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1.
Pediatr Obes ; 19(6): e13097, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38583983

RESUMO

BACKGROUND: Obesity is prevalent among children and adults. Yet, understanding the relationship between parent and child weight trajectories is limited. OBJECTIVE: (1) Examine the association between parent/child undesirable body mass index (BMI) category change. (2) Assess whether parental BMI category predicts child modified BMI z-score (mBMIz) annual change. METHODS: We conducted a cross-sectional study of weight trajectories of 3821 parent-child dyads between March 2020 and December 2021 within the NYC Health + Hospitals system. Undesirability of child and parental BMI category change and the magnitude of mBMIz change by parental BMI are analysed. RESULTS: Of 3821 children (mean [SD] baseline age, 9.84 [3.51]), 1889 were female. Of the 3220 parents (mean [SD] baseline age, 39.9 [8.51]), 2988 were female. Most children (53.52%) and parents (81.94%) presented with overweight and obesity. Undesirable BMI change in children was associated with concordant change in parents (adjusted OR: 1.7, 95% CI [1.45, 2.01], adjusted p < 0.001). Children of parents with obesity (adjusted coef: 0.076, 95% CI [0.004, 0.147], p < 0.038) and severe obesity (adjusted coef: 0.1317, 95% CI [0.024, 0.239], adjusted p < 0.016) demonstrated greater change in mBMIz than those of parents with normal weight or underweight. CONCLUSION: Parents and children have concordant weight trajectories, and public health interventions targeting both populations are essential.


Assuntos
Índice de Massa Corporal , Relações Pais-Filho , Pais , Obesidade Infantil , Humanos , Feminino , Masculino , Criança , Estudos Transversais , Obesidade Infantil/epidemiologia , Pais/psicologia , Adulto , Redução de Peso , Aumento de Peso , Adolescente
2.
Neurosurgery ; 88(3): 443-456, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33588442

RESUMO

Neoplasms of the peripheral nervous system represent a heterogenous group with a wide spectrum of morphological features and biological potential. They range from benign and curable by complete excision (schwannoma and soft tissue perineurioma) to benign but potentially aggressive at the local level (plexiform neurofibroma) to the highly malignant (malignant peripheral nerve sheath tumors [MPNST]). In this review, we discuss the diagnostic and pathologic features of common peripheral nerve sheath tumors, particularly those that may be encountered in the intracranial compartment or in the spine and paraspinal region. The discussion will cover schwannoma, neurofibroma, atypical neurofibromatous neoplasms of uncertain biological potential, intraneural and soft tissue perineurioma, hybrid nerve sheath tumors, MPNST, and the recently renamed enigmatic tumor, malignant melanotic nerve sheath tumor, formerly referred to as melanotic schwannoma. We also discuss the diagnostic relevance of these neoplasms to specific genetic and familial syndromes of nerve, including neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis. In addition, we discuss updates in our understanding of the molecular alterations that represent key drivers of these neoplasms, including neurofibromatosis type 1 and type 2, SMARCB1, LZTR1, and PRKAR1A loss, as well as the acquisition of CDKN2A/B mutations and alterations in the polycomb repressor complex members (SUZ12 and EED) in the malignant progression to MPNST. In summary, this review covers practical aspects of pathologic diagnosis with updates relevant to neurosurgical practice.


Assuntos
Nervos Periféricos/diagnóstico por imagem , Neoplasias do Sistema Nervoso Periférico/diagnóstico por imagem , Neoplasias do Sistema Nervoso Periférico/genética , Animais , Humanos , Neoplasias de Bainha Neural/diagnóstico por imagem , Neoplasias de Bainha Neural/genética , Neoplasias de Bainha Neural/patologia , Neurilemoma/diagnóstico por imagem , Neurilemoma/genética , Neurilemoma/patologia , Neurofibroma/diagnóstico por imagem , Neurofibroma/genética , Neurofibroma/patologia , Neurofibromatoses/diagnóstico por imagem , Neurofibromatoses/genética , Neurofibromatoses/patologia , Nervos Periféricos/patologia , Neoplasias do Sistema Nervoso Periférico/patologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Fatores de Transcrição/genética
3.
EBioMedicine ; 61: 103047, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33099086

RESUMO

BACKGROUND: Prioritization of breast cancer patients based on the risk of resistance to tamoxifen plays a significant role in personalized therapeutic planning and improving disease course and outcomes. METHODS: In this work, we demonstrate that a genome-wide pathway-centric computational framework elucidates molecular pathways as markers of tamoxifen resistance in ER+ breast cancer patients. In particular, we associated activity levels of molecular pathways with a wide spectrum of response to tamoxifen, which defined markers of tamoxifen resistance in patients with ER+ breast cancer. FINDINGS: We identified five biological pathways as markers of tamoxifen failure and demonstrated their ability to predict the risk of tamoxifen resistance in two independent patient cohorts (Test cohort1: log-rank p-value = 0.02, adjusted HR = 3.11; Test cohort2: log-rank p-value = 0.01, adjusted HR = 4.24). We have shown that these pathways are not markers of aggressiveness and outperform known markers of tamoxifen response. Furthermore, for adoption into clinic, we derived a list of pathway read-out genes and their associated scoring system, which assigns a risk of tamoxifen resistance for new incoming patients. INTERPRETATION: We propose that the identified pathways and their read-out genes can be utilized to prioritize patients who would benefit from tamoxifen treatment and patients at risk of tamoxifen resistance that should be offered alternative regimens. FUNDING: This work was supported by the Rutgers SHP Dean's research grant, Rutgers start-up funds, Libyan Ministry of Higher Education and Scientific Research, and Katrina Kehlet Graduate Award from The NJ Chapter of the Healthcare Information Management Systems Society.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/etiologia , Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Receptores de Estrogênio/metabolismo , Transdução de Sinais , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Estudo de Associação Genômica Ampla/métodos , Humanos , Curva ROC , Receptores de Estrogênio/genética , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico
4.
Clin Rheumatol ; 37(9): 2497-2504, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29728929

RESUMO

Higher levels of moderate to vigorous physical activity improve all-cause mortality and cardiovascular events. However, the effect of running, a moderate to vigorous activity, in those with knee osteoarthritis (OA), a common arthritis that occurs with aging, a high-risk group for mortality and cardiovascular events, is unclear. Therefore, we aimed to evaluate the association of self-selected running on OA symptom and structure progression in people with knee OA. This nested cohort study within the Osteoarthritis Initiative (OAI) (2004-2014) included those at least 50 years old with OA in at least one knee. Runners were defined using a self-administered questionnaire at the 96-month visit. At baseline and 48-months, symptoms were assessed and radiographs were scored for Kellgren-Lawrence (KL) grade (2-4) and medial Joint Space Narrowing (JSN) score (0-3). We evaluated the association of self-selected running with outcomes: KL worsening, medial JSN worsening, new knee pain, and improved knee pain over 48 months, adjusting for baseline age, sex, body mass index (BMI), KL score, contralateral KL score, contralateral knee pain, and injury. If data were not available at the 48-month visit, then they were imputed from the 36-month visit. One thousand two hundred three participants had a mean age of 63.2 (7.9) years, BMI of 29.5 (4.6) kg/m2, 45.3% male, and 11.5% runners. Data from 8% of participants required imputation. Adjusted odds ratios for KL grade worsening and new frequent knee pain were 0.9 (0.6-1.3) and 0.9 (0.6-1.6) respectively. Adjusted odds ratio for frequent knee pain resolution was 1.7 (1.0-2.8). Among individuals 50 years old and older with knee OA, self-selected running is associated with improved knee pain and not with worsening knee pain or radiographically defined structural progression. Therefore, self-selected running, which is likely influenced by knee symptoms and may result in lower intensity and shorter duration sessions of exercise, need not be discouraged in people with knee OA.


Assuntos
Progressão da Doença , Osteoartrite do Joelho , Corrida , Artrografia , Estudos de Coortes , Feminino , Humanos , Articulação do Joelho , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/fisiopatologia , Medição da Dor , Avaliação de Sintomas
5.
Sci Total Environ ; 610-611: 1147-1153, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28847135

RESUMO

The contribution of the sorption processes in the elimination of pharmaceuticals (PhACs) during the fungal treatment of wastewater has been evaluated in this work. The sorption of four PhACs (carbamazepine, diclofenac, iopromide and venlafaxine) by 6 different fungi was first evaluated in batch experiments. Concentrations of PhACs in both liquid and solid (biomass) matrices from the fungal treatment were measured. Contribution of the sorption to the total removal of pollutants ranged between 3% and 13% in relation to the initial amount. The sorption of 47 PhACs in fungi was also evaluated in a fungal treatment performed in 26days in a continuous bioreactor treating wastewater from a veterinary hospital. PhACs levels measured in the fungal biomass were similar to those detected in conventional wastewater treatment (WWTP) sludge. This may suggest the necessity of manage fungal biomass as waste in the same manner that the WWTP sludge is managed.


Assuntos
Preparações Farmacêuticas/metabolismo , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/microbiologia , Poluentes Químicos da Água/metabolismo , Biodegradação Ambiental , Reatores Biológicos/microbiologia , Preparações Farmacêuticas/análise , Águas Residuárias/química , Poluentes Químicos da Água/análise
6.
Water Res ; 116: 65-75, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28314209

RESUMO

Hospital wastewaters are a main source of pharmaceutical active compounds, which are usually highly recalcitrant and can accumulate in surface and groundwater bodies. Fungal treatments can remove these contaminants prior to discharge, but real wastewater poses a problem to fungal survival due to bacterial competition. This study successfully treated real non-spiked, non-sterile wastewater in a continuous fungal fluidized bed bioreactor coupled to a coagulation-flocculation pretreatment for 56 days. A control bioreactor without the fungus was also operated and the results were compared. A denaturing gradient gel electrophoresis (DGGE) and sequencing approach was used to study the microbial community arisen in both reactors and as a result some bacterial degraders are proposed. The fungal operation successfully removed analgesics and anti-inflammatories, and even the most recalcitrant pharmaceutical families such as antibiotics and psychiatric drugs.


Assuntos
Floculação , Águas Residuárias , Reatores Biológicos/microbiologia , Fungos , Hospitais , Preparações Farmacêuticas , Eliminação de Resíduos Líquidos
7.
J Hazard Mater ; 318: 561-570, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27469044

RESUMO

Hospital wastewaters have a high load of pharmaceutical active compounds (PhACs). Fungal treatments could be appropriate for source treatment of such effluents but the transition to non-sterile conditions proved to be difficult due to competition with indigenous microorganisms, resulting in very short-duration operations. In this article, coagulation-flocculation and UV-radiation processes were studied as pretreatments to a fungal reactor treating non-sterile hospital wastewater in sequential batch operation and continuous operation modes. The influent was spiked with ibuprofen and ketoprofen, and both compounds were successfully degraded by over 80%. UV pretreatment did not extent the fungal activity after coagulation-flocculation measured as laccase production and pellet integrity. Sequential batch operation did not reduce bacteria competition during fungal treatment. The best strategy was the addition of a coagulation-flocculation pretreatment to a continuous reactor, which led to an operation of 28days without biomass renovation.


Assuntos
Eliminação de Resíduos de Serviços de Saúde/métodos , Resíduos de Serviços de Saúde , Trametes/metabolismo , Eliminação de Resíduos Líquidos/métodos , Biomassa , Reatores Biológicos , Hospitais , Ibuprofeno/química , Ibuprofeno/metabolismo , Cetoprofeno/química , Cetoprofeno/metabolismo , Lacase/biossíntese , Raios Ultravioleta , Microbiologia da Água , Poluentes Químicos da Água
8.
Mucosal Immunol ; 7(6): 1467-79, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24850427

RESUMO

In inflammatory bowel disease (IBD), tissue damage is driven by an excessive immune response, poorly controlled by counter-regulatory mechanisms. SIRT1, a class III NAD+-dependent deacetylase, regulates negatively the expression of various proteins involved in the control of immune-inflammatory pathways, such as Stat3, Smad7, and NF-κB. Here we examined the expression, regulation, and function of SIRT1 in IBD. SIRT1 RNA and protein expression was less pronounced in whole biopsies and lamina propria mononuclear cells (LPMCs) of IBD patients in comparison with normal controls. SIRT1 expression was downregulated in control LPMC by tumor necrosis factor (TNF)-α and interleukin (IL)-21, and upregulated in IBD LPMC by neutralizing TNF-α and IL-21antibodies. Consistently, SIRT1 expression was increased in mucosal samples taken from IBD patients successfully treated with Infliximab. Treatment of IBD LPMC with Cay10591, a specific SIRT1 activator, reduced NF-κB activation and inhibited inflammatory cytokine synthesis, whereas Ex527, an inhibitor of SIRT1, increased interferon (IFN)-γ in control LPMC. SIRT1 was also reduced in mice with colitis induced by 2,4,6-trinitrobenzenesulphonic acid or oxazolone. Cay10591 prevented and cured experimental colitis whereas Ex527 exacerbated disease by modulating T cell-derived cytokine response. Data indicate that SIRT1 is downregulated in IBD patients and colitic mice and suggest that SIRT1 activation can help attenuate inflammatory signals in the gut.


Assuntos
Regulação Enzimológica da Expressão Gênica/imunologia , Doenças Inflamatórias Intestinais/imunologia , Intestinos/imunologia , Sirtuína 1/imunologia , Adjuvantes Imunológicos/efeitos adversos , Adjuvantes Imunológicos/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Feminino , Regulação Enzimológica da Expressão Gênica/genética , Humanos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Infliximab , Interferon gama/genética , Interferon gama/imunologia , Interleucinas/genética , Interleucinas/imunologia , Intestinos/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Oxazolona/efeitos adversos , Oxazolona/farmacologia , Sirtuína 1/genética , Ácido Trinitrobenzenossulfônico/toxicidade , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
9.
J Environ Manage ; 130: 242-7, 2013 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-24091159

RESUMO

The life cycle assessment (LCA) environmental tool was implemented to quantify the potential environmental impacts associated with the activated carbon (AC) production process from olive-waste cakes in Tunisia. On the basis of laboratory investigations for AC preparation, a flowchart was developed and the environmental impacts were determined. The LCA functional unit chosen was the production of 1 kg of AC from by-product olive-waste cakes. The results showed that impregnation using H3PO4 presented the highest environmental impacts for the majority of the indicators tested: acidification potential (62%), eutrophication (96%), ozone depletion potential (44%), human toxicity (64%), fresh water aquatic ecotoxicity (90%) and terrestrial ecotoxicity (92%). One of the highest impacts was found to be the global warming potential (11.096 kg CO2 eq/kg AC), which was equally weighted between the steps involving impregnation, pyrolysis, and drying the washed AC. The cumulative energy demand of the AC production process from the by-product olive-waste cakes was 167.63 MJ contributed by impregnation, pyrolysis, and drying the washed AC steps. The use of phosphoric acid and electricity in the AC production were the main factors responsible for the majority of the impacts. If certain modifications are incorporated into the AC production, such as implementing synthesis gas recovery and reusing it as an energy source and recovery of phosphoric acid after AC washing, additional savings could be realized, and environmental impacts could be minimized.


Assuntos
Carbono/química , Conservação dos Recursos Naturais , Olea , Óleos de Plantas , Gerenciamento de Resíduos , Meio Ambiente , Indústria Alimentícia , Resíduos Industriais , Azeite de Oliva , Ácidos Fosfóricos/química , Tunísia
10.
Environ Technol ; 34(1-4): 113-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23530321

RESUMO

Laccase production by pre-growth pellets of Trametes versicolor using two types of textile dyes as inducers was studied. By decoupling the enzyme production phase from the growth phase, it is possible to reduce the time and nutrients required for laccase production. At the glucose maintenance level, the effect of the nitrogen source and textile dye was analysed using response surface methodology. Ammonium chloride was used as the inorganic nitrogen source. Two types of dyes were tested: Grey Lanaset G (GLG), a metal complex dye mixture containing nitrogen; and Alizarin Red (AR), an anthraquinonic dye with no nitrogen in its chemical structure. GLG induces laccase production at a higher extent than AR. Despite the limiting conditions required for the production of laccase, enzyme production increases with increasing ammonium chloride. When AR, the N-free dye, was used as an inducer, the optimal supply of N for laccase production was 1.2 mg/(g dry cell weight x d) as ammonium chloride. The reuse of fungal pellets in the repeated-batch mode under maintenance conditions was found to be a good strategy for improving laccase production, as enzyme production increased to up to seven times the production of the first cycle. It was demonstrated that GLG can be used as an inducer and as an N source and, thus, it is possible to decolorize the dye and to induce laccase production at the same time without adding an extra N source.


Assuntos
Corantes/química , Lacase/metabolismo , Trametes/enzimologia , Antraquinonas , Glucose/metabolismo , Nitrogênio/metabolismo
11.
Mucosal Immunol ; 6(2): 244-55, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22785229

RESUMO

Celiac disease (CD)-associated inflammation is characterized by high interleukin- 21 (IL-21), but the mechanisms that control IL-21 production are not fully understood. Here we analyzed IL-21 cell sources and examined how IL-21 production is regulated in CD. Intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs), isolated from CD patients and non-CD controls, were analyzed for cell markers, cytokines, and transcription factors by flow cytometry. IL-21 was highly produced by CD4+ and CD4+/CD8+ IELs and LPLs in active CD. IL-21-producing cells coexpressed interferon-γ (IFN-γ) and to a lesser extent T helper type 17 (Th17) cytokines. Treatment of control LPLs with IL-15, a cytokine overproduced in CD, activated Akt and STAT3 (signal transducer and activator of transcription 3), thus enhancing IL-21 synthesis. Active CD biopsies contained elevated levels of Akt, and blockade of IL-15 in those samples reduced IL-21. Similarly, neutralization of IL-15 in biopsies of inactive CD patients inhibited peptic-tryptic digest of gliadin-induced IL-21 expression. These findings indicate that in CD, IL-15 positively regulates IL-21 production.


Assuntos
Doença Celíaca/metabolismo , Interleucina-15/metabolismo , Interleucinas/biossíntese , Mucosa Intestinal/metabolismo , Doença Celíaca/genética , Doença Celíaca/patologia , Células Cultivadas , Expressão Gênica , Humanos , Interferon gama/metabolismo , Interleucinas/genética , Mucosa Intestinal/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Receptores CXCR5/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
12.
Panminerva Med ; 55(1): 99-105, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23241839

RESUMO

Internet and dematerialization have greatly facilitated the medical profession. Contractual physicians and national health service doctors now have efficient tools for the electronic management of their routine administrative workload. A recent innovation is the medical sickness certificate issued by primary care providers and national health service physicians. Following postponements and uncertainties, procedures for the electronic completion and online transmission of the sickness certificate are now complete. The changes introduced by the so-called "Brunetta decree", however, have made its application difficult and continuous improvement to the system is needed, considering also the severe penalties imposed for violations. In the light of serious legal repercussions for health care professionals, this article examines various critical issues, highlighting the pitfalls and the network's enormous potential for ascertaining evidence of irregularities. The overheated debate on absenteeism due to illness, the diverse roles of national health physicians and self-employed doctors responsible for issuing a sickness certificate, and problems related to circumstances in which a doctor operates, are the key topics in this discussion. Computerization is an effective tool for optimizing public resources; however, it also seeks to ferret out, through the traceability of certification, abuse of medical certification, with severe penalties applied if certificates are discovered to contain misleading or untrue information.


Assuntos
Absenteísmo , Registros Eletrônicos de Saúde , Definição da Elegibilidade , Emprego , Licença Médica , Avaliação da Capacidade de Trabalho , Registros Eletrônicos de Saúde/legislação & jurisprudência , Definição da Elegibilidade/legislação & jurisprudência , Emprego/legislação & jurisprudência , Fraude , Regulamentação Governamental , Política de Saúde , Humanos , Itália , Responsabilidade Legal , Programas Nacionais de Saúde , Atenção Primária à Saúde , Licença Médica/legislação & jurisprudência
13.
Clin Ter ; 163(5): e357-63, 2012.
Artigo em Italiano | MEDLINE | ID: mdl-23099987

RESUMO

Over the last decades, the increase in the global population's mean age has implied a corresponding increase in degenerative disease affecting various anatomical areas and tissues, including bones and cartilages, thus provoking a rising number of disabilities and a wider usage of drugs, mostly anti-inflammatory and cortisone. New developments in technologic and biomedical fields gave birth to new subjects, such as tissue engineering, cell therapy, gene therapy that, by and large, create a knowledge network falling under the concept of Regenerative Medicine. This science is essentially based on the usage of stem cells that can replicate and renovate themselves originating, if adequately stimulated, a number of cell types. Inter alia, in orthopaedic field a particular type of adult stem cells is used, the mesenchymal stem cells (MSCs). If combined with synthetic material produced in laboratories, the usage of these cells has provided inspiration for new study interests; today, it can be applied in various degenerative and post-traumatic pathologies, with great therapeutic benefits for the patient. Actually, many studies write about an improvement in patients' life quality. In this sense appear significant reflections on legal medicine, both in accidents and insurance, of this innovative therapeutic alternative and is hopefully an equally valid process of improvement of regulatory and case law.


Assuntos
Ortopedia/legislação & jurisprudência , Ortopedia/métodos , Medicina Regenerativa/legislação & jurisprudência , Humanos
14.
Curr Mol Med ; 12(5): 592-7, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22515978

RESUMO

T helper (Th)17 cells and other interleukin (IL)-17-producing cells are supposed to play critical roles in several human immune-mediated diseases, including Crohn's disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel diseases (IBD) in man. Th17 cells infiltrate massively the inflamed intestine of IBD patients and in vitro and in vivo studies have shown that Th17-type cytokines may trigger and amplify multiple inflammatory pathways. Nonetheless, some Th17-related cytokines, such as interleukin (IL)-17A and IL-22, may target gut epithelial cells and promote the activation of counter-regulatory mechanisms. This observation together with the demonstration that Th17 cells are not stable and can be converted into either regulatory T cells or Th1 cells if stimulated by immune-suppressive (e.g. TGF-ß1) or inflammatory (e.g. IL-12, IL-23) cytokines have contributed to advance our understanding of mechanisms that regulate mucosal homeostasis and inflammation in the gut.


Assuntos
Doenças Inflamatórias Intestinais/metabolismo , Interleucina-17/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Animais , Colite/imunologia , Colite/metabolismo , Humanos , Doenças Inflamatórias Intestinais/imunologia , Modelos Biológicos , Linfócitos T Auxiliares-Indutores/imunologia
15.
Gut ; 58(12): 1629-36, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19740775

RESUMO

BACKGROUND AND AIMS: Interleukin 17 (IL17) is now known to be involved in a number of chronic inflammatory disorders. However, the mechanisms regulating its production in inflammatory bowel disease (IBD) are still unclear. METHODS: Endoscopic biopsies or surgical specimens were taken from inflamed and uninflamed colonic mucosa of 72 patients with IBD (38 with Crohn's disease and 34 with ulcerative colitis), and normal colon of 38 control subjects. IL17 and interferon gamma (IFNgamma) were detected by ELISA in the supernatants of biopsies cultured ex vivo, and anti-CD3/CD28-stimulated lamina propria mononuclear cells (LPMCs) incubated with IL12, IL23, IL1beta plus IL6, transforming growth factor beta1 (TGFbeta1), or anti-IL21 neutralising antibody. Intracellular flow cytometry was performed to analyse mucosal Th17 and Th1/Th17 cells. RESULTS: IL17 production by organ culture biopsies was higher in IBD inflamed mucosa than IBD uninflamed mucosa and controls, and was equivalent in amount to IFNgamma. Anti-CD3/CD28-stimulated IBD LPMCs produced higher IL17 amounts compared to controls. The percentages of Th17 and Th1/Th17 cells were increased in patients with IBD. IL23 and IL1beta plus IL6 had no effect on IBD LPMC production of IL17; however, IL12 markedly increased IFNgamma production and decreased IL17 production. TGFbeta1 dose-dependently decreased IFNgamma, but had no significant inhibitory effect on IL17 production. Blocking IL21 significantly downregulated IL17 production. CONCLUSIONS: Our findings support a role for IL12, TGFbeta and IL21 in modulating IL17/IFNgamma production in IBD. The abundant IL17 in inflamed IBD mucosa may help explain the relative lack of efficacy of anti-IFNgamma antibodies in clinical trials of Crohn's disease.


Assuntos
Doenças Inflamatórias Intestinais/imunologia , Interferon gama/biossíntese , Interleucina-17/biossíntese , Adolescente , Adulto , Células Cultivadas , Colite Ulcerativa/imunologia , Doença de Crohn/imunologia , Citocinas/imunologia , Relação Dose-Resposta Imunológica , Proteínas da Matriz Extracelular/imunologia , Humanos , Imunidade nas Mucosas , Mediadores da Inflamação/imunologia , Mucosa Intestinal/imunologia , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos , Subpopulações de Linfócitos T/imunologia , Células Th1/imunologia , Fator de Crescimento Transformador beta/imunologia , Adulto Jovem
16.
Gut ; 57(7): 887-92, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17965065

RESUMO

BACKGROUND: In coeliac disease (CD), the upper bowel lesion is associated with a marked infiltration of the mucosa with Th1 cells secreting interferon gamma (IFNgamma) and expressing the Th1-associated transcription factor, T-bet. However, the molecular mechanisms which regulate T-bet and promote the Th1 cell response are unknown. OBJECTIVE: To examine whether interleukin 21 (IL21), a cytokine that regulates T cell activation, has a role in CD. METHODS: Duodenal mucosal samples were taken from CD patients and normal controls. IL21 and T-bet were examined by real-time PCR and western blotting, and IFNgamma was assessed by real-time PCR and ELISA. The effect of blockade of endogenous IL21 on the expression of T-bet was examined in an ex vivo culture of biopsies taken from untreated CD patients. Finally, the role of IL21 in controlling T-bet and IFNgamma was also evaluated in cultures of biopsies taken from treated CD patients and cultured with a peptic-tryptic digest of gliadin (PT) in the presence or absence of a neutralising IL21 antibody. RESULTS: Enhanced IL21 RNA and protein expression was seen in duodenal samples from untreated CD patients. Blockade of IL21 activity in biopsies of untreated CD patients reduced T-bet and IFNgamma secretion. Stimulation of treated CD biopsies with PT enhanced IL21 expression, and neutralisation of IL21 largely prevented PT-driven T-bet and IFNgamma induction. CONCLUSIONS: IL21 is overproduced in the mucosa of CD patients, where it helps sustain T-bet expression and IFNgamma production.


Assuntos
Doença Celíaca/imunologia , Interleucinas/imunologia , Células Th1/imunologia , Adulto , Duodeno/imunologia , Regulação da Expressão Gênica/imunologia , Gliadina/imunologia , Humanos , Imunidade nas Mucosas , Interferon gama/metabolismo , Interleucinas/antagonistas & inibidores , Interleucinas/genética , Mucosa Intestinal/imunologia , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos , Proteínas com Domínio T/metabolismo
17.
Environ Technol ; 28(10): 1103-10, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17970516

RESUMO

Biodegradation of the Orange G azo dye by pellets of Trametes versicolor in a fluidized bioreactor operating under conditions of laccase production was studied. The percentage of decolorization obtained was 97% in batch mode and both the biomass and the broth, were colorless. In vitro degradations carried out with purified commercial laccase from Trametes versicolor demonstrated that laccase is able to degrade the dye. In spite of the high level of decolorization reached in both processes, an important difference between the fungal and enzymatic treatments was detected. At the end of the experiments carried out in vitro, a final residual color appears (different to the initial one). Consequently, measuring the yield of decolorization as a percentage of absorbance lambdamax variation is not the best indicator of the treated wastewater quality, but the analysis of the visible color spectrum makes it possible to detect changes in color. The results demonstrate that better results are obtained with fungal Orange G biodegradation because a further breakdown of the enzymatic products is achieved with the fungus.


Assuntos
Compostos Azo/metabolismo , Basidiomycota/enzimologia , Lacase/metabolismo , Reatores Biológicos , Cor , Hidrólise , Espectroscopia de Ressonância Magnética
18.
Water Res ; 40(8): 1650-6, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16616292

RESUMO

The long-term continuous decolourisation treatment of the textile dye Grey Lanaset G (150 mg/l) was carried out in an air-pulsed bed bioreactor with retained pellets of the white-rot fungus Trametes versicolor. Maximum cellular retention time (CRT) was established at 40 days. During this time period, colour reduction remained at 90% and laccase activity was over 400 AU/l. Higher CRTs involved operational problems related to biomass conglomerates formed at the top of the bioreactor, which made individual movement of the pellets difficult. In order to carry out the long-term continuous treatment, a strategy of purge and biomass renovation that had to allow fungal stable activity levels to be maintained was planned. The purge and biomass renovation strategy consists of partial biomass renovations: 1/3 of the total biomass of the system is renewed every 1/3 of the CRT. Different CRTs were tested; with a CRT of 21 days carrying out partial biomass renovations every 7 days and with a hydraulic retention time of 2 days, decolourisation percentages higher than 80% were obtained, maintaining a young culture in the bioreactor and guaranteeing microbial activity. In accordance with the strategy observed, different simulations of the age of the biomass in the bioreactor were carried out, obtaining suitable age distributions for CRT of 20-21 days.


Assuntos
Biomassa , Cor , Fungos/metabolismo , Fungos/citologia
19.
Water Res ; 38(8): 2166-72, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15087198

RESUMO

The biodegradation of Grey Lanaset G, which consists of a mixture of metal complexed dye, was studied. Experiments were carried out in a bioreactor with retained pellets of the fungus Trametes versicolor that was operated under conditions of laccase production. Although decolorization was highly efficient (90%), no direct relationship to extracellular enzyme was apparent. Moreover, the extracellular enzyme was found to be unable to degrade the dye in vitro. The process involves several steps. Thus, the initial adsorption of the dye and its transfer into cells is followed by breaking of the metal complex bond in the cells release of the components. The metal (Cr and Co) contents of the biomass and treated solutions, and their closer relationship to intracellular enzyme and degradation of the dye, confirm the initial hypothesis.


Assuntos
Basidiomycota/enzimologia , Corantes/química , Fungos/metabolismo , Metais/química , Indústria Têxtil , Têxteis , Basidiomycota/metabolismo , Biodegradação Ambiental , Biomassa , Reatores Biológicos , Biotransformação , Cromo/química , Cobalto/química , Cor , Fungos/enzimologia , Glucose/análise , Glucose/metabolismo , Lacase/metabolismo , Fatores de Tempo
20.
Biotechnol Prog ; 18(3): 660-2, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12052089

RESUMO

Olive oil mill wastewater (OMW) is produced as waste in olive oil extraction. With the purpose of treating this highly polluting waste, a number of experiments were conducted in a laboratory-scale bioreactor with the white rot fungus Phanerochaete flavido-alba (P. flavido-alba). It is known that this fungus is capable of decolorizing OMW in static or semistatic cultures at Erlenmeyer scale and at 30 degrees C. The objective of this work was to prove that P. flavido-alba could decolorize OMW in submerged cultures and that it is capable of reducing OMW toxicity at room temperature (25 degrees C) and in a laboratory-scale bioreactor. In the experiments conducted, manganese peroxidase (MnP) and laccase enzymes were detected; however, unlike other studies, lignin peroxidase was not found to be present. Decoloration obtained after treatment was 70%. The reduction of aromatic compounds obtained was 51%, and the toxicity of the culture medium was reduced by up to 70%. We can therefore state that P. flavido-alba is capable of reducing important environmental parameters of industrial effluents and that prospects are positive for the use of this process at a larger scale, even when working at room temperature.


Assuntos
Reatores Biológicos , Resíduos Industriais , Phanerochaete/metabolismo , Poluentes Químicos da Água/metabolismo , Biodegradação Ambiental , Cor
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