bluuebunny/crossref_metadata_2025 huggingface dataset:
Phosphoramidon treatment improves the consequences of chagasic heart disease in mice
Authors: JELICKS Linda A. , CHANDRA Madluhika , SHTUTIN Vitaliy , PETKOVA Stefka B. , TANG Baiyu , CHRIST George J. , FACTOR Stephen M. , WITTNER Murray , HUANG Huan , DOUGLAS Stephen A. , WEISS Louis M. , D'ORLEANS-JUSTE Pedro , SHIRANI Jamshid , TANOWITZ Herbert B.
Published: August 2015

Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, is an important cause of cardiomyopathy. Microvascular spasm and matrix dissolution, modulated by endothelin-1 (ET-1), is implicated in the pathogenesis of chagasic heart disease. To further elucidate the role of ET-1 in murine chagasic heart disease, C57BL/6×129sv mice were infected with T. cruzi (103 trypomastigotes of the Brazil strain). These mice are resistant to death during the acute phase but progress to chronic cardiomyopathy. Infected mice were compared with infected mice treated with phosphoramidon, a non-specific metalloprotease inhibitor that is also a potent inhibitor of endothelin-converting enzyme, at a dose of 10mg/kg. Mice were treated with phosphoramidon for the initial 15 days post infection (PI). All mice were evaluated 200 days PI. Examination of infected, untreated mice revealed marked inflammation, vasculitis and fibrosis. The hearts of infected treated mice had significantly less pathology. Cardiac magnetic resonance imaging (MRI) revealed that right ventricular internal diameter (RVID) was significantly greater (P<0.05) in the infected untreated group (2.9±0.22mm) as compared with the infected treated group (1.73±0.35mm). In another experiment phosphoramidon treatment was also tested in CD1 mice, which have a high mortality during the acute phase of infection with 5×104 trypomastigotes of the Brazil strain. One group of CD1 mice was untreated while the other group received phosphoramidon for the initial 15 days PI. The mortality rate in untreated mice was 70% by day 35 PI, while all treated infected mice lived. The parasitemia in both groups was similar. The cardiac pathology was more severe in untreated mice. MRI revealed the RVID to be significantly greater in the untreated infected group as compared with the phosphoramidon-treated infected mice (2.74±0.03mm versus 1.64±0.4mm P<0.05). Transthoracic echocardiography revealed that the percentage fractional shortening was reduced in infected CD1 mice but not in those infected mice treated with phosphoramidon. There was no effect of phosphoramidon in uninfected mice. Phosphoramidon (100µg/ml) had no effect on parasites in vitro. These data are consistent with the hypothesis that ET-1 contributes to the pathogenesis of murine chagasic cardiomyopathy and suggests that interventions targeting ET-1 would improve the outcome in chagasic heart disease.
Effects of increased pulmonary flow on the expression of endothelial nitric oxide synthase and endothelin-1 in the rat
Authors: DAI Zen-Kong , TAN Mian-Shin , CHAI Chee-Yin , CHEN Ing-Jun , JENG Arco Y. , WU Jiunn-Ren
Published: August 2015

The purpose of the study was to assess whether increased pulmonary flow and subsequent development of pulmonary vascular remodelling could alter the expression of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) in the rat lung. Nine 42-day-old Wistar rats underwent abdominal aortocaval shunt to increase pulmonary blood flow for 12 weeks. The shunt resulted in significant medial hypertrophy of pulmonary artery without significant alterations in pulmonary or systemic blood pressure. Using competitive reverse transcription–PCR, significant increases in the preproET-1 mRNA expression and eNOS mRNA expression in the lungs of rats with abdominal aortocaval shunt were detected. Increased eNOS protein in the lung of shunt rats was also found by Western blot analysis. However, the plasma ET-1 concentration in the pulmonary artery (sham: 5±0.7pg/ml; shunt: 6±0.8pg/ml) or the lung ET-1 content (sham: 218±41ng/g protein; shunt: 224±40ng/g protein) was unchanged. There was an elevated immunohistochemical expression of eNOS, but not ET-1, in the pulmonary vascular endothelium in rats with the shunt. These results suggest that eNOS and ET-1 may be involved in remodelling prior to the development of pulmonary hypertension.
Oestrogen protects against ischaemic acute renal failure in rats by suppressing renal endothelin-1 overproduction
Authors: TAKAOKA Masanori , YUBA Mikihiro , FUJII Toshihide , OHKITA Mamoru , MATSUMURA Yasuo
Published: August 2015

We investigated whether the treatment with 17β-oestradiol has renal protective effects in male rats with ischaemic acute renal failure (ARF). We also examined if the effect of 17β-oestradiol is accompanied by suppression of enhanced endothelin-1 production in postischaemic kidneys. Ischaemic ARF was induced by clamping the left renal artery and vein for 45min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function parameters such as blood urea nitrogen, plasma creatinine and creatinine clearance were measured to test the effectiveness of the steroid hormone. Renal function in ARF rats markedly decreased 24h after reperfusion. The ischaemia/reperfusion-induced renal dysfunction was dose-dependently improved by pretreatment with 17β-oestradiol (20 or 100µg/kg, intravenously). Histopathological examination of the kidney of untreated ARF rats revealed severe lesions, such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion, all of which were markedly improved by the higher dose of 17β-oestradiol. In addition, endothelin-1 content in the kidney after the ischaemia/reperfusion increased significantly by approx. 2-fold over sham-operated rats, and this elevation was dose-dependently suppressed by the 17β-oestradiol treatment. These results suggest that oestrogen exhibits protective effects against renal dysfunction and tissue injury induced by ischaemia/reperfusion, possibly through the suppression of endothelin-1 overproduction in postischaemic kidneys.
Effect of aging on gene expression rates of endothelin-1 and endothelin-2/vasoactive intestinal contractor in ethanol-induced gastric mucosal injury of the mouse
Authors: KOZAKAI Takaharu , ZHAO Hong , SAKATE Mitsue , MASUO Yoshinori , UCHIDE Tsuyoshi , SAIDA Kaname
Published: August 2015

To elucidate the physiological roles of endothelin-1 (ET-1) and endothelin-2 (ET-2)/vasoactive intestinal contractor (VIC) in gastric injury of mice, we measured the gene expression rates of ET-1 and ET-2/VIC in gastric injury induced by ethanol in young (8 weeks) and old (>33 weeks) mice. Mice that were fasted for 24h were injected with absolute ethanol intragastrically and killed after 1 or 4h of ethanol exposure. The size of the gastric lesions increased gradually after ethanol exposure and was at its greatest after 4 h, in both young and old mice. The gene expression of ET-1 tended to increase after 1h and to decrease by 4h of ethanol exposure in both young and old mice. However, the gene expression of ET-2/VIC in young mice increased significantly after 1 and 4h of ethanol exposure, whereas the gene expression of ET-2/VIC in the old mice did not change after ethanol exposure. Based on these results, we conclude that aging influences the gene expression of ET-2/VIC but not lesion size or gene expression of ET-1 in ethanol-induced gastric injury in the mouse. We therefore suggest that regulation of gene expression of these two genes differs during the course of aging.
(Ab)normal saline and physiological Hartmann's solution: a randomized double-blind crossover study
Authors: REID Fiona , LOBO Dileep N. , WILLIAMS Robert N. , ROWLANDS Brian J. , ALLISON Simon P.
Published: August 2015

In this double-blind crossover study, the effects of bolus infusions of 0.9% saline (NaCl) and Hartmann's solution on serum albumin, haematocrit and serum and urinary biochemistry were compared in healthy subjects. Nine young adult male volunteers received 2-litre intravenous infusions of 0.9% saline and Hartmann's solution on separate occasions, in random order, each over 1h. Body weight, haematocrit and serum biochemistry were measured pre-infusion and at 1h intervals for 6h. Biochemical analysis was performed on pooled post-infusion urine. Blood and plasma volume expansion, estimated by dilutional effects on haematocrit and serum albumin, were greater and more sustained after saline than after Hartmann's solution (P<0.01). At 6h, body weight measurements suggested that 56% of the infused saline was retained, in contrast with only 30% of the Hartmann's solution. Subjects voided more urine (median: 1000 compared with 450ml) of higher sodium content (median: 122 compared with 73mmol) after Hartmann's than after saline (both P = 0.049), despite the greater sodium content of the latter. The time to first micturition was less after Hartmann's than after saline (median: 70 compared with 185min; P = 0.008). There were no significant differences between the effects of the two solutions on serum sodium, potassium, urea or osmolality. After saline, all subjects developed hyperchloraemia (>105mmol/l), which was sustained for >6h, while serum chloride concentrations remained normal after Hartmann's (P<0.001 for difference between infusions). Serum bicarbonate concentration was significantly lower after saline than after Hartmann's (P = 0.008). Thus excretion of both water and sodium is slower after a 2-litre intravenous bolus of 0.9% saline than after Hartmann's solution, due possibly to the more physiological [Na+]/[Cl-] ratio in Hartmann's solution (1.18:1) than in saline (1:1) and to the hyperchloraemia caused by saline.
Chemokines in the pathogenesis of liver disease: so many players with poorly defined roles
Authors: SIMPSON Kenneth J. , HENDERSON Neil C. , BONE-LARSON Cynthia L. , LUKACS Nicholas W. , HOGABOAM Cory M. , KUNKEL Steven L.
Published: August 2015

Many new chemokines have been described in recent years, resulting in a new classification of these chemoattractant proteins. The characterization of the biological functions of most chemokines relates to their ability to induce chemotaxis in circulating inflammatory cells. However, it is now clear that chemokines have a much wider biological role, including angiogenesis, carcinogenesis and involvement in the pathogenesis of HIV infection. Our understanding of the role of chemokines in the pathogenesis of disorders of the lungs and brain outstrips that with regard to disorders of the liver. An increased understanding of the role of chemokines in the pathogenesis of liver disease may lead to the development of novel therapies for hepatic disease.
Peripheral blood leucocyte functional responses to acute eccentric exercise in humans are influenced by systemic stress, but not by exercise-induced muscle damage
Authors: SAXTON John M. , CLAXTON David , WINTER Edward , POCKLEY A. Graham
Published: August 2015

The effects of comparable lower-limb eccentric exercise that induces high (bench-stepping; STEP) and low (repeated eccentric muscle action; ECC) systemic stress on neutrophil and monocyte phagocytic and respiratory burst activity, and activation antigen (CD11b, CD66b, CD64) expression, were compared in recreationally active subjects (20–37 years old). Leucocyte responses were determined before and 4, 24, 48 and 72h after exercise using whole-blood flow cytometry. Serum creatine kinase (CK) activity and perceived muscle soreness [delayed-onset muscle soreness (DOMS)] were assessed at the same time points up to 96 h; as a control, measurements were taken during 5 days of rest. DOMS in quadriceps and contralateral triceps surae peaked 24–72h after STEP (P<0.05) and 48–72h after ECC (P<0.05), whereas serum CK activity (mean±S.E.M.) was only higher than baseline after ECC (15123±3488 at 96h compared with 115±29 units·l-1 pre-exercise; P<0.01). The total leucocyte count increased from (5.4±0.4)×109·l-1 and (5.7±0.5)×109·l-1 at baseline to (7.6±0.5)×109·l-1 and (7.0±0.5)×109·l-1 at 4h after STEP and ECC respectively; this was largely attributable to changes in the neutrophil count (P<0.05). The proportion of neutrophils undergoing phagocytosis and respiratory burst was unchanged 4h after ECC and STEP, which, given the increase in neutrophil count after exercise, would suggest an overall improvement in systemic neutrophil microbicidal potential. The intensity of neutrophil (P = 0.01) and monocyte (P<0.05) phagocytosis and neutrophil respiratory burst responses (P<0.05) was only increased 24h after STEP, whereas no changes in these measures were observed after ECC. Activation antigen expression was unchanged in all groups. These findings suggest that systemic stress evoked during an acute bout of eccentric exercise has a greater influence on subsequent leucocyte functional responses than the degree of muscle damage induced.
Effects of angiotensin-converting enzyme inhibition and calcium channel blockade on cardiac apoptosis in rats with 2K1C (two-kidney/one-clip) renovascular hypertension
Authors: THÖNE-REINEKE Christa , OLIVIER Jan , GODES Michael , ZART Rüdiger , GEORGE Ines , BAUER Christian , NEUMAYER Hans-Helmut , HOCHER Berthold
Published: August 2015

Apoptosis plays a role in the regulation of heart mass and architecture, and might contribute to the cardiac remodelling seen in renovascular hypertension. It is not known whether the beneficial effects of angiotensin-converting enzyme (ACE) inhibition or calcium channel blockade on cardiac remodelling are linked to the modulation of apoptosis. To test this hypothesis, we established four groups of rats: (i) sham-operated controls, (ii) a group that underwent the two-kidney/one-clip (2K1C) procedure, (iii) a group with 2K1C treated for 12 weeks with quinapril (6mg·day-1·kg-1), and (iv) a group with 2K1C treated for 12 weeks with diltiazem (24mg·day-1·kg-1). Treatment started 2 weeks after clipping. Systolic blood pressure was reduced to a similar extent by quinapril and diltiazem (2K1C, 223±19mmHg; 2K1C+quinapril, 149±15mmHg; 2K1C+diltiazem, 160±40mmHg; both P<0.01 compared with 2K1C alone). Left ventricular weight, interstitial fibrosis and perivascular fibrosis were reduced significantly by both drugs. The apoptotic index (apoptotic cells/total cell number) was increased 21.6-fold (P<0.01) after quinapril treatment as compared with the 2K1C group, but was not affected by calcium channel blockade. In conclusion, our study demonstrates that ACE inhibition, in contrast with calcium channel blockade, may cause regression of cardiac hypertrophy/remodelling in 2K1C renovascular hypertensive rats through enhanced apoptosis.
Urinary microalbumin/creatinine ratios: reference range in uncomplicated pregnancy
Authors: WAUGH Jason , BELL Stephen C. , KILBY Mark D. , LAMBERT Paul C. , BLACKWELL Claire N. , SHENNAN Andrew , HALLIGAN Aidan
Published: August 2015

During uncomplicated pregnancy, the development of proteinuria is accepted as a poor prognostic sign and is associated with increasing maternal and perinatal mortality and morbidity. Physiological proteinuria increases with increasing gestation and one of its largest constituents is albumin. The reference range for the (micro)albumin/creatinine ratio (ACR) has not been described for normal pregnancy. This prospective cross-sectional study describes the gestation-specific 95% reference ranges for urinary microalbumin concentration, creatinine concentration and ACR in uncomplicated pregnancy. There is a significant increase (P = 0.016) in the ACR in the third trimester. The mean difference is 0.091mg of albumin/mmol of creatinine (95% confidence interval, 0.014–0.168). Our results describe the first well-defined gestation-specific 95% reference range for a point-of-care measurement of the ACR. These data are essential if such testing is to be employed in antenatal care.
Changes in the transthoracic impedance signal predict the outcome of a 70° head-up tilt test
Authors: BELLARD Elisabeth , FORTRAT Jacques-Olivier , SCHANG Daniel , DUPUIS Jean-Marc , VICTOR Jacques , LEFTHÉRIOTIS Georges
Published: August 2015

We determined whether early changes in central haemodynamics, as determined by transthoracic impedance, induced by a 70° head-up tilt (HUT) test could predict syncope. Heart rate, arterial blood pressure and central haemodynamics [pre-ejection period and rapid left ventricular ejection time (T1), slow ejection time (T2) and dZ/dtmax (where Z is thoracic impedance), assessed by the transthoracic impedance technique], were recorded during supine rest and during a 45min 70° HUT test in 68 patients (40±2 years) with a history of unexplained recurrent syncope. We found that 38 patients (42±3 years) had a symptomatic outcome to 70° HUT (fainters) and 30 (39±2 years) had a negative outcome (non-fainters). When measured between 5 and 10min of 70° HUT, T2 had increased significantly only in the fainters, and a change in T2 of >40ms from baseline predicted a positive outcome with a sensitivity of 68% and a specificity of 70%. During supine rest prior to 70° HUT, the fainters exhibited a shorter T2 than non-fainters (183±10 compared with 233±14ms; P<0.01), and a T2 of <199ms predicted a positive outcome to 70° HUT with a sensitivity of 68% and a specificity of 63%. Incorporation of the changes that occurred from rest to 70° HUT in other haemodynamic variables (heart rate >11 beats/min, systolic pressure <2 mmHg, diastolic pressure <7 mmHg and pulse pressure <-3 mmHg) increased the specificity to 97% and the positive predictive value to 93%. Thus transthoracic impedance could detect differences in central haemodynamics between fainters and non-fainters during supine rest and during the initial period of 70° HUT with a consistent sensitivity and specificity when combined with peripheral haemodynamic variables.
Aspects of organ protein, amino acid and glucose metabolism in a porcine model of hypermetabolic sepsis
Authors: BRUINS Maaike J. , DEUTZ Nicolaas E.P. , SOETERS Peter B.
Published: August 2015

Although glucose and protein metabolism have been investigated extensively in experimental models of hypodynamic sepsis, relatively little information is available regarding the compensated stage of sepsis. We investigated interorgan amino acid and glucose metabolism in a porcine model of compensated hyperdynamic sepsis. Fasting catheterized pigs received endotoxin (Escherichia coli lipopolysaccharide; 3µg·h-1·kg-1; intravenous) or saline (controls) and volume resuscitation over 24h to reproduce hyperdynamic sepsis. Primed-constant infusions of p-aminohippurate and 3H-labelled isotopes were used to measure glucose, amino acid and protein metabolism across the portal-drained viscera, liver and hindquarters (to represent muscle) at 0 and 24h of endotoxaemia. Whole-body protein and glucose flux were increased during hyperdynamic compensated sepsis. In endotoxaemic pigs, visceral protein was conserved, and hindquarter protein breakdown exceeded the increase in liver protein synthesis, resulting in net whole-body protein loss. Endotoxaemia increased hindquarter and visceral glycolysis and branched-chain amino acid transamination. The rate of efflux of glutamine and alanine from the hindquarters was higher than anticipated from protein breakdown, indicating de novo synthesis of these amino acids during endotoxaemia. In addition to the hindquarters, the portal-drained viscera provided substantial gluconeogenic amino acids and lactate to the liver. Although increased liver glutamate release constitutes an important nitrogen-sparing mechanism and carbon skeletons are effectively being cycled in glucose, net body protein is lost through increased ureagenesis during the hyperdynamic stage of sepsis. Specific amino acid requirements may develop in compensated hyperdynamic sepsis that is characterized by maintained organ perfusion and increased substrate utilization at the expense of body protein.
Polyunsaturated and monounsaturated fatty acids increase neutral lipid accumulation, caspase activation and apoptosis in a neutrophil-like, differentiated HL-60 cell line
Authors: HEALY Declan A. , WATSON R. William G. , NEWSHOLME Philip
Published: August 2015

We report here that monounsaturated fatty acids and polyunsaturated fatty acids (PUFAs) provoke the accumulation of neutral lipids and apoptosis in retinoic acid-treated HL-60 cells in a concentration- and time-dependent manner. The PUFAs (arachidonic acid, docosahexanoic acid and eicosapentaenoic acid) provoked higher levels of HL-60 apoptosis compared with the monounsaturated oleic acid or the saturated palmitic acid. Cell size and granularity were also altered by fatty acid treatment. The PUFA-induced apoptosis was correlated with increased activity of caspase 3 and caspase 9. Lipid peroxidation was also increased in the presence of PUFAs, but was not responsible for activating cell apoptosis. Lipid derived metabolites may be responsible for activation of caspases and induction of cell apoptosis.
Levels of adhesion molecules do not decrease after 3 months of statin therapy in moderate hypercholesterolaemia
Authors: JILMA Bernd , JOUKHADAR Christian , DERHASCHNIG Ulla , RASSOUL Fausi , RICHTER Volker , WOLZT Michael , DORNER Guido T. , PETTERNEL Vanessa , WAGNER Oswald F.
Published: August 2015

Studies in animals and humans indicate a pivotal role for adhesion molecules (AMs) in the pathogenesis of atherosclerosis. Whereas an association between hypercholesterolaemia and AM expression has been suggested, it is unclear whether lowering cholesterol decreases AM expression and release. We compared the effects of a 3-month treatment with standard doses of three different statins (atorvastatin, simvastatin and pravastatin) on plasma levels of circulating AM (cAM) in 75 hypercholesterolaemic patients in a randomized clinical trial. Plasma levels of circulating (c)E-selectin, circulating intercellular adhesion molecule-1 (cICAM-1) and circulating vascular cell adhesion molecule-1 (cVCAM-1) were measured before and after 3 months of therapy. None of the statins lowered plasma cAM levels and pooled analyses of all patients showed a 1.7% [95% confidence interval (CI), -1.4–4.9%] increase in cE-selectin, a 2.1% (95% CI, -0.2–4.4%) increase in cICAM-1, and a 2.7% (95% CI, -0.6–6.1%) increase in cVCAM-1 levels. cAM levels did not decrease, even in patients with a >50% decrease (n = 19) in low-density lipoprotein cholesterol levels. This study provides strong evidence that 3 months of therapy with three different statins does not decrease cAM levels, despite normalization of cholesterol levels, and a minor decrease in C-reactive protein levels in patients with moderate hypercholesterolaemia.
Testosterone suppression in men with prostate cancer leads to an increase in arterial stiffness and hyperinsulinaemia
Authors: DOCKERY Frances , BULPITT Christopher J. , AGARWAL Sanjiv , DONALDSON Mandy , RAJKUMAR Chakravarthi
Published: August 2015

The role of androgens in cardiovascular disease is uncertain. We aimed to determine the vascular effects of androgen suppression in men with prostate cancer. Arterial stiffness (or ‘compliance’) was measured in 16 men (71±9 years, mean±S.D.) prior to, and 3 months after, complete androgen suppression with gonadotrophin-releasing hormone analogues as treatment for prostate cancer. Fifteen control men (70±7 years) also had arterial stiffness studies at baseline and 3 months later. Two measures of arterial stiffness were employed: systemic arterial compliance (SAC) was measured by simultaneous recording of aortic flow and carotid artery pressure (‘area method’), and pulse wave velocities (PWVs) were recorded with the ‘Complior’ system. The 16 cases underwent glucose-tolerance and fasting-lipids tests on both visits. After 3 months of testosterone suppression, there was a significant fall in SAC, which was not seen in the controls [mean change±S.E.M., -0.26±0.09a.c.u. (arbitrary compliance unit) in the cases versus +0.06±0.11 in the controls; P = 0.03). Central, but not peripheral, PWVs tended to increase in the cases (mean change±S.E.M. for aorto-femoral PWV, +0.5±0.4m/s for cases versus -0.3±0.3m/s for controls; P = 0.08). After testosterone suppression, fasting insulin levels increased from 6.89±4.84m-units/l to 11.34±8.16m-units/l (mean±S.D.), total cholesterol increased from 5.32±0.77mmol/l to 5.71±0.82mmol/l and high-density lipoprotein cholesterol increased from 1.05±0.24mmol/l to 1.26±0.36mmol/l; P<0.005 for all. No significant change occurred in body-mass index, serum glucose, low-density lipoprotein cholesterol or triacylglycerol (triglyceride) levels. Our results indicate that loss of androgens in men leads to an increase in aortic stiffness and serum insulin levels, and may therefore adversely affect cardiovascular risk.
Obesity, Type II diabetes and the β2 adrenoceptor gene Gln27Glu polymorphism in the Tongan population
Authors: DUARTE Natalia L. , COLAGIURI Stephen , PALU Taniela , WANG Xing L. , WILCKEN David E.L.
Published: August 2015

As there is a high prevalence of obesity in Tonga, we aimed to determine the distribution of the β2 adrenoceptor gene Gln27Glu polymorphism and to assess its relevance to obesity and to Type II diabetes, known to be prevalent in that population. A random sample of 1022 individuals from Tonga were genotyped for the Gln27Glu polymorphism in the β2 adrenoceptor gene. To assess the prevalence of obesity we measured body-mass index (BMI), fat-free mass, percentage fat and waist-to-hip ratio (WHR). To assess glucose metabolism we measured HbA1c, fasting blood glucose, fasting serum insulin, and 1- and 2-h glucose; we also measured serum lipid and creatinine levels. We found that 84% of the Tongan men and 93% of the women were overweight or obese (BMI⩾25kg/m2) and 15.1% had Type II diabetes. Genotype frequencies among the 1022 Tongans were: Gln/Gln 90.3% and Gln/Glu 9.6%; we found one Glu/Glu homozygote. The mean BMI (±S.D.) for men was not significantly different for those who were homozygous (30.2±5.4kg/m2) or heterozygous (30.1±5.5kg/m2) for the Gln allele; this was also true for women (33.7±6.2kg/m2 for homozygous and 34.0±5.6kg/m2 for heterozygous). The Glu allele was not associated with other measures of obesity or abnormal glucose metabolism in this generally overweight population. There is a unique frequency of the Gln/Glu β2 adrenoceptor polymorphism among Tongans. We found no association of the polymorphism with obesity measures or Type II diabetes-related variables in the Tongan population among whom we documented a high prevalence of obesity and Type II diabetes and a low frequency of the Glu allele.
Free insulin-like growth factor 1 in the vitreous fluid of diabetic patients with proliferative diabetic retinopathy: a case-control study
Authors: SIMÓ Rafael , HERNÁNDEZ Cristina , SEGURA Rosa M. , GARCÍA-ARUMÍ José , SARAROLS Laura , BURGOS Rosa , CANTÓN Ana , MESA Jordi
Published: August 2015

The aim of the study was to evaluate the vitreous levels of free insulin-like growth factor 1 (IGF-1) in patients with proliferative diabetic retinopathy (PDR). For this, a total of 36 diabetic patients with PDR (group A) and 28 non-diabetic patients (group B) in whom a vitrectomy was performed were compared. Both groups were matched by age, sex and serum-free IGF-1. In a subgroup of diabetic patients (n = 21) and non-diabetic patients (n = 13), vitreous and serum total IGF-1, IGF-binding protein 1 (IGFBP-1) and IGFBP-3 were also determined. Serum and vitreous levels of free IGF-1, total IGF-1, IGFBP-1 and IGFBP-3 were measured by immunological methods. Vitreal proteins were assessed by a turbidimetric method and adjusted for vitreous haemoglobin. Vitreous levels of free IGF-1 were elevated in group A (median, 0.16ng/ml; range 0.06–0.57ng/ml) in comparison with group B (median, 0.12ng/ml; range 0.06–0.22ng/ml; P<0.001); however, after adjusting for vitreal proteins, free IGF-1 levels were significantly lower in group A in comparison with group B [0.05ng/mg (0.01–0.45ng/mg) versus 0.15ng/mg (0.07–0.66ng/mg); P<0.001]. The relatively lower free IGF-1 level observed in group A could not be attributed to differences in the distribution of intravitreous IGFBP-1 and IGFBP-3 in relation to total IGF-1. Notably, the contribution of free IGF-1 to total IGF-1 in vitreous fluid was 10% in group A and 42% in group B; these percentages largely exceed that obtained in serum (<1%). Our results suggest that although there is an enhancement of intravitreous free IGF-1 in diabetic patients due to serum diffusion, a deficit in its intraocular production also exists. In addition, these findings support the concept that intraocular-produced free IGF-1 plays a relevant role in retinal homoeostasis.
Short-term aerobic training and circulatory function in women: age and hormone-replacement therapy
Authors: KATYAL Sonia , FREEMAN Michael , MILLER Judith A. , THOMAS Scott G.
Published: August 2015

The physiological basis of training responses in women, and particularly older women, is not well understood. Short-term aerobic training (STAT) was used to probe the effects of age and hormone-replacement therapy (HRT) on women's ability to rapidly change peak uptake (VO2max), plasma volume and cardiac function. A total of 39 females participated in the STAT programme: 15 younger (Y; aged 19–29 years), 12 postmenopausal women undergoing HRT and 12 non-medicating postmenopausal (PM) women (aged 60–75 years). Training consisted of ten sessions of cycling over a 2-week period, which progressed in duration from 20 to 60min and in intensity from 60–75% of maximum heart rate. Plasma volume (PV; as determined by Evan's Blue dye dilution), VO2max (cycle ergometry) and cardiac function (radionuclide ventriculography) were analysed using analysis of covariance or repeated measures ANOVA. All groups demonstrated similar increase in VO2max (Y, 13%; PM, 17%; HRT, 13%), but without a significant change in left-ventricular ejection fraction and diastolic function or volumes during supine exercise. PV expansion was observed among the Y group (7%; P<0.05) but not the PM group (2%; P>0.05) or women undergoing HRT (1%; P>0.05). Age and hormone-replacement status did not affect the magnitude of VO2max change. This study suggests that STAT improves VO2max, independent of central adaptations.
Glutamine attenuates post-traumatic glutathione depletion in human muscle
Authors: FLÄRING U.B. , ROOYACKERS O.E. , WERNERMAN J. , HAMMARQVIST F.
Published: August 2015

Glutathione is quantitatively the most important endogenous scavenger system. Glutathione depletion in skeletal muscle is pronounced following major trauma and sepsis in intensive care unit patients. Also, following elective surgery, glutathione depletion occurs in parallel with a progressive decline in muscle glutamine concentration. The present study was designed to test the hypothesis that glutamine supplementation may counteract glutathione depletion in a human trauma model. A homogeneous group of patients (n = 17) undergoing a standardized surgical procedure were prospectively randomly allocated to receive glutamine (0.56g·day-1·kg-1) or placebo as part of isonitrogenous and isocaloric nutrition. Percutaneous muscle biopsies and blood samples were taken pre-operatively and at 24 and 72h after surgery. The concentrations of muscle glutathione and related amino acids were determined in muscle tissue and plasma. In the control (unsupplemented) subjects, total muscle glutathione had decreased by 47±8% and 37±11% and reduced glutathione had decreased by 53±10% and 45±16% respectively at 24 and 72h after surgery (P<0.05). In contrast, in the glutamine-supplemented group, no significant post-operative decreases in total or reduced glutathione were seen following surgery. Muscle free glutamine had decreased at 72h after surgery in both groups, by 41.4±14.8% (P<0.05) in the glutamine-supplemented group and by 46.0±14.3% (P<0.05) in the control group. In conclusion, the present study demonstrates that intravenous glutamine supplementation attenuates glutathione depletion in skeletal muscle in humans following standardized surgical trauma.
Relationships between cholesterol homoeostasis and triacylglycerol-rich lipoprotein remnant metabolism in the metabolic syndrome
Authors: CHAN Dick C. , WATTS Gerald F. , BARRETT P. Hugh R. , O'NEILL Frans H. , REDGRAVE Trevor G. , THOMPSON Gilbert R.
Published: August 2015

The dysmetabolic syndrome of insulin resistance and visceral obesity is characterized by elevated plasma concentration of triacylglycerol-rich lipoprotein (TRL) remnants that may be related to increased cardiovascular risk. Perturbed hepato-intestinal cholesterol metabolism may play a contributory role in this abnormality. We therefore investigated the association between plasma markers of cholesterol absorption and synthesis with TRL remnant metabolism in 35 men with the metabolic syndrome (MS). Plasma campesterol:cholesterol and lathosterol:cholesterol ratios were measured as estimates of cholesterol absorption and synthesis respectively. Remnant metabolism was assessed by measuring remnant-like particle-cholesterol (RLP-C), apolipoprotein (apo)B-48 and the fractional catabolic rate (FCR) of a labelled remnant-like emulsion. Compared with controls, subjects with the MS had significantly lower plasma campesterol:cholesterol ratio, but higher lathosterol:cholesterol ratio (P<0.05). Plasma RLP-C and apoB-48 concentrations were also higher (P<0.01) and the remnant-like emulsion FCR was lower (P<0.05). The plasma campesterol:cholesterol ratio was inversely correlated (P<0.05) with plasma triacylglycerols (r =-0.346), RLP-C (r =-0.443), apoB-48 (r =-0.427) and plasma lathosterol:cholesterol ratio (r =-0.366); the campesterol:cholesterol ratio was also positively correlated with the remnant-like emulsion FCR (r = 0.398, P<0.05). In multiple regression analysis, the significant correlations between plasma campesterol:cholesterol ratio and plasma triacylglycerols, RLP-C, apoB-48 and FCR of the remnant-like emulsion were independent of age, dietary energy and plasma lathosterol. Our findings suggest that in subjects with the MS alterations in cholesterol absorption and synthesis may be closely linked with the kinetic defects in TRL metabolism.
Indeterminate Chagas’ disease: Trypanosoma cruzi strain and re-infection are factors involved in the progression of cardiopathy
Authors: BUSTAMANTE Juan M. , RIVAROLA Héctor W. , FERNÁNDEZ Alicia R. , ENDERS Julio E. , FRETES Ricardo , PALMA José A. , PAGLINI-OLIVA Patricia A.
Published: August 2015

Chagas' disease is caused by Trypanosoma cruzi, which is transmitted by reduviid bugs. The World Health Organization has estimated that about 16–18 million people in the Americas are infected, and that more than 100 million are at risk. In the present study we have used a murine model to analyse if particular T. cruzi strains (Tulahuen strain and SGO-Z12 isolate from a chronic patient) and/or re-infection may determine, during the indeterminate phase of experimental Chagas' disease, changes that could explain the different evolution of cardiac lesions. Re-infected mice reached higher parasitaemias than those infected for the first time. The survival in the indeterminate phase of mice infected with Tulahuen strain was 50.0%, while the SGO-Z12-infected group presented a significantly higher survival rate (77.1%; P<0.01). The SGO-Z12-re-infected group showed a survival rate (70.9%) significantly higher than that of the Tulahuen-re-infected group (37.0%; P<0.01). Electrocardiographic abnormalities were found in 66% of Tulahuen-infected mice, while in SGO-Z12-infected group such abnormalities were found in only 36% of animals (P<0.01). The two groups exhibited similar percentages of electrocardiographic dysfunction on re-infection, although intraventricular blocks were more frequent in Tulahuen-re-infected mice (P<0.01). Hearts from infected or re-infected mice with either parasite showed mononuclear infiltrates. The SGO-Z12-re-infected and Tulahuen-re-infected groups exhibited a significantly diminished affinity (P<0.05) and a significantly increased density (P<0.05) of cardiac β-adrenergic receptors compared with the infected and non-infected groups. The indeterminate phase of Chagas' disease is defined as a prolonged period that is clinically silent, but the present findings show that different T. cruzi strains and re-infection are able to alter the host–parasite equilibrium, and these factors may be responsible for inducing progressive cardiopathy.
CR-39 track detector calibration for H, He, and C ions from 0.1-0.5 MeV up to 5 MeV for laser-induced nuclear fusion product identification
Authors: Baccou C. , Yahia V. , Depierreux S. , Neuville C. , Goyon C. , Consoli F. , De Angelis R. , Ducret J. E. , Boutoux G. , Rafelski J. , Labaune C.
Published: August 2015

Laser-accelerated ion beams can be used in many applications and, especially, to initiate nuclear reactions out of thermal equilibrium. We have experimentally studied aneutronic fusion reactions induced by protons accelerated by the Target Normal Sheath Acceleration mechanism, colliding with a boron target. Such experiments require a rigorous method to identify the reaction products (alpha particles) collected in detectors among a few other ion species such as protons or carbon ions, for example. CR-39 track detectors are widely used because they are mostly sensitive to ions and their efficiency is near 100%. We present a complete calibration of CR-39 track detector for protons, alpha particles, and carbon ions. We give measurements of their track diameters for energy ranging from hundreds of keV to a few MeV and for etching times between 1 and 8 h. We used these results to identify alpha particles in our experiments on proton-boron fusion reactions initiated by laser-accelerated protons. We show that their number clearly increases when the boron fuel is preformed in a plasma state.
Reference interaction site model with hydrophobicity induced density inhomogeneity: An analytical theory to compute solvation properties of large hydrophobic solutes in the mixture of polyatomic solvent molecules
Authors: Cao Siqin , Sheong Fu Kit , Huang Xuhui
Published: August 2015

Reference interaction site model (RISM) has recently become a popular approach in the study of thermodynamical and structural properties of the solvent around macromolecules. On the other hand, it was widely suggested that there exists water density depletion around large hydrophobic solutes (>1 nm), and this may pose a great challenge to the RISM theory. In this paper, we develop a new analytical theory, the Reference Interaction Site Model with Hydrophobicity induced density Inhomogeneity (RISM-HI), to compute solvent radial distribution function (RDF) around large hydrophobic solute in water as well as its mixture with other polyatomic organic solvents. To achieve this, we have explicitly considered the density inhomogeneity at the solute-solvent interface using the framework of the Yvon-Born-Green hierarchy, and the RISM theory is used to obtain the solute-solvent pair correlation. In order to efficiently solve the relevant equations while maintaining reasonable accuracy, we have also developed a new closure called the D2 closure. With this new theory, the solvent RDFs around a large hydrophobic particle in water and different water-acetonitrile mixtures could be computed, which agree well with the results of the molecular dynamics simulations. Furthermore, we show that our RISM-HI theory can also efficiently compute the solvation free energy of solute with a wide range of hydrophobicity in various water-acetonitrile solvent mixtures with a reasonable accuracy. We anticipate that our theory could be widely applied to compute the thermodynamic and structural properties for the solvation of hydrophobic solute.
Bandgap engineering of Magnéli phase TinO2n−1: Electron-hole self-compensation
Authors: Niu Mang , Tan Huaqiao , Cheng Daojian , Sun Zaicheng , Cao Dapeng
Published: August 2015

An electron-hole self-compensation effect is revealed and confirmed in nitrogen doped Magnéli phase TinO2n−1 (n = 7, 8, and 9) by using hybrid density functional theory calculations. We found that the self-compensation effect between the free electrons in Magnéli phase TinO2n−1 (n = 7, 8, and 9) and the holes induced by p-type nitrogen doping could not only prevent the recombination of photo-generated electron-hole pairs, but also lead to an effective bandgap reduction. This novel electron-hole self-compensation effect may provide a new approach for bandgap engineering of Magnéli phase metal suboxides.
Fabrication of high-aspect-ratio platinum probes by two-step electrochemical etching
Authors: Yi Z. , Zhang M.
Published: August 2015

In this paper, a two-step AC electrochemical etching process was investigated for the fabrication of platinum probes with controllable aspect ratio from 10 to 30, and tip apex radius less than 300 nm. Experiment results show that the shape of the obtained probes is quite sensitive to the etching time of the first step and the voltage applied in the second step. A graphite crucible was used as the counter electrode during etching. It is proved that the shape of the counter electrode also play a key role for realizing high-aspect-ratio probes. The method presented here provides a simple way in the fabrication of micro-tool for the construction of high-aspect-ratio microstructures, especially for the 3D electrochemical micromachining.
Kinetics and magnitude of the reversible stress evolution during polycrystalline film growth interruptions
Authors: Flötotto D. , Wang Z. M. , Jeurgens L. P. H. , Mittemeijer E. J.
Published: August 2015

During the deposition of polycrystalline thin films, often intrinsic compressive stresses develop, which reversibly change in tensile direction once the deposition process is interrupted. Up to date, the underlying mechanism of such reversible stress changes during growth interruptions have been controversially discussed, mainly because the correlations between the growth conditions, the developing film microstructure and the reversible stress change were still largely unclear. The present study has experimentally established the separate effects of the pre-interruption deposition rate and the average lateral film grain size on both the magnitude and the kinetics of the reversible tensile stress rise during polycrystalline film growth interruption. To this end, real-time in situ substrate-curvature measurements were performed during polycrystalline Ag growth and upon subsequent growth interruptions for well-defined and controlled adjusted microstructures. It is shown that the magnitude of the reversible tensile stress rise during growth interruption is predominantly governed by the grain-boundary density, while the rate of the tensile stress rise during growth interruption increases with increasing pre-interruption deposition rate and increasing (lateral) Ag grain size. These phenomena can be rationalized by taking deposition-rate and lateral-grain-size dependent surface morphological developments into account.
Cycling excitation process: An ultra efficient and quiet signal amplification mechanism in semiconductor
Authors: Liu Yu-Hsin , Yan Lujiang , Zhang Alex Ce , Hall David , Niaz Iftikhar Ahmad , Zhou Yuchun , Sham L. J. , Lo Yu-Hwa
Published: August 2015

Signal amplification, performed by transistor amplifiers with its merit rated by the efficiency and noise characteristics, is ubiquitous in all electronic systems. Because of transistor thermal noise, an intrinsic signal amplification mechanism, impact ionization was sought after to complement the limits of transistor amplifiers. However, due to the high operation voltage (30-200 V typically), low power efficiency, limited scalability, and, above all, rapidly increasing excess noise with amplification factor, impact ionization has been out of favor for most electronic systems except for a few applications such as avalanche photodetectors and single-photon Geiger detectors. Here, we report an internal signal amplification mechanism based on the principle of the phonon-assisted cycling excitation process (CEP). Si devices using this concept show ultrahigh gain, low operation voltage, CMOS compatibility, and, above all, quantum limit noise performance that is 30 times lower than devices using impact ionization. Established on a unique physical effect of attractive properties, CEP-based devices can potentially revolutionize the fields of semiconductor electronics.
Airflow assisted printhead for high-resolution electrohydrodynamic jet printing onto non-conductive and tilted surfaces
Authors: Tse Leo , Barton Kira
Published: August 2015

Electrohydrodynamic jet printing (e-jet printing) is a growing high resolution (<20 μm) printing technology. It is cost effective for small scale and highly customized feature production and it is compatible with a large range of materials. Conventional e-jet is generally restricted to surfaces with high flatness, therefore limiting the application of e-jet in research and industry. This paper will present an airflow assisted e-jet printhead that incorporates the use of airflow within the printhead to direct electrohydrodynamically generated ink droplets onto non-conductive and tilted surfaces. The printhead runs in open loop yet achieves consistent printing performance across large changes in standoff height (800 μm) between the printhead and printing surface. The printhead is able to print <20 μm droplets, which surpasses traditional inkjet technology. In conclusion, this printhead design has the potential to enable e-jet printing to be applied in unprecedented application areas.
Host–Guest Inclusion System of Luteolin with Polyamine-β-cyclodextrin: Preparation, Characterisation, Anti-oxidant and Anti-cancer Activity
Authors: Liu Manshuo , Liao Rongqiang , Zhao Yulin , Yang Bo
Published: August 2015

The characterisation, inclusion complexation behaviours, and binding ability of inclusion complexes of luteolin (LU) with four polyamine-modified β-cyclodextrins (NH2-βCD, EN-βCD, DETA-βCD, TETA-βCD; where EN = ethylenediamine; DETA = diethylenediamine; TETA = triethylenetetramine) were investigated in both the solid and solution forms by photoluminescence spectroscopy, 1H and 2D NMR spectroscopy, differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy. The results showed that the water solubility, and the anti-oxidant activity and anti-cancer activity of LU were significantly increased in the inclusion complex with polyamine-β-cyclodextrin. The LU/CDs complex will be useful for its application as herbal medicine or healthcare product.
Response of leaf water status, stomatal characteristics, photosynthesis and yield in black gram and green gram genotypes to soil water deficit
Authors: Baroowa Bhaswatee , Gogoi Nirmali , Paul Sreyashi , Baruah Kushal Kumar
Published: August 2015

Drought is one of the most important abiotic stresses constraining crop productivity worldwide. The objective of the present study was to investigate the differences in drought tolerance at leaf and stomatal level of black gram (genotypes: T9, KU 301, PU 19, USJD 113) and green gram (genotypes: Pratap, SG 21–5, SGC 16, TMB 37). Drought was applied for fifteen consecutive days at flowering stage (35 days after sowing). Mid-day leaf water potential (ΨL), leaf area, photosynthesis rate (PN), leaf chlorophyll, stomatal conductance (gs) and seed yield of drought- treated plants were calculated relative to those of well watered plants. Stomatal characteristics were observed in terms of stomatal frequency (SF) and stomatal aperture size (SA). Among the studied genotypes, T9 (black gram) and Pratap (green gram) proved their better tolerance capacity to drought by maintaining higher leaf area, ΨL, PN, leaf chlorophyll, gs and SA which contributed to better seed yield. Between the two crops, green gram appeared to be affected to a greater extent, as it experienced higher reduction in yield than black gram. A highly significant positive correlation (level 0.01) of seed yield was obtained with leaf area, ΨL, PN, leaf chlorophyll, gs and SA, whereas SF was found to be poorly correlated with seed yield.