bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombin Does Not Alter Vascular Hyporeactivity in Models of Endotoxin-Induced Septic Shock in Rats
Authors: Martin Viviane , Wiesel Marie-Louise , Albert Anne , Beretz Alain 
Published: August 2015

1. Hypotension and vascular hyporesponsiveness to vasoconstrictors are observed during endotoxic shock, and are associated with increased production of nitric oxide in the vascular wall. Disseminated intravascular coagulation is another feature of septicaemia. We hypothesized that thrombin generated during disseminated intravascular coagulation might modulate the changes in vascular tone induced by endotoxin.
2. Incubation of rat aortic rings for 4 h with α-thrombin (0.003–3.0 NIH units/ml) did not change their reactivity to noradrenaline. Incubation for 4 h with lipopolysaccharide increased the EC50 for noradrenaline, whereas co-incubation of thrombin (0.5 NIH units/ml) with lipopolysaccharide did not alter this hyporeactivity to noradrenaline.
3. In vivo in rats, lipopolysaccharide caused early (1 h) and late (4–6 h) hyporeactivity to noradrenaline. In rats infused with lipopolysaccharide and heparin (1 U min−1 kg−1, 0.4 ml/h) or hirudin (2.2 mg ml−1 kg−1, 0.8 ml/h), vasopressor responses to noradrenaline were not different from those after infusion of lipopolysaccharide alone. Aortic rings taken from rats receiving both anticoagulant treatment and lipopolysaccharide had the same sensitivity to noradrenaline as those obtained from rats receiving lipopolysaccharide alone.
4. Our results suggest that, in vivo, disseminated intravascular coagulation does not modify the early and late effects of lipopolysaccharide on arterial pressure and that, in vitro, thrombin neither induces hyporeactivity to noradrenaline nor modifies lipopolysaccharide-induced hyporeactivity. We propose that thrombin generated during disseminated intravascular coagulation in rats does not play a major role in the alterations of vascular tone observed during endotoxic shock.
Haemodynamic and Hormonal Responses to Cardiac Pacing in Humans: Influence of Different Stimulation Sequences and Rates
Authors: Berglund Hans , Edlund Anders , Theodorsson Elvar , Vallin Hans 
Published: August 2015

1. To examine the effects of rate and pressure on release of vasoactive hormones, 10 healthy subjects were examined.
2. A standardized pacing protocol was used to achieve different haemodynamic responses at two predetermined heart rates. Haemodynamic variables, and plasma concentrations of atrial natriuretic peptide, arginine vasopressin, adrenaline and noradrenaline were measured.
3. Right atrioventricular pacing at a rate of 150 impulses/min resulted in disparate responses in right atrial pressure (slight decrease) and pulmonary capillary wedge pressure (increase). Change in arterial plasma concentration of atrial natriuretic peptide correlated to change in pulmonary capillary wedge pressure, and change in arterial plasma concentration of noradrenaline correlated to change in total systemic vascular resistance, whereas concentrations of adrenaline and arginine vasopressin did not alter significantly during the stimulation periods. A significant influence of rate in addition to the pressure related influence on plasma concentration of atrial natriuretic peptide was found. In contrast, an increase in rate in the absence of an increase in atrial pressures did not raise the plasma concentration of atrial natriuretic peptide. There was no significant relationship between change in atrial natriuretic peptide and noradrenaline.
4. These data support the concept of a rate dependence of atrial natriuretic peptide release in man. Increased atrial pressure and thus presumed atrial stretch seems to be a prerequisite for increased plasma concentration of atrial natriuretic peptide. In addition, these results highlight the importance of monitoring both left and right atrial pressure in clinical investigations assessing modulation of atrial natriuretic peptide release.
Haemodynamic Effects of Continuous Positive Airway Pressure in Humans with Normal and Impaired Left Ventricular Function
Authors: De Hoyos Alberto , Liu Peter P. , Benard Dean C. , Bradley T. Douglas 
Published: August 2015

1. Continuous positive airway pressure increases intrathoracic pressure, thereby decreasing left ventricular preload and afterload. We hypothesized that there would be a dose-related alteration in cardiac and stroke volume indices in response to continuous positive airway pressure in normal subjects and patients with congestive heart failure and that the direction of response among those with heart failure would be related to left ventricular preload.
2. Cardiac and stroke volume indices were measured at baseline and after 10 min of continuous positive airway pressure at both 5 and 10 cmH2O (0.5 and 0.99 kPa respectively) in 16 patients with heart failure and five control subjects with normal cardiac function. Among the eight patients with heart failure and elevated pulmonary capillary wedge pressure (≧12 mmHg) (≦ 1.6 kPa), cardiac index increased from 2.47 ± 0.34 at baseline to 2.91 ± 0.32 to 3.12 ± 0.40 l min−1 m−2 (P &lt; 0.025) while on 5 and 10 cm H2O of continuous positive airway pressure respectively. In the same patients stroke volume index increased from 27.8 ± 3.9 to 33.9 ± 4.2 to 36.8 ± 5.5 ml/m2 (P &lt; 0.05). In contrast, in both the control subjects and patients with heart failure and normal pulmonary capillary wedge pressure (&lt; 12 mmHg) there was a dose-related decrease in cardiac and stroke volume indices while on continuous positive airway pressure.
3. Continuous positive airway pressure causes dose-related increases in cardiac and stroke volume indices among patients with chronic heart failure and elevated left ventricular filling pressure. However, it induces dose-related reductions in cardiac and stroke volume indices among normal subjects as well as patients with heart failure and normal left ventricular filling pressures.
Participation of Endogenous Atrial Natriuretic Peptide in the Regulation of Urinary Protein Excretion in Experimental Diabetic Rats
Authors: Hirata Yasunobu , Suzuki Yasuko , Hayakawa Hiroshi , Suzuki Etsu , Kimura Kenjiro , Goto Atsuo , Kangawa Kenji , Matsuo Hisayuki , Omata Masao 
Published: August 2015

1. In order to determine whether atrial natriuretic peptide might play a role in the development of glomerular hyperfiltration in diabetes mellitus, we examined the effects of administration of glucose, albumin, atrial natriuretic peptide and an atrial natriuretic peptide receptor antagonist on renal function in rats with streptozotocin-induced diabetes mellitus and vehicle-treated control rats.
2. Four weeks after treatment, rats with diabetes mellitus had a higher mean plasma atrial natriuretic peptide concentration than controls [152 ± 5 (SE) versus 115 ± 6 pg/ml, P &lt; 0.01] and a higher glomerular filtration rate (3.3 ± 0.1 versus 2.7 ± 0.2 ml min−1 kg−1, P &lt; 0.05).
3. Infusion of albumin or glucose caused significant increases in atrial pressure, plasma atrial natriuretic peptide concentration and urinary excretion of sodium and protein in both groups of rats.
4. Increasing plasma atrial natriuretic peptide concentration by 60% via atrial natriuretic peptide infusion increased urinary excretion of sodium and protein in both control rats and rats with diabetic mellitus.
5. Administration of the atrial natriuretic peptide receptor antagonist HS-142-1 to diabetic rats resulted in diminished urinary excretion of both sodium (−61 ± 14%, P &lt; 0.02) and protein (−51 ± 17%, P &lt; 0.05). These changes were associated with a significant reduction in glomerular filtration rate (−32 ± 11%, P &lt; 0.05) and urinary cGMP excretion (−40 ± 14%, P &lt; 0.05). No significant effects of HS-42-1 on renal function were observed in control rats.
6. These results suggest that elevated plasma glucose may lead to an increase in atrial natriuretic peptide secretion via a rise in atrial pressure, which in turn results in increased urinary sodium and protein excretion. Elevated plasma atrial natriuretic peptide appears to contribute to the proteinuria in diabetic rats.
Sympathoadrenal Responses to Bronchoconstriction in Asthma: An Invasive and Kinetic Study of Plasma Catecholamines
Authors: Larsson Kjell , Carlens Per , Bevegård Sture , Hjemdahl Paul 
Published: August 2015

1. Bronchoconstriction does not seem to be a stimulus for sympathoadrenal activation, as judged by venous plasma concentrations of noradrenaline, adrenaline or neuropeptide Y-like immunoreactivity. However, venous measurements have methodological drawbacks. In the present study arterial and mixed venous (pulmonary arterial) levels of these variables were determined before and after histamine-induced bronchoconstriction in non-medicated asthmatic subjects. In addition, noradrenaline kinetics in plasma (isotope dilution) and the pulmonary overflows of noradrenaline and neuropeptide Y-like immunoreactivity were determined.
2. Histamine inhalation induced bronchoconstriction; forced expiratory volume in 1 s decreased by 38.7% ± 4.1% (SE) and arterial Po2 by 3.0 ± 0.9 kPa. This acute bronchoconstriction induced significant elevations of arterial and mixed venous plasma noradrenaline from ≤1.18 nmol/l to ≥1.40 nmol/l. The clearance of NA from plasma increased marginally. Thus, the arterial plasma NA response was due to increased spillover of noradrenaline to plasma (from 1.80 ± 0.18 to 2.52 ± 0.36 mmol min−1/m2 at maximal bronchoconstriction, with a subsequent further increase). There were no elevations of adrenaline or neuropeptide Y-like immunoreactivity in arterial plasma.
3. No sympathetic activation could be demonstrated in the lungs (pulmonary noradrenaline or neuropeptide Y-like immunoreactivity overflow), and no alterations in pulmonary vascular resistance or cardiac output were observed. Neither arterial nor mixed venous plasma concentrations of adrenaline were influenced by bronchoconstriction.
4. Acute bronchoconstriction thus leads to peripheral sympathetic activation (possibly due to the increased work of breathing) which does not involve the lungs. Adrenaline is not secreted in response to induced bronchoconstriction, and thus is of no functional importance as a counter-regulatory hormone in this situation.
Expression of the α- and β-Subunits of the Stimulatory and Inhibitory G-Proteins in β1-Adrenoceptor-Blocked and non-β-Adrenoceptor-Blocked Human Atrium
Authors: Jia Haiyan , Monteith Sue , Brown Morris J. 
Published: August 2015

1. Chronic β1-adrenoceptor blocker therapy induces hyperresponsiveness of the β2-adrenoceptor in human atrium. To investigate whether the β2-adrenoceptor sensitization induced by β1-adrenoceptor blockade is associated with altered gene expression of G-proteins, which couple the receptors to adenylate cyclase, we determined the mRNA expression of the α- and β-subunits of the stimulatory G-protein, Gs, and inhibitory G-protein, Gi, in human right atrial appendage by polymerase chain reaction and by enhanced chemiluminescence Northern blot analysis.
2. The polymerase chain reaction revealed bands of predicted size of Gsα, both short form and long form, all three Giα subtypes and three Gβ subtypes. In Northern blots, the digoxigenin-labelled antisense cRNA probe specific for Giα2 hybridized to a predominant band at 2.3 kb, whereas the Giα3 cRNA probe detected a message of 1.8 kb in total RNA extracted from human atrium. The cRNA probe encoding Gsα revealed one major band at 1.9 kb and one minor band at 1.7 kb. The Gβ cRNA probes detected messages of 3.4 kb for Gβ1, 1.8 kb for Gβ2 and 1.9 kb for Gβ3 in human atrium.
3. The mRNA levels of Gsα in β1-adrenoceptor-blocked atria (n = 12) were not significantly different from those in non-β-adrenoceptor-blocked atria (n = 12), nor were there any significant differences in the Giα2 mRNA levels between atria from patients treated with β1-adrenoceptor blockers and untreated patients. The ratios of 1.9-kb Gsα mRNA to 1.7-kb Gsα mRNA and of 1.9-kb Gsα mRNA to 2.3-kb Giα2 mRNA in β1-adrenoceptor-blocked patients were almost identical to those in non-β-adrenoceptor-blocked patients. Neither Gβ1 mRNA nor Gβ2 mRNA expression in β1-adrenoceptor-blocked atria differed significantly from that in non-β-adrenoceptor-blocked atria.
4. We conclude that the previously observed sensitization following β1-adrenoceptor-blockade of β2-adrenoceptors in human atria is unlikely to be mediated by altered gene expression of the α- and β-subunits of G-proteins.
Reduced Expression of Neurofibromin in the Soft Tissue Tumours Obtained from Patients with Neurofibromatosis Type 1
Authors: Takahashi Kazuhiro , Suzuki Hiroyuki , Hatori Masahito , Abe Yoshiyuki , Kokubun Shoichi , Sakurai Minoru , Shibahara Shigeki 
Published: August 2015

1. We analysed the expression of neurofibromin mRNAs, encoded by the gene responsible for neurofibromatosis type 1, and of neurofibromin protein in nine soft tissue tumours by S1 nuclease mapping and Western blot analyses. Four tumours were obtained from patients with neurofibromatosis type 1, comprising two neurofibromas, one fibrolipoma and one malignant schwannoma, and five neurogenic tumours were obtained from non-neurofibromatosis type 1 patients.
2. All tumours, except for a malignant schwannoma, similarly expressed three species of mRNA encoding neurofibromin, an isoform with the insertion of 21 amino acids in the domain related to ras GTPase-activating protein, and an N-terminal isoform lacking this domain.
3. Western blot analysis demonstrated deficiency of neurofibromin in the tumours derived from three out of the four neurofibromatosis type 1 patients: a fibrolipoma, a malignant schwannoma and a neurofibroma. In contrast, reduction in neurofibromin was not detected in the five tumours obtained from non-neurofibromatosis type 1 patients. Furthermore, the expression of ras GTPase-activating protein was detected in all nine tumours examined.
4. The undetectable or reduced level of neurofibromin in the tumours obtained from neurofibromatosis type 1 patients suggests that this deficiency is closely related to their tumourigenesis.
Plasminogen Activator and Plasminogen Activator Inhibitor I Release during Experimental Endotoxaemia in Chimpanzees: Effect of Interventions in the Cytokine and Coagulation Cascades
Authors: Biemond Bart J. , Levi Marcel , Ten Cate Hugo , Van Der Poll Tom , Büller Harry R. , Hack C. Erik , Ten Cate Jan W. 
Published: August 2015

1. Disseminated intravascular coagulation frequently accompanies Gram-negative sepsis and may contribute to widespread deposition of microthrombi. Besides the endotoxin-induced activation of coagulation, an important role for the fibrinolytic system has been postulated. The precise mechanisms underlying these fibrinolytic changes during endotoxaemia are not known but have been suggested to be mediated directly by cytokines or secondary to thrombin generation.
2. In the present study we have delineated in detail the fibrinolytic response to a bolus injection of endotoxin in non-human primates and analysed the contribution of cytokines and thrombin generation to the endotoxin-induced release of tissue-type plasminogen activator and plasminogen activator inhibitor 1. Chimpanzees received a bolus injection of endotoxin alone or in combination with blocking monoclonal antibodies directed against tumour necrosis factor or interleukin 6 or in combination with pentoxifylline. Furthermore, to assess the effect of coagulation activation on the activation of fibrinolysis, another group of chimpanzees received endotoxin in combination with either anti-tissue factor antibodies or recombinant hirudin.
3. Infusion of endotoxin induced a rapid increase in plasminogen activator activity and tissue-type plasminogen activator antigen levels and subsequent plasmin generation, reaching peak levels 2 h after endotoxin administration. Plasminogen activator inhibitor 1 levels remained constant for the first 2 h, after which time a steep increase was observed. Plasminogen activator activity and plasmin generation decreased simultaneously with the rise in plasminogen activator inhibitor 1 levels. Fibrinolytic activity remained suppressed during the remainder of the study owing to sustained increased levels of plasminogen activator inhibitor 1. The administration of pentoxifylline strongly attenuated the release of tissue-type plasminogen activator and plasminogen activator inhibitor 1, whereas the antitumour necrosis factor antibodies blocked the fibrinolytic response entirely. In contrast, interleukin 6-neutralizing antibodies did not affect the fibrinolytic response. Although endotoxin-induced generation of thrombin was completely prevented by the administration of tissue factor-neutralizing antibodies or by hirudin, no effect on the fibrinolytic response was observed. 4. In conclusion, the present study demonstrates that, after initial activation during endotoxaemia, fibrinolysis is inhibited by high levels of plasminogen activator inhibitor 1 and shows the pivotal role of tumour necrosis factor in the release of tissue-type plasminogen activator and plasminogen activator inhibitor 1 during endotoxaemia, which appears to be regulated independently of coagulation activation.
Comparison of Arterial Occlusion and Ischaemic Exercise for the Study of Vasodilatation in the Human Calf
Authors: Rueckert Patricia A. , Hanson Peter 
Published: August 2015

1. Calf blood flow was measured by venous occlusion plethysmography to compare two stimuli for eliciting maximal calf vascular conductance: (i) 10 min of arterial occlusion and (ii) isolated exhaustive calf exercise with ischaemic occlusion. The subjects were semi-supine with the calf in position for immediate blood flow measurements after release of the occluding cuff. Three groups of subjects were studied: young [35 years (SD 9, n = 9)], old [57 years (SD 5, n = 10)] and patients with congestive heart failure [63 years (SD 7, n = 7)].
2. Occlusion and ischaemic exercise were equally effective in producing maximal calf vascular conductance in each of the subject groups. Maximal calf vascular conductance (ml min−1 100 ml−1 mmHg−1) was equivalent in the young [ischaemic exercise 0.54 (SEM 0.03), occlusion 0.54 (SEM 0.05)] and old [ischaemic exercise 0.47 (SEM 0.05), occlusion 0.48 (SEM 0.04)] subjects. However, patients with congestive heart failure exhibited significantly reduced maximal calf vascular conductance [ischaemic exercise 0.20 (SEM 0.02), occlusion 0.20 (SEM 0.01)].
3. Analysis of the curves, generated by plotting serial calf vascular conductance values obtained immediately and every 15 s after occlusion cuff release for 165 s, revealed differences in the pattern of vasodilatation after occlusion and ischaemic exercise. Maximal calf vascular conductance was more sustained after ischaemic exercise, and the shape of the calf vascular conductance curve was similar in all subject groups. After occlusion in the patients with congestive heart failure, maximal calf vascular conductance occurred at 6 s (SEM 3) after cuff release and declined rapidly, whereas, in the healthy subjects, calf vascular conductance increased after the first measurement, with maximal calf vascular conductance at 20 s (SEM 4) in the old and 27 s (SEM 6) in the young groups. The time delay for maximal calf vascular conductance in the healthy subjects is consistent with a velocity-mediated proximal arterial dilatation, and the rapid decline in the patients with congestive heart failure may reflect sympathetic vasoconstriction and endothelial dysfunction.
4. In conclusion, both occlusion and ischaemic exercise are equally useful for the determination of vasodilatory capacity of the human calf. The prolonged vasodilatation after ischaemic exercise allows more time for the measurement of maximal calf vascular conductance. However, analysis of the entire calf vascular conductance recovery curve after occlusion provides more information on the relative contributions of factors which sustain vasodilatation after a maximal stimulus.
Plasma Semicarbazide-Sensitive Amine Oxidase Activity is Elevated in Diabetes Mellitus and Correlates with Glycosylated Haemoglobin
Authors: Boomsma Frans , Derkx Frans H. M. , van den Meiracker Anton H. , man in't Veld Arie J. , Schalekamp Maarten A. D. H. 
Published: August 2015

1. Semicarbazide-sensitive amine oxidase is a common name for a group of heterogeneous amine oxidases which are present in various mammalian tissues, especially in vascular smooth muscle cells, cartilage and adipose tissue, but also in plasma.
2. Plasma semicarbazide-sensitive amine oxidase activity was elevated in a group of 104 patients with insulin-dependent diabetes mellitus compared with normal control subjects (555 ± 172 versus 352 ± 102 m-units/l, P &lt; 0.0005).
3. Plasma semicarbazide-sensitive amine oxidase activity was higher in subgroups with either retinopathy or nephropathy or both [583 ± 116 (n = 34), 581 ± 229 (n = 10) and. 646 ± 249 m-units/l (n = 19), respectively] than in the subgroup without overt complications [486 ± 129 m-units/l (n = 41), P &lt; 0.005].
4. Plasma semicarbazide-sensitive amine oxidase activity was positively correlated with plasma glycosylated haemoglobin (r = 0.40; P &lt; 0.0001) and with log urinary albumin excretion (r = 0.26; P &lt; 0.025).
5. The possibility that semicarbazide-sensitive amine oxidase, by its conversion of endogenous amines like methylamine and aminoacetone into cytotoxic aldehydes, plays a role in the development of microvascular complications in diabetes mellitus, needs further investigation.
Clinical Significance of Urinary Ferritin Excretion in Patients with Transitional Cell Carcinoma
Authors: Chow Nan-Haw , Chang Chih-Jen , Cheng Pi-Er , Tzai Tzong-Shin , Huang Chun-Mei , Lin Johnny Shinn-Nan 
Published: August 2015

1. The serum ferritin level provides a valuable index of the body iron store. An increase in serum ferritin has often been observed in patients with neoplastic disease and correlates well with the stage of cancer. A few studies have suggested the potential of urinary ferritin as a marker for transitional cell carcinoma. The rationale of the measurement, however, has not been investigated in detail.
2. Urinary ferritin levels were evaluated in patients with diverse urological diseases to investigate their potential clinical implications.
3. Analysis of logarithmic transformed values (ng/mg creatinine) showed that patients with both neoplastic and non-neoplastic urological diseases had significantly higher ferritin levels than normal control subjects (P = 0.02). There was no apparent difference between subgroups of patients with urological disease (P &gt; 0.5). For patients with urothelial carcinoma, univariate analysis revealed a strong positive relationship between urinary ferritin levels and the density of lymphoid cells in tumour stroma (P = 0.0001), while no important association was observed with tumour grade (P = 0.32), stage (P = 0.29) or urinary cytology detection (P = 0.33). Patients with muscle-invasive tumour had significantly higher ferritin levels than those with papillary, superficial cancer (P &lt; 0.05). For patients with non-neoplastic urological disease (n = 19), urinary ferritin levels tend to correlate with the severity of tissue inflammation (P = 0.03).
4. The results suggest that urinary ferritin may reflect the degree of local inflammatory reaction in the urinary tract. For patients with urothelial carcinoma, the measurement may provide objective information regarding the amplitude of the local host response to tumour development. The potential of this test in determination of tumour treatment strategy needs further investigation.