MicroRNA profiling in patients with abdominal aortic aneurysms: the significance of miR-155
Abdominal aortic aneurysm (AAA) is a potentially life threatening late onset degenerative condition. MicroRNAs, the small non-coding RNA molecules that regulate gene expression, have been previously shown to be associated with a broad range of human pathologies, including cardiovascular diseases. The aim of this study was to identify AAA-associated microRNAs potentially contributing to AAA pathology. We analyzed the expression of 124 microRNAs within AAA biopsies and serum of 10 patients undergoing AAA repair, and serum from 10 age- and sex-matched subjects without AAA, using the FlexmiR™ MicroRNA Assay. RNA extracte...
Source: Clinical Science - November 28, 2013 Category: Biomedical Science Authors: E Biros, C S. Moran, Y Wang, P J. Walker, J Cardinal, J Golledge Source Type: research

Detection of mutations in KLHL3 and CUL3 in families with Familial Hyperkalaemic Hypertension (FHHt or Gordon Syndrome)
The study of families with rare inherited forms of hypo- and hypertension has been one of the most successful strategies to probe the molecular pathophysiology of blood pressure control and has revealed dysregulation of distal nephron sodium reabsorption to be a common mechanism. Familial Hyperkalaemic Hypertension (FHHt, Gordon Syndrome) is a salt-dependent form of hypertension caused by mutations in regulators of the thiazide-sensitive NaCl cotransporter, NCC, and is effectively treated by thiazide diuretics and/or dietary salt restriction. Variation in at least four genes can cause FHHt, including ‘With No lysine ...
Source: Clinical Science - November 25, 2013 Category: Biomedical Science Authors: M Glover, J S. Ware, A Henry, M Wolley, R Walsh, L V. Wain, S Xu, W G. Van’t Hoff, M D. Tobin, I P. Hall, S Cook, R D. Gordon, M Stowasser, K M. O'Shaughnessy Source Type: research

Suppression of abdominal aortic aneurysm formation by inhibition of prolyl hydroxylase domain protein through attenuation of inflammation and extracellular matrix disruption
We sought to determine the effect of cobalt chloride (CoCl2), an inhibitor of prolyl hydroxylase domain protein (PHD), on the development of abdominal aortic aneurysm (AAA). Abdominal aortic aneurysm was induced in C57BL/6 mice by periaortic application of calcium chloride (CaCl2) (AAA group). NaCl (0.9%)-applied mice were used as a sham contrrol (SHAM group). Mice were treated with 0.05% CoCl2 in drinking water (AAA/CoCl2 group). One and 6 weeks after the operation, aortic tissue was excised for further examinations. After 6 weeks of CaCl2 application, aortic diameter and macrophage infiltration into the aortic adventitia...
Source: Clinical Science - November 21, 2013 Category: Biomedical Science Authors: A Watanabe, T Ichiki, C Sankoda, Y Takahara, J Ikeda, E Inoue, T Tokunou, S Kitamoto, K Sunagawa Source Type: research

In vivo evidence of an age-related increase in ATP cost of contraction in the plantar flexor muscles
Impaired skeletal muscle efficiency potentially contributes to the age-related decline in exercise capacity and may explain the altered hemodynamic response to exercise in the elderly. Thus, we examined whether 1) the ATP cost of contraction increases with age, and 2) this results in altered convective O2 delivery to maintain microvascular oxygenation in the calf muscle. To this aim, we used an integrative experimental approach combining phosphorus magnetic resonance spectroscopy (31P-MRS), Doppler ultrasound imaging, and near-infrared spectroscopy (NIRS) during dynamic plantar flexion exercise at 40% of maximal power outp...
Source: Clinical Science - November 14, 2013 Category: Biomedical Science Authors: G Layec, J D. Trinity, C R. Hart, S Kim, H Jonathan Groot, Y Le Fur, J R. Sorensen, E Jeong, R S. Richardson Source Type: research

Muscle disuse atrophy is not accompanied by changes in skeletal muscle satellite cell content
Muscle disuse leads to a considerable loss of skeletal muscle mass and strength. However, the cellular mechanisms underlying disuse-induced muscle fibre atrophy remain to be elucidated. Therefore, we assessed the impact of muscle disuse on quadriceps muscle cross-sectional area (CSA), muscle fibre size and satellite cell content, and associated myocellular signalling pathways. Methods: Twelve healthy, young (24±1 y) men were subjected to 2 wks of one-legged knee immobilisation via a full leg cast. Before and immediately after the immobilisation period and after six weeks of natural rehabilitation, muscle strength (o...
Source: Clinical Science - November 12, 2013 Category: Biomedical Science Authors: T Snijders, B T. Wall, M L. Dirks, J M.G. Senden, F Hartgens, J Dolmans, M Losen, L B. Verdijk, L J.C. van Loon Source Type: research

C-reactive protein promotes acute kidney injury by impairing the G1/S-dependent tubular epithelial cell regeneration
C-reactive protein (CRP) is regarded as a inflammatory biomarker in acute kidney injury (AKI), but its exact role in AKI remains unclear. Thus, we sought to investigate the role of CRP in AKI. Clinically, elevated serum CRP were closely associated with an increased serum creatinine and urea (p
Source: Clinical Science - November 8, 2013 Category: Biomedical Science Authors: Y Tang, X Huang, J Lv, A Chi-Kong Chung, Y Zhang, J Chen, A J Szalai, A Xu, H Y Lan Source Type: research

Valsartan slows the progression of diabetic nephropathy in db/db mice via reduction in podocyte injury and renal oxidative stress and inflammation
This study sought to determine whether doses of angiotensin II receptor blocker (ARB) that maximally reduce proteinuria could slow the progression of glomerulosclerosis in the uninephrectomized db/db mouse, a model of type 2 diabetes. Untreated uninephrectomized db/db mice had normal blood pressure but developed progressive albuminuria and mesangial matrix expansion between weeks 18 and 22, associated with increased renal expression of TGFß1, PAI-1, type IV collagen and fibronectin. Treatment with valsartan in drinking water from weeks 18 to 22 at a dose that maximally reduced proteinuria determined previously preven...
Source: Clinical Science - November 6, 2013 Category: Biomedical Science Authors: G Zhou, A K. Cheung, X Liu, Y Huang Source Type: research

MicroRNA-122 down-regulation may play a role in severe myocardial fibrosis in human aortic stenosis through TGF-{beta}1 up-regulation
In conclusion, for the first time we show that myocardial down-regulation of miR-122 might be involved in myocardial fibrosis in AS patients, likely through TGF-β1 up-regulation. (Source: Clinical Science)
Source: Clinical Science - October 29, 2013 Category: Biomedical Science Authors: J Beaumont, B López, N Hermida, B Schroen, G San José, S Heymans, F Valencia, J Gómez-Doblas, E de Teresa, J Díez, A González Source Type: research

Development of a mouse model mimicking key aspects of a viral asthma exacerbation
Viral respiratory tract infections are known triggers of asthma exacerbations in both adults and children. Current standard of care (inhaled corticosteroids (CS) and long-acting β2-adrenoceptor agonists (LABA)) fails to prevent the loss of control that manifests as an exacerbation. In order to better understand the mechanisms underlying viral asthma exacerbations we established an in vivo model using the clinically-relevant aeroallergen house dust mite (HDM) and the viral mimetic / TLR3 agonist poly I:C. Poly I:C-alone induced a similar neutrophilic inflammatory profile in the bronchoalveolar lavage (BAL) to that of h...
Source: Clinical Science - October 24, 2013 Category: Biomedical Science Authors: D L Clarke, N H.E. Davis, J B Majithiya, S C Piper, A Lewis, M A Sleeman, D J Corkill, R D May Source Type: research

Epigenetic regulation of angiotensin converting enzyme-2 (ACE2) by SIRT1 under conditions of cell energy stress
In conclusion,here we establish that the expression of the ACE2 transcript is controlled by the activity of SIRT1 under conditions of energy stress. (Source: Clinical Science)
Source: Clinical Science - October 23, 2013 Category: Biomedical Science Authors: N E Clarke, N D Belyaev, D W Lambert, A J Turner Source Type: research

Involvement of proteinase activated receptor-2 in vascular response to sphingosine-1-phosphate
This study has been performed by using isolated mouse aortas. Both S1P and PAR-2 agonists induce endothelium-dependent vasorelaxation. L-NAME and wortmannin abrogate S1P-induced vasorelaxatioin, while significantly inhibit PAR-2 mediated effect. Either ENMD1068, a PAR-2 antagonist or gabexate, a serine protease inhibitor, significantly inhibit S1P-induced vasorelaxation. Aortic tissues harvested from mice overexpressing PAR-2 display a significant increased vascular response to S1P as opposite to PAR-2 null mice. Immunoprecipitation and immunofluorescence studies demonstrate that S1P1 interacts with PAR-2 and co-localizes ...
Source: Clinical Science - October 17, 2013 Category: Biomedical Science Authors: F Roviezzo, A De Angelis, L De Gruttola, A Bertolino, N Sullo, V Brancaleone, M Bucci, R De Palma, K Urbanek, B D'Agostino, A Ianaro, R Sorrentino, G Cirino Source Type: research

Analysis of cytokine profile in the duodenal mucosa of refractory celiac disease patients
Refractory celiac disease (RCD) is characterized by severe symptoms/signs of malabsorption and mucosal damage unresponsive to a gluten-free diet. The pathogenesis of RCD is not fully understood. Here we characterized the mucosal profile of effector cytokines in RCD. Duodenal biopsies were taken from patients with RCD, patients with active CD, and normal controls, and analyzed for inflammatory cytokines by real-time PCR and ELISA. IFN-γ and IL-21 transcripts were increased in active CD patients but not in RCD patients as compared to normal controls, while IL-17A RNA was up-regulated in both active CD and RCD. No signi...
Source: Clinical Science - October 15, 2013 Category: Biomedical Science Authors: R Caruso, I Marafini, S Sedda, G Del Vecchio Blanco, P Giuffrida, T T. MacDonald, G Roberto Corazza, F Pallone, A Di Sabatino, G Monteleone Source Type: research

MAS promoter regulation: a role of Sry and tyrosine nitration of the KRAB domain of ZNF274 as a feedback mechanism
The ACE2/Ang-(1-7)/MAS axis of the renin-angiotensin system has emerged as a pathway of interest in treating both cardiovascular disorders and cancer. The MAS protein is known to bind and be activated by Ang-(1-7); however mechanisms of this activation are just starting to be understood. Whereas there are strong biochemical data regarding regulation and activation of the AT1 and AT2 receptors, with models of how Ang II binds each receptor, fewer studies have characterized MAS. We characterize the MAS promoter and provide a potential feedback mechanism that would compensate for the MAS degradation following activation by An...
Source: Clinical Science - October 15, 2013 Category: Biomedical Science Authors: J W. Prokop, F J. Rauscher III, H Peng, Y Liu, F C. Araujo, I Watanabe, F M. Reis, A Milsted Source Type: research

Stability of cerebral metabolism and substrate availability in humans during hypoxia and hyperoxia
Characterization of the influence of O2 availability on brain metabolism is an essential step toward a better understanding of brain energy homeostasis and has obvious clinical implications. Yet, how brain metabolism depends on O2 availability has not been clearly examined in humans. We therefore assessed the influence of O2 on cerebral blood flow (CBF), and cerebral metabolic rates for oxygen (CMRO2) and carbohydrates. Arterial PO2 was decreased for ∼15 min each to ∼60, ∼44, and ∼35 mmHg (to target a SaO2 of 90%, 80%, and 70%, respectively), and elevated to ∼320 mmHg and ∼430 mmHg. Isocapnia was ma...
Source: Clinical Science - October 14, 2013 Category: Biomedical Science Authors: P N Ainslie, A D Shaw, K J Smith, C K Willie, K Ikeda, J Graham, D B Macleod Source Type: research

Genetic variation and gender determine bradykinin type 1 receptor responses in human tissue: implications for the ACE inhibitor-induced effects in patients with coronary artery disease
The efficacy of angiotensin-converting enzyme inhibitor perindopril in coronary artery disease (EUROPA study) associates with the rs12050217 A/G single nucleotide polymorphism in the bradykinin B1 receptor gene. To investigate the underlying mechanism, we examined the effect of this polymorphism on B1 receptor-mediated coronary artery dilation and peripheral blood mononuclear cell activation. Vasorelaxant responses of human coronary microarteries from subjects without coronary disease to des-Arg9-bradykinin and to bradykinin were studied in organ bath experiments. Des-Arg9-bradykinin responses were endothelium-dependent an...
Source: Clinical Science - October 14, 2013 Category: Biomedical Science Authors: H Wu, A J.M. Roks, F Leijten, I Garrelds, U Musterd-Bhaggoe, A J. van den Bogaerdt, M P. M. de Maat, M L. Simoons, A Danser, H Oeseburg Source Type: research

Urocortin 2 is associated with abdominal aortic aneurysm and mediates anti-proliferative effects on vascular smooth muscle cells via corticotrophin releasing factor receptor 2
In conclusion, UCN2 is significantly associated with AAA and inhibits VSMC proliferation by inducing a G1 cell cycle arrest suggesting a plausible regulatory role in AAA pathogenesis. (Source: Clinical Science)
Source: Clinical Science - October 10, 2013 Category: Biomedical Science Authors: T I Emeto, J V Moxon, E Biros, C M Rush, P Clancy, L Woodward, C S Moran, R J Jose, T Nguyen, P J Walker, J Golledge Source Type: research

Green tea polyphenol decreases the severity of portosystemic collaterals and mesenteric angiogenesis in rats with liver cirrhosis
In conclusion, GTP ameliorates the severity of portosystemic shunting and mesenteric angiogenesis via the suppression of HIF-1α, Akt activation, and VEGF. GTP appears as an appropriate agent to control portal hypertension-related complications via anti-angiogenesis. (Source: Clinical Science)
Source: Clinical Science - September 25, 2013 Category: Biomedical Science Authors: S Hsu, S Wang, I Hsin, F Lee, H Huang, T Huo, W Lee, H Lin, S Lee Source Type: research

Angiotensin II and the ERK pathway mediate the induction of leptin by mechanical cyclic stretch in cultured rat neonatal cardiomyocytes
This study evaluated the expression of leptin under cyclic stretch and its role in regulating genetic transcription in cardiomyocytes. Cultured rat neonatal cardiomyocytes were subjected to cyclic stretch, and the expression levels of leptin, reactive oxygen species (ROS) and, angiotensin II (AngII) were evaluated. Signal transduction inhibitors were used to identify the pathway of leptin expression. Electrophoretic motility shift assays (EMSA) were used to identify the binding of leptin/STAT3 (signal transducer and activator of transcription 3), and luciferase assays were used to identify the transcription of leptin in ca...
Source: Clinical Science - September 24, 2013 Category: Biomedical Science Authors: C Chiu, B Wang, K Shyu Source Type: research

MicroRNA profiles in celiac patients distinguish different clinical phenotypes and are modulated by gliadin peptides in primary duodenal fibroblasts
In this study the duodenal mucosa microRNA expression was profiled in adult untreated CD presenting with a classic phenotype or iron deficiency anemia, treated patients with or without duodenal normalization, and non-CD subjects as controls. Deregulation of seven miRNAs (miR-31-5p, miR-192-3p, miR-194-5p, miR-551a, miR-551b-5p, miR-638, and miR-1290) could be determined in a larger series of CD patients with different clinical phenotypes compared to non-CD subjects. These 7 microRNAs were then analyzed in duodenal fibroblasts obtained from CD patients and incubated with gliadin peptides (13 and 33mer). The microRNA cluster...
Source: Clinical Science - September 24, 2013 Category: Biomedical Science Authors: V Vaira, L Roncoroni, D Barisani, G Gaudioso, S Bosari, G Bulfamante, L Doneda, D Conte, C Tomba, M Bardella, S Ferrero, M Locatelli, L Elli Source Type: research

All-trans-retinoic acid improves immunocompetence in a murine model of lipopolysaccharide-induced immunosuppression
Secondary infections due to post-sepsis immunosuppression is a major cause of death in septic patients. Strategies aimed at restoring immune functions offer a new perspective. We used LPS-immunosuppressed (IS) mice to analyze the effects of all-trans Retinoic Acid (ATRA) on different immune parameters. IS mice showed decreased lymphocyte and increased myeloid-derived suppressor cells (MDSC) counts in lymph nodes. They also showed an impaired in vitro T cell proliferation, mediated by MDSC. ATRA administration restored T cell proliferation, associated to a decreased number of live MDSC. IS mice treated with ATRA showed an i...
Source: Clinical Science - September 20, 2013 Category: Biomedical Science Authors: D Martire-Greco, V I. Landoni, P Chiarella, N Rodriguez-Rodrigues, P Schierloh, B Rearte, M A. Isturiz, G C. Fernandez Source Type: research

A comprehensive analysis of oxidative stress in the ozone-induced lung inflammation mouse model
In this study we investigated the acute and chronic effects of ozone exposure-induced oxidative stress related inflammation mechanics in mouse lung. In particular we investigated the oxidative stress-induced effects on HDAC2 modification and activation of the Nrf2 and HIF-1α signalling pathways. Male C57BL/6 mice were exposed to ozone (3 ppm) for 3 hours a day, 2 times a week for a period 1, 3 and 6 weeks. Control mice were exposed to normal air. After the last exposure mice were sacrificed for bronchoalveolar lavage (BAL) fluid and lung tissue collection. BAL total cell counts were elevated at all time points studie...
Source: Clinical Science - September 16, 2013 Category: Biomedical Science Authors: C H. Wiegman, F Li, C J. Clarke, E Jazrawi, P Kirkham, P J. Barnes, I M. Adcock, K F. Chung Source Type: research

Serum 25-hydroxyvitamin D predicts the short-term outcomes of Chinese patients with acute ischemic stroke
Background Low vitamin D levels have been reported to contribute to the risk of cardiovascular events and mortality, especially stroke. We therefore evaluated the short-term prognostic value of serum 25-hydroxyvitamin D [25(OH) D] in Chinese patients with an acute ischemic stroke (AIS). Methods From February 1, 2010 to September 30, 2012, consecutive stroke patients admitted to the emergency department at two hospitals in Beijing, China were identified. Clinical information was collected. Serum concentration of 25(OH) D and NIH stroke scale (NIHSS) were measured at the time of admission. Short-term functional outcome was ...
Source: Clinical Science - September 11, 2013 Category: Biomedical Science Authors: W Tu Sr., S Zhao, D Xu, H Chen Source Type: research

Fragment-based design for the development of N-domain selective angiotensin-1 converting enzyme inhibitors
Angiotensin-1 converting enzyme (ACE) is a zinc metallopeptidase that plays a prominent role in blood pressure regulation and electrolyte homeostasis. ACE consists of two homologous domains that despite similarities of sequence and topology display differences in substrate processing and inhibitor binding. The design of inhibitors that selectively inhibit the N-domain (N-selective) could be useful in treating conditions of tissue injury and fibrosis due to build-up of N-domain specific substrate N-acetyl-Ser-Asp-Lys-Pro. Using a receptor-based scaffold hopping approach with N-selective inhibitor RXP407, a shortlist of scaf...
Source: Clinical Science - September 9, 2013 Category: Biomedical Science Authors: R Gavin Douglas, R K. Sharma, G Masuyer, L Lubbe, I Zamora, K Ravi Acharya, K Chibale, E D. Sturrock Source Type: research

Hypoxia activates muscle-restricted coiled-coil protein (MURC) expression via transforming growth factor-{beta} in cardiac myocytes
In conclusion, hypoxia in cultured rat neonatal cardiomyocytes increased MURC expression via the induction of TGF-β, SRF and the ERK pathway. These findings suggest that MURC plays a role in hypoxia-induced hypertrophy in cardiomyocytes. (Source: Clinical Science)
Source: Clinical Science - September 4, 2013 Category: Biomedical Science Authors: K Shyu, W Cheng, B Wang, H Chang Source Type: research

A double-blind, placebo-controlled, crossover study of the vascular effects of midodrine in neuropathic versus hyperadrenergic Postural Tachycardia Syndrome
Postural tachycardia syndrome (POTS) is a chronic form of orthostatic intolerance. Neuropathic POTS is characterized by decreased adrenergic vasoconstriction, while hyperadrenergic POTS exhibits increased adrenergic vasoconstriction. We hypothesized that midodrine, an α1-adrenergic receptor agonist, would increase calf vascular resistance (CVR), decrease calf venous capacitance (Cv), and decrease orthostatic tachycardia in neuropathic POTS but not alter hemodynamics in hyperadrenergic POTS. 20 POTS patients (12 neuropathic, 8 hyperadrenergic), ages 12-20, participated in this randomized, placebo-controlled, double-bl...
Source: Clinical Science - August 27, 2013 Category: Biomedical Science Authors: A J Ross, A J Ocon, M S Medow, J Mark Stewart Source Type: research

The profile of maternal CD4 T cell effector function during normal pregnancy and in women with a history of recurrent miscarriage
The traditional paradigm suggests that during normal pregnancy maternal immunological tolerance of the allogenic fetus is association with a maternal T lymphocyte shift from a Th1 to a Th2 phenotype, with the opposite effect reported in patients with recurrent miscarriage. However, studies on maternal peripheral blood are conflicting. We characterised the maternal CD4 T cell effector subsets, including the recently described Th17 subset, during normal pregnancy (cross-sectional cohort n=71, longitudinal cohort n=17) and contrasted this with women with recurrent miscarriage (n=24). Longitudinal analysis of peripheral blood...
Source: Clinical Science - August 20, 2013 Category: Biomedical Science Authors: D Lissauer, O Goodyear, R Khanum, P AH Moss, M D Kilby Source Type: research

Left Atrial Deformation Parameters in Patients with Non-alcoholic Fatty Liver Disease- A 2D Speckle Tracking Imaging Study
Background. The presence of metabolic syndrome is a strong predictor for the presence of steatohepatitis (NASH) in patients with non-alcoholic fatty liver disease (NAFLD). We assessed left atrium (LA) deformation parameters in patients with NAFLD using two-dimensional speckle tracking echocardiography (2D-STE) and to investigate if any changes exists between subgroups of the NAFLD. Methods. A total of 55 NAFLD patients and 21 healthy controls were included in the study. The diagnosis of NAFLD was based on liver biopsy. After patients were categorized into groups according to histopathologic analysis (simple steatosis, bord...
Source: Clinical Science - August 15, 2013 Category: Biomedical Science Authors: G Kocabay, C Yucel Karabay, Y Colak, V Oduncu, A Kalaycı, T Akgun, A Guler, C Kırma Source Type: research

NLRP3 inflammasome activation in coronary artery disease: Results from prospective and randomized study of treatment with atorvastatin or rosuvastatin
This study included 60 patients with CAD and 30 subjects without CAD (non-CAD). Patients with CAD were randomized to 8 months of treatment with atorvastatin or rosuvastatin. PBMCs (peripheral blood mononuclear cells) were obtained from peripheral blood at baseline and after 8 months of statin therapy. Levels of NLRP3 inflammasome, IL-1β and IL-18 were measured by real-time RT-PCR and fluorescence-activated cell sorting. Levels of NLRP3 inflammasome were higher in the CAD group than in the non-CAD group. There was a positive correlation between NLRP3 inflammasome and cytokines (IL-1β and IL-18) levels. A randomiz...
Source: Clinical Science - August 14, 2013 Category: Biomedical Science Authors: M Satoh, T Tabuchi, T Itoh, M Nakamura Source Type: research

CRAC channel inhibition produces greater anti-inflammatory effects than glucocorticoids in COPD CD8 cells.
Background: There are increased numbers of pulmonary CD8 lymphocytes in COPD. Calcium-release activation calcium (CRAC) channels play a central role in lymphocyte activation though the regulation of the transcription factor nuclear factor of activated T cells (NFAT). Objective: We studied the expression of NFAT in COPD lungs compared to controls, and evaluated the effects of CRAC inhibition compared to corticosteroids on NFAT activation and cytokine production from COPD CD8 cells. Methods: The effects of the corticosteroid dexamethasone, the calcineurin inhibitor cyclosporin and the CRAC inhibitor synta-66 were studied on...
Source: Clinical Science - August 1, 2013 Category: Biomedical Science Authors: S Grundy, M Kaur, J Plumb, S Reynolds, S Hall, D House, M Begg, D Ray, D Singh Source Type: research

Carbamylation of LDL and its relationship with myeloperoxidase in type 2 diabetes mellitus
Background: LDL is subjected to proatherogenic modifications in the circulation. A novel uremia-independent mechanism of carbamylation of lipoproteins mediated by myeloperoxidase (MPO) has recently been reported. We have investigated whether carbamylation of LDL was increased in type 2 diabetic patients without renal impairment and the role of MPO. Methods: Carbamylated LDL (cLDL) and MPO was measured by ELISA in a cross sectional study of 198 patients and 174 non-diabetic controls. The impact of lowering MPO on plasma cLDL was determined by assaying cLDL and MPO in archived samples from a previous randomized, open-label,...
Source: Clinical Science - August 1, 2013 Category: Biomedical Science Authors: S W.M. Shiu, S Xiao, Y Wong, W Chow, K S.L. Lam, K C.B. Tan Source Type: research

Combining risk markers improves cardiovascular risk prediction in women
Conclusions: In all women cardiovascular risk stratification improved by adding combinations and in women at intermediate risk also by adding individual non-invasive risk markers. The additive value of individual and combined non-invasive risk markers in men is limited to men at intermediate risk only, and to a lesser extent than in women. (Source: Clinical Science)
Source: Clinical Science - July 24, 2013 Category: Biomedical Science Authors: S Holewijn, M den Heijer, L A. Kiemeney, A F.H. Stalenhoef, J de Graaf Source Type: research

Involvement of the HIF-1{alpha} and Wnt/{beta}-catenin pathways on the protective effects of losartan on fatty liver graft with ischemia/reperfusion injury
This study aims to determine whether Wnt-HIF axis is part of the mechanistic positive effect of angiotensin-II inhibition by losartan in the rat with liver IRI. Various measurements were performed in methionine and choline-deficient/high fat diet-induced nonalcoholic steatohepatitis (MCD/HF-NASH) rats with liver IRI. Acute losartan pre-administration markedly reversed IR-suppressed hepatic protective factors-IL-6, INF-γ, Wnt3α, β-catenin, HIF-1α levels, hepatic blood flow, and IR-elevated serum ALT, hepatic TNF-α, IL-1α, hepatic congestion, vacuolization and necrosis, hepatic Suzuki IRI s...
Source: Clinical Science - July 23, 2013 Category: Biomedical Science Authors: Y Yang, P Lee Jr., Y Huang Sr., W Lee, Y Kuo Jr., K Lee, Y Hsieh, T Lee, H Lin Source Type: research

Relationship between Urinary Sodium Excretion and Serum Aldosterone in Patients with Diabetes in the Presence and Absence of Modifiers of the Renin Angiotensin Aldosterone System
Conclusions: Low 24hUNa is associated with increased serum aldosterone in people with diabetes, in the presence and absence of RAAS modifying agents. This raises the possibility that stimulation of the RAAS may be a mechanism which contributes to adverse outcomes observed in patients with low 24hUNa. (Source: Clinical Science)
Source: Clinical Science - July 23, 2013 Category: Biomedical Science Authors: R Libianto, G Jerums, Q Lam, A Chen, S Baqar, F Pyrlis, R MacIsaac, J Moran, E I. Ekinci Source Type: research

The composition of cigarette smoke determines inflammatory cell recruitment to the lung in COPD mouse models
Chronic obstructive pulmonary disease (COPD) is caused by exposure to toxic gases and particles, most often cigarette smoke (CS), leading to emphysema, chronic bronchitis, mucus production and a subsequent decline in lung function. The disease pathogenesis is related to an abnormal CS-induced inflammatory response of the lungs. Similar to active (mainstream) smoking second hand (sidestream) smoke exposure severely affects respiratory health. These processes can be studied in vivo in models of CS exposure of mice. We compared the acute inflammatory response of female C57BL/6 mice exposed to two concentrations (250 and 500 ...
Source: Clinical Science - July 23, 2013 Category: Biomedical Science Authors: G John, K Kohse, J Orasche, A Reda, J Schnelle-Kreis, R Zimmermann, O Schmid, O Eickelberg, A Önder Yildirim Source Type: research

Airway hyperresponsiveness in lipopolysaccharide-challenged common marmosets (Callithrix jacchus)
Animal models with a high predictive value for human trials are needed to develop novel human-specific therapeutics against respiratory diseases. The aim of the study was to examine lung function parameters in marmoset monkeys (Callithrix jacchus) that can be used to detect pharmacologically or provocation induced airway hyperresponsiveness. Therefore, a custom-made lung function device which allows application of defined aerosol doses during measurement was developed. It was hypothesized that LPS-challenged marmosets show airway hyperresponsiveness compared to non-challenged, healthy subjects. Invasive plethysmography wa...
Source: Clinical Science - July 23, 2013 Category: Biomedical Science Authors: C Curths, J Wichmann, S Dunker, H Windt, H Hoymann, H D Lauenstein, J Hohlfeld, T Becker, F Kaup, A Braun, S Knauf Source Type: research

Fibulin-2 Deficiency Attenuates Angiotensin II-Induced Cardiac Hypertrophy By Reducing Transforming Growth Factor-{beta} Signaling
Conclusions: Our data indicate that fibulin-2 is essential for Ang II-induced TGF-β-mediated cardiac hypertrophy via enhanced TGF-β activation and suggest that fibulin-2 is a potential therapeutic target to inhibit Ang II-induced cardiac remodeling. (254 words) (Source: Clinical Science)
Source: Clinical Science - July 10, 2013 Category: Biomedical Science Authors: H Zhang, J Wu, H Dong, S A Khan, M Chu, T Tsuda Source Type: research

N-acetyl-seryl-aspartyl-lysyl-proline reduces cardiac collagen cross-linking and inflammation in angiotensin II induced hypertensive rats
In conclusion, the effect of Ac-SDKP on collagen cross-linking and total collagen may be due to reduced TGF-β1, LOXL1 and lymphocyte and macrophages infiltration, and its effect on inflammation could be due to lower NFκB. (Source: Clinical Science)
Source: Clinical Science - July 9, 2013 Category: Biomedical Science Authors: G E González, N Rhaleb, P Nakagawa, T Liao, Y Liu, P Leung, X Dai, X Yang, O A. Carretero Source Type: research

Endothelial dysfunction in hyperandrogenic polycystic ovary syndrome is not explained by either obesity or ectopic fat deposition
Polycystic ovary syndrome (PCOS) is associated with insulin resistance, increased visceral fat and non-alcoholic fatty liver disease (NAFLD) all of which may contribute to endothelial dysfunction, an early marker of cardiovascular disease risk. Our objective was to examine the relationships between endothelial dysfunction in PCOS, the volume of adipose tissue compartments and the size of intracellular triglyceride pools in liver and skeletal muscle. Thirty-five women with PCOS (mean±SD; 26±6y, 36±5kg/m2) and 16 control women (31±8y, 30±6kg/m2) were recruited. Endothelial function was asse...
Source: Clinical Science - July 5, 2013 Category: Biomedical Science Authors: V Spencer Sprung, H Jones, C JA Pugh, N F Aziz, C Daousi, G J Kemp, D J Green, N Cable, D J Cuthbertson Source Type: research

Proof of concept evaluation of trough airway hyper-responsiveness following regular racemic or levosalbutamol in genotype-stratified steroid-treated persistent asthmatics
Asthmatic patients receiving inhaled corticosteroids may take frequent add-on therapy with salbutamol despite on-demand prescription. Frequent salbutamol use can be detrimental in asthma. The isomeric formulation of salbutamol and the beta-2 adrenoceptor 16 genotype may also influence this phenomenon. We performed a randomised, double-blind, placebo-controlled, triple crossover, proof of concept trial comparing 2 weeks of regular therapy with inhaled racemic salbutamol (200µg qid); levosalbutamol (100µg qid); or placebo on trough methacholine PC20 6 hours post dose (the primary outcome) in 30 persistent asthmat...
Source: Clinical Science - July 5, 2013 Category: Biomedical Science Authors: W J Anderson, P M Short, P A Williamson, A E Morrison, C Palmer, R Tavendale, B J Lipworth Source Type: research

Radiofrequency Ablation Suppresses Distant Tumor Growth in a Novel Rat Model of Multifocal Hepatocellular Carcinoma
Conclusions: RFA and sorafenib alone resulted in significant volume reduction of the non-RFA targeted tumor; this effect was enhanced when both modalities were combined. (Source: Clinical Science)
Source: Clinical Science - July 4, 2013 Category: Biomedical Science Authors: C Erös de Bethlenfalva-Hora, J C. Mertens, A Piguet, J Kettenbach, J Schmitt, L Terracciano, R Weimann, J Dufour, A Geier Source Type: research

No exacerbation but impaired anti-viral mechanisms in a rhinovirus-chronic allergic asthma mouse model
Conclusions: Although superimposed HRV1B infection did not provoke asthma exacerbation in this severe model, a deficient anti-viral immune response to HRV1B was present under chronic allergic airway inflammatory conditions. Thus, this model is able to reflect some aspects of the complex interplay of respiratory virus infection in chronic allergic asthma. (Source: Clinical Science)
Source: Clinical Science - July 3, 2013 Category: Biomedical Science Authors: S Rochlitzer, H Hoymann, M Müller, A Braun Source Type: research

Mast cell mediators cause the early allergic bronchoconstriction in guinea pigs in vivo: a model of relevance to asthma
One feature of allergic asthma, the early allergic reaction (EAR), is not present in the commonly used mouse models. We therefore investigated the mediators involved in EAR in a guinea pig in vivo model of allergic airway inflammation. Animals were sensitized using a single ovalbumin (OVA)/alum injection and challenged with aerosolized OVA on day 14. On day 15, airway resistance was assessed after challenge with OVA or methacholine using the forced oscillation technique, and lung tissue was prepared for histology. The contribution of mast cell mediators was investigated using inhibitors of the main mast cell mediators (his...
Source: Clinical Science - June 25, 2013 Category: Biomedical Science Authors: J P Riley, B Fuchs, L Sjöberg, G P Nilsson, L Karlsson, S Dahlén, N L Rao, M Adner Source Type: research

Differences in Respiratory Syncytial Virus and Influenza Infection in a House Dust Mite Induced Asthma Mouse Model: Consequences for Steroid Sensitivity
A significant number of clinical asthma exacerbations are triggered by viral infection. We aimed to characterise the effect of virus infection in a house dust mite (HDM) mouse model of asthma and assess the effect of oral corticosteroids. HDM alone significantly increased eosinophils, lymphocytes, neutrophils, macrophages and a number of cytokines in bronchoalveolar lavage (BAL), all of which were sensitive to treatment with prednisolone (with the exception of neutrophils). Virus infection also induced cell infiltration and cytokines. Respiratory Syncytial Virus (RSV) infection in HDM-treated animals further increased ...
Source: Clinical Science - June 24, 2013 Category: Biomedical Science Authors: H Mori, N S Parker, D Rodrigues, K Hulland, D Chappell, J S Hincks, H Bright, S M Evans, D J Lamb Source Type: research

Mineralocorticoid Receptors Modulate Vascular Endothelial Function in Human Obesity
Obesity increases linearly with age and is associated with impaired vascular endothelial function and increased risk for cardiovascular disease. Mineralocorticoid receptors (MR) contribute to impaired vascular endothelial function in cardiovascular disease; however, their role in uncomplicated human obesity is unknown. Because plasma aldosterone levels are elevated in obesity and adipocytes may be a source of aldosterone, we hypothesized that MR modulate vascular endothelial function in older adults in an adiposity-dependent manner. To test this hypothesis, we administered MR blockade (Eplerenone; 100 mg/day) for 1 month i...
Source: Clinical Science - June 20, 2013 Category: Biomedical Science Authors: M Hwang, J Yoo, M Luttrell, H Kim, T H. Meade, M English, M S. Segal, D D. Christou Source Type: research

Effects of moderate-intensity aerobic cycling and swim exercise on post-exertional blood pressure in healthy, young untrained and triathlon-trained men and women
Aerobic exercise such as running, walking and cycling is known to elicit a post-exercise hypotensive (PEH) response in both trained and untrained subjects. However, it is not known if swim exercise produces a similar effect in normotensive individuals. The complex acute physiological responses to water immersion suggest swimming may affect blood pressure (BP) differently than other forms of aerobic exercise. We tested the hypothesis that an acute bout of swimming would fail to elicit a post-exercise hypotensive BP response compared to an equivalent bout of stationary cycling, regardless of training state. We studied 11 unt...
Source: Clinical Science - June 14, 2013 Category: Biomedical Science Authors: R A Lakin, C Notarius, S G Thomas, J M Goodman Source Type: research

Impact of PPAR-{alpha} induction on glucose homesostasis in alcohol-fed mice
Conclusions : Our study shows that chronic alcohol consumption induces steatosis, Kuffer cell activation and hepatic insulin resistance in mice. PPAR-α agonist treatment that prevents steatosis and dampens hepatic inflammation also prevents alcohol-induced hepatic insulin resistance. However, Kupffer cell depletion little impacts on OH-induced metabolic disturbances. (Source: Clinical Science)
Source: Clinical Science - June 12, 2013 Category: Biomedical Science Authors: V Lebrun, O Molendi-Coste, N Lanthier, C Sempoux, P D. Cani, N Van Rooijen, P Stärkel, Y Horsmans, I A Leclercq Source Type: research

Relaxin Improves Multiple Markers of Wound Healing and Ameliorates the Disturbed Healing Pattern of the Genetically Diabetic Mice.
Diabetic mice are characterized by a disrupted expression pattern of vascular-endothelial-growth-factor (VEGF), and impaired vasculogenesis during healing. Experimental evidence suggest that relaxin (RLX) can improve several parameters associated with wound healing. Therefore, we investigated the effects of porcine derived relaxin in diabetes-related wound healing defects in genetically diabetic mice. An incisional wound model was produced on the back of female diabetic C57BL/KsJ-m+/+Leptdb (db+/db+) mice and their normal littermates (db+/+m). Animals were treated daily with porcine RLX (25µg mouse/day/s.c.) or its...
Source: Clinical Science - June 6, 2013 Category: Biomedical Science Authors: A Bitto, N Irrera, L Minutoli, M Calò, P Lo Cascio, P Caccia, G Pizzino, G Pallio, A Micali, M Vaccaro, A Saitta, F Squadrito, D Altavilla Source Type: research

Glycine restores glutathione and protects against oxidative stress in vascular tissue from sucrose-fed rats
The attenuation of oxidative stress could be an important mechanism whereby the incidence of vascular complications in the metabolic syndrome may be diminished. This work was undertaken to investigate the mechanism by which glycine, supplemented to the diet of sucrose-fed (SF) rats, modulates glutathione biosynthesis and protects against oxidative stress and altered endothelium-dependent relaxation in isolated aorta. Glycine reduced superoxide anion release in the presence of NADPH, and decreased protein carbonyl and lipid peroxidation. This glycine effect can be due to increased amount of glutathione synthetase which may ...
Source: Clinical Science - June 6, 2013 Category: Biomedical Science Authors: A Ruiz-Ramírez, E Ortiz-Balderas, G Cardozo-Saldaña, E Diaz-Diaz, M El-Hafidi Source Type: research

Interleukin-6 neutralization alleviates pulmonary inflammation in mice exposed to cigarette smoke and poly I:C
Increased systemic and pulmonary levels of interleukin-6 (IL-6) are associated with the severity of exacerbations and decline of lung function in patients with chronic obstructive pulmonary disease (COPD). Whether IL-6 is directly involved or plays a bystander role in the pathophysiology of COPD remains unclear. Here we hypothesized that neutralizing circulating levels of IL-6 would modulate episodes of acute pulmonary inflammation following cigarette smoke (CS) exposure and virus-like challenges. For this purpose, we used a model where C57BL/6 mice were exposed to CS twice daily via a nose-only system, and concomitant per...
Source: Clinical Science - June 5, 2013 Category: Biomedical Science Authors: C Hubeau, J E Kubera, K Masek-Hammerman, C MM Williams Source Type: research

Longitudinal characterisation of a model of chronic allergic lung inflammation in mice using imaging, functional and immunological methods
The present study investigated the role that imaging could have for assessing lung inflammation in a mouse model of a HDM provoked allergic inflammation. Inflammation is usually assessed using terminal procedures such as bronchoalveolar lavage (BAL) and histopathology; however, magnetic resonance imaging (MRI) and computed tomography (CT) methods have the potential to allow longitudinal, repeated study of individual animals. Female BALB/c mice were administered daily either saline, or a solution of mixed HDM proteins sufficient to deliver a dose of 12µg or 25µg total HDM protein ± budesonide (1mg/kg, dur...
Source: Clinical Science - May 31, 2013 Category: Biomedical Science Authors: K Changani, C Pereira, S Young, R Shaw, S P Campbell, K Pindoria, S Jordan, K Wiley, S Bolton, T Nials, M Haase, M Pedrick, R Knowles Source Type: research