bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of ACE polymorphisms on the association between noise and hypertension in a Pakistani population
Authors: Nawaz Syed Kashif , Hasnain Shahida 
Published: March 2011

Introduction: This study investigates the effect of angiotensin converting enzyme (ACE) polymorphisms on the association between noise and hypertension. Subjects and methods: A cross sectional study was conducted involving 385 male volunteers. In the control group 156 participants were exposed to a sound level of ≤80 dB; in the exposed group 229 individuals were exposed to a sound level ≥80 dB. Both groups were subdivided into categories on the basis of blood pressure. A polymerase chain reaction (PCR)-based strategy was used to differentiate the various genotypes of ACE ID and ACE G2350A. Association of noise with genotypes as modifiers was estimated after adjustment of data for age and body mass index. Results: These showed the following odds ratios (OR) with 95% confidence interval (CI) indicating that noise is associated with hypertension in a Pakistani population (OR: 3.196; CI: 1.803–5.666). ACE ID and ACE G2350A polymorphism affects this association. ID (OR: 2.844: CI: 1.32–6.110) and DD allele carriers (OR: 4.487; CI: 1.549–12.99) were at increased risk of hypertension. GG (OR: 3.970; CI: 1.628–9.681) and GA (OR: 3.705; CI: 1.407–9.758) carriers were also at increased risk of hypertension associated with noise. However II and AA allele carriers were not found to be at increased risk of hypertension. Conclusion: ACE ID polymorphism and ACE G2350A polymorphism modulates the effects of noise on blood pressure.
Maternal/newborn genotype contribution of the renin–angiotensin system (Met235Thr, Thr174Met, I/D-ACE, A2350G-ACE, A1166C-AT2R1, C3123A- AT2R2, 83A/G-REN) to the risk of pre-eclampsia: a Romanian study
Authors: Procopciuc Lucia Maria , Caracostea Gabriela , Zaharie Gabriela , Puscas Mariana , Iordache Georgiana , Popa Monica , Colcear Doina , Olteanu Ileana , Stamatian Florin 
Published: March 2011

Introduction: We evaluated the association of the mutated genotypes Met235Thr-AGT, Thr174Met-AGT, I/D-ACE, A2350G-ACE, A1166C-AT2R1, C3123A-AT2R2, 83A/G-REN with the risk and outcome of pre-eclampsia; we also investigated whether genes in newborns increase maternal risk of pre-eclampsia. Materials and methods: Thirty-six pairs of pre-eclamptic women and their newborns were genotyped, along with 71 pairs of controls (mothers/newborns) using PCR-RFLP analysis. Results: The Thr235/Thr235 (OR 3.44, p = 0.01), DD (OR 2.66, p = 0.039), CC1166 (OR 5.56, p = 0.04), AA3123 (OR 3.77, p = 0.03) and GG83 (OR 8.32, p = 0.006) genotypes are significantly associated with pre-eclampsia. Women with pre-eclampsia positive for Met235Thr (34.64 ± 3.92 weeks vs. 38 ± 2 weeks), Thr174Met (32.58 ± 3.92 weeks vs. 36.38 ± 3.25 weeks), I/D (34.47 ± 3.67 weeks vs. 38.33 ± 3.5 weeks) delivered at a significant lower gestational age compared with pre-eclamptic women with a normal genotype. Newborns from women with pre-eclampsia positive for Thr174Met (2190 ± 820.21 g vs. 2702.08 ± 967.23 g), I/D (2399.33 ± 938.38 g vs. 3191.66 ± 684.40 g) had a significant lower birth weight compared with newborns from women with normal pregnancies. When both the mother and the newborn were positive for Met235Thr, I/D, A2350G, A1166C or 83A/G polymorphisms, the risk for pre-eclampsia was significantly increased at 6.67 ( p < 0.01), 5 ( p < 0.01), 3.33 ( p = 0.006), 2.72 ( p = 0.04) and 7.8 ( p < 0.01), respectively. Conclusions: The results of our study confirm that, in pre-eclampsia, both maternal and newborn genetic variations implicated in blood pressure regulation are important.
Effect of spironolactone and vitamin E on serum metabolic parameters and insulin resistance in patients with nonalcoholic fatty liver disease
Authors: Polyzos Stergios A , Kountouras Jannis , Zafeiriadou Efthimia , Patsiaoura Kalliopi , Katsiki Evangelia , Deretzi Georgia , Zavos Christos , Tsarouchas Georgios , Rakitzi Pantelitsa , Slavakis Aristidis 
Published: March 2011

Aim: The renin–angiotensin–aldosterone system has been implicated in the pathogenesis of insulin resistance and nonalcoholic fatty liver disease (NAFLD). The beneficial effect of spironolactone in a mouse model with diabetes and NAFLD has recently been reported. The main aim was assessment of the effect of spironolactone on serum metabolic parameters and insulin resistance in patients with NAFLD. Methods: This study includes preliminary results of a single-centre randomised controlled trial of treatment with vitamin E (group 1, 10 patients) versus spironolactone plus vitamin E (group 2, 10 patients) in biopsy-proven NAFLD. Serum transaminases, lipids, potassium, sodium, glucose and insulin were measured, and homeostatic model assessment-insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were calculated before and 8 weeks after baseline assessment. Results: Insulin was decreased within group 2 (15.3 ± 2.7 at baseline vs. 10.3 ± 5.0 at week 8, p = 0.013). Although no difference in glucose was observed, HOMA-IR significantly decreased (4.4 ± 0.9 vs. 2.8 ± 0.5, respectively, p = 0.047). QUICKI was increased, but not statistically significantly. Conclusions: Spironolactone and vitamin E combined therapy seems to exhibit a favourable effect on serum insulin and HOMA-IR in patients with NAFLD. If validated in a large-scale clinical trial, it may prove an inexpensive therapeutic approach for the management of NAFLD patients.
Antifungal medication is efficient in the treatment of sarcoidosis
Authors: Terčelj Marjeta , Salobir Barbara , Zupancic Mirjana , Rylander Ragnar 
Published: March 2011

Objectives: Fungi have been suspected of contributing to the pathogenesis of sarcoidosis. A previous intervention study demonstrated an improvement in the clinical condition in 15 out of 18 patients with a long-term history of sarcoidosis when antifungal medication was added to corticosteroids. The present study was performed to compare the effects of antifungal treatment with corticosteroid treatment in sarcoidosis. Methods: Patients with newly diagnosed sarcoidosis were recruited. Corticosteroids were given to 39 subjects, corticosteroid + antifungal to 31, and antifungal only to 22 subjects. The effects of the treatments were evaluated at 6 months. X-ray scores were measured before and after treatment together with pulmonary diffusion capacity and two markers of sarcoidosis activity, that is, angiotensin-converting enzyme in serum (sACE) and chitotriosidase (CTO). Results: X-ray scores as well as sACE and CTO decreased significantly in all groups. The X-ray score decreased slightly more among subjects in the groups that received antifungal medication compared with corticosteroids only ( p < 0.001). Conclusion: The results suggest that antifungal treatment is as efficient as corticosteroid treatment against the granulomatous and inflammatory manifestations of sarcoidosis. This is probably because this treatment is directed towards the causative agent. Additional studies are required to define the phenotype, where the antifungal treatment was not efficient (4/22) and to perform long‐term follow up to determine the risk of recurrence.
In LNCaP cells enhanced expression of the androgen receptor compensates for Bcl-2 suppression by antisense oligonucleotides
Authors: Rubenstein Marvin , Hollowell Courtney M.P. , Guinan Patrick 
Published: March 2011

Background and methods: Antisense oligonucleotides (oligos) have been employed against in vivo and in vitro prostate cancer models targeting growth stimulatory gene products. While most oligos have targeted growth factors or their receptors, others have been directed against inhibitors of apoptosis. In LNCaP cells we evaluated a set of oligos which targeted and comparably suppressed the expression of the apoptosis inhibitor protein Bcl-2. LNCaP cells adapted to this restoration of apoptosis with a compensatory suppression of caspase-3 expression, a nontargeted promoter of this process. In a continuation of this study we now evaluate the expression of the androgen receptor (AR) following oligo mediated regulation of apoptosis with suppression of Bcl-2. Results: Monospecific and bispecific oligos directed against Bcl-2 suppressed both the targeted Bcl-2 protein (an inhibitor of apoptosis) and the nontargeted caspase-3 (a promoter of apoptosis), potentially negating the effect on apoptosis produced by specific inhibition of Bcl-2. In contrast, the expression of the AR was significantly enhanced by each type of oligo. Conclusions: This suggests that when Bcl-2 expression is inhibited there are compensatory changes in the expression of additional proteins which regulate tumor growth, apoptosis and cell survival, and in this scenario might increase or re-establish hormonal sensitivity. If tumors variants are selected which evade gene therapy additional mechanisms of compensation must be identified and subsequently suppressed. These experiments identify pathways by which tumors can develop resistance to gene therapy and suggests additional targets for intervention.
A mouse GM-CSF receptor antibody attenuates neutrophilia in mice exposed to cigarette smoke
Authors: Botelho F.M. , Nikota J.K. , Bauer C. , Davis N.H.E. , Cohen E.S. , Anderson I.K. , Coyle A.J. , Kolbeck R. , Humbles A.A. , Stämpfli M.R. , Sleeman M.A. 
Published: March 2011

We investigated the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in a subchronic exposure model of cigarette smoke (CS)-induced inflammation using antibodies directed against GM-CSF or the GM-CSF receptor (GM-CSFR) α-chain.CS-induced mononuclear and neutrophilic inflammation following 4 days of CS exposure in BALB/c mice was assessed in bronchoalveolar lavage (BAL) fluid. An increase in mature dendritic cells (DCs) (CD11c+ and major histocompatibility complex II+) and Gr-1-high neutrophils was also observed by flow cytometric analysis of whole-lung tissue.Dailyi.p.injection of 400 μg GM-CSF or GM-CSFR antibody prior to daily smoke exposure attenuated the accumulation of neutrophils within the BAL by 60%. A reduction in mature DCs was also observed. Anti-GM-CSFR antibody administration did not have an effect on the percentage of lung T-cells; however, a significant decrease in activated CD69+ CD8+ T-cells was observed. Anti-GM-CSFR antibody administration decreased the mRNA and protein expression of interleukin-12 p40 and matrix metalloproteinase 12.Taken together, intervention with this receptor antibody implicates the GM-CSF pathway as an important mediator of smoke-induced inflammation.
Exercise capacity, muscle strength and fatigue in sarcoidosis
Authors: Marcellis R.G.J. , Lenssen A.F. , Elfferich M.D.P. , De Vries J. , Kassim S. , Foerster K. , Drent M. 
Published: March 2011

The aim of this case–control study was to investigate the prevalence of exercise intolerance, muscle weakness and fatigue in sarcoidosis patients. Additionally, we evaluated whether fatigue can be explained by exercise capacity, muscle strength or other clinical characteristics (lung function tests, radiographic stages, prednisone usage and inflammatory markers).124 sarcoidosis patients (80 males) referred to the Maastricht University Medical Centre (Maastricht, the Netherlands) were included (mean age 46.6±10.2 yrs). Patients performed a 6-min walk test (6MWT) and handgrip force (HGF), elbow flexor muscle strength (EFMS), quadriceps peak torque (QPT) and hamstring peak torque (HPT) tests. Maximal inspiratory pressure (PI,max) was recorded. All patients completed the Fatigue Assessment Scale (FAS) questionnaire.The 6MWT was reduced in 45% of the population, while HGF, EFMS, QPT and HPT muscle strength were reduced in 15, 12, 27 and 18%, respectively.PI,maxwas reduced in 43% of the population. The majority of the patients (81%) reported fatigue (FAS ≥22). Patients with reduced peripheral muscle strength of the upper and/or lower extremities were more fatigued and demonstrated impaired lung functions, fat-free mass,PI,max, 6MWT and quality of life. Fatigue was neither predicted by exercise capacity, nor by muscle strength.Besides fatigue, exercise intolerance and muscle weakness are frequent problems in sarcoidosis. We therefore recommend physical tests in the multidisciplinary management of sarcoidosis patients, even in nonfatigued patients.
Pseudomonas aeruginosainduces vascular endothelial growth factor synthesis in airway epitheliumin vitroandin vivo
Authors: Martin C. , Thévenot G. , Danel S. , Chapron J. , Tazi A. , Macey J. , Dusser D.J. , Fajac I. , Burgel P-R. 
Published: March 2011

Pseudomonas aeruginosa(PA) airway infection and bronchial blood vessel proliferation are features of bronchiectasis. Because vascular endothelial growth factor (VEGF)-A regulates angiogenesis, we hypothesised that PA infection induces VEGF synthesis in epithelium and peribronchial angiogenesis. Because epidermal growth factor receptor (EGFR) activation regulates VEGF synthesis in cancer, we also evaluated the roles of EGFR.Airway epithelial cells were incubated for 24 h with PA supernatants and VEGF concentrations were measured in culture medium by ELISA. C57BL/6N mice were instilled intratracheally with sterile agarose beads or with agarose beads coated with the PA strain PAO1 (mean±sem6×105±3×105cfu·animal−1), with or without the EGFR inhibitor AG1478 (12.5 mg·kg−1·day−1intraperitoneally). Epithelial immunostaining for VEGF and phosphorylated EGFR, and peribronchial vascularity, were quantified using morphometric analysis. VEGF expression was further assessed by western blot in mouse lung homogenates.PA supernatants induced dose-dependent VEGF synthesis in cultured airway epithelial cells, effects which were prevented by EGFR antagonists. In mice, persistent PAO1 infection increased immunostaining for VEGF and phosphorylated EGFR in airway epithelium, and resulted in increased peribronchial vascularity within 7 days. These effects were reduced by EGFR inhibition.Persistent PA infection induced VEGF synthesis in airway epithelium and peribronchial angiogenesis, at least in partviaEGFR-dependent mechanisms.
Guideline-concordant therapy and outcomes in healthcare-associated pneumonia
Authors: Attridge R.T. , Frei C.R. , Restrepo M.I. , Lawson K.A. , Ryan L. , Pugh M.J.V. , Anzueto A. , Mortensen E.M. 
Published: March 2011

Healthcare-associated pneumonia (HCAP) guidelines were first proposed in 2005 but have not yet been validated. The objective of this study was to compare 30-day mortality in HCAP patients treated with either guideline-concordant (GC)-HCAP therapy or GC community-acquired pneumonia (CAP) therapy.We performed a population-based cohort study of >150 hospitals in the US Veterans Health Administration. Patients were included if they had one or more HCAP risk factors and received antibiotic therapy within 48 h of admission. Critically ill patients were excluded. Independent risk factors for 30-day mortality were determined in a generalised linear mixed-effect model, with admitting hospital as a random effect. Propensity scores for the probability of receiving GC-HCAP therapy were calculated and incorporated into a second logistic regression model.A total of 15,071 patients met study criteria and received GC-HCAP therapy (8.0%), GC-CAP therapy (75.7%) or non-GC therapy (16.3%). The strongest predictors of 30-day mortality were recent hospital admission (OR 2.49, 95% CI 2.12–2.94) and GC-HCAP therapy (OR 2.18, 95% CI 1.86–2.55). GC-HCAP therapy remained an independent risk factor for 30-day mortality (OR 2.12, 95% CI 1.82–2.48) in the propensity score analysis.In nonsevere HCAP patients, GC-HCAP therapy is not associated with improved survival compared with GC-CAP therapy.
ADRB2Gly16Arg polymorphism, asthma control and lung function decline
Authors: Rebordosa C. , Kogevinas M. , Guerra S. , Castro-Giner F. , Jarvis D. , Cazzoletti L. , Pin I. , Siroux V. , Wjst M. , Antò J.M. , de Marco R. , Estivill X. , Corsico A.G. , Nielsen R. , Janson C. 
Published: March 2011

Arg/Arg homozygotes for the Gly16Arg polymorphism in the β2-adrenoreceptor gene (ADRB2) have a reduced response to short-acting β2-agonists but no effect has been associated with long-acting β2-agonists (LABAs).We selected 604 subjects with current asthma from the European Community Respiratory Health Study to evaluate whether asthma control and lung function decline were associated with Gly16Arg polymorphism, and to test whether LABA or inhaled corticosteroid (ICS) use modified these effects.There was an increased risk of noncontrolled asthma (OR 1.33, 95% CI 1.01–1.75; p=0.046) for each Arg allele. Among nonusers of ICS, the odds ratio of noncontrolled asthma among Arg/ArgversusGly/Gly subjects was 2.73 (95% CI 1.28–5.82; p=0.009). No increased risk of noncontrolled asthma associated with the Arg allele was observed among ICS and/or LABA users. For each Arg allele, a mean±sedecrease in decline in forced expiratory volume in 1 s of 7.7±2.5 mL·yr−1was found (p-value for trend 0.003), irrespective of ICS or LABA use. Arg/Arg subjects had an increased risk of bronchial hyperresponsiveness (BHR)versusGly/Gly subjects, with an odds ratio of 2.51 (95% CI 1.12–5.63; p=0.025) if they did not use ICS.The Arg allele was associated with poorer asthma control, a steeper lung function decline and BHR. Absence of genotypic effects on asthma control among ICS users may be due to reversed β2-adrenoreceptor desensitisation.
Management of occupational asthma: cessation or reduction of exposure? A systematic review of available evidence
Authors: Vandenplas O. , Dressel H. , Wilken D. , Jamart J. , Heederik D. , Maestrelli P. , Sigsgaard T. , Henneberger P. , Baur X. 
Published: March 2011

Reduction of exposure to sensitising agents causing occupational asthma has been proposed as an alternative to total avoidance in order to minimise the adverse socio-economic impact of the condition.The aim of this systematic review was to compare the effects of these two management options on asthma and socio-economic outcomes.A bibliographic search was conducted to identify studies examining the outcome of workers with occupational asthma after reduction or cessation of exposure to the causal agent.The changes in asthma symptoms and nonspecific bronchial hyperresponsiveness after reduction or cessation of exposure were described in nine and five studies, respectively. The meta-analysis of pooled data showed that a reduction of exposure was associated with a lower likelihood of improvement (OR 0.16, 95% CI 0.03–0.91) and recovery (OR 0.30, 95% CI 0.11–0.84) of asthma symptoms and a higher risk of worsening of the symptoms (OR 10.23, 95% CI 2.97–35.28) and nonspecific bronchial hyperresponsiveness (OR 5.65, 95% CI 1.11–28.82), compared with complete avoidance of exposure.This systematic review indicates that reduction of exposure cannot be routinely recommended as an alternative to cessation of exposure in the management of occupational asthma. However, further investigations are required before drawing evidence-based conclusions on the cost-effectiveness of this approach.
Short-term safety of thoracoscopic talc pleurodesis for recurrent primary spontaneous pneumothorax: a prospective European multicentre study
Authors: Bridevaux P-O. , Tschopp J-M. , Cardillo G. , Marquette C-H. , Noppen M. , Astoul P. , Driesen P. , Bolliger C.T. , Froudarakis M.E. , Janssen J.P. 
Published: March 2011

The safety of talc pleurodesis is under dispute following reports of talc-induced acute respiratory distress syndrome (ARDS) and death. We investigated the safety of large-particle talc for thoracoscopic pleurodesis to prevent recurrence of primary spontaneous pneumothorax (PSP).418 patients with recurrent PSP were enrolled between 2002 and 2008 in nine centres in Europe and South Africa. The main exclusion criteria were infection, heart disease and coagulation disorders. Serious adverse events (ARDS, death or other) were recorded up to 30 days after the procedure. Oxygen saturation, supplemental oxygen use and temperature were recorded daily at baseline and after thoracoscopic pleurodesis (2 g graded talc).During the 30-day observation period following talc poudrage, no ARDS (95% CI 0.0–0.9%), intensive care unit admission or death were recorded. Seven patients presented with minor complications (1.7%, 95% CI 0.7–3.4%). After pleurodesis, mean body temperature increased by 0.41°C (95% CI 0.33–0.48°C; p<0.001) at day 1 and returned to baseline value at day 5. Pleural drains were removed after day 4 in 80% of patients.Serious adverse events, including ARDS or death, did not occur in this large, multicentre cohort. Thoracoscopic talc poudrage using larger particle talc to prevent recurrence of PSPS can be considered safe.
Concerted Action of Aldehyde Dehydrogenases Influences Depot-Specific Fat Formation
Authors: Reichert Barbara , Yasmeen Rumana , Jeyakumar Shanmugam M. , Yang Fangping , Thomou Thomas , Alder Hansjuerg , Duester Gregg , Maiseyeu Andrei , Mihai Georgeta , Harrison Earl H. , Rajagopalan Sanjay , Kirkland James L. , Ziouzenkova Ouliana 
Published: March 2011

Abstract
Vitamin A metabolite retinoic acid (RA) regulates life-sustaining differentiation processes and metabolic homeostasis. The aldehyde dehydrogenase-1 (Aldh1) family of enzymes (Aldh1a1, a2, and a3) catalyzes RA production from retinaldehyde and thereby controls concentrations of this transcriptionally active metabolite. The hierarchy of Aldh1 functions in adipose tissue has not been elucidated. We hypothesized that Aldh1 enzymes produce endogenous RA and regulate adipogenesis and fat formation in a fat depot-specific manner. We demonstrate that adipogenesis in vitro is accompanied by RA production generated primarily by Aldh1a1. In Aldh1a1-deficient adipocytes, adipogenesis is impaired compared with wild-type adipocytes due to markedly reduced expression of PPARγ regulated through zinc-finger protein 423 (ZFP423)-dependent mechanisms. These effects were recovered to some extent either by RA stimulation or overexpression of any of the Aldh1 enzymes in Aldh1a1−/− cells arguing that Aldh1a1 plays a dominant role in autocrine RA production. In vivo studies in C57/BL6 and Aldh1a1−/− mice on a regular diet revealed that multiple Aldh1 enzymes regulate differences in the formation of sc and visceral fat. In Aldh1a1−/− mice, visceral fat essentially lacked all Aldh1 expression. This loss of RA-producing enzymes was accompanied by 70% decreased expression of ZFP423, PPARγ, and Fabp4 in visceral fat of Aldh1a1−/−vs. wild-type mice and by the predominant loss of visceral fat. Subcutaneous fat of Aldh1a1−/− mice expressed Aldh1a3 for RA production that was sufficient to maintain expression of ZFP423 and PPARγ and sc fat mass. Our data suggest a paradigm for regulation of fat depots through the concerted action of Aldh1 enzymes that establish RA-dependent tandem regulation of transcription factors ZFP423 and PPARγ in a depot-specific manner.