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1.
Breast Cancer Res Treat ; 203(1): 163-172, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37773555

RESUMO

PURPOSE: Molecular subtyping based on gene expression profiling (i.e., PAM50 assay) aids in determining the prognosis and treatment of breast cancer (BC), particularly in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors, where luminal A and B subtypes have different prognoses and treatments. Several surrogate classifications have been proposed for distinguishing between the luminal A and B subtypes. This study determines the accuracy of local immunohistochemistry (IHC) techniques for classifying HR-positive/HER2-negative (HR+/HER2-) tumors according to intrinsic subtypes using the nCOUNTER PAM50 assay as reference and the HR status definition according the ASCO/CAP recommendations. METHODS: Molecular subtypes resulting from nCOUNTER PAM50 performed in our laboratory between 2014 and 2020 were correlated with three different proxy surrogates proposed in the literature based on ER, PR, HER2, and Ki67 expression with different cut-off values. Concordance was measured using the level of agreement and kappa statistics. RESULTS: From 1049 samples with the nCOUNTER test, 679 and 350 were luminal A and B subtypes, respectively. Only a poor-to-fair correlation was observed between the three proxy surrogates and real genomic subtypes as determined by nCOUNTER PAM50. Moreover, 5-11% and 18-36% of the nCOUNTER PAM50 luminal B and A tumors were classified as luminal A and B, respectively, by these surrogates. CONCLUSION: The concordance between luminal subtypes determined by three different IHC-based classifiers and the nCOUNTER PAM50 assay was suboptimal. Thus, a significant proportion of luminal A and B tumors as determined by the surrogate classifiers could be undertreated or over-treated.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Imuno-Histoquímica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Prognóstico , Perfilação da Expressão Gênica , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo
2.
Environ Res ; 233: 116442, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37343755

RESUMO

Perchlorate has been described as an emerging pollutant that compromises water sources and human health. In this study, a new electrotrophic perchlorate reducing microorganism (EPRM) isolated from the Atacama Desert, Dechloromonas sp. CS-1, was evaluated for perchlorate removal in water in a bioelectrochemical reactor (BER) with a chemically modified electrode. BERs were operated for 17 days under batch mode conditions with an applied potential of -500 mV vs. Ag/AgCl. Surface analysis (i.e., SEM, XPS, FT-IR, RAMAN spectroscopy) on the modified electrode demonstrated heterogeneous transformation of the carbon fibers with the incorporation of nitrogen functional groups and the oxidation of the carbonaceous material. The BERs with the modified electrode and the presence of the EAM reached high cathodic efficiency (90.79 ± 9.157%) and removal rate (0.34 ± 0.007 mol m-3-day) compared with both control conditions. The observed catalytic enhancement of CS-1 was confirmed by a reduction in the charge transfer resistance obtained by electrochemical impedance spectroscopy (EIS). Finally, an electrochemical kinetic study revealed an eight-electron perchlorate bioreduction reaction at -638.33 ± 24.132 mV vs. Ag/AgCl. Therefore, our results show the synergistic effect of EPRM and chemically modified electrodes on perchlorate removal in a BER.


Assuntos
Nitrogênio , Percloratos , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier , Nitrogênio/metabolismo , Eletrodos , Oxirredução
3.
Molecules ; 28(16)2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37630246

RESUMO

Endocrine-disrupting compounds (EDCs) constitute a wide variety of chemistries with diverse properties that may/can pose risks to both humans and the environment. Herein, a total of 26 compounds, including steroids, flame retardants, and plasticizers, were monitored in three major and heavily urbanized river catchments: the R. Liffey (Ireland), the R. Thames (UK), and the R. Ter (Spain), by using a single solid-phase extraction liquid chromatography-mass spectrometry (SPE-LC-MS/MS) method. Occurrence and frequency rates were investigated across all locations over a 10-week period, with the highest concentration obtained for the flame retardant tris(2-chloroethyl) phosphate (TCEP) at 4767 ng∙L-1 in the R. Thames in Central London. Geographical variations were observed between sites and were partially explained using principal component analysis (PCA) and hierarchical cluster analysis (HCA). In particular, discrimination between the R. Ter and the R. Thames was observed based on the presence and concentration of flame retardants, benzotriazole, and steroids. Environmental risk assessment (ERA) across sites showed that caffeine, a chemical marker, and bisphenol A (BPA), a plasticizer, were classified as high-risk for the R. Liffey and R. Thames, based on relative risk quotients (rRQs), and that caffeine was classified as high-risk for the R. Ter, based on RQs. The total risks at each location, namely ΣRQriver, and ΣrRQriver, were: 361, 455, and 723 for the rivers Liffey, Thames, and Ter, respectively. Caffeine, as expected, was ubiquitous in all 3 urban areas, though with the highest RQ observed in the R. Ter. High contributions of BPA were also observed across the three matrices. Therefore, these two compounds should be prioritized independently of location. This study represents a comprehensive EDC monitoring comparison between different European cities based on a single analytical method, which allowed for a geographically independent ERA prioritization to be performed.


Assuntos
Disruptores Endócrinos , Retardadores de Chama , Humanos , Irlanda , Espanha , Cafeína , Cromatografia Líquida , Rios , Espectrometria de Massas em Tandem , Medição de Risco , Plastificantes , Reino Unido
4.
J Environ Manage ; 323: 116294, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36261994

RESUMO

Municipal and industrial wastewater discharges in coastal and marine environments are of major concern due to their high carbon and nitrogen loads and the resulted phenomenon of eutrophication. Bioelectrochemical reactors (BERs) for simultaneous nitrogen and carbon removal have gained attention owing to their cost efficiency and versatility, as well as the possibility of electrochemical enrich specific groups. This study presented a scalable two-chamber BERs using graphite granules as electrode material. BERs were inoculated and operated for 37 days using natural seawater with high concentrations of ammonium and acetate. The BERs demonstrated a maximum current density of 0.9 A m-3 and removal rates of 7.5 mg NH4+-N L-1 d-1 and 99.5 mg L-1 d-1 for total organic carbon (TOC). Removals observed for NH4+-N and TOC were 96.2% and 68.7%, respectively. The results of nutrient removal (i.e., ammonium, nitrate, nitrite and TOC) and microbial characterization (i.e., next-generation sequencing of the 16S rRNA gene and fluorescence in situ hybridization) showed that BERs operated with a poised cathode at -260 mV (vs. Ag/AgCl) significantly enriched nitrifying microorganisms in the anode and denitrifying microorganisms and planctomycetes in the cathode. Interestingly, the electrochemical enrichment did not increase the total number of microorganisms in the formed biofilms but controlled their composition. Thus, this work shows the first successful attempt to electrochemically enrich marine nitrifying and denitrifying microorganisms and presents a technique to accelerate the start-up process of BERs to remove dissolved inorganic nitrogen and total organic carbon from seawater.


Assuntos
Compostos de Amônio , Grafite , Nitrogênio/química , Desnitrificação , Nitrificação , Águas Residuárias , Carbono , Nitratos , Reatores Biológicos , RNA Ribossômico 16S , Nitritos , Hibridização in Situ Fluorescente , Água do Mar
5.
Environ Microbiol ; 23(7): 3682-3694, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32996242

RESUMO

In previous work, lab-scale reactors designed to study microbial Fe(II) oxidation rates at low pH were found to have stable rates under a wide range of pH and Fe(II) concentrations. Since the stirred reactor environment eliminates many of the temporal and spatial variations that promote high diversity among microbial populations in nature, we were surprised that the reactors supported multiple taxa presumed to be autotrophic Fe(II) oxidizers based on their phylogeny. Metagenomic analyses of the reactor communities revealed differences in the metabolic potential of these taxa with respect to Fe(II) oxidation and carbon fixation pathways, acquisition of potentially growth-limiting substrates and the ability to form biofilms. Our findings support the hypothesis that the long-term co-existence of multiple autotrophic Fe(II)-oxidizing populations in the reactors are due to distinct metabolic potential that supports differential growth in response to limiting resources such as nitrogen, phosphorus and oxygen. Our data also highlight the role of biofilms in creating spatially distinct geochemical niches that enable the co-existence of multiple taxa that occupy the same apparent metabolic niche when the system is viewed in bulk. The distribution of key metabolic functions across different co-existing taxa supported functional redundancy and imparted process stability to these reactors.


Assuntos
Metagenômica , Nitrogênio , Processos Autotróficos , Reatores Biológicos , Compostos Ferrosos , Oxirredução
6.
An Acad Bras Cienc ; 93(suppl 3): e20201351, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468491

RESUMO

Obesity is a major risk factor for type 2 diabetes mellitus development and is characterized by an abnormal expansion of adipose tissue and low-grade chronic inflammation that contribute to insulin resistance. Although there are multiple treatments, most therapies can produce undesirable side effects and therefore, new and effective treatments with fewer side effects are necessary. Previously, we demonstrated that a natural extract from the leaves of Eucalyptus tereticornis (OBE100) has anti-inflammatory, hypoglycemic and hypolipidemic activities. The major compounds identified in OBE100 were three pentacyclic triterpenoids, ursolic acid, oleanolic acid, and ursolic acid lactone. Triterpenoids have shown multiples biological activities. This current study compared the biological effect produced by OBE100 with five different reconstituted mixtures of these triterpenoids. Different cell lines were used to evaluate cytotoxicity, reactive oxygen species production, inflammatory cytokine expression, glucose uptake induction, leptin and adiponectin expression, and lipid accumulation. OBE100 treatment was the most efficacious and none of the formulated triterpenoid mixtures significantly improved on this. Moreover, OBE100 was less toxic and reduced reactive oxygen species production. Our study showed that the proven beneficial properties of triterpenoids may be enhanced due to the interaction with minor secondary metabolites present in the natural extract improving their anti-inflammatory properties.


Assuntos
Diabetes Mellitus Tipo 2 , Eucalyptus , Resistência à Insulina , Triterpenos , Extratos Vegetais/farmacologia , Triterpenos/farmacologia
7.
Molecules ; 26(8)2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33920841

RESUMO

Obesity has a strong relationship to insulin resistance and diabetes mellitus, a chronic metabolic disease that alters many physiological functions. Naturally derived drugs have aroused great interest in treating obesity, and triterpenoids are natural compounds with multiple biological activities and antidiabetic mechanisms. Here, we evaluated the bioactivity of ursolic acid lactone (UAL), a lesser-known triterpenoid, obtained from Eucalyptus tereticornis. We used different cell lines to show for the first time that this molecule exhibits anti-inflammatory properties in a macrophage model, increases glucose uptake in insulin-resistant muscle cells, and reduces triglyceride content in hepatocytes and adipocytes. In 3T3-L1 adipocytes, UAL inhibited the expression of genes involved in adipogenesis and lipogenesis, enhanced the expression of genes involved in fat oxidation, and increased AMP-activated protein kinase phosphorylation. The range of biological activities demonstrated in vitro indicates that UAL is a promising molecule for fighting diabetes.


Assuntos
Eucalyptus/química , Lactonas/química , Lactonas/farmacologia , Triterpenos/química , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Macrófagos , Camundongos , Células Musculares/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Triglicerídeos/metabolismo , Triterpenos/farmacologia , Ácido Ursólico
9.
Exp Eye Res ; 197: 108114, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32561484

RESUMO

The corneal endothelium is the inner cell monolayer involved in the maintenance of corneal transparence by the generation of homeostatic dehydration. The glycosaminoglycans of the corneal stroma develop a continuous swelling pressure that should be counteracted by the corneal endothelial cells through active transport mechanisms to move the water to the anterior chamber. Protein transporters for sodium (Na+), potassium (K+), chloride (Cl-) and bicarbonate (HCO3-) are involved in this endothelial "pump function", however despite its physiological importance, the efflux mechanism is not completely understood. There is experimental evidence describing transendothelial diffusion of water in the absence of osmotic gradients. Therefore, it is important to get a deeper understanding of alternative models that drive the fluid transport across the endothelium such as the electrochemical gradients. Three transcriptomic datasets of the corneal endothelium were used in this study to analyze the expression of genes that encode proteins that participate in the transport and the reestablishment of the membrane potential across the semipermeable endothelium. Subsequently, the expression of the identified channels was validated in vitro both at mRNA and protein levels. The results of this study provide the first evidence of the expression of KCNN2, KCNN3 and KCNT2 genes in the corneal endothelium. Differences among the level of expression of KCNN2, KCNT2 and KCNN4 genes were found in a differentially expressed gene analysis of the dataset. Taken together these results underscore the potential importance of the ionic channels in the pathophysiology of corneal diseases. Moreover, we elucidate novel mechanisms that might be involved in the pivotal dehydrating function of the endothelium and in others physiologic functions of these cells using in silico pathways analysis.


Assuntos
Simulação por Computador , Endotélio Corneano/metabolismo , Regulação da Expressão Gênica , Potenciais da Membrana/fisiologia , Canais de Potássio Ativados por Sódio/genética , RNA Mensageiro/genética , Endotélio Corneano/citologia , Humanos , Transporte de Íons , Canais de Potássio Ativados por Sódio/biossíntese , Transdução de Sinais
10.
Pharm Res ; 37(8): 152, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32700034

RESUMO

PURPOSE: Anthocyanins (ACNs) are polyphenols that might reduce pathological processes associated with type 2 diabetes mellitus and other chronic diseases, but their bioavailability is still controversial. In this study, the metabolic activity of oral delivery of ACN-loaded niosomes was investigated and evaluated in a diet-induced obesity (DIO) mice model. METHODS: ACNs extracted from Vaccinium Meridionale by the supercritical fluid extraction method were loaded in niosomes. The niosomal formulation was physically characterized and further administrated in drinking water to obese, insulin resistant mouse. We evaluated the effect of ACN loaded niosomes on hyperglycemia, glucose and insulin intolerance and insulin blood levels in C57BL/6 J mice fed with a high-fat diet. RESULTS: The ACN-loaded particles were moderately monodisperse, showed a negative surface charge and 57% encapsulation efficiency. The ACN-loaded niosomes ameliorated the insulin resistance and glucose intolerance in the DIO mice model. Additionally, they reduced animal weight and plasma insulin, glucose, leptin and total cholesterol levels in obese mice. CONCLUSION: ACN-loaded niosomes administration, as a functional drink, had a beneficial effect on the reversal of metabolic abnormalities associated with obesity.


Assuntos
Antocianinas/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/química , Lipossomos/química , Nanocápsulas/química , Extratos Vegetais/química , Estreptófitas/química , Animais , Antocianinas/administração & dosagem , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Colesterol/metabolismo , Diabetes Mellitus Experimental , Dieta Hiperlipídica , Composição de Medicamentos , Liberação Controlada de Fármacos , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/sangue , Insulina/metabolismo , Insulina/farmacologia , Resistência à Insulina , Leptina/sangue , Leptina/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem
11.
Molecules ; 25(7)2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32218297

RESUMO

Plant extracts from Cecropia genus have been used by Latin-American traditional medicine to treat metabolic disorders and diabetes. Previous reports have shown that roots of Cecropia telenitida that contains serjanic acid as one of the most prominent and representative pentacyclic triterpenes. The study aimed to isolate serjanic acid and evaluate its effect in a prediabetic murine model by oral administration. A semi-pilot scale extraction was established and serjanic acid purification was followed using direct MALDI-TOF analysis. A diet induced obesity mouse model was used to determine the impact of serjanic acid over selected immunometabolic markers. Mice treated with serjanic acid showed decreased levels of cholesterol and triacylglycerols, increased blood insulin levels, decreased fasting blood glucose and improved glucose tolerance, and insulin sensitivity. At transcriptional level, the reduction of inflammation markers related to adipocyte differentiation is reported.


Assuntos
Biomarcadores/metabolismo , Obesidade/imunologia , Obesidade/metabolismo , Triterpenos/uso terapêutico , Tecido Adiposo/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Metabolismo dos Carboidratos/efeitos dos fármacos , Dieta Hiperlipídica , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Secreção de Insulina/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos , Obesidade/sangue , Obesidade/tratamento farmacológico , Tamanho do Órgão/efeitos dos fármacos , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
12.
Environ Res ; 173: 12-22, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30884434

RESUMO

Antibiotics accumulation in aquatic organisms may be of great concern from an ecological point of view but also from a human perspective, especially when they are accumulated in edible animals like marine mussels. In this work, mussels (Mytilus galloprovincialis) were exposed to sulfamethoxazole antibiotic (SMX) at 10 µg/L during 96 h, followed by 24 h of depuration. The experiment was carried out at summer and winter conditions. SMX showed a bioconcentration factor in mussel of 1.5 L/kg (dry weight) and 69% of the compound was eliminated from the organism in 24 h. The metabolomics approach revealed alterations in amino acids levels (aspartate, phenylalanine, valine and tryptophan) pinpointing disturbances in osmotic regulation and energy metabolism. Besides, the levels of some nucleotides (guanosine and inosine) and a carboxylic acid were also affected. However, SMX exposed mussels did not show any significant alteration in the enzymatic activities related to the xenobiotic metabolism and oxidative stress. Moreover, some of the changes observed in mussel's metabolites suggested alterations in mussel's organoleptic characteristics that can affect its quality as seafood commodity. Overall, our results showed that SMX exposure to marine mussels may have ecological implications by provoking sub-lethal effects to exposed organisms. Nevertheless, no risk for consumers derived from mussel ingestion is expected due to the low bioconcentration capacity of SMX and fast depuration in this seafood type.


Assuntos
Mytilus/fisiologia , Sulfametoxazol/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Bioacumulação , Metabolômica
13.
J Med Internet Res ; 21(9): e15505, 2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-31538948

RESUMO

BACKGROUND: Although electronic health interventions are considered safe and efficient, evidence regarding the cost-effectiveness of telemonitoring in inflammatory bowel disease is lacking. OBJECTIVE: We aimed to evaluate the cost-effectiveness and cost-utility of the Telemonitorización de la Enfermedad de Crohn y Colitis Ulcerosa (Telemonitoring of Crohn's Disease and Ulcerative Colitis [TECCU]) Web platform (G_TECCU intervention group) for telemonitoring complex inflammatory bowel disease, compared with standard care (G_control) and nurse-assisted telephone care (G_NT intervention group). METHODS: We analyzed cost-effectiveness from a societal perspective by comparing the 3 follow-up methods used in a previous 24-week randomized controlled trial, conducted at a tertiary university hospital in Spain. Patients with inflammatory bowel disease who initiated immunosuppressants or biologic agents, or both, to control inflammatory activity were recruited consecutively. Data on the effects on disease activity (using clinical indexes) and quality-adjusted life-years (using the EuroQol 5 dimensions questionnaire) were collected. We calculated the costs of health care, equipment, and patients' productivity and social activity impairment. We compared the mean costs per patient, utilities, and bootstrapped differences. RESULTS: We included 63 patients (21 patients per group). TECCU saved €1005 (US $1100) per additional patient in remission compared with G_control (95% CI €-13,518 to 3137; US $-14,798 to 3434), with a 79.96% probability of being more effective at lower costs. Compared with G_NT, TECCU saved €2250 (US $2463) per additional patient in remission (95% CI €-15,363 to 11,086; US $-16,817 to 12,135), and G_NT saved €538 (US $589) compared with G_control (95% CI €-6475 to 5303; US $-7088 to 5805). G_TECCU and G_NT showed an 84% and 67% probability, respectively, of producing a cost saving per additional quality-adjusted life-year (QALY) compared with G_control, considering those simulations that involved negative incremental QALYs as well. CONCLUSIONS: There is a high probability that the TECCU Web platform is more cost-effective than standard and telephone care in the short term. Further research considering larger cohorts and longer time horizons is required. TRIAL REGISTRATION: ClinicalTrials.gov NCT02943538; https://clinicaltrials.gov/ct2/show/NCT02943538 (http://www. webcitation.org/746CRRtDN).


Assuntos
Colite Ulcerativa/economia , Colite Ulcerativa/epidemiologia , Análise Custo-Benefício/métodos , Doença de Crohn/economia , Doença de Crohn/epidemiologia , Telemedicina/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
J Med Internet Res ; 20(11): e11602, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30482739

RESUMO

BACKGROUND: The reported efficacy of telemedicine in patients with inflammatory bowel disease (IBD) is inconsistent among studies, and data for complex IBD are lacking. OBJECTIVE: We aimed to evaluate the impact of remote monitoring using a Web system-Telemonitorización de la Enfermedad de Crohn y Colitis Ulcerosa or Telemonitoring of Crohn's Disease and Ulcerative Colitis (TECCU)-as compared to standard care and telephone care on health outcomes and health care in patients with complex IBD. METHODS: We performed a 3-arm randomized controlled trial. Adult patients with IBD who received immunosuppressants and biological agents were recruited from the IBD Unit of a tertiary university hospital. The patients were randomized into groups to receive remote monitoring (G_TECCU), nurse-assisted telephone care (G_NT), or standard care with in-person visits (G_control). All patients completed the study visits at baseline and at 12 and 24 weeks in addition to each type of intervention. The primary outcome was the percentage of patients in remission at 24 weeks. Secondary health outcomes were quality of life, medication adherence, adverse effects, satisfaction, and social activities. Data on the number of outpatient visits and telephone calls, emergency visits, hospitalizations, IBD-related surgeries, and corticosteroid courses were also collected. RESULTS: A total of 63 patients were selected (21 patients in each group). During the study, 90.5% (19/21) of patients in G_control, 95.2% (20/21) in G_NT, and 85.7% (18/21) in G_TECCU were compliant to the intervention. After 24 weeks, the percentage of patients in remission was higher in G_TECCU (17/21, 81%) than in G_NT (14/21, 66.7%) and G_control (15/21, 71.4%). A higher improvement in disease activity was observed in G_TECCU than in G_control in terms of the Harvey-Bradshaw/Mayo (odds ratio=0.12, 95% CI=0.003-2.162, P=.19) and Harvey-Bradshaw/Walmsley (odds ratio=0.11, 95% CI=0.004-1.55, P=.13) indexes. Improvement in disease activity was associated with a larger reduction in fecal calprotectin values in G_TECCU compared to G_control (estimated intervention effect: odds ratio=-0.90; 95% CI=-1.96 to 0.16, P=.11). All completers adhered to treatment in G_TECCU. In addition, the quality of life, social activities, and satisfaction improved in all 3 groups. Although the number of outpatient visits and telephone calls was lower in G_TECCU than in G_NT and G_control, the safety profile was similar in all 3 groups. CONCLUSIONS: This pilot clinical trial suggests that the TECCU Web-based system is a safe strategy for improving health outcomes in patients with complex IBD and reducing the use of health care resources. TRIAL REGISTRATION: ClinicalTrials.gov NCT02943538; https://clinicaltrials.gov/ct2/show/NCT02943538 (Archived by WebCite at http://www.webcitation.org/746CRRtDN).


Assuntos
Colite Ulcerativa/psicologia , Colite Ulcerativa/terapia , Doença de Crohn/psicologia , Doença de Crohn/terapia , Doenças Inflamatórias Intestinais/psicologia , Doenças Inflamatórias Intestinais/terapia , Qualidade de Vida/psicologia , Telemedicina/métodos , Adulto , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto Jovem
15.
Neural Plast ; 2018: 5257285, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29755512

RESUMO

Alzheimer's disease (AD) is the most common type of dementia, mainly encompassing cognitive decline in subjects aged ≥65 years. Further, AD is characterized by selective synaptic and neuronal degeneration, vascular dysfunction, and two histopathological features: extracellular amyloid plaques composed of amyloid beta peptide (Aß) and neurofibrillary tangles formed by hyperphosphorylated tau protein. Dementia and AD are chronic neurodegenerative conditions with a complex physiopathology involving both genetic and environmental factors. Recent clinical studies have shown that proton pump inhibitors (PPIs) are associated with risk of dementia, including AD. However, a recent case-control study reported decreased risk of dementia. PPIs are a widely indicated class of drugs for gastric acid-related disorders, although most older adult users are not treated for the correct indication. Although neurological side effects secondary to PPIs are rare, several preclinical reports indicate that PPIs might increase Aß levels, interact with tau protein, and affect the neuronal microenvironment through several mechanisms. Considering the controversy between PPI use and dementia risk, as well as both cognitive and neuroprotective effects, the aim of this review is to examine the relationship between PPI use and brain effects from a neurobiological and clinical perspective.


Assuntos
Demência/induzido quimicamente , Demência/metabolismo , Inibidores da Bomba de Prótons/metabolismo , Inibidores da Bomba de Prótons/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Estudos de Casos e Controles , Demência/tratamento farmacológico , Humanos , Emaranhados Neurofibrilares/efeitos dos fármacos , Emaranhados Neurofibrilares/metabolismo , Placa Amiloide/induzido quimicamente , Placa Amiloide/tratamento farmacológico , Placa Amiloide/metabolismo , Inibidores da Bomba de Prótons/efeitos adversos , Proteínas tau/metabolismo
16.
J Med Virol ; 88(1): 144-52, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26113443

RESUMO

Human Papillomavirus (HPV) is the most common sexually transmitted infection worldwide and it is responsible for most cases of uterine cancer. In Ecuador there is limited information about HPV types (and variants) in cancerous lesions; however, identifying the type-specific HPV prevalence in cervical lesions of women living in Ecuador is important to better predict the impact of HPV prophylactic vaccination in this country. We studied the prevalence of HPV types in cervical cancerous or precancerous lesions from 164 Ecuadorian women and found that 86.0% were HPV positive. The most common types were HPV16 (41.8%) and HPV58 (30.5%). Interestingly, HPV18 was detected only in 2.8% of the HPV-positive samples. Fifteen DNA sequences (genes E6 and L1) from 16 samples positive for HPV16 belonged to the European lineage, considered one of the least carcinogenic lineages, and 1 (6.25%) to the Asian-American lineage. Similar analysis in 12 HPV58 positive samples showed that 10 (83.3%) sequences grouped in sublineage A2, which belongs to the oldest HPV58 lineage, 1 belonged to A3 and 1 to lineage C. This study suggests that the currently used HPV vaccines (bivalent and tetravalent) may have lower effectiveness in Ecuador than in other geographic locations where HPV18 is more prevalent.


Assuntos
Genótipo , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Equador/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Filogenia , Lesões Pré-Cancerosas/epidemiologia , Prevalência , Análise de Sequência de DNA , Neoplasias do Colo do Útero/epidemiologia
18.
Proc Natl Acad Sci U S A ; 110(35): 14378-83, 2013 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-23942126

RESUMO

Gliomas represent the most common type of brain tumor, but show considerable variability in histologic appearance and clinical outcome. The phenotypic differences between types and grades of gliomas have not been explained solely on the grounds of differing oncogenic stimuli. Several studies have demonstrated that some phenotypic differences may be attributed to regional differences in the neural stem cells from which tumors arise. We hypothesized that temporal differences may also play a role, with tumor phenotypic variability reflecting intrinsic differences in neural stem cells at distinct developmental stages. To determine how the tumorigenic potential of lineally related stem cells changes over time, we used a conditional transgenic system that integrates Cre-Lox-mediated and Tet-regulated expression to drive K-ras(G12D) expression in neuro-glial progenitor populations at different developmental time points. Using this model, we demonstrate that K-ras(G12D)-induced transformation is dependent on the developmental stage at which it is introduced. Diffuse malignant brain tumors develop during early embryogenesis but not when K-ras(G12D) expression is induced during late embryogenesis or early postnatal life. We show that differential expression of cell-cycle regulators during development may be responsible for this differing susceptibility to malignant transformation and that loss of p53 can overcome the transformation resistance seen at later developmental stages. These results highlight the interplay between genetic alterations and the molecular changes that accompany specific developmental stages; early progenitors may lack the regulatory mechanisms present at later, more lineage-restrictive, developmental time points, making them more susceptible to transformation.


Assuntos
Diferenciação Celular , Transformação Celular Neoplásica , Células-Tronco Neurais/citologia , Neuroglia/citologia , Animais , Sequência de Bases , Encéfalo/metabolismo , Encéfalo/patologia , Primers do DNA , Células-Tronco Embrionárias/citologia , Genes ras , Camundongos , Camundongos Transgênicos , Oncogenes , Reação em Cadeia da Polimerase
19.
ScientificWorldJournal ; 2016: 6589751, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27200408

RESUMO

Aim. To report a new surgical technique for the treatment of conjunctivochalasis. Methods. A new surgical technique in which specially designed bipolar electrocautery forceps facilitate the complete reduction of the conjunctival folds without creating lesions near the corneoscleral limbus was designed. A retrospective revision of the medical records of patients treated with this technique between the years 2011 and 2013 was made, and eighteen eyes of sixteen patients with conjunctivochalasis treated with this new technique were included. Results. All the eyes treated showed a significant improvement with no evidence of scar lesions after a mean follow-up time of 10 months. Conclusions. The surgical technique presented here could be a good alternative for the management of conjunctivochalasis.


Assuntos
Doenças da Túnica Conjuntiva/cirurgia , Procedimentos Cirúrgicos Oftalmológicos/métodos , Instrumentos Cirúrgicos , Túnica Conjuntiva/cirurgia , Eletrocoagulação , Humanos , Estudos Retrospectivos
20.
Antimicrob Agents Chemother ; 59(9): 5804-13, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26169411

RESUMO

An evaluation of the leishmanicidal activity in vitro and in vivo of hypericin, an expanded-spectrum photosensitizer found in Hypericum perforatum, is presented. Hypericin was evaluated against intracellular amastigotes in vitro of Leishmania (Viannia) panamensis. A topical formulation containing 0.5% hypericin was developed and assayed in vivo in a hamster model of cutaneous leishmaniasis. Results demonstrate that hypericin induces a significant antiamastigote effect in vitro against L. panamensis by decreasing the number of parasites inside infected cells. The topical formulation of 0.5% hypericin allows healing of L. panamensis-induced lesions upon a topical application of 40 mg/day plus visible-light irradiation (5 J/cm(2), 15 min), twice a week for 3 weeks.


Assuntos
Leishmaniose Cutânea/tratamento farmacológico , Perileno/análogos & derivados , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Antracenos , Linhagem Celular , Cricetinae , Humanos , Leishmania/efeitos dos fármacos , Leishmania/patogenicidade , Leishmaniose Cutânea/terapia , Perileno/uso terapêutico , Células U937 , Cicatrização/efeitos dos fármacos
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