bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity of Erythrocyte Sodium-Hydrogen Exchange in Normal Pregnancy
Authors: Matteucci Elena , Giampietro Ottavio
Published: August 2015

1. Pregnancy is associated with a 30–50% rise in cardiac output and a 50% increase in blood volume. The contribution of changes in the activity of primary and secondary active transporters to these haemodynamic adaptations remains unknown. For the first time, we measured sodium—hydrogen exchange activity over the course of normal pregnancy.

2. Eighteen healthy pregnant women were studied at 14, 24 and 33 weeks of gestation and compared with 18 non-pregnant healthy women. None of the pregnancies was complicated by hypertension. At each antenatal visit, body weight and blood pressure were recorded, blood and 24 h-urine samples were taken to control renal function and metabolic equilibrium, maternal glucose tolerance was evaluated by oral glucose test and glycated haemoglobin testing, and erythrocyte sodium-hydrogen antiport was also measured.

3. Erythrocyte antiport activity values were 10.0 ± 3.0, 9.6 ± 2.9 and 8.4 ± 3.5 mmol h−1 (litre of cells)−1 in the three gestational trimesters respectively, significantly higher at each trimester than in control women [6.8 ± 2.5 mmol h−1 (litre of cells)−1]. The clearances of urea and creatinine were constantly elevated in pregnant women; at each trimester their serum concentrations were lower than in non-pregnant women. Serum potassium significantly decreased during pregnancy. Serum total cholesterol and triacylglycerol levels, already above the normal range from the first trimester, further increased until the third trimester. The area under the glycaemic curve became larger during pregnancy, and the area under the insulinaemic curve increased to a lesser extent. There was a significant association between antiport activity and serum triacylglycerol levels.

4. The observed hyperactivity of the transporter, peaking at the fourteenth week of gestation, may be a contributing factor to the haemodynamic adjustments attending upon normal pregnancy.
Time-Course of Iron Overload and Biochemical, Histopathological and Ultrastructural Evidence of Pancreatic Damage in Hypotransferrinaemic Mice
Authors: Simpson Robert J. , Deenmamode Jean , McKie Andrew T. , Raja Kishor B. , Salisbury Jonathan R. , Iancu Theodore C. , Peters Timothy J.
Published: August 2015

1. The time course of iron overload of the pancreas in hypotransferrinaemic mice maintained on a standard rodent diet was compared with biochemical and histological markers of tissue damage.

2. Pancreatic iron levels increased linearly from weaning till 9 months of age [73.3 nmol/mg of tissue (SEM 9.9; n = 5) compared with 0.9 nmol/mg of tissue (SEM 0.1; n = 4) in age-matched controls] then decreased linearly till at least 18 months of age.

3. Investigation of tissue distribution of newly absorbed radioiron suggested that significant redistribution of iron from liver to pancreas (rather than direct dietary iron sources) must be invoked to explain the rate of pancreatic iron loading in hypotransferrinaemic mice.

4. Pancreatic epithelial cells first showed altered morphology at 9 months of age. At 12 months of age, the pancreatic epithelium had developed a micronodular appearance, with large numbers of acini replaced by atrophic, degenerated acinar cells. Increased collagen fibre deposition was evident by trichrome staining and by electron microscopy. Biochemical markers of pancreatitis (serum lipase, tissue pancreatitis-associated protein mRNA) were elevated before 9 months of age, whereas the levels of pancreatic amylase mRNA declined from 9 months of age.

5. The data suggest that iron loading of hypotransferrinaemic mouse pancreas proceeds up to a threshold level at 9 months of age followed by a progressive atrophy of secretory epithelium. The hypotransferrinaemic mouse pancreas is a useful model system for investigation of parenchymal cell damage by iron.
Xenotransplantation: Immune Barriers beyond Hyperacute Rejection
Authors: Dorling Anthony , Lechler Robert I.
Published: August 2015

1. The use of organs from animal donors (xenotransplantation) is a potential solution to the chronic shortage of allogeneic organs and currently the pig is thought to be the most suitable donor for man. However, porcine organs are rejected rapidly by a vascular process called hyperacute rejection which has so far prevented clinical xenotransplantation. Although it is likely that this barrier will be overcome in the near future by the application of novel strategies, probably involving the use of organs from transgenic pigs, data from animal models indicate that multiple other immune mechanisms will contribute to the rejection of xenografts.

2. We have described two aspects of these immune mechanisms. First, the phenomenon of ‘accommodation’, whereby xenografts acquire in vivo resistance to vascular rejection, has been explored in an in vitro model utilizing immortalized porcine endothelial cells. The results indicate that human anti-pig antibodies induce a concentration-dependent and time-dependent change in porcine endothelial cells compatible with the development of accommodation.

3. Secondly, the in vitro human anti-porcine T-cell response has been documented in detail, with particular emphasis on quantitative and qualitative comparisons with the in vitro T-cell alloresponse. The results of this work, which indicate that the response to porcine xenografts is likely to be significantly stronger than that against allografts, have important implications for the level of conventional immunosuppression that may be necessary to prevent xenograft rejection, and provide an important basis for the development of strategies to promote xenograft-specific immunosuppression and tolerance.
Vasoconstrictor Sensitivity to Noradrenaline and NG-monomethyl-l-arginine in Men and Women
Authors: Kneale Barry J. , Chowienczyk Philip J. , Cockcroft John R. , Coltart D. John , Ritter James M.
Published: August 2015

1. Nitric oxide has potential anti-atherogenic actions as well as regulating vascular tone. Animal studies suggest that there are sex differences in basal nitric oxide biosynthesis, but it is not known whether such differences exist between men and women.

2. We have investigated this question by measuring forearm blood flow responses, using venous occlusion plethysmography, to brachial artery infusion of NG-monomethyl-l-arginine (an inhibitor of NO biosynthesis) and noradrenaline in 40 healthy subjects (20 men and 20 premenopausal women). Mean arterial blood pressure was 89 ± 10 mmHg (mean ± SD) in men and 87 ± 9 mmHg in women, and mean total cholesterol was 4.25 ± 0.99 mmol/l (mean ± SD) and 4.26 ± 0.80 mmol/l respectively.

3. In men, vasoconstrictor responses to NG-monomethyl-l-arginine, 1–4 μmol/min (15–28% mean reduction in blood flow), were consistently less than responses to noradrenaline, 60–240 pmol/min (26–37%), whereas in women, vasoconstrictor responses to NG-monomethyl-l-arginine (19–30%) were consistently greater than those to noradrenaline(11–17%). The sex difference in relative sensitivity to vasoconstrictors was significant (P < 0.001).

4. Our findings are consistent with either greater sensitivity to noradrenaline in men compared with premenopausal women, or a greater basal nitric oxide biosynthesis in premenopausal women compared with men.
Effect of Acute Hyperglycaemia on Basal and Fat-Induced Exocrine Pancreatic Secretion in Humans
Authors: Lam W. F. , Muller E. S. M. , Souverijn J. H. M. , Lamers C. B. H. W. , Masclee A. A. M.
Published: August 2015

1. We have investigated the effect of acute hyperglycaemia on pancreatico-biliary secretion in healthy subjects. Duodenal outputs of trypsin, lipase, amylase, bicarbonate and bilirubin were measured for 90 min under basal conditions and for 90 min in response to intrajejunal fat administration (1 g/h) on 2 separate days: during normoglycaemia (blood glucose 5 mmol/l) and during acute hyperglycaemia aimed at 15 mmol/l. Plasma cholecystokinin levels, as the major hormonal stimulus of pancreatic and biliary secretion, and plasma pancreatic polypeptide levels, as an indirect measure of vagal-cholinergic tone, were determined at regular intervals.

2. In the basal period pancreatico-biliary secretion was significantly (P < 0.05) reduced during hyperglycaemia compared with normoglycaemia. During normoglycaemia and hyperglycaemia intrajejunal fat significantly (P < 0.05) stimulated pancreaticobiliary secretion. However, during hyperglycaemia, fat-stimulated 90 min pancreatico-biliary secretion was significantly (P < 0.05) reduced compared with normoglycaemia: trypsin (23 ± 7 units versus 66 ± 20 units), lipase (36 ± 8 k-units versus 74 ± 18 k-units), amylase (8 ± 2 k-units versus 18 ± 5 k-units) and bilirubin (32 ± 8 μmol versus 71 ± 14 μmol). Plasma cholecystokinin levels increased significantly (P < 0.05) during fat administration and were not different between the two experiments. Plasma pancreatic polypeptide levels were significantly (P < 0.05) reduced during hyperglycaemia both in the basal period and during intrajejunal fat administration.

3. It is concluded that basal and fat-stimulated pancreatico-biliary secretion are significantly reduced during acute hyperglycaemia. Acute hyperglycaemia does not affect intrajejunal fat-stimulated cholecystokinin secretion. Acute hyperglycaemia inhibits basal and stimulated pancreatic polypeptide secretion suggesting vagal-cholinergic inhibition of pancreatico-biliary secretion during hyperglycaemia.
Pcr Detection of the Human Papillomavirus: Improved DNA Recovery from Frozen Biopsies
Authors: Mota Fernando F. , Kanan Joao H.
Published: August 2015

1. One of the main obstacles to the reliable detection of human papillomavirus in cervical intraepithelial neoplasia is that a minute quantity of infected tissue is often all that is available.

2. In this work, proteinase K-phenol-chloroform-treated sections of frozen cervical biopsies were split in two. Half of the material was precipitated by ethanol in the presence of glycogen, and in the remaining half glycogen was absent.

3. On average a 15-fold increase in total DNA yield was obtained with glycogen. As a result, in 63 cases analysed by PCR for human papillomavirus type 16, we were able to detect nearly 20% more positive samples when glycogen was used.

4. The implications of the improved accuracy of diagnosis are that women requiring a closer follow-up can be identified, and conversely rescreening intervals can be extended for those testing negative for oncogenic human papillomavirus types with more confidence than in the past.
Just How Big is the Pulmonary Granulocyte Pool?
Authors: Peters A. M.
Published: August 2015

1. It is widely believed that a large fraction of the blood granulocyte population is located in the pulmonary circulation.

2. Evidence in favour of this belief is based on several independent and complementary techniques including studies of granulocyte deformability in relation to pulmonary capillary diameter, isolated perfused lungs, direct videomicroscopic observations, cellular and capillary morphometry, physiological studies and labelled blood cell kinetics.

3. Inconsistencies in this body of evidence can be identified and traced in many cases to doubts concerning the physiological integrity of labelled granulocytes.

4. In addition to the lungs, other regions of the body undoubtedly pool granulocytes, and there is good quantitative evidence, based mainly on clinical studies, pointing to the liver, bone marrow and especially the spleen.

5. Clinical studies, furthermore, have generally not supported major granulocyte pooling in the lung, except in association with systemic inflammatory diseases, such as inflammatory bowel disease and systemic vasculitis.

6. Compromises based on technical considerations permit reconciliation of the literature, and an overall whole-body model of granulocyte distribution is proposed with which all the existing data are broadly compatible.
Membrane Microviscosity and Plasma Triacylglycerols in the Rat
Authors: Devynck Marie-Aude , Kuneš J. , Le Quan Sang Kim Hanh , Zicha J.
Published: August 2015

1. Multiple cell membrane alterations have been described in humans and animals with various genetic forms of hypertension and/or dyslipidaemia. The aim of our study was to characterize membrane microviscosity, using two different fluorescent probes exploring either the outer membrane leaflet [trimethylamino-diphenylhexatriene (TMA-DPH)] or the lipid membrane core [diphenylhexatriene (DPH)], in platelets and erythrocytes of genetically hypertensive rats of the Prague hereditary hypertriglyceridaemic (HTG) strain. The relationships of membrane microviscosity to hypertension, hypertriglyceridaemia and cell calcium handling were also investigated.

2. Membrane microviscosity was similar in HTG and normotensive control Wistar rats when measured in platelets or erythrocyte ghosts incubated in Na+-containing medium. On the contrary, TMA-DPH fluorescence anisotropy was significantly reduced in HTG platelets incubated in Na+-free medium because external Na+ removal elicited a larger rise of TMA-DPH anisotropy in Wistar platelets.

3. Plasma triacylglycerols were associated positively with platelet TMA-DPH anisotropy and negatively with DPH anisotropy in both strains. The slopes of these relationships were reduced in HTG compared with Wistar rats. Platelet TMA-DPH anisotropy correlated positively and DPH anisotropy negatively with the cytosolic calcium concentration in unstimulated platelets, the slopes being almost identical in both strains.

4. Pulse pressure correlated negatively with TMA-DPH anisotropy and positively with DPH anisotropy found in erythrocyte ghosts.

5. The present results suggest that plasma triacylglycerols and cytosolic calcium are capable of modulating the membrane microviscosity in this new animal model of genetic hypertension associated with hypertriglyceridaemia.
Angiotensin-Converting Enzyme Inhibition Does Not Correct Early Defects in Renal and Vascular Permeability in Diabetes Mellitus
Authors: Zietse Robert , Derkx Frans H. , Weimar Willem , Schalekamp Maarten A.
Published: August 2015

1. In diabetes mellitus a selective increase in the excretion of albumin generally precedes the occurrence of demonstrable loss of glomerular size-selectivity. However, even in this (microalbuminuric) phase of diabetic nephropathy a defect in glomerular barrier function can be demonstrated during infusion of atrial natriuretic peptide.

2. The aim of this study was to investigate whether angiotensin-converting enzyme inhibition could prevent the proteinuric response to atrial natriuretic peptide in these patients. We performed infusions of atrial natriuretic peptide (0.01 μg min−1 kg−1) in 10 patients with insulin-dependent diabetes mellitus and microalbuminuria (urinary albumin excretion 90 ± 44 mg/day), both before and after 1 month of treatment with enalapril (20 mg once daily).

3. Despite a 40% reduction in proteinuria, angiotensin-converting enzyme inhibition did not prevent the atrial natriuretic peptide-induced increase in protein excretion. Both before and during angiotensin-converting enzyme inhibition, atrial natriuretic peptide infusion resulted in a significant increase in the fractional excretion of large dextran molecules, which is compatible with an increase in flow through large unrestrictive ‘shunt' pores. Atrial natriuretic peptide infusion also induced an increase in the transcapillary escape rate of albumin and angiotensin-converting enzyme inhibition also failed to prevent this effect of atrial natriuretic peptide on peripheral capillary permeability.

4. We conclude that angiotensin-converting enzyme inhibition during 1 month does not correct the capillary barrier function defect in patients with diabetes mellitus and microalbuminuria that is unmasked by atrial natriuretic peptide infusion.
Systemic Nitric Oxide Synthase Inhibition Increases Insulin Sensitivity in Man
Authors: Butler R. , Morris A.D. , Struthers A. D.
Published: August 2015

1. Recent evidence shows that skeletal muscle blood flow is an important determinant of insulin sensitivity and that insulin-mediated vasodilatation is nitric oxide dependent. These results have given rise to the hypothesis that endothelial nitric oxide inhibition may decrease insulin sensitivity in humans.

2. We examined this hypothesis directly by evaluating the effects of systemic nitric oxide synthase inhibition with NG-monomethyl l-arginine (3 mg h−1 kg−1) on whole-body glucose uptake (euglycaemic hyperinsulinaemic clamp) and calf blood flow (bilateral calf venous occlusion plethysmography) in 16 healthy male subjects in a randomized, double-blind, placebo-controlled, crossover study.

3. NG-Monomethyl l-arginine infusion was associated with a pressor effect (119/61 ± 2/2 compared with 114/58 ± 2/2 mmHg for placebo; P < 0.001), and a negative chronotropic response (57 ± 2 compared with 62 ± 2 beats/min for placebo; P < 0.001). The glucose infusion rate was significantly increased after infusion of NG-monomethyl l-arginine (8.9 ± 0.9 compared with 7.9 ± 0.8 mg min−1 kg−1 for placebo; P = 0.002). Whole-body glucose uptake increased during the clamp, with values of 9.4 ± 0.7 and 10.9 ± 0.8 mg min−1 kg−1 for placebo and NG-monomethyl l-arginine respectively (P = 0.036; 95% confidence interval 0.2,2.8). NG-Monomethyl l-arginine was associated with increased calf blood flow by comparison with placebo (P < 0.05, area under curve).

4. These data show for the first time that systemic inhibition of nitric oxide synthesis increases rather than decreases whole-body glucose uptake. We suggest that the higher skeletal muscle blood flow seen after NG-monomethyl l-arginine may explain the observed increase in whole-body glucose uptake.
Pancreatic Bile-Salt-Dependent Lipase Activity in Serum of Diabetic Patients: Is There a Relationship with Glycation?
Authors: Caillol Nathalie , Pasqualini Eric , Mas Eric , Guieu Régis , Valette Anne , Boyer Jean , Lombardo Dominique
Published: August 2015

1. Pancreatic bile-salt-dependent lipase has been detected in human plasma where it has the capability to modify normal low- and high-density lipoprotein composition and structure and to reduce the atherogenicity of oxidized low-density lipoprotein (Shamir R, Johnson WJ, Morlock-Fitzpatrick K, Zolfaghari R, Li L, Mas E, Lombardo D, Morel DW, Fisher EA. Pancreatic carboxyl ester lipase: a circulating enzyme that modifies normal and oxidized lipoproteins in vitro. J Clin Invest 1996; 97: 1696–704).

2. In the present study, we investigated the effect of glycation and particularly that of human serum albumin on the activity of bile-salt-dependent lipase. In vitro, bile-salt-dependent lipase activity decreased in the presence of human serum albumin; however, this was less pronounced in the presence of glycated human serum albumin. In vivo, bile-salt-dependent lipase specific activity was about 2-fold higher in the sera of diabetic patients than in the sera of normal subjects.

3. A significant increase in the specific activity of bile-salt-dependent lipase related to the serum level of glycation was observed. The increase in bile-salt-dependent lipase specific activity was not related to the glucose concentration in serum suggesting that glycation of bile-salt-dependent lipase could not be involved in the observed effects. Although the stability of serum bile-salt-dependent lipase was important enough to allow a systemic action of the enzyme on lipoproteins, it could not explain the higher activity of the enzyme in diabetic serum.

4. We concluded that bile-salt-dependent lipase could be helpful against the premature development of atherosclerosis in diabetes.
Metabolic and Myoelectrical Effects of Acute Hypoxaemia during Isometric Contraction of Forearm Muscles in Humans: A Combined 31P-Magnetic Resonance Spectroscopy-Surface Electromyogram (MRS—SEMG) Study
Authors: Bendahan D. , Badier M. , Jammes Y. , Confort-Gouny S. , Salvan A. M. , Guillot C. , Cozzone P. J.
Published: August 2015

1. Failure of muscle force during sustained fatiguing contraction is associated with myoelectrical and metabolic alterations. However, the inter-relationships between these two types of events remain unclear. The purpose of this study was to examine the effects of decreased oxygen availability during sustained contraction on myoelectrical and metabolic changes, thereby addressing the issue of fatigue.

2. 31P-Magnetic resonance spectra and surface electromyograms were simultaneously recorded in six subjects (three women and three men) performing isometric contraction of forearm flexor muscles sustained at 60% maximum value of force under aerobic or acute hypoxaemic conditions (inhalation of a gas mixture containing 12% O2).

3. The 5 min hypoxaemic rest preceding contraction did not affect the phosphocreatine level and pH value. Under both conditions of oxygen availability, the magnitude of metabolic changes remained similar and the duration of contraction was unaffected (similar workload). However, hypoxaemia significantly reduced the rate of changes in integrated surface electromyogram activity measured in the high-frequency band. Correlative analysis of magnetic resonance spectroscopy and surface electromyogram data shows that for a given surface electromyogram change, metabolic variations were always larger under hypoxaemic conditions.

4. These results suggest that hypoxaemia does not alter metabolic changes, i.e. decrease in pH and phosphocreatine during static contraction. The downward shift of the relationships between myoelectrical and metabolic changes under hypoxaemia points to the existence of a better excitation—contraction coupling in acute hypoxaemia compared with normoxia and this is indicative of an adaptative mechanism.
Early Administration of Angiotensin-Converting Enzyme Inhibitor Captopril, Prevents the Development of Hypertension Programmed by Intrauterine Exposure to a Maternal Low-Protein Diet in the Rat
Authors: Sherman Rachel C. , Langley-Evans Simon C.
Published: August 2015

1. Associations of intrauterine exposure to maternal undernutrition with later hypertension and coronary heart disease in the human population have been duplicated in the rat. Fetal exposure to low protein diets produces offspring that develop raised systolic blood pressure by the age of weaning. This animal model of ‘programmed’ hypertension was used to investigate the role of the renin—angiotensin system in the initiation and maintenance of high blood pressure.

2. Pregnant rats were fed diets containing 18 or 9% casein from conception until littering. The offspring from these pregnancies were administered captopril either between 2 and 4 weeks of age, or from 10 to 12 weeks of age.

3. The feeding of low protein diets in pregnancy had no effect upon the reproductive ability of female rats and the offspring generated were of normal birthweight. By 4 weeks of age the male and female offspring of low-protein-fed dams had systolic blood pressures that were 24–25 mmHg higher than those of rats exposed to a control diet in utero.

4. Treatment of 10-week-old female offspring with captopril for 2 weeks indicated that angiotensin II formation may play a role in the maintenance of high blood pressure in low-protein-exposed rats. While captopril had no significant effect upon systolic pressures of rats exposed to the control diet in intrauterine life, the systolic blood pressures of low-protein animals rapidly declined by 31 mmHg.

5. Administration of captopril to male and female offspring between 2 and 4 weeks of age exerted long-term effects upon systolic blood pressure. Eight weeks after cessation of treatment, at an age where maximal blood pressures are achieved, captopriltreated, low-protein-exposed rats had similar blood pressures to normotensive rats exposed to the protein-replete diet in utero.

6. In conclusion, we have demonstrated that the elevation of adult blood pressure associated with fetal exposure to a maternal low-protein diet, is prevented by early administration of an angiotensin-converting enzyme inhibitor. The actions of angiotensin II in the late suckling period may be a critical determinant of long-term cardiovascular functions in these animals.
Human Muscle Sympathetic Activity and Cardiac Catecholamine Spillover: No Support for Augmented Sympathetic Noradrenaline Release by Adrenaline Co-Transmission
Authors: Thompson Jane M. , Wallin B. Gunnar , Lambert Gavin W. , Jennings Garry L. , Esler Murray D.
Published: August 2015

1. Evidence from animal studies indicates that circulating adrenaline may be taken up into sympathetic nerves, facilitating the release of noradrenaline. To test whether adrenaline acts as a co-transmitter in humans we studied eight healthy men (aged 19–23 years) during isometric handgrip before and after an adrenaline infusion (1–3 μg/min for > 30 rain). Sympathetic activity was assessed using radiotracer kinetic techniques to measure total and cardiac spillovers of noradrenaline and adrenaline, and microneurography to measure muscle sympathetic activity.

2. During the adrenaline infusion systolic blood pressure and heart rate increased significantly and diastolic blood pressure decreased. Total noradrenaline spillover, and arterial and coronary sinus plasma noradrenaline concentrations, increased significantly. Muscle sympathetic nerve traffic increased both during and after the end of the infusion.

3. Thirty minutes after the end of the adrenaline infusion there was adrenaline release from the heart (1.5 ± 0.4 ng/min, mean ± S.E.M.) indicating that significant adrenaline loading of cardiac sympathetic nerves had occurred. At this time muscle sympathetic nerve traffic and total body and cardiac noradrenaline spillovers were similar (P > 0.05) to pre-adrenaline infusion values (nerve traffic 24 ± 4 versus 21 ± 3 bursts/min; total noradrenaline spillover 698 ± 98 versus 618 ± 119 ng/min; cardiac noradrenaline spillover 16.2 ± 2.8 versus 13.9 ± 3.9 ng/min).

4. Isometric handgrip contraction evoked similar responses pre- and post-adrenaline infusion in total and cardiac noradrenaline spillovers and in muscle sympathetic activity.

5. The results do not support the theory that adrenaline is a co-transmitter facilitating noradrenaline release from human sympathetic nerves.
Time Course and Pattern of Pulmonary Flow Distribution following Unilateral Airway Occlusion in Sheep
Authors: Johansen B. , Melsom M. N. , Flatebø T. , Nicolaysen G.
Published: August 2015

1. Unilateral bronchial occlusion causes ipsilateral hypoxic pulmonary vasoconstriction, which shifts blood flow towards the other lung. We studied the time course of flow diversion following acute bronchial occlusion, and the temporal effect of the latter on blood gases and vertical distribution of blood flow within the two lungs.

2. Serial infusions of radioactive or fluorescent microspheres were given to each of seven adult standing sheep before, during occlusion of the left mainstem bronchus for up to 6 min, and after release of occlusion. Pulmonary and systemic arterial pressures were recorded continuously and arterial and mixed venous blood gases were determined intermittently. Post-mortem, the lungs were inflated, dried and cut into slices. Relative blood flow at the time of infusion was expressed as the weight-normalized intensity of each tracer in each slice or lung divided by the weight-normalized intensity in the two lungs.

3. Within 30 s, 1 min and 2 min after onset of occlusion, flow in the occluded lung had decreased to 68–84% (range), 51–78% and 43–79% respectively, of the initial value. In the contralateral lung, flow increased by 10–24%, 14–37% and 23–39% respectively. The distribution of flow along the gravitational axis within each lung varied widely between animals, both before and during occlusion. The during-occlusion profiles in the occluded lung differed from those in the non-occluded lung. In either lung, during-occlusion profiles could not be predicted with certainty from the pre-occlusion profiles. Two minutes post-occlusion, inter- and intra-lung flow distribution were nearly the same as before occlusion. Arterial oxygen tension fell in the first minute of occlusion, but never below 7.5 kPa, and increased slowly thereafter. Arterial carbon dioxide tension increased slightly throughout the occlusion period. No appreciable changes in systemic or pulmonary artery pressure were observed. Post-occlusion, arterial oxygen tension was still sub-normal, while carbon dioxide tension continued to increase.

4. We conclude that acute unilateral bronchial occlusion diverts blood flow within 30 s towards the contralateral lung. This rapidly occurring flow diversion prevents the development of severe arterial hypoxaemia. The variable and largely unpredictable distribution of blood flow in the hyperfused non-occluded lung might explain some of the gas-exchange abnormalities observed in physiologically hyperfused lungs and in patients with one hyperfused lung.
Haemodynamic Responses in Young and Elderly, Healthy Subjects during Ambient and Warm Head-up Tilt
Authors: Lye Michael , Walley Tom
Published: August 2015

1. Postural hypotension is common in elderly people and is usually multifactorial in origin. In young subjects increased ambient temperature is associated with postural symptoms. We hypothesized that such increases in skin temperature due to the use of bed clothes might contribute to nocturnal postural hypotension in the elderly. We therefore studied haemodynamic responses to head-up tilt in healthy elderly and young subjects, with and without passive heating induced by covering with blankets.

2. Nine young (28.7 ± 1.5 years; mean ± S.E.M.) and nine elderly (71.9 ± 1.8 years) subjects were studied. All had been carefully screened to exclude factors likely to affect responses to tilt. All subjects underwent a standard head-up tilt procedure at ambient room temperature while haemodynamic responses were monitored. The subjects were then covered in blankets for 55 min and the tilt repeated. Skin temperature before the second tilt had increased from approximately 32.5 °C to approximately 35.2 °C (P < 0.001).

3. The elderly subjects maintained higher blood pressures throughout both tilts (P < 0.001) and both groups showed similar qualitative responses to tilt. Supine heart rates were higher in the elderly group (P < 0.01) with a tendency to increase more in the young group in response to tilt, especially while warm (P = 0.370). Stroke volumes and cardiac indices were consistently higher in the young group who showed larger changes during both head-up tilts. In both groups the haemodynamic responses to ambient and warm tilt were essentially the same.

4. Healthy elderly subjects, who are carefully screened to exclude individuals with cardiovascular pathology, respond to head-up tilt in the same qualitative fashion as young subjects. Quantitative responses in older subjects are ‘damped’. Short-term natural body warming does not impair the reflexes in young or old subjects.
Vasopressin V1a and V2 Receptor mRNA in Deoxycorticosterone Acetate-Salt Hypertension in the Rat
Authors: Risvanis J. , Johnston C. I. , Phillips P. A. , Burrell L. M.
Published: August 2015

1. Vasopressin V1a and V2 receptors are differentially regulated in deoxycorticosterone acetate-salt hypertension. This paper investigated whether the changes were due to transcription changes in receptor mRNA assessed by in situ hybridization histochemistry (liver V1a receptor) and by reverse transcription—polymerase chain reaction (kidney V1a and V2 receptor).

2. Systolic blood pressure and plasma vasopressin levels were significantly elevated in deoxycorticosterone acetate-salt rats (n = 24) compared with water-control (n = 28) and salt-control rats (n = 28) (P < 0.001). Plasma sodium was elevated in deoxycorticosterone acetate-salt rats compared with both control groups (P < 0.01) and plasma osmolality was elevated in deoxycorticosterone acetate-salt rats compared with water-control rats (P < 0.05).

3. Binding kinetic studies demonstrated downregulation of liver V1a and kidney V2 receptors in deoxycorticosterone acetate-salt rats compared with water-control and salt-control rats (P < 0.05). This was not associated with any change in liver V1a receptor mRNA (P = 0.95), or in kidney V1a (P = 0.79) or V2 receptor mRNA (P = 0.96).

4. In deoxycorticosterone acetate-salt hypertension, downregulation of liver V1a and kidney V2 receptors occurs in the setting of stable vasopressin gene transcription. These results suggest that changes in receptor processing may be responsible for the differential regulation of vasopressin receptors that occurs in deoxycorticosterone acetate-salt hypertension.
Serum total sialic acid, a reputed cardiovascular risk factor, and its relationship to lipids, plasma fasting insulin, blood pressure and body mass index in normal individuals
Authors: CROOK M. , LUMB P. , ANDREWS V. , SWAMINATHAN R.
Published: August 2015

1.Serum sialic acid is a reputed cardiovascular risk factor, but the reason why this is so is not clear. We therefore studied its relationship with other known cardiovascular risk factors (particularly those associated with insulin resistance) in 100 healthy young subjects (54 females and 46 males, age 20.7±0.89 years).

2.There was a significant univariate correlation between serum total sialic acid and fasting plasma insulin. Serum total sialic acid also correlated with fasting plasma glucose concentration and serum cholesterol and triacylglycerol.

3.In females there was a strong univariate correlation between serum total sialic acid and plasma fasting insulin and glucose concentrations, although in males there was a weaker univariate correlation between serum total sialic acid and fasting plasma glucose and the insulin resistance index. In addition, serum total sialic acid significantly correlated with systolic blood pressure, fasting serum cholesterol and triacylglycerol concentrations and body mass index in the females. In males serum total sialic acid significantly positively correlated with fasting serum cholesterol and triacylglycerol concentrations, and correlated inversely with the hip/waist ratio.

4.In multiple regression analysis of the 100 subjects serum total sialic acid correlated independently with fasting serum cholesterol, glucose and also plasma insulin concentrations. In females serum total sialic acid independently correlated with systolic and diastolic blood pressure, and serum cholesterol and fasting plasma glucose concentrations, although there was no significant independent correlation between serum total sialic acid and any of the other variables in the males.
Alterations in renal degradation of albumin in early experimental diabetes in the rat: a new factor in the mechanism of albuminuria
Authors: BURNE Melissa J. , PANAGIOTOPOULOS Sianna , JERUMS George , COMPER Wayne D.
Published: August 2015

1.Albumin is normally excreted as a mixture of intact protein and fragments that are produced during renal passage. The purpose of this study was to investigate the ratio of intact versus degraded forms of excreted albumin to ascertain whether changes in this ratio could account for the apparent increase in albumin excretion seen in diabetes, as measured by standard radioimmunoassay techniques.

2.Four-week male Sprague–Dawley rats with streptozotocin-induced diabetes and age-matched control rats were intravenously injected with [3H]albumin. Urine collected over 2 h was analysed by size exclusion chromatography and radioimmunoassay. A standard radioimmunoassay found a 7-fold increase in albumin excretion rate in diabetic rats, whereas there was only a 2-fold increase in albumin excretion (intact plus fragments). Urine analysed by size exclusion chromatography showed severe degradation for control rats (% monomer = 4±2%); in diabetic rats there was a significant amount of monomer albumin excreted, along with moderately degraded and heavily degraded albumin (% monomer = 17±5%).

3.This study has shown that the radioimmunoassay, which specifically detects intact albumin, considerably underestimates the amount of total urinary albumin which consists of intact and degraded material. The increase in albumin excretion rate observed in diabetes as measured by radioimmunoassay is mainly due to a change in the amount of intact albumin excreted and this is specifically due to the inhibition of albumin degradation at a post-glomerular site and not due to the onset of any type of glomerular ‘shunt' pathway.
A novel method for the visualization of the in situ mucus layer in rat and man
Authors: JORDAN NICOLA , NEWTON JULIA , PEARSON JEFFREY , ALLEN ADRIAN
Published: August 2015

1.The observed thickness of the gastric mucus barrier varies widely, even appearing discontinuous, depending on the methods used. Here we describe the development and application of a modified periodic acid Schiff/Alcian Blue staining technique for use on cryostat sections of gastric mucosa. This technique for the first time enables the preservation and visualization of the full thickness of the adherent gastric mucus layer and the underlying mucosa.

2.In designing this novel method we have selected those procedures which would result in the least alteration to the mucus layer. The methods used were snap freezing, cryostat sectioning of the whole stomach followed by brief ethanol pretreatment (10 min in 100% ethanol), a prolonged staining with periodic acid Schiff/Alcian Blue (15 min and 2.5 h respectively), a gentle post-fixation (45 min paraformaldehyde vapour at 37 °C) and the use of a water-soluble mountant.

3.A continuous, adherent mucus layer was observed over the surface of the rat gastric mucosa (periodic acid Schiff/Alcian Blue stained) and human gastric antral biopsies (periodic acid Schiff stained). In the rat the mean (S.D.) mucus thickness measurements along the antrum to oesophageal axis (which was divided histologically into four regions, A to D) were: A, 166 (47) μm; B, 179 (48) μm; C, 184 (50) μm; D (the non-glandular stratified epithelium at the top of the stomach), Absent. In human gastric antral biopsies the mean (S.D.) mucus thickness was 144 (52) μm.

4.This new technique has enabled the visualization and precise measurement of thickness of the gastric mucus layer in rat and man. The adherent gastric mucus layer was observed to be continuous in the rat glandular stomach and human antrum. In validation experiments in rat the mean mucus thickness measurements were found to be twice those measured by conventional histological techniques, in which the mucus layer appeared discontinuous and patchy. However, they were within the range of thickness values seen in unfixed tissues and in the rat in vivo preparation.
In utero programming of chronic disease
Authors: BARKER D. J. P.
Published: August 2015

1.Many human fetuses have to adapt to a limited supply of nutrients. In doing so they permanently change their structure and metabolism.

2.These ‘programmed' changes may be the origins of a number of diseases in later life, including coronary heart disease and the related disorders stroke, diabetes and hypertension.

3.This review examines the evidence linking these diseases to fetal undernutrition and provides an overview of previous studies in this area.
Activation of myocardial and renal natriuretic peptides during acute intravascular volume overload in dogs: functional cardiorenal responses to receptor antagonism
Authors: BORGESON Daniel D. , STEVENS Tracy L. , HEUBLEIN Denise M. , MATSUDA Yuzuru , BURNETT John C.
Published: August 2015

1.A family of structurally related but genetically distinct natriuretic peptides exist which include atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) of myocardial cell origin and C-type natriuretic peptide (CNP) of endothelial and renal epithelial cell origin. All three exert actions via cGMP, with ANP and BNP functioning via the natriuretic peptide A receptor and CNP via the natriuretic peptide B receptor.

2.Circulating and urinary natriuretic peptides were determined in response to acute intravascular volume overload (AVO). Additionally, their functional role in cardiorenal regulation during AVO was investigated by utilizing the natriuretic peptide receptor antagonist HS-142-1. Control (n = 5) and study dogs (HS-142-1, n = 9) underwent AVO with normal saline equal to 10% of body weight over 1 ;h. Both groups demonstrated similar significant increases in right atrial pressure, pulmonary capillary wedge pressure, pulmonary artery pressure and cardiac output. Circulating ANP paralleled increases in right atrial pressure and pulmonary capillary wedge pressure, with no changes in plasma BNP or CNP. At peak AVO, urinary CNP excretion was increased compared with baseline (7.0±4.2 versus 62±8.0 ;pg/min, P< 0.05).

3.In the HS-142-1-treated group, plasma cGMP was decreased compared with the control group (9.6±1.1 to 5.0±1.2 ;pmol/ml, P< 0.05). A significant attenuation of natriuresis (566±91 versus 1241±198 ;μEq/min, P< 0.05) and diuresis (4.8±0.7 versus 10.1±2.0 ;ml/min, P< 0.05) was also observed at peak AVO in the HS-142-1 treated group.

4.These findings support differential and selective responses of the three natriuretic peptides to AVO, in which plasma ANP and urinary CNP are markers for AVO. Secondly, these studies confirm the role of ANP and CNP but not BNP in the natriuretic and diuretic response to acute volume overload.
Control of the forearm microcirculation: interactions with measures of obesity and noradrenaline kinetics
Authors: NESTEL Paul J. , YAMASHITA Takeshi , SASAHARA Takayuki , CHIN-DUSTING Jaye P. F. , ESLER Murray D. , DART Anthony M. , JENNINGS Garry L.
Published: August 2015

1.Obesity influences the responsiveness of the microcirculation; constriction is augmented probably reflecting heightened sympathetic nervous activity.

2.The responsiveness of the microcirculation in the forearm to constriction and dilation was therefore examined in 14 men and women with varying degrees of abdominal adiposity, to determine the potential effects of sympathetic nervous activity and adiposity on flow. Changes in basal blood flow were measured by venous occlusion plethysmography during intra-arterial infusions of noradrenaline, acetylcholine and sodium nitroprusside and after temporary ischaemia. Total body noradrenaline spillover was also measured, as an index of sympathetic neuronal activity.

3.Parameters of obesity were found to influence the responsiveness of the microcirculation. Changes in vascular resistance with noradrenaline (100 ;ng/min) were positively correlated with body weight, body mass index and waist circumference (r = 0.63, P = 0.02), whereas waist circumference was negatively correlated with post-ischaemia vasodilatation (r = -0.76, P = 0.002). Acetylcholine-induced vasodilatation was inversely related to body mass index (r = -0.53, P = 0.053).

4.Basal blood flow did not correlate with adiposity. Furthermore, vasodilatation with 800 ;ng/min sodium nitroprusside was inversely correlated with total body noradrenaline spillover (r = -0.77, P< 0.001); and changes in flows with noradrenaline (constriction) and post-ischaemia (dilation) were inversely related (r = -0.56, P = 0.035).

5.These findings, taken together, are consistent with increased local sympathetic neuronal responsiveness and diminished nitric-oxide-mediated dilation in the forearm vasculature with increasing body adiposity.
Prolonged stability of brain natriuretic peptide: importance for non-invasive assessment of cardiac function in clinical practice
Authors: BUCKLEY Martin G. , MARCUS Neil J. , YACOUB Magdi H. , Donald R. J.
Published: August 2015

1.BNP and ANP are important research indices of severity of heart failure. However, uncertainty regarding the stability of these peptides at room temperature has limited their use to assess cardiac function in routine clinical practice.

2.We assessed the stability of BNP and ANP in blood samples left for 2 ;h or 2 days at room temperature compared with levels in blood processed immediately (initial). These times were chosen to reflect possible times for samples to be processed in a hospital outpatient clinic (2 ;h) or a blood sample posted to a laboratory from general practice (2 days). Samples were obtained from eight heart transplant recipients. Blood was separated and plasma stored immediately after collection (initial) and after 2 ;h or 2 days at room temperature respectively.

3.Initial plasma BNP and ANP values measured by radioimmunoassay after Sep-Pak extraction were 38.9±11.1(S.E.M.) pg/ml and 113.6±28.1 ;pg/ml, respectively. After 2 ;h at room temperature there was no significant fall in either peptide level (35.5±9.9 ;pg/ml, BNP; 104.9±30.6 ;pg/ml, ANP). However, after 2 days at room temperature there was a significant fall in ANP to 38.1±12.6 ;pg/ml (P< 0.005 versus initial level). In contrast, there was no significant fall in BNP after 2 days (32.0±8.4 ;pg/ml). After 2 days at room temperature only 30.4±4.3% of the ANP remained, but 86.0±5.0% of BNP compared with the initial ANP and BNP measurements.

4.Our study clearly showed that ANP is stable for 2 ;h and thus could be useful as a screening test for heart disease in hospital. In contrast, BNP remained stable for 2 days. Measuring BNP may thus be practical as a test of heart function both for routine use in hospital and by general practitioners in the community.
Factors determining cardiac hypertrophy in hypertensive patients with or without peripheral vascular disease
Authors: BRAHIMI M. , LEVY B. I. , SAFAR M. E. , DABIRÉ H.
Published: August 2015

1.Coronary ischaemic disease and congestive heart failure are the principal causes of mortality in patients with peripheral vascular disease. Whether cardiac hypertrophy is present and even more pronounced in peripheral vascular disease than in other populations has never been explored.

2.Twenty-five hypertensive patients were investigated, 11 without and 14 with peripheral vascular disease, matched for age, sex, mean arterial pressure and antihypertensive drug treatment. Cardiac mass was determined using echocardiography together with measurement of systemic blood pressure, ratio between ankle systolic pressure (ASP) and brachial systolic pressure (BSP), and standard biochemical parameters including natriuresis per 24 ;h.

3.At the same mean arterial pressure, patients with peripheral vascular disease had a significantly higher cardiac mass (157±12 versus 116±6 ;g/m2; P< 0.01), pulse pressure (81±5 versus 55±4 ;mmHg; P< 0.01) and natriuresis (180±17 versus 144±6 ;mmol/24 h; P< 0.01) than controls. Using univariate correlations, cardiac mass was positively associated with pulse pressure, mean arterial pressure and natriuresis, and negatively with the ASP/BSP ratio. On the basis of multivariate regression analysis, only natriuresis was positively correlated to cardiac mass.

4.Patients with peripheral vascular disease develop a higher degree of cardiac hypertrophy in comparison with hypertensive subjects with the same level of mean arterial pressure. Sodium intake rather than mechanical factors seems to be the major modulating factor which influences the degree of cardiac hypertrophy.