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1.
J Esthet Restor Dent ; 35(6): 980-986, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36856070

RESUMO

OBJECTIVE: To evaluate the effectiveness of a black light lens as visual aid in composite restoration removal. Lost tooth structure, residual composite, and removal time were compared for operators with different levels of experience. METHODS: Occlusal preparations in 24 matched-pair extracted molars were etched, bonded, restored with composite, and thermocycled. The restored teeth were radiographed and two faculty and two student doctors removed the restorations with or without a black light lens while time was recorded. Digital scans of the cavity before and after restoration removal were used to calculate lost tooth structure and residual composite. RESULTS: Removal of restorations resulted in tooth structure loss and left residual composite. The use of the black light lens had no significant effect (two-way ANOVA; p value >0.05). However, operator experience significantly affected operating times and average depth of tooth structure loss (two-way ANOVA; p value <0.05). Student doctors assisted by the black light lost less tooth structure than experienced operators and improved their operating times (multiple comparisons; p value <0.05). CONCLUSIONS: The black light lens did not conserve tooth structure or avoid composite remnants compared to routine operation, nor affected the operating time. However, less-experienced operators did benefit from the black light in conserving tooth structure and time. CLINICAL SIGNIFICANCE: Replacement of defective composite restorations is a regular practice in restorative dentistry. When existing composite restorations are removed, loss of tooth structure is unavoidable. A black light lens might improve the ability of operators with less experience to conserve tooth structure even though it did not provide benefits for the experienced operators.


Assuntos
Resinas Compostas , Restauração Dentária Permanente , Raios Ultravioleta , Humanos , Resinas Compostas/efeitos adversos , Resinas Compostas/química , Odontólogos , Estudantes de Odontologia
2.
Sci Total Environ ; 876: 162710, 2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-36906016

RESUMO

As a result of regulatory decisions, atmospheric deposition of most toxic metals and metalloids (MEs) has decreased in Europe over the past few decades. However, little is known about how this reduction translates into exposure at higher trophic levels in the terrestrial environment where temporal trends may be spatially heterogeneous due to local current or legacy sources of emissions (e.g., industry) or long-range transport of elements (e.g., marine transport). The aim of this study was to characterize temporal and spatial trends of exposure to MEs in terrestrial food webs using a predatory bird, the tawny owl Strix aluco, as a biomonitor. Toxic (Al, As, Cd, Hg, Pb) and essential/beneficial (B, Co, Cu, Mn, Se) elemental concentrations were measured in feathers of nest-captured females from 1986 to 2016, extending a previous study published over the time-series 1986-2005 (n = 1051), in a breeding population in Norway. A drastic decline over time was shown for the toxic MEs (-97 % for Pb, -89 % for Cd, -48 % for Al, and -43 % for As) except Hg. The beneficial elements B, Mn, and Se showed oscillations but an overall decline (-86 %, -34 %, and -12 %, respectively) whereas the essentials Co and Cu did not exhibit significant trends. The distance to potential sources of contamination influenced both the spatial patterns of concentrations in owl feathers and their temporal trends. The accumulation of As, Cd, Co, Mn and Pb was overall higher in the vicinity of sites recorded as polluted, and a greater temporal decrease of As, B, and Cd concentrations was found in the areas of further distance to polluted sites. The decrease of Pb concentrations was sharper further from the coast during the 1980s than in coastal areas, while the opposite was observed for Mn. The levels of Hg and Se were higher in coastal areas, and Hg temporal trends differed according to the distance to the coast. This study highlights the valuable insights provided by long-term survey of wildlife exposure to pollutants and landscape indicators to reveal regional or local patterns and detect unexpected events, data that are crucial for regulation and conservation of ecosystem health.


Assuntos
Mercúrio , Metaloides , Metais Pesados , Estrigiformes , Animais , Feminino , Monitoramento Ambiental , Cádmio , Ecossistema , Chumbo , Metais Pesados/análise
3.
J Dent Res ; 102(5): 525-535, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36726292

RESUMO

Saliva-secreting and transporting cells are part of the complex cellular milieu of the human salivary gland, where they play important roles in normal glandular physiology and diseased states. However, comprehensive molecular characterization, particularly at single-cell resolution, is still incomplete, in part due to difficulty in procuring normal human tissues. Here, we perform an in-depth analysis of male and female adult human submandibular gland (SMG) samples by bulk RNA sequencing (RNA-seq) and examine the molecular underpinnings of the heterogeneous cell populations by single-cell (sc) RNA-seq. Our results from scRNA-seq highlight the remarkable diversity of clusters of epithelial and nonepithelial cells that reside in the SMG that is also faithfully recapitulated by deconvolution of the bulk-RNA data sets. Our analyses reveal complex transcriptomic heterogeneity within both the ductal and acinar subpopulations and identify atypical SMG cell types, such as mucoacinar cells that are unique to humans and ionocytes that have been recently described in the mouse. We use CellChat to explore ligand-receptor interactome predictions that likely mediate crucial cell-cell communications between the various cell clusters. Finally, we apply a trajectory inference method to investigate specific cellular branching points and topology that offers insights into the dynamic and complex differentiation process of the adult SMG. The data sets and the analyses herein comprise an extensive wealth of high-resolution information and a valuable resource for a deeper mechanistic understanding of human SMG biology and pathophysiology.


Assuntos
Glândula Submandibular , Transcriptoma , Humanos , Masculino , Camundongos , Feminino , Animais , Glândulas Salivares , Perfilação da Expressão Gênica , Diferenciação Celular
4.
J Dent Res ; 100(13): 1492-1500, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33978512

RESUMO

The parotid, submandibular, and sublingual glands represent a trio of oral secretory glands whose primary function is to produce saliva, facilitate digestion of food, provide protection against microbes, and maintain oral health. While recent studies have begun to shed light on the global gene expression patterns and profiles of salivary glands, particularly those of mice, relatively little is known about the location and identity of transcriptional control elements. Here we have established the epigenomic landscape of the mouse submandibular salivary gland (SMG) by performing chromatin immunoprecipitation sequencing experiments for 4 key histone marks. Our analysis of the comprehensive SMG data sets and comparisons with those from other adult organs have identified critical enhancers and super-enhancers of the mouse SMG. By further integrating these findings with complementary RNA-sequencing based gene expression data, we have unearthed a number of molecular regulators such as members of the Fox family of transcription factors that are enriched and likely to be functionally relevant for SMG biology. Overall, our studies provide a powerful atlas of cis-regulatory elements that can be leveraged for better understanding the transcriptional control mechanisms of the mouse SMG, discovery of novel genetic switches, and modulating tissue-specific gene expression in a targeted fashion.


Assuntos
Epigenômica , Glândula Submandibular , Animais , Camundongos , Glândula Parótida , Glândulas Salivares , Glândula Sublingual
5.
J Clin Microbiol ; 58(10)2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32817226

RESUMO

Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. There are limited data in the United States on the molecular epidemiological characteristics of M. pneumoniae We collected 446 M. pneumoniae-positive specimens from 9 states between August 2012 and October 2018. Culture, antimicrobial susceptibility testing, P1 subtyping, and multilocus VNTR (variable-number tandem repeats) analysis (MLVA) were performed to characterize the isolates. Macrolide-resistant M. pneumoniae (MRMp) was detected in 37 (8.3%) specimens. P1 subtype 2 (P1-2) was the predominant P1 subtype (59.8%). P1 subtype distribution did not change significantly chronologically or geographically. The macrolide resistance rate in P1 subtype 1 (P1-1) samples was significantly higher than that in P1-2 (12.9% versus 5.5%). Six P1-2 variants were identified, including two novel types, and variant 2c was predominant (64.6%). P1-2 variants were distributed significantly differently among geographic regions. Classical P1-2 was more frequent in lower respiratory tract specimens and had longer p1 trinucleotide repeats. Classical P1-2 was most common in MRMp (35.7%), while variant 2c was most common in macrolide-susceptible M. pneumoniae (67.5%). Fifteen MLVA types were identified; 3-5-6-2 (41.7%), 4-5-7-2 (35.3%), and 3-6-6-2 (16.6%) were the major types, and four MLVA clusters were delineated. The distribution of MLVA types varied significantly over time and geographic location. The predominant MLVA type switched from 4-5-7-2 to 3-5-6-2 in 2015. MLVA type was associated with P1 subtypes and P1-2 variant types but not with macrolide resistance. To investigate the M. pneumoniae genotype shift and its impact on clinical presentations, additional surveillance programs targeting more diverse populations and prolonged sampling times are required.


Assuntos
Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Genótipo , Humanos , Macrolídeos/farmacologia , Mycoplasma pneumoniae/genética , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/epidemiologia , Estados Unidos/epidemiologia
6.
J Pharmacol Toxicol Methods ; 101: 106652, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31734280

RESUMO

A wipe sampling procedure followed by a simple ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneous quantification of six cytotoxic drugs: 5-fluorouracil (5FU), doxorubicin (DOXO), epirubicin (EPI), ifosfamide (IF), cyclophosphamide (CP) and gemcitabine (GEM), as surrogate markers for occupational exposure. After a solid-phase extraction of wiping filter on 10 × 10 cm surface, the separation was performed within 6.5 min, using a gradient mobile phase and the analytes were detected by mass spectrometry in the multiple reaction ion monitoring mode. The method was validated according to the recommendations of the US Food and Drug Administration. The method was linear (r2 > 0.9912) between 2.5 and 200 ng per wiping sample (25 to 2000 pg/cm2) for 5FU, doxorubicin and epirubicin and between 0.2 and 40 ng per wiping sample (2 to 400 pg/cm2) for cyclophosphamide, ifosfamide and gemcitabine. The lower limits of quantification were 2.5 ng (25 pg/ cm2) for 5FU, doxorubicin and epirubicin, and 0.2 ng (2 pg/cm2) for CP, IF and GEM. Within-day and between-day imprecisions were <14.0, 10.6, 11.1, 8.7, 11.2 and 10.9% for 5-fluorouracil, doxorubicin, epirubicin, ifosfamide cyclophosphamide and gemcitabine, respectively. The inaccuracies did not exceed 2.7, 10.9, 1.1, 4.5, 1.6 and 2.9% for the studied molecules, respectively. This new sensitive validated method for surface contamination studies of cytotoxics was successfully applied on different localizations in hospital. This approach is particularly suitable to assess occupational exposure risk to cytotoxic drugs.


Assuntos
Citotoxinas/análise , Monitoramento Ambiental/métodos , Exposição Ocupacional/análise , Exposição Ocupacional/prevenção & controle , Antineoplásicos/análise , Cromatografia Líquida , Ciclofosfamida/análise , Desoxicitidina/análogos & derivados , Desoxicitidina/análise , Doxorrubicina/análise , Epirubicina/análise , Contaminação de Equipamentos/prevenção & controle , Fluoruracila/análise , Ifosfamida/análise , Estudos de Amostragem , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem , Gencitabina
7.
J Dent Res ; 98(13): 1539-1547, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31623513

RESUMO

The salivary complex of mammals consists of 3 major pairs of glands: the parotid, submandibular, and sublingual glands. While the 3 glands share similar functional properties, such as saliva secretion, their differences are largely based on the types of secretions they produce. While recent studies have begun to shed light on the underlying molecular differences among the glands, few have examined the global transcriptional repertoire over various stages of gland maturation. To better elucidate the molecular nature of the parotid gland, we have performed RNA sequencing to generate comprehensive and global gene expression profiles of this gland at different stages of maturation. Our transcriptomic characterization and hierarchical clustering analysis with adult organ RNA sequencing data sets has identified a number of molecular players and pathways that are relevant for parotid gland biology. Moreover, our detailed analysis has revealed a unique parotid gland-specific gene signature that may represent important players that could impart parotid gland-specific biological properties. To complement our transcriptomic studies, we have performed single-cell RNA sequencing to map the transcriptomes of parotid epithelial cells. Interrogation of the single-cell transcriptomes revealed the degree of molecular and cellular heterogeneity of the various epithelial cell types within the parotid gland. Moreover, we uncovered a mixed-lineage population of cells that may reflect molecular priming of differentiation potentials. Overall our comprehensive studies provide a powerful tool for the discovery of novel molecular players important in parotid gland biology.


Assuntos
Glândula Parótida/citologia , Glândula Parótida/metabolismo , Análise de Célula Única , Transcriptoma , Animais , Camundongos
8.
J Clin Microbiol ; 57(11)2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31484701

RESUMO

There are sparse data to indicate the extent that macrolide-resistant Mycoplasma pneumoniae (MRMp) occurs in the United States or its clinical significance. Between 2015 and 2018, hospitals in 8 states collected and stored respiratory specimens that tested positive for M. pneumoniae and sent them to the University of Alabama at Birmingham, where real-time PCR was performed for detection of 23S rRNA mutations known to confer macrolide resistance. MRMp was detected in 27 of 360 specimens (7.5%). MRMp prevalence was significantly higher in the South and East (18.3%) than in the West (2.1%). A2063G was the predominant 23S rRNA mutation detected. MICs for macrolide-susceptible M. pneumoniae (MSMp) were ≤0.008 µg/ml, whereas MICs for MRMp were 16 to 32 µg/ml. Patients with MRMp infection were more likely to have a history of immunodeficiency or malignancy. Otherwise, there were no other significant differences in the clinical features between patients infected with MRMp and those infected with MSMp, nor were there any differences in radiographic findings, hospitalization rates, viral coinfections, the mean duration of antimicrobial treatment, or clinical outcomes. There was no significant change in MRMp incidence over time or according to age, sex, race/ethnicity, or status as an inpatient or an outpatient. Patients with MRMp were more likely to have received a macrolide prior to presentation, and their treatment was more likely to have been changed to a fluoroquinolone after presentation. This is the first national surveillance program for M. pneumoniae in the United States. Additional surveillance is needed to assess the clinical significance of MRMp and to monitor changes in MRMp prevalence.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Macrolídeos/farmacologia , Mycoplasma pneumoniae/efeitos dos fármacos , Pneumonia por Mycoplasma/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Monitoramento Epidemiológico , Feminino , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , Mycoplasma pneumoniae/genética , Pneumonia por Mycoplasma/microbiologia , Prevalência , RNA Ribossômico 23S/genética , Estados Unidos/epidemiologia , Adulto Jovem
9.
Sci Rep ; 9(1): 8674, 2019 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-31209240

RESUMO

FcRn mediates recycling and transcytosis of IgG and albumin in various cell types. The MHC-class-I-like protein of the FcRn heterodimer is encoded by FCGRT. Few determinants of variable FCGRT expression in humans have been identified so far. In this study, we investigated the presence of DNA methylation in regulatory regions of FCGRT in samples of human liver and myocardium tissue, and we examined the impact of FCGRT methylation on FcRn expression in model cell lines. Quantitative DNA methylation analysis of the FCGRT locus revealed differentially methylated regions in DNA from liver and myocardium. Methylation status in individual CpG sites correlated with FCGRT mRNA expression. Data from model cell lines suggest that differential methylation in the -1058 to -587 bp regulatory region of FCGRT contributes to FcRn expression. Chromatin immunoprecipitation assays indicate that CpG site methylation impacts the binding of the methylation sensitive transcription factors Zbtb7a and Sp1. This study provides a foundation to further define the contribution of epigenetic factors during the control of FcRn expression and IgG traffic in human tissues.


Assuntos
Proteínas de Ligação a DNA/genética , Epigênese Genética , Hepatócitos/metabolismo , Antígenos de Histocompatibilidade Classe I/genética , Miócitos Cardíacos/metabolismo , Receptores Fc/genética , Fator de Transcrição Sp1/genética , Fatores de Transcrição/genética , Albuminas/metabolismo , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina , Ilhas de CpG , Metilação de DNA , Proteínas de Ligação a DNA/metabolismo , Hepatócitos/citologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Imunoglobulina G/metabolismo , Fígado/citologia , Fígado/metabolismo , Miocárdio/citologia , Miocárdio/metabolismo , Miócitos Cardíacos/citologia , Regiões Promotoras Genéticas , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Fc/metabolismo , Fator de Transcrição Sp1/metabolismo , Fatores de Transcrição/metabolismo , Transcitose/genética
10.
Diabetes Metab ; 45(6): 573-581, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30862472

RESUMO

AIM: Ageing HIV-infected patients controlled by antiretroviral therapy (ART) frequently present age-related comorbidities, such as cardiovascular (CV) events, diabetes, dyslipidaemia, hypertension and chronic kidney disease (CKD). The prevalence of these comorbidities was evaluated in a cohort of long-term-monitored ART-controlled HIV-infected patients, then followed by a search into whether oxidative stress, like inflammation, might be associated with metabolic parameters and/or comorbidities. METHODS: Included were 352 long-term ART patients who started with protease inhibitors (PIs) in 1997-1999. They were evaluated at their final visit, 11 years later, for previous CV events, prevalence of diabetes, LDL-related and atherogenic (high TG/HDL) dyslipidaemias, hypertension and CKD. Also measured were circulating biomarkers to explore oxidative stress (Lp-PLA2, oxLDL, oxLDL/LDL ratio, paraoxonase and arylesterase activities), inflammation/immune activation (hsCRP, hsIL-6, D dimer, soluble CD14, ß2 microglobulin, cystatin C), adipokines and insulin resistance. Levels were compared in patients with and without each comorbidity or condition using non-parametric correlation tests and multivariate adjusted analyses. RESULTS: At the final visit, 81.5% of patients were male and were aged (median, IQR) 49 years (45-56); BMI was 23.0 kg/m2 (21.1-25.4), CD4+ lymphocytes were 620 cells/mm3 (453-790) and 91.5% had undetectable HIV-1 viral loads. The prevalence of diabetes was 11%, and LDL-related dyslipidaemia 28%, atherogenic dyslipidaemia 9%, hypertension 28%, CKD 9% and previous CV events 9%. Diabetes and atherogenic dyslipidaemia were associated with increased oxidative stress and independently with inflammation. LDL-related dyslipidaemia and impaired fasting glucose were associated with increased oxidative stress. No association of these biomarkers was detected with hypertension, CKD and previous CV events. CONCLUSION: In long-term-treated HIV-infected patients with frequent comorbid conditions, oxidative stress could be contributing to diabetes and LDL-related and atherogenic dyslipidaemias independently of inflammation.


Assuntos
Antirretrovirais/uso terapêutico , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Infecções por HIV , Inflamação/epidemiologia , Estresse Oxidativo/fisiologia , Aterosclerose/sangue , Aterosclerose/epidemiologia , Biomarcadores/sangue , LDL-Colesterol/sangue , Estudos de Coortes , Comorbidade , Complicações do Diabetes/sangue , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/sangue , Dislipidemias/sangue , Dislipidemias/complicações , Feminino , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Sobreviventes de Longo Prazo ao HIV/estatística & dados numéricos , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Inflamação/sangue , Inflamação/complicações , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo
11.
J Clin Microbiol ; 57(2)2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30463893

RESUMO

Group A Streptococcus (GAS) is one of the leading causes of bacterial pharyngitis. Early GAS diagnosis is critical for appropriate antibiotic administration that reduces the risk of GAS sequelae and limits spread of the infection. The Aries Group A Strep (GAS) assay (Luminex, Austin, TX) is a fully automated PCR assay for direct detection of GAS in throat swab specimens in less than 2 h with minimum hands-on time. This multicenter prospective study evaluated the clinical performance of the Aries GAS assay compared to that of Streptococcus pyogenes culture. Subjects with symptoms consistent with pharyngitis were enrolled across four sites in the United States, and a throat swab in liquid Amies medium was obtained. Aries and reference testing was performed within 72 and 48 h after sample collection, respectively. Of 623 throat swab specimens from patients with pharyngitis (93.6% <18 years old, 54.3% female), the reference method yielded valid results for 618 specimens. Reference and Aries assay testing showed GAS-positive results for 160 (25.9%) and 166 (26.9%) specimens, respectively. Compared to the reference method, Aries assay sensitivity was 97.5% (95% confidence interval [CI], 93.7% to 99.0%), specificity was 97.8% (95% CI, 96.0 to 98.8%), positive predictive value was 94.0% (95% CI, 89.3% to 96.7%), and negative predictive value was 99.1% (95% CI, 97.7% to 99.7%). There were 10 false-positive and four false-negative detections with the Aries assay. Discrepant analysis with bidirectional sequencing yielded concordant results with the Aries assay for nine of 14 discordant samples. The Aries assay had high sensitivity and specificity for qualitative detection of group A Streptococcus from patients with pharyngitis.


Assuntos
Automação Laboratorial/métodos , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Infecções Estreptocócicas/diagnóstico , Streptococcus pyogenes/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Faringe/microbiologia , Estudos Prospectivos , Sensibilidade e Especificidade , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/classificação , Streptococcus pyogenes/genética , Fatores de Tempo , Estados Unidos , Adulto Jovem
12.
Science ; 363(6425): 367-374, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30538164

RESUMO

In 2018, Kilauea Volcano experienced its largest lower East Rift Zone (LERZ) eruption and caldera collapse in at least 200 years. After collapse of the Pu'u 'O'o vent on 30 April, magma propagated downrift. Eruptive fissures opened in the LERZ on 3 May, eventually extending ~6.8 kilometers. A 4 May earthquake [moment magnitude (M w) 6.9] produced ~5 meters of fault slip. Lava erupted at rates exceeding 100 cubic meters per second, eventually covering 35.5 square kilometers. The summit magma system partially drained, producing minor explosions and near-daily collapses releasing energy equivalent to M w 4.7 to 5.4 earthquakes. Activity declined rapidly on 4 August. Summit collapse and lava flow volume estimates are roughly equivalent-about 0.8 cubic kilometers. Careful historical observation and monitoring of Kilauea enabled successful forecasting of hazardous events.

13.
Cell Death Differ ; 23(6): 1073-85, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26768665

RESUMO

Atopic dermatitis (AD) is the most common inflammatory skin disease with no well-delineated cause or effective cure. Here we show that the p53 family member p63, specifically the ΔNp63, isoform has a key role in driving keratinocyte activation in AD. We find that overexpression of ΔNp63 in transgenic mouse epidermis results in a severe skin phenotype that shares many of the key clinical, histological and molecular features associated with human AD. This includes pruritus, epidermal hyperplasia, aberrant keratinocyte differentiation, enhanced expression of selected cytokines and chemokines and the infiltration of large numbers of inflammatory cells including type 2 T-helper cells - features that are highly representative of AD dermatopathology. We further demonstrate several of these mediators to be direct transcriptional targets of ΔNp63 in keratinocytes. Of particular significance are two p63 target genes, IL-31 and IL-33, both of which are key players in the signaling pathways implicated in AD. Importantly, we find these observations to be in good agreement with elevated levels of ΔNp63 in skin lesions of human patients with AD. Our studies reveal an important role for ΔNp63 in the pathogenesis of AD and offer new insights into its etiology and possible therapeutic targets.


Assuntos
Dermatite Atópica/patologia , Interleucina-33/metabolismo , Fosfoproteínas/metabolismo , Transativadores/metabolismo , Animais , Citocinas/metabolismo , Dermatite Atópica/metabolismo , Ensaio de Imunoadsorção Enzimática , Epiderme/metabolismo , Humanos , Imunoglobulina E/sangue , Interleucinas/genética , Interleucinas/metabolismo , Camundongos , Camundongos Transgênicos , Microscopia de Fluorescência , Fenótipo , Fosfoproteínas/genética , Ligação Proteica , Receptores de Interleucina/genética , Receptores de Interleucina/metabolismo , Receptores de Oncostatina M/genética , Receptores de Oncostatina M/metabolismo , Transdução de Sinais , Pele/metabolismo , Pele/patologia , Células Th2/citologia , Células Th2/imunologia , Células Th2/metabolismo , Transativadores/genética
14.
J Clin Microbiol ; 54(3): 535-42, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26607988

RESUMO

Staphylococcus pseudintermedius is a coagulase-positive species that colonizes the nares and anal mucosa of healthy dogs and cats. Human infections with S. pseudintermedius range in severity from bite wounds and rhinosinusitis to endocarditis; historically, these infections were thought to be uncommon, but new laboratory methods suggest that their true incidence is underreported. Oxacillin and cefoxitin disk and MIC tests were evaluated for the detection of mecA- or mecC-mediated methicillin resistance in 115 human and animal isolates of the Staphylococcus intermedius group (SIG), including 111 Staphylococcus pseudintermediusand 4 Staphylococcus delphini isolates, 37 of which were mecA positive. The disk and MIC breakpoints evaluated included the Clinical and Laboratory Standards Institute (CLSI) M100-S25 Staphylococcus aureus/Staphylococcus lugdunensis oxacillin MIC breakpoints and cefoxitin disk and MIC breakpoints, the CLSI M100-S25 coagulase-negative Staphylococcus (CoNS) oxacillin MIC breakpoint and cefoxitin disk breakpoint, the CLSI VET01-S2 S. pseudintermedius oxacillin MIC and disk breakpoints, and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) S. pseudintermedius cefoxitin disk breakpoint. The oxacillin results interpreted by the VET01-S2 (disk and MIC) and M100-S25 CoNS (MIC) breakpoints agreed with the results of mecA/mecC PCR for all isolates, with the exception of one false-resistant result (1.3% of mecA/mecC PCR-negative isolates). In contrast, cefoxitin tests performed poorly, ranging from 3 to 89% false susceptibility (very major errors) and 0 to 48% false resistance (major errors). BD Phoenix, bioMérieux Vitek 2, and Beckman Coulter MicroScan commercial automated susceptibility test panel oxacillin MIC results were also evaluated and demonstrated >95% categorical agreement with mecA/mecC PCR results if interpreted by using the M100-S25 CoNS breakpoint. The Alere penicillin-binding protein 2a test accurately detected all mecA-positive isolates, although for four isolates, cefoxitin induction was required prior to testing. These data demonstrate that the cefoxitin surrogate test does not reliably detect the presence of mecA in S. pseudintermedius isolates and that laboratories should perform oxacillin disk or MIC tests of these isolates when they are encountered.


Assuntos
Cefoxitina/farmacologia , Resistência a Meticilina , Testes de Sensibilidade Microbiana/normas , Oxacilina/farmacologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/veterinária , Staphylococcus intermedius/efeitos dos fármacos , Animais , Humanos , Testes de Sensibilidade Microbiana/métodos
15.
Diabetes Metab ; 41(1): 69-75, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25497967

RESUMO

Plant sterols and stanols are well-known to reduce LDL-cholesterol (LDL-C) concentrations. It is generally accepted that supplementation with 2g/day of sterols/stanols leads to a 10% reduction in LDL. However, most of the clinical trials supporting this conclusion were of short-term duration, and the results of longer interventions are scanty. In four studies, interventions lasting>6 months were carried out and the LDL-C-lowering effects were maintained over this longer duration, although some results suggest that a reduced effect may be observed with sterols, while stanols maintain their effect. In any case, the data are too limited to be definitive. In a free-living population as well as in multiparametric interventional studies, however, the LDL-C-lowering effect has been confirmed, although to a lesser extent than in clinical studies. In the absence of data on cardiovascular morbidity and mortality, data for surrogate markers of cardiovascular risk could be considered adequate alternatives. Several studies have been conducted on this basis, but their results failed to demonstrate any favourable effects. The present report summarizes the different results obtained in long-term studies, and in those comparing the effects of sterols and stanols on lipids and other surrogate markers of cardiovascular risk.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/sangue , LDL-Colesterol/sangue , Fitosteróis/farmacologia , Doenças Cardiovasculares/epidemiologia , Eritrócitos/química , Eritrócitos/efeitos dos fármacos , Humanos , Estresse Oxidativo/efeitos dos fármacos , Fitosteróis/administração & dosagem , Fatores de Risco
16.
Environ Toxicol Chem ; 32(11): 2520-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23861300

RESUMO

The extent to which persistent organic pollutants (POPs) with different physicochemical properties originated from the food (dietary input) was assessed in raptor nestlings. Lipophilic polychlorinated biphenyl (PCB) 153, 1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), and hexachlorobenzene (HCB), and protein-bound perfluorooctane sulfonate (PFOS), were measured repeatedly in blood plasma of individual goshawk (Accipiter gentilis) and white-tailed eagle (Haliaeetus albicilla) nestlings, 1 to 3 wk after hatching and near fledging. Maternally derived POPs dilute as nestlings grow (growth dilution), and increasing plasma concentrations would indicate dietary input. First, plasma concentrations given no dietary input were estimated, and concentrations of p,p'-DDE, HCB, and notably PFOS were significantly higher than predicted from a growth-dilution scenario (approximately 1.5-fold to 2.5-fold higher; p < 0.001). In contrast, PCB 153 declined in both species, although concentrations were still higher than predicted in white-tailed eagle nestlings (p < 0.05). Second, the relationships between plasma POP concentrations and trophic position (δ(15) N) and dietary carbon source (δ(13) C) were analyzed, controlling for growth rate. Both δ(15) N and δ(13) C (measured in body feathers) were significantly associated to the accumulation of most POPs, except PFOS. In conclusion, pollutant data acquired in plasma of nestling raptors should be interpreted and further investigated in the light of individual feeding ecology, and the use of raptor nestlings as sentinels for POP monitoring could be optimized by correcting for different factors such as body condition, brood size, and age.


Assuntos
Diclorodifenil Dicloroetileno/sangue , Poluentes Ambientais/sangue , Falconiformes/sangue , Falconiformes/crescimento & desenvolvimento , Hexaclorobenzeno/sangue , Bifenilos Policlorados/sangue , Animais , Diclorodifenil Dicloroetileno/toxicidade , Águias/sangue , Águias/crescimento & desenvolvimento , Poluentes Ambientais/toxicidade , Alimentos , Hexaclorobenzeno/toxicidade , Bifenilos Policlorados/toxicidade , Especificidade da Espécie
17.
Neuroscience ; 248: 1-16, 2013 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-23727008

RESUMO

Acoustic trauma, a leading cause of sensorineural hearing loss in adults, induces a complex degenerative process in the cochlea. Although previous investigations have identified multiple stress pathways, a comprehensive analysis of cochlear responses to acoustic injury is still lacking. In the current study, we used the next-generation RNA-sequencing (RNA-Seq) technique to sequence the whole transcriptome of the normal and noise-traumatized cochlear sensory epithelia (CSE). CSE tissues were collected from rat inner ears 1d after the rats were exposed to a 120-dB (sound pressure level) noise for 2 h. The RNA-Seq generated over 176 million sequence reads for the normal CSE and over 164 million reads for the noise-traumatized CSE. Alignment of these sequences with the rat Rn4 genome revealed the expression of over 17,000 gene transcripts in the CSE, over 2000 of which were exclusively expressed in either the normal or noise-traumatized CSE. Seventy-eight gene transcripts were differentially expressed (70 upregulated and 8 downregulated) after acoustic trauma. Many of the differentially expressed genes are related to the innate immune system. Further expression analyses using quantitative real time PCR confirmed the constitutive expression of multiple complement genes in the normal organ of Corti and the changes in the expression levels of the complement factor I (Cfi) and complement component 1, s subcomponent (C1s) after acoustic trauma. Moreover, protein expression analysis revealed strong expression of Cfi and C1s proteins in the organ of Corti. Importantly, these proteins exhibited expression changes following acoustic trauma. Collectively, the results of the current investigation suggest the involvement of the complement components in cochlear responses to acoustic trauma.


Assuntos
Cóclea/metabolismo , Perfilação da Expressão Gênica , Perda Auditiva Provocada por Ruído/genética , Animais , Feminino , Masculino , Ratos , Ratos Sprague-Dawley , Análise de Sequência de RNA , Transdução de Sinais
18.
Sci Total Environ ; 458-460: 101-6, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-23644358

RESUMO

In the recent decades, the atmospheric deposition of many metals has declined in northern Europe, mostly due to reductions of emissions in other parts of the Europe. However, less is known about the temporal trends at higher trophic levels in terrestrial food chains. In this study we measured 39 different essential and non-essential elements in tawny owl (Strix aluco) tail-feathers (n=633) collected annually between 1986 and 2005 in Central Norway. There was a strong decline in lead (Pb) concentrations (~94%) consistent with the termination of the use of Pb as a petrol additive. There were also significant declines in cadmium (Cd), cobalt (Co) and arsenic (As) concentrations. Zinc (Zn) may also have declined after 2000, but this is not yet clear due to possible analytical problems. More unexpected was a strong decline of boron (B) in the late 1980s and early 1990s with a subsequent leveling-off, but with high concentrations in 1999. The decline in B could be related to changes in the agricultural practices and use of fertilizers. Tin (Sn) showed an abrupt decline in the mid-1990s, after which the concentrations established at one fifth of the level before this time. Iron (Fe) was stable until the late 1990s, but showed an increase afterwards, whereas lanthanum (La) tended to increase up to the mid-1990s and then leveled-off. Aluminum (Al) showed decreasing levels until the mid-1990s, but a considerable increase afterwards. There was a small increase in praseodymium (Pr), but the only element showing a consistent strong increase over the study period (61%) was rubidium (Rb). The causes of the temporal trends in different elements may be changed input to the local ecosystem from local and trans-boundary sources, but possibly also variation in climate and feeding conditions for the owls.


Assuntos
Monitoramento Ambiental/estatística & dados numéricos , Poluentes Ambientais/análise , Poluição Ambiental/estatística & dados numéricos , Plumas/química , Metais Pesados/análise , Estrigiformes/metabolismo , Animais , Monitoramento Ambiental/métodos , Poluição Ambiental/análise , Espectrometria de Massas , Modelos Estatísticos , Noruega , Fatores de Tempo
19.
PLoS One ; 8(2): e56450, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23451049

RESUMO

Global warming is expected to cause earlier springs and increased primary productivity in the Arctic. These changes may improve food availability for Arctic herbivores, but may also have negative effects by generating a mismatch between the surge of high quality food in the spring and the timing of reproduction. We analyzed a 10 year dataset of satellite derived measures of vegetation green-up, population densities, calf body masses and female reproductive success in 19 reindeer (Rangifer tarandus) populations in Northern Norway. An early onset of spring and high peak plant productivity had positive effects on calf autumn body masses and female reproductive success. In addition, body masses and reproductive success were both negatively related to population density. The quantity of food available, as determined by the onset of vegetation green-up and plant productivity over the summer were the main drivers of body mass growth and reproductive success. We found no evidence for an effect of the speed of spring green-up. Nor did we detect a negative mismatch between early springs and subsequent recruitment. Effects of global warming on plant productivity and onset of spring is likely to positively affect sub-Arctic reindeer.


Assuntos
Densidade Demográfica , Rena/crescimento & desenvolvimento , Rena/fisiologia , Animais , Aquecimento Global , Plantas , Reprodução/fisiologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-23375583

RESUMO

Conjugated linoleic acids (CLA), naturally found in dairy products and ruminant meat, are positional and geometric isomers (trans: t or cis: c) of linoleic acid, and have been widely reported to possess anti-tumoral activity against breast cancer both in vitro and in vivo. CLA isomer t9,t11 was recently proposed as an agonist of the transcriptional factor LXR, which is known for inducing genes implicated in cholesterol efflux. In this study, the growth inhibitory effect of three CLA isomers (c9,t11-CLA, t9,t11-CLA and t10,c12-CLA) was investigated on MCF-7 breast cancer cells, as well as their effect on LXR target genes. Our results revealed that t9,t11-CLA was the most efficient isomer by decreasing MCF-7 proliferation, inhibiting migration, and inducing apoptosis after 24h of treatment. t9,t11-CLA treatment led to an increase in the mRNA levels of LXR target genes involved in cholesterol efflux (ABCG1 and ARL7), as well as an increase of HMG-CoA-reductase which is the rate-limiting step of cholesterol biosynthesis. Interestingly, confocal microscopy analysis showed that t9,t11-CLA treatment remarkably reduced the intracellular and membrane-associated cholesterol levels. LXR activation through t9,t11-CLA isomer could lead to cholesterol cell deprivation by stimulating its efflux, which results in the inhibition of cell proliferation and stimulation of apoptosis.


Assuntos
Neoplasias da Mama/metabolismo , Ácidos Linoleicos Conjugados/farmacologia , Receptores Nucleares Órfãos/genética , Fatores de Ribosilação do ADP/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Proliferação de Células/efeitos dos fármacos , Humanos , Receptores X do Fígado , Células MCF-7
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