RESUMO
It has been shown, in animal models, that gastrointestinal tract (GIT) motility is influenced by temperature; nevertheless, the basic mechanism governing thermal GIT smooth muscle responses has not been fully investigated. Studies based on physiologically tuned mathematical models have predicted that thermal inhomogeneity may induce an electrochemical destabilization of peristaltic activity. In the present study, the effect of thermal cooling on human colonic muscle strip (HCMS) contractility was studied. HCMSs were obtained from disease-free margins of resected segments for cancer. After removal of the mucosa and serosa layers, strips were mounted in separate chambers. After 30 min, spontaneous contractions developed, which were measured using force displacement transducers. Temperature was changed every hour (37, 34, and 31°C). The effect of cooling was analyzed on mean contractile activity, oscillation amplitude, frequency, and contraction to ACh (10(-5) M). At 37°C, HCMSs developed a stable phasic contraction (~0.02 Hz) with a significant ACh-elicited mean contractile response (31% and 22% compared with baseline in the circular and longitudinal axis, respectively). At a lower bath temperature, higher mean contractile amplitude was observed, and it increased in the presence of ACh (78% and 43% higher than the basal tone in the circular and longitudinal axis, respectively, at 31°C). A simplified thermochemomechanical model was tuned on experimental data characterizing the stress state coupling the intracellular Ca(2+) concentration to tissue temperature. In conclusion, acute thermal cooling affects colonic muscular function. Further studies are needed to establish the exact mechanisms involved to better understand clinical consequences of hypothermia on intestinal contractile activity.
Assuntos
Temperatura Baixa , Colo/fisiologia , Motilidade Gastrointestinal , Modelos Biológicos , Contração Muscular , Músculo Liso/fisiologia , Acetilcolina/farmacologia , Idoso , Cálcio/metabolismo , Resposta ao Choque Frio , Colo/efeitos dos fármacos , Colo/metabolismo , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Técnicas In Vitro , Masculino , Mecanotransdução Celular , Pessoa de Meia-Idade , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Fatores de TempoRESUMO
The differences in systemic T-cell responses between patients with psoriatic arthritis (PsA) and patients with cutaneous psoriasis (Ps) are still largely unknown. To determine differential features that could be used to distinguish PsA from Ps, we compared the cytokine secretion profile of circulating T cells in patients with PsA, patients with cutaneous Ps and control subjects. We determined Th1, Th2 and Th17 cytokine secretion of anti-CD3-stimulated peripheral blood mononuclear cells (PBMCs) using a cytokine bead array. Normality of data distribution was assessed by the Shapiro-Wilk test, and statistical significance was calculated by the Mann-Whitney test. Phenotypic characterization of circulating T cells was performed by fluorescence-activated cell sorting analysis. We found that the major systemic differences distinguishing PsA from cutaneous Ps were the increased secretion of interleukin (IL)-2 by α-CD3-stimulated PBMCs and a higher percentage of circulating CD3+ T cells expressing the proliferation marker CD71 in PsA. These results indicate IL-2 as a possible biomarker of PsA, and suggest a role of circulating T cells with high proliferative capacity in the pathogenesis of PsA.
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Artrite Psoriásica/metabolismo , Complexo CD3/imunologia , Interleucina-2/metabolismo , Leucócitos Mononucleares/metabolismo , Psoríase/metabolismo , Adolescente , Adulto , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Linfócitos T Auxiliares-Indutores/metabolismo , Adulto JovemRESUMO
Proanthocyanidins (PACs), the predominant constituents within Grape Seed Extract (GSE), are intricate compounds composed of interconnected flavan-3-ol units. Renowned for their health-affirming properties, PACs offer a shield against a spectrum of inflammation associated diseases, such as diabetes, obesity, degenerations and possibly cancer. While monomeric and dimeric PACs undergo some absorption within the gastrointestinal tract, their larger oligomeric and polymeric counterparts are not bioavailable. However, higher molecular weight PACs engage with the colonic microbiota, fostering the production of bioavailable metabolites that undergo metabolic processes, culminating in the emergence of bioactive agents capable of modulating physiological processes. Within this investigation, a GSE enriched with polymeric PACs was employed to explore in detail their impact. Through comprehensive analysis, the present study unequivocally verified the gastrointestinal-mediated transformation of medium to high molecular weight polymeric PACs, thereby establishing the bioaccessibility of a principal catabolite termed 5-(3',4'-dihydroxyphenyl)-γ-valerolactone (VL). Notably, our findings, encompassing cell biology, chemistry and proteomics, converge to the proposal of the notion of the capacity of VL to activate, upon oxidation to the corresponding quinone, the nuclear factor E2-related factor 2 (Nrf2) pathway-an intricate process that incites cellular defenses and mitigates stress-induced responses, such as a challenge brought by TNFα. This mechanistic paradigm seamlessly aligns with the concept of para-hormesis, ultimately orchestrating the resilience to stress and the preservation of cellular redox equilibrium and homeostasis as benchmarks of health.
Assuntos
Proantocianidinas , Humanos , Proantocianidinas/farmacologia , Trato Gastrointestinal/metabolismo , Colo/metabolismo , Inflamação/metabolismoRESUMO
In the present study we investigated the potential role of Toll-like receptor 4 (TLR-4) Asp299Gly and Thr399Ile polymorphisms as risk factors in the development of gastric cancer. TLR-4 Asp299Gly and Thr399Ile polymorphisms were investigated in 171 Italian patients with sporadic gastric cancer and in 151 controls. Unconditional regression (odds ratio and 95% confidence intervals) were used to investigate the association of the studied polymorphisms with gastric cancer. TLR-4 Thr399Ile polymorphism is linked with an increased susceptibility to gastric cancer (P = 0.023 and hazard ratio = 3.62). No significant association for TLR-4 Asp299Gly polymorphism was found. In the subgroup of patients with intestinal-type gastric cancer, a significant risk of gastric cancer was associated with TLR-4 Thr399Ile genotype (P = 0.006). Our results demonstrated that TLR-4 Thr399Ile polymorphism is linked with an increased susceptibility to gastric cancer. An increased risk for intestinal gastric cancer in carriers of the TLR4 Thr399Ile allele was observed. Future epidemiological studies should consider the possible interactions between proinflammatory genotypes (such as TLR and interleukin-1R polymorphisms) and other risk factors for cancer such as dietary habits and/or exposure to environmental carcinogens.
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Adenocarcinoma/genética , Polimorfismo Genético , Neoplasias Gástricas/genética , Receptor 4 Toll-Like/genética , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias Gástricas/patologiaRESUMO
Chronic intestinal pseudo-obstruction represents a cause of persistent functional intestinal failure either "secondary" to specific conditions or "chronic intestinal idiopathic pseudo-obstruction" in origin. The diagnosis is mainly clinical, supported by radiological and/or endoscopic findings excluding any mechanical cause of intestinal obstruction. We reported a case of a 39-year-old woman with chronic intestinal idiopathic pseudo-obstruction, who underwent colectomy with ileorectal anastomosis; histological examination of the surgical specimen did not reveal myogenic or neurogenic defects or other pathological abnormalities indicative of an underlying neuromuscular impairment. Because of the apparent integrity of the gut neuromuscular layer, we tested whether a functional impairment affected colonic single smooth muscle cells. Muscle cells were isolated from the right colon and their contractile response to a receptor-dependent agonist evaluated in comparison to that obtained from controls. The cell contraction induced by acetylcholine in a dose response manner was markedly decreased in the patient affected by chronic intestinal idiopathic pseudo-obstruction compared with cells from controls (percentage of cell shortening with maximal dose of acetylcholine [10(-6)M]: 10.7+/-3% versus 34.2+/-4%, respectively). The present findings indicate a specific defect of colonic smooth muscle cells likely related to an ineffective response to acetylcholine.
Assuntos
Colo/patologia , Pseudo-Obstrução do Colo/fisiopatologia , Motilidade Gastrointestinal/fisiologia , Contração Muscular/fisiologia , Músculo Liso/fisiopatologia , Acetilcolina , Adulto , Colinérgicos , Doença Crônica , Colo/efeitos dos fármacos , Colo/fisiopatologia , Pseudo-Obstrução do Colo/patologia , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Manometria , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/patologia , Pressão , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The aim of this work was to study in vivo the perilesional skin in vitiligo with a colorimetric method. METHODS: Twenty-five patients affected by vitiligo were included. For each patient, three different areas were considered: the lesional, the perilesional and the normal skin as far as 5 cm from the nearest vitiligo spot. Skin pigmentation measurements were performed with a chromameter. RESULTS: The results showed that luminance L* decreased significantly in relation to increasing distance from the vitiligo spot. As expected, L* in the vitiligo spot was significantly higher than in the perilesional (P<0.0001) and normal skin (P<0.0001). There was a small difference in L* between normal skin as far as 5 cm from the nearest vitiligo spot and perilesional skin. In contrast, the pigmentation index (b*) gradually increased from lesional to perilesional to normal skin. Furthermore, the comparison of the b* value between the normal skin as far as 5 cm from the nearest vitiligo spot was higher than perilesional skin and it was statistically significant (P<0.0001). CONCLUSION: Our results in vivo underline that the perilesional skin near the vitiligo spot is lighter than normal skin as far as 5 cm from the vitiligo spot.
Assuntos
Vitiligo/patologia , Adolescente , Adulto , Idoso , Colorimetria , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The aim of the present investigation was to better understand the pharmacokinetic profile of bilberry (Vaccinium Myrtillus) anthocyanins and the role of glucose transporters (sGLT1 and GLUT2) on their absorption. In particular, the absorption of 15 different anthocyanins contained in a standardized bilberry extract (Mirtoselect®) was measured in rats by a validated LC-ESI-MS/MS approach. The plasma concentration peak (Cmax) of 11.1ng/mL was reached after 30min and fasting condition significantly increased the bioavailability of anthocyanins by more than 7 fold in respect to fed rats. Glucose co-administration did not interfere with the overall anthocyanin uptake. Bioavailability of each anthocyanin was then estimated by comparing the relative content in plasma vs extract. The 15 anthocyanins behaved differently in term of bioavailability and both the aglycone and the sugar moiety were found to affect the absorption. For instance, arabinoside moiety was detrimental while cyanidin enhanced bioavailability. Computational studies permitted to rationalize such results, highlighting the role of glucose transporters (sGLT1 and GLUT2) in anthocyanins absorption. In particular a significant correlation was found for the 15 anthocyanins between sGLT1 and GLUT2 recognition and absorption.
Assuntos
Vaccinium myrtillus , Animais , Antocianinas , Cromatografia Líquida de Alta Pressão , Proteínas Facilitadoras de Transporte de Glucose , Extratos Vegetais , Ratos , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Changes in intestinal motility are likely to contribute to irritable bowel syndrome (IBS) pathophysiology. The aim of the study was to investigate the effects of IBS mucosal supernatants on human colonic muscle contractility. METHODS: Supernatants were obtained from biopsies of 18 IBS patients-nine with constipation (IBS-C) and nine with diarrhea-predominant IBS (IBS-D)-and nine asymptomatic subjects, used as controls. Colonic circular smooth muscle strips or isolated cells (SMC) were exposed to control or IBS supernatants. Spontaneous phasic contractions on strips and morphofunctional parameters on cells were evaluated in basal conditions and in response to acetylcholine (Ach). Incubation with IBS supernatants was also conducted in the presence of antagonists and inhibitors (namely histamine, protease and prostaglandin antagonists, nuclear factor-kappa B inhibitor, catalase, NADPH oxidase inhibitor, and the cAMP- and/or cGMP-cyclase inhibitors). KEY RESULTS: Exposure to IBS-C and IBS-D supernatants induced a significant reduction in basal tone and Ach-elicited contraction of muscle strips and a significant shortening and impairment of Ach contraction of SMCs. The NADPH oxidase inhibitor prevented the effect of supernatants, while the protease antagonist only IBS-C effect. No effect was observed with the other antagonists and inhibitors. Dilution of IBS-D supernatants partially restored the effects only on SMCs, whereas dilution of IBS-C supernatants significantly reverted the effects on muscle strips and Ach-elicited response on SMC. CONCLUSIONS & INFERENCES: Supernatants from mucosal biopsies of IBS patients reduce colonic contractility. The observed impairment was concentration dependent, likely occurring through intracellular oxidative stress damage, involving different neuromotor mechanisms depending on the IBS subtype.
Assuntos
Colo/fisiopatologia , Mucosa Intestinal/metabolismo , Secreções Intestinais , Síndrome do Intestino Irritável/fisiopatologia , Contração Muscular/fisiologia , Músculo Liso/fisiopatologia , Adulto , Idoso , Colo/metabolismo , Feminino , Seguimentos , Humanos , Mucosa Intestinal/patologia , Secreções Intestinais/metabolismo , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/patologia , Masculino , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos , Adulto JovemRESUMO
Granuloma annulare is an anatomo-clinical entity that is frequently encountered in everyday dermatological practice. We report our experience regarding 4 patients with disseminated granuloma annulare. Each patient was treated with a cycle of cyclosporine therapy for six weeks. A cycle of systemic cyclosporine therapy was started at a dose of 4 mg/kg/day for four weeks, subsequently reduced by 0.5 mg/kg/day every two weeks. The clinical picture more or less completely resolved within three weeks in all of the patients, and there were no relapses during the dose-tapering period or the following 12 months. Cyclosporine was optimally tolerated by all four patients, none of whom experienced any therapy-related side effects. Cyclosporine is a valid therapeutic option for the treatment of disseminated granuloma annulare, although we recommend its use in a protected hospital environment that facilitates patient monitoring.
Assuntos
Ciclosporina/uso terapêutico , Granuloma Anular/tratamento farmacológico , Imunossupressores/uso terapêutico , Feminino , Granuloma Anular/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pele/patologiaRESUMO
Metastable silver tungstate (ß-Ag2WO4) has attracted much attention lately because of its many potential applications. However, the synthesis of metastable phases of inorganic compounds is challenging because of the ease of transformation to the stable phase. We have overcome this challenge and have successfully synthesized ß-Ag2WO4 microcrystals using a dropwise precipitation (DP) method in aqueous media at low temperature. The microcrystals were characterized by X-ray diffraction (XRD), including powder X-ray diffraction structural determination, field-emission scanning electron microscopy (FE-SEM), and micro-Raman/ultraviolet-visible (UV-vis) diffuse reflectance spectroscopy. To complement the experimental data, we present first-principles quantum-mechanical density functional theory (DFT) calculations. Using XRD data, Raman/UV-vis data, and the determined optical band gap, together with geometric optimization calculations, we confirmed the structure of this compound. ß-Ag2WO4 has a hexagonal structure with a P63/m space group. The building blocks of the lattice comprise two types of W-O clusters, [WO4] and [WO5], coordinated to four and five O atoms, respectively, and two types of Ag-O clusters, [AgO6], and [AgO5], linked to six and five O atoms, respectively. This type of fundamental study, combining multiple experimental methods and first-principles calculations, helps to obtain a basic understanding of the local structure and bonding in the material.
RESUMO
OBJECTIVE: To evaluate whether a virtual reality workstation (Fetouch system) offering three-dimensional (3D) fetal visual and kinesthetic interaction may affect maternal stress. METHODS: Maternal-fetal visual and kinesthetic interaction was obtained through a haptic interface based on 3D reconstruction of sequencial bi-dimensional ultrasound images of the fetus. Maternal stress was assessed before and after visual/kinesthetic interaction with the fetus: 1) by using the State Trait Anxiety Inventory-Form Y (STAI) test, and 2) by measuring salivary cortisol levels. Statistical analysis was performed by paired t test and analysis of variance for repeated measures. RESULTS: After the fetal visual and kinesthetic experiences, a significant reduction was observed in anxiety (low state anxiety group, P < .0034; high state anxiety group, P < .0108), as well as in salivary cortisol concentration (P < .0004). CONCLUSION: Physical interaction with the fetus through a 3D model may reduce maternal stress.
Assuntos
Ansiedade , Relações Mãe-Filho , Estresse Psicológico , Tato , Interface Usuário-Computador , Adulto , Feminino , Humanos , Hidrocortisona/análise , Imageamento Tridimensional , Cinestesia , Entrevista Psiquiátrica Padronizada , Gravidez , Saliva/químicaAssuntos
Colagogos e Coleréticos/uso terapêutico , Vesícula Biliar/efeitos dos fármacos , Macrófagos/fisiologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Ácido Ursodesoxicólico/uso terapêutico , Adulto , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Colelitíase/diagnóstico , Feminino , Vesícula Biliar/metabolismo , Humanos , Ativação de Macrófagos , Macrófagos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismoRESUMO
BACKGROUND: Non-erosive reflux disease (NERD) patients are more sensitive than erosive esophagitis patients to weakly acidic reflux and to the presence of gas in the refluxate. Intra-esophageal acid perfusion sensitizes esophageal receptors to mechanical and chemical stimuli. METHODS: To establish whether acid sensitization plays a role in the perception of weakly acidic and mixed reflux episodes, 29 NERD patients, responders and 14 non-responders to proton pump inhibitors (PPIs), underwent pH-impedance monitoring. Non-responders repeated the study while on PPIs. To assess the effect of acid exposure on symptom perception, the time period with pH below 4 was measured in 15- and 30-minute time-windows preceding the onset of each reflux episode. KEY RESULTS: Considering weakly acidic and mixed refluxes, both in responder and non-responder patients (off PPIs), the symptomatic refluxes were preceded by a significantly higher cumulative acid exposure than the asymptomatic refluxes. In all patients, following acid reflux, the percentage of symptomatic weakly acidic reflux episodes was significantly higher than that of asymptomatic refluxes. Non-responder patients, off-treatment, were characterized by a lower proportion of weakly acidic reflux and mixed reflux episodes. In the non-responder patients on PPI, only mixed and weakly symptomatic reflux episodes were preceded by a higher cumulative acid exposure. CONCLUSIONS & INFERENCES: In NERD patients, spontaneous acid reflux enhances subsequent reflux perception, regardless of acidity or liquid/mixed composition of episodes; in non-responder patients on PPIs, only the perception of mixed and weakly acidic reflux episodes seems to be mediated by a preceding acid exposure.
Assuntos
Monitoramento do pH Esofágico , Esôfago/fisiologia , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/fisiopatologia , Azia/diagnóstico , Azia/fisiopatologia , Percepção/fisiologia , Adulto , Idoso , Feminino , Determinação da Acidez Gástrica , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The aim of the present work was to monitor the covalent modifications of human serum albumin (HSA) in end stage renal diseases (ESRD) non-diabetic patients, before and after hemodialysis (HD), by direct infusion electrospray mass spectrometry (ESI-MS). Human serum samples were collected from healthy subjects (n = 10, 20-60 yr) and age-matched ESRD patients (n = 8) before and after HD, purified by affinity chromatography and analyzed by a triple-quadrupole mass spectrometer. The deconvoluted spectra from healthy subjects were all characterized by three peaks attributed to non-glycated mercaptoalbumin (HSA-SH) and to the corresponding adducts with cysteine (HSA-Cys) and glucose (HSA-Glc); relative contents: mercaptoalbumin in both glycated and non-glycated form, HSA-SHt (74 ± 6%), HSA-Cys (26 ± 5%) and HSA-Glc (24 ± 3%). HSA isolated from ESRD patients before HD was characterized by a significant reduction of HSA-SHt (42 ± 7%), and by a concomitant increase of the HSA-Cys adduct (58 ± 7%). Hemodialysis significantly reduced the cysteinylated form (37 ± 7%) and restored HSA-SHt (63 ± 8%) in all the ESRD patients. The mechanism of thiol oxidation and cysteinylation was then studied by mass spectrometry, using LQQCPF as a model peptide and H(2)O(2) as an oxidizing agent.
Assuntos
Falência Renal Crônica/sangue , Processamento de Proteína Pós-Traducional , Diálise Renal , Albumina Sérica/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Cisteína/metabolismo , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/química , Padrões de Referência , Espectrometria de Massas por Ionização por Electrospray/normas , Adulto JovemRESUMO
BACKGROUND: Lactobacillus species might positively affect gastrointestinal motility. These Gram-positive bacteria bind Toll-like receptor 2 (TLR2) that elicits anti-inflammatory activity and exerts protective effects on damage induced by lipopolysaccharide (LPS). Whether such effect occurs in gastrointestinal smooth muscle has not been established yet. Aim of this study was to characterize the effects of Lactobacillus rhamnosus GG (LGG) and of supernatants harvested from LGG cultures on human colonic smooth muscle and to explore their protective activity against LPS-induced myogenic morpho-functional alterations. METHODS: The effects of LGG (ATCC 53103 strain) and of supernatants have been tested on both human colonic smooth muscle strips and isolated cells in the absence or presence of LPS obtained from a pathogenic strain of Escherichia coli. Their effects on myogenic morpho-functional properties, on LPS-induced NFκB activation, and on cytokine production have been evaluated. Toll-like receptor 2 expression has been analyzed by qPCR and flow cytometry. KEY RESULTS: Lactobacillus rhamnosus GG exerted negligible transient effects per se whereas it was capable of activating an intrinsic myogenic response counteracting LPS-induced alterations. In particular, both LGG and supernatants significantly reduced the LPS-induced morpho-functional alterations of muscle cells, i.e. cell shortening and inhibition of contractile response. They also hindered LPS-induced pro-inflammatory effects by decreasing pro-inflammatory transcription factor NFκB activation and pro-inflammatory cytokine IL-6 secretion, and restored the secretion levels of anti-inflammatory cytokine IL10. CONCLUSIONS & INFERENCES: Taken together these data demonstrate that LGG protects human colonic smooth muscle from LPS-induced myogenic damage and might be beneficial on intestinal motor disorders due to bacterial infection.
Assuntos
Colo/microbiologia , Lacticaseibacillus rhamnosus , Lipopolissacarídeos/toxicidade , Músculo Liso/microbiologia , Probióticos/farmacologia , Células Cultivadas , Colo/efeitos dos fármacos , Motilidade Gastrointestinal , Humanos , Músculo Liso/efeitos dos fármacosRESUMO
BACKGROUND: A distinction between symptomatic non-erosive reflux disease (NERD) and erosive esophagitis (EE) patients is supported by the presence of inflammatory response in the mucosa of EE patients, leading to a damage of mucosal integrity. To explore the underlying mechanism of this difference, we assessed inflammatory mediators in mucosal biopsies from EE and NERD patients and compared them with controls. METHODS: Nineteen NERD patients, 15 EE patients, and 16 healthy subjects underwent endoscopy after a 3-week washout from PPI or H(2) antagonists. Biopsies obtained from the distal esophagus were examined by quantitative real-time polymerase chain reaction (qPCR) and multiplex enzyme-linked immunosorbent assay for selected chemokines and lyso-PAF acetyltransferase (LysoPAF-AT), the enzyme responsible for production of platelet-activating factor (PAF). KEY RESULTS: Expression of LysoPAF-AT and multiple chemokines was significantly increased in mucosal biopsies derived from EE patients, when compared with NERD patients and healthy controls. Upregulated chemokines included interleukin 8, eotaxin-1, -2, and -3, macrophage inflammatory protein-1α (MIP-1α), and monocyte chemoattractant protein-1 (MCP-1). LysoPAF-AT and the chemokine profile in NERD patients were comparable with healthy controls. CONCLUSIONS & INFERENCES: Levels of selected cytokines and Lyso-PAF AT were significantly higher in the esophageal mucosa of EE patients compared with NERD and control patients. This difference may explain the distinct inflammatory response occurring in EE patients' mucosa. In contrast, as no significant differences existed between the levels of all mediators in NERD and control subjects, an inflammatory response does not appear to play a major role in the pathogenesis of the abnormalities found in NERD patients.
Assuntos
Quimiocinas/biossíntese , Refluxo Gastroesofágico/metabolismo , Refluxo Gastroesofágico/patologia , Fator de Ativação de Plaquetas/biossíntese , Adulto , Idoso , Biópsia , Quimiocinas/análise , Ensaio de Imunoadsorção Enzimática , Esofagite Péptica/etiologia , Esofagite Péptica/patologia , Feminino , Refluxo Gastroesofágico/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Fator de Ativação de Plaquetas/análise , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: Transient receptor potential channel vanilloid subfamily member-1 (TRPV1) may play a role in esophageal perception. TRPV1 mRNA and protein expression were examined in the esophageal mucosa of non-erosive reflux disease (NERD) and erosive esophagitis (EE) patients and correlated to esophageal acid exposure. METHODS: Seventeen NERD patients, eight EE patients and 10 healthy subjects underwent endoscopy after a 3-week washout from proton pump inhibitors or H2 antagonists. Biopsies, obtained from the distal esophagus, were used for conventional histology, for Western blot analysis and/or quantitative real-time polymerase chain reaction (qPCR). Overall 13 NERD patients, four EE patients and five controls underwent ambulatory pH-testing. KEY RESULTS: TRPV1 expression was increased in all NERD and EE patients, as measured by Western blot analysis (0.65 +/- 0.07 and 0.8 +/- 0.05 VS 0.34 +/- 0.04 in controls; P < 0.01) and by qPCR (1.98 +/- 0.21 and 2.52 +/- 0.46 VS 1.00 +/- 0.06; P < 0.01). Neutrophilic infiltration, in the mucosa, was detected only in EE patients. CONCLUSIONS & INFERENCES: Non-erosive reflux disease and EE patients presented increased TRPV1 receptors mRNA and protein, although no correlation with acid exposure was demonstrated. Increased TRPV1 in the esophageal mucosa may contribute to symptoms both in NERD and EE patients and possibly account for peripheral mechanisms responsible for esophageal hypersensitivity in NERD patients.
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Esôfago/metabolismo , Esôfago/patologia , Refluxo Gastroesofágico/genética , Canais de Cátion TRPV/genética , Adulto , Idoso , Western Blotting , Monitoramento do pH Esofágico , Esofagoscopia , Feminino , Ácido Gástrico , Refluxo Gastroesofágico/patologia , Expressão Gênica , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Mucosa/metabolismo , Mucosa/patologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
Psoriasis is an immune-mediated disease with a chronic relapsing course, and the particularly severe forms that are refractory to traditional therapies are often difficult to manage. Everolimus (Certican; Novartis, Basel, Switzerland) is a new rapamycin-derived macrolide that is used in the prophylaxis of rejection in heart and kidney transplant patients. The mechanism underlying its immunosuppressant and antiproliferative activity is different from, but complementary to, that of calcineurin inhibitors such as ciclosporin. We describe a woman with severe psoriasis treated with everolimus combined with subtherapeutic doses of ciclosporin.
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Ciclosporina/uso terapêutico , Imunossupressores/uso terapêutico , Psoríase/tratamento farmacológico , Sirolimo/análogos & derivados , Sinergismo Farmacológico , Quimioterapia Combinada , Everolimo , Feminino , Humanos , Pessoa de Meia-Idade , Sirolimo/uso terapêutico , Resultado do TratamentoRESUMO
A new molecule-based weak ferromagnet of formula Fe[C6H5PO3].H2O was synthesized. It was characterized by thermogravimetric analysis and UV-visible and infrared spectroscopy, and the magnetic properties were studied using a superconducting quantum interference device magnetometer. The crystal structure of the compound was determined "ab initio" from X-ray powder diffraction data and refined by the Rietveld method. The crystals of Fe[C6H5PO3].H2O are orthorhombic, space group Pmn2(1), with a = 5.668(8) A, b = 14.453(2) A, c = 4.893(7) A, and Z = 2. The title compound is isostructural with the previously reported lamellar M[C6H5PO3].H2O, M = Mn(II), Zn(II), and Cd(II). The inorganic layers are made of Fe(II) ions octahedrally coordinated by five phosphonate oxygen atoms and one from oxygen of the water molecule. These layers are then separated by bilayers of the phenyl groups, and van der Waals contacts are established between them. The refinement has shown that the phenyl rings are disordered in the lattice. The oxidation state of the metal ion is +2, and the electronic configuration is d6 (S = 2) high-spin, as determined from dc magnetic susceptibility measurements from 150 K to room temperature. Below 100 K, the magnetic moment of Fe[C6H5PO3].H2O rises rapidly to a maximum at TN = 21.5 K, and then it decreases again. The peak at TN is associated with the 3D antiferromagnetic long-range ordering. Below the critical temperature, the title compound behaves as a "weak" ferromagnet, which represents the third type of magnetic materials characterized by having a finite zero-field magnetization, ferromagnets and ferrimagnets being the other two types. The large coercive field (i.e., 6400 G) observed in the hysteresis loop at T = 10 K is rare in molecule-based materials; it can be ascribed to a pronounced spin-orbit coupling for the 5T2g ground state of the Fe(II) ion in the octahedral environment.