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1.
Valentina Spigoni Angela Picconi Monia Cito Valentina Ridolfi Sabrina Bonomini Chiara Casali Ivana Zavaroni Luigi Gnudi Marco Metra Alessandra Dei Cas 《PloS one》2012,7(11)
Background
Evidence suggests that the PPARγ-agonist insulin sensitizer pioglitazone, may provide potential beneficial cardiovascular (CV) effects beyond its anti-hyperglycaemic function. A reduced endothelial progenitor cell (EPC) number is associated with impaired glucose tolerance (IGT) or diabetes, conditions characterised by increased CV risk.Aim
To evaluate whether pioglitazone can provide benefit in vitro in EPCs obtained from IGT subjects.Materials and Methods
Early and late-outgrowth EPCs were obtained from peripheral blood mononuclear cells of 14 IGT subjects. The in vitro effect of pioglitazone (10 µM) with/without PPARγ-antagonist GW9662 (1 µM) was assessed on EPC viability, apoptosis, ability to form tubular-like structures and pro-inflammatory molecule expression.Results
Pioglitazone increased early and late-outgrowth EPC viability, with negligible effects on apoptosis. The capacity of EPCs to form tubular-like structures was improved by pioglitazone in early (mean increase 28%; p = 0.005) and late-outgrowth (mean increase 30%; p = 0.037) EPCs. Pioglitazone reduced ICAM-1 and VCAM-1 adhesion molecule expression in both early (p = 0.001 and p = 0.012 respectively) and late-outgrowth (p = 0.047 and p = 0.048, respectively) EPCs. Similarly, pioglitazone reduced TNFα gene and protein expression in both early (p = 0.034;p = 0.022) and late-outgrowth (p = 0.026;p = 0.017) EPCs compared to control. These effects were prevented by incubation with the PPARγ-antagonist GW9662.Conclusion
Pioglitazone exerts beneficial effects in vitro on EPCs isolated from IGT subjects, supporting the potential implication of pioglitazone as a CV protective agents. 相似文献2.
Background
Efficacy of tumor necrosis factor alpha (TNF-α) blockers for treatment of ulcerative colitis that is unresponsive to conventional therapy is unclear due to recent studies yielding conflicting results.Aim
To assess the efficacy and safety of anti-TNF-α agents for treatment of ulcerative colitis patients who were intolerant or refractory to conventional medical therapy.Methods
Pubmed, Embase, and the Cochrane database were searched. Analysis was performed on randomized controlled trials that assessed anti-TNF-α therapy on ulcerative colitis patients that had previously failed therapy with corticosteroids and/or immunosuppressants. The primary outcome focused on was the frequency of patients that achieved clinical remission. Further trial outcomes of interest included rates of remission without patient use of corticosteroids during the trial, extent of mucosal healing, and the number of cases that resulted in colectomy and serious side effects.Results
Eight trials from seven studies (n = 2122) met the inclusion criteria and were thus included during analysis. TNF-α blockers demonstrated clinical benefit as compared to placebo control as evidenced by an increased frequency of clinical remission (p<0.00001), steroid-free remission (p = 0.01), endoscopic remission (p<0.00001) and a decrease in frequency of colectomy (p = 0.03). No difference was found concerning serious side effects (p = 0.05). Three small trials (n = 57) comparing infliximab to corticosteroid treatment, showed no difference in frequency of clinical remission (p = 0.93), mucosal healing (p = 0.80), and requirement for a colectomy (p = 0.49). One trial compared infliximab to cyclosporine (n = 115), wherein no difference was found in terms of mucosal healing (p = 0.85), colectomy frequency (p = 0.60) and serious side effects (p = 0.23).Conclusion
TNF-α blockers are effective and safe therapies for the induction and maintenance of long-term remission and prevention of treatment by colectomy for patients with refractory ulcerative colitis where conventional treatment was previously ineffective. Furthermore, infliximab and cyclosporine were found to be comparable for treating acute severe steroid-refractory ulcerative colitis. 相似文献3.
Yan-Wei Yin Qian-Qian Sun Bei-Bei Zhang Ai-Min Hu Hong-Li Liu Qi Wang Zhi-Zhen Hou 《PloS one》2013,8(6)
Background
Epidemiological studies have evaluated the association between apolipoprotein E (ApoE) gene polymorphism and coronary artery disease (CAD) risk which developed inconsistent conclusions. To derive a more precise estimation of the relationship in Chinese population, we performed this meta-analysis.Methods
Databases, including PubMed, EMbase, Web of Science, CBMdisc and CNKI, were searched to get the genetic association studies. Additionally, hand searching of the references of identified articles were performed. All the statistical tests were performed using Review Manager 5.1.2 and Stata 11.0.Results
We identified a total of 40 studies, including 4,564 CAD cases and 3,985 controls. The results showed evidence for significant association between ApoE ε4 allele and CAD risk (for ε2/ε4 vs. ε3/ε3: OR = 1.86, 95% CI = 1.42–2.43, p<0.00001; for ε3/ε4 vs. ε3/ε3: OR = 2.34, 95% CI = 2.07–2.65, p<0.00001; for ε4/ε4 vs. ε3/ε3: OR = 2.89, 95% CI = 1.87–4.47, p<0.00001; for ε4 allele vs. ε3 allele: OR = 2.11, 95% CI = 1.91–2.35, p<0.00001).Conclusions
The present meta-analysis suggests an association between ApoE ε4 allele and increased risk of CAD in Chinese population. However, due to the small sample size in most of the included studies and the selection bias existed in some studies, the results should be interpreted with caution. 相似文献4.
Background
Evaluating the influence of climate variability on enteric disease incidence may improve our ability to predict how climate change may affect these diseases.Objectives
To examine the associations between regional climate variability and enteric disease incidence in New Zealand.Methods
Associations between monthly climate and enteric diseases (campylobacteriosis, salmonellosis, cryptosporidiosis, giardiasis) were investigated using Seasonal Auto Regressive Integrated Moving Average (SARIMA) models.Results
No climatic factors were significantly associated with campylobacteriosis and giardiasis, with similar predictive power for univariate and multivariate models. Cryptosporidiosis was positively associated with average temperature of the previous month (β = 0.130, SE = 0.060, p <0.01) and inversely related to the Southern Oscillation Index (SOI) two months previously (β = −0.008, SE = 0.004, p <0.05). By contrast, salmonellosis was positively associated with temperature (β = 0.110, SE = 0.020, p<0.001) of the current month and SOI of the current (β = 0.005, SE = 0.002, p<0.050) and previous month (β = 0.005, SE = 0.002, p<0.05). Forecasting accuracy of the multivariate models for cryptosporidiosis and salmonellosis were significantly higher.Conclusions
Although spatial heterogeneity in the observed patterns could not be assessed, these results suggest that temporally lagged relationships between climate variables and national communicable disease incidence data can contribute to disease prediction models and early warning systems. 相似文献5.
Edwin Leeansyah Jingling Zhou Geza Paukovics Sharon R. Lewin Suzanne M. Crowe Anthony Jaworowski 《PloS one》2010,5(3)
Background
FcRγ is an immunoreceptor tyrosine-based activation motif (ITAM)-signalling protein essential for immunoreceptor signaling and monocyte, macrophage and NK cell function. Previous study from our laboratory showed that FcRγ is down-regulated in HIV-infected macrophages in vitro. FcRγ expression in immune cells present in HIV-infected individuals is unknown.Methodology/Principal Findings
We compared FcRγ expression in peripheral blood mononuclear cells isolated from HIV-1-infected individuals receiving combination antiretroviral therapy and healthy, HIV-1-uninfected individuals. FcRγ mRNA and protein levels were measured using quantitative real-time PCR and immunoblotting, respectively. CD56+ CD94+ lymphocytes isolated from blood of HIV-1 infected individuals had reduced FcRγ protein expression compared to HIV-uninfected individuals (decrease = 76.8%, n = 18 and n = 12 respectively, p = 0.0036). In a second group of patients, highly purified NK cells had reduced FcRγ protein expression compared to uninfected controls (decrease = 50.2%, n = 9 and n = 8 respectively, p = 0.021). Decreased FcRγ expression in CD56+CD94+ lymphocytes was associated with reduced mRNA (51.7%, p = 0.021) but this was not observed for the smaller group of patients analysed for NK cell expression (p = 0.36).Conclusion/Significance
These data suggest biochemical defects in ITAM-dependent signalling within NK cells in HIV-infected individuals which is present in the context of treatment with combination antiretroviral therapy. 相似文献6.
Hugo Cogo-Moreira Clara Regina Brand?o de ávila George B. Ploubidis Jair de Jesus Mari 《PloS one》2013,8(3)
Introduction
Difficulties in word-level reading skills are prevalent in Brazilian schools and may deter children from gaining the knowledge obtained through reading and academic achievement. Music education has emerged as a potential method to improve reading skills because due to a common neurobiological substratum.Objective
To evaluate the effectiveness of music education for the improvement of reading skills and academic achievement among children (eight to 10 years of age) with reading difficulties.Method
235 children with reading difficulties in 10 schools participated in a five-month, randomized clinical trial in cluster (RCT) in an impoverished zone within the city of São Paulo to test the effects of music education intervention while assessing reading skills and academic achievement during the school year. Five schools were chosen randomly to incorporate music classes (n = 114), and five served as controls (n = 121). Two different methods of analysis were used to evaluate the effectiveness of the intervention: The standard method was intention-to-treat (ITT), and the other was the Complier Average Causal Effect (CACE) estimation method, which took compliance status into account.Results
The ITT analyses were not very promising; only one marginal effect existed for the rate of correct real words read per minute. Indeed, considering ITT, improvements were observed in the secondary outcomes (slope of Portuguese = 0.21 [p<0.001] and slope of math = 0.25 [p<0.001]). As for CACE estimation (i.e., complier children versus non-complier children), more promising effects were observed in terms of the rate of correct words read per minute [β = 13.98, p<0.001] and phonological awareness [β = 19.72, p<0.001] as well as secondary outcomes (academic achievement in Portuguese [β = 0.77, p<0.0001] and math [β = 0.49, p<0.001] throughout the school year).Conclusion
The results may be seen as promising, but they are not, in themselves, enough to make music lessons as public policy. 相似文献7.
Erika J. Lampert Kingshuk Roy Choudhury Christopher A. Hostage Jeffrey R. Petrella P. Murali Doraiswamy the Alzheimer’s Disease Neuroimaging Initiative 《PloS one》2013,8(4)
Objective
A positive family history (FH) is a risk factor for late-onset Alzheimer’s disease (AD). Our aim was to examine the effects of FH on pathological and neuronal loss biomarkers across the cognitive spectrum.Design
Cross-sectional analyses of data from a national biomarker study.Setting
The Alzheimer’s Disease Neuroimaging Initiative national study.Patients
257 subjects (ages 55–89), divided into cognitively normal (CN), mild cognitive impairment (MCI), and AD groups, with CSF and FH data.Outcome Measures
Cerebrospinal fluid (CSF) Aβ42, tau, and tau/Aβ42 ratio, MRI-measured hippocampal volumes.Statistics
Univariate and multivariate analyses.Results
In MCI, CSF Aβ42 was lower (p = .005), t-tau was higher (p = 0.02) and t-tau/Aβ42 ratio was higher (p = 0.002) in FH+ than FH− subjects. A significant residual effect of FH on pathologic markers in MCI remained after adjusting for ApoE4 (p<0.05). Among CN, 47% of FH+ exhibited “pathologic signature of AD” (CSF t-tau/Aβ42 ratio >0.39) versus 21% of FH− controls (p = 0.03). The FH effect was not significant in AD subjects. Hippocampal and intracranial volumes did not differ between FH+ and FH− subjects in any group.Conclusions
A positive family history of late-onset AD is associated with a higher prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in MCI. The unexplained genetic heritability in family history is about the half the size of the ApoE4 effect. Longitudinal studies are warranted to more definitively examine this issue. 相似文献8.
Pavel Strnad Guido von Figura Regina Gruss Katja-Marlen Jareis Adolf Stiehl Hasan Kulaksiz 《PloS one》2013,8(1)
Background and Study Aims
Bile stones represent a highly prevalent condition and abnormalities of the biliary tree predispose to stone recurrence due to development of biliary stasis. In our study, we assessed the importance of an altered bile duct course for stone formation.Patients and Methods
1,307 patients with choledocholithiasis in the absence of any associated hepatobiliary disease who underwent endoscopic retrograde cholangiopancreatography (ERCP) between 2002 and 2009 were analysed. The angle enclosed between the horizontal portion of the common bile duct (CBD) and the horizontal plane was measured (angle α). Oblique common bile duct (OCBD) was defined as a CBD with angle α<45°.Results
103 patients (7.9%) were found to harbour OCBD and these were compared to 104 randomly selected control subjects. Compared to controls, OCBD patients were (i) significantly older (72±13 vs. 67±13, p<0.00001); (ii) more frequently underwent a cholecystectomy (p = 0.02) and biliary surgery (p = 0.003) prior to the diagnosis and (iii) more often developed chronic pancreatitis (p = 0.04) as well as biliary fistulae (p = 0.03). Prior to and after ERCP, OCBD subjects displayed significantly elevated cholestatic parameters and angle α negatively correlated with common bile duct diameter (r = -0.29, p = 0.003). OCBD subjects more often required multiple back-to-back ERCP sessions to remove bile stones (p = 0.005) as well as more ERCPs later on due to recurrent stone formation (p<0.05).Conclusion
OCBD defines a novel variant of the biliary tree, which is associated with chronic cholestasis, hampers an efficient stone removal and predisposes to recurrence of bile duct stones. 相似文献9.
Ruan Kruger Rudolph Schutte Hugo W. Huisman Peter Hindersson Michael H. Olsen Jesper Eugen-Olsen Aletta E. Schutte 《PloS one》2013,8(3)
Objective and design
This cross-sectional study aimed to investigate associations between a marker of cardiac strain, the N-terminal prohormone B-type natriuretic peptide (NT-proBNP), and inflammation as reflected by either a conventional or novel inflammatory marker in a bi-ethnic South African cohort.Methods and subjects
We measured NT-proBNP, C-reactive protein (CRP) and plasma-soluble urokinase plasminogen activator receptor (suPAR) levels along with conventional biomarkers in black (n = 117) and white (n = 116) men.Results
NT-proBNP, CRP and suPAR levels were higher in black compared to white men. NT-proBNP was significantly associated with both CRP (r = 0.38; p = 0.001) and suPAR (r = 0.42; p<0.001) in black men only. After full adjustment in multiple regression analyses, the above associations of NT-proBNP with CRP (β = 0.199; p = 0.018) and suPAR (β = 0.257; p<0.01) were confirmed in black men.Conclusion
These results suggest that a low-grade inflammatory state as reflected by both a conventional and novel marker of inflammation may contribute to higher cardiovascular risk as reflected by the associations obtained with a marker of cardiac strain in black South African men. 相似文献10.
Basima Almomani Ahmed F. Hawwa Jeffrey S. Millership Liam Heaney Isabella Douglas James C. McElnay Michael D. Shields 《PloS one》2013,8(4)
Objective
We tested the hypothesis that patients with difficult asthma have an increased frequency of certain genotypes that predispose them to asthma exacerbations and poor asthma control.Methods
A total of 180 Caucasian children with confirmed asthma diagnosis were selected from two phenotypic groups; difficult (n = 112) versus mild/moderate asthma (n = 68) groups. All patients were screened for 19 polymorphisms in 9 candidate genes to evaluate their association with difficult asthma.Key Results
The results indicated that LTA4H A-9188>G, TNFα G-308>A and IL-4Rα A1727>G polymorphisms were significantly associated with the development of difficult asthma in paediatric patients (p<0.001, p = 0.019 and p = 0.037, respectively). Haplotype analysis also revealed two haplotypes (ATA haplotype of IL-4Rα A1199>C, IL-4Rα T1570>C and IL-4Rα A1727>G and CA haplotype of TNFα C-863>A and TNFα G-308>A polymorphisms) which were significantly associated with difficult asthma in children (p = 0.04 and p = 0.018, respectively).Conclusions and Clinical Relevance
The study revealed multiple SNPs and haplotypes in LTA4H, TNFα and IL4-Rα genes which constitute risk factors for the development of difficult asthma in children. Of particular interest is the LTA4H A-9188>G polymorphism which has been reported, for the first time, to have strong association with severe asthma in children. Our results suggest that screening for patients with this genetic marker could help characterise the heterogeneity of responses to leukotriene-modifying medications and, hence, facilitate targeting these therapies to the subset of patients who are most likely to gain benefit. 相似文献11.
Krithiga Shridhar Preet Kaur Dhillon Liza Bowen Sanjay Kinra Ankalmadugu Venkatsubbareddy Bharathi Dorairaj Prabhakaran Kolli Srinath Reddy Shah Ebrahim for the Indian Migration Study group 《PloS one》2014,9(10)
Background
Studies in the West have shown lower cardiovascular disease (CVD) risk among people taking a vegetarian diet, but these findings may be confounded and only a minority selects these diets. We evaluated the association between vegetarian diets (chosen by 35%) and CVD risk factors across four regions of India.Methods
Study participants included urban migrants, their rural siblings and urban residents, of the Indian Migration Study from Lucknow, Nagpur, Hyderabad and Bangalore (n = 6555, mean age-40.9 yrs). Information on diet (validated interviewer-administered semi-quantitative food frequency questionnaire), tobacco, alcohol, physical history, medical history, as well as blood pressure, fasting blood and anthropometric measurements were collected. Vegetarians ate no eggs, fish, poultry or meat. Using robust standard error multivariate linear regression models, we investigated the association of vegetarian diets with blood cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides, fasting blood glucose (FBG), systolic (SBP) and diastolic blood pressure (DBP).Results
Vegetarians (32.8% of the study population) did not differ from non-vegetarians with respect to age, use of smokeless tobacco, body mass index, and prevalence of diabetes or hypertension. Vegetarians had a higher standard of living and were less likely to smoke, drink alcohol (p<0.0001) and were less physically active (p = 0.04). In multivariate analysis, vegetarians had lower levels of total cholesterol (β = −0.1 mmol/L (95% CI: −0.03 to −0.2), p = 0.006), triglycerides (β = −0.05 mmol/L (95% CI: −0.007 to −0.01), p = 0.02), LDL (β = −0.06 mmol/L (95% CI: −0.005 to −0.1), p = 0.03) and lower DBP (β = −0.7 mmHg (95% CI: −1.2 to −0.07), p = 0.02). Vegetarians also had decreases in SBP (β = −0.9 mmHg (95% CI: −1.9 to 0.08), p = 0.07) and FBG level (β = −0.07 mmol/L (95% CI: −0.2 to 0.01), p = 0.09) when compared to non-vegetarians.Conclusion
We found beneficial association of vegetarian diet with cardiovascular risk factors compared to non-vegetarian diet. 相似文献12.
Elena Chiappini Chiara Della Bella Francesca Bonsignori Sara Sollai Amedeo Amedei Luisa Galli Elena Niccolai Gianfranco Del Prete Mahavir Singh Mario M. D'Elios Maurizio de Martino 《PloS one》2012,7(9)
Background
Although currently available IGRA have been reported to be promising markers for TB infection, they cannot distinguish active tuberculosis (TB) from latent infection (LTBI).Objective
Children with LTBI, active TB disease or uninfected were prospectively evaluated by an in-house ELISPOT assay in order to investigate possible immunological markers for a differential diagnosis between LTBI and active TB.Methods
Children at risk for TB infection prospectively enrolled in our infectious disease unit were evaluated by in-house IFN-γ and IL-2 based ELISPOT assays using a panel of Mycobacterium tuberculosis antigens.Results
Twenty-nine children were classified as uninfected, 21 as LTBI and 25 as active TB cases (including 5 definite and 20 probable cases). Significantly higher IFN-γ ELISPOT responses were observed in infected vs. uninfected children for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p = 0.003), and AlaDH (p = 0.001), while differences were not significant considering Ag85B (p = 0.063), PstS1 (p = 0.512), and HspX (16 kDa) (p = 0.139). IL-2 ELISPOT assay responses were different for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p<0.0001), HspX (16 kDa) (p<0.0001), PstS1 (p<0.0001) and AlaDH (p = 0.001); but not for Ag85B (p = 0.063). Comparing results between children with LTBI and those with TB disease differences were significant for IFN-γ ELISPOT only for AlaDH antigen (p = 0.021) and for IL-2 ELISPOT assay for AlaDH (p<0.0001) and TB 10.3 antigen (p = 0.043). ROC analyses demonstrated sensitivity of 100% and specificity of 81% of AlaDH-IL-2 ELISPOT assay in discriminating between latent and active TB using a cut off of 12.5 SCF per million PBMCs.Conclusion
Our data suggest that IL-2 based ELISPOT with AlaDH antigen may be of help in discriminating children with active from those with latent TB. 相似文献13.
Daniel Dylan Cohen Diego Gómez-Arbeláez Paul Anthony Camacho Sandra Pinzon Claudia Hormiga Juanita Trejos-Suarez John Duperly Patricio Lopez-Jaramillo 《PloS one》2014,9(4)
Purpose
In youth, poor cardiorespiratory and muscular strength are associated with elevated metabolic risk factors. However, studies examining associations between strength and risk factors have been done exclusively in high income countries, and largely in Caucasian cohorts. The aim of this study was to assess these interactions in schoolchildren in Colombia, a middle income Latin American country.Methods
We measured body mass index, body composition, handgrip strength (HG), cardiorespiratory fitness (CRF) and metabolic risk factors in 669 low-middle socioeconomic status Colombian schoolchildren (mean age 11.52±1.13, 47% female). Associations between HG, CRF and metabolic risk factors were evaluated.Results
HG and CRF were inversely associated with blood pressure, HOMA index and a composite metabolic risk score (p<0.001 for all) and HG was also inversely associated with triglycerides and C-reactive protein (CRP) (both p<0.05). Associations between HG and risk factors were marginally weakened after adjusting for CRF, while associations between CRF and these factors were substantially weakened after adjusting for HG. Linear regression analyses showed inverse associations between HG and systolic BP (β = −0.101; p = 0.047), diastolic BP (β = −0.241; p> = 0.001), HOMA (β = −0.164; p = 0.005), triglycerides (β = −0.583; p = 0.026) and CRP (β = −0.183; p = 0.037) but not glucose (p = 0.698) or HDL cholesterol (p = 0.132). The odds ratios for having clustered risk in the weakest quartile compared with the strongest quartile were 3.0 (95% confidence interval: 1.81–4.95).Conclusions
In Colombian schoolchildren both poorer handgrip strength/kg body mass and cardiorespiratory fitness were associated with a worse metabolic risk profile. Associations were stronger and more consistent between handgrip and risk factors than between cardiorespiratory fitness and these risk factors. Our findings indicate the addition of handgrip dynamometry to non-invasive youth health surveillance programs would improve the accuracy of the assessment of cardio-metabolic health. 相似文献14.
Juan P. de-Torres David Blanco Ana B. Alcaide Luis M. Seijo Gorka Bastarrika María José Pajares Arrate Mu?oz-Barrutia Carlos Ortiz-de-Solorzano Ruben Pio Arantza Campo Usua Montes Victor Segura Jesús Pueyo Luis M. Montuenga Javier J. Zulueta 《PloS one》2013,8(4)
Rationale
Low-grade inflammation and emphysema have been shown to be associated with an increased risk of lung cancer. However, the systemic inflammatory response in patients with emphysema is still unknown.Objective
To compare the plasma cytokine profiles in two groups of current or former smokers without airway obstruction: a control group of individuals without computed tomography (CT) detected emphysema vs. a study group of individuals with CT detected emphysema.Methods
Subjects underwent a chest CT, spirometry, and determination of EGF, IL-15, IL-1ra, IL-8, MCP-1, MIP-1β, TGFα, TNFα, and VEGF levels in plasma. Cytokine levels in each group were compared adjusting for confounding factors.Results
160 current smokers and former smokers without airway obstruction participated in the study: 80 without emphysema and 80 subjects with emphysema. Adjusted group comparisons revealed significant reductions in EGF (−0.317, p = 0.01), IL-15 (−0.21, p = 0.01), IL-8 (−0.180, p = 0.02) and IL-1ra (−0.220, p = 0.03) in subjects with emphysema and normal spirometry.Conclusions
Current or former smokers expressing a well-defined disease characteristic such as emphysema, has a specific plasma cytokine profile. This includes a decrease of cytokines mainly implicated in activation of apoptosis or decrease of immunosurveillance. This information should be taken into account when evaluated patients with tobacco respiratory diseases. 相似文献15.
Melania Manco Maria Rita Spreghini Rosa Luciano Cecilia Pensini Rita Wietrzycowska Sforza Carmela Rustico Marco Cappa Giuseppe Stefano Morino 《PloS one》2013,8(7)
Background
Insulin sensitivity decreases at puberty transition, but little information has been provided on its earlier time-course. Aim of the present study was to describe the time-course of insulin sensitivity in severely obese children at the transition from preschool to school age.Research design and methods
Retrospective study of a cohort of 47 severely obese [Body Mass Index (BMI) ≥99° percentile] preschoolers evaluated twice, once between 2 and 6 years of age, and once before age 8. Glucose tolerance, Whole Body Insulin Sensitivity Index (WBISI), Insulinogenic Index (IGI); β-cell demand index (BCDI) and Insulin Secretion-Sensitivity Index 2 (ISSI-2) were longitudinally estimated during the oral glucose tolerance test.Results
After a median follow-up of 2.23 (1–4.52) y, obese patients showed significant decrease in WBISI (p<0.0001), and increase in fasting (p = 0.005) and 2 h glucose (2HG, p = 0.001). One child in preschool age and 4 school age children presented with 2HG between 7.8–11.1 mmol/l. Best predictors of WBISI, 2HG and BCDI in the school age were changes in BMI z-score (R2 = 0.309; p = 0.002; β = −0.556), ISSI-2 (R2 = 0.465; p<0.0001; β = −0.682), and BMI z-score (R2 = 0.246; p = 0.008; 0.496), respectively.Conclusions
In morbidly obese children, insulin sensitivity seems to decline even before pubertal transition, but changes in total adiposity can only partially explain this variation. 相似文献16.
17.
Angela Marie Abbatecola Fabrizia Lattanzio Liana Spazzafumo Anna Maria Molinari Michele Cioffi Raffaele Canonico Luigi DiCioccio Giuseppe Paolisso 《PloS one》2010,5(4)
Background
The mechanisms related to cognitive impairment in older persons with Type 2 diabetes (DM) remains unclear. We tested if adiposity parameters and body fat distribution could predict cognitive decline in older persons with DM vs. normal glucose tolerance (NGT).Methodology
693 older persons with no dementia were enrolled: 253 with DM in good metabolic control; 440 with NGT (age range:65–85 years). Longitudinal study comparing DM and NGT individuals according to the association of baseline adiposity parameters (body mass index (BMI), waist-hip-ratio (WHR), waist circumference (WC) and total body fat mass) to cognitive change (Mini Mental State Examination (MMSE), a composite score of executive and attention functioning (CCS) over time.Findings
At baseline, in DM participants, MMSE correlated with WHR (β = −0.240; p = 0.043), WC (β = −0.264; p = 0.041) while CCS correlated with WHR (β = −0.238; p = 0.041), WC (β = −0.326; p = 0.013) after adjusting for confounders. In NGT subjects, no significant correlations were found among any adiposity parameters and MMSE, while CCS was associated with WHR (β = −0.194; p = 0.036) and WC (β = −0.210; p = 0.024). Participants with DM in the 3rd tertile of total fat mass showed the greatest decline in cognitive performance compared to those in 1st tertile (tests for trend: MMSE(p = 0.007), CCS(p = 0.003)). Logistic regression models showed that 3rd vs. 1st tertile of total fat mass, WHR, and WC predicted an almost two-fold decline in cognitive function in DM subjects at 2nd yr (OR 1.68, 95%IC 1.08–3.52).Conclusions
Total fat mass and central adiposity predict an increased risk for cognitive decline in older person with DM. 相似文献18.
Jonel Trebicka Aleksander Krag Stefan Gansweid Peter Schiedermaier Holger M. Strunk Rolf Fimmers Christian P. Strassburg Fleming Bendtsen S?ren M?ller Tilman Sauerbruch Ulrich Spengler 《PloS one》2013,8(12)
Background
TNFα levels are increased in liver cirrhosis even in the absence of infection, most likely owing to a continuous endotoxin influx into the portal blood. Soluble TNFα receptors (sTNFR type I and II) reflect release of the short-lived TNFα, because they are cleaved from the cells after binding of TNFα. The aims were to investigate the circulating levels of soluble TNFR-I and -II in cirrhotic patients receiving TIPS.Methods
Forty-nine patients with liver cirrhosis and portal hypertension (12 viral, 37 alcoholic) received TIPS for prevention of re-bleeding (n = 14), therapy-refractory ascites (n = 20), or both (n = 15). Portal and hepatic venous blood was drawn in these patients during the TIPS procedure and during the control catheterization two weeks later. sTNFR-I and sTNFR-II were measured by ELISA, correlated to clinical and biochemical characteristics.Results
Before TIPS insertion, sTNFR-II levels were lower in portal venous blood than in the hepatic venous blood, as well as in portal venous blood after TIPS insertion. No significant differences were measured in sTNFR-I levels. Hepatic venous levels of sTNFR-I above 4.5 ng/mL (p = 0.036) and sTNFR-II above 7 ng/mL (p = 0.05) after TIPS insertion were associated with decreased survival. A multivariate Cox-regression survival analysis identified the hepatic venous levels of sTNFR-I (p = 0.004) two weeks after TIPS, and Child score (p = 0.002) as independent predictors of mortality, while MELD-score was not.Conclusion
Hepatic venous levels of sTNFR-I after TIPS insertion may predict mortality in patients with severe portal hypertension. 相似文献19.
Salvatore Petta Fabio Salvatore Macaluso Maria Rosa Barcellona Calogero Cammà Daniela Cabibi Vito Di Marco Antonio Craxì 《PloS one》2012,7(12)
Background and Aims
Serum levels of γ-glutamyl-transpeptidase(γ-GT) were associated with liver disease severity and metabolic alterations, which in turn are able to affect hepatic damage. In patients with nonalcoholic fatty liver disease (NAFLD), genotype 1 chronic hepatitis C (G1CHC) and chronic hepatitis B (CHB), we assessed the link between liver fibrosis and γ-GT serum levels, and we evaluated if normal or high γ-GT serum levels affect the association between insulin resistance (IR) and severity of liver fibrosis.Methods
843 consecutive patients with chronic liver disease (CLD)(193 NAFLD, 481 G1CHC, 169 CHB) were evaluated by liver biopsy (Kleiner and Scheuer scores) and clinical and metabolic measurements. IR was diagnosed if HOMA>3. A serum γ-GT concentration of >36 IU/L in females and >61 IU/L in males was considered the threshold value for identifying high levels of γ-GT.Results
By multivariate logistic regression analysis, abnormal γ-GT serum levels were independently linked to severe liver fibrosis in patients with NAFLD (OR2.711,CI1.120–6.564,p = 0.02), G1CHC (OR3.461,CI2.138–5.603,p<0.001) and CHB (OR2.778,CI1.042–7.414,p = 0.04), together with IR and liver necroinflammation, and with a negative predictive value>80%. Interestingly, among patients with high or normal γ-GT values, even if IR prevalence was significantly higher in patients with severe fibrosis compared to those without, IR remained significantly associated with severe fibrosis in patients with abnormal γ-GT values only (OR4.150,CI1.079–15.970,p = 0.03 for NAFLD; OR2.250,CI1.211–4.181,p = 0.01 for G1CHC; OR3.096,CI2.050–34.220,p = 0.01 for CHB).Conclusions
In patients with CLD, IR is independently linked to liver fibrosis only in patients with abnormal γ-GT values, without differences according to liver disease etiology, and suggesting a role of γ-GT as a marker of metabolic-induced liver damage. These data could be useful for the clinical and pharmacologic management of patients with CLD. 相似文献20.
Yoke-Leng Ng Borut Klopcic Frances Lloyd Cynthia Forrest Wayne Greene Ian C. Lawrance 《PloS one》2013,8(10)