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1.
Phys Chem Chem Phys ; 25(22): 15555-15566, 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37252735

RESUMO

We studied N 1s-1 inner-shell processes of the free base Phthalocyanine molecule, H2Pc, in the gas-phase. This complex organic molecule contains three different nitrogen sites defined by their covalent bonds. We identify the contribution of each site in ionized, core-shell excited or relaxed electronic states by the use of different theoretical methods. In particular, we present resonant Auger spectra along with a tentative new theoretical approach based on multiconfiguration self-consistent field calculations to simulate them. These calculations may pave the road towards resonant Auger spectroscopy in complex molecules.

2.
Rep Prog Phys ; 83(12): 124201, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33226008

RESUMO

The combination of the high intensity proton beam facilities and massive detectors for precision measurements of neutrino oscillation parameters including the charge-parity violating (CPV) phase will open the door to help make beyond the standard model (BSM) physics reachable even in low energy regimes in the accelerator-based experiments. Large-mass detectors with highly precise tracking and energy measurements, excellent timing resolution, and low energy thresholds will enable the searches for BSM phenomena from cosmogenic origin, as well. Therefore, it is also conceivable that BSM topics in the next-generation neutrino experiments could be the dominant physics topics in the foreseeable future, as the precision of the neutrino oscillation parameter and CPV measurements continue to improve.This paper provides a review of the current landscape of BSM theory in neutrino experiments in two selected areas of the BSM topics-dark matter and neutrino related BSM-and summarizes the current results from existing neutrino experiments to set benchmarks for both theory and experiment. This paper then provides a review of upcoming neutrino experiments throughout the next 10 to 15 year time scale and their capabilities to set the foundation for potential reach in BSM physics in the two aforementioned themes. An important outcome of this paper is to ensure theoretical and simulation tools exist to carry out studies of these new areas of physics, from the first day of the experiments, such as Deep Underground Neutrino Experiment in the U.S. and Hyper-Kamiokande Experiment in Japan.

3.
Int Endod J ; 53(8): 1140-1152, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32299123

RESUMO

AIM: To analyse the cytotoxicity, colour change and radiopacity of MTA Flow (MTA), UltraCal XS (UC) and Bio-C Temp (BT). METHODOLOGY: Human dental pulp cells (hDPCs) stimulated with lipopolysaccharide (LPS) were placed in contact with several dilutions of culture media previously exposed to the experimental materials and tested for cell viability using MTT. Bovine teeth were prepared to simulate an open apex and to mimic extensive crown fracture. The roots were filled with a mixture of agar and blood, and the materials placed over this mixture. The control group consisted of teeth filled only with agar and blood. Colour assessment analyses were performed before and immediately after material insertion and repeated at 30, 45 and 60 days using a spectrophotometer. The total colour change (ΔEab , ΔE00 and whiteness index (WI)) was calculated based on the CIELAB colour space. Digital radiographs were acquired for radiopacity analysis. Cell viability was analysed by one-way anova, whilst differences in colour parameters (ΔEab , ΔE00 and WI) were assessed by two-way repeated measures anova (α = 0.05). Tukey's test was used to compare the experimental groups, and Dunnett's test was used to compare the experimental groups with the control group. RESULTS: MTA, UC and BT had similar cell viability to that of the control group (DMEM) (P > 0.05), except for the BT group at the 1 : 1 and 1 : 2 dilutions, which had significantly lower viability (P < 0.001). All materials were associated with discoloration values greater than what is considered to be the acceptable threshold, and BT resulted in less or similar tooth colour change than MTA and UC, respectively. Decreasing radiopacity over time was observed only in the MTA group (P = 0.007). Lower values of radiopacity were found in the BT group compared with the UC and MTA groups (P < 0.001). CONCLUSIONS: The new bioceramic material (BT) had acceptable cell viability, similar to that of MTA and UC at the highest dilutions, and BT resulted in less tooth colour change than MTA and UC. Despite its lower radiopacity, BT was identified radiographically.


Assuntos
Materiais Restauradores do Canal Radicular , Descoloração de Dente , Compostos de Alumínio , Animais , Compostos de Cálcio , Bovinos , Sobrevivência Celular , Combinação de Medicamentos , Humanos , Óxidos , Endodontia Regenerativa , Silicatos
4.
Dermatol Online J ; 26(4)2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32621686

RESUMO

Gout is a multisystem disease that may present in different ways. We report an elderly man who presented with a large ulcer of the left leg with hard yellow projections evolving for one year. Analytical study revealed a normal uric acid level, but histopathology showed a focal basophilic acellular material compatible with a gouty tophus. This tophus represents the cardinal feature of advanced gout and may present several challenges to wound care professionals. In fact, the ulcer in our patient persisted after one-year follow-up. Our aim is to alert clinicians about a rare cutaneous presentation of gout that may be increasingly diagnosed.


Assuntos
Gota/patologia , Úlcera da Perna/patologia , Idoso de 80 Anos ou mais , Gota/complicações , Humanos , Úlcera da Perna/etiologia , Masculino , Obesidade/complicações , Ácido Úrico/sangue
5.
Scand J Rheumatol ; 48(2): 121-127, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30112959

RESUMO

OBJECTIVE: To assess the risk of hospitalized infection among initiators of disease-modifying anti-rheumatic drugs (DMARDs) and/or anti-tumour necrosis factor (anti-TNF) agents in ankylosing spondylitis (AS). METHOD: We studied AS patients, new users of anti-TNF drugs and/or DMARDs between 1 January 2001 and 31 December 2011. Cohort entry was defined as the date of first prescription of any of these drugs. We used Cox regression with three time-varying drug exposures: current use of DMARDs without biologics, current use of anti-TNF agents alone or in combination with DMARDs (anti-TNF ± DMARDs), and current non-use. Models were adjusted for baseline patient sociodemographic characteristics, comorbidity, outpatient visits and procedures, previous infection, non-steroidal anti-inflammatory drugs, and corticosteroids. Hospitalized infection was defined on the basis of hospitalization discharge diagnoses (primary or non-primary) coding for infection. RESULTS: The cohort included 747 AS patients, with a mean age of 51.1 years (sd 14.6), and 466 (62.4%) were men. During the median follow-up of 1.98 years, 57 hospitalized infections occurred, for an incidence rate of 2.9/100 person-years. The adjusted hazard ratio of infection (relative to unexposed) was 1.00 [95% confidence interval (CI) 0.47-2.11] for the anti-TNF ± DMARDs group and 0.96 (95% CI 0.45-2.04) for DMARDs alone. Use of healthcare, corticosteroids, and previous hospitalized infections were associated with infection. CONCLUSION: We found no clear evidence that the risk of hospitalized infection was linked to DMARD and/or anti-TNF drug use. Because of scarce published literature on infection risk in AS patients, our results have important implications for clinicians.


Assuntos
Antirreumáticos/efeitos adversos , Infecções/induzido quimicamente , Espondilite Anquilosante/tratamento farmacológico , Estudos de Coortes , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/antagonistas & inibidores
6.
Int Endod J ; 52(5): 629-638, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30388307

RESUMO

AIM: To evaluate the in vitro cytotoxicity and cytokine release of three fresh root canal sealers and to determine the type of cell death they induce. METHODOLOGY: The sealers tested were Sealer 26 (S26), AH Plus (AHP), and Endosequence BC Sealer (END). Fresh sealers were cultivated in contact with monocytes and polymorphonuclears (PMNs) obtained from the peripheral blood of humans. Cell viability, apoptosis and necrosis were analysed at 4 h (PMNs) or 24 h (monocytes) using Annexin-V and propidium iodide in a cytometer. The supernatants were used to quantify Interleukin (IL)-4, IL-6, IL-10, IL-12 and tumour necrosis factor-α (TNF-α) in monocytes and IL-8 in PMNs by ELISA. One-way ANOVA and the Tukey post-test were used to compare data for cytotoxicity, and the multiple T-test was used to determine the differences between sealers in the release of cytokines that were statistically significant. RESULTS: After 4 h of treatment, S26 was associated with greater cell viability than the other sealers (P < 0.05) in the PMN culture and had similar values of necrosis as END (P > 0.05). After 24 h of treatment, AHP and END had greater monocyte cell viability than S26 (P < 0.05), which had more necrosis (P < 0.05). END had the lowest levels of IL-12 compared to the other sealers (P < 0.05) and higher levels of IL-6 compared to S26 (P < 0.05). The tested sealers did not differ in the release of IL-8, IL-10, TNF-α and IL-4 (P > 0.05). CONCLUSIONS: The effect of toxic agents released varied depending on the cell type studied. The composition of the sealers appeared to alter the form of self-regulation in the production of these cytokines by cells.


Assuntos
Materiais Restauradores do Canal Radicular , Apoptose , Citocinas , Cavidade Pulpar , Humanos , Monócitos
7.
Lupus ; 26(2): 204-207, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27365372

RESUMO

The relationship between primary hematologic disease and rheumatologic manifestations is well known, especially acute lymphocytic leukemia, lymphomas, plasma cell dyscrasias and myelodysplastic syndrome (MDS). Currently, more has been described about autoimmune manifestations in chronic myelomonocytic leukemia (CMML). Many different clinical scenarios may lead a patient with MDS/CMML initially to seek a rheumatological unit. Autoimmune features such as polymyalgia rheumatic symptoms, myositis, neutrophilic dermatosis, cutaneous vasculitis and positive antinuclear antibodies (ANA) are some examples of clinical presentation of MDS/CMML. Moreover, peripheral cytopenias are a common initial presentation both for systemic lupus erythematous (SLE) and MDS/CMML. The aim of this study was to describe a case of an elderly woman with thrombocytopenia and positivity of antibodies to anti-extractable nuclear antigens (anti-ENA) as initial manifestation of CMML mimicking SLE, and to present some clues that encourage the clinician to perform a bone marrow study in such a clinical scenario.


Assuntos
Anticorpos Antinucleares/sangue , Leucemia Mielomonocítica Crônica/sangue , Lúpus Eritematoso Sistêmico/sangue , Trombocitopenia/sangue , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Biomarcadores/sangue , Exame de Medula Óssea , Diagnóstico Diferencial , Feminino , Hemólise , Humanos , Leucemia Mielomonocítica Crônica/diagnóstico , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Leucemia Mielomonocítica Crônica/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Valor Preditivo dos Testes , Trombocitopenia/diagnóstico , Trombocitopenia/imunologia
8.
Int Endod J ; 50(12): 1185-1191, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27977860

RESUMO

AIM: To perform multiparametric analysis of the effects of soya milk (SM), whole milk (WM) and Hank's balanced salt solution (HBSS) on the viability of fibroblasts (HGF). The study also aimed to evaluate the influence of these solutions on bovine root dentine according to OH- and PO43- on the surface. METHODOLOGY: The HGF cytotoxicity was determined according to XTT, NR and SRB assays at 1, 3 and 6 h. Root dentine fragments were assessed by Fourier infrared (FTIR) spectrophotometer before and after immersion in the solutions for the same periods. The positive control group included cells and tooth fragments maintained in Dulbecco's modified Eagle's medium (DMEM), and the negative control included tooth fragments that were kept dry. Data were analysed using anova and Tukey's test. RESULTS: No significant difference was found in cell viability evaluated by XTT (P > 0.05). Using the NR assay, WM and HBSS had significantly lower cell viability compared to the positive control group at 6 h (P < 0.05). SM had similar cell viability to the positive control group at all periods evaluated when assessed using all three tests (P > 0.05). A significant difference was found in values of OH- for the negative control group at 1 h (P = 0.002). CONCLUSIONS: Soya milk promoted better cell viability, whereas on dentine composition, the solutions behaved similarly. The association of different assay methods is promising for improving cell viability analysis. The 1-h time-point is a crucial factor in the prognosis of dental replantation because the teeth remain more hydrated and help maintain cell viability.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Dentina/efeitos dos fármacos , Leite , Leite de Soja/farmacologia , Animais , Bovinos , Fibroblastos/efeitos dos fármacos , Incisivo/efeitos dos fármacos , Soluções para Preservação de Órgãos/farmacologia , Raiz Dentária/efeitos dos fármacos
9.
Int Endod J ; 50(1): 84-89, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26667879

RESUMO

AIM: To investigate the ability of newly developed powdered coconut water formulas (ACP) with different osmolarities to maintain the viability of periodontal ligament (PDL) cells over time compared with other solutions. METHODOLOGY: Dogs teeth were extracted and stored for two periods, 3 h or 24 h, in the following media: long-shelf life CW (CW), pH-adjusted long-shelf life CW (pH-CW) and powdered CW that was pH and osmolality adjusted (ACP-404-I, 250 mOsm kg-1 H2 O; pH 7.0; ACP-404-II, 372 mOsm kg-1 H2 O; pH 7.0; ACP-404-III, 300 mOsm kg-1 H2 O; pH 7.4). The positive control group (Pc) corresponded to immediate measurement after tooth extraction, and two negative controls (Nc) corresponded to 3 h and 24 h of dry time. PDL cells were extracted, and cell viability analysed by Trypan blue exclusion. Data were analysed statistically using two-way anova followed by the Tukey test and one-way anova followed by the Dunnett test (P < 0.05). RESULTS: At 3 h and 24 h, ACP-404-I had a performance similar to those of ACP-404-II and pH-CW, with significantly higher (P = 0.004) percentages of viable cells than ACP-404-III and CW. The positive control group had a significantly higher (P = 0.002) percentage of viable cells than the negative control groups, CW and ACP-404-III, irrespective of the period evaluated. CONCLUSION: Powdered coconut water formulas, ACP-404-I and ACP-404-II, preserved viability for up to 24 h.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Cocos , Soluções para Preservação de Órgãos/farmacologia , Ligamento Periodontal/citologia , Animais , Cães , Concentração Osmolar , Pós
10.
Horm Metab Res ; 48(12): 854-861, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27756093

RESUMO

Neuromedin B (NB) and gastrin-releasing peptide (GRP) are bombesin-like peptides, found in the gastrointestinal tube and pancreas, among other tissues. Consistent data proposed that GRP stimulates insulin secretion, acting directly in pancreatic cells or in the release of gastrointestinal hormones that are incretins. However, the role of NB remains unclear. We examined the glucose homeostasis in mice with deletion of NB receptor (NBR-KO). Female NBR-KO exhibited similar fasting basal glucose with lower insulinemia (48.4%) and lower homeostasis model assessment of insulin resistance index (50.5%) than wild type (WT). Additionally, they were more tolerant to oral glucose, demonstrated by a decrease in the area under the glucose curve (18%). In addition, 15 min after an oral glucose load, female and male NBR-KO showed lower insulin serum levels (45.6 and 26.8%, respectively) than WT, even though blood glucose rose to similar levels in both groups. Single injection of NB, one hour before the oral glucose administration, tended to induce higher serum insulin in WT (28.9%, p=0.3), however the same did not occur in NBR-KO. They showed no changes in fasting insulin content in pancreatic islets by immunohistochemistry, however, the fasting serum levels of glucagon-like peptide, a potent incretin, exhibited a strong trend to reduction (40%, p=0.07). Collectively, mice with deletion of NB receptor have lower insulinemia, especially in response to oral glucose, and females also exhibited a better glucose tolerance, suggesting the involvement of NB and its receptor in regulation of insulin secretion induced by incretins, and also, in insulin sensitivity.


Assuntos
Deleção de Genes , Glucose/administração & dosagem , Glucose/farmacologia , Insulina/metabolismo , Receptores da Bombesina/metabolismo , Administração Oral , Animais , Jejum , Feminino , Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Teste de Tolerância a Glucose , Homeostase/efeitos dos fármacos , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurocinina B/administração & dosagem , Neurocinina B/análogos & derivados , Neurocinina B/farmacologia , Receptores da Bombesina/deficiência
11.
Eur J Nutr ; 55(2): 601-610, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25801629

RESUMO

PURPOSE: Perinatal high-fat diet is associated with obesity and metabolic diseases in adult offspring. Resveratrol has been shown to exert antioxidant and anti-obesity actions. However, the effects of resveratrol on leptinemia and leptin signaling are still unknown as well as whether resveratrol treatment can improve metabolic outcomes programmed by maternal high-fat diet. We hypothesize that resveratrol treatment in male rats programmed by high-fat diet would decrease body weight and food intake, and leptinemia with changes in central leptin signaling. METHODS: Female Wistar rats were divided into two groups: control group (C), which received a standard diet containing 9 % of the calories as fat, and high-fat group (HF), which received a diet containing 28 % of the calories as fat. Dams were fed in C or HF diet during 8 weeks before mating and throughout gestation and lactation. C and HF male offspring received standard diet throughout life. From 150 until 180 days of age, offspring received resveratrol (30 mg/Kg body weight/day) or vehicle (carboxymethylcellulose). RESULTS: HF offspring had increased body weight, hyperphagia and increased subcutaneous and visceral fat mass compared to controls, and resveratrol treatment decreased adiposity. HF offspring had increased leptinemia as well as increased SOCS3 in the arcuate nucleus of the hypothalamus, which suggest central leptin resistance. Resveratrol treatment rescued leptinemia and increased p-STAT3 content in the hypothalamus with no changes in SOCS3, suggesting improvement in leptin signaling. CONCLUSIONS: Collectively, our data suggest that resveratrol could reverse hyperleptinemia and improve central leptin action in adult offspring from HF mothers attenuating obesity.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Leptina/sangue , Fenômenos Fisiológicos da Nutrição Materna , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Estilbenos/farmacologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Composição Corporal , Feminino , Hiperfagia/fisiopatologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Masculino , Obesidade/fisiopatologia , Gravidez , Ratos , Ratos Wistar , Resveratrol , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Aumento de Peso
12.
J Chem Phys ; 144(11): 114305, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-27004874

RESUMO

Plant volatiles are emitted by plants in response to several forms of stress, including interaction with energetic photons. In the present work, we discuss the interaction of extreme UV and soft X-ray photons with a plant volatile, vanillin. The single and double (multiple) ionization of the vanillin molecule have been studied for the first time using time-of-flight mass spectrometry and VUV and soft X-ray photons (synchrotron radiation, at 12.0 eV, 21.2 eV, 130 eV, 310 eV, 531 eV, and 550 eV). At 12.0 and 21.2 eV, only singly charged species are observed and the parent ion, C8H8O3 (+), is the dominant species. Energy differences for some selected fragments were calculated theoretically in this energy region. At 130 eV, direct double and triple ionization of the valence electrons may occur. The fragmentation increases and CHO(+) becomes one of the main cations in the mass spectrum. The molecular ion is still the dominant species, but other fragments, such as C6H5O(+), begin to present similar intensities. At 310 eV, C 1s electrons may be ionized and Auger processes give rise to dissociative doubly ionized cations. Ionization around the O 1s edge has been studied both at the 531 eV resonance and above the ionization edge. Resonant and normal Auger processes play a significant role in each case and a large fragmentation of the molecule is observed at both photon energies, with intense fragments such as CHO(+) and CH3 (+) being clearly observed. A near edge X-ray absorption fine structure spectrum of the vanillin molecule was obtained around the O 1s ionization threshold. In addition, the fragmentation of vanillin has also been studied using a fast beam of electrons (800 eV), for the sake of comparison.


Assuntos
Benzaldeídos/efeitos da radiação , Compostos Orgânicos Voláteis/efeitos da radiação , Benzaldeídos/química , Espectrometria de Massas , Modelos Químicos , Fótons , Espectrofotometria , Raios Ultravioleta , Compostos Orgânicos Voláteis/química , Raios X
13.
Eur J Gynaecol Oncol ; 37(6): 814-816, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29943927

RESUMO

AIM: To evaluate the clinical and epidemiological profile of women with breast cancer, managed in the Breast Service at Hospital Get6lio Vargas (HGV). MATERIALS AND METHODS: A descriptive, observational cross-sectional study, involving 174 breast cancer patients, managed at the Breast Service at HGV in Teresina, in the northeast of Brazil, from May 2011 to June 2014. Epidemiological variables included age group, age at menarche, age at first childbirth, and menopause. The tumor characteristics studied were histological type, TNM classification, and staging. The results were organized in distribution tables. RESULTS: Breast carcinoma was more common in patients aged 60 and over, in multiparous women, and in women who were menopausal before age 55. The most common histological type was ductal invasive carcinoma T2N1MO (Stage IIB) in 83 (48%) women. CONCLUSION: The current study shows that the majority of carcinomas were Stage II or advanced tumors, with clinically positive axillary lymph node status and weak correlation with reproductive risk factors.


Assuntos
Neoplasias da Mama/epidemiologia , Encaminhamento e Consulta , Adulto , Idoso , Neoplasias da Mama/patologia , Estudos Transversais , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias
14.
J Contemp Dent Pract ; 17(12): 969-972, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27965481

RESUMO

INTRODUCTION: This study evaluated the cervical fit of cemented metal-ceramic and In-Ceram implant-supported crowns, before and after the cementing procedure. MATERIALS AND METHODS: Twenty crowns cemented on implant abutments are divided into two groups (n = 10): Group 1 -cemented metal-ceramic crowns and group 2 - cemented In-Ceram crowns. The marginal adaptations before and after cementation were evaluated in a comparison microscope with an error of 1 µm. All crowns were cemented with zinc phosphate cement. RESULTS: The cervical misalignment of cemented crowns before cementation (52.65 ± 11.83 and 85.73 ± 14.06 µm) was lower than that after cementation (66.80 ± 15.86 and 89.36 ± 22.66 µm). CONCLUSION: The cementing procedure interferes with the marginal fit of cemented crowns on implant abutments, with the prosthesis having better adaptation before cementation. Cemented metal-ceramic crowns exhibited better cervical adaptation than In-Ceram crowns cemented before and after the cementing procedure. CLINICAL SIGNIFICANCE: The maintenance of gum health and the longevity of prosthetic restorations are closely related to the restoration's marginal integrity.


Assuntos
Óxido de Alumínio , Cimentação/métodos , Coroas , Cimentos Dentários , Porcelana Dentária , Ligas Metalo-Cerâmicas , Planejamento de Prótese Dentária , Falha de Restauração Dentária , Humanos
15.
Clin Genet ; 88(5): 456-61, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25307543

RESUMO

Pathogenic mutations in genes COL4A3/COL4A4 are responsible for autosomal Alport syndrome (AS) and thin basement membrane nephropathy (TBMN). We used Sanger sequencing to analyze all exons and splice site regions of COL4A3/COL4A4, in 40 unrelated Portuguese probands with clinical suspicion of AS/TBMN. To assess genotype-phenotype correlations, we compared clinically relevant phenotypes/outcomes between homozygous/compound heterozygous and apparently heterozygous patients. Seventeen novel and four reportedly pathogenic COL4A3/COL4A4 mutations were identified in 62.5% (25/40) of the probands. Regardless of the mutated gene, all patients with ARAS manifested chronic renal failure (CRF) and hearing loss, whereas a minority of the apparently heterozygous patients had CRF or extrarenal symptoms. CRF was diagnosed at a significantly younger age in patients with ARAS. In our families, the occurrence of COL4A3/COL4A4 mutations was higher, while the prevalence of XLAS was lower than expected. Overall, a pathogenic COL4A3/COL4A4/COL4A5 mutation was identified in >50% of patients with fewer than three of the standard diagnostic criteria of AS. With such a population background, simultaneous next-generation sequencing of all three genes may be recommended as the most expedite approach to diagnose collagen IV-related glomerular basement membrane nephropathies.


Assuntos
Autoantígenos/genética , Colágeno Tipo IV/genética , Hematúria/genética , Mutação , Nefrite Hereditária/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Análise Mutacional de DNA , Exoma , Feminino , Estudos de Associação Genética , Hematúria/diagnóstico , Hematúria/metabolismo , Humanos , Falência Renal Crônica/genética , Falência Renal Crônica/metabolismo , Masculino , Pessoa de Meia-Idade , Nefrite Hereditária/diagnóstico , Nefrite Hereditária/metabolismo , Portugal , Adulto Jovem
16.
Clin Genet ; 88(5): 462-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25307721

RESUMO

Alport syndrome (AS) is caused by pathogenic mutations in the genes encoding α3, α4 or α5 chains of collagen IV (COL4A3/COL4A4/COL4A5), resulting in hematuria, chronic renal failure (CRF), sensorineural hearing loss (SNHL) and ocular abnormalities. Mutations in the X-linked COL4A5 gene have been identified in 85% of the families (XLAS). In this study, 22 of 60 probands (37%) of unrelated Portuguese families, with clinical diagnosis of AS and no evidence of autosomal inheritance, had pathogenic COL4A5 mutations detected by Sanger sequencing and/or multiplex-ligation probe amplification, of which 12 (57%) are novel. Males had more severe and earlier renal and extrarenal complications, but microscopic hematuria was a constant finding irrespective of gender. Nonsense and splice site mutations, as well as small and large deletions, were associated with younger age of onset of SNHL in males, and with higher risk of CRF and SNHL in females. Pathogenic COL4A3 or COL4A4 mutations were subsequently identified in more than half of the families without a pathogenic mutation in COL4A5. The lower than expected prevalence of XLAS in Portuguese families warrants the use of next-generation sequencing for simultaneous COL4A3/COL4A4/COL4A5 analysis, as first-tier approach to the genetic diagnosis of collagen type IV-related nephropathies.


Assuntos
Colágeno Tipo IV/genética , Mutação , Nefrite Hereditária/diagnóstico , Nefrite Hereditária/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Análise Mutacional de DNA , Exoma , Feminino , Estudos de Associação Genética , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Nefrite Hereditária/metabolismo , Portugal , Adulto Jovem
18.
Osteoporos Int ; 25(5): 1473-81, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24566587

RESUMO

UNLABELLED: We used data from a large, prospective Canadian cohort to assess the association between selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) and fracture. We found an increased risk of fractures in individuals who used SSRI or SNRI, even after controlling for multiple risk factors. INTRODUCTION: Previous studies have suggested an association between SSRIs and increasing risk of fragility fractures. However, the majority of these studies were not long-term analyses or were performed using administrative data and, thus, could not fully control for potential confounders. We sought to determine whether the use of SSRIs and SNRIs is associated with increased risk of fragility fracture, in adults aged 50 + . METHODS: We used data from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective randomly selected population-based community cohort; our analyses focused on subjects aged 50+. Time to event methodology was used to assess the association between SSRI/SNRI use, modeled time-dependently, and fragility fracture. RESULTS: Among 6,645 subjects, 192 (2.9%) were using SSRIs or/and SNRIs at baseline. During the 10-year study period, 978 (14.7%) participants experienced at least one fragility fracture. In our main analysis, SSRI/SNRI use was associated with increased risk of fragility fracture (hazard ratio (HR), 1.88; 95% confidence intervals (CI), 1.48-2.39). After controlling for multiple risk factors, including Charlson score, previous falls, and bone mineral density hip and lumbar bone density, the adjusted HR for current SSRI/SNRI use remained elevated (HR, 1.68; 95% CI, 1.32-2.14). CONCLUSIONS: Our results lend additional support to an association between SSRI/SNRI use and fragility fractures. Given the high prevalence of antidepressants use, and the impact of fractures on health, our findings may have a significant clinical impact.


Assuntos
Antidepressivos/efeitos adversos , Fraturas por Osteoporose/induzido quimicamente , Acidentes por Quedas/estatística & dados numéricos , Idoso , Antidepressivos/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Canadá/epidemiologia , Relação Dose-Resposta a Droga , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/fisiopatologia , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos
19.
Ann Oncol ; 24(8): 2147-50, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23585512

RESUMO

BACKGROUND: Well-differentiated papillary mesothelioma (WDPM) is a rare variant of epithelioid mesothelioma and is considered to be associated with good prognosis due to its clinically indolent behavior and long survival. Most reported cases involve the peritoneum of women at reproductive age with no history of exposure to asbestos, with pleural involvement being less common. The optimal management, including the role of chemotherapy in the treatment of WDPM, remains unsettled. PATIENTS AND METHODS: The authors describe two cases of WDPM in women of the same family (siblings); the elder with WDPM of the pleura and peritoneum with a 12-year survival period and the younger with a WDPM of the peritoneum diagnosed in 2011 and uveal melanoma diagnosed in 2012. Neither patient had any known exposure to asbestos fibers or any other mineral carcinogens. RESULTS: After the concurrent diagnosis of WDPM and uveal melanoma, genetic diagnosis was carried out taking into consideration that these two malignancies were recently associated with hereditary BAP1 gene mutations and it was positive for both the patients. CONCLUSIONS: To our knowledge, this is the first description of WDPM in two siblings who also presented with a germline BAP1 mutation. This article provides evidence of the wide clinical spectrum of cancer susceptibility associated with a BAP1 germline mutation.


Assuntos
Melanoma/genética , Mesotelioma/genética , Neoplasias Peritoneais/genética , Neoplasias Pleurais/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Neoplasias Uveais/genética , Adulto , Amianto/efeitos adversos , Análise por Conglomerados , Exposição Ambiental , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Mesotelioma/mortalidade , Pessoa de Meia-Idade , Portugal , Prognóstico , Irmãos , Sobrevida
20.
Horm Metab Res ; 45(1): 22-30, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22948547

RESUMO

Early weaning is associated with changes in the developmental plasticity. Here, we studied the adipocytes morphology, adipokines expression or content in adipose tissue as well as adrenal and thyroid function of neonate and adult offspring primed by early weaning. After birth, lactating rats were divided into 2 groups: EW (early weaning)--dams were wrapped with a bandage to block access to milk during the last 3 days of lactation, and Control--dams whose pups had free access to milk throughout lactation (21 days). At postnatal day (PN) 21, EW pups had lower visceral and subcutaneous adipocyte area (-67.7% and -62%, respectively), body fat mass (-26%), and leptin expression in visceral adipocyte (-64%) but higher leptin expression in subcutaneous adipocyte (2.9-fold increase). Adrenal evaluations were normal, but neonate EW pups presented lower serum T3 (-55%) and TSH (-44%). At PN 180, EW offspring showed higher food intake, higher body fat mass (+21.6%), visceral and subcutaneous adipocyte area (both 3-fold increase), higher leptin (+95%) and ADRß3 (2-fold increase) content in visceral adipose tissue, and higher adiponectin expression in subcutaneous adipose tissue (+47%) but lower in visceral adipose tissue (-40%). Adult EW offspring presented higher adrenal catecholamine content (+31%), but no changes in serum corticosterone or thyroid status. Thus, early weaning primed for hypothyroidism at weaning, which can be associated with the adipocyte hypertrophy at adulthood. The marked changes in catecholamine adrenal content and visceral adipocyte ADRB3 are generally found in obesity, contributing to the development of other cardiovascular and metabolic disturbances.


Assuntos
Doenças do Sistema Endócrino/fisiopatologia , Crescimento e Desenvolvimento , Obesidade/fisiopatologia , Desmame , Absorciometria de Fóton , Adiposidade , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia , Glândulas Suprarrenais/fisiopatologia , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Doenças do Sistema Endócrino/genética , Doenças do Sistema Endócrino/patologia , Regulação da Expressão Gênica , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/fisiopatologia , Leptina/genética , Leptina/metabolismo , Obesidade/genética , Obesidade/patologia , Ratos , Ratos Wistar , Receptores Adrenérgicos beta 3/metabolismo , Gordura Subcutânea/diagnóstico por imagem , Gordura Subcutânea/metabolismo , Gordura Subcutânea/fisiopatologia , Testes de Função Tireóidea
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