bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low paraoxonase activity in type II diabetes mellitus complicated by retinopathy
Authors: MACKNESS Bharti , DURRINGTON Paul N. , ABUASHIA Bashir , BOULTON Andrew J. M. , MACKNESS Michael I. 
Published: August 2015

Human serum paraoxonase 1 (PON1) is located on high-density lipoprotein and has been implicated in the detoxification of organophosphates, and possibly in the prevention of lipid peroxidation of low-density lipoprotein. PON1 has two genetic polymorphisms, both due to amino acid substitutions: one involving glutamine (Q genotype) and arginine (R genotype) at position 192, and the other involving leucine (L genotype) and methionine (M genotype) at position 55. We investigated the effects of these polymorphisms, and of a polymorphism of the PON2 gene at position 310 (Cys/Ser; C and S genotypes respectively), on serum PON1 activity and concentration, plasma lipids and lipoproteins and glycaemic control in 93 individuals with type II diabetes with no complications and in 101 individuals with type II diabetes with retinopathy. Serum PON1 activity in the group with no complications [median 164.1 nmol·min-1·ml-1 (range 8.0–467.8)] was significantly higher than in the group with retinopathy [113.4 nmol·min-1·ml-1 (3.0–414.6)] (P< 0.001), but the serum PON1 concentration was not different between the groups. The gene frequencies of the PON1-55 and PON1-192 polymorphisms and of the PON2-310 polymorphism were not different between the study populations. The PON1-55 and PON1-192 polymorphisms affected PON1 activity in the way described in a previous study of a control group and subjects with type II diabetes. The PON2-310 polymorphism also significantly affected serum PON1. PON1 activity was significantly higher in individuals with the PON2-310 CC genotype in both groups with type II diabetes, and the PON1 concentration was significantly higher in PON2-310 CC homozygotes with no complications than in the group with retinopathy. Neither the PON1-55 nor the PON1-192 polymorphism was correlated with the serum lipid or lipoprotein concentration in either group. In the group with retinopathy (but not the group with no complications), all three PON polymorphisms were correlated with glycaemic control, which was worse for the PON1-55 genotypes in the order MM > LM > LL (P = 0.0032), for the PON1-192 genotypes in the order RR > QR > QQ (P = 0.011) and for the PON2-310 genotypes in the order CC > CS > SS (P = 0.010). Low serum PON1 activity in retinopathy may be related to an increased tendency for lipid peroxidation. Our findings thus raise the possibility that, in retinopathy, the PON2 gene may influence PON1, and that an inter-relationship between the PON1 and PON2 genes may influence glycaemic control in subjects with type II diabetes complicated by retinopathy.
Assessment of baroreflex sensitivity in patients with preserved and impaired left ventricular function by means of the Valsalva manoeuvre and the phenylephrine test
Authors: RACZAK Grzegorz , LA ROVERE Maria Teresa , PINNA Gian Domenico , MAESTRI Roberto , ŚWITECKA Grayna 
Published: August 2015

The purpose of the present study was to assess the agreement between measurements of baroreflex sensitivity (BRS) obtained by the Valsalva manoeuvre and by the phenylephrine test in patients with previous myocardial infarction and different degrees of left ventricular dysfunction. Patients with a previous myocardial infarction were enrolled consecutively into two groups according to their left ventricular ejection fraction (LVEF): ⩽ 40% (n = 52) or > 40% (n = 52). All patients underwent BRS assessment by the phenylephrine technique (Phe-BRS) and by the Valsalva manoeuvre, with the latter using both the overshoot part of phase IV (Ov-VM-BRS) and the whole of phase IV (IV-VM-BRS). The linear association between methods was assessed by correlation analysis and the agreement was evaluated by computing the bias and the limits of agreement. IV-VM-BRS and Ov-VM-BRS could not be computed in 26% and 39% of patients respectively. For both indices a much higher percentage of non-computable Valsalva manoeuvre slopes was found in the group of patients with LVEF ⩽ 40%. Phe-BRS was significantly lower in patients with non-computable Valsalva manoeuvre slopes; 55% and 59% of patients with non-computable Ov-VM-BRS and IV-VM-BRS respectively had a markedly depressed Phe-BRS (i.e. < 3 ms/mmHg, as defined by the ATRAMI study). On comparing Phe-BRS and Ov-VM-BRS in patients with LVEF ⩽ 40%, we obtained the following results: r = 0.75 (P < 0.001), bias = 0.5 ms/mmHg (P = 0.5) and limits of agreement from -6.7 to 7.8 ms/mmHg. In patients with LVEF > 40% the results were: r = 0.91 (P < 0.001), bias = 0.1 ms/mmHg (P = 0.84) and limits of agreement from -4.8 to 5 ms/mmHg. When comparing Phe-BRS and IV-VM-BRS, we found r = 0.67 (P = 0.001), bias =-1.5 ms/mmHg (P = 0.06) and limits of agreement from -8.8 to 5.7 ms/mmHg in the group of patients with LVEF ⩽ 40%; and r = 0.66 (P < 0.001), bias =-3.1 ms/mmHg (P < 0.001) and limits of agreement from -12.1 to 5.9 ms/mmHg in the group of patients with LVEF > 40%. Dichotomizing Ov-VM-BRS, the best cut-off value to identify patients with a Phe-BRS of < 3 ms/mmHg was found to be 7 ms/mmHg, giving 100% sensitivity and 69% specificity. In conclusion, estimation of BRS by the Valsalva manoeuvre in post-myocardial infarction patients is limited by a large number of non-measurable results. When computable, measurements are well correlated with those obtained by Phe-BRS, but, because of large limits of agreement, the two methods cannot be used interchangeably. If used as a screening test for risk stratification, the Valsalva manoeuvre could reduce by about one-third the need for phenylephrine injection.
The active molecular form of plasma adrenomedullin is extracted in the pulmonary circulation in patients with mitral stenosis: possible role of adrenomedullin in pulmonary hypertension
Authors: NISHIKIMI Toshio , NAGATA Seiki , SASAKI Tatsuya , YOSHIHARA Fumiki , NAGAYA Noritoshi , HORIO Takeshi , MATSUO Hisayuki , MATSUOKA Hiroaki , KANGAWA Kenji 
Published: August 2015

Adrenomedullin (AM), a novel hypotensive peptide, preferentially dilates pulmonary vessels rather than systemic vessels. This suggests the possibility that AM is a circulating hormone which participates in regulation of the pulmonary circulation. A recent study revealed that two molecular forms of AM, i.e. a mature, active form of AM (AM-m) and an intermediate, inactive, glycine-extended form of AM (AM-Gly), circulate in human plasma. In the present study we investigated the production and clearance sites and pathophysiological significance of the two molecular forms of AM in the pulmonary circulation in patients with mitral stenosis. We measured the plasma levels of AM-m and total AM (AM-T; AM-m+AM-Gly) using a recently developed specific immunoradiometric assay, and thus calculated plasma AM-Gly levels, in blood samples obtained from the femoral vein, pulmonary artery, left atrium and aorta of 28 consecutive patients with mitral stenosis (20 females and eight males; age 53±10 years). Patients with mitral stenosis had significantly higher venous concentrations of AM-T, AM-Gly and AM-m than age-matched normal controls (AM-T, 15.9±2.5 and 10.6±2.1 pmol/l respectively; AM-Gly, 14.0±2.1 and 9.8±1.9 pmol/l respectively; AM-m, 1.9±0.6 and 1.1±0.3 pmol/l respectively; each P < 0.001). There was a significant decrease in the concentrations of AM-m and AM-T between the pulmonary artery and the left atrium (AM-T, 16.1±2.7 and 14.0±2.4 pmol/l respectively; AM-m, 2.0±0.6 and 0.7±0.2 pmol/l respectively; each P < 0.001); however, there were no differences in plasma AM-Gly levels between the pulmonary artery and the left atrium (14.1±2.3 and 13.5±2.3 pmol/l respectively). The venous concentrations of AM-m, AM-Gly and AM-T showed similar correlations with mean pulmonary artery pressure (AM-T, r = 0.67; AM-Gly, r = 0.63; AM-m, r = 0.59; each P < 0.001) and total pulmonary vascular resistance (AM-T, r = 0.77; AM-Gly, r = 0.70; AM-m, r = 0.75; each P < 0.001). These results suggest that the plasma concentration of AM-m is increased in parallel with those of AM-Gly and AM-T, and that the main site for clearance of AM-m from the plasma is the lung; the extracted AM-m in the lungs may help to attenuate the increased pulmonary arterial resistance in secondary pulmonary hypertension due to mitral stenosis.
Carbon dioxide contributes to the beneficial effect of pressurization in a portable hyperbaric chamber at high altitude
Authors: IMRAY Christopher H. E. , CLARKE Timothy , FORSTER Peter J. G. , HARVEY Timothy C. , HOAR Helen , WALSH Sarah , WRIGHT Alexander D. 
Published: August 2015

Regional cerebral oxygenation (rSO2) and peripheral oxygen saturation (SpO2) have been studied in subjects inside a portable hyperbaric chamber at altitude during pressurization. The effects of the accumulation of carbon dioxide within the chamber on rSO2 and SpO2 have also been investigated. Three studies of cerebral regional oxygenation were undertaken, using near-IR spectroscopy, in subjects who had ascended to 3475 m in the Alps, 4680 m in the Andes or 5005 m in the Himalayas. At 3475 m and 5005 m the effects of the removal of inspired carbon dioxide by a soda lime scavenger were also studied. On pressurization of the chamber to 19.95 kPa, inspired carbon dioxide rose within the chamber from 0.03% (0.06 kPa) ambient to over 1% (1.3 kPa). At 5005 m, SpO2 rose from a baseline of 79.5% (S.D. 4.5%) to 95.9% (2.0%) (P &lt; 0.0001), and cerebral rSO2 rose from 64.6% (3.4%) to 69.4% (3.6%) (P &lt; 0.0001). The introduction of a soda lime CO2 scavenger into the breathing circuit resulted in a drop in SpO2 from 95.9% (2.03%) to 93.6% (2.07%) (P &lt; 0.001) and a fall in rSO2 from 69.4% (3.64%) to 68.5% (3.5%) (P &lt; 0.01). Chamber pressure was maintained throughout at 19.95 kPa. Similar changes were seen at the other altitudes. Cerebral rSO2 increased rapidly following pressurization at all three altitudes. Scavenging of inspired carbon dioxide was associated with a significant fall in cerebral rSO2 and SpO2, and we estimate that the contribution of carbon dioxide may account for up to one-third of the beneficial effect of the portable hyperbaric chamber.
Elevation of asymmetrical dimethylarginine may mediate endothelial dysfunction during experimental hyperhomocyst(e)inaemia in humans
Authors: BÖGER Rainer H. , LENTZ Steven R. , BODE-BÖGER Stefanie M. , KNAPP Howard R. , HAYNES William G. 
Published: August 2015

Hyperhomocyst(e)inaemia is associated with endothelial dysfunction in animals and humans. Mechanisms responsible for endothelial dysfunction in hyperhomocyst(e)inaemia are poorly understood, but may involve impaired bioavailability of endothelium-derived nitric oxide (NO). We hypothesized that acute elevation of homocyst(e)ine by oral methionine loading may stimulate the formation of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, due to a transmethylation reaction during the formation of homocyst(e)ine from methionine. We studied nine healthy human subjects (five males, four females) aged 29±2 years. Flow-mediated vasodilation (FMD) in the brachial artery (endothelium-dependent) and vasodilation induced by nitroglycerine (endothelium-independent) were measured with high-resolution ultrasound before and 8 h after oral methionine (100 mg/kg in cranberry juice) or placebo (cranberry juice), on separate days and in random order. Plasma homocyst(e)ine and ADMA concentrations were measured by specific HPLC methods. After a methionine bolus, elevation of homocyst(e)ine (28.4±3.5 µmol/l) was associated with an increased plasma concentration of ADMA (2.03±0.18 µmol/l) and reduced FMD (1.54±0.92%). Placebo had no effect on these parameters. There was a significant inverse linear relationship between ADMA concentration and FMD (r =-0.49; P &lt; 0.05), which was stronger than the relationship between the homocyst(e)ine concentration and FMD (r =-0.36; not significant). We conclude that acute elevation of the homocyst(e)ine concentration impairs vascular endothelial function by a mechanism in which an elevated concentration of ADMA may be involved. This finding may have importance for understanding the mechanism(s) leading to homocyst(e)ine-associated vascular disease, and its potential treatment.
Influence of aging on cardiac baroreflex sensitivity determined non-invasively by power spectral analysis
Authors: PICCIRILLO Gianfranco , CACCIAFESTA Mauro , VIOLA Emanuela , SANTAGADA Elvira , NOCCO Marialuce , LIONETTI Marco , BUCCA Carmela , MOISÈ Antonio , TARANTINI Sabrina , MARIGLIANO Vincenzo 
Published: August 2015

Aging reduces cardiac baroreflex sensitivity. Our primary aim in the present study was to assess the effects of aging on cardiac baroreflex sensitivity, as determined by power spectral analysis (α index), in a large population of healthy subjects. We also compared the α indexes determined by power spectral analysis with cardiac baroreflex sensitivity measured by the phenylephrine method (BSphen). We studied 142 subjects (79 males/63 females; age range 9–94 years), who were subdivided into five groups according to percentiles of age (25, 50, 75 and 95). Power spectral analysis yields three α indexes: an α low-frequency (LF) index of cardiac baroreflex sensitivity that ranges around 0.1 Hz; an α high-frequency (HF) index reflecting cardiac baroreflex sensitivity corresponding to the respiratory rate; and α total frequency (α TF), a new index whose spectral window includes all power in the range 0.03–0.42 Hz. Spectra were recorded during controlled and uncontrolled respiration. Under both conditions, all three α indexes were higher in the youngest age group (⩽ 34 years old) than in the three oldest groups. Notably, α TF was significantly higher in younger subjects than in the three oldest groups [14±1 ms/mmHg compared with 9±1 (P < 0.05), 8.1±1 (P < 0.001) and 8.1±1 (P < 0.05) ms/mmHg respectively]. BSphen showed a similar pattern [12±1 ms/mmHg compared with 8±0.5 (P < 0.001), 6±0.5 (P < 0.05) and 6±1 (P < 0.05) ms/mmHg respectively]. No significant differences were found for cardiac baroreflex sensitivity among the three oldest groups. All α indexes were correlated inversely with age. The index yielding the closest correlation with BSphen was α TF (r = 0.81, P < 0.001). Cardiac baroreflex sensitivity in normotensive individuals declines with age. It falls predominantly in middle age (from approx. 48 years onwards) and remains substantially unchanged thereafter. The elderly subjects we selected for this study probably had greater resistance to cardiovascular disease that is manifested clinically, with preserved cardiac baroreceptor sensitivity.
Insulin stimulates laser Doppler signal by rat muscle in vivo, consistent with nutritive flow recruitment
Authors: CLARK Andrew D. H. , BARRETT Eugene J. , RATTIGAN Stephen , WALLIS Michelle G. , CLARK Michael G. 
Published: August 2015

Insulin-mediated increases in limb blood flow are thought to enhance glucose uptake by skeletal muscle. Using the perfused rat hindlimb, we report that macro laser Doppler flowmetry (LDF) probes positioned on the surface of muscle detect changes in muscle capillary (nutritive) flow. With this as background, we examined the effects of insulin and adrenaline (epinephrine), which are both known to increase total leg blood flow, on the LDF signals from scanning and stationary probes on the muscle surface in vivo. The aim is to assess the relationship between capillary recruitment, total limb blood flow and glucose metabolism. Glucose infusion rate, femoral arterial blood flow (FBF) and muscle LDF, using either scanning or a stationary probe positioned over the biceps femoris muscle, were measured. With scanning LDF, animals received insulin (10 m-units·min-1·kg-1), adrenaline (0.125 µg·min-1·kg-1) or saline. By 1 h, insulin had increased the glucose infusion rate from 0 to 128 µmol·min-1·kg-1 and the scanning LDF had increased by 62±8% (P < 0.05), but FBF was unaffected. Adrenaline increased FBF by 49% at 15 min, but LDF was unchanged. With saline at 1 h, neither FBF nor LDF had changed. With the stationary LDF surface probe, insulin at 1 h had increased FBF by 47% (P < 0.05) and LDF by 47% (P < 0.05) relative to saline controls. Adrenaline increased FBF (39%), but LDF was unaltered. The stimulation of LDF by insulin is consistent with capillary recruitment (nutritive flow) as part of the action of this hormone in vivo. The recruitment may be independent of changes in total flow, as adrenaline, which also increased FBF, did not increase LDF. The time of onset suggests that LDF closely parallels glucose uptake. Thus, depending on probe design, measurement of muscle haemodynamic effects mediated by insulin in normally responsive and insulin-resistant patients should be possible.
Attenuated cardiac baroreflex in men with presyncope evoked by lower body negative pressure
Authors: WIJEYSUNDERA Duminda N. , BUTLER Gary C. , ANDO Shin-ichi , POLLARD Michael J. , PICTON Peter , FLORAS John S. 
Published: August 2015

Mechanisms responsible for presyncope during lower body negative pressure (LBNP) in otherwise healthy subjects are poorly understood. Muscle sympathetic nerve activity (MSNA), blood pressure, heart rate (HR), HR power spectra, central venous pressure (CVP) and stroke volume were determined in 14 healthy men subjected to incremental LBNP. Of these, seven experienced presyncope at LBNP >-15 mmHg. Subjects who tolerated LBNP >-15 mmHg had significantly lower CVP (2.6±1.0 versus 7.2±1.2 mmHg; means±S.E.M., P < 0.02), HR (59±2 versus 66±3 beats/min, P < 0.05) and MSNA burst frequency (29.0±2.4 versus 39.0±3.5 bursts/min, P < 0.05) during supine rest. LBNP at -15 mmHg had no effect on blood pressure, but caused similar and significant reductions in stroke volume and cardiac output in both groups. Subjects who tolerated LBNP had significant reflex increases in HR, MSNA burst frequency and burst amplitude with LBNP of -15 mmHg. These responses were absent in those who experienced presyncope. The gain of the cardiac baroreflex regulation of MSNA was markedly attenuated in pre-syncopal subjects (1.2±0.6 versus 8.8±1.4 bursts/100 heart beats per mmHg; P < 0.001). Healthy subjects who experience presyncope in response to LBNP appear more dependent, when supine, upon MSNA to maintain preload, and less able to increase sympathetic vasoconstrictor discharge to skeletal muscle reflexively in response to orthostatic stimuli.
Effects of nitric oxide synthase inhibition on angiotensin receptors and metabolism in the pregnant hypertensive rat
Authors: YANG Y. , MACDONALD G. J. , DUGGAN K. A. 
Published: August 2015

Endothelial dysfunction and a consequent decrease in nitric oxide production have been implicated in the pathogenesis of pre-eclampsia. A prominent feature of the pre-eclamptic syndrome is a loss of the pregnancy-induced refractoriness to infused pressor agents, such as angiotensin. In this study, we sought to determine whether a decrease in nitric oxide production might be linked via changes in angiotensin II receptors and angiotensin II metabolism to changes in pressor sensitivity to infused angiotensin II. Pregnant and non-pregnant spontaneously hypertensive rats (SHRs) were randomly allocated to receive 5 mg·kg-1·day-1NG-nitro-L-arginine methyl ester (L-NAME) in the drinking water or drinking water alone from days 7 to 14 of gestation. Steady-state metabolic clearance studies of angiotensin II were then performed, or tissues were harvested for angiotensin II receptor studies. Treatment with L-NAME caused an increase in systolic pressure (P < 0.001) in both pregnant and non-pregnant rats, while urinary protein excretion increased only in the pregnant SHRs (P< 0.001). Plasma angiotensin II levels were significantly increased in the L-NAME-treated SHRs compared with controls (non-pregnant, P< 0.0005; pregnant, P < 0.01). The metabolic clearance rate of angiotensin II was decreased by L-NAME treatment in non-pregnant SHRs (P < 0.05), but was increased by L-NAME treatment in the pregnant rats (P < 0.01). In the aorta, the angiotensin II receptor number increased after treatment with L-NAME in both non-pregnant (P < 0.0005) and pregnant (P < 0.05) SHRs, and the dissociation constant increased in the non-pregnant SHRs (P < 0.005). Thus treatment of SHRs with L-NAME increased blood pressure, as well as the circulating angiotensin II concentration and vascular angiotensin II receptor expression. However, treatment with L-NAME did not affect pressor sensitivity to infused angiotensin II. We conclude, therefore, that although a decrease in nitric oxide production is associated with changes in angiotensin II concentrations and receptor numbers, it does not induce changes in pressor sensitivity to infused angiotensin II in the SHR.
Comparison of nasal pH values in black and white individuals with normal and high blood pressure
Authors: IRESON N. J. , TAIT J. S. , MACGREGOR G. A. , BAKER E. H. 
Published: August 2015

Salt-sensitive hypertension is common in people of African origin, and may be caused by increased transepithelial sodium absorption. The pH of nasal secretions is negatively correlated with the difference in Na+ concentration between nasal secretions and plasma, and may be a marker of transepithelial sodium absorption. Nasal pH was measured using a probe sited under the inferior turbinate. Measurements of nasal pH were reproducible, with a coefficient of variation of 3.3% for repeated measurements on the same day and of 2.7% between measurements on different days. Nasal pH did not correlate with nasal potential difference, a measure of transepithelial sodium absorption. Nasal pH was significantly lower in 89 black individuals (24 normotensive and 65 hypertensive) than in 51 white individuals (26 normotensive and 25 hypertensive) (black normotensive. 6.44±0.08; black hypertensive, 6.62±0.05; white normotensive, 6.91±0.06; white hypertensive, 6.98±0.06), after adjustment for age, gender, current smoking status, body mass index and 24 h urinary sodium excretion (P = 0.002), but was not significantly different between the normotensive and hypertensive individuals. Nasal pH was more acidic in black than in white individuals, which may represent generalized up-regulation of sodium transport in black people. However, the lack of correlation between nasal pH and potential difference suggests that nasal pH is, at best, only weakly related to transepithelial sodium absorption. Ethnic differences in nasal pH may be of direct relevance in the airways, as many of the functions of airway surface liquid are dependent on pH.