bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microdialysis assessment of local adipose tissue lipolysis during β-adrenergic stimulation in upper-body-obese subjects with type II diabetes
Authors: BLAAK Ellen E. , KEMERINK Gerrit J. , PAKBIERS Marie Therese W. , WOLFFENBUTTEL Bruce H. R. , HEIDENDAL Guido A. , SARIS Wim H. M. 
Published: August 2015

The present study was designed to investigate indicators of abdominal adipose tissue lipolysis (microdialysis), and subcutaneous adipose tissue blood flow and whole-body lipolysis, in obesity-associated type II diabetes during overnight-fasted conditions (baseline) and during intravenous infusion of the non-selective β-agonist isoprenaline. Basal subcutaneous adipose tissue blood flow and isoprenaline-induced increases in adipose tissue blood flow were not signifcantly different between subjects with type II diabetes and non-obese, non-diabetic controls. Adipose tissue interstitial glycerol concentrations were significantly higher in subjects with type II diabetes compared with controls (P< 0.01), and during isoprenaline infusion there was a decrease in interstitial glycerol in both groups (P< 0.001). Arterial glycerol concentrations were higher in subjects with type II diabetes compared with controls (P< 0.05), whereas the increases in arterial glycerol concentration in response to isoprenaline infusion were of a similar magnitude in the two groups. Estimated subcutaneous adipose tissue glycerol release was not significantly different between the groups (controls and subjects with type II diabetes: baseline, -129±32 and -97±72 μmol·min-1·100 g-1 adipose tissue respectively; isoprenaline, -231±76 and -286±98 μmol·min-1·100 g-1 respectively). Values for fat oxidation were not significantly different between groups, whereas the isoprenaline-induced increase in fat oxidation tended to be less pronounced in subjects with type II diabetes compared with controls (0.022±0.008 and 0.038±0.003 g/min respectively; P = 0.058). Thus estimated basal subcutaneous adipose tissue glycerol release, expressed per unit of fat mass, is not different in controls and in subjects with type II diabetes. Additionally, the isoprenaline-induced increases in indicators of local abdominal subcutaneous adipose tissue, systemic lipolysis and abdominal adipose tissue blood flow responses were comparable in obese subjects with type II diabetes and in controls. The last two findings contrast with previous data from obese subjects, indicating that the regulation of lipolysis may differ in obesity and obesity-associated type II diabetes.
Effects of branched-chain-enriched amino acids and insulin on forearm leucine kinetics
Authors: ZANETTI Michela , BARAZZONI Rocco , KIWANUKA Edward , TESSARI Paolo 
Published: August 2015

Although amino acid mixtures enriched in branched-chain amino acids (BCAA) and deficient in aromatic amino acids (AAA) are often used together with insulin and glucose in clinical nutrition, their physiological effects on muscle protein anabolism are not known. To this aim, we studied forearm leucine kinetics in post-absorptive volunteers, before and after the systemic infusion of BCAA-enriched, AAA-deficient amino acids along with insulin and the euglycaemic clamp. The results were compared with the effects of insulin infusion alone. A compartmental leucine forearm model was employed at steady state. Hyperaminoacidaemia with hyperinsulinaemia (to ≈ 80–100 μ-units/ml) increased the leucine plasma concentration (+70%; P< 0.001), inflow into the forearm cell (+150%; P< 0.01), disposal into protein synthesis (+100%; P< 0.01), net intracellular retention (P< 0.01), net forearm balance (by ≈ 6-fold; P< 0.01) and net deamination to α-ketoisocaproate (4-methyl-2-oxopentanoate) (+9%; P< 0.05). Leucine release from forearm proteolysis and outflow from the forearm cell were unchanged. In contrast, hyperinsulinaemia alone decreased plasma leucine concentrations (-35%; P< 0.001) and leucine inflow (-20%; P< 0.05) and outflow (-30%; P< 0.01) into and out of forearm cell(s), it increased net intracellular leucine retention (P< 0.03), and it did not change leucine release from forearm proteolysis (-20%; P = 0.138), net leucine deamination to α-ketoisocaproate, leucine disposal into protein synthesis or net forearm protein balance. By considering all data together, leucine disposal into protein synthesis was directly correlated with leucine inflow into the cell (r = 0.71; P< 0.0001). These data indicate that the infusion of BCAA-enriched, AAA-deficient amino acids along with insulin is capable of stimulating forearm (i.e. muscle) protein anabolism in normal volunteers by enhancing intracellular leucine transport and protein synthesis. These effects are probably due to hyperaminoacidaemia and/or its interaction with hyperinsulinaemia, since they were not observed under conditions of hyperinsulinaemia alone.
Oximetry spectral analysis in the diagnosis of obstructive sleep apnoea
Authors: ZAMARRÓN C. , ROMERO P. V. , RODRIGUEZ J. R. , GUDE F. 
Published: August 2015

Using spectral analysis of oximetry data, we prospectively evaluated the validity of this methodology in patients clinically suspected of suffering from obstructive sleep apnoea (OSA). A total of 233 outpatients were studied. Nocturnal oximetry was performed simultaneously with conventional polysomnography for all participants. The power density of oxygen saturation was analysed using Fast-Fourier transformation of the oximetric signal. Nocturnal oximetry test results were considered as abnormal (suspicion of OSA) if a peak in the spectrum between the period boundaries 30 and 70 s was observed. A normal test result was defined as the absence of the 30–70 s peak from the spectrum. Single-blind evaluation was performed by three independent observers, and agreement of two or more of these was considered definitive. The peak amplitude and the ratio of the area enclosed in the 30–70 s peak to the total area of the spectrum (rS) were measured. The presence of a peak has a sensitivity of 78%, a specificity of 89%, a positive predictive value of 89% and a negative predictive value of 78%. Apnoea–hypopnoea indexes were correlated significantly with peak amplitude (r = 0.74; P< 0.001) and with rS (r = 0.69; P< 0.001). For a peak amplitude threshold of 0.7%2, the sensitivity was 94% and the specificity was 65% for OSA diagnosis. Using a threshold for rS of 0.15, the sensitivity was 91% and the specificity was 67%. Thus the spectral analysis of nocturnal oximetry and identification of a peak at 30–70 s could be useful as a diagnostic technique for OSA subjects.
Is proteinuric pre-eclampsia a different disease in primigravida and multigravida?
Authors: BARDEN Anne E. , BEILIN Lawrence J. , RITCHIE Jackie , WALTERS Barry N. , GRAHAM Dorothy , MICHAEL Constantine A. 
Published: August 2015

This study aimed to identify if the clinical features of proteinuric pre-eclampsia or the biochemical markers of endothelial dysfunction associated with this syndrome are altered according to parity in a direction that would suggest a different pathophysiology. Groups of 27 primigravid and 35 multigravid women with pre-eclampsia (defined as blood pressure > 140/90 mmHg and 2+ proteinuria) were studied ante-partum, and at 6 weeks and 6 months post-partum. Clinical markers of severity of pre-eclampsia, including blood pressure, markers of renal, hepatic and coagulatory function, and biochemical markers of endothelial dysfunction were measured. Fetal outcome was assessed by birthweight and birthweight percentile. Ante-partum systolic blood pressure was 10 mmHg higher in the primigravida, and this difference was independent of age and anti-hypertensive medication. Analysis of systolic blood pressure before and after delivery showed the primigravid women to have elevated systolic blood pressure over the whole time period (P< 0.01). The primigravid women had more severe hepatic dysfunction, with elevated aspartate aminotransferase levels, but plasma creatinine, proteinuria, platelet counts and haematocrit were similar, indicating that renal and coagulatory function and plasma volume were affected to the same extent in the two groups and were independent of parity. Birthweight was similar in the two groups, and the percentage of infants weighing less than the 10th centile for gestation was also similar. Biochemical markers of endothelial dysfunction, assessed by measuring the urinary prostacyclin metabolite 2,3-dinor-6-oxo-prostaglandin F1α and plasma endothelin 1, did not differ according to parity. There were no differences in a number of other biochemical markers of pre-eclampsia, including plasma albumin, uric acid, triacylglycerol, and total, low-density lipoprotein and high-density lipoprotein cholesterol. Basophil, monocyte and lymphocyte counts were elevated before delivery in primigravid women with pre-eclampsia. The differences in lymphocyte counts persisted post-partum. Further studies are required to clarify the role, if any, of monocytes, basophils and lymphocytes in the pathophysiology of pre-eclampsia. In conclusion, the elevated systolic blood pressure and raised aspartate aminotransferase levels observed in primigravida suggest a more severe form of pre-eclampsia. The lack of differences in birthweight and other biochemical and endothelial markers of severity of pre-eclampsia do not suggest a different pathophysiology; however, the persistently higher white cell counts in the primigravid pre-eclamptics are of interest, and might reflect differences in immune responses in the two groups. We suggest that studies of the pathophysiology of pre-eclampsia should include multigravida, as long as there is adequate post-partum follow-up to exclude underlying disease.
Reproducibility of methods for assessing baroreflex sensitivity in normal controls and in patients with chronic heart failure
Authors: DAVIES L. Ceri , FRANCIS Darrel P. , JURÁK Pavel , KÁRA Tomas , PIEPOLI Massimo , COATS Andrew J. S. 
Published: August 2015

Baroreflex sensitivity (BRS) conveys useful prognostic information in patients with heart disease, yet methods for its quantification suffer from poor reproducibility and test failure in some patients with heart failure. We set out to compare the short-term reproducibility and success rate of four different methods of assessing BRS in normal subjects and patients with chronic heart failure (CHF). A total of 31 patients with CHF and 18 normal controls underwent BRS testing using four techniques: (1) bolus phenylephrine (BRSPhe), (2) α-index in both low- and high-frequency bands (BRSαLF and BRSαHF respectively), (3) the sequence method (BRSSeq), and (4) a new 0.1 Hz controlled-breathing, time-domain analysis method (BRSCbr). Each subject underwent two test episodes with each method on the same day. The average values for BRS in patients and controls respectively were: BRSPhe, 4.4 (±4.4) ms/mmHg and 19.8 (±11.5) ms/mmHg; BRSαLF, 5.6 (±4.1) ms/mmHg and 15.4 (±5.0) ms/mmHg; BRSαHF, 7.1 (±7.0) ms/mmHg and 25.1 (±8.3) ms/mmHg; BRSSeq, 7.7 (±6.3) ms/mmHg and 22.5 (±8.4) ms/mmHg; BRSCbr, 6.6 (±5.9) ms/mmHg and 22.8 (±10.8) ms/mmHg. The coefficients of variation (S.D. of the difference in repeated values divided by mean) in patients and controls respectively were: BRSPhe, 85.6% and 52.2%; BRSαLF, 65.9% and 33.7%; BRSαHF, 99.7% and 52.1%; BRSSeq, 30.7% and 40.4%; BRSCbr, 30.7% and 19.6%. The numbers of test failures in patients were: BRSPhen, 15; BRSαLF, 7; BRSαHF, 5; BRSSeq, 14; BRSCbr, 1. Of the four techniques assessed for measuring BRS, the controlled breathing time-domain method yielded the best reproducibility and lowest failure rate in controls and in patients with CHF.
Metabolism of lactose-[13C]ureide and lactose-[15N,15N]ureide in normal adults consuming a diet marginally adequate in protein
Authors: JACKSON A. A. , BUNDY R. , HOUNSLOW A. , MURPHY J. L. , WOOTTON S. A. 
Published: August 2015

Oral lactose-ureide is resistant to human digestive enzymes, but is fermented by the colonic microflora. Nine normal adults consuming a diet which provided 36 g of protein/day were given oral doses of lactose-[13C]ureide and lactose-[15N,15N]ureide. The appearance on breath of 13CO2 derived from lactose-[13C]ureide was followed for 48 h. The fate of 15N derived from lactose-[15N,15N]ureide was determined by measuring the recovery of 15N in stools and urine in various forms. About 80% of the label given as lactose-[13C]ureide was recovered on the breath, and about 80% of label given as lactose-[15N,15N]ureide was not recovered in stool, indicating that 80% of the dose was completely fermented. At least 5% of the labelled urea was absorbed and excreted as the intact molecule. Of the 15N derived from lactose-[15N,15N]ureide and available for further metabolic interaction, 67% was retained and 33% was excreted in urine. The time taken for [15N,15N]urea to appear in urine was similar for all subjects, but the appearance of either 13CO2 on the breath or [15N,14N]urea in urine varied. It is concluded that the hydrolysis of the sugar–urea bond may reflect oro–caecal transit time, but that other factors related to colonic bacterial metabolism determine the duration and extent of hydrolysis of urea by urease enzymes. Lactose-ureide can be used to probe the metabolic activity of the colonic microflora in normal individuals.
Small-intestinal mucosal protein synthesis and whole-body protein turnover in alcoholic liver disease
Authors: NAKSHABENDI I. M. , DOWNIE S. , RUSSELL R. I. , RENNIE M. J. 
Published: August 2015

We used stable-isotope-labelled amino acids to measure the effects of alcoholic liver disease (ALD) on whole-body protein turnover and small-intestinal mucosal protein synthesis. Groups comprising eight patients with ALD and eight healthy control subjects were studied. They received primed, continuous intravenous infusions of L-[1-13C]leucine after an overnight fast; after 4 h, duodenal biopsies were obtained via endoscopy. Protein synthesis was calculated from protein labelling relative to intracellular leucine enrichment. Rates of duodenal mucosal protein synthesis were 2.58±0.32%·h-1 (mean±S.D.) in the normal subjects and 2.04±0.18%·h-1 in the ALD patients (P< 0.003), despite the fact that the protein synthetic capacity (μg of RNA/mg of protein) was higher in ALD patients (160±14 compared with 137±6 μg/mg; P < 0.003). The mucosal cell size (protein/DNA ratio) was lower in ALD patients (9.23±0.91 compared with 13±2.2 μg/mg; P< 0.002). Although the mean rates of whole-body protein turnover were not significantly different between the two groups (204±18 and 196±44 μmol leucine·h-1·kg-1 for ALD and control subjects respectively), there was, in the ALD patients, an inverse relationship between the rate of small-intestinal mucosal protein synthesis and the severity of ALD; furthermore, there was a direct relationship between the rate of whole-body protein turnover and the severity of ALD. Thus there was an inverse relationship between the rate of small-intestinal mucosal protein synthesis and the rate of whole-body protein turnover in ALD patients, which was not seen in the normal subjects.
Albumin stimulates p44/p42 extracellular-signal-regulated mitogen-activated protein kinase in opossum kidney proximal tubular cells
Authors: DIXON Richard , BRUNSKILL Nigel J. 
Published: August 2015

The presence of protein in the urine of patients with renal disease is an adverse prognostic feature. It has therefore been suggested that proteinuria per se may be responsible for the development of renal tubulo-interstitial scarring and fibrosis, and disturbances in tubular cell growth and proliferation. We have used the opossum kidney proximal tubular cell line to investigate the effects of albumin on cell growth. The effect of albumin on cell proliferation was investigated by cell counting and measurement of [3H]thymidine incorporation. We studied the effect of recombinant human albumin on the activity of p44/p42 extracellular-signal-regulated mitogen-activated protein kinase (MAP kinase) using an in vitro kinase assay, and immunoblotting with antibodies against active extracellular-signal-regulated kinase (ERK). The effects of the ERK inhibitor PD98059 were also examined. Recombinant human albumin was found to stimulate proliferation of opossum kidney cells in a dose-dependent manner, with maximal stimulation at a concentration of 1 mg/ml. In addition, recombinant human albumin activated ERK in a time-dependent (maximal after 5 min) and dose-dependent (maximal at 1 mg/ml) fashion. These effects on cell proliferation and ERK activity were inhibited by PD98059, and were not reproduced by ovalbumin or mannitol. The data therefore indicate that albumin is able to stimulate growth and proliferation of proximal tubular cells that is dependent on the ERK family of MAP kinases. The potential importance of this pathway in the development of renal disease is discussed.
Magnesium regulates hypoxia-stimulated apoptosis in the human placenta
Authors: GUDE N. M. , STEVENSON J. L. , MOSES E. K. , KING R. G. 
Published: August 2015

Apoptosis (programmed cell death) in the human placenta is likely to play a major role in determining the structure and function of that organ. Fetal growth restriction (FGR) has been shown to be associated with increased levels of placental apoptosis. Altered regulation of apoptosis may play an important pathophysiological role in FGR. As reduced placental perfusion and reduced oxygenation are features of FGR, one aim of this study was to determine the effects of hypoxia on apoptotic activity, as assessed by DNA laddering, of placental tissue in vitro. In addition, levels of placental apoptosis may be affected by pharmacological agents routinely used in obstetric patient management. Thus an additional aim of this study was to determine the effects of several relevant pharmacological agents on the levels of DNA laddering during in vitro incubation of human placentae under hypoxic conditions. Incubation of normal placental explant tissue at 37 °C for 1–2 h under hypoxic conditions significantly increased placental DNA laddering compared with that in non-incubated tissue, whereas levels of DNA laddering during incubation for up to 2 h under normoxic conditions were not significantly higher than those in non-incubated tissue. The DNA laddering activity of placental explants after 2 h of incubation under hypoxic conditions was significantly increased with increased concentrations of magnesium, but remained unchanged by the inclusion of pethidine, aspirin, nifedipine, dexamethasone, heparin or indomethacin in the incubation mixture. These results suggest that hypoxia may stimulate apoptotic activity in cultured human placental tissues, and that hypoxia-stimulated placental apoptosis may be further increased by increasing the extracellular magnesium concentration.
Regulation of β-adrenoceptor-mediated relaxation of the rat aorta is modulated by endogenous ovarian hormones
Authors: CONDE María V. , MARÍN Jesús , FERNÁNDEZ-CRIADO Carmen , BALFAGÓ NGloria 
Published: August 2015

The aim of this study was to assess the influence of the endogenous status of ovarian hormones on the relaxation induced by the β-adrenoceptor agonists isoprenaline (isoproterenol) and dobutamine in thoracic aorta segments, precontracted with noradrenaline, from age-matched (13-week-old) virgin (oestrus) and ovariectomized (OVX) prepubertal female Wistar rats. Isoprenaline-induced relaxation was decreased in intact aortic segments from OVX rats compared with that in segments from oestrus rats. Relaxation was significantly reduced by endothelium removal, 1 µmol/l propranolol or 100 µmol/l NG-nitro-l-arginine methyl ester (l-NAME). The β1-adrenoceptor agonist dobutamine induced less relaxation in intact arteries from oestrus rats than did isoprenaline, and dobutamine-induced relaxation was markedly less in intact segments from OVX compared with oestrus rats. This dobutamine-induced relaxation was abolished by endothelium removal, and reduced by 1 µmol/l propranolol, 100 µmol/l l-NAME or 1 µmol/l yohimbine. Cholera toxin (an activator of the stimulatory G-protein Gs) caused relaxation in intact arteries from oestrus rats; this relaxation was decreased by both deprivation of ovarian hormones and endothelium removal. Forskolin (a direct activator of the catalytic subunit of adenylate cyclase) and sodium nitroprusside (a nitric oxide donor and cGMP-dependent vasodilator agonist) induced similar endothelium-independent relaxation in arteries from both oestrus and OVX rats. These results suggest that the relaxation elicited by endothelial β-adrenoceptor activation in the rat thoracic aorta is impaired by deprivation of female ovarian hormones; this impairment is caused, at least in part, by decreases in both the endothelial release of NO and Gs function.
Sequential changes in plasma cytokine and endotoxin levels in cirrhotic patients with bacterial infection
Authors: WANG Sun-Sang , LEE Fa-Yauh , CHAN Che-Chang , LU Rei-Hwa , CHAO Yee , LIN Han-Chieh , WU Shwu-Ling , TSAI Yang-Te , LEE Shou-Dong 
Published: August 2015

To delineate the clinical roles of plasma cytokine or endotoxin levels in the natural course of infection in patients with decompensated cirrhosis, 66 cirrhotic patients were studied within a 1.5-year period. Plasma levels of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8 and endotoxin were determined on days 1, 4 and 7 after admission when hospital infection was suspected and 4 months later. A total of 24 patients (36.4%) were proven to be infected during hospitalization (group A), while 42 others were not infected (group B). Fever occurred in a very high proportion (22/24) of group A patients. Baseline levels of TNF-α (37.7±15.2 compared with 8.7±1.2 pg/ml; P < 0.01) and IL-6 (180.5±20.5 compared with 24.6±7.5 pg/ml; P < 0.0001) were higher in group A patients, while IL-1β, IL-8 and endotoxin levels were not significantly different between the two groups. For patients with hospital infection, IL-6 levels determined during the episode were significantly higher than baseline levels. Using IL-6 > 80 pg/ml as a baseline cut-off level to diagnose bacterial infection, the sensitivity, specificity and accuracy were 87.5, 100 and 95.5% respectively. The one-year cumulative probability of mortality (61.1% compared with 23.7%; P < 0.001) and of bacterial re-infection (72.2% compared with 18.4%; P < 0.0001) was higher in group A than in group B. Plasma TNF-α and IL-6 levels determined at 4 months were not different between the two groups. In conclusion, fever or elevated plasma IL-6 levels in patients with decompensated cirrhosis calls for early antibiotic treatment to prevent life-threatening bacterial infection. Bacterial infection is likely to recur in those patients with increased IL-6 levels, while severe episodes of infection occur in patients with increased TNF-α levels.