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1.
Methods Mol Biol ; 2206: 143-150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32754816

RESUMO

Pericytes are integral part of neurovascular unit and play a role in the maintenance of blood-brain barrier integrity, angiogenesis, and cerebral blood flow regulation. Despite their important functional roles, a univocal phenotypic identification is still emerging also for the lack of a "pan-pericyte" marker. In the present study, we describe in detail the method for performing fluorescence immunohistochemistry on thick free-floating sections from human fetal brain in high resolution laser confocal microscopy. This method enables to obtain three-dimensional images of pericytes and provides insights about their distribution and localization in the microvessels of human developing brain.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32911543

RESUMO

OBJECTIVE: Dysphagia is a life-threating manifestation of idiopathic inflammatory myopathies (IIM). However, we lack a univocal protocol for its treatment. The aim of this retrospective analysis was to evaluate the effectiveness of a step-up strategy by adding a 1-day pulse of IVIGs to immunosuppressants in IIM patients with refractory dysphagia diagnosed by Eating Assessment Tool (EAT)-10 and fibreoptic endoscopic evaluation of swallowing (FEES). METHODS: Dysphagia was defined as a pharyngo-oesophageal disturbance associated with EAT-10 score ≥3 and at least one FEES abnormality among propulsion failure, solid or liquid stasis. Eighteen out of 154 IIM patients had FEES-confirmed dysphagia and underwent 1 day IVIG 2 g/kg repeated 1 month apart for 3 months, because of dysphagia refractory to high-dose glucocorticoids with methotrexate and/or azathioprine. Clinical characteristics along with myositis-specific antibodies and muscle histopathological findings were studied in FEES-dysphagia IIM and IIM control patients. RESULTS: After three monthly doses of IVIG, EAT-10 score dropped with complete recover of defective propulsion and progressive decrease in percentage of both solid and liquid stasis. At 52-weeks' follow-up, reached in 12 patients, all these parameters were stable or further improved. An improvement in manual muscle strength test and a steroid-sparing effect of IVIG were also observed. Anti-PM/Scl 75/100 antibodies were much more frequent in the FEES-dysphagia group, while anti-Jo1 antibody was rarely detected. CONCLUSION: Our treatment schedule with 2 g/kg IVIG was effective for IIM-associated refractory dysphagia assessed by the combination of EAT-10 and FEES. These findings need to be prospectively tested in a larger cohort of IIM patients.

3.
IBRO Rep ; 9: 164-182, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32803016

RESUMO

Vanadium, a transition series metal released during some industrial activities, induces oxidative stress and lipid peroxidation. Ameliorative effect of a pure compound from the methanolic extract of Moringa oleifera leaves, code-named MIMO2, in 14-day old mice administered with vanadium (as sodium metavanadate 3 mg/kg) for 2 weeks was assessed. Results from body weight monitoring, muscular strength, and open field showed slight reduction in body weight and locomotion deficit in vanadium-exposed mice, ameliorated with MIMO2 co-administration. Degeneration of the Purkinje cell layer and neuronal death in the hippocampal CA1 region were observed in vanadium-exposed mice and both appeared significantly reduced with MIMO2 co-administration. Demyelination involving the midline of the corpus callosum, somatosensory and retrosplenial cortices was also reduced with MIMO2. Microglia activation and astrogliosis observed through immunohistochemistry were also alleviated. Immunohistochemistry for myelin, axons and oligodendrocyte lineage cells were also carried out and showed that in vanadium-treated mice brains, oligodendrocyte progenitor cells increased NG2 immunolabelling with hypertrophy and bushy, ramified appearance of their processes. MIMO2 displayed ameliorative and antioxidative effects in vanadium-induced neurotoxicity in experimental murine species. This is likely the first time MIMO2 is being used in vivo in an animal model.

4.
Microchem J ; 157: 104928, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: covidwho-155253

RESUMO

The highest risk of novel coronavirus SARS-CoV-2 to be spread through human-to-human transmission has boosted the use of personal protective equipment at worldwide level. In Europe, the medical face masks must be tested to certify the essential requirements in agreement with European Standard EN 14683:2019, and face masks for industrial use in agreement with European Standard EN 149:2009. Due to the need of large quantitative of medical and non-medical face masks in coronavirus outbreak, several Italian industries are working for shift a portion of their manufacturing capacity for producing medical and non-medical face mask. For screening evaluation of the effectiveness of personal protective equipment produced by reconverted industries, ARPA Lazio and the Department of Chemical Science and Technologies of Tor Vergata University have set-up an analytical system able to simulate the respiratory action and to measure the percentage of particles that pass through the face masks using optical particle counter (based on the EN 16890: 2017 that uses the same light scattering principle to evaluate the filter filtration efficiency). This set-up was challenged using face masks produced by reconverted industries and the data were compared with ones obtained using medical face mask.

5.
Microchem J ; 157: 104928, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32501301

RESUMO

The highest risk of novel coronavirus SARS-CoV-2 to be spread through human-to-human transmission has boosted the use of personal protective equipment at worldwide level. In Europe, the medical face masks must be tested to certify the essential requirements in agreement with European Standard EN 14683:2019, and face masks for industrial use in agreement with European Standard EN 149:2009. Due to the need of large quantitative of medical and non-medical face masks in coronavirus outbreak, several Italian industries are working for shift a portion of their manufacturing capacity for producing medical and non-medical face mask. For screening evaluation of the effectiveness of personal protective equipment produced by reconverted industries, ARPA Lazio and the Department of Chemical Science and Technologies of Tor Vergata University have set-up an analytical system able to simulate the respiratory action and to measure the percentage of particles that pass through the face masks using optical particle counter (based on the EN 16890: 2017 that uses the same light scattering principle to evaluate the filter filtration efficiency). This set-up was challenged using face masks produced by reconverted industries and the data were compared with ones obtained using medical face mask.

6.
Eur J Pain ; 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32478943

RESUMO

BACKGROUND: Fibromyalgia (FM) is a syndrome characterized by altered pain processing at central and peripheral level, whose pathophysiologic mechanisms remain obscure. We aimed at exploring the structural changes of peripheral nociceptor measured by skin biopsy, the functional changes of central nociceptive pathway assessed by laser-evoked potentials (LEP), and their correlation with clinical features and comorbidities. METHODS: In all, 81 patients diagnosed with FM underwent skin biopsies with quantification of intraepidermal nerve fibre density (IENFD) at the thigh and distal leg, and LEP recording by stimulating hand, thigh and foot. Nerve conduction study (NCS), clinical features, comorbidity with migraine and mood disorders, and previous, non-active immune-mediated disorders were recorded. RESULTS: Intraepidermal nerve fibre density was reduced in 85% of patients at the thigh and in 12.3% of patients at the distal leg, whereas it was normal in 14.8% of patients. N2P2 habituation index from laser stimulation at the thigh was altered in 97.5% of patients and correlated with reduced IENFD at the thigh. LEP latencies and amplitudes did not differ among groups. No association was found between IENFD, LEP, clinical features and comorbidities. CONCLUSIONS: Fibromyalgia patients most commonly showed a mild loss of peripheral nociceptors at the thigh rather than distal small fibre neuropathy. This finding was associated with an altered habituation index and strengthened the hypothesis that central sensitization plays a key role in the pathogenesis of the disease. SIGNIFICANCE: Central impairment of pain processing likely underlies FM, which in most patients is associated with mild proximal small fibre pathology.

7.
Curr Pharm Des ; 26(13): 1428-1437, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32186270

RESUMO

P-Glycoprotein (P-gp) is a 170-kDa transmembrane glycoprotein that works as an efflux pump and confers multidrug resistance (MDR) in normal tissues and tumors, including nervous tissues and brain tumors. In the developing telencephalon, the endothelial expression of P-gp, and the subcellular localization of the transporter at the luminal endothelial cell (EC) plasma membrane are early hallmarks of blood-brain barrier (BBB) differentiation and suggest a functional BBB activity that may complement the placental barrier function and the expression of P-gp at the blood-placental interface. In early fetal ages, P-gp has also been immunolocalized on radial glia cells (RGCs), located in the proliferative ventricular zone (VZ) of the dorsal telencephalon and now considered to be neural progenitor cells (NPCs). RG-like NPCs have been found in many regions of the developing brain and have been suggested to give rise to neural stem cells (NSCs) of adult subventricular (SVZ) neurogenic niches. The P-gp immunosignal, associated with RG-like NPCs during cortical histogenesis, progressively decreases in parallel with the last waves of neuroblast migrations, while 'outer' RGCs and the deriving astrocytes do not stain for the efflux transporter. These data suggest that in human glioblastoma (GBM), P-gp expressed by ECs may be a negligible component of tumor MDR. Instead, tumor perivascular astrocytes may dedifferentiate and resume a progenitor-like P-gp activity, becoming MDR cells and contribute, together with perivascular P-gpexpressing glioma stem-like cells (GSCs), to the MDR profile of GBM vessels. In conclusion, the analysis of Pgp immunolocalization during brain development may contribute to identify the multiple cellular sources in the GBM vessels that may be involved in P-gp-mediated chemoresistance and can be responsible for GBM therapy failure and tumor recurrence.

8.
Cognition ; 195: 104111, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31731115

RESUMO

The Spatial-Numerical Association of Response Codes (SNARC) effect suggests that numbers are represented along a horizontal left-to-right oriented, mental number line, with small numbers on the left and large numbers on the right. Much less evidence exists for vertical (down-to-up) and sagittal (near-to-far) SNARC effects. This might be due to the employment of different experimental paradigms among studies and to the, sometimes, inexact definition of the vertical and sagittal axes. We investigated for the first time the SNARC effect along the horizontal, vertical, and sagittal axes, by means of a classic SNARC task. Our results suggest the presence of three equally-strong SNARC effects. Our findings can be considered as evidence in favor of a three-dimensional, mental representation of numbers, in the form of a mental number space, defined by Cartesian coordinates.

9.
Muscle Nerve ; 60(3): 315-327, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31172530

RESUMO

INTRODUCTION: The molecular mechanism of immune-mediated necrotizing myopathy (IMNM) remains unknown. Autophagy impairment, described in autoimmune diseases, is a key process in myofiber protein degradation flux and muscle integrity and has not been studied in IMNM. METHODS: Muscle biopsies from patients with IMNM (n = 40), dermatomyositis (DM; 24), polymyositis (PM; 8), polymyositis with mitochondrial pathology (4), sporadic inclusion body myositis (8), and controls (6) were compared by immunohistochemistry. RESULTS: The proportions of myofibers containing autophagy markers LC3b and p62 were higher in IMNM than in DM or PM and correlated with creatine kinase levels. In IMNM, compartmentalized LC3b puncta were located in regenerating and degenerating myofibers surrounded by major histocompatibility complex type II+ inflammatory cells. Several IMNM myofibers accumulated ubiquitin and misfolded protein. DISCUSSION: The detection of LC3b+ or p62+ myofibers could be used in differentiating IMNM from PM. The identification of autophagy-modifying molecules potentially could improve patients' outcomes. Muscle Nerve, 2019.


Assuntos
Autofagia/imunologia , Músculo Esquelético/patologia , Miosite/imunologia , Miosite/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Biópsia , Dermatomiosite/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miosite de Corpos de Inclusão/patologia , Polimiosite/imunologia , Polimiosite/patologia
10.
PLoS One ; 14(3): e0213508, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30870435

RESUMO

During experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis associated with blood-brain barrier (BBB) disruption, oligodendrocyte precursor cells (OPCs) overexpress proteoglycan nerve/glial antigen 2 (NG2), proliferate, and make contacts with the microvessel wall. To explore whether OPCs may actually be recruited within the neurovascular unit (NVU), de facto intervening in its cellular and molecular composition, we quantified by immunoconfocal morphometry the presence of OPCs in contact with brain microvessels, during postnatal cerebral cortex vascularization at postnatal day 6, in wild-type (WT) and NG2 knock-out (NG2KO) mice, and in the cortex of adult naïve and EAE-affected WT and NG2KO mice. As observed in WT mice during postnatal development, a higher number of juxtavascular and perivascular OPCs was revealed in adult WT mice during EAE compared to adult naïve WT mice. In EAE-affected mice, OPCs were mostly associated with microvessels that showed altered claudin-5 and occludin tight junction (TJ) staining patterns and barrier leakage. In contrast, EAE-affected NG2KO mice, which did not show any significant increase in vessel-associated OPCs, seemed to retain better preserved TJs and BBB integrity. As expected, absence of NG2, in both OPCs and pericytes, led to a reduced content of vessel basal lamina molecules, laminin, collagen VI, and collagen IV. In addition, analysis of the major ligand/receptor systems known to promote OPC proliferation and migration indicated that vascular endothelial growth factor A (VEGF-A), platelet-derived growth factor-AA (PDGF-AA), and the transforming growth factor-ß (TGF-ß) were the molecules most likely involved in proliferation and recruitment of vascular OPCs during EAE. These results were confirmed by real time-PCR that showed Fgf2, Pdgfa and Tgfb expression on isolated cerebral cortex microvessels and by dual RNAscope-immunohistochemistry/in situ hybridization (IHC/ISH), which detected Vegfa and Vegfr2 transcripts on cerebral cortex sections. Overall, this study suggests that vascular OPCs, in virtue of their developmental arrangement and response to neuroinflammation and growth factors, could be integrated among the classical NVU cell components. Moreover, the synchronized activation of vascular OPCs and pericytes during both BBB development and dysfunction, points to NG2 as a key regulator of vascular interactions.


Assuntos
Antígenos/biossíntese , Barreira Hematoencefálica/metabolismo , Encefalomielite Autoimune Experimental/metabolismo , Microvasos/metabolismo , Oligodendroglia/metabolismo , Proteoglicanas/biossíntese , Células-Tronco/metabolismo , Animais , Antígenos/genética , Barreira Hematoencefálica/patologia , Movimento Celular/genética , Proliferação de Células/genética , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Claudina-5/genética , Claudina-5/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/patologia , Camundongos , Camundongos Knockout , Microvasos/patologia , Oligodendroglia/patologia , Fator de Crescimento Derivado de Plaquetas/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteoglicanas/genética , Células-Tronco/patologia , Junções Íntimas/genética , Junções Íntimas/metabolismo , Junções Íntimas/patologia , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
Acta Biomed ; 90(1): 51-55, 2019 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-30889155

RESUMO

BACKGROUND: Management of neuropathic pain (Neu P) is complex and difficult. Although there are several therapeutic options, treatment with Neu P is often inadequate, which led to undertreated patients. Thus, it would be desirable, for Neu P treatment, further multimechanistics approaches. OBJECTIVE: The aim of the present study was to evaluate, in Neu P management, the effectiveness of "FISIONERV, a gel for topical use. SETTING: This study was conducted in the "Rehabilitation Unit of N. Melli's Hospital, Brindisi, Italy". PATIENTS AND INTERVENTION: In this study a double- blind randomized controlled clinical trial was conducted over 8-week treatment on 58 outpatients affected by Neu P caused by lumbar sciatica or lumbar disk herniation and/or lumbar canal stenosis (31 subjects), or with carpal tunnel syndrome (27 subjects), randomly assigned to the following two groups: Group A; n=29, received (fisionerv® gel, 3 times/day) added to physiotherapy (forty minutes-daily session). Group B; n=29 received a vehicle gel (placebo, 3 times/day) added to physiotherapy (forty minutes-daily session). MEASUREMENTS: Pain was assessed by a visual analogue scale (VAS). Neuropathic symptoms frequency (pain, burning, paraesthesiae and numbness) were scored at baseline and at the end of the treatment. Treatment compliance and safety were also evaluated. RESULTS: Both groups experienced a significant reduction in VAS and neuropathic symptoms after 8-treatment weeks. However, a significant (p<0.05) improvement was observed in group A (VAS mean 5.3 (1.10) with respect to group B (VAS mean=6.17 (0.80), already after 4 weeks of treatment. A further VAS reduction was recorded at 8 treatment weeks, with significant difference between the treatments (group A: VAS mean=1.89 (0.77); group B: VAS mean=3.79 (1.20) (p<0.001). In addition, more patients of the group A, than in group B, reported an improvement of their neurophatc pain (p<0.01). No adverse drug reaction was observed. CONCLUSION: Use of fisionerv®, in combination with physiotherapy, resulted a useful approach to NP treatment. CLINICAL REHABILITATION IMPACT: These preliminary observations suggest that some interesting goals (better pain control and physical wellbeing) could be achieved by a multimodal therapy in NP patients.


Assuntos
Neuralgia/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modalidades de Fisioterapia , Escala Visual Analógica
12.
Fluids Barriers CNS ; 15(1): 28, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30290761

RESUMO

BACKGROUND: Nanotubular structures, denoted tunneling nanotubes (TNTs) have been described in recent times as involved in cell-to-cell communication between distant cells. Nevertheless, TNT-like, long filopodial processes had already been described in the last century as connecting facing, growing microvessels during the process of cerebral cortex vascularization and collateralization. Here we have investigated the possible presence and the cellular origin of TNTs during normal brain vascularization and also in highly vascularized brain tumors. METHODS: We searched for TNTs by high-resolution immunofluorescence confocal microscopy, applied to the analysis of 20-µm, thick sections from lightly fixed, unembedded samples of both developing cerebral cortex and human glioblastoma (GB), immunolabeled for endothelial, pericyte, and astrocyte markers, and vessel basal lamina molecules. RESULTS: The results revealed the existence of pericyte-derived TNTs, labeled by proteoglycan NG2/CSPG4 and CD146. In agreement with the described heterogeneity of these nanostructures, ultra-long (> 300 µm) and very thin (< 0.8 µm) TNTs were observed to bridge the gap between the wall of distant vessels, or were detected as short (< 300 µm) bridging cables connecting a vessel sprout with its facing vessel or two apposed vessel sprouts. The pericyte origin of TNTs ex vivo in fetal cortex and GB was confirmed by in vitro analysis of brain pericytes, which were able to form and remained connected by typical TNT structures. CONCLUSIONS: None of the multiple roles described for TNTs can be excluded from a possible involvement during the processes of both normal and pathological vessel growth. A possible function, suggested by the pioneering studies made during cerebral cortex vascularization, is in cell searching and cell-to-cell recognition during the processes of vessel collateralization and vascular network formation. According to our results, it is definitely the pericyte-derived TNTs that seem to actively explore the surrounding microenvironment, searching for (site-to-site recognition), and connecting with (pericyte-to-pericyte and/or pericyte-to-endothelial cell communication), the targeted vessels. This idea implies that TNTs may have a primary role in the very early phases of both physiological and tumor angiogenesis in the brain.


Assuntos
Neoplasias Encefálicas/fisiopatologia , Córtex Cerebral/fisiopatologia , Células Endoteliais/fisiologia , Glioblastoma/fisiopatologia , Nanotubos , Neovascularização Patológica , Neovascularização Fisiológica , Pericitos/fisiologia , Adulto , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/patologia , Comunicação Celular , Células Cultivadas , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/citologia , Células Endoteliais/citologia , Feminino , Glioblastoma/irrigação sanguínea , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pericitos/citologia
13.
Nutrients ; 10(9)2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30189627

RESUMO

Human milk composition is dynamic, and substitute formulae are intended to mimic its protein content. The purpose of this study was to investigate the potentiality of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), followed by multivariate data analyses as a tool to analyze the peptide profiles of mammalian, human, and formula milks. Breast milk samples from women at different lactation stages (2 (n = 5), 30 (n = 6), 60 (n = 5), and 90 (n = 4) days postpartum), and milk from donkeys (n = 4), cows (n = 4), buffaloes (n = 7), goats (n = 4), ewes (n = 5), and camels (n = 2) were collected. Different brands (n = 4) of infant formulae were also analyzed. Protein content (<30 kDa) was analyzed by MS, and data were exported for statistical elaborations. The mass spectra for each milk closely clustered together, whereas different milk samples resulted in well-separated mass spectra. Human samples formed a cluster in which colostrum constituted a well-defined subcluster. None of the milk formulae correlated with animal or human milk, although they were specifically characterized and correlated well with each other. These findings propose MALDI-TOF MS milk profiling as an analytical tool to discriminate, in a blinded way, different milk types. As each formula has a distinct specificity, shifting a baby from one to another formula implies a specific proteomic exposure. These profiles may assist in milk proteomics for easiness of use and minimization of costs, suggesting that the MALDI-TOF MS pipelines may be useful for not only milk adulteration assessments but also for the characterization of banked milk specimens in pediatric clinical settings.


Assuntos
Fórmulas Infantis/química , Mamíferos , Proteínas do Leite/análise , Leite/química , Peptídeos/análise , Proteômica/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Animais , Camelus , Equidae , Contaminação de Alimentos , Humanos , Lactente , Recém-Nascido , Leite Humano/química , Análise Multivariada , Ruminantes
14.
Germs ; 8(2): 58-66, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29951378

RESUMO

Introduction: Yeast pathogens are emerging agents of nosocomial as well as community-acquired infections and their rapid and accurate identification is crucial for a better management of high-risk patients and for an adequate treatment. Methods: We performed a retrospective review of 156 yeast isolates collected during a 17 months' period of regular clinical practice at the Microbiology Department of San Camillo Hospital in Treviso, Italy and analyzed by the traditional culture-based method combined with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Results: Out of all the samples collected MALDI-TOF MS was able to characterize with a MT score ≥1.7 (accurate result at species level) 12 different yeast and yeast-like species from 140 samples: Candida albicans (63.7%), Candida glabrata (13.6%), Saccharomyces cerevisiae (6.5%), Candida parapsilosis (5.7%), Candida tropicalis (2.1%), Candida pararugosa (2.1%), Candida guilliermondii (2.1%), Candida kefyr (1.4%), Candida lusitaniae (0.7%), Candida palmioleophila (0.7%), Geotrichum silvicola (0.7%), Rhodotorula mucilaginosa (0.7%). Susceptibility testing toward seven common antifungal agents showed a characteristic MIC distribution of C. albicans isolates for echinocandins: particularly we noticed that 72% and 46% of C. albicans showed an MIC value close to clinical breakpoint as defined by EUCAST, respectively for anidulafungin and micafungin. Conclusion: Accurate identification of microorganisms and the study of their antifungal susceptibility allow to understand the epidemiology of a particular area, permitting the choice of the most appropriate early antifungal treatment.

15.
PLoS Negl Trop Dis ; 11(11): e0005916, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29095820

RESUMO

The human gut has been continuously exposed to a broad spectrum of intestinal organisms, including viruses, bacteria, fungi, and parasites (protozoa and worms), over millions of years of coevolution, and plays a central role in human health. The modern lifestyles of Western countries, such as the adoption of highly hygienic habits, the extensive use of antimicrobial drugs, and increasing globalisation, have dramatically altered the composition of the gut milieu, especially in terms of its eukaryotic "citizens." In the past few decades, numerous studies have highlighted the composition and role of human intestinal bacteria in physiological and pathological conditions, while few investigations exist on gut parasites and particularly on their coexistence and interaction with the intestinal microbiota. Studies of the gut "parasitome" through "omic" technologies, such as (meta)genomics, transcriptomics, proteomics, and metabolomics, are herein reviewed to better understand their role in the relationships between intestinal parasites, host, and resident prokaryotes, whether pathogens or commensals. Systems biology-based profiles of the gut "parasitome" under physiological and severe disease conditions can indeed contribute to the control of infectious diseases and offer a new perspective of omics-assisted tropical medicine.


Assuntos
Trato Gastrointestinal/parasitologia , Genômica , Interações Hospedeiro-Parasita , Metabolômica , Parasitos/fisiologia , Proteômica , Animais , Entamoeba histolytica/genética , Entamoeba histolytica/metabolismo , Microbioma Gastrointestinal , Giardia/genética , Giardia/metabolismo , Helmintos/genética , Helmintos/fisiologia , Humanos , Camundongos , Taenia solium/genética , Taenia solium/metabolismo
16.
Brain Behav Immun ; 65: 68-89, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28676349

RESUMO

When related to central nervous system (CNS) health and disease, brain mast cells (MCs) can be a source of either beneficial or deleterious signals acting on neural cells. We review the current state of knowledge about molecular interactions between MCs and glia in neurodegenerative diseases such as Multiple Sclerosis, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, Epilepsy. We also discuss the influence on MC actions evoked by the host microbiota, which has a profound effect on the host immune system, inducing important consequences in neurodegenerative disorders. Gut dysbiosis, reduced intestinal motility and increased intestinal permeability, that allow bacterial products to circulate and pass through the blood-brain barrier, are associated with neurodegenerative disease. There are differences between the microbiota of neurologic patients and healthy controls. Distinguishing between cause and effect is a challenging task, and the molecular mechanisms whereby remote gut microbiota can alter the brain have not been fully elucidated. Nevertheless, modulation of the microbiota and MC activation have been shown to promote neuroprotection. We review this new information contributing to a greater understanding of MC-microbiota-neural cells interactions modulating the brain, behavior and neurodegenerative processes.


Assuntos
Mastócitos/imunologia , Mastócitos/fisiologia , Doenças Neurodegenerativas/imunologia , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/microbiologia , Barreira Hematoencefálica/fisiologia , Encéfalo/imunologia , Comunicação Celular , Permeabilidade da Membrana Celular/imunologia , Sistema Nervoso Central/imunologia , Microbioma Gastrointestinal/imunologia , Microbioma Gastrointestinal/fisiologia , Motilidade Gastrointestinal/imunologia , Humanos , Intestinos/microbiologia , Mastócitos/microbiologia , Microbiota , Doenças Neurodegenerativas/microbiologia , Neuroglia/imunologia
17.
Acta Biomed ; 88(1): 45-48, 2017 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-28467333

RESUMO

Phenytoin is normally used in epilepsy treatment. One of the side effect affecting a significative part of the treated patients is the gingival overgrowth. It could surely be a correlation between this stimulatory effect and the assessment of phenytoin in wound healing. In fact, some studies of the literature have shown that topical phenytoin promotes healing of traumatic wounds, burns and ulcers by decubitus or stasis (diabetic or venous) and we emphasize, in vitiligo, a particular attention into repigmentation. The related mechanism of action seems to be multifactorial. In the present paper topical phenytoin has been used as wound-healing agent in 19 documented cases of bedsores, divided in treated and placebo group. The used concentration of phenytoin was 5 mg/L dissolved in a water solution of 9 g NaCl /L (0.9% P/V of NaCl). Patches soaked with phenytoin solution were applied over the bedsores along 3 hours every 12 hours. Results showed that phenytoin treated patients healed their wounds significantly before (p<0.001) with respect to controls.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Fenitoína/uso terapêutico , Lesão por Pressão/tratamento farmacológico , Adesivo Transdérmico , Administração Tópica , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cicatrização
18.
Curr Opin Allergy Clin Immunol ; 17(3): 204-211, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28403019

RESUMO

PURPOSE OF REVIEW: We review the laws on labeling in the international community, the difficulties they pose to the food manufacturers to prepare the food labels and the methodologies to determine the concentration of potential allergens in foods. RECENT FINDINGS: European Food Safety Authority and International Life Sciences Institute Europe are evaluating strategies to identify the threshold level of allergen that can trigger a reaction in individuals. The most used techniques to detect the presence of protein in food are Enzyme-linked immunosorbent assay, polymerase chain reaction and real time polymerase chain reaction. Researchers are now trying to apply proteomics to estimate the amount of protein within the food.In order to protect the health of consumers, the Codex Alimentarius Commission updates constantly the list of allergens. In response to these regulations, some industries have also added some precautionary allergen labeling (PAL). It was generally agreed that PAL statements needed to be visible, simple, and safe. It was suggested that PAL be standardized, an action that would occur if the 'Voluntary Incidental Trace Allergen Labelling' process was made mandatory. SUMMARY: So far, no laboratory technique is able to reassure the consumers about the composition of foods found on the packaging. International authorities produced increasingly stringent laws, but more is still to do.


Assuntos
Alérgenos/imunologia , Qualidade de Produtos para o Consumidor , Hipersensibilidade Alimentar/epidemiologia , Rotulagem de Alimentos , Alérgenos/análise , Europa (Continente) , Alimentos , Inocuidade dos Alimentos , Regulamentação Governamental , Humanos , Padrões de Referência
19.
Acta Neuropathol ; 132(1): 23-42, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27026411

RESUMO

In adult CNS, nerve/glial-antigen 2 (NG2) is expressed by oligodendrocyte progenitor cells (OPCs) and is an early marker of pericyte activation in pathological conditions. NG2 could, therefore, play a role in experimental autoimmune encephalomyelitis (EAE), a disease associated with increased blood-brain barrier (BBB) permeability, inflammatory infiltrates, and CNS damage. We induced EAE in NG2 knock-out (NG2KO) mice and used laser confocal microscopy immunofluorescence and morphometry to dissect the effect of NG2 KO on CNS pathology. NG2KO mice developed milder EAE than their wild-type (WT) counterparts, with less intense neuropathology associated with a significant improvement in BBB stability. In contrast to WT mice, OPC numbers did not change in NG2KO mice during EAE. Through FACS and confocal microscopy, we found that NG2 was also expressed by immune cells, including T cells, macrophages, and dendritic cells (DCs). Assessment of recall T cell responses to the encephalitogen by proliferation assays and ELISA showed that, while WT and NG2KO T cells proliferated equally to the encephalitogenic peptide MOG35-55, NG2KO T cells were skewed towards a Th2-type response. Because DCs could be responsible for this effect, we assessed their expression of IL-12 by PCR and intracellular FACS. IL-12-expressing CD11c+ cells were significantly decreased in MOG35-55-primed NG2KO lymph node cells. Importantly, in WT mice, the proportion of IL-12-expressing cells was significantly lower in CD11c+ NG2- cells than in CD11c+ NG2+ cells. To assess the relevance of NG2 at immune system and CNS levels, we induced EAE in bone-marrow chimeric mice, generated with WT recipients of NG2KO bone-marrow cells and vice versa. Regardless of their original phenotype, mice receiving NG2KO bone marrow developed milder EAE than those receiving WT bone marrow. Our data suggest that NG2 plays a role in EAE not only at CNS/BBB level, but also at immune response level, impacting on DC activation and thereby their stimulation of reactive T cells, through controlling IL-12 expression.


Assuntos
Células Dendríticas/imunologia , Encefalomielite Autoimune Experimental/imunologia , Animais , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/patologia , Células da Medula Óssea/imunologia , Transplante de Medula Óssea , Células Dendríticas/patologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Índice de Gravidade de Doença , Medula Espinal/imunologia , Medula Espinal/patologia , Linfócitos T/imunologia , Linfócitos T/patologia
20.
J Crohns Colitis ; 10(10): 1194-204, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26995183

RESUMO

BACKGROUND AND AIMS: Intestinal fibrosis is a complication of inflammatory bowel disease [IBD]. Although fibrostenosis is a rare event in ulcerative colitis [UC], there is evidence that a fibrotic rearrangement of the colon occurs in the later stages. This is a retrospective study aimed at examining the histopathological features of the colonic wall in both short-lasting [SL] and long-lasting [LL] UC. METHODS: Surgical samples of left colon from non-stenotic SL [≤ 3 years, n = 9] and LL [≥ 10 years, n = 10] UC patients with active disease were compared with control colonic tissues from cancer patients without UC [n = 12] to assess: collagen and elastic fibres by histochemistry; vascular networks [CD31/CD105/nestin] by immunofluorescence; parameters of fibrosis [types I and III collagen, fibronectin, RhoA, alpha-smooth muscle actin [α-SMA], desmin, vimentin], and proliferation [proliferating nuclear antigen [PCNA]] by western blot and/or immunolabelling. RESULTS: Colonic tissue from both SL-UC and LL-UC showed tunica muscularis thickening and transmural activated neovessels [displaying both proliferating CD105-positive endothelial cells and activated nestin-positive pericytes], as compared with controls. In LL-UC, the increased collagen deposition was associated with an up-regulation of tissue fibrotic markers [collagen I and III, fibronectin, vimentin, RhoA], an enhancement of proliferation [PCNA] and, along with a loss of elastic fibres, a rearrangement of the tunica muscularis towards a fibrotic phenotype. CONCLUSIONS: A significant transmural fibrotic thickening occurs in colonic tissue from LL-UC, together with a cellular fibrotic switch in the tunica muscularis. A full-thickness angiogenesis is also evident in both SL- and LL-UC with active disease, as compared with controls.


Assuntos
Colite Ulcerativa/patologia , Colo/patologia , Remodelação Vascular , Doença Aguda , Adulto , Idoso , Biomarcadores/metabolismo , Western Blotting , Estudos de Casos e Controles , Colo/irrigação sanguínea , Colo/metabolismo , Progressão da Doença , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Método Simples-Cego
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