bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations in high-density lipoprotein subfractions during postprandial lipidaemia induced by fat with and without ethanol
Authors: Franceschini G. , Moreno Y. , Apebe P. , Calabresi L. , Gatti E. , Noé D. , De Fabiani E. , Zoppi F. , Sirtori C. R.
Published: August 2015

1. Serum lipid and apolipoprotein levels, distribution and composition of high-density lipoprotein (HDL) sub-fractions and lecithin:cholesterol acryltransferase activity were analysed in nine normolipidaemic subjects, in whom a hypertriglyceridaemic state was induced by the acute administration of ethanol (40 g) plus fat (70 g) or of fat only.

2. Triglyceride (TG) levels increased by 180% 4–6 h after fat plus ethanol intake, the hypertriglyceridaemic response being inversely correlated with the basal HDL2 mass (r = −0.82). Serum apolipoprotein (apo) B levels rose by 8%, HDL–cholesterol decreased by 10% and HDL–TG increased by 57% at 6–8 h.

3. When ethanol was omitted, serum cholesterol and TG rose by 6% and 70%, respectively; both apo AI and apo B levels went up by 8%, whereas HDL-cholesterol rose progressively (15%) at 12 h.

4. The flotation rates of both HDL2 and HDL, increased, reaching a maximum 6–8 h after ethanol plus fat intake. These changes were due to an increase in TG and phospholipid contents, whereas cholesteryl esters and proteins decreased.

5. The alterations in HDL are attributable to the increase in TG-rich lipoproteins, to the stimulated cholesterol esterification (+ 15%) and to an enhanced transfer of newly formed cholesteryl esters to apo-B-containing lipoproteins in exchange for TG.

6. Changes in HDL properties were evident only when ethanol was given concomitantly with fat.

7. These findings suggest that in the postprandial phase lipoprotein changes may occur, which facilitate an improved removal of cholesterol from tissues.
Effect of high salt intake on sodium, potassium-dependent adenosine triphosphatase activity in the erythrocytes of normotensive men
Authors: Quintanilla Antonio P. , Weffer Maria I. , Koh Haengil , Rahman Mohammed , Molteni Agostino , Del Greco Francesco
Published: August 2015

1. We measured ouabain-insensitive adenosine triphosphatase (ATPase), sodium, potassium-dependent adenosine triphosphatase (Na+,K+-ATPase) and intracellular Na+ and K+ in the erythrocytes of 19 healthy volunteers, before and after supplementation of their normal diet with 6.0–8.9 g of salt (102–137 mmol of NaCl) per day, for 5 days.

2. The subjects had a small but significant gain in weight. Mean plasma renin activity decreased from 1.57 to 0.73 pmol of angiotensin I h−1 ml−1 and plasma aldosterone from 0.46 to 0.24 nmol/l.

3. Total ATPase activity fell from 197.9 nmol of inorganic phosphate h−1 mg−1 during the control period to 173.5 during the high-salt period (P < 0.0125). Na+,K+-ATPase activity fell from 162.2 to 141.4 nmol of inorganic phosphate h−1 mg−1 (P < 0.05). Intracellular Na + and intracellular K+ did not change.

4. These results are consistent with the hypothesis that salt-induced volume expansion causes the release of a factor inhibitory to the Na+ pump.
Sodium influx in human leucocytes: A novel technique for assessment of sodium–proton antiport activity
Authors: Ng L. L. , Harker M.
Published: August 2015

1. A triple-isotope method for measuring initial 22Na uptake rates in unactivated human leucocytes in the presence of serum, using 3H2O, [14C]sucrose and 22Na, is described.

2. This 22Na influx is inhibited by amiloride, with half-maximal inhibition at a concentration of 10−5 mol/l.

3. About 70% of the 22Na influx in normal human leucocytes is inhibited by 1 mmol/l amiloride, with an external Na+ concentration of 10 mmol/l.

4. External Na+ antagonizes this inhibition by amiloride. The Km for external Na+ is 9 mmol/l.

5. Intracellular acidification from either external Na+ depletion or ammonium chloride incubation leads to an activation of amiloride-sensitive Na+ influx.

6. The amiloride-sensitive Na+–H+ antiport provides the major influx pathway for Na+ in unactivated human leucocytes in the presence of serum.
Differences in glomerular binding and response to angiotensin II between normotensive and spontaneously hypertensive rats
Authors: Messenger E. A. , Stonier C. , Aber G. M.
Published: August 2015

1. Angiotensin II (ANG II) binding and the physiological response to exogenous ANG II have been studied in isolated glomerular preparations from normotensive (NTR) and spontaneously hypertensive (SHR) rats.

2. The binding of 125I-labelled ANG II by glomeruli from SHR was significantly greater than that by glomeruli from NTR, whereas the binding affinity constant (Ka) showed that the SHR ANG II glomerular receptor had a lower affinity for the hormone than the NTR glomerular receptor.

3. Glomeruli from SHR were significantly less responsive to exogenous ANG II than those from NTR.

4. Sodium loading resulted in a significant increase in ANG II binding by glomeruli from NTR, whereas a decrease in binding occurred in glomeruli from SHR.

5. Although a high sodium intake caused a reduction in the response of glomeruli from both NTR and SHR to exogenous ANG II, these changes were not statistically significant. In NTR this was associated with a decrease in the concentration of agonist required to cause half-maximal response (EC50), whereas an increase in EC50 was shown by glomeruli from SHR.
Adenine phosphoribosyltransferase deficiency: A simple diagnostic test
Authors: Maddocks J. L. , Al-Safi S. A.
Published: August 2015

1. A simple method for diagnosing adenine phosphoribosyltransferase (APRT) deficiency using urine is described.

2. T.l.c. of 1 μl of urine from a child with APRT deficiency was performed and adenine was easily detected by its brilliant blue phosphorescence at liquid nitrogen temperature.

3. Four physicochemical characteristics of adenine were recorded: RF value, and the colour, decay time and pH sensitivity of phosphorescence.

4. Adenine was not detected in the urine of 116 subjects used as controls. These included healthy individuals and patients with inherited metabolic disorders, diseases of purine metabolism and of the kidney and urinary tract. Some of them were taking a variety of drugs including purine derivatives.

5. The test correctly diagnosed three cases of APRT deficiency out of 10 urine samples tested blind.
Muscle adenosine 5′-triphosphate and creatine phosphate concentrations in relation to nutritional status and sepsis in man
Authors: Tresadern J. C. , Threlfall C. J. , Wilford K. , Irving M. H.
Published: August 2015

1. Intramuscular concentrations of adenosine 5′-triphosphate (ATP) and creatine phosphate were measured in the vastus lateralis muscle of 28 non-septic malnourished patients and 31 septic malnourished patients. Similar measurements were made on the rectus abdominis muscle of about one-third of these patients. All results were compared with those obtained from 15 normally nourished non-septic control subjects.

2. Objective measurements of nutritional status (both anthropometric and biochemical) and sepsis were recorded in all subjects.

3. The vastus lateralis muscle of the non-septic and septic malnourished patients had intramuscular concentrations of ATP and total adenine nucleotides (TAN) that were up to 30% lower than control values, depending on the reference base used.

4. In the rectus abdominis muscle, ATP and TAN concentrations were up to 60% lower than control values, and creatine phosphate up to 47% lower, again depending on the reference base used.

5. In both muscles, the changes were more marked in those patients who were septic as well as malnourished.
Unimpaired excretion of an acute salt load in conscious hypoproteinaemic dogs
Authors: Joles J. A. , Koomans H. A. , Boer P. , Dorhout Mees E. J.
Published: August 2015

1. The role of hypoproteinaemia in the sodium retention seen in conditions such as the nephrotic syndrome is incompletely known.

2. To define the influence of severe hypoproteinaemia on kidney function, we studied the effect of an intravenous infusion of an isotonic saline load (133 mmol of sodium), as 1 litre of Ringer lactate solution, on sodium excretion and renal haemodynamics in conscious dogs before and after reduction of plasma protein from 68 ± 3 to 36 ±2 g/l by repeated plasmapheresis and a low protein diet.

3. During hypoproteinaemia, 2 days after a period of plasmapheresis, glomerular filtration rate and effective renal plasma flow were lower than in the control study. After the sodium load, both rose to values nearly identical with the pre-infusion levels found in normoproteinaemia, the filtration fraction remaining unchanged. This contrasted with the rise in filtration fraction after expansion in normoproteinaemia, where filtration fraction increased from 32 to 39% due to a rise in glomerular filtration rate.

4. After expansion, natriuresis rose to similar levels in normoproteinaemia (0.18 ±0.06 mmol/min) and hypoproteinaemia (0.20 ± 0.06 mmol/min), and increments in fractional excretion of sodium, potassium and chloride were also similar. However, baseline excretion was higher in the hypoproteinaemic dogs due to their overhydrated condition in this period immediately after plasmapheresis.

5. The fractional excretion of lithium, an alleged marker of proximal tubular sodium reabsorption, rose to comparable levels.

6. Hence, both the increase in filtration and decrease in reabsorption of sodium after an isotonic saline load are not affected by severe reduction in plasma protein concentration. Apparently, the pathways to augment natriuresis after acute expansion function normally in hypoproteinaemia.
Metabolic and cardiovascular effects of infusions of low doses of isoprenaline in man
Authors: Mansell P. I. , Fellows I. W. , Birmingham A. T. , Macdonald I. A.
Published: August 2015

1. The cardiovascular and metabolic responses to low doses of isoprenaline (15 and 5 ng min−1 kg−1 body weight infused over 30 min) were determined in six healthy males. The study was performed to investigate whether there were sustained effects after the termination of the isoprenaline infusions, as has been observed previously after the infusion of adrenaline.

2. The isoprenaline infusions produced dose-dependent increases in heart rate, systolic blood pressure and metabolic rate, but similar increases in calf blood flow and decreases in diastolic blood pressure for the two infusion rates. Finger tremor was increased in amplitude by the 15 ng min−1 kg−1 infusion only. The changes in each of these physiological variables largely resolved within a few minutes of discontinuing the isoprenaline infusions.

3. There were no changes in arterialized venous plasma adrenaline or noradrenaline levels during the isoprenaline infusions. Mean peak plasma isoprenaline levels were 0.16 ±0.02 nmol/l during the 5 ng min−1 kg−1 infusion and 0.71 ±0.05 nmol/l during the 15 ng min−1 kg−1 infusion.

4. Plasma insulin levels increased with isoprenaline but blood glucose concentrations were unchanged, consistent with a direct effect of isoprenaline on β2-adrenoceptors mediating insulin release from pancreatic β-cells. Blood glycerol concentration also increased with isoprenaline but blood lactate concentration was unaltered.

5. The present study demonstrates pronounced cardiovascular and metabolic effects of low dose isoprenaline infusions. Differences in the rate of resolution of the changes induced by isoprenaline and by adrenaline seen in previous studies may result from a significant difference in their metabolism.
Effects of opioid antagonism on the haemodynamic and hormonal responses to exercise
Authors: Staessen Jan , Fiocchi Roberto , Bouillon Roger , Fagard Robert , Hespel Peter , Lijnen Paul , Moerman Emmanuel , Amery Antoon
Published: August 2015

1. Physical effort involves, along with an increase in the plasma concentration of β-endorphin, profound adaptations of the circulation and the endocrine system. The effects of opioid antagonism on the responses of blood pressure, heart rate and several hormones to exercise were therefore studied in 10 normal men. They exercised in the supine position up to 33% and 66% of their maximal exercise capacity and received in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg intravenously, followed by a continuous infusion of 10 mg/h).

2. Intra-arterial pressure and heart rate were continuously monitored, but were not affected by naloxone.

3. At rest, opioid antagonism produced a rise in plasma renin activity and in plasma adrenocorticotropin, Cortisol and aldosterone, but only the stimulation of the two adrenocortical hormones differed significantly from the control experiments; at rest naloxone also prevented the fall in plasma adrenaline, which occurred with saline infusion. Furthermore, the exercise-induced rises in plasma angiotensin II, aldosterone, Cortisol, noradrenaline and adrenaline were higher on naloxone than on saline, while a similar tendency was also present for the increases with exercise in plasma renin activity and plasma adrenocorticotropin. Neither at rest nor during exercise did opioid antagonism alter plasma lactate and glucose and serum insulin and growth hormone.

4. In conclusion, (1) endogenous opioids are not involved in the responses of blood pressure and heart rate to supine exercise; (2) at rest and during exercise, the endogenous opioids inhibit the secretion of adrenocorticotropin, aldosterone, Cortisol, noradrenaline and adrenaline; (3) they also inhibit the plasma renin-angiotensin II system indirectly via the catecholamines.
Angiotensin II augments sympathetically induced venoconstriction in man
Authors: Benjamin N. , Collier J. G. , Webb D. J.
Published: August 2015

1. The constriction produced by a single deep breath was measured simultaneously in two adjacent hand veins in normal volunteers. One vein was infused with angiotensin II (ANG II) while the other acted as a control.

2. At a dose lower than that required to produce direct venous constriction (1 pmol/min), ANG II significantly augmented the constriction caused by a deep breath in eight subjects (P < 0.01). The same dose had no effect on the venoconstriction caused by infused noradrenaline (NA) in a further six subjects.

3. It is concluded that ANG II at low doses may cause venoconstriction indirectly by augmenting sympathetically induced venous tone via a presynaptic mechanism. This observation may help to explain the apparent venodilating property of angiotensin-converting enzyme inhibitors in clinical situations where the renin–angiotensin system is stimulated.
Free and total carnitine and acylcarnitine content of plasma, urine, liver and muscle of alcoholics
Authors: De Sousa C. , Leung N. W. Y. , Chalmers R. A. , Peters T. J.
Published: August 2015

1. Plasma and urine free and total carnitine and acylcarnitine levels were assayed in 12 control subjects and 20 chronic alcoholics with fatty liver. Although the alcoholics had a wider range of values than the controls, there was no significant difference between the two groups.

2. Hepatic free and total carnitine and long- and short-chain acylcarnitines were assayed by a radioenzymatic method in samples from seven control subjects and seven alcoholics. No significant differences in any of the indices were noted between the patient and control groups and it was concluded that carnitine deficiency did not contribute to alcoholic fatty liver in patients without cirrhosis.

3. Skeletal muscle free and total carnitine and long-and short-chain acylcarnitines were assayed in eight alcoholics and seven control subjects. The alcoholics had significantly higher total and free carnitine levels. It is suggested that this reflects a selective enrichment of the biopsy sample with type I carnitine-rich fibres due to the type II fibre atrophy found in approximately half the patients.
Vasopressin-mediated contractions in mesenteric arteries from spontaneously hypertensive rats: Differences in response compared with Wistar–Kyoto animals
Authors: Bund S. J. , Heagerty A. M. , Aalkjaer C. , Swales J. D.
Published: August 2015

1. The sensitivity of mesenteric resistance arterioles to [arginine]vasopressin (AVP) was investigated in spontaneously hypertensive rats (SHR) and control Wistar–Kyoto rats (WKY). No difference in pAVP (–log dose of AVP producing 50% of the maximum response) was observed [SHR 0.21 ±0.03 m-units/ml (n = 10) vs WKY 0.15 ±0.06 m-units/ml (n = 9)], although SHR vessels exhibited greater absolute tension development.

2. Both strains of rat displayed tachyphylaxis to repeated stimulation with AVP, and oscillatory tension changes were observed in all vessels from SHR and rarely in WKY vessels at activating concentrations of AVP.

3. AVP did not elicit a contractile response after noradrenaline-induced calcium depletion.

4. After vessels were depleted of calcium by using a combination of calcium-free media and noradrenaline stimulation, restoration of calcium in the presence of AVP elicited a greater contractile response in SHR vessels.

5. The results therefore provide evidence for an increased calcium response to AVP in SHR resistance vessels, although this was only demonstrable by calcium recovery experiments.
Atrial natriuretic factor increases after a protein meal in man
Authors: Rodríguez-Iturbe Bernardo , Herrera José , Gutkowska Jolanta , Parra Gustavo , Coello Jesús
Published: August 2015

1. The renal function changes induced by dietary protein are thought to result from the activity of hormonal factors that remain as yet undefined. Since a meat meal and high dose atrial natriuretic factor (ANF) infusions have similar effects on glomerular filtration rate, natriuresis and kaliuresis, we decided to investigate the possibility that a protein meal could stimulate ANF activity.

2. We studied 10 normal volunteers who had a fixed protein and sodium intake for 7 days before the experiments. The subjects received a meat meal (1–1.5 g of protein/kg) and, on a separate occasion, a carbohydrate meal that had a similar caloric, sodium and potassium content. Diuresis was stimulated with water ingestion, and urine collections were obtained before the meals (baseline) and after the meals for a period of 3 h. Blood samples were obtained 30 min and 5 min before the meals and every hour for 3 h in the period after the meal.

3. The protein meal, but not the carbohydrate meal, was associated with parallel increments in plasma immunoreactive ANF (i-ANF), natriuresis, kaliuresis and glomerular filtration rate (estimated from creatinine clearances) which reached peak values 2–3 h after the meal. The mean increment of plasma i-ANF after the protein meal represented a twofold increase over baseline levels.

4. We conclude that ANF may participate in the physiological response to an oral protein load.
Reciprocal renal effects of dopamine and 5-hydroxytryptamine formed within the rat kidney
Authors: Itskovitz Harold D. , Chen Yih-Huey , Stier Charles T.
Published: August 2015

1. Clearance of inulin and p-aminohippurate and excretion of water and sodium were measured for eight to 11 clearance periods of 20 min duration in anaesthetized, 3% volume-expanded rats, before and after intravenous infusions of the amino acids l-dopa (l-3,4-dihydroxyphenylalanine) and 5-hydroxytryptophan. During the final two clearance periods, the peripheral decarboxylase inhibitor, carbidopa (S-α-hydrazino-3,4-dihydroxy-α-methylbenzenepropanoic acid monohydrate), was infused additionally.

2. Renal formation of dopamine (3,4-dihydroxyphenethylamine) and 5-hydroxytryptamine was demonstrated during infusions of l-dopa and 5-hydroxytryptophan, respectively; carbidopa blocked the renal formation of these biogenic amines.

3. During infusion of dopa, a diuresis and a natriuresis were observed; during the infusion of 5-hydroxytryptophan, slight reductions in clearances of inulin and p-aminohippurate, but significant reductions in sodium and water excretion, were measured.

4. The addition of carbidopa diminished diuretic and natriuretic responses to dopa as renal dopamine excretion decreased; the infusion of carbidopa also ameliorated the antinatriuretic and antidiuretic effects of 5-hydroxytryptophan, as 5-hydroxytryptamine excretion decreased.

5. Although dopa and 5-hydroxytryptophan are substrates for the same enzyme, aromatic l-amino-acid decarboxylase, simultaneous infusions of both amino acids at comparable rates gave no evidence of competitive inhibition of amine synthesis. However, the infusion of dopa, after 5-hydroxytryptophan, decreased its antinatriuretic and antidiuretic effects.

6. These data raise the possibility that dopamine and 5-hydroxytryptamine are formed as reciprocal intrarenal hormones by the identical enzyme, aromatic l-amino-acid decarboxylase, which is located within cells of the renal tubule.
Rebound of aldosterone but not of corticosterone after suppression of adrenal function by triamcinolone acetonide in rats
Authors: Meier Gabriele
Published: August 2015

1. The effects of microcrystalline ‘depot’ triamcinolone acetonide on renal excretion and blood levels of aldosterone, 18-hydroxycorticosterone and corticosterone were studied in rats over a 13 day period. The renal excretion of all of these steroids was found to be suppressed on day 1 after triamcinolone acetonide administration. Corticosterone excretion remained suppressed for 6 days, whereas aldosterone and 18-hydroxycorticosterone excretion normalized within 3 days.

2. While corticosterone excretion was returning to control values, the excretion of aldosterone rose to values above the pretreatment levels (the rebound phenomenon). 18-Hydroxycorticosterone excretion paralleled that of aldosterone, but the rebound was of less statistical significance.

3. The findings in urine were confirmed by plasma steroid determinations. A suppression of plasma aldosterone, 18-hydroxycorticosterone and corticosterone was observed in the first 24 h after triamcinolone acetonide injection. On day 4 only corticosterone showed lowered levels. An aldosterone rebound could be seen at 18.00 hours, the circadian maximum in rats.

4. These findings suggest that in addition to the effects on glucocorticoids, mineralocorticoids have to be taken into account in the restoration of the adrenal function after corticoid therapy. The aldosterone rebound observed during this sensitive period may be important in preventing disturbances of electrolyte and water homoeostasis.
Electrocardiographic diagnosis of left ventricular hypertrophy: Influence of body build
Authors: McLenachan James M. , Henderson Esther , Morris Karen I. , Dargie Henry J.
Published: August 2015

1. The sensitivity and specificity of four sets of electrocardiographic criteria for detection of left ventricular hypertrophy were evaluated in an echocardiographic study of 100 hypertensive patients.

2. All criteria gave reasonable specificity (87–94%) but poor sensitivity (39–52%).

3. When non-obese and obese patients were studied separately, criteria based on chest lead voltages were more sensitive than limb lead criteria for detection of left ventricular hypertrophy in non-obese subjects; however, the reverse was true in obese hypertensive patients, where criteria based on limb lead voltages were more sensitive than chest lead voltage criteria.

4. These data suggest that stratification of subjects by body build might improve the diagnostic performance of the electrocardiogram for detection of left ventricular hypertrophy.
Evidence for lipid-associated serine proteases and metalloproteases in human bronchoalveolar lavage fluid
Authors: Burnett David , Afford Simon C. , Campbell Edward J. , Rios-Mollineda Raul A. , Buttle David J. , Stockley Robert A.
Published: August 2015

1. We have investigated the nature of elastase activity in bronchoalveolar lavage samples from healthy cigarette smokers and subjects with emphysema.

2. Initial experiments with pure human leucocyte elastase showed this enzyme to be inhibited by high concentrations (> 10 mmol/l) of ethylenediaminetetraacetate, indicating that results of previous studies of ‘metalloelastase’ activity in bronchoalveolar lavage were ambiguous.

3. We have nevertheless demonstrated the presence in bronchoalveolar lavage of an elastase with the characteristics of a metalloproteinase, although samples also contained a substantial amount of activity that was sensitive to serine proteinase inhibitors.

4. Fractionation of lavage fluid supernatant by size-exclusion chromatography demonstrated most of the elastase activity to be of molecular mass > 300 kDa. Treatment of samples with lipase or detergent caused a reduction in metalloelastase activity and the generation of lower-molecular-mass components (90–100 kDa and 40 kDa) which were predominantly serine elastases. This suggested that the enzymes were associated with lipid.
A prospective controlled trial of topical irrigation in the treatment of delayed cutaneous healing in human leg ulcers
Authors: Bulstrode C. J. K. , Goode A. W. , Scott P. J.
Published: August 2015

1. Topical irrigation with normal saline is known to produce rapid healing in chronic leg ulcers. This study was designed to determine if the rate of healing could be improved by the addition of topical nutrition to the irrigating solution.

2. Forty-eight patients with chronic leg ulcers were admitted to hospital for a minimum of 6 weeks bed-rest. During this time the ulcers were continuously irrigated by one of four test solutions. The solutions were: normal saline; a dilute amino acid solution isotonic with the normal saline; a hyperosmolar saline solution; a hyperosmolar amino acid solution. There were 12 ulcers in each group.

3. The amino acid solutions produced significantly faster healing than the saline solutions (P < 0.01). Concentration had no significant effect on healing (P > 0.15).

4. The application of amino acids does appear to enhance healing in this model of delayed wound healing. This effect does not depend only on the osmolarity of the solution used.
Magnesium aspartate hydrochloride attenuates monocrotaline-induced pulmonary artery hypertension in rats
Authors: Mathew R. , Gloster E. S. , Altura B. T. , Altura B. M.
Published: August 2015

1. The effect of oral magnesium aspartate hydrochloride on monocrotaline (MCT)-induced pulmonary arterial hypertension was evaluated in rats.

2. A single subcutaneous injection of MCT, a pyrrolizidine alkaloid of plant origin, induces significant morphological changes in pulmonary vessels, pulmonary arterial hypertension and right ventricular hypertrophy in rats by 3 weeks.

3. Two groups of rats (Mg2+ control and Mg2+ + MCT) were started on oral Mg2+ (15.4 g/l magnesium aspartate hydrochloride dissolved in deionized water) 2 weeks before the MCT injection. The rest were given deionized water. At the start of the experiment, the control groups (deionized water and Mg2+) were given normal saline subcutaneously; the other groups (deionized water and Mg2+) were given MCT (60 mg/kg) subcutaneously.

4. Pulmonary artery pressure, right ventricular hypertrophy, lung pathology, organ weights and serum electrolytes were assessed 3 weeks after a single subcutaneous injection of MCT. Seventy-five per cent of the rats treated with MCT and oral Mg2+ (12 out of 16) showed significant reduction in pulmonary arterial hypertension, arterial pathology and right ventricular hypertrophy.

5. Our data indicate that Mg2+ attenuates experimentally induced pulmonary hypertension, possibly either by modulating the intracellular Ca2+ level and/or by directly affecting the pulmonary endothelial cell–smooth muscle cell complex involved in metabolism and maintenance of pulmonary vascular resistance.
Platelet intracellular free calcium concentration in normotensive and hypertensive pregnancies in the human
Authors: Barr S. M. , Lees K. R. , Butters L. , O'Donnell A. , Rubin P. C.
Published: August 2015

1. Basal and stimulated platelet intracellular free calcium concentrations were measured in non-pregnant women and in third trimester patients who were either normotensive or who had pregnancy-induced hypertension or pre-eclampsia. There were 15 subjects in each group.

2. A trend for a reduction of the maximal response of platelet calcium levels to stimulation by 5-hydroxytryptamine was seen in pregnant groups compared with nonpregnant subjects, but this was significant only in pre-eclampsia.

3. No significant differences in basal or adenosine 5′-pyrophosphate-stimulated levels of platelet intracellular free calcium concentration were observed between the four groups.

4. These results illustrate that basal platelet calcium levels are unchanged in hypertension of pregnancy. Alterations in basal platelet calcium levels may not be involved in the platelet activation that is a feature of pre-eclampsia.
Effects of an olive-oil-rich diet on erythrocyte membrane lipid composition and cation transport systems
Authors: Pagnan Antonio , Corrocher Roberto , Ambrosio Giovanni B. , Ferrari Silvana , Guarini Patrizia , Piccolo Diana , Opportuno Aldo , Bassi Antonella , Olivieri Oliviero , Baggio Giovannella
Published: August 2015

1. In this study we sought to test the possibility that an olive-oil-rich diet might influence the membrane lipid composition and cation transport mechanisms in erythrocytes.

2. To this end, 11 normotensive normolipidaemic healthy volunteers were given a standard relatively low fat diet (28% of total energy) for 3 weeks, followed by a high fat (38% of total energy), olive-oil (100 g/day)-enriched diet for the 3 subsequent weeks, in a metabolic ward. The two diets contained the same amount of cholesterol (400 mg), and the polyunsaturated fatty acid/saturated fatty acid ratio was similar and comparatively low (0.35 on the standard vs 0.36 on the olive oil diet).

3. At the end of the study the lipid composition of the erythrocyte membranes showed the following changes: the oleic acid content increased by 15.7% and the amount of saturated fatty acid decreased by 3.2%. The polyunsaturated fatty acid content tended to decrease, while the polyunsaturated fatty acid/saturated fatty acid ratio did not change significantly. The cholesterol/phospholipid molar ratio increased significantly by 7.8%, still remaining within the reference range.

4. At the same time, the mean values of the maximum rates of the cation fluxes mediated by the Na+-K+ pump, and by Na+-K+ co-transport rose significantly, while the maximal rate of Na+-Li+ countertransport showed a non-significant trend towards lower values.

5. Urinary excretion of Na+ and K+, body weight and blood pressure did not change significantly.
A method of quantifying sinus arrhythmia: parallel effect of respiration on P-P and P-R intervals
Authors: Rawles J. M. , Pai G. R. , Reid Susan R.
Published: August 2015

1. The electrocardiogram was recorded for 3 min during spontaneous respiration in 70 subjects aged 15–86 years who were in sinus rhythm. Using a signal-averaging approach, the presence of respiratory variation of P-P intervals was analysed by multiple regression against a cosine function (cosinor analysis).

2. By cosinor analysis the phase of respiration when the intervals were longest was determined, together with the amplitude of the variation of the intervals around their mean value.

3. Respiratory variation of P-P intervals (respiratory sinus arrhythmia) was demonstrated in 84% of subjects; its amplitude decreased with age and respiratory rate. On average, the duration of P-P intervals varied by 2.8% around the mean, and the maximum duration occurred around the time of end-expiration.

4. By cosinor analysis, and allowing for variation of heart rate, P-R intervals showed an independent respiratory variation in 39% of cases, and its average amplitude was 1.2% around the mean.

5. The respiratory variation of P-R and P-P intervals showed similar phase relationships to respiration, suggesting that during respiration there is parallel alteration of sinoatrial and atrioventricular node function.
Effect of passive muscle stretching in osteoarthritis of the hip
Authors: Leivseth Gunnar , Torstensson Johnas , Reikerås Olav
Published: August 2015

1. Twenty-five minute daily muscle stretching, perpendicular to the fibre direction of the adductor muscles without movement of the hip, was performed in patients with osteoarthritis of the hip.

2. Before and after treatment hip abduction was measured and muscle biopsies were taken for analysis of fibre cross-sectional areas of type 1 and type 2 fibres as well as adenosine 5′-triphosphate, creatine phosphate and glycogen contents.

3. From the results it is concluded that passive muscle stretching leads to a significant increase in hip abduction of 8.3° (P < 0.05). There was also a significant increase of type 1 and type 2 fibre cross-sectional area and of glycogen content after the treatment period (P < 0.05), but the concentrations of adenosine 5′-triphosphate and creatine phosphate did not change significantly.
Attenuation of streptozotocin-induced diabetes in rats by pretreatment with chloroquine
Authors: Asamoah Kojo A. , Furman Brian L. , Robb Donald A.
Published: August 2015

1. The effect of chronic administration of chloroquine on glucose homoeostasis was investigated in normal and diabetic rats by determining fasting plasma glucose, glycated plasma protein, plasma immunoreactive insulin, plasma protein and glycated haemoglobin. Animal weights, as well as the survival of the diabetic animals without insulin therapy, were also observed.

2. Apart from an elevation in the plasma immunoreactive insulin levels (4.1 ± 0.6 vs 2.1 ± 0.4 μg/l, P < 0.025), there were no significant differences among the other parameters compared with age-matched controls up to week 12 for the normal rats on chloroquine treatment. After 20 weeks of treatment, however, plasma glucose (7.2 ± 0.1 vs 8.4 ± 0.2 mmol/l, P < 0.005) and glycated haemoglobin (2.9 ± 0.1 vs 3.3 ± 0.1%, P < 0.01) levels were lower in the treated animals. Diabetic rats treated with chloroquine for 12 weeks before the onset of diabetes showed significantly higher plasma insulin and protein levels than control diabetic animals, while plasma glucose (17.7 ± 2.5 vs 29.4 ± 1.7 mmol/l, P < 0.005), glycated plasma protein and glycated haemoglobin (6.6 ± 0.4 vs 7.8 ± 0.4%, P < 0.05) levels were lower.

3. It is concluded that after a prolonged administration of chloroquine there is a hypoglycaemic effect in normal animals, and pretreatment with the drug ameliorates diabetes induced subsequently.
Endogenous digoxin-like immunoreactivity and erythrocyte sodium transport in uraemic patients undergoing dialysis
Authors: Bosch Ricardo J. , Hernando Natividad , Casado Santos , Lopez-Novoa José M.
Published: August 2015

1. Erythrocyte Na+ transport (Na+ pump activity, co-transport, countertransport and passive Na+ efflux) and intracellular Na+ concentration were studied in 10 normal individuals and in 29 uraemic patients on chronic haemodialysis, before and after a haemodialysis session. Eight of them fulfilled the criteria of hypertension.

2. Normotensive patients before haemodialysis were classified in two groups: group 1 (pump –) with decreased erythrocyte Na+ pump activity, and group 2 (normal pump) with normal erythrocyte Na+ pump activity. Group 1 showed, compared with controls, a normal intracellular Na+ concentration and a decreased co-transport, but no difference in either countertransport or passive Na+ efflux. After haemodialysis this difference disappeared. Before haemodialysis, group 2 showed a high intracellular Na+ concentration, but activities of the Na+ transport systems studied were similar to those of controls. After haemodialysis, cell Na+ concentration decreased to a level not significantly different from that of controls.

3. Both before and after haemodialysis, hypertensive patients showed Na+ transport system activities and an intracellular Na+ concentration similar to those of controls.

4. Endogenous digoxin-like immunoreactivity (EDLI) and erythrocyte Na+ transport were studied in five normotensive and five hypertensive patients, before and after haemodialysis. EDLI in plasma was similar in both groups before and after haemodialysis. No correlation was found between EDLI and erythrocyte Na+ pump activity.

5. These results suggest the existence in some dialysed uraemic patients of alterations in erythrocyte Na+ fluxes, which may be corrected by haemodialysis. EDLI and erythrocyte Na+ fluxes do not seem to be markers of secondary hypertension in these patients.
Metabolic effects of intravenous medium- and long-chain triacylglycerols in critically ill patients
Authors: Ball M. J. , White K.
Published: August 2015

1. The metabolic effects of an intravenous lipid emulsion containing medium-chain triacylglycerols (MCT) and long-chain triacylglycerols (LCT) were studied in 16 critically ill, ventilated patients. The effects were compared in a cross-over study with those of a conventional emulsion containing only LCT.

2. The lipid was well tolerated but the metabolic effects of the MCT/LCT infusion differed from those of the LCT infusion.

3. The major differences were a 60% higher insulin concentration and a significantly greater increase in the plasma concentrations of non-esterified fatty acids during MCT/LCT infusion than during LCT infusion. The mean rise in plasma ketone concentration was also higher during MTC/LCT infusion, although this did not reach statistical significance.
Study of DNA polymorphisms of the apolipoprotein AI-CIII-AIV gene cluster in patients with peripheral arterial disease
Authors: Monsalve M. V. , Young R. , Wiseman S. A. , Dhamu S. , Powell J. T. , Greenhalgh R. M. , Humphries S. E.
Published: August 2015

1. We have determined the frequency of DNA polymorphisms of the human apolipoprotein AI-CIII-AIV gene cluster, detected with XmnI, PstI, and PvuII, in a group of patients with peripheral arterial disease.

2. Of the patients, 81 had no evidence of disease in the coronary and carotid arteries, 73 had coronary artery disease but no evidence of carotid artery disease, 25 patients had carotid artery disease but no evidence of coronary artery disease, and 38 had both coronary and carotid artery disease.

3. Levels of triacylglycerol, cholesterol, apolipoprotein B and apolipoprotein AI were not significantly different between the four patient groups.

4. The frequencies of the alleles for the apolipoprotein AI-CIII-AIV polymorphisms, detected with XmnI, PstI and PvuII, did not differ significantly in the patient groups when compared with a sample of clinically well normolipidaemic individuals also from a London population.

5. All five patients with the XmnI genotype we designate X2X2 had high levels of cholesterol, apolipoprotein B and apolipoprotein AI.

6. Patients with the rare VB2 allele of the apolipoprotein CIII-AIV restriction fragment length polymorphism had lower levels of cholesterol, acylglycerol and significantly lower levels of serum apolipoprotein.

7. Our observations suggest that variation in the apolipoprotein AI-CIII-AIV gene cluster may not be contributing significantly to the development of peripheral arterial disease, but variation associated with some of the restriction fragment length polymorphisms may be involved in determining levels of cholesterol- and apolipoprotein-B-containing lipoproteins.
Absorption and metabolism of cholesterol in familial hypercholesterolemia
Authors: Gylling Helena , Miettinen Tatu A.
Published: August 2015

1. The present study investigated the role of intestinal cholesterol absorption in the regulation of cholesterol metabolism and serum lipoprotein levels in 22 patients with heterozygous familial hypercholesterolaemia on low to normal cholesterol intake.

2. The results showed that the higher the dietary cholesterol absorption, the lower was the overall synthesis of cholesterol. Efficient cholesterol absorption actually reduced the elimination of cholesterol as faecal neutral sterols but not consistently as bile acids.

3. In multifactorial analysis, body mass index and dietary plant sterols were negatively associated with cholesterol absorption, but were unrelated to cholesterol synthesis.

4. Fractional cholesterol absorption was related only to the serum very-low-density triacylglycerol level. It was not associated with the total or low-density lipoprotein cholesterol levels. On the other hand, cholesterol synthesis was significantly associated with the serum concentrations of very-low-density lipoprotein and intermediate-density lipoprotein cholesterol and triacylglycerols, and with those of low-density lipoprotein triacylglycerols.

5. In conclusion, dietary cholesterol absorption is an essential regulator of cholesterol homoeostasis in familial hypercholesterolaemia, even in patients on low cholesterol intake.
Inhibition of endogenous oxalate production: biochemical considerations of the roles of glycollate oxidase and lactate dehydrogenase
Authors: Bais Renze , Rofe Allan M. , Conyers Robert A. J.
Published: August 2015

1. Both the peroxisomal, flavin-linked glycollate oxidase [(S)-2-hydroxy-acid oxidase; EC 1.1.3.15] and the cytosolic, nicotinamide–adenine dinucleotide (NAD)-linked lactate dehydrogenase (l-lactate dehydrogenase; EC 1.1.1.27) are thought to contribute to the formation of oxalate from its immediate precursors, glycollate and glyoxylate, but the relative contributions of each enzyme to endogenous oxalate production is not known.

2. In rat liver homogenates, [14C]oxalate production from labelled glycollate is halved and that from labelled glyoxylate is increased fourfold by the addition of either NAD or NADH.

3. In isolated rat hepatocytes, the 3-hydroxy-1H-pyrrole-2,5-dione derivatives of glycollate, which are specific inhibitors of glycollate oxidase, have a greater effect on glycollate metabolism than on glyoxylate metabolism.

4. These findings are consistent with an important role for lactate dehydrogenase in oxalate formation from glyoxylate.

5. With human and rat liver homogenates and with purified human liver glycollate oxidase and rabbit muscle lactate dehydrogenase, dl-phenyl-lactate (2 mmol/l) completely inhibits glycollate oxidase but has no effect on lactate dehydrogenase. On the other hand, the reduced form of a chemically synthesized, NAD–pyruvate adduct (1 mmol/l) almost completely inhibited lactate dehydrogenase but had no effect on glycollate oxidase.

6. Either alone or in combination, dl-phenyl-lactate and reduced NAD–pyruvate adduct reduce oxalate production from glycollate and glyoxylate in isolated rat hepatocytes, but do not abolish it completely.

7. These findings support a role for another enzyme, probably glycollate dehydrogenase (EC 1.1.99.14), in oxalate production in integrated cell metabolism.

8. In relation to renal oxalate stone disease, these results suggest that the therapeutic inhibition of glycollate oxidase or lactate dehydrogenase would not completely prevent the endogenous formation of oxalate.
Renal kallikrein activity in rats developing spontaneous hypertension
Authors: Praddaude Françoise , Tran-Van Tuan , Ader Jean-Louis
Published: August 2015

1. Spontaneously hypertensive rats (SHR) excrete less kallikrein in urine than Wistar–Kyoto rats (WKY) during the developmental phase of hypertension. The present study was designed to examine whether the urinary defect is related to abnormalities in the renal kallikrein content in this hypertensive model.

2. Active and total kallikrein were measured (amidolytic assay) in the renal cortex of newborn and 4-, 8- and 12-week-old SHR and age-matched WKY. Active and total kallikrein were also measured in urine at the same ages, except at birth.

3. Tissue active kallikrein was significantly lower in SHR at birth, representing on average 53% of the values in WKY expressed as content per total cortex weight. Tissue total kallikrein did not differ between newborn SHR and WKY.

4. SHR at 4, 8 and 12 weeks of age had lower urinary active and total kallikrein excretion. Tissue active kallikrein, but not total kallikrein, was higher than in age-matched WKY per g of cortex weight or per mg of protein, whereas both tissue active and total kallikrein were lower in SHR when expressed as content per total cortex weight. At these three ages, active kallikrein represented, on average 86%, while total kallikrein represented 77%, of the values in age-matched WKY.

5. Our results indicate a defect in prokallikrein activation rather than in kallikrein synthesis in the renal cortex of SHR at birth. The reduction in urinary kallikrein excretion during the developmental phase of hypertension in young SHR is similar to the reduction observed in the renal tissue.
Altered interactions between glycogenesis and lipid synthesis after liver resection: specific effects of liver regeneration, coupled with non-specific effects of surgery
Authors: Holness Mark J. , Schofield Paul S. , Sugden Mary C.
Published: August 2015

1. This work investigated the relationship between glycogenesis and lipid synthesis during liver regeneration after partial hepatectomy in the rat.

2. Rates of lipid synthesis were increased during the first 2 post-operative days; these elevated rates were unaffected by starvation. By contrast, glycogen concentrations were decreased even after 8 post-operative days, by which time liver mass had been restored and concentrations were sensitive to nutritional status.

3. The results of experiments involving the intragastric or intraperitoneal administration of glucose indicated that increased lipid synthesis was unlikely to be a consequence of decreased glycogenesis, but that depletion of liver glycogen might be linked both to liver cell division and, in the longer term, surgical stress.
Sodium and lithium handling in the isolated hypertensive rat kidney
Authors: Firth J. D. , Raine A. E. G. , Ledingham J. G. G.
Published: August 2015

1. Isolated kidneys taken from spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto rats (WKY) were perfused over a range of perfusion pressures.

2. Lithium clearance was used as an index of proximal tubule sodium handling.

3. When the perfusate contained an oncotic agent (albumin, 6.7 g/dl) the SHR kidneys performed differently from the WKY kidneys with a reduction in inulin clearance, sodium excretion, fractional sodium excretion and fractional lithium excretion [at 105 mmHg (14 kPa) perfusion pressure, SHR 6.0 ± 1.1% vs WKY 12.6 ± 2.4% (mean ± sem); at 150 mmHg (20 kPa), SHR 17.1 ± 1.6% vs WKY 27.0 ± 2.3%]. Calculated indices of distal tubular function showed no major differences between SHR and WKY.

4. When kidneys were perfused without oncotic agent in the perfusate the differences between SHR and WKY in tubular handling of sodium and lithium were largely abolished.

5. These findings are consistent with the hypothesis that increased sodium reabsorption occurs in the proximal tubules of the kidneys of SHR and suggest that this is an intrinsic property of the kidney, not immediately dependent on neural or humoral factors. Increased sodium reabsorption in the proximal tubule may contribute significantly to the existence of hypertension in the SHR.