Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 67
Filtrar
1.
Brief Bioinform ; 24(2)2023 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-36736370

RESUMO

As the number of protein sequences increases in biological databases, computational methods are required to provide accurate functional annotation with high coverage. Although several machine learning methods have been proposed for this purpose, there are still two main issues: (i) construction of reliable positive and negative training and validation datasets, and (ii) fair evaluation of their performances based on predefined experimental settings. To address these issues, we have developed ProFAB: Open Protein Functional Annotation Benchmark, which is a platform providing an infrastructure for a fair comparison of protein function prediction methods. ProFAB provides filtered and preprocessed protein annotation datasets and enables the training and evaluation of function prediction methods via several options. We believe that ProFAB will be useful for both computational and experimental researchers by enabling the utilization of ready-to-use datasets and machine learning algorithms for protein function prediction based on Gene Ontology terms and Enzyme Commission numbers. ProFAB is available at https://github.com/kansil/ProFAB and https://profab.kansil.org.


Assuntos
Benchmarking , Software , Anotação de Sequência Molecular , Algoritmos , Proteínas/metabolismo , Biologia Computacional/métodos
2.
Lung ; 199(6): 677-680, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34741227

RESUMO

Pulmonary hypertension (PH) is associated with decreased survival in patients with pulmonary fibrosis and combined pulmonary fibrosis and emphysema. Main pulmonary artery (PA) diameter and PA diameter/ascending aortic diameter (PA/AA) ratio, as measured on CT, have recently emerged as specific markers for PH. Our single-center retrospective study found that PA/AA ratio > 1 is associated with decreased survival in individuals with pulmonary fibrosis, with or without emphysema. Our study also describes markers of cardiac remodeling, and the echocardiographic diagnosis of PH in this patient population.


Assuntos
Enfisema , Fibrose Pulmonar , Aorta/diagnóstico por imagem , Enfisema/patologia , Humanos , Prognóstico , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/patologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
3.
J Oncol Pharm Pract ; 27(8): 1940-1947, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33342356

RESUMO

In Ethiopia, cancer accounts for about 5.8% of total national mortality, with an estimated annual incidence of cancer of approximately 60,960 cases and an annual mortality of over 44,000 persons. This is likely an underestimation. Survival rates for pediatric malignancies are likewise suboptimal although exact figures are unknown since a national cancer registry is unavailable. The World Health Organization (WHO) provides recommendations for the creation of cancer registries to track such data. Here we describe our pharmacist-led, pre-implementation assessment of introducing an enhanced national pediatric cancer registry in Ethiopia. Our assessment project had three specific aims around which the methods were designed: 1) characterization of the current spreadsheet-based tool across participating sites, including which variables were being collected, how these variables compared to standards set by the WHO, and a description of how the data were entered and its completeness; 2) assessment of the perceptions of an enhanced registry from hospital staff; and 3) evaluation of workflow gaps regarding documentation. The hospital staff and leadership have generally positive perceptions of an enhanced pediatric cancer registry, which were further improved by our interactions. The workflow assessment revealed several gaps, which were addressed systematically using a three-phase implementation science approach. The assessment also demonstrated that the existing spreadsheet-based tool was missing WHO-recommended variables and had inconsistent completion due to the workflow gaps. A pediatric oncology summary sheet will be implemented in upcoming trips in patient charts to better summarize the patients' journey starting from diagnosis. This document will be used by the data clerks in an enhanced-spreadsheet to have a more complete data set.


Assuntos
Neoplasias , Criança , Documentação , Etiópia/epidemiologia , Humanos , Oncologia , Neoplasias/epidemiologia , Sistema de Registros
4.
Niger J Clin Pract ; 24(6): 853-859, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34121733

RESUMO

AIMS: The aim of this study was to identify C. parapsilosis complex strains isolated from various clinical samples by sequence analysis and to investigate whether there are any differences between the species in terms of virulence factors and antifungal susceptibility. METHODS: The study included a total of 42 isolates identified as C. parapsilosis complex based on the color they formed in chromogenic medium, colony morphology, and microscopic appearance in Corn Meal-Tween 80 Agar and they were confirmed with API 20 C AUX. For the DNA sequence analysis of clinical isolates, V9G forward and LS reverse primers were used as well as internal transcribed spacers (ITS1 and ITS4). Biofilm formation, esterase, phospholipase, and protease activities were evaluated as virulence factors. Antifungal susceptibility was investigated via colorimetric microdilution method. RESULTS: A total of 75 non-C. albicans isolates were obtained from various clinical samples between 2016 and 2017 in a Turkish Tertiary Care Hospital. Of them, 42 were identified as members of the C. parapsilosis complex. Of the 42 strains, 41 were identified as C. parapsilosis sensu stricto (CpSS), while only one was identified as C. orthopsilosis. Of the CpSS strains, 31 (75.6%) were biofilm-positive, six (14.6%) were esterase-positive, nine (21.9%) were positive for phospholipase activity, and 31 (75.6%) were positive for protease formation, whereas all virulence factors of C. orthopsilosis strain were found to be negative. All CpSS strains were found susceptible to amphotericin B, echinocandins, and flucytosine. CONCLUSIONS: It has been concluded that the use of molecular methods to identify CpSS would not be effective in routine laboratory practices as it is the most commonly isolated species from the C. parapsilosis complex and there are no significant differences between species in terms of antifungal susceptibility.


Assuntos
Antifúngicos , Candida parapsilosis , Antifúngicos/farmacologia , Biofilmes , Candida parapsilosis/genética , Humanos , Testes de Sensibilidade Microbiana , Fatores de Virulência/genética
5.
Mikrobiyol Bul ; 54(4): 638-646, 2020 Oct.
Artigo em Turco | MEDLINE | ID: mdl-33107293

RESUMO

Bloodstream infections due to yeast species especially Candida spp. have been reported to be important healthcare associated infections with high mortality and morbidity rates. Candidemia causes prolonged hospital stays as well as increased cost. In order to prevent or treat these life-threatening bloodstream infections successfully, nationwide epidemiological data should be available about the etiological agents of these infections. Multi-centre national epidemiological data on yeast bloodstream infections in Turkey is lacking. A retrospective study was designed and data from six different centres in Turkey between 2011 and 2016 years were gathered and analysed for the distribution and frequency of yeast species in order to assist clinicians in their choice of early and appropriate antifungal therapy. All laboratories used automated blood culture systems for the isolation of blood strains. All the participating centres performed the identification of their own isolates by conventional methods using germ tube test, morphology on corn meal agar with tween 80 and chromogenic media and the identification was confirmed by API 20C AUX, API ID 32C or matrix-assisted laser desorption/ionization time of flight mass spectrophotometry (MALDI-TOF MS) systems. The analysis of the results was performed on the basis of intensive care units (ICUs), other inpatient clinics (OICs) and totally all clinics (ACs). Totally 2547 yeast isolates were determined from six participating centres during six years. According to the total ACs results, Candida albicans was the most prevalent species (43.1%), followed by Candida parapsilosis complex (29.1%), Candida glabrata (10.1%), Candida tropicalis (7.5%), Candida krusei (2.4%) and Candida kefyr (1.6%) and the remaining (6.2%) of them consisted of other yeast species. The distribution of the Candida species did not show statistically significant difference between the years, however the increase of C.parapsilosis complex in 2016 was statistically significant, (p= 0.02). During the study period, totally 1054 yeast isolates were obtained from the ICUs of the centres. C.albicans predominated with 476 (45.2%) isolates and C.parapsilosis complex (28.7%), C.glabrata (10.7%) and C.tropicalis (7.3%) were the other leading species in ICUs. Among 1493 isolates of the OICs of six centres participated in the study, C.albicans was the most prevalent species with 622 (41.7%) isolates. The other frequent species of OICs were C.parapsilosis complex (29.5%), C.glabrata (9.6%) and C.tropicalis (7.6%) resembling ICU results. It can be concluded that C.albicans is still the leading cause of bloodstream infections in the six different centres located in various geographical areas of Turkey.


Assuntos
Hemocultura , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Kluyveromyces , Testes de Sensibilidade Microbiana , Filogenia , Pichia , Estudos Retrospectivos , Turquia/epidemiologia
6.
Int J Obes (Lond) ; 42(1): 111-114, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28947836

RESUMO

Increased sedentariness has been linked to the growing prevalence of obesity in children, but some longitudinal studies suggest that sedentariness may be a consequence rather than a cause of increased adiposity. We used Mendelian randomization to examine the causal relations between body mass index (BMI) and objectively assessed sedentary time and physical activity in 3-8 year-old children from one Finnish and two Danish cohorts [NTOTAL=679]. A genetic risk score (GRS) comprised of 15 independent genetic variants associated with childhood BMI was used as the instrumental variable to test causal effects of BMI on sedentary time, total physical activity, and moderate-to-vigorous physical activity (MVPA). In fixed effects meta-analyses, the GRS was associated with 0.05 SD/allele increase in sedentary time (P=0.019), but there was no significant association with total physical activity (beta=0.011 SD/allele, P=0.58) or MVPA (beta=0.001 SD/allele, P=0.96), adjusting for age, sex, monitor wear-time and first three genome-wide principal components. In two-stage least squares regression analyses, each genetically instrumented one unit increase in BMI z-score increased sedentary time by 0.47 SD (P=0.072). Childhood BMI may have a causal influence on sedentary time but not on total physical activity or MVPA in young children. Our results provide important insights into the regulation of movement behaviour in childhood.


Assuntos
Adiposidade/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Comportamento Sedentário , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Dinamarca/epidemiologia , Exercício Físico/fisiologia , Finlândia/epidemiologia , Humanos , Obesidade/epidemiologia , Obesidade/genética
7.
Int J Obes (Lond) ; 42(4): 775-784, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28990592

RESUMO

BACKGROUND: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. PARTICIPANTS AND METHODS: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight). RESULTS: Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG. CONCLUSIONS: We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.


Assuntos
Feto/fisiologia , Ganho de Peso na Gestação/genética , Gravidez/genética , Feminino , Estudo de Associação Genômica Ampla , Ganho de Peso na Gestação/fisiologia , Humanos , Gravidez/fisiologia , Gravidez/estatística & dados numéricos
8.
Scand J Med Sci Sports ; 28(7): 1808-1817, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29474750

RESUMO

Impaired expression of heat shock proteins (HSPs) and increased oxidative stress may contribute to the pathophysiology of diabetes by disrupted tissue protection. Acute exercise induces oxidative stress, whereas exercise training up-regulates endogenous antioxidant defenses and HSP expression. Although diabetic nephropathy is a major contributor to diabetic morbidity, information regarding the effect of HSPs on kidney protection is limited. This study evaluated the effects of eight-week exercise training on kidney HSP expression and markers of oxidative stress at rest and after acute exercise in rats with or without streptozotocin-induced diabetes. Induction of diabetes increased DNA-binding activity of heat shock factor-1, but decreased the expression of HSP72, HSP60, and HSP90. The inflammatory markers IL-6 and TNF-alpha were increased in the kidney tissue of diabetic animals. Both exercise training and acute exercise increased HSP72 and HSP90 protein levels only in non-diabetic rats. On the other hand, exercise training appeared to reverse the diabetes-induced histological changes together with decreased expression of TGF-beta as a key inducer of glomerulosclerosis, and decreased levels of IL-6 and TNF-alpha. Notably, HSP72 and TGF-beta were negatively correlated. In conclusion, impaired HSP defense seems to contribute to kidney injury vulnerability in diabetes and exercise training does not up-regulate kidney HSP expression despite the improvements in histopathological and inflammatory markers.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Resposta ao Choque Térmico , Rim/fisiopatologia , Condicionamento Físico Animal , Animais , Chaperonina 60/metabolismo , Proteínas de Choque Térmico HSP72/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Interleucina-6/metabolismo , Masculino , Proteínas Mitocondriais/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
9.
Med Mycol ; 55(5): 535-540, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-27915301

RESUMO

Galactomannan (GM) assay is commonly used as an early diagnostic tool for invasive fungal infection (IFI) in high-risk hematology patients. False positivity is frequently observed in GM with the use of piperacillin/tazobactam. The usage of generic drugs over the original brand has a significant cost advantage. The aim of this study was to assess the performance of GM test among patients receiving original and generic piperacillin/tazobactam formulations. The study included 85 adult patients; 62.4% were male with hematological malignancy currently receiving piperacillin/tazobactam. The study group was divided into two groups: patients receiving original and generic piperacillin/tazobactam. Serum GM index was positive in one of 35 patients receiving original piperacillin/tazobactam, whereas it was positive in 46 out of 50 patients receiving generic piperacillin/tazobactam (P < .001). However, the patients receiving generic piperacillin/tazobactam underwent computed tomography (CT) scans more frequently than those receiving original piperacillin/tazobactam (P = .047). In addition, in vitro analysis of GM was performed in two generics and one original piperacillin/tazobactam vials. One generic piperacillin/tazobactam vial included high GM level. False positivity of serum GM with generic formulations of piperacillin/tazobactam is still an ongoing issue in hematology patients. A high rate of serum GM index false positivity may unexpectedly lead to a higher rate of CT scan. Selected piperacillin/tazobactam vials in each batch should be checked for GM to identify a false positivity of GM before purchase.


Assuntos
Antibacterianos/uso terapêutico , Antígenos de Fungos/sangue , Neutropenia Febril/complicações , Neutropenia Febril/tratamento farmacológico , Mananas/sangue , Ácido Penicilânico/análogos & derivados , Antibacterianos/normas , Reações Falso-Positivas , Neutropenia Febril/microbiologia , Feminino , Galactose/análogos & derivados , Humanos , Aspergilose Pulmonar Invasiva/diagnóstico , Masculino , Técnicas Microbiológicas/normas , Pessoa de Meia-Idade , Ácido Penicilânico/normas , Ácido Penicilânico/uso terapêutico , Piperacilina/normas , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam
10.
Niger J Clin Pract ; 20(1): 61-63, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27958248

RESUMO

BACKGROUND: The germ tube test (GTT) is inexpensive, easy, and well-defined test that differentiates Candida albicans (excluding Candida dubliniensis and Candida africana) from other species. The aim of this study was to evaluate various serums (i.e., human, rabbit, horse, and fetal bovine serum) used in the GTT and Mueller-Hinton agar (MHA). MATERIALS AND METHODS: Fifty species isolated from various clinical samples that were defined as C. albicans by both conventional and DNA sequence analysis methods were included in the study. One to two colonies of C. albicans were mixed into 0.5-1 ml of fetal bovine serum, horse serum, rabbit serum, and human serum. Serums and MHA were incubated at 37°C for GTT. They were removed from the incubator and evaluated after 30 min, 1 h, 2 h, and 3 h of incubation. The GTT was accepted to be positive only if germ tube was 1/2 the width and 3 times the length of the parent yeast cell and with no constriction at the point of origin. RESULTS: When the use of serums and MHA for GTT was statistically evaluated, according to the positive scoring, the best results were obtained with MHA and with rabbit, horse, and fetal bovine serum, respectively. The best definition over time statistically was the third hour. CONCLUSION: It is suggested that inexpensive MHA is a fast, appropriate, and reliable medium for the probable diagnosis of GTT and C. albicans; however, additional studies are still needed to define other Candida species.


Assuntos
Ágar , Candida albicans/isolamento & purificação , Candidíase/diagnóstico , Candidíase/microbiologia , Soro , Animais , Candida albicans/genética , Candida albicans/crescimento & desenvolvimento , Candida albicans/metabolismo , Bovinos , Meios de Cultura , Cavalos , Humanos , Tipagem Molecular , Reação em Cadeia da Polimerase Multiplex , Técnicas de Tipagem Micológica/métodos , Coelhos , Sensibilidade e Especificidade , Especificidade da Espécie
11.
Clin Exp Obstet Gynecol ; 43(1): 98-102, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27048026

RESUMO

BACKGROUND: It is theorized that adipokines play a critical role in the pathophysiology of preeclampsia, particularly with their pro-inflammatory and inflammatory features. AIM: To investigate serum leptin levels in pregnancies complicated with preeclampsia and severe preeclampsia. MATERIALS AND METHODS: Maternal serum leptin levels were analyzed by solid phase enzyme amplified sensitivity immunoassay (EASIA) method in 23 patients with mild preeclampsia, 29 patients with severe preeclampsia, and 28 healthy pregnant controls. RESULTS: Mean serum leptin levels did not differ statistically between patients with mild preeclampsia, severe preeclampsia, and the controls (10.77 ng/ml, 13.40 ng/ml, and 8.43 ng/ml, respectively). Also, there was no relationship between serum leptin levels and the gestational ages of the participants. DISCUSSION: Serum leptin levels are not associated with preeclampsia. Leptin measurements are not affected with the gestational age. The role of leptin in the pathophysiology of preeclampsia should be evaluated cautiously.


Assuntos
Leptina/sangue , Pré-Eclâmpsia/sangue , Adulto , Biomarcadores/sangue , Feminino , Idade Gestacional , Humanos , Pré-Eclâmpsia/diagnóstico , Gravidez , Índice de Gravidade de Doença , Adulto Jovem
12.
Clin Exp Obstet Gynecol ; 42(4): 462-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26411212

RESUMO

OBJECTIVE: To assign tendency to thrombosis in patients with preeclampsia and inherited thrombophilia using thromboelastography (TEG), and therefore to evaluate possible relationship between thrombophilia and preeclampsia. MATERIALS AND METHODS: Kinetics of clot formation was assessed with TEG analyzer in 49 patients with severe preeclampsia, 54 cases with previous diagnosis of inherited thrombophilia, and 31 controls. RESULTS: 'r, 'k', TMA, coagulation index (CI) parameters were found statistically discrete between patients with inherited thrombophilia and controls. The difference between preeclampsia and control groups was not statistically significant. The difference in a angle was statistically significant between thrombophilics and preeclamptics (p = 0.01), and between thrombophilics and controls (p = 0.004). CI was found statistically lower in thrombophilia group than control group (p = 0.006). Particularly, clot lysis time (CLT) was measured to shorten in preeclampsia when compared with controls and patients with thrombophilia (p = 0.032, p = 0.028, respectively). CONCLUSIONS: Not only the inherited thrombophilia group but also preeclampsia group demonstrated elongated clot initiation patterns when compared to the controls. Moreover, apart from the patients with inherited thrombophilia, preeclamptics exposed shorter CLT values indicating a possible increment in clot turn over, which eventually results in increased depletion of coagulation substrates, and thus, increased frequencies of oxidative cycle injury.


Assuntos
Pré-Eclâmpsia/sangue , Tromboelastografia , Trombofilia/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Valor Preditivo dos Testes , Gravidez , Diagnóstico Pré-Natal
13.
Niger J Clin Pract ; 18(1): 52-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25511344

RESUMO

BACKGROUND: The Candida species, which are one of the most common causes of nosocomial bloodstream infections, present with high mortality and morbidity rates. This study aims to investigate the production of esterase, phospholipase, proteinase, and biofilm formation ability of the Candida strains isolated from the blood cultures. MATERIALS AND METHODS: Between June 2011 and July 2012, the Candida strains, which were isolated from blood cultures of a total of 50 patients, were studied. The esterase activity was analyzed in the Tween-80 agar, while phospholipase activity was studied in the egg yolk agar. The proteinase activity and biofilm formation were identified by using the petri dish method and microplate method, respectively. RESULTS: Of 50 specimens obtained from individual patients, 17 (34%) were identified as C. albicans, 14 (28%) as C. glabrata, 9 (18%) as C. parapsilosis, 5 (10%) as C. krusei, 4 (8%) as C. kefyr, and 1 (2%) as C. tropicalis. The rate of proteinase, phospholipase, and esterase positivity was higher in the C. albicans isolates. Biofilm formation was the highest in the C. parapsilosis strains. CONCLUSIONS: Higher rate of virulence factors in the most commonly isolated Candida species than other species indicates that these virulence factors play a crucial role in the pathogenesis.


Assuntos
Biofilmes/crescimento & desenvolvimento , Candida/patogenicidade , Candidemia/microbiologia , Infecção Hospitalar/microbiologia , Esterases/metabolismo , Peptídeo Hidrolases/metabolismo , Fosfolipases/metabolismo , Fatores de Virulência/metabolismo , Candida/isolamento & purificação , Candida/fisiologia , Candida albicans , Candida glabrata , Candida tropicalis , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
West Indian Med J ; 63(4): 300-6, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25429472

RESUMO

AIM: The aim of this study was to investigate whether the glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) gene polymorphisms contributed to development of gestational diabetes mellitus (GDM). SUBJECTS AND METHODS: Fifty women with diagnosis of GDM and 50 control individuals without GDM or altered glucose intolerance during their pregnancy were enrolled in the study. Multiplex polimerase chain reaction-restriction fragment length polymorphism method was applied to determine the GSTM1 and GSTT1 gene polymorphisms. Genotypes were determined according to bands detected with the agarose gel electrophoresis. RESULTS: The difference in the frequencies of GSTM1 null genotypes between GDM and control groups was not statistically significant (60% and 54%, respectively). There was no statistically significant difference between GDM and control groups with respect to GSTT1 null genotype rates (22% and 20%, respectively).There was no statistically significant difference between GDM and control groups with respect to GSTT1 null genotype rates (22% and 20%, respectively). CONCLUSION: This study shows no association between GST gene polymorphisms and GDM.

15.
bioRxiv ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38915485

RESUMO

Idiopathic pulmonary fibrosis is a fatal disease characterized by the TGF-ß-dependent activation of lung fibroblasts, leading to excessive deposition of collagen proteins and progressive replacement of healthy lung with scar tissue. We and others have shown that fibroblast activation is supported by metabolic reprogramming, including the upregulation of the de novo synthesis of glycine, the most abundant amino acid found in collagen protein. How fibroblast metabolic reprogramming is regulated downstream of TGF-ß is incompletely understood. We and others have shown that TGF-ß-mediated activation of the Mechanistic Target of Rapamycin Complex 1 (mTORC1) and downstream upregulation of Activating Transcription Factor 4 (ATF4) promote increased expression of the enzymes required for de novo glycine synthesis; however, whether mTOR and ATF4 regulate other metabolic pathways in lung fibroblasts has not been explored. Here, we used RNA sequencing to determine how both ATF4 and mTOR regulate gene expression in human lung fibroblasts following TGF-ß. We found that ATF4 primarily regulates enzymes and transporters involved in amino acid homeostasis as well as aminoacyl-tRNA synthetases. mTOR inhibition resulted not only in the loss of ATF4 target gene expression, but also in the reduced expression of glycolytic enzymes and mitochondrial electron transport chain subunits. Analysis of TGF-ß-induced changes in cellular metabolite levels confirmed that ATF4 regulates amino acid homeostasis in lung fibroblasts while mTOR also regulates glycolytic and TCA cycle metabolites. We further analyzed publicly available single cell RNAseq data sets and found increased expression of ATF4 and mTOR metabolic targets in pathologic fibroblast populations from the lungs of IPF patients. Our results provide insight into the mechanisms of metabolic reprogramming in lung fibroblasts and highlight novel ATF4 and mTOR-dependent pathways that may be targeted to inhibit fibrotic processes.

16.
Eur J Gynaecol Oncol ; 34(1): 42-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23589999

RESUMO

OBJECTIVE: To investigate the polymorphism rates and possible roles of glutathione-s-transferase M1, T1, and P1 gene polymorphisms in the predisposition to endometrial cancer in Caucasian women. MATERIALS AND METHODS: Serum samples and medical records were collected from 53 Caucasian women with newly diagnosed endometrial cancer and 67 women of the same race without any known history of cancer. Multiplex polymerase chain reaction (PCR) analysis was used to assess glutathione-s-transferase M1 (GSTM1) and T1 gene polymorphisms. Polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method was used in salvage of GSTP1 gene polymorphism. RESULTS: Frequencies of GSTM1 and GSTT1 null genotypes were not significantly different between the controls and patients with endometrial cancer (56.7% vs 52.8%, p = 0.671; 32.8% vs 26.4%, p = 0.574, respectively). The authors were not able to demonstrate any association between neither GSTP1 genotypes nor allele frequencies and endometrial carcinoma in the population studied (p = 0.310, p = 0.318, respectively). Moreover, no significant association could be demonstrated with GSTM1 and GSTT1 polymorphisms and clinical stages of endometrial cancer. Nevertheless, there was a significant difference between the frequencies of GSTP1 AA and GG genotypes in relation to Stage I disease when compared with advanced stages of endometrial carcinoma (p = 0.03). In addition, no association was found between polymorphisms of GST suspergene family and non-endometrioid type endometrial carcinomas. CONCLUSION: These results suggest that GSTT1, GSTM1, and GSTP1 polymorphisms are not associated with endometrial cancer in the Caucasian population.


Assuntos
Neoplasias do Endométrio/genética , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Polimorfismo Genético , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Clin Exp Obstet Gynecol ; 40(2): 261-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23971255

RESUMO

OBJECTIVE: To evaluate the role of adiponectin and visfatin in the pathophysiology of pre-eclampsia (PE) and how their concentrations correlate with the severity of the disease and neonatal outcomes. STUDY DESIGN: A prospective case-control study was carried out in 52 preeclamptic and 28 healthy pregnant women during the third trimester. The maternal plasma concentrations of adiponectin and visfatin were determined. Neonatal outcomes were also recorded. RESULTS: Mean maternal plasma adiponectin concentrations in healthy pregnant women did not differ significantly from those of mild PE and severe PE groups. The plasma adiponectin levels of PE patients with small for gestational age (SGA) and those without SGA did not differ significantly, but the median plasma visfatin concentration of patients with SGA fetus was significantly higher if the patient was preeclamptic (p = 0.036). CONCLUSION: The severity of preeclampsia did not change the plasma levels of adiponectin and visfatin, but the median plasma visfatin concentration of patients with SGA fetuses were significantly higher if the patient was preeclamptic. Altered levels of adipocytokines strongly imply that the regulation of adipocytokines in PE is different and more complex compared to that in healthy pregnancy.


Assuntos
Adiponectina/sangue , Nicotinamida Fosforribosiltransferase/sangue , Pré-Eclâmpsia/sangue , Adulto , Índice de Apgar , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Pré-Eclâmpsia/fisiopatologia , Gravidez , Resultado da Gravidez , Terceiro Trimestre da Gravidez , Estudos Prospectivos
18.
Genet Mol Res ; 11(4): 4739-45, 2012 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-23315815

RESUMO

Vascular endothelial growth factor (VEGF) regulates endothelial cell proliferation, migration and differentiation. VEGF plays a critical role in angiogenesis during placenta formation. We investigated whether VEGF gene polymorphisms are associated with recurrent pregnancy loss. Thirty-eight women with recurrent pregnancy loss and 30 control women with live-born children were recruited from 2010 to 2011 in the region of Bursa, Turkey. VEGF gene polymorphisms were assessed with PCR-RFLP analysis of DNA samples obtained from leukocytes. DNA fragments were investigated by using appropriate primers. SNP scanning was performed using MnII, BgIII, BshI2361, Hsp92II restriction enzymes for 1154 G/A, 2578 C/A, 460 C/T, and 936 C/T polymorphisms, respectively. The frequencies of 2578 C/A, 460 C/T, 936 C/T polymorphisms were not significantly different between the controls and women with recurrent pregnancy loss. However, the prevalence of the 1154 G/A polymorphism A/A genotype was significantly higher in the recurrent pregnancy loss group (23.7 vs 3.4%). One of the four common polymorphisms of the VEGF gene was found to be more frequent in women with recurrent pregnancy loss. It is possible that disruption of VEGF function and placental angiogenesis can contribute to pregnancy loss in women with recurrent pregnancy loss.


Assuntos
Aborto Habitual/genética , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Sequência de Bases , Estudos de Casos e Controles , Primers do DNA/genética , Feminino , Estudos de Associação Genética , Humanos , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Gravidez , Análise de Sequência de DNA , Adulto Jovem
19.
Clin Exp Obstet Gynecol ; 39(4): 466-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23444745

RESUMO

AIMS: This study was conducted to investigate whether insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) gene and polymorphisms in glutathione S-transferase (GST) M1 and T1 genes are associated with increased risk for preeclampsia. MATERIALS AND METHODS: Sixty-three patients with hypertensive disorder of pregnancy and 85 controls were evaluated in a prospective case-control study. All subjects were genotyped by polymerase chain reaction (PCR) followed by agarose gel electrophoresis. RESULTS: Allele frequencies of ACE gene I/D polymorphism were found significantly different between preeclampsia and the control groups (p = 0.001). Differences in genotype frequencies of ACE gene I/D polymorphism between the two groups were statistically significant (p = 0.004). Individuals homozygous for D allele were more likely to develop preeclampsia (OR = 2.29; 95% CI, 1.39-3.79), whereas heterozygous individuals were not at increased risk (OR = 0.92; 95% CI, 0.56-1.49), compared to individuals homozygous for I allele. The differences in frequencies of functional and null alleles of GSTM1 and GSTT1 genes between the two groups were not significant (p = 0.46 and p = 0.44, respectively). CONCLUSION: ACE gene DD genotype was found to be associated with increased risk of preeclampsia development, whereas the authors did not find any significant relationship with polymorphisms of the GSTM1 and GSTT1 genes and preeclampsia.


Assuntos
Glutationa Transferase/genética , Pré-Eclâmpsia/genética , Renina/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Polimorfismo Genético , Gravidez , Sistema Renina-Angiotensina/genética , Turquia
20.
Clin Radiol ; 66(5): 405-11, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21300329

RESUMO

AIM: To determine the size and three-dimensional spatial distribution of pulmonary emboli (PE) at computed tomography angiography (CTA) to optimize the scan length. MATERIALS AND METHODS: Two experienced radiologists jointly reviewed 100 consecutive, positive PE CTA studies performed in the Emergency Department (53 women; age 61±17 years). All studies were conducted on a 16-detector row CT machine. In each case, the number of emboli was counted and the proximal and distal spatial coordinates of each embolus documented. Coordinates of the main pulmonary artery bifurcation (MPAb) and carina were recorded. For normalization, the thoracic cavity height (H)-from inlet to lowest hemidiaphragm-was measured. The minimal scan lengths for (a) capturing all emboli and (b) rendering a positive diagnosis were determined. RESULTS: Three hundred and seventy (370) emboli were detected. The average number of PE per patient was 3.7 (maximum 12, minimum 1). Their average length was 2.7 cm. Nine patients had saddle emboli (9%), and 71% of emboli were at or below the MPAb. An 18 cm (0.90×H) scan length, centred 4 cm (0.18×H) below the carina, captures all PE in this dataset while reducing z-axis coverage by 29% (34% for normalized data). Moreover, a 14.2 cm (0.78×H) scan length appropriately centred captures at least one embolus in all patients while reducing coverage by 44% (43%). Decreasing scan length to the lesser of 14.2 cm and 0.78×H per patient reduces coverage by 47%. CONCLUSION: Scan length at CTA for PE can be reduced by up to 47% while preserving diagnostic accuracy for PE detection.


Assuntos
Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Diagnóstico Precoce , Feminino , Humanos , Imageamento Tridimensional , Pessoa de Meia-Idade , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos , Sensibilidade e Especificidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA