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991.
Marta Rubio Daniele Avitabile Kimberlee Fischer Natalie Gude Shikha Mishra Eric M. Schaefer Mark A. Sussman 《Journal of molecular and cellular cardiology》2009,47(1):96-103
The phosphoinositide 3-kinase (PI3K)/phosphoinositide dependent kinase 1 (PDK1) signaling pathway exerts cardioprotective effects in the myocardium through activation of key proteins including Akt. Activated Akt accumulates in nuclei of cardiomyocytes suggesting that biologically relevant targets are located in that subcellular compartment. Nuclear Akt activity could be potentiated in both intensity and duration by the presence of a nuclear-associated PI3K/PDK1 signaling cascade as has been described in other non-myocyte cell types. PI3K/PDK1 distribution was determined in vitro and in vivo by immunostaining and nuclear extraction of cultured rat neonatal cardiomyocytes or transgenic mouse hearts. Results show that PI3K and PDK1 are present at a basal level in cardiomyocytes nuclei and that cardioprotective stimulation with atrial natriuretic peptide (ANP) increases their nuclear localization. In comparison, overexpression of nuclear-targeted Akt does not mediate increased translocation of either PI3K or PDK1 indicating that accumulation of Akt does not drive PI3K or PDK1 into the nuclear compartment. Furthermore, PI3K and phospho-Akt473 show parallel temporal accumulation in the nucleus following (MI) infarction challenge. These findings demonstrate the presence of a dynamically regulated nuclear-associated signaling cascade involving PI3K and PDK that presumably influences nuclear Akt activation. 相似文献
992.
Filip M Faron-Górecka A Kuśmider M Gołda A Frankowska M Dziedzicka-Wasylewska M 《Brain research》2006,1071(1):218-225
In the present study, we used in situ hybridization to examine the influence of acute or repeated cocaine administrations and withdrawal from repeated cocaine treatment on the level of brain-derived neurotrophic factor (BDNF) and its receptor trkB mRNAs in rat brain. Cocaine (10 mg/kg i.p.) injected acutely produced locomotor hyperactivation, while repeated (single injection for 5 days) administrations of cocaine (10 mg/kg) induced a two-fold increases in the locomotor activity in rats in response to a challenge cocaine dose (10 mg/kg) on day 10, as compared to the saline-treated animals (sensitization). Cocaine treatments induced a brain-region-specific decrease in the levels of trkB mRNA. On the other hand, BDNF mRNA in the rat hippocampus was increased only in the group of rats subjected to cocaine withdrawal. Animals under cocaine withdrawal demonstrated a significant increase in the immobility time measured by the use of modified forced swimming test. Therefore, the increases in the levels of BDNF mRNA in the rat hippocampus seem to be correlated with "depressive-like" behavioral effects during withdrawal from repeated cocaine treatment. In the shell (but not in the core) of the nucleus accumbens, the levels of BDNF mRNA were significantly increased following acute and repeated cocaine treatment as well as during cocaine withdrawal, which indicates that the alterations in the neurotrophin level in the brain region important for the expression of cocaine-induced sensitization involve other mechanisms. 相似文献
993.
Toro C Jiménez V Rodríguez C Del Romero J Rodés B Holguín A Alvarez P García-Campello M Gómez-Hernando C Guelar A Sheldon J de Mendoza C Simón A Soriano V 《Journal of medical virology》2006,78(12):1599-1608
The increased immigration from developing regions to Western countries raises public health concerns related to blood-borne viruses. The prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-lymphotropic virus (HTLV) infections among recent immigrants attending several Spanish diagnostic centers in years 2002 and 2003 was examined. Genetic characterization of viral subtypes and its relationship with distinct at-risk populations was carried out. A total of 1,303 immigrants were identified. They originated in Latin America (46.9%), Sub-Saharan Africa (23.7%), Eastern Europe (9.4%), and the Maghreb (9.2%). Seroprevalence rates were as follows: HIV-1 4.2%, HBV 4.1%, HCV 2.9%, and HTLV-1 0.8%. All patients with HIV-1 non-B subtypes, HBV genotypes E and A3, and HCV genotype 4 were sub-Saharan Africans, and had been infected mainly through heterosexual contacts. In contrast, Latin American homo/bisexual men carried HIV-1 subtype B most likely acquired after their arrival to Spain. In conclusion, while Sub-Saharan Africans carry wide diverse genetic variants of blood-borne viruses, the absence of high-risk practices in most cases could limit the spread of these variants. In contrast, Latin Americans with high-risk sexual practices may be a particularly vulnerable collective to acquire blood-borne viruses in the receptor country. 相似文献
994.
Rita Faria Marta O. Soares Eldon Spackman Hashim U. Ahmed Louise C. Brown Richard Kaplan Mark Emberton Mark J. Sculpher 《European urology》2018,73(1):23-30
Background
The current recommendation of using transrectal ultrasound-guided biopsy (TRUSB) to diagnose prostate cancer misses clinically significant (CS) cancers. More sensitive biopsies (eg, template prostate mapping biopsy [TPMB]) are too resource intensive for routine use, and there is little evidence on multiparametric magnetic resonance imaging (MPMRI).Objective
To identify the most effective and cost-effective way of using these tests to detect CS prostate cancer.Design, setting, and participants
Cost-effectiveness modelling of health outcomes and costs of men referred to secondary care with a suspicion of prostate cancer prior to any biopsy in the UK National Health Service using information from the diagnostic Prostate MR Imaging Study (PROMIS).Intervention
Combinations of MPMRI, TRUSB, and TPMB, using different definitions and diagnostic cut-offs for CS cancer.Outcome measurements and statistical analysis
Strategies that detect the most CS cancers given testing costs, and incremental cost-effectiveness ratios (ICERs) in quality-adjusted life years (QALYs) given long-term costs.Results and limitations
The use of MPMRI first and then up to two MRI-targeted TRUSBs detects more CS cancers per pound spent than a strategy using TRUSB first (sensitivity = 0.95 [95% confidence interval {CI} 0.92–0.98] vs 0.91 [95% CI 0.86–0.94]) and is cost effective (ICER = £7,076 [€8350/QALY gained]). The limitations stem from the evidence base in the accuracy of MRI-targeted biopsy and the long-term outcomes of men with CS prostate cancer.Conclusions
An MPMRI-first strategy is effective and cost effective for the diagnosis of CS prostate cancer. These findings are sensitive to the test costs, sensitivity of MRI-targeted TRUSB, and long-term outcomes of men with cancer, which warrant more empirical research. This analysis can inform the development of clinical guidelines.Patient summary
We found that, under certain assumptions, the use of multiparametric magnetic resonance imaging first and then up to two transrectal ultrasound-guided biopsy is better than the current clinical standard and is good value for money. 相似文献995.
Matching the evaluation of the clinical efficacy of clopidogrel to platelet function tests relevant to the biological properties of the drug 总被引:6,自引:0,他引:6
Labarthe B Théroux P Angioï M Ghitescu M 《Journal of the American College of Cardiology》2005,46(4):638-645
OBJECTIVES: This study aimed to explore platelet function tests relevant to the biological effects of clopidogrel that could help the clinical monitoring of drug efficacy. BACKGROUND: Clopidogrel selectively inhibits the P2Y12 receptor, the major role of which is stabilization of aggregation, whereas initiation of aggregation depends on activity of both P2Y1 and P2Y12 receptors. METHODS: Tests used were peak aggregation (Agg(max)) and late aggregation (Agg(6min)), and disaggregation, relating to P2Y1 and P2Y12 activity, respectively; and monoclonal antibody binding activated glycoprotein (GP) IIb/IIIa receptors (PAC-1) and P-selectin, measuring activation and secretion. A first study compared hirudin/PPACK (r-hirudin and D-phenylalanyl-prolyl-arginine chloromethyl ketone) with citrate as blood anticoagulant (16 patients), and a second control study compared the effects of clopidogrel, aspirin, or both (20 normal controls). RESULTS: Clopidogrel similarly inhibited adenosine 5'-diphosphate (ADP)-induced Agg(max) with either anticoagulant, but significantly more Agg(6min) (75% vs. 31%), P-selectin (72% vs. 53%), and PAC-1 (62% vs. 24%) in hirudin/PPACK. In the control study, it inhibited Agg(max) by 22%, and Agg(6min), P-selectin, and PAC-1, by 69%, 66%, and 55%, respectively (all p < 0.05). Disaggregation at six min reached 62% with clopidogrel, but was virtually absent with placebo and aspirin. Non-responsiveness as evaluated by inhibition of Agg(max) in citrate was diagnosed in 35% of patients; in half this rate by Agg(6min), P-selectin, and PAC-1; and in 6% to 12% with the latter tests performed in hirudin/PPACK. CONCLUSIONS: The evaluation of clopidogrel responsiveness by platelet function tests is largely influenced by the choice of blood preservative and functional tests. Measures of aggregation stabilization, and of consequent secretion and activation, identified most patients as responders, contrasting with measures of peak aggregation, by likely reflecting better the interactions clopidogrel and the P2Y12 receptor. 相似文献
996.
Marta Manovel López Miguel Maldonado López Isabel de la Torre Díez José Carlos Pastor Jimeno Miguel López-Coronado 《Journal of medical systems》2017,41(5):81
Decision support systems (DSS) are increasingly demanded due that diagnosis is one of the main activities that physicians accomplish every day. This fact seems critical when primary care physicians deal with uncommon problems belonging to specialized areas. The main objective of this paper is the development and user evaluation of a mobile DSS for iOS named OphthalDSS. This app has as purpose helping in anterior segment ocular diseases’ diagnosis, besides offering educative content about ophthalmic diseases to users. For the deployment of this work, firstly it has been used the Apple IDE, Xcode, to develop the OphthalDSS mobile application using Objective-C as programming language. The core of the decision support system implemented by OphthalDSS is a decision tree developed by expert ophthalmologists. In order to evaluate the Quality of Experience (QoE) of primary care physicians after having tried the OphthalDSS app, a written inquiry based on the Likert scale was used. A total of 50 physicians answered to it, after trying the app during 1 month in their medical consultation. OphthalDSS is capable of helping to make diagnoses of diseases related to the anterior segment of the eye. Other features of OphthalDSS are a guide of each disease and an educational section. A 70% of the physicians answered in the survey that OphthalDSS performs in the way that they expected, and a 95% assures their trust in the reliability of the clinical information. Moreover, a 75% of them think that the decision system has a proper performance. Most of the primary care physicians agree with that OphthalDSS does the function that they expected, it is a user-friendly and the contents and structure are adequate. We can conclude that OphthalDSS is a practical tool but physicians require extra content that makes it a really useful one. 相似文献
997.
Direct evidence for accumulation of 1,2,3,4-tetrahydroisoquinoline (TIQ), an endo- and exogenous substance suspected of producing Parkinsonism in humans, has not yet been shown. This study aimed to examine TIQ disposition in the whole rat brain and in the striatum and substantia nigra (SN). TIQ was administered to male Wistar and Dark Agouti rats (20, 40 and 100 mg/kg i.p.) alone or jointly with specific CYP2D inhibitor quinine (20, 40, 80 mg/kg i.p.), acutely or chronically. TIQ concentration in brain of both strains was several-fold higher than in plasma. The level of its metabolite, 4-OH-TIQ, was very low in the brain and plasma of TIQ-treated Wistar while in those receiving additionally quinine or in Dark Agouti rats, 4-OH-TIQ was absent or negligible. Inhibition of CYP2D catalyzing TIQ 4-hydroxylation in the liver had no influence on TIQ accumulation in the brain. Exogenous TIQ was actively transported from periphery into the brain by the organic cation transporter system, mainly OCT3, and quickly eliminated from it by P-glycoprotein. TIQ accumulation after chronic injection to Wistar rats was short-lasting and limited to SN. High concentration of TIQ in SN induces while in the liver inhibits the nigral and hepatic activity CYP2D, respectively. 相似文献
998.
Ewelina Kazimierczyk Andrzej Eljaszewicz Paula Zembko Ewa Tarasiuk Malgorzata Rusak Agnieszka Kulczynska-Przybik Marta Lukaszewicz-Zajac Karol Kaminski Barbara Mroczko Maciej Szmitkowski Milena Dabrowska Bozena Sobkowicz Marcin Moniuszko Agnieszka Tycinska 《Pharmacological reports : PR》2019,71(1):73-81
Background
Acute myocardial infarction (AMI) causes irreversible myocardial damage and release of inflammatory mediators, including cytokines, chemokines and miRNAs. We aimed to investigate changes in the levels of cytokines (IL-6, TNF-α and IL-10), miRNAs profiles (miR-146 and miR-155) and distribution of different monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) in the acute and post-healing phases of AMI.Methods
In eighteen consecutive AMI patients (mean age 56.78?±?12.4 years, mean left ventricle ejection fraction – LVEF: 41.9?±?9.8%), treated invasively, monocyte subsets frequencies were evaluated (flow cytometry), cytokine concentrations were analyzed (ELISA) as well as plasma miRNAs were isolated twice – on admission and after 19.2?±?5.9 weeks of follow-up. Measurements were also performed among healthy volunteers.Results
AMI patients presented significantly decreased frequencies of classical cells in comparison to healthy controls (median 71.22% [IQR: 64.4–79.04] vs. 84.35% [IQR: 81.2–86.7], p?=?0.001) and higher percent of both intermediate and non-classical cells, yet without statistical significance (median 6.54% [IQR: 5.14–16.64] vs. 5.87% [IQR: 4.48–8.6], p?=?0.37 and median 5.99% [IQR: 3.39–11.5] vs. 5.26% [IQR: 3.62–6.2], p?=?0.42, respectively). In AMI patients both, analyzed plasma miRNA concentrations were higher than in healthy subjects (miR-146: median 5.48 [IQR: 2.4–11.27] vs. 1.84 [IQR: 0.87–2.53], p?=?0.003; miR-155: median 25.35 [IQR: 8.17–43.15] vs. 8.4 [IQR: 0.08–16.9], p?=?0.027, respectively), and returned back to the values found in the control group in follow-up. miR-155/miR-146 ratio correlated with the frequencies of classical monocytes (r=0.6, p?=?0.01) and miR-155 correlated positively with the concentration of inflammatory cytokines ? IL-6 and TNF-α.Conclusions
These results may suggest cooperation of both pro-inflammatory and anti-inflammatory signals in AMI in order to promote appropriate healing of the infarcted myocardium. 相似文献999.
Aleksandra Kalu
niak-Szymanowska Roma Krzymiska-Siemaszko Ewa Deskur-
mielecka Marta Lewandowicz Beata Kaczmarek Katarzyna Wieczorowska-Tobis 《Nutrients》2022,14(1)
Purpose: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the world population. In addition to airflow obstruction, COPD is associated with multiple systemic manifestations, including impaired nutritional status or malnutrition and changes in body composition (low muscle mass, LMM). Poor nutritional status and sarcopenia in subjects with COPD leads to a worse prognosis and increases health-related costs. Data from previous studies indicate that 30–60% of subjects with COPD are malnourished, 20–40% have low muscle mass, and 15–21.6% have sarcopenia. This study aimed to assess the prevalence of malnutrition, sarcopenia, and malnutrition-sarcopenia syndrome in elderly subjects with COPD and investigate the relationship between COPD severity and these conditions.Patients and methods: A cross-sectional study involving 124 patients with stable COPD, aged ≥60, participating in a stationary pulmonary rehabilitation program. Nutritional status was assessed following the Global Leadership Initiative on Malnutrition (GLIM) criteria and sarcopenia with the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. The results of pulmonary function tests and exercise capacity were obtained from the hospital database. Results: 22.6% of participants had malnutrition according to the GLIM criteria. Subjects with malnutrition had lower gait speed (p = 0.0112) and worse results of the Six Minute Walk Test. Sixteen participants (12.9%) had sarcopenia; 12 subjects with sarcopenia had concomitant malnutrition. The prevalence of severe and very severe obstruction (GOLD3/GOLD4) was 91.7%. It was significantly higher in patients with malnutrition-sarcopenia syndrome. Conclusions: Malnutrition was found in nearly one out of four subjects with COPD, while sarcopenia was one out of seven patients. About 10% of our study sample had malnutrition-sarcopenia syndrome. The prevalence of severe and very severe obstruction was significantly higher in patients with malnutrition-sarcopenia syndrome. 相似文献
1000.
Clinical and histologic characteristics of breast cancers in women with previous pathologic diagnosis of benign breast disease in Spain 下载免费PDF全文
Marta Román PhD Martin Caicoya MD Josep Espinàs PhD Maria Sala PhD Isabel Torá‐Rocamora PhD Maria J. Quinta PhD Mar Vernet PhD Francina Saladié MD Anabel Romero PhD Mar Sánchez MD Marisa Baré PhD Carmen Vidal MPH S. Servitja MD Carmen Natal PhD Joosep Corominas MD Joana Ferrer MD Ana Rodríguez‐Arana MD Xavier Castells PhD the BELE Project study group 《The breast journal》2018,24(4):509-518
Women with a benign breast disease (BBD) have an increased risk of subsequent breast carcinoma. Information is scarce regarding the characteristics of breast carcinomas diagnosed after a BBD. Our aim was to point out the differences in clinical and histologic characteristics of breast carcinomas diagnosed in women with and without a previous pathologic diagnosis of BBD in the context of population‐based mammography screening. Retrospective cohort study of all women aged 50‐69 years who were screened at least once in a population‐based screening program in Spain, between 1994 and 2011 and followed up until December 2012. The mean follow‐up was 6.1 years. We analyzed 6645 breast carcinomas, of whom 238 had a previous pathologic diagnosis of BBD. Information on clinical and histologic characteristics was collected from pathology reports. Logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (95%CI) of occurrence of selected histologic characteristics of breast carcinomas in women with and without a previous BBD. Women with a previous BBD had a higher proportion of ductal carcinoma in situ (DCIS) compared with women without a BBD (22.1% and 13.6%, respectively). Among those diagnosed with an invasive breast carcinoma, women with previous BBD were more likely to be diagnosed with carcinomas sized >2 cm (OR = 1.46; 95%CI = 1.03‐2.08), metastatic positive (OR = 2.66; 95%CI = 1.21‐5.86), and with a high Ki‐67 proliferation rate (OR = 1.93; 95%CI = 1.24‐2.99). No differences were found across histologic subtypes of BBD. Screening participants with a previous pathologic diagnosis of BBD had a higher proportion of DCIS. However, invasive carcinomas detected in women with a BBD were associated with clinical and histologic characteristics conferring a worst prognosis. 相似文献