Impact of meal fatty acid composition on postprandial lipaemia, vascular function and blood pressure in postmenopausal women

Cardiovascular diseases (CVD) are the leading cause of death in women globally, with aging associated with progressive endothelial dysfunction and increased CVD risk. Natural menopause is characterised by raised non-fasting triacylglycerol (TAG) concentrations and impairment of vascular function compared with premenopausal women. However, the mechanisms underlying the increased CVD risk after women have transitioned through the menopause are unclear. Dietary fat is an important modifiable risk factor relating to both postprandial lipaemia and vascular reactivity. Meals rich in saturated (SFA) and monounsaturated fatty acids (MUFA) are often associated with greater postprandial TAG responses compared with those containing n-6 polyunsaturated fatty acids (PUFA), but studies comparing their effects on vascular function during the postprandial phase are limited, particularly in postmenopausal women. This review aimed to evaluate the acute effects of test meals rich in SFA, MUFA and n-6 PUFA on postprandial lipaemia, vascular reactivity and other CVD risk factors in postmenopausal women. The systematic literature search identified 778 publications. The impact of fat-rich meals on postprandial lipaemia was reported in seven relevant studies, of which meal fat composition was compared in one study described by three papers. An additional study determined the impact of a high fat meal on vascular reactivity. Although moderately consistent evidence suggests detrimental effects of high fat meals on postprandial lipaemia in postmenopausal (than premenopausal) women, there is insufficient evidence to establish the impact of meals of differing fat composition. Furthermore, there is no robust evidence to conclude the effect of meal fatty acids on vascular function or blood pressure. In conclusion, there is an urgent requirement for suitably powered robust randomised controlled trials to investigate the impact of meal fat composition on postprandial novel and established CVD risk markers in postmenopausal women, an understudied population at increased cardiometabolic risk

The Functions of Auxilin and Rab11 in Drosophila Suggest That the Fundamental Role of Ligand Endocytosis in Notch Signaling Cells Is Not Recycling

Notch signaling requires ligand internalization by the signal sending cells. Two endocytic proteins, epsin and auxilin, are essential for ligand internalization and signaling. Epsin promotes clathrin-coated vesicle formation, and auxilin uncoats clathrin from newly internalized vesicles. Two hypotheses have been advanced to explain the requirement for ligand endocytosis. One idea is that after ligand/receptor binding, ligand endocytosis leads to receptor activation by pulling on the receptor, which either exposes a cleavage site on the extracellular domain, or dissociates two receptor subunits. Alternatively, ligand internalization prior to receptor binding, followed by trafficking through an endosomal pathway and recycling to the plasma membrane may enable ligand activation. Activation could mean ligand modification or ligand transcytosis to a membrane environment conducive to signaling. A key piece of evidence supporting the recycling model is the requirement in signaling cells for Rab11, which encodes a GTPase critical for endosomal recycling. Here, we use Drosophila Rab11 and auxilin mutants to test the ligand recycling hypothesis. First, we find that Rab11 is dispensable for several Notch signaling events in the eye disc. Second, we find that Drosophila female germline cells, the one cell type known to signal without clathrin, also do not require auxilin to signal. Third, we find that much of the requirement for auxilin in Notch signaling was bypassed by overexpression of both clathrin heavy chain and epsin. Thus, the main role of auxilin in Notch signaling is not to produce uncoated ligand-containing vesicles, but to maintain the pool of free clathrin. Taken together, these results argue strongly that at least in some cell types, the primary function of Notch ligand endocytosis is not for ligand recycling

Endothelial NOS (NOS3) impairs myocardial function in developing sepsis

Endothelial nitric oxide synthase (NOS)3-derived nitric oxide (NO) modulates inotropic response and diastolic interval for optimal cardiac performance under non-inflammatory conditions. In sepsis, excessive NO production plays a key role in severe hypotension and myocardial dysfunction. We aimed to determine the role of NOS3 on myocardial performance, NO production, and time course of sepsis development. NOS3(−/−) and C57BL/6 wildtype mice were rendered septic by cecum ligation and puncture (CLP). Cardiac function was analyzed by serial echocardiography, in vivo pressure and isolated heart measurements. Cardiac output (CO) increased to 160 % of baseline at 10 h after sepsis induction followed by a decline to 63 % of baseline after 18 h in wildtype mice. CO was unaltered in septic NOS3(−/−) mice. Despite the hyperdynamic state, cardiac function and mean arterial pressure were impaired in septic wildtype as early as 6 h post CLP. At 12 h, cardiac function in septic wildtype was refractory to catecholamines in vivo and respective isolated hearts showed impaired pressure development and limited coronary flow reserve. Hemodynamics remained stable in NOS3(−/−) mice leading to significant survival benefit. Unselective NOS inhibition in septic NOS3(−/−) mice diminished this survival benefit. Plasma NO(x)- and local myocardial NO(x)- and NO levels (via NO spin trapping) demonstrated enhanced NO(x)- and bioactive NO levels in septic wildtype as compared to NOS3(−/−) mice. Significant contribution by inducible NOS (NOS2) during this early phase of sepsis was excluded. Our data suggest that NOS3 relevantly contributes to bioactive NO pool in developing sepsis resulting in impaired cardiac contractility. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00395-013-0330-8) contains supplementary material, which is available to authorized users

Inter-scan variability of coronary artery calcium scoring assessed on 64-multidetector computed tomography vs. dual-source computed tomography: a head-to-head comparison

Aims Coronary artery calcium (CAC) scoring has emerged as a tool for risk stratification and potentially for monitoring response to risk factor modification. Therefore, repeat measurements should provide robust results and low inter-scanner variability for allowing meaningful comparison. The purpose of this study was to investigate inter-scanner variability of CAC for Agatston, volume, and mass scores by head-to-head comparison using two different cardiac computed tomography scanners: 64-detector multislice CT (MSCT) and 64-slice dual-source CT (DSCT). Methods and results Thirty patients underwent CAC measurements on both 64-MSCT (GE LightSpeed XT scanner: 120 kV, 70 mAs, 2.5 mm slices) and 64-DSCT (Siemens Somatom Definition: 120 kV, 80 mAs, 3 mm slices) within <100 days (0-97). Retrospective intra-scan comparison revealed an excellent correlation. The excellent intra-scan (inter-observer) agreement was documented by narrow limits of agreement and a correlation coefficient of variation (COV) of r ≥ 0.99 (P < 0.001) for all CAC scores with a low COV for both scanners (64-MSCT/64-DSCT), i.e. Agatston (2.0/2.1%), mass (3.0/2.0%), and volume (4.7/3.9%). Inter-scanner comparison revealed larger Bland-Altman (BA) limits of agreement, despite high correlation (r ≥ 0.97) for all scores, with COV at 15.1, 21.6, and 44.9% for Agatston, mass, and volume scores. The largest BA limits were observed for volume scores (−1552.8 to 574.2), which was massively improved (−241.0 to 300.4, COV 11.5%) after reanalysing the 64-DSCT scans (Siemens) with GE software/workstation (while Siemens software/workstation does not allow cross-vendor analysis). Phantom measurements confirmed overestimation of volume scores by ‘syngo Ca-Scoring' (Siemens) software which should therefore be reviewed (vendor has been notified). Conclusion Intra- and inter-scan agreement of CAC measurement in a given data set is excellent. Inter-scanner variability is reasonable, particularly for Agatston units in the clinically most relevant range <1000. The use of different software solutions has a greater influence particularly on volume scores than the use of different scanner type

Preparation and characterization of cotton fabrics with antimicrobial properties through the application of chitosan/silver-zeolite film

The development of antimicrobial cotton fabrics using chitosan/silver-zeolite film has been investigated in the present work. The film was applied to 100% cotton fabric using a common pad-dry-cure technique and citric acid was used as crosslinking agent. The resulting fabrics were characterized through infrared spectroscopy (FTIR), contact angle and scanning electron microscopy with X-ray microanalysis (SEM/EDS). The antimicrobial activity of the fabrics was assessed through the viable-cell counting method and the materials showed activity against S. aureus and T. rubrum. The textile performance of the fabrics was analysed regarding their characteristics of hydrophilicity and breathability. The finishing did not change the hydrophilic behaviour of the material. Although the permeability to air has reduced 20%, the permeability to water vapour remained practically unchanged. Therefore, the results suggested that the process approach of applying chitosan/silver-zeolite film is recommended to produce textiles with antibacterial properties.CNPq-Brazil (Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brazil/National Council of Scientific and Technological Development – Brazil) for the doctoral scholarship (233550/2014-3). This work is also financed by FEDER funds through the Competitivity Factors Operational Programme – COMPETE and by national funds through FCT – Foundation for Science and Technology within the scope of the project POCI-01-0145-FEDER-007136. This research was partially supported by the Strategic Funding UID/Multi/04423/2013 through national funds provided by FCT - Foundation for Science and Technology and European Regional Development Fund (ERDF), in the framework of the program PT2020.info:eu-repo/semantics/publishedVersio

Modular titanium alloy neck adapter failures in hip replacement - failure mode analysis and influence of implant material

<p>Abstract</p> <p>Background</p> <p>Modular neck adapters for hip arthroplasty stems allow the surgeon to modify CCD angle, offset and femoral anteversion intraoperatively. Fretting or crevice corrosion may lead to failure of such a modular device due to high loads or surface contamination inside the modular coupling. Unfortunately we have experienced such a failure of implants and now report our clinical experience with the failures in order to advance orthopaedic material research and joint replacement surgery.</p> <p>The failed neck adapters were implanted between August 2004 and November 2006 a total of about 5000 devices. After this period, the titanium neck adapters were replaced by adapters out of cobalt-chromium. Until the end of 2008 in total 1.4% (n = 68) of the implanted titanium alloy neck adapters failed with an average time of 2.0 years (0.7 to 4.0 years) postoperatively. All, but one, patients were male, their average age being 57.4 years (36 to 75 years) and the average weight 102.3 kg (75 to 130 kg). The failures of neck adapters were divided into 66% with small CCD of 130° and 60% with head lengths of L or larger. Assuming an average time to failure of 2.8 years, the cumulative failure rate was calculated with 2.4%.</p> <p>Methods</p> <p>A series of adapter failures of titanium alloy modular neck adapters in combination with a titanium alloy modular short hip stem was investigated. For patients having received this particular implant combination risk factors were identified which were associated with the occurence of implant failure. A Kaplan-Meier survival-failure-analysis was conducted. The retrieved implants were analysed using microscopic and chemical methods. Modes of failure were simulated in biomechanical tests. Comparative tests included modular neck adapters made of titanium alloy and cobalt chrome alloy material.</p> <p>Results</p> <p>Retrieval examinations and biomechanical simulation revealed that primary micromotions initiated fretting within the modular tapered neck connection. A continuous abrasion and repassivation process with a subsequent cold welding at the titanium alloy modular interface. Surface layers of 10 - 30 μm titanium oxide were observed. Surface cracks caused by fretting or fretting corrosion finally lead to fatigue fracture of the titanium alloy modular neck adapters. Neck adapters made of cobalt chrome alloy show significantly reduced micromotions especially in case of contaminated cone connection. With a cobalt-chromium neck the micromotions can be reduced by a factor of 3 compared to the titanium neck. The incidence of fretting corrosion was also substantially lower with the cobalt-chromium neck configuration.</p> <p>Conclusions</p> <p>Failure of modular titanium alloy neck adapters can be initiated by surface micromotions due to surface contamination or highly loaded implant components. In the present study, the patients at risk were men with an average weight over 100 kg. Modular cobalt chrome neck adapters provide higher safety compared to titanium alloy material.</p

Bullet-induced synovitis as a cause of secondary osteoarthritis of the hip joint: A case report and review of literature

<p>Abstract</p> <p>Background</p> <p>With increasing prevalence of gunshot injuries we are seeing more patients with retained bullet fragments lodged in their bodies. Embedded lead bullets are usually considered inert after their kinetic energy has dissipated hence these are not removed routinely. However, exposure of any foreign body to synovial fluid may lead to rapid degradation and hence result in systemic absorption, causing local and systemic symptoms. We present the case of a thirty year old man who came to our out patient department with a history of progressive, severe hip pain ten years after a gun shot injury to his right hip.</p> <p>Conclusion</p> <p>The common belief that intraarticular bullets should not be removed has no benefit and may result in unwanted long term complications.</p

D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile

Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients

The Functions of Auxilin and Rab11 in Drosophila Suggest That the Fundamental Role of Ligand Endocytosis in Notch Signaling Cells Is Not Recycling

Notch signaling requires ligand internalization by the signal sending cells. Two endocytic proteins, epsin and auxilin, are essential for ligand internalization and signaling. Epsin promotes clathrin-coated vesicle formation, and auxilin uncoats clathrin from newly internalized vesicles. Two hypotheses have been advanced to explain the requirement for ligand endocytosis. One idea is that after ligand/receptor binding, ligand endocytosis leads to receptor activation by pulling on the receptor, which either exposes a cleavage site on the extracellular domain, or dissociates two receptor subunits. Alternatively, ligand internalization prior to receptor binding, followed by trafficking through an endosomal pathway and recycling to the plasma membrane may enable ligand activation. Activation could mean ligand modification or ligand transcytosis to a membrane environment conducive to signaling. A key piece of evidence supporting the recycling model is the requirement in signaling cells for Rab11, which encodes a GTPase critical for endosomal recycling. Here, we use Drosophila Rab11 and auxilin mutants to test the ligand recycling hypothesis. First, we find that Rab11 is dispensable for several Notch signaling events in the eye disc. Second, we find that Drosophila female germline cells, the one cell type known to signal without clathrin, also do not require auxilin to signal. Third, we find that much of the requirement for auxilin in Notch signaling was bypassed by overexpression of both clathrin heavy chain and epsin. Thus, the main role of auxilin in Notch signaling is not to produce uncoated ligand-containing vesicles, but to maintain the pool of free clathrin. Taken together, these results argue strongly that at least in some cell types, the primary function of Notch ligand endocytosis is not for ligand recycling