bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating C-type natriuretic peptide is increased in orthotopic cardiac transplant recipients and associated with cardiac allograft vasculopathy
Authors: BUCKLEY Martin G. , JENKINS Geraint H. , MITCHELL Andrew G. , YACOUB Magdi H. , SINGER Donald R. J. 
Published: August 2015

C-type natriuretic peptide (CNP) is a potent, endothelial-derived relaxant and growth-inhibitory factor. Accelerated vascular disease is an important cause of morbidity in cardiac transplant recipients, and endothelial dysfunction is now well recognized in patients with cardiovascular disease. CNP has not previously been investigated following cardiac transplantation. We therefore studied plasma levels of immunoreactive CNP in patients early and late after heart transplantation, compared with levels in healthy subjects. We measured CNP in extracted human plasma using an antibody against human CNP-(1–22). CNP levels were significantly elevated in 13 cardiac recipients 2 weeks post-transplant [2.64±0.26 pmol/l (mean±S.E.M.)] compared with those in the normal healthy subjects (0.62±0.04 pmol/l; n = 20, P < 0.001). Plasma levels of CNP were also significantly elevated in a second group of established cardiac transplant recipients (1.15±0.07 pmol/l; n = 46) studied 1–13 years post-transplant when compared with the healthy subjects (P < 0.001). In the group studied later after transplantation, CNP levels were significantly associated with systolic blood pressure (P < 0.05) and were higher in patients with angiographic post-transplant coronary artery disease (P = 0.032). In conclusion, these findings clearly demonstrate that CNP is elevated soon after cardiac transplantation and remains raised in patients even several years post-transplant. CNP may be important as a circulating or local hormone involved in vascular contractile function and in the pathophysiology of cardiac allograft vasculopathy following heart transplantation.
Non-invasive quantification of liver perfusion with dynamic computed tomography and a dual-input one-compartmental model
Authors: MATERNE Roland , VAN BEERS Bernard E. , SMITH Anne M. , LECONTE Isabelle , JAMART Jacques , DEHOUX Jean-Paul , KEYEUX André , HORSMANS Yves 
Published: August 2015

Various liver diseases lead to significant alterations of the hepatic microcirculation. Therefore, quantification of hepatic perfusion has the potential to improve the assessment and management of liver diseases. Most methods used to quantify liver perfusion are invasive or controversial. This paper describes and validates a non-invasive method for the quantification of liver perfusion using computed tomography (CT). Dynamic single-section CT of the liver was performed after intravenous bolus administration of a low-molecular-mass iodinated contrast agent. Hepatic, aortic and portal-venous time—density curves were fitted with a dual-input one-compartmental model to calculate liver perfusion. Validation studies consisted of simultaneous measurements of hepatic perfusion with CT and with radiolabelled microspheres in rabbits at rest and after adenosine infusion. The feasibility and reproducibility of the CT method in humans was assessed by three observers in 10 patients without liver disease. In rabbits, significant correlations were observed between perfusion measurements obtained with CT and with microspheres (r = 0.92 for total liver perfusion, r = 0.81 for arterial perfusion and r = 0.85 for portal perfusion). In patients, total liver plasma perfusion measured with CT was 112±28 ml·min-1·100 ml-1, arterial plasma perfusion was 18±12 ml·min-1·100 ml-1 and portal plasma perfusion was 93±31 ml·min-1·100 ml-1. The measurements obtained by the three observers were not significantly different from each other (P > 0.1). Our results indicate that dynamic CT combined with a dual-input one-compartmental model provides a valid and reliable method for the non-invasive quantification of perfusion in the normal liver.
Elevated circulating leptin levels in arterial hypertension: relationship to arteriovenous overflow and extraction of leptin
Authors: HENRIKSEN Jens H. , HOLST Jens J. , MØLLER Søren , ANDERSEN Ulrik B. , BENDTSEN Flemming , JENSEN Gorm 
Published: August 2015

Leptin, a peptide hormone produced mainly in fat cells, appears to be important for the regulation of metabolism, insulin secretion/sensitivity and body weight. Recently, elevated plasma leptin levels have been reported in patients with arterial hypertension. Because a change in circulating leptin concentrations in such patients could be caused by altered rates of production or disposal, or both, the aim of the present study was to identify regions of leptin overflow into the bloodstream and of leptin extraction. Patients with arterial hypertension (n = 12) and normotensive controls (n = 20) were studied during catheterization with elective blood sampling from different vascular beds (artery, and renal, hepatic, iliac and cubital veins). Plasma leptin was determined by a radioimmunoassay. Patients with hypertension had significantly elevated levels of circulating leptin (12.8 ng/l, compared with 4.1 ng/l in the controls; P < 0.001), and this was also the case when adjusted for body mass index (BMI) [0.435 and 0.167 ng/l per unit BMI (kg/m2) respectively; P < 0.001]. Circulating leptin was directly related to arterial blood pressure (r = 0.38–0.62, P ⩽ 0.05–0.005) and immunoreactive insulin (r = 0.51, P < 0.62), but not to plasma renin activity. A significant renal extraction ratio for leptin was seen in the hypertensive patients, but this was not significantly lower than that in the controls (0.09 compared with 0.16; P = 0.1). The hypertensive patients had a significantly higher hepatic venous/arterial leptin ratio than the controls (1.02 compared with 0.93; P < 0.02), and this ratio was correlated directly with the BMI (r = 0.38, P = 0.05) and immunoreactive insulin (r = 0.43, P < 0.05). In both hypertensive patients and controls there was a significant spillover of leptin into the iliac vein, but not into the cubital vein. In conclusion, the high concentration of circulating leptin in patients with arterial hypertension is probably caused by increased release of leptin from abdominal (especially mesenteric and omental) and gluteal adipose tissue stores, and renal extraction is slightly reduced. Leptin kinetics in arterial hypertension require further investigation.
Effects of the Ca2+ sensitizer EMD 57033 on intracellular Ca2+ in rat ventricular myocytes: relevance to arrhythmogenesis during positive inotropy
Authors: KAWAI Makoto , LEE John A. , ORCHARD Clive H. 
Published: August 2015

We have investigated the effects of the calcium-sensitizing inotropic agent EMD 57033 on Ca2+ handling in intact and skinned rat ventricular myocytes. Intracellular Ca2+ was monitored using fura 2. Myocytes were saponin-skinned, allowing study of sarcoplasmic reticulum (SR) function. In intact myocytes EMD 57033 (1–10 µmol/l) produced a concentration-dependent decrease in the amplitude of the Ca2+ transient and prolonged its declining phase, but had no effect on the rise time. In skinned myocytes, the amplitude of spontaneous Ca2+ release from the SR was decreased by EMD 57033 (5 and 10 µmol/l), although this agent had no significant effect on the frequency of spontaneous Ca2+ release. In the presence of the cross-bridge inhibitor 2,3-butanedione monoxime (5 mmol/l), or in a low bathing Ca2+ concentration (1 mmol/l), EMD 57033 (10 µmol/l) had smaller effects on both the amplitude and time course of the Ca2+ transient in intact cells than in the absence of 2,3-butanedione monoxime or in the presence of 2 and 5 mmol/l Ca2+ respectively. These data suggest that the effects of EMD 57033 on Ca2+ are due to changes in Ca2+ binding to troponin C, secondary to cross-bridge formation. Thus, during positive inotropy, EMD 57033 is unlikely to provoke arrhythmias due to effects on SR Ca2+ handling. In intact cells, its effects on Ca2+ handling would be expected to protect against arrhythmias.
Hyperhomocysteinaemia in young adults is not associated with impaired endothelial function
Authors: HANRATTY Colm G. , MCAULEY Daniel F. , MCGRATH Lawrence T. , YOUNG Ian S. , JOHNSTON G. Dennis 
Published: August 2015

A mild to moderate elevation of the total homocysteine concentration (tHcy) is now recognized as a risk factor for vascular disease. It is also associated with endothelial dysfunction in middle-aged and elderly individuals without overt atherosclerotic vascular disease. This is important, as endothelial dysfunction is a well recognized early and potentially reversible marker of the atherosclerotic process. We investigated whether mild hyperhomocysteinaemia was associated with endothelial dysfunction in otherwise healthy young males. We compared endothelial function, by measuring forearm blood flow, in 17 males with mild hyperhomocysteinaemia (defined as tHcy > 10 µmol/l) and 14 controls with low tHcy (defined as < 5 µmol/l). Forearm blood flow was measured in response to the intra-arterial infusion of acetylcholine (endothelial-dependent response) or sodium nitroprusside (endothelial-independent response). Responses to the vasoactive substances were expressed as the area under the curve of the change in forearm blood flow from baseline. Data are given as mean (95% confidence interval). The two groups were well matched for age, body mass index, pulse rate and blood pressure. tHcy was significantly different between the groups [12.3 (10.4–14.2) µmol/l compared with 4.9 (4.6–5.1) µmol/l; P < 0.001]. Concentrations of vitamin B12 and folate were significantly higher in the control group. There was no difference in basal forearm blood flow between the group with mild hyperhomocysteinaemia and the controls, and both the endothelial-dependent [37.5 (26.2–38.8) and 35.3 (26.1–44.4) arbitrary units respectively] and -independent [26.1 (22.2–29.9) and 25.9 (21.0–30.8) units respectively] responses were not significantly different between the groups. Thus the present study demonstrates that, in healthy adults, mild elevation of tHcy was not associated with impaired endothelial-dependent vasodilation. These data suggest an age effect with regard to homocysteine and endothelial dysfunction. The development of vascular disease in individuals with hyperhomocysteinaemia may only result with higher concentrations or after prolonged exposure.
Role of aminothiols as a component of the plasma antioxidant system and relevance to homocysteine-mediated vascular disease
Authors: MOAT Stuart J. , BONHAM James R. , POWERS Hilary J. 
Published: August 2015

Hyperhomocysteinaemia is considered to be an independent risk factor for vascular disease. Elevated plasma homocysteine may pose an oxidative stress, leading to the development of vascular damage. A component of this effect may be a disturbance of the extracellular aminothiol redox state. The relative contributions of plasma total homocysteine (tHcy) and plasma total cysteine (tCys) to the total antioxidant capacity (TAOC) of plasma was established in subjects with normal and elevated plasma tHcy. A total of 10 subjects with severe hyperhomocysteinaemia (due to inherited metabolic defects), 13 of their heterozygous parents and 72 normal healthy subjects were recruited to the study. The mean plasma tHcy in the patients was 91.8 µmol/l, compared with 13.2 µmol/l in the parents and 14.7 µmol/l in healthy control subjects. Plasma tCys and plasma TAOC were significantly lower in the subjects with severe hyperhomocysteinaemia compared with the parents and healthy control subjects (P < 0.05). In blood samples from subjects with a normal tHcy, a positive correlation was observed between tCys and tHcy (P = 0.0001). In contrast, in blood samples with tHcy ⩾ 20 µmol/l, plasma tCys was negatively correlated with tHcy (P = 0.0001). In samples with tHcy ⩾ 20 µmol/l, tHcy was inversely correlated with TAOC (P = 0.0001), whereas tCys was positively associated with TAOC (P = 0.0001). Multiple regression analysis revealed that tCys was the most important independent determinant of TAOC in the patient and control groups when the effects of tHcy and several factors known to influence TAOC, such as urate, were taken into account. Thus hyperhomocysteinaemia may pose an oxidative stress not only through the direct cytotoxicity of homocysteine, but also from an associated fall in plasma cysteine.
Effects of acute methionine loading and vitamin Con endogenous fibrinolysis, endothelium-dependent vasomotion and platelet aggregation
Authors: LABINJOH Catherine , NEWBY David E. , WILKINSON Ian B. , MEGSON Ian L. , MACCALLUM Helen , MELVILLE Vanessa , BOON Nicholas A. , WEBB David J. 
Published: August 2015

We assessed forearm blood flow and plasma fibrinolytic factors in eight healthy males who received unilateral brachial artery infusions of the endothelium-dependent vasodilator, substance P, and the endothelium-independent vasodilator, sodium nitroprusside. These measurements, together with platelet aggregation studies, were performed on four occasions after double-blind randomized ingestion of placebo, methionine (0.1 mg/kg), vitamin C (2 g) and methionine plus vitamin C. Blood flow and platelet aggregation responses were unaffected by methionine loading. Substance P caused dose-dependent increases in plasma tissue plasminogen activator (t-PA) antigen (from 3.0±0.1 to 4.7±0.4 ng/ml; P &lt; 0.001) and activity (from 1.2±0.2 to 4.2±0.4 i.u./ml; P &lt; 0.001), which were augmented during acute methionine loading (4.7±0.4 to 5.6±0.5 ng/ml and 4.2±0.4 to 5.5±0.9 i.u./ml respectively; P⩽0.05). Moreover, the estimated net release of t-PA was enhanced during methionine loading (two-way ANOVA; P = 0.02), but this was unaffected by vitamin C supplementation. We conclude that, in the absence of alterations in endothelium-dependent vasomotion or platelet aggregation, substance P-induced t-PA release is enhanced following methionine loading. This suggests that the acute endogenous fibrinolytic capacity is augmented during acute hyperhomocysteinaemia in healthy humans via an oxidation-independent mechanism.
Left ventricular performance during prolonged exercise: absence of systolic dysfunction
Authors: GOODMAN Jack M. , McLAUGHLIN Peter R. , LIU Peter P. 
Published: August 2015

We assessed left ventricular systolic and diastolic performance during and after prolonged exercise under controlled conditions in a group of healthy, trained men. Previous studies have examined the effects of prolonged effort on left ventricular function, yet it remains unclear whether or not left ventricular dysfunction (e.g. cardiac fatigue) can be produced under such conditions. We studied 15 healthy men, aged 27±1 years (mean±S.E.M.). Subjects exercised on bicycles at a constant work rate (60% of maximum oxygen uptake per min) for 150 min. Measurements of gas exchange, blood pressure and haematocrit were obtained, concurrent with the assessment of left ventricular function using equilibrium radionuclide angiography, at rest, during exercise (every 30 min) and after 30 min of recovery. Fluid replacement was provided and monitored during the exercise period. The baseline resting and exercise ejection fractions were 66±2% and 78±2% respectively. During exercise, subjects consumed 1816±136 ml of fluid, and the haematocrit had increased at 120 min of exercise (from 47.2%±0.6 to 49.9±0.8%; P < 0.05). There was no change in either systolic or diastolic blood pressure throughout the exercise period, but heart rate drifted upwards from 141±2 beats/min after 30 min to 154±3 beats/min after 150 min (P < 0.05). There was a small decline (8%; P < 0.05) in end-diastolic volume at 150 min. No changes were observed in left ventricular ejection fraction, the pressure/volume ratio or end-systolic volume. After 30 min of sitting in recovery, heart rate was still higher than the pre-exercise value (84±3 compared with 69±2 beats/min; P < 0.05), as were measures of peak filling rate and time to peak filling (P < 0.05). The ejection fraction in the post-exercise recovery period was similar to the pre-exercise value. The results indicate that prolonged exercise of moderate duration may not induce abnormal left ventricular systolic function or cardiac fatigue during exercise.
C-reactive protein: a marker or a player?
Authors: Nyström Thomas 
Published: August 2015

It has been suggested that Type 2 diabetes may, in part, be precipitated or accelerated by an acute-phase reaction as part of the innate immune response, in which large amounts of cytokines are released from adipose tissue, creating a low-grade inflammatory milieu. There is also firm evidence that atherosclerosis is an immune-mediated inflammatory disease. Therefore it is reasonable to imply that low-grade inflammation is an important pathogenetic factor in atherosclerosis and cardiovascular events in patients with Type 2 diabetes. Over the last few years, there have been a lot of promising clinical markers proposed to link inflammation and atherosclerosis. Of these markers, hs-CRP (high-sensitivity C-reactive protein) might be a prognostic marker for further cardiovascular events, although this has been refuted recently. In this issue of Clinical Science, Castoldi and co-workers have demonstrated that, in patients with Type 2 diabetes categorized into low (&lt;1.0 mg/l), medium (1.0–3.0 mg/l) and high (&gt;3.0 mg/l) hs-CRP groups, serum levels of hs-CRP correlated with lipopolysaccharide-stimulated release of interleukin-1β and interleukin-6 in whole blood. This finding may indicate that low-grade inflammatory activity might influence cytokine production in these patients.
Integratable trench MOSFET with ultra‐low specific on‐resistance
Authors: Yin Chao , Wei Jie , Zhou Kun , Luo Xiaorong 
Published: August 2015

A novel integratable metal–oxide–semiconductor field‐effect transistor (MOSFET) with a trench source (TS) and a trench gate (TG) (TS–TG MOSFET) is proposed. The TS and TG cause a strong assistant depletion effect and thus dramatically increase the N‐drift doping concentration (Nd). Moreover, an accumulation layer beside the TG is formed and offers a continuous low‐resistance path in the on‐state. Therefore, the novel MOSFET effectively reduces specific on‐resistance (Ron,sp). The TS–TG MOSFET not only has the merits of low Ron,sp and the easy parallel connection of vertical double‐diffused MOS, but also possesses the advantage of ease of integration like the LDMOS. The breakdown voltage (BV) of 61 V and the Ron,sp of 0.133 mΩ cm2 are obtained for the TS–TG MOSFET, with a significant optimised trade‐off between Ron,sp and BV.
Microfabrication of conical microfunnels for drug delivery applications
Authors: Liu L.W.Y. , Virdee B.S. , Inal J. , Steer M.B. 
Published: August 2015

A cost‐effective fabrication methodology for the mass production of conical microfunnels for drug delivery applications is presented. The fabrication methodology originates from a technique previously used for fabricating suspended or hollow microstructures. The process comprises six stages: in stage 1, a UV‐opaque resin substrate is formed by mixing photocurable SU‐8 with a UV‐opaque impurity; in stage 2, an embossing stamp with an array of microrods is fabricated; in stage 3, the upper surface of the UV‐opaque resin substrate (from the first stage) is mechanically deformed by stamping with the embossing stamp from stage 2; in stage 4, the regions in which microfunnels are photolithographically defined are selectively exposed to UV light; in stage 5, the wafer from stage 4 is subjected to heat and then developed in 1‐methoxy‐2‐propanol acetate; finally, a hole on the tip of each microfunnel is formed by dry etching with oxygen plasma. The sharpness of the funnel tips can be flexibly adjusted by changing the stroke speed of the stamping in stage 3. The overall process can be carried out photolithographically with conventional photolithographic equipment. Using the proposed fabrication methodology, a matrix of polymeric microfunnels tapering from the base measuring 300 μm to the tip measuring 50 μm over a funnel height of 100 μm has been fabricated. Each fabricated microfunnel features a wide base and a sharp tip so that it has sufficient mechanical strength and sharpness to pierce the human skin. The conical geometry used in this study had a volume in excess of 24.4 nl.
Al2O3 and Sn/Al2O3 nanowires: fabrication and characterisation
Authors: Shaban Mohamed , Ali Mona , Abdel‐Hady Kamal , Hamdy Hany 
Published: August 2015

Self‐ordered anodised aluminium oxide membranes can be used as a base for the growth of different nanoarrays. In this reported work, an efficient and effective method is implemented to fabricate highly ordered alumina nanowires (ANWs) covered with a uniform shell of 12 ± 2 nm Sn nanoparticles (Sn/ANWs). A two‐step anodisation process followed by a selective etching process was used to prepare highly ordered ANWs with diameters smaller than 36 nm. The thermal evaporation technique was used to ensure the deposition of a Sn nanoshell on the fabricated nanowires. The fabricated nanostructures were characterised by energy‐dispersive X‐ray spectroscopy, X‐ray diffraction, field emission‐scanning electron microscopy and an ultraviolet–visible–near‐infrared spectrophotometer. Analysis of the scanning electron microscopy images showed that the etching rate is 0.73 nm/min and ANWs are obtained after etching the membrane for 110 min. The measured reflection spectra revealed that Sn/ANWs exhibit a redshift of the UV absorption band relative to the ANWs and a reflectance of nearly 100% in the near‐infrared region. For optical comparison, glass slides were coated with Sn under the same conditions for 90 and 120 s. The reflection spectrum of the 120 s Sn‐coated glass slide shows three modes at 210, 296 and 700 nm because of the excitation and interference of plasmonic waves.
Transient Elastography to Assess the Cervical Ripening during Pregnancy: A Preliminary Study
Authors: Peralta Laura , Molina Francisca , Melchor Juan , Gómez Luisa , Massó Paloma , Florido Jesús , Rus Guillermo 
Published: August 2015

Abstract
Purpose To explore the feasibility of transient elastography (TE) to quantify cervical stiffness changes during normal pregnancy and its spatial variability.
Materials and Methods TE was used to quantify the cervical stiffness in four anatomical regions. 42 women between 17 and 43 years of age and at 6 – 41 weeks of gestation were studied. The stiffness was related to gestational age at the time of examination, interval from ultrasound examination to delivery and cervical length to evaluate the potential of TE to assess cervical ripening. In addition, a sensitivity analysis based on Cronbach’s alpha coefficient was carried out to assess the concordance between inter/intra-operator measurements.
Results There were significant correlations between cervical stiffness measured in the four regions with gestational age and the remaining time for delivery. Results confirm stiffness variability within the cervix. No significant association was found between cervical length and stiffness in the four ROIs. Associations between gestational age and remaining time for delivery with cervical length present weaker correlations than with cervical stiffness. The external part of the cervix was significantly softer than the internal one, and these stiffness values vary significantly in the anterior compared to the posterior cervix. The measurements taken by the same and by two different observers for different regions in the cervix were reliable and reproducible.
Conclusion It is feasible to objectively quantify the decrease of cervical stiffness correlated to gestational age. Transient elastography is a valuable promising tool to provide additional information on the process of cervical effacement to that obtained from digital examination and conventional ultrasound. Further studies are needed to assess the feasibility of the technique in obstetric clinical applications, such as prediction of preterm birth or success in labor induction.