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1.
Colorectal Dis ; 21(10): 1175-1182, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31124259

RESUMO

AIM: This study aimed to investigate the association between Twitter exposure and the number of citations for coloproctology articles. METHOD: Original articles from journals using Twitter between June 2015 and May 2016 were evaluated for the following characteristics: publishing journal; article subject; study design; nationality, speciality and affiliation of the author(s); and reference on Twitter. Citation data for these articles were retrieved from Google Scholar (https://scholar.google.com) in January 2018. We performed a univariate analysis using these data followed by a multivariate, logistic regression analysis to search for factors associated with a high citation level, which was defined as accrual of more than five citations. RESULTS: Out of six coloproctology journals listed on the InCites JCR database, three (Diseases of the Colon & Rectum, Colorectal Disease and Techniques in Coloproctology) used Twitter, where 200 (49.5%) out of a total of 404 articles had been featured. Citation rates of articles that featured on Twitter were significantly higher than those that did not (11.4 ± 9.2 vs 4.1 ± 3.1, P < 0.001). In multivariate analysis, Twitter exposure (OR 8.6, P = 0.001), European Union nationality (OR 2.4, P = 0.004), Colorectal Disease journal (OR 3.3, P = 0.005) and systematic review articles (OR 3.4, P = 0.009) were associated with higher citation levels. CONCLUSION: Article exposure on Twitter was strongly associated with a high citation level. Medical communities should encourage journals as well as physicians to actively utilize social media to expedite the spread of new ideas and ultimately benefit medical society as a whole.


Assuntos
Cirurgia Colorretal/estatística & dados numéricos , Fator de Impacto de Revistas , Mídias Sociais/estatística & dados numéricos , Humanos , Análise Multivariada
2.
Pol J Vet Sci ; 20(3): 611-613, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-29166276

RESUMO

This study compared the pharmacokinetics of Prednisolone (PDS) in small- and large breed dogs with a dosing format based on body surface area (BSA) or body weight (BW). The maximum concentration and area under the curve in large-breed dogs orally administered 2 mg/kg PDS were significantly greater than those in small-breed dogs given 2 mg/kg and in large-breed dogs given 40 mg/m2. The higher blood concentrations that result from BW-based dosing of oral PDS in large-breed dogs can be more than required for effect. Meanwhile, BSA dosing at 40 mg/m may be suboptimal. These findings confirm important differences between standard PDS dosing schemes in dogs while highlighting the need to further optimize PDS dosing in large-breed dogs.


Assuntos
Superfície Corporal , Peso Corporal , Cães/sangue , Prednisolona/administração & dosagem , Prednisolona/farmacocinética , Animais , Área Sob a Curva , Cães/fisiologia , Relação Dose-Resposta a Droga , Glucocorticoides/administração & dosagem , Glucocorticoides/sangue , Glucocorticoides/farmacocinética , Meia-Vida
3.
J Vet Pharmacol Ther ; 39(6): 560-565, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27302674

RESUMO

Meropenem, a second carbapenem antimicrobial agent with a broad spectrum of activity, is used to treat sepsis and resistant-bacterial infections in veterinary medicine. The objective of this study was to identify the pharmacokinetics of meropenem in dogs receiving intermittent hemodialysis (IHD) and to determine the proper dosing in renal failure patients receiving IHD. Five healthy beagle dogs were given a single i.v. dose of 24 mg/kg of meropenem and received IHD. The blood flow rate, dialysate flow, and ultrafiltration rate were maintained at 40 mL/min, 300 mL/min, and 40 mL/h, respectively. Blood samples were collected for 24 h from the jugular vein and from the extracorporeal arterial and venous line. Urine samples and dialysate were also collected. The concentrations of meropenem were assayed using HPLC/MS/MS determination. The peak plasma concentration was 116 ± 37 µg/mL at 15 min. The systemic clearance was 347 ± 117 mL/h/kg, and the steady-state volume of distribution was 223 ± 67 mL/kg. Dialysis clearance was 71.1 ± 34.3 mL/h/kg, and the extraction ratio by hemodialysis was 0.455 ± 0.150. The half-life (T1/2 ) in dogs with IHD decreased compared with those without IHD, and the reduction in T1/2 was greater in renal failure patients than in normal patients. Sixty-nine percent and 21% of the administered drug were recovered by urine and dialysate in the unchanged form, respectively. In conclusion, additional dosing of 24 mg/kg of meropenem after dialysis could be necessary according to the residual renal function of the patient based on the simulated data.


Assuntos
Antibacterianos/farmacocinética , Cães/sangue , Diálise Renal/veterinária , Tienamicinas/farmacocinética , Animais , Antibacterianos/administração & dosagem , Área Sob a Curva , Meia-Vida , Injeções Intra-Arteriais , Injeções Intravenosas , Masculino , Meropeném , Tienamicinas/administração & dosagem
4.
Hum Reprod ; 30(12): 2881-91, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26370665

RESUMO

STUDY QUESTION: Are microRNAs (miRs) altered in the eutopic endometrium (EuE) of baboons following the induction of endometriosis? SUMMARY ANSWER: Induction of endometriosis causes significant changes in the expression of eight miRs, including miR-451, in the baboon endometrium as early as 3 months following induction of the disease. WHAT IS KNOWN ALREADY: Endometriosis is one of the most common gynecological disorders and causes chronic pelvic pain and infertility in women of reproductive age. Altered expression of miRs has been reported in women and has been suggested to play an important role in the pathophysiology of several gynecological disorders including endometriosis. STUDY DESIGN, SIZE, DURATION: EuE was obtained from the same group of baboons before and 3 months after the induction of endometriosis. The altered expression of miR-451 was validated in the eutopic and ectopic endometrium of additional baboons between 3 and 15 months following disease induction. Timed endometrial biopsies from women with and without endometriosis were also used to validate the expression of miR-451. PARTICIPANTS/MATERIALS, SETTING, METHODS: Total RNA was extracted from EuE samples before and after the induction of endometriosis, and miRNA expression was analyzed using a 8 × 15 K miR microarray. Microarray signal data were preprocessed by AgiMiRna software, and an empirical Bayes model was used to estimate the changes. The present study focused on quantitative RT-PCR validation of the microarray data, specifically on miR-451 and its target genes in both baboons (n = 3) and women [control (n = 7) and endometriosis (n = 19)]. Descriptive and correlative analysis of miR-451 and target gene expression was conducted using in situ hybridization and immunohistochemistry, while functional analysis utilized an in vitro 3' untranslated region (UTR) luciferase assay and overexpression of miR-451 in human endometrial and endometriotic cell lines. MAIN RESULTS AND THE ROLE OF CHANCE: Induction of endometriosis results in the altered expression of miR-451, -141, -29c, -21, -424, -19b, -200a and -181a in the baboon endometrium. In the baboon, induction of endometriosis significantly decreased the expression of miR-451 at 3 months (P < 0.001), which was also associated with increased expression of its target gene YWHAZ (14.3.3ζ). A similar significant (P < 0.0001) decrease in miR-451 expression was observed in women with endometriosis. The 3' UTR luciferase assay confirmed the regulation of YWHAZ expression by miR-451. Furthermore, overexpression of miR-451 in 12Z cells (immortalized human endometriotic epithelial cell line) led to the decreased expression of its target YWHAZ and this was correlated with decreased cell proliferation. LIMITATIONS, REASONS FOR CAUTION: The study focused only on miR-451 and one of its targets, namely YWHAZ. A single miR could target number of genes and a single gene could also be regulated by number of miRs; hence, it is possible that other miRs and their regulated genes may contribute to the pathophysiology of endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggest that the presence of ectopic lesions in baboon causes changes in EuE miR expression as early as 3 months postinduction of the disease, and some of these changes may persist throughout the course of the disease. We propose that the marked down-regulation of miR-451 in both baboons and women with endometriosis increases the expression of multiple target genes. Increased expression of one of the target genes, YWHAZ, increases proliferation, likely contributing to the pathophysiology of the disease.


Assuntos
Endometriose/metabolismo , Endométrio/metabolismo , Regulação da Expressão Gênica , MicroRNAs/metabolismo , Adulto , Animais , Proliferação de Células , Endometriose/genética , Endometriose/patologia , Endométrio/patologia , Feminino , Humanos , MicroRNAs/genética , Papio anubis
5.
Phys Rev Lett ; 115(19): 196401, 2015 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-26588400

RESUMO

The intrinsic field effect, the change in surface conductance with an applied transverse electric field, of prototypal strongly correlated VO(2) has remained elusive. Here we report its measurement enabled by epitaxial VO(2) and atomic layer deposited high-κ dielectrics. Oxygen migration, joule heating, and the linked field-induced phase transition are precluded. The field effect can be understood in terms of field-induced carriers with densities up to ∼5×10(13) cm(-2) which are trongly localized, as shown by their low, thermally activated mobility (∼1×10(-3) cm(2)/V s at 300 K). These carriers show behavior consistent with that of Holstein polarons and strongly impact the (opto)electronics of VO(2).

6.
J Appl Microbiol ; 117(3): 834-45, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24925305

RESUMO

AIMS: The aim of this study was to evaluate the effects of Bifidobacterium lactis HY8101 on insulin resistance induced using tumour necrosis factor-α (TNF-α) in rat L6 skeletal muscle cells and on the KK-A(Y) mouse noninsulin-dependent diabetes mellitus (NIDDM) model. METHODS AND RESULTS: The treatment using HY8101 improved the insulin-stimulated glucose uptake and translocation of GLUT4 via the insulin signalling pathways AKT and IRS-1(Tyr) in TNF-α-treated L6 cells. HY8101 increased the mRNA levels of GLUT4 and several insulin sensitivity-related genes (PPAR-γ) in TNF-α-treated L6 cells. In KK-A(Y) mice, HY8101 decreased fasting insulin and blood glucose and significantly improved insulin tolerance. HY8101 improved diabetes-induced plasma total cholesterol and triglyceride (TG) levels and increased the muscle glycogen content. We observed concurrent transcriptional changes in the skeletal muscle tissue and the liver. In the skeletal muscle tissue, the glycogen synthesis-related gene pp-1 and GLUT4 were up-regulated in mice receiving HY8101 treatment. In the liver, the hepatic gluconeogenesis-regulated genes (PCK1 and G6PC) were down-regulated in mice receiving HY8101 treatment. CONCLUSIONS: Bifidobacterium lactis HY8101 can be used to moderate glucose metabolism, lipid metabolism and insulin sensitivity in mice and in cells. SIGNIFICANCE AND IMPACT OF THE STUDY: Bifidobacterium lactis HY8101 might have potential as a probiotic candidate for alleviating metabolic syndromes such as diabetes.


Assuntos
Bifidobacterium , Diabetes Mellitus Tipo 2/terapia , Resistência à Insulina , Probióticos/uso terapêutico , Animais , Glicemia/análise , Linhagem Celular , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Glicogênio/metabolismo , Insulina/farmacologia , Proteínas Substratos do Receptor de Insulina/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Ratos , Transdução de Sinais , Fator de Necrose Tumoral alfa/farmacologia
7.
Indoor Air ; 24(6): 629-38, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24750197

RESUMO

UNLABELLED: The objective of this study was to quantify the influence of ventilation systems on indoor particle concentrations in residential buildings. Fifteen occupied, single-family apartments were selected from three sites. The three sites have three different ventilation systems: unbalanced mechanical ventilation, balanced mechanical ventilation, and natural ventilation. Field measurements were conducted between April and June 2012, when outdoor air temperatures were comfortable. Number concentrations of particles, PM2.5 and CO2 , were continuously measured both outdoors and indoors. In the apartments with natural ventilation, I/O ratios of particle number concentrations ranged from 0.56 to 0.72 for submicron particles, and from 0.25 to 0.60 for particles larger than 1.0 µm. The daily average indoor particle concentration decreased to 50% below the outdoor level for submicron particles and 25% below the outdoor level for fine particles, when the apartments were mechanically ventilated. The two mechanical ventilation systems reduced the I/O ratios by 26% for submicron particles and 65% for fine particles compared with the natural ventilation. These results showed that mechanical ventilation can reduce exposure to outdoor particles in residential buildings. PRACTICAL IMPLICATIONS: Results of this study confirm that mechanical ventilation with filtration can significantly reduce indoor particle levels compared with natural ventilation. The I/O ratios of particles substantially varied at the naturally ventilated apartments because of the influence of variable window opening conditions and unsteadiness of wind flow on the penetration of outdoor air particles. For better prediction of the exposure to outdoor particles in naturally ventilated residential buildings, it is important to understand the penetration of outdoor particles with variable window opening conditions.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Ventilação , Filtração/instrumentação , Habitação , Humanos , Tamanho da Partícula , Material Particulado/análise , República da Coreia , Ventilação/instrumentação , Vento
8.
Dement Geriatr Cogn Disord ; 25(4): 321-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18319591

RESUMO

BACKGROUND/AIMS: This study aimed to develop a brief, reliable and valid test for cognitive function of severely demented patients. METHODS: We constructed the Severe Cognitive Impairment Rating Scale, which consisted of 11 items covering memory, language, visuospatial function, frontal function and orientation, and investigated its reliability and validity on 267 subjects [normal: 65, very mild Alzheimer's disease (AD): 42, mild AD: 58, moderate AD: 36, severe AD: 44, profound AD: 22]. RESULTS: The internal consistency obtained by Cronbach's coefficient alpha was 0.93. The interrater reliability and test-retest reliability in the moderately to severely impaired subjects with an MMSE score of

Assuntos
Doença de Alzheimer/diagnóstico , Transtornos Cognitivos/diagnóstico , Testes Neuropsicológicos/normas , Índice de Gravidade de Doença , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , Variações Dependentes do Observador , Reprodutibilidade dos Testes
9.
Oncogene ; 37(2): 255-262, 2018 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-28925396

RESUMO

Endometrial cancer is the most common malignancy of the female genital tract. Progesterone (P4) has been used for several decades in endometrial cancer treatment, especially in women who wish to retain fertility. However, it is unpredictable which patients will respond to P4 treatment and which may have a P4-resistant cancer. Therefore, identifying the mechanism of P4 resistance is essential to improve the therapies for endometrial cancer. Mitogen-inducible gene 6 (Mig-6) is a critical mediator of progesterone receptor (PGR) action in the uterus. In order to study the function of Mig-6 in P4 resistance, we generated a mouse model in which we specifically ablated Mig-6 in uterine epithelial cells using Sprr2f-cre mice (Sprr2fcre+Mig-6f/f). Female mutant mice develop endometrial hyperplasia due to aberrant phosphorylation of signal transducers and activators of transcription 3 (STAT3) and proliferation of the endometrial epithelial cells. The results from our immunoprecipitation and cell culture experiments showed that MIG-6 inhibited phosphorylation of STAT3 via protein interactions. Our previous study showed P4 resistance in mice with Mig-6 ablation in Pgr-positive cells (Pgrcre/+Mig-6f/f). However, Sprr2fcre+Mig-6f/f mice were P4-responsive. P4 treatment significantly decreased STAT3 phosphorylation and epithelial proliferation in the uterus of mutant mice. We showed that Mig-6 has an important function of tumor suppressor via inhibition of STAT3 phosphorylation in uterine epithelial cells, and the antitumor effects of P4 are mediated by the endometrial stroma. These data help to develop a new signaling pathway in the regulation of steroid hormones in the uterus, and to overcome P4 resistance in human reproductive diseases, such as endometrial cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias do Endométrio/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Progesterona/farmacologia , Receptores de Progesterona/genética , Fator de Transcrição STAT3/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Knockout , Fosforilação , Progesterona/uso terapêutico , Receptores de Progesterona/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Supressoras de Tumor/genética , Útero/efeitos dos fármacos , Útero/patologia
10.
J Vet Intern Med ; 31(3): 743-750, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28407418

RESUMO

BACKGROUND: Esomeprazole is an S-enantiomer of omeprazole that has favorable pharmacokinetics and efficacious acid suppressant properties in humans. However, the pharmacokinetics and effects on intragastric pH of esomeprazole in dogs have not been reported. OBJECTIVE: To determine the pharmacokinetics of esomeprazole administered via various routes (PK study) and to investigate the effect of esomeprazole on intragastric pH with a Bravo pH monitoring system (PD study). ANIMALS: Seven adult male Beagle dogs and 5 adult male Beagle dogs were used for PK and PD study, respectively. METHODS: Both studies used an open, randomized, and crossover design. In the PK study, 7 dogs received intravenous (IV), subcutaneous (SC), and oral doses (PO) of esomeprazole (1 mg/kg). Each treatment period was separated by a washout period of at least 10 days. Esomeprazole plasma concentrations were measured by HPLC/MS/MS. In the efficacy study, intragastric pH was recorded without medication (baseline pH) and following IV, SC, and PO esomeprazole dosing regimens (1 mg/kg) in 5 dogs. RESULTS: The bioavailability of esomeprazole administered as PO enteric-coated granules and as SC injections was 71.4 and 106%, respectively. The half-life was approximately 1 hour. Mean ± SD percent time intragastric pH was ≥3 and ≥4 was 58.9 ± 21.1% and 40.9 ± 17.3% for IV group, 75.8 ± 16.4% and 62.7 ± 17.7% for SC group, 88.2 ± 8.9% and 82.5 ± 7.7% for PO group, and 12.5 ± 3.6% and 3.7 ± 1.8% for baseline. The mean percent time with intragastric pH was ≥3 or ≥4 was significantly increased regardless of the dosing route (P < .05). CONCLUSION: The PK parameters for PO and SC esomeprazole administration were favorable, and esomeprazole significantly increased intragastric pH after IV, PO, and SC administration. IV and SC administration of esomeprazole might be useful when PO administration is not possible. No significant adverse effects were observed.


Assuntos
Antiulcerosos/farmacocinética , Esomeprazol/farmacocinética , Administração Oral , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/sangue , Antiulcerosos/farmacologia , Área Sob a Curva , Estudos Cross-Over , Cães , Esomeprazol/administração & dosagem , Esomeprazol/sangue , Esomeprazol/farmacologia , Esôfago/efeitos dos fármacos , Feminino , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Injeções Intravenosas/veterinária , Injeções Subcutâneas/veterinária , Masculino , Valores de Referência
11.
Chem Commun (Camb) ; 53(75): 10459-10462, 2017 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-28890969

RESUMO

UltraLink was functionalized with a triazolium cyclodextrin click cluster (CCC) which provides a well-oriented, multivalent, positively charged binding site for PtdIns(3,4,5)P3. MALDI TOF MS and LC ESI MS/MS MRM analysis of spiked PtdIns(3,4,5)P3 in lipid extract suggest that triazolium CCC-UltraLink conjugate can be used as an enrichment material for PtdIns(3,4,5)P3.

12.
J Endocrinol ; 189(3): 473-84, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16731779

RESUMO

Progesterone (P4) and its cognate receptor, the progesterone receptor (PGR), have important roles in the establishment and maintenance of pregnancy in the murine uterus. In previous studies, using high-density DNA microarray analysis, we identified a subset of genes whose expression is repressed by chronic P4-PGR activation in the uterus. The Clca3 gene is one of the genes whose expression is the most significantly downregulated by P4 and PGR. In the present study, we performed real-time RT-PCR and in situ hybridization to investigate the regulation of Clca3 by P4 and determine the pattern of expression of Clca3 in the uterus during early pregnancy. This analysis shows that Clca3 mRNA transcripts were detected in the luminal and glandular epithelium of the pseudopregnant uterus at day 0.5 and that the expression of Clca3 was not detected after day 3.5. P4 represses Clca3 mRNA synthesis in the luminal epithelial and glandular epithelial cells of the uterus in ovariectomized wild-type mice, but not in Pgr knockout (PRKO) mice. Conversely, estrogen (E2) induces Clca3 expression in the luminal epithelium and glandular epithelium, and this induction was repressed by P4 in the murine uterus. Analysis of the promoter region of Clca3 by in silico and transient transfection analysis in HEC-1A cells identified the regulation of Clca3 by estrogen receptor-alpha (ESR1) within the first 528 bp of 5'-flanking region of the Clca3 gene. Our studies identified Clca3 as a novel downregulated gene of PGR that is a direct target of E2 regulation.


Assuntos
Canais de Cloreto/genética , Regulação da Expressão Gênica , Progesterona/metabolismo , Regiões Promotoras Genéticas , Receptores de Progesterona/metabolismo , Útero/metabolismo , Animais , Linhagem Celular , Estradiol/metabolismo , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Hibridização In Situ/métodos , Camundongos , Camundongos Knockout , Ovariectomia , Gravidez , Progesterona/genética , Pseudogravidez , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção/métodos
13.
AJNR Am J Neuroradiol ; 37(6): 1170-7, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26797142

RESUMO

BACKGROUND AND PURPOSE: Pure speech delay is a common developmental disorder which, according to some estimates, affects 5%-8% of the population. Speech delay may not only be an isolated condition but also can be part of a broader condition such as global developmental delay. The present study investigated whether diffusion tensor imaging tractography-based connectome can differentiate global developmental delay from speech delay in young children. MATERIALS AND METHODS: Twelve children with pure speech delay (39.1 ± 20.9 months of age, 9 boys), 14 children with global developmental delay (39.3 ± 18.2 months of age, 12 boys), and 10 children with typical development (38.5 ± 20.5 months of age, 7 boys) underwent 3T DTI. For each subject, whole-brain connectome analysis was performed by using 116 cortical ROIs. The following network metrics were measured at individual regions: strength (number of the shortest paths), efficiency (measures of global and local integration), cluster coefficient (a measure of local aggregation), and betweeness (a measure of centrality). RESULTS: Compared with typical development, global and local efficiency were significantly reduced in both global developmental delay and speech delay (P < .0001). The nodal strength of the cognitive network is reduced in global developmental delay, whereas the nodal strength of the language network is reduced in speech delay. This finding resulted in a high accuracy of >83% ± 4% to discriminate global developmental delay from speech delay. CONCLUSIONS: The network abnormalities identified in the present study may underlie the neurocognitive and behavioral consequences commonly identified in children with global developmental delay and speech delay. Further validation studies in larger samples are required.


Assuntos
Encéfalo/diagnóstico por imagem , Conectoma/métodos , Deficiências do Desenvolvimento/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Transtornos do Desenvolvimento da Linguagem/diagnóstico por imagem , Criança , Feminino , Humanos , Masculino
14.
Curr Mol Med ; 16(3): 276-87, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26917262

RESUMO

Endometriosis is a major cause of infertility and pelvic pain, affecting more than 10% of reproductive-aged women. Progesterone resistance has been observed in the endometrium of women with this disease, as evidenced by alterations in progesterone-responsive gene and protein expression. cAMPResponse Element-Binding 3-like protein 1 (Creb3l1) has previously been identified as a progesterone receptor (PR) target gene in mouse uterus via high density DNA microarray analysis. However, CREB3L1 function has not been studied in the context of endometriosis and uterine biology. In this study, we validated progesterone (P4) regulation of Creb3l1 in the uteri of wild-type and progesterone receptor knockout (PRKO) mice. Furthermore, we observed that CREB3L1 expression was significantly higher in secretory phase human endometrium compared to proliferative phase and that CREB3L1 expression was significantly decreased in the endometrium of women with endometriosis. Lastly, by transfecting CREB3L1 siRNA into cultured human endometrial stromal cells (hESCs) prior to hormonal induction of in vitro decidualization, we showed that CREB3L1 is required for the decidualization process. Interestingly, phosphorylation of ERK1/2, critical factor for decidualization, was also significantly reduced in CREB3L1-silenced hESCs. It is known that hESCs from patients with endometriosis show impaired decidualization and that dysregulation of the P4-PR signaling axis is linked to a variety of endometrial diseases including infertility and endometriosis. Therefore, these results suggest that CREB3L1 is required for decidualization in mice and humans and may be linked to the pathogenesis of endometriosis in a P4-dependent manner.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Endometriose/genética , Endométrio/metabolismo , Proteínas do Tecido Nervoso/genética , Progesterona/farmacologia , Receptores de Progesterona/genética , Adulto , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/antagonistas & inibidores , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Endometriose/metabolismo , Endometriose/patologia , Endometriose/cirurgia , Endométrio/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Histerectomia , Ciclo Menstrual/efeitos dos fármacos , Ciclo Menstrual/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/metabolismo , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptores de Progesterona/deficiência , Transdução de Sinais , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/patologia
15.
Mol Cells ; 12(1): 77-83, 2001 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-11561733

RESUMO

Budding cells of the yeast Saccharomyces cerevisiae possess a ring of septin filaments of unknown biochemical nature that lies under the inner surface of the plasma membrane in the neck that connects the mother cell to its bud. Mutants, defective in any of the four genes (CDC3, CDC10, CDC11, CDC12), lack these septin filaments and display a pleiotropic phenotype that involves abnormal bud growth and an inability to complete cytokinesis. The cloned CDC10 was fused to bacterial genes to generate antibodies specific for the CDC10 product was a constituent of the septin filaments. Cdc10p-specific antibodies for septin staining and actin-specific rhodamine-phalloidine were used to investigate the timing of the localization of septin and actin at the budding site using the immunofluorescence microscopic technique. In wild-type cells, the timing of the appearance and disappearance of these proteins was indistinguishable. In addition, the cdc10 mutant did not prevent actin localization at the budding site. The mutant that was blocked in the actin function also did not prevent the septin localization of the Cdc10p. This result may suggest an organizational independence between these proteins in the bud formation. Finally, the localization of septin and actin in the cdc24 mutant cell was examined. It was found that the CDC24 function was necessary for the organization of septin and actin at the budding site.


Assuntos
Actinas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas Fúngicas/metabolismo , Fatores de Troca do Nucleotídeo Guanina , Saccharomyces cerevisiae/fisiologia , Actinas/genética , Anticorpos Antifúngicos/imunologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/imunologia , Proteínas Fúngicas/genética , GTP Fosfo-Hidrolases , Proteínas de Membrana , Microscopia de Fluorescência , Fenótipo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Schizosaccharomyces pombe , Temperatura , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
16.
Mol Cells ; 9(5): 476-83, 1999 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-10597035

RESUMO

We examined the effects of the purified ginseng components, panaxadiol (PD) and panaxatriol (PT), on the expression of matrix metalloproteinase-9 (MMP-9) in highly metastatic HT1080 human fibrosarcoma cell line. A significant down-regulation of MMP-9 by PD and PT was detected by Northern blot analysis. However, the expression of MMP-2 was not changed by treatment with PD and PT. Quantitative gelatin based zymography confirmed a markedly reduced expression of MMP-9, but not MMP-2 in the treatment of PD and PT. To investigate whether the reduced level of MMP-9 by PD and PT affects the invasive capacity of HT1080 cells, we conducted an in vitro invasion assay with PD and PT treated cells. The results of the in vitro invasion assay revealed that PD and PT reduced tumor cell invasion through a reconstituted basement membrane in the transwell chamber. Because of the similarity of chemical structure between PD, PT and dexamethasone (Dexa), a synthetic glucocorticoid, we investigated whether the down-regulation of MMP-9 by PD and PT were mediated by the nuclear translocation of glucocorticoid receptor (GR). Increased GR in the nucleus of HT1080 human fibrosarcoma cells treated by PD and PT was detected by immunocytochemistry. Western blot and gel retardation assays confirmed the increase of GR in the nucleus after treatment with PD and PT. These results suggest that GR-induced down-regulation of MMP-9 by PD and PT contributes to reduce the invasive capacity of HT1080 cells.


Assuntos
Fibrossarcoma/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos , Metaloproteinase 9 da Matriz/biossíntese , Invasividade Neoplásica , Proteínas de Neoplasias/biossíntese , Panax/química , Plantas Medicinais , Receptores de Glucocorticoides/efeitos dos fármacos , Triterpenos/farmacologia , Núcleo Celular/metabolismo , Citosol/metabolismo , Dexametasona/química , Indução Enzimática/efeitos dos fármacos , Humanos , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Proteínas de Neoplasias/genética , RNA Mensageiro/biossíntese , Receptores de Glucocorticoides/fisiologia , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificação , Células Tumorais Cultivadas/efeitos dos fármacos
17.
Ann Thorac Surg ; 59(4): 891-5, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7695414

RESUMO

Various annuloplasty techniques are used to correct tricuspid or mitral valve regurgitation. We performed a partial annular plication procedure, a modification of the annuloplasty introduced by Davila, in 23 consecutive patients with moderate to severe tricuspid regurgitation or moderate mitral regurgitation. A slender plastic tube was used to tighten snugly the suture during intraoperative saline flushing test for assessment of the valve competency. This technique enabled us to add one stitch or two for more plication before the suture was tied if necessary. During a mean follow-up period of 13.8 months postoperatively, 10 patients (43.5%) had no valve regurgitation, 12 patients (52.2%) had grade 1+ regurgitation, and 1 patient (4.3%) grade 2+ on color Doppler echocardiography. The regurgitation grade remained unchanged or improved after the initial postoperative study. Our surgical experience indicates that the adjustable procedure of partial annular plication is a simple, exact, and durable procedure in patients of all ages with moderate to severe functional atrioventricular regurgitation.


Assuntos
Ecocardiografia , Insuficiência da Valva Mitral/cirurgia , Técnicas de Sutura , Insuficiência da Valva Tricúspide/cirurgia , Adolescente , Adulto , Idoso , Valva Aórtica/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Tricúspide/diagnóstico por imagem
18.
J Am Soc Echocardiogr ; 10(2): 185-8, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9083975

RESUMO

An 80-year-old man was admitted to the hospital because of recurrent syncope caused by sick sinus syndrome. Conventional transthoracic echocardiography showed a membranelike echo-dense structure across the left atrium. Subsequently we confirmed the diagnosis of cor triatriatum with multiple defects and shunt flows across the membrane by transesophageal color flow Doppler echocardiography. There were no other associated congenital anomalies. The patient recovered well and was discharged from the hospital after implantation of a permanent VVI pacemaker for sinus node dysfunction. No other cardiac intervention for the cor triatriatum was done except follow-up with echocardiography. About 1 year after discharge, he died of massive cerebral infarction. The cardiac autopsy findings were compatible with the transesophageal echocardiogram. This is a rare case of uncorrected cor triatriatum in an elderly patient.


Assuntos
Coração Triatriado/diagnóstico por imagem , Ecocardiografia Doppler em Cores , Ecocardiografia Transesofagiana , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Marca-Passo Artificial , Síndrome do Nó Sinusal/complicações , Síndrome do Nó Sinusal/terapia
19.
Med Sci Sports Exerc ; 28(10): 1336-41, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8897394

RESUMO

The purpose of the study was to reexamine the relationship between the Wingate and Critical Power tests of anaerobic capacity (AC) and anaerobic reserve (AR), respectively. A second purpose was to observe gender differences. Both tests were administered to 16 female and 13 male subjects (N = 29) on a Monark cycle ergometer with six subjects repeating AR measurement. The results show that AC (240.2 +/- 30.5 J-kg-1, calculated from total work for 30 s) and AR (184.0 +/- 1.2 J.kg-1) were not well-correlated (r = 0.07, P > 0.72). When expressed as total energy independent of body mass, the relationship was significant but low (r = 0.41, P > 0.02). Since AR was 23% lower than AC, which is believed to underestimate true anaerobic capacity, the data suggest that the Critical Power and Wingate tests do not assess the same anaerobic compartments. AR from the Critical Power test may not include the energy component of anaerobic glycolysis. Therefore, intrinsic methodological and theoretical differences between the tests make the absolute comparison of AC and AR problematic.


Assuntos
Limiar Anaeróbio , Teste de Esforço/métodos , Adulto , Feminino , Humanos , Masculino , Consumo de Oxigênio , Fatores Sexuais
20.
Eur J Cardiothorac Surg ; 20(6): 1267-9, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11717047

RESUMO

We report a case of esophagopericardial fistula with subsequent purulent pericarditis that was diagnosed with computed tomography and echocardiography. In a patient with non-specific chest pain and vague past history, serial echocardiography demonstrated rapid aggravation of pyopneumopericardium and chest CT scan showed a foreign body that caused the fistula in the esophageal wall. Removal of a piece of fish bone, closure of the fistula, and creation of a pericardial window for continuous drainage were performed through a low lateral thoracotomy.


Assuntos
Fístula Esofágica/complicações , Fístula/complicações , Pericardite/diagnóstico , Pericárdio , Adulto , Ecocardiografia , Fístula Esofágica/etiologia , Esôfago , Fístula/etiologia , Corpos Estranhos , Humanos , Masculino , Pericardite/etiologia , Supuração , Tomografia Computadorizada por Raios X
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