bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antecedent Insulin Level and Pattern of Induction of Acute Hypoglycaemia do Not Affect Subsequent Counterregulatory Responses in Healthy Subjects
Authors: Moriarty K. T. , Simpson E. J. , Mullinger R. N. , MaCdonald I. A. , Tattersall R. B. 
Published: August 2015

1. This study was designed to determine whether the duration and pattern of prior insulin exposure modulate the symptomatic and counterregulatory responses to hypoglycaemia.
2. Ten healthy non-obese subjects (five males/five females age 25 + 1 years, mean + SEM) were made hypoglycaemic in three ways: (i) a hyperinsulinaemic (60 m-units min−1 m−2; plasma insulin concentration 95 m-units/l) clamp, with 1 h of euglycaemia, blood glucose level 4.5 mmol/l, followed by 30 min of hypoglycaemia, at a stable glucose nadir of 2.0 mmol/l (i.e. euglycaemic then hypoglycaemic clamp: E+HC); (ii) an identical hypoglycaemic clamp without preceding hyperinsulinaemic euglycaemia (i.e. a hypoglycaemic clamp: HC); (iii) insulin infusion only, discontinued at a blood glucose level of 3.0 mmol/l (II). Blood glucose level reached the same nadir as on E+HC and HC, and did not fall further. At the glucose nadir, and 15 and 30 min after, the plasma insulin concentration was 23, 7 and 4 m-units/l, respectively, on the II visit.
3. At the glucose nadir, plasma glucagon level, plasma adrenaline level, sweating rate, heart rate, blood pressure, and overall and individual symptom scores (using visual analogue scales) were the same on E+HC, HC and II.
4. There were no significant differences in neurohormonal response between E+HC and HC, but more subjects felt hypoglycaemic on E+HC on arrival at the glucose nadir (P &lt;0.05). There was significantly more blurring of vision (1.3+0.5 versus 0.2+0.1 cm) and tingling (1.2+0.4 versus 0.2+0.1 cm) 30 min after arriving at the glucose nadir on E+HC than HC (P &lt;0.05, analysis of variance).
5. Significant differences were only found between E+HC or HC and the II visit 15 min after arriving at the glucose nadir, when the blood glucose level had risen significantly to 2.9 mmol/l, and 30 min after arrived at the glucose nadir, by which time the blood glucose level had recovered to 3.8 mmol/l.
6. A 1 h run-in period of euglycaemic hyperinsulinaemia does not affect the hormonal or physiological response to an identical degree of hypoglycaemia, but appears to cause increased symptoms of neuroglycopenia during subsequent stable hypoglycaemia.
7. A difference in plasma insulin level within the physiological range does not affect the magnitude of symptomatic, hormonal or physiological responses to the same degree of hypoglycaemia.
Induction of Enhanced Responsiveness of Human Articular Chondrocytes to Extracellular ATP by Tumour Necrosis Factor-α
Authors: Leong Weng S. , Graham R. , Russell G. , Caswell Alison M. 
Published: August 2015

1. We have observed previously that extracellular ATP acting at P2-purinoceptors promotes the production of prostaglandin E2 by human articular chondrocytes, and that this response is enhanced synergistically by interleukin-1β. Since other cytokines that influence the metabolism of articular cartilage may have a similar effect, we have investigated whether tumour necrosis factor-α also modulates the stimulation of the production of prostaglandin E2 in these cells by ATP.
2. Tumour necrosis factor-α enhanced the response of cultured human articular chrondrocytes to a maximally stimulating concentration of ATP (100 μmol/l). This effect was present when the cells were co-incubated with tumour necrosis factor-α and ATP for 4 h, was augmented when the cells were also preincubated with the cytokine for 24 h, and remained constant or declined on extending the preincubation period to 72 h. The enhancement of responsiveness to ATP by tumour necrosis factor-α was dose-dependent, and the minimum effective concentration (6 pmol/l) did not consistently increase prostaglandin E2 production when the cytokine was tested alone. The presence of tumour necrosis factor-α during the incubation with ATP was required for maximum enhancement of the response. Tumour necrosis factor-α did not alter the minimum concentration of ATP that stimulated production of prostaglandin E2.
3. Cytokines such as interleukin-1 and tumour necrosis factor-α are involved in the pathogenesis of some forms of arthritis, and these data provide additional evidence that their actions in articular cartilage may be modulated by other agents which originate from chondrocytes. Moreover, although both these cytokines enhance responsiveness of human articular chondrocytes to extracellular ATP, differences in their effects were observed which suggest that they may act independently.
Control of Sodium Excretion in Patients with Cranial Diabetes Insipidus Maintained on Desamino-[8-d-Arginine]Vasopressin
Authors: Sutters M. , Brace C. , Hatfield E. , Whitehurst A. , Lightman S. L. , Peart W. S. 
Published: August 2015

1. We have studied the response of six patients with cranial diabetes insipidus and six age-matched control subjects to dietary sodium restriction during constant administration of the synthetic vasopressin analogue desamino-[8-D-arginine]vasopressin.
2. Urine flow increased on the first low salt day in the normal control subjects but not in the patients with cranial diabetes insipidus. Body weight fell 1.35 kg in the control subjects but was constant in the patients with cranial diabetes insipidus.
3. Urinary sodium excretion fell at the same rate in both groups. Diurnal variation of urinary sodium excretion and creatinine clearance was present in the control subjects but not in the patients with cranial diabetes insipidus.
4. Changes in plasma sodium concentration and osmolality were similar. Plasma protein concentration increased more in the control subjects (from 69.1 + 13 to 73 + 1.2 versus from 71.7 + 1 to 73.2 + 1.1 g/l). The responses of plasma atrial natriuretic peptide, plasma renin activity and salivary aldosterone concentration were similar between the two groups. Salivary aldosterone concentration levels were consistently higher in the patients with cranial diabetes insipidus.
5. We confirm that the low salt diuresis is triggered by release from the antidiuretic activity of arginine vasopressin. In the patients with cranial diabetes insipidus extracellular fluid osmoregulation appeared to be achieved by the movement of water out of and sodium into the extracellular fluid.
6. Absent posterior pituitary function and hypothalamic disturbances did not alter renal sodium conservation. Total extracellular fluid sodium appeared to be lower in the patients with cranial diabetes insipidus than in the control subjects. Disturbances of hypothalamic and pituitary function may have caused resetting of overall sodium balance and altered diurnal cycles of urinary sodium excretion and creatinine clearance.
Modulation of Small-Intestinal Secretion and Absorption in Chronic Vitamin E Deficiency: Studies in Rat Jejunum in vitro
Authors: Lindley K. J. , Muller D. P. R. , Milla P. J. 
Published: August 2015

1. A vicious cycle of malabsorption and malnutrition has been implicated in the pathogenesis of protracted diarrhoeal disease in infancy. Vitamin E deficiency is common in malnourished infants with protracted diarrhoea. We have studied the effects of chronic vitamin E deficiency on small-inestinal secretion and absorption in the rat.
2. Weanling rats were fed vitamin E-sufficient or -deficient diets for 21 weeks. Jejunal function was studied in vitro in an Ussing chamber after this period.
3. Steady-state isotopic flux experiments in unstimulated tissues demonstrated net Na+ and Cl−secretion in vitamin E-deficient jejuna but net Na+ and Cl− absorption in vitamin E-sufficient jejuna.
4. Basal intestinal short-circuit current was the same in both groups.
5. Cyclic nucleotide and maximal non-neuronal acetylcholine-mediated electrogenic secretion were increased in vitamin E-deficient jejuna.
6. Exogenous 5-hydroxytryptamine (serotonin) induced a smaller increment in electrogenic secretion in vitamin E-deficient jejuna.
7. Vitamin E-deficient jejuna were less responsive to exogenous noradrenaline, resulting in a smaller α2-adrenergic-mediated decrease in intestinal short-circuit current.
8. Fasting for 72 h produced a greater increment in intestinal short-circuit current in vitamin E-deficient jejuna.
9. Chronic vitamin E deficiency is prosecretory in the small intestine and may predispose to the perpetuation of protracted diarrhoeal diseases.
Occurrence of Presyncope in Subjects without Ventricular Innervation
Authors: Lightfoot J. Timothy , Rowe Stuart A. , Fortney Suzanne M. 
Published: August 2015

1. To determine whether activation of the left ventricular C-fibre mechanoreceptors initiates the vasodepressor reflex that often causes syncope, we exposed six orthotopic cardiac transplant patients and six matched, healthy control subjects to progressively increasing lower body negative pressure until the onset of vasodepressor responses.
2. There was no significant difference (P = 0.78) between the central hypovolemia tolerances of the cardiac transplant and the control groups.
3. The decrease in systolic blood pressure before the onset of vasodepressor reflexes was greater in the cardiac transplant group. The cardiac transplant group did not maintain diastolic blood pressure during central hypovolaemia. From baseline to the onset of vasodepression, there were no differences in leg circumference, forearm blood flow and forearm vascular resistance responses between the two groups.
4. We conclude that the left ventricular mechanoreceptors may not be the primary afferent trigger for syncope.
Role of Haematocrit in Mediating the Actions of Chronic Erythropoietin Treatment on Blood Pressure and Renal Haemodynamics in the Rat
Authors: Huang Chunlong , Davis Gerard , Johns Edward J. 
Published: August 2015

1. This investigation aimed to study the effect of chronic administration of human recombinant erythropoietin on haematocrit, blood pressure, renal cortical and papillary resistances and vascular responsiveness to vasoconstrictor agents.
2. Rats were treated with placebo or 25, 50 or 100 units/kg erythropoietin subcutaneously, every other day for 3 weeks. Animals were then anaesthetized with sodium pentobarbitone and were prepared for laser-Doppler flowmetry measurement in the renal cortex and papilla.
3. Haematocrit in the placebo-treated group was 48.0 + 0.5% and was raised to 52.5 + 0.7, 55.9 + 0.8 and 62.4 + 1.1% (all P &lt;0.05) by the chronic administration of 25, 50 and 100 units/kg doses of the hormone, respectively. Blood pressure was 107 + 1 mmHg in the placebo-treated group and was elevated to 116 + 2 and 130 + 1 mmHg (both P &lt;0.05), respectively, by the two highest doses of erythropoietin. Cortical and papillary perfusions were reduced at the highest dose of erythropoietin, but calculated resistances were increased by 15 and 40% (P &lt;0.05) at 50 and 100 units/kg doses of the hormone, respectively.
4. Infusion of the vasopressor hormones vasopressin and phenylephrine caused increases in blood pressure and decreases in renal cortical and papillary perfusion, the magnitudes of which were only marginally changed by the highest dose of the erythropoietin. Angiotensin II increased blood pressure and decreased cortical perfusion, and the magnitudes of these responses were unchanged by the chronic treatment with erythropoietin.
5. Acute graded increases in haematocrit resulted in significantly (P &lt;0.05) raised blood pressure above a value of 58%. However, renal cortical and papillary perfusions decreased and resistances were increased significantly (P &lt;0.05) when the haematocrit was raised above 56%.
6. The acute transfusion study demonstrated that elevations in blood pressure and renal vascular resistances occurred at haematocrit values somewhat higher than when it was raised by chronic erythropoietin treatment. Thus this would be consistent with the suggestion that erythropoietin has some direct action on the vasculature beyond that resulting from the raised haematocrit. These data show that a low dose regimen of erythropoietin can modestly increase haematocrit without other cardiovascular changes becoming apparent. The findings add weight to the recent clinical practice of using very low doses of the hormone in the treatment of chronic renal failure.
Effect of Induced Bronchoconstriction on Nasal Airflow Resistance in Patients with Asthma
Authors: Yap J. C. H. , Pride N. B. 
Published: August 2015

1. Reflex bronchial changes have been demonstrated after nasal stimulation in both man and experimental animals. The existence of a pulmonary-nasal reflex is less established. We have examined whether induced narrowing of the intrathoracic airways leads to increases in nasal airflow resistance (R naw) in patients with asthma.
2. We have used a non-invasive forced oscillation method to measure total respiratory resistence (R rs) at 8 Hz during tidal breathing sequentially via the nose (R rs, na) and via the mouth (R rs, mo) and derived R naw by subtracting R rs, mo from R rs, na. We examined whether changes in R naw occurred when increases in R rs, mo were induced by inhaling histamine aerosol via the mouth with the nose occluded in 11 patients with stable, mild asthma (six males, age 28.1 + 2.1 years, forced expiratory volume in 1 s 97 +6% of predicted, means +SEM). Six of the patients had a history of rhinitis. The patients were first challenged with doubling concentrations of histamine via a dosimeter to establish the dose which reduced the forced expiratory volume in 1 s by ≧ 20%. Two hours later when the forced expiratory volume in 1 s had returned to baseline, they were challenged with saline and again 2 h later with the concentration of histamine that had earlier caused a ≧ 20% fall in the forced expiratory volume is 1 s.
3. Between 0.5 and 10 min after histamine inhalation, a sustained increase in R rs, mo was achieved with mean increases averaging 68–77% above baseline over this period (P &lt;0.001). This was associated with a slower rise in mean R naw which reached a maximum of 53% above baseline at 5 min after histamine inhalation. The rise in R naw varied between patients, but was sustained for 10 min in eight of the patients; the extent of rise was not related to a history of rhinitis.
4. The results suggest that, in some asthmatic patients, bronchoconstriction results in an increase in R naw, probably due to a pulmonary-nasal reflex. Further studies are required to investigate the mechanisms of this increase.
Effect of Local Inhibition of Nitric Oxide Synthesis on Forearm Blood Flow and Dorsal Hand Vein Size in Patients with Alcoholic Cirrhosis
Authors: Calver Alison , Harris Adam , Maxwell J. Douglas , Vallance Patrick 
Published: August 2015

1. Nitric oxide (NO) is a potent endogenous vasodilator and plays a role in the control of resting vascular tone. Patients with cirrhosis have a hyperdynamic circulation with reduced blood pressure and decreased peripheral resistance, and it is possible that increased production of NO due to induction of NO synthase may be involved in maintaining this vasodilatation. We have examined this possibility by studying the effects of local infusions of NG-monomethyl-l-arginine (an inhibitor of NO synthase) in the forearm arteriolar bed and the superficial dorsal hand veins of patients with alcoholic cirrhosis.
2. Drugs were either infused locally into the brachial artery and forearm blood flow was measured by venous occlusion plethysmography, or into a vein on the back of the hand and vein diameter was measured using a linear displacement technique.
3. Basal forearm blood flow was increased and vascular resistance was decreased in the patients with alcoholic cirrhosis compared with healthy control subjects. Noradrenaline and NG-monomethyl-l-arginine caused dose-dependent falls in forearm blood flow in both healthy control subjects and patients with cirrhosis. There was no significant difference in the responses to either noradrenaline or NG-monomethyl-l-arginine between the two groups.
4. In the superficial hand veins there was no change in vein size in response to NG-monomethyl-l-arginine infused alone, and venoconstriction to local infusion of noradrenaline was unaffected by co-infusion with NG-monomethyl-l-arginine.
5. Our results confirm that patients with alcoholic cirrhosis are vasodilated compared with healthy control subjects. Our findings show that basal NO-mediated vasodilatation occurs in the forearm arterial bed, but not the superficial hand veins, of these patients. However, since the response to local NO synthesis inhibition was similiar in the two groups, increased production of NO due to induction of NO synthase is unlikely to account fully for the vasodilatation seen in patients with mild to moderate alcoholic cirrhosis.
Altered Dynamics of the Circadian Relationship between Systemic Arterial Pressure and Cardiac Sympathetic Drive Early on in Mild Hypertension
Authors: Guzzetti S. , Dassi S. , Balsamà M. , Ponti G. B. , Pagani M. , Malliani A. 
Published: August 2015

1. This study was designed to test the hypothesis that simultaneous non-invasive assessment of the circadian variations in both intermittent arterial pressure and the continuous 24 h changes of spectral markers of cardiac neural control could provide new information on cardiovascular regulatory mechanisms, in hypertensive patients and normotensive subjects. To test this hypothesis we studied 18 subjects with mild hypertension and 11 normotensive subjects in whom we recorded simultaneously non-invasive intermittent arterial pressure and Holter electrocardiogram for 24 h. We also studied the same subjects during resting and standing conditions in the clinical laboratory.
2. The normalized power of the low-frequency (∼0.1 Hz) spectral component of R-R interval variability, considered mainly a marker of sympathetic drive to the sino-atrial node, was, at rest, significantly higher in the hypertensive than in the normotensive subjects, as already reported. Moreover, the values of the low-frequency component at rest recorded in the clinical laboratory were significantly correlated with those obtained from ambulatory recording during night rest. The decrease in the values of arterial pressure during the night-time was accompanied by a reduction in the power of the low-frequency component only in the case of normotensive subjects. Accordingly, the slope of the regression of the low-frequency component as a function of systolic arterial pressure during ambulatory recordings was steep in normotensive subjects and flat in hypertensive subjects.
3. The computer analysis of Holter recordings combined with ambulatory arterial pressure monitoring seems to provide a new method with which to quantify the early changes in cardiovascular regulatory mechanisms that could help to identify individuals at higher risk.
Involvement of Nitric Oxide in the Vasodilatory Response to Parathyroid Hormone-Related Peptide in the Isolated Rabbit Kidney
Authors: Simeoni Umberto , Massfelder Thierry , Saussine Christian , Judes Clément , Geisert Jean , Helwig Jean-Jacques 
Published: August 2015

1. The present study was designed to explore the role of NO derived from l-arginine in the vasodilatory response to synthetic human parathyroid hormone-related peptide-(1–34) in the isolated rabbit kidney perfused in the presence of indomethacin (10 μmol/l) and preconstricted with noradrenaline (7.2 nmol/min).
2. Under control conditions, bolus administrations of acetylcholine (10 μmol/l), an NO-dependent renal vasodilator, verapamil (0.1 mmol/l), an NO-independent renal vasodilator, and parathyroid hormone-related peptide (87 nmol/l) decreased the preconstriction pressure, by 31%, 71% and 43%, respectively.
3. Bolus administration of 100 μmol/l NG-nitro-l-arginine-methyl ester caused a 20% increment in the perfusion pressure of the noradrenaline-preconstricted kidney. NG-nitro-l-arginine methyl ester inhibited the vasodilatory effect of acetylcholine and parathyroid hormone-related peptide, by 68% and 44%, respectively, but did not alter the verapamil-induced vasodilatation.
4. Unlike l-arginine, the bolus administration of 1 μmol/l of a mono-substituted l-arginine derivative, N-α-benzoyl-l-arginine ethyl ester, durably decreased the noradrenaline/NG-nitro-l-arginine methyl ester-induced preconstriction by 57%.
5. Both l-arginine and N-α-benzoyl-l-arginine ethyl ester effectively reversed the inhibition induced by NG-nitro-l-arginine methyl ester on the vasodilatation elicited by acetylcholine and parathyroid hormone-related peptide.
6. In conclusion, the formation of NO from l-arginine contributes a substantial part to the vasodilatory action of parathyroid hormone-related peptide. Therefore, parathyroid hormone-related peptide appears to have a place among the renal haemodynamically active substances, whose vasodilatory actions are tuned by NO.
Ethanol Decreases Nocturnal Plasma Levels of Atrial Natriuretic Peptide (ANP 99-126) but Not the N-Terminal Fragment of Pro-Atrial Natriuretic Peptide (ANP 1-98) in Man
Authors: Ekman Ann-Charlotte , Vakkuri Olli , Vuolteenaho Olli , Leppäluoto Juhani 
Published: August 2015

1. The aim of this study was to elucidate the role of atrial natriuretic peptides in the regulation of water and electrolyte balance after alcohol intake. To this end we measured the plasma concentrations of ethanol, atrial natriuretic peptide 99–126 and the N-terminal fragment of pro-atrial natriuretic peptide (atrial natriuretic peptide 1–98), serum osmolality and serum sodium concentration, and urine output, urine osmolality and urinary sodium excretion for 12 h after administration of ethanol (0, 0.5 and 1.0 g body weight/kg) and placebo drinks to nine healthy subjects according to a double-blind cross-over design.
2. Intake of ethanol (at 19.00–19.45 hours) inhibited the nocturnal increase in the plasma atrial natriuretic peptide 99–126 level dose-dependently (P &lt; 0.05), but had no effect on the plasma atrial natriuretic peptide 1–98 level. Serum osmolality and serum sodium concentration were elevated dose-dependently for 2–5 h after the ethanol intake. Urine volume increased after the higher ethanol dose (net loss of 0.6 litre of water).
3. Since the plasma atrial natriuretic peptide 1–98 level was not changed after ethanol intake, we propose that the alcohol-induced inhibition of the nocturnal rise in the plasma atrial natriuretic peptide 99–126 level is not caused by an inhibition of release, but may rather reflect an increased peripheral elimination of atrial natriuretic peptide 99–126.
α- and β-Cell Function in Obese Zucker (fa/fa) Rats: A Study with the Isolated Perfused Pancreas
Authors: Hirose Dr Hiroshi , Maruyama Hiroshi , Kido Koichi , Ito Katsuhiko , Koyama Kazunori , Tashiro Yukio , Saruta Takao 
Published: August 2015

1. The effects of various stimuli, including changes in glucose concentration, arginine, tyramine and noradrenaline, on insulin and glucagon secretion were investigated using isolated perfused pancreata of obese and lean male Zucker rats at 12 months of age.
2. In Zucker fatty rats, the insulin secretion rate was significantly (P &lt; 0.01) higher than that of lean rats at all glucose concentrations tested (8.3, 16.7 and 1.4 mmol/l). However, the integrated insulin secretory response to raising the glucose concentration from 8.3 to 16.7 mmol/l was almost absent in these rats. The glucagon secretion rates were significantly lower at 8.3 and 1.4 mmol/l glucose (P &lt; 0.001 for both), and in responses to 10 μg/ml tyramine and 0.1 μmol/l noradrenaline (P &lt; 0.05 for both), in Zucker fatty rats. Integrated insulin and glucagon responses to 10 mmol/l arginine were identical in the two groups.
3. Histopathological and immunochemical studies revealed hyperplasia of β-cells and scattered α-cells in the enlarged islets of Zucker fatty rats.
4. These results suggest that, in Zucker fatty rats, the decreased glucagon secretion in the isolated perfused pancreas is attributable to changes in the environment of α-cells and/or the inhibitory effects of hypersecreted insulin.