticilina/farmacologia , Animais , Feminino , Itália/epidemiologia , Masculino
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