bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue distribution of human calcium‐binding protein (28 000 g mol‐1)
Authors: PARKES C. O. , THOMASSET M. , BAIMBRIDGE K. G. , HENIN E.
Published: March 2008

Abstract. Immunoreactive calcium‐binding protein (28 000 g mol‐1, L‐CaBP) has been quantified using a specific radioimmunoassay to human cerebellar L‐CaBP. The level of L‐CaBP in post‐mortem tissue samples varied from undetectable in muscle to 8 μg/mg‐1 protein in the cerebellum and 16 μg mg‐1 protein in the dentate nucleus. L‐CaBP was found to be widely distributed throughout the nervous system while the only non‐nervous tissue which contained appreciable levels was the renal cortex.
Triglyceride metabolism in human liver: studies on hepatic phosphatidic‐acid phosphatase in obese and non‐obese subjects
Authors: BJÖRKHEM INGEMAR , ANGELIN BO , BACKMAN LARS , LILJEQVIST LARS , NILSELL KLAS , EINARSSON KURT
Published: March 2008

Abstract. According to current concepts, soluble phosphatidic‐acid phosphatase, converting phosphatidic acid into a diglyceride, is a rate‐limiting enzyme in the hepatic biosynthesis of triglycerides. The present paper is the first report on this enzyme in human liver. The enzyme activity was assayed in ammonium sulphate precipitates of cytosol obtained from human liver biopsies. The activity was stimulated by preincubation with alkaline phosphatase and inhibited by Mg‐ATP, suggesting that phosphorylation‐dephosphorylation may be of some importance for the expression of the activity of the enzyme. When assayed under optimal conditions, the activity obtained in liver biopsies from normal‐weight gallstone patients averaged 12·8 ± 2·0 nmol min‐1 (mg protein)‐1 (mean ± SEM) (n= 17). The enzyme activity was slightly higher in liver biopsies from morbidly obese subjects 16·4 ± 2·8 nmol min‐1 (mg protein)‐1 (n= 14). The difference between the two groups of subjects was probably in part sex‐dependent and was not statistically significant. A similar small and insignificant difference between the two groups of subjects was found when the enzyme activity was assayed in the maximally stimulated state—i.e. after incubation with alkaline phosphate.

These findings suggest that an increased capacity of the soluble phosphatidic‐acid phosphatase is not of major importance for the increased triglyceride synthesis known to occur in obesity. Other factors (i.e. availability of substrate and cofactors) may be of greater importance.
Early changes in sodium and water balances in patients with acute myocardial infarction: relationship to haemodynamics and creatine kinase
Authors: COL JACQUES , PETEIN MARC , EYLL CHRISTIAN VAN , CHERON PAUL , CHARLIER ANDRÉ A. , POULEUR HUBERT
Published: March 2008

Abstract. The changes in sodium and water balances during the first 4 days after an uncomplicated transmural myocardial infarction (MI) were determined in forty patients. The sodium balance was positive 4 days after MI in 80% of the patients but negative in 20%. Neither in anterior (n= 23) nor in inferior (n= 17) MI were rank correlations found between the haemodynamic parameters (cardiac index, mean arterial pressure, mean right atrial or pulmonary capillary pressures, right or left ventricular work indices) and sodium balance. However, the sodium balances correlated with the total creatine kinase (CK) release in anterior MI after 1 day (r= 0·60; P < 0·002) and after 4 days (r= 0·65; P < 0·001) but not in inferior MI. Furthermore, in anterior and inferior MI matched for their CK release, the sodium handling was different both after 1 day (– 70 in anterior v.+ 44 mmol (24 h)‐1 in inferior MI; P < 0·001) and after 4 days (–36 v.+ 147 mmol (72 h)‐1; P < 0·01), a difference unexplained by differences in medical management or in sodium intake. Finally, sodium balance correlated with the changes in left ventricular stroke work index (LVSWI) observed during this period (r= 0·48, P < 0·001), LVSWI being more stable when sodium balance was more positive.

In conclusion, sodium balance after uncomplicated acute MI is related to MI location, to the size of anterior MI, and cannot be predicted from initial haemodynamics. Finally, the relation between LVSWI stability and positive sodium balance suggests that arbitrary sodium restrictions or diuretics might be deleterious to the haemodynamics after uncomplicated myocardial infarction.
Blood acetaldehyde concentration gradient between hepatic and antecubital venous blood in ethanol‐intoxicated alcoholics and controls*
Authors: NUUTINEN H. U. , SALASPURO M. P. , VALLE M. , LINDROS K. O.
Published: March 2008

Abstract. After ethanol (0·8 g kg‐1 body weight orally) significant concentrations of acetaldehyde (2–20 μmol l‐1) were found in hepatic venous blood of moderately intoxicated non‐alcoholic male Caucasians in spite of the absence of detectable levels (<2 μmol l‐1) in simultaneously taken antecubital blood. In thirteen chronic lcoholics the elevation of blood acetaldehyde was more constant in the hepatic than in the peripheral vein.

Fructose infusion caused a marked elevation of acetaldehyde both in the hepatic and peripheral vein of four controls, but not of four alcoholics, who eliminated ethanol about 50% faster than controls. The rate of disappearance of acetaldehyde from sampled and in vitro incubated hepatic venous blood was similar to that observed after addition of acetaldehyde in vitro to ethanol‐free control blood (2 nmol ml‐1 min‐1 at 20 μmol l‐1 acetaldehyde; Km about 30 μmol l‐1). Uptake of acetaldehyde in blood was calculated to explain maximally 30–40% of the concentration gradient between central and peripheral blood.
Whole‐body elemental composition in patients with renal failure and after transplantation studied using total‐body neutron‐activation analysis
Authors: WILLIAMS E. D. , HENDERSON I. S. , BODDY K. , KENNEDY A. C. , ELLIOTT H. L. , HAYWOOD J. K. , HARVEY I. R.
Published: March 2008

Abstract. Whole body elemental composition in seventy‐five patients with either renal failure or a kidney transplant was measured by neutron‐activation analysis and whole‐body counting. Comparison was made with expected normal values and with a control group; between undialysed, dialysed and transplanted patients; and between those receiving dialysis treatment for various periods. A frequent finding was low body calcium, reflecting the prevalence of renal osteo‐dystrophy. Sodium and chlorine were increased in undialysed patients, a consequence of their renal disease. Patients with transplanted kidneys had reduced amounts of most elements, indicating decreased lean body mass, but increased body weight, probably due to excess fat.
Distal renal tubular dysfunction: a common feature in calcium stone formers
Authors: MEGEVAND M. , FAVRE H.
Published: March 2008

Abstract. Distal renal tubular acidosis has been reported as an uncommon cause of urinary calcium stone disease. However, this defect appears to be more frequent when appropriate tests are performed systematically. Twenty‐nine patients with recurrent calcium stones have been separated into three groups: normocalciuric (group A), renal hypercalciuric (group B) and absorptive hypercalciuric (group C). Distal tubular functions were investigated by the (urine‐blood) pCO2 gradient and by an ammonium chloride test. (Urine–blood) pCO2 gradient was (mean pL SEM), 3·33 pL 0·59 in group A, 2·95 pL 0·34 in group B and 3·31 pL 0·58 kPa in group C. All these values differ significantly from those observed in controls (4·11 pL 0·28 kPa; P < 0·05). After 3 days of ammonium chloride loading, ammonium excretion averaged 54·7 pL 4·2 in group A, 54·4 pL 4·3 in group B and 64·3 pL 5·5 μmol min‐1 in group C. Values obtained in the first two groups were significantly lower than that achieved by control subjects (76·4 pL 14·9 μmol min‐1). It is concluded that tubular dysfunctions defined as impairments in hydrogen ion secretion and ammonium excretion after an acid challenge are a common feature of the urinary calcium stone disease and play a contributory role in its pathogenesis.
Effects of physical exercise on serum calcium and parathyroid hormone
Authors: LJUNGHALL SVERKER , JOBORN HENRIK , BENSON LARS , FELLSTRÖM BENGT , WIDE LEIF , ÅKERSTROM GÖRAN
Published: March 2008

Abstract. The effects of physical exercise on plasma ionized calcium, total serum calcium and parathyroid hormone (PTH) concentrations were evaluated in healthy subjects submitted to work on an ergometer bicycle.

When the workload was increased stepwise there was a significant increase (P < 0·001) in the calcium concentrations (ionized calcium from 1·13 pL 0·03 (SD) to 1·24 pL 0·03 mmol l‐1 and total calcium from 2·35 pL 0·07 to 2·48 pL 0·07 mmol l‐1) when the workload exceeded approximately 65% of the estimated maximum—i.e. a load that caused accumulation in blood of lactic acid. The rise in plasma ionized calcium was, therefore, presumably largely attributed to the acidosis but reduction of plasma volume and influx from extracellular sources might also have contributed.

Beta blockade (with oral intake of propranolol) reduced physical capacity, shortened the duration of work and caused less acidosis. These factors were probably responsible for a smaller rise in ionized calcium during beta blockade (7 pL 4%) than in control studies (21 pL 5%) without medication in subjects examined during short‐term maximal exercise.

Long‐term (1 h) steady‐state work which caused fatigue without producing lactic acidosis did not affect the calcium concentrations.

Despite the effects of work on calcium levels there was no discernible suppression of the PTH concentrations. This might have been due to a concomitant stimulation of PTH secretion by work.
Effect of carbamazepine on haem biosynthesis in man
Authors: RAPEPORT W. G. , CONNELL J. C. , THOMPSON G. G. , MOORE M. R. , BRODIE M. J.
Published: March 2008

Summary. The effects of the enzyme‐inducing anticonvulsant carbamazepine on haem biosynthesis in healthy male subjects is reported. A dose‐dependent increase in the activity of leucocyte δ‐aminolaevulinicacid synthase, the rate‐limiting enzyme of haem biosynthesis, was noted following 400 and 600 mg carbamazepine daily in the same eight subjects. This rise was maximal after 1 week's treatment (400 mg:509%± 285 of baseline; 600 mg: 1062%± 170 of baseline; P < 0·01). Values fell from this peak during the second week despite continuing carbamazepine administration. This pattern was confirmed in a further six subjects taking carbamazepine 400 mg daily for 3 weeks in whom more frequent enzyme measurements were made. The activity of uroporphyrinogen‐1‐synthase in the erythrocyte fell by 10–15% during the treatment periods (P < 0·01). Uroporphyrin and penta‐, hexa‐ and hepta‐carboxylic porphyrins appeared in the urine of all subjects during CBZ therapy. Changes in daily urinary porphyrin and precursor excretion were inconsistent.

CBZ is a porphyrinogenic drug which mimics the changes in enzyme activities and urinary porphyrin ester profile found in patients with latent acute intermittent porphyria, who have a genetic deficiency in uroporphyrinogen‐1‐synthase activity. Leucocyte δ‐aminolaevulinic‐acid synthase may provide a suitable in vivo system for testing the porphyrinogenicity of drags in man.
Coexistence of hypocalciuric hypercalcaemia and interstitial lung disease in a family: a cross‐sectional study
Authors: AUWERX JOHAN , DEMEDTS MAURITS , BOUILLON ROGER , DESMET JOHAN
Published: March 2008

Abstract. In a prospective investigation, a large kindred (twenty‐one subjects) with unexplained association of familial hypocalciuric hypercalcaemia and idiopathic interstitial lung disease was studied. Serum calcium was increased in fifteen patients (the youngest being 7 years old) and was associated with hypo‐ or normocalciuria. The abnormalities were not age‐dependent. The serum concentrations of parathyroid hormone, 25–hydroxyvitamin D3, 1,25‐dihydroxyvitamin D3 and calcitonin were normal. In twelve patients the diffusing capacity (DLco) and/or DLco per unit lung volume was less than 75% predicted. This was often accompanied by a vital capacity of less than 80% predicted, an increased Tiffeneau index, and a reticulo‐micronodular pattern with high diaphragm on chest X‐ray. The decrease in DLco was more pronounced in older non‐smoking as well as smoking subjects (P < 0·02) suggesting a progressing interstitial disease with age. The fibrosing alveolitis, which had been confirmed by open lung biopsy in three subjects, could not be attributed to sarcoïdosis, collagen‐vascular disease, or exogenous causes. The disturbances in the calcium homeostasis and in the diffusing capacity of the lung coexisted in seven of the twenty‐one patients. Apparently, both abnormalities were inherited following an autosomal‐dominant pattern but with a different penetration in each person, and seemed not be causally related to each other.
Defective renal water excretion in nephrotic syndrome: the relationship between renal water excretion and kidney function, arginine vasopressin, angiotensin II and aldosterone in plasma before and after oral water loading
Authors: PEDERSEN E. B. , DANIELSEN H. , MADSEN M. , JENSEN T.
Published: March 2008

Abstract. An oral water load of 20 ml (kg body wt)‐1 was given to seventeen patients with the nephrotic syndrome and fifteen healthy control subjects. Diuresis (D), free water clearance (CH2O), plasma concentrations of arginine vasopressin (AVP), angiotensin II (AII) and aldosterone (Aldo) were determined before and 3 times during the first 4 h after loading. In the nephrotic syndrome D was significantly lower 1–2 h after loading than in the control subjects, predominantly due to a lower CH2O (2·61 and 7·01 ml min‐1 (medians), P < 0·01).

Creatinine clearance and the maximum increase in CH2O were significantly correlated in patients with the nephrotic syndrome (ρ= 0·721, n= 17, P < 0·01) and the control subjects (ρ= 0·596, n= 15, P < 0·01). AVP was reduced in both groups during loading, but AVP was clearly elevated in the patients with the nephrotic syndrome when compared to the control subjects both before (3·0 and 1·9 pmol 1‐1, P < 0·01) and during loading. There was a significantly negative correlation between CH2O and AVP in both groups. AII and Aldo were reduced during loading, but the levels were the same in the patients and in the control group, and AII and Aldo were not correlated to CH2O. It is concluded that patients with the nephrotic syndrome excrete an oral water load more slowly than healthy control subjects, and that this phenomenon partly is due to reduced glomerular filtration rate and partly to increased AVP.
Granulocyte migration in ulcerative colitis
Authors: SAVERYMUTTU SETHNA H. , CHADWICK VINTON S. , HODGSON HUMPHREY J. F.
Published: March 2008

Abstract. Although histologically relapses in ulcerative colitis are characterized by an intense granulocyte infiltrate, there is evidence both from in vitro function tests and skin window migration studies in vivo that there is defective granulocyte function in ulcerative colitis. We have recently developed a method for non invasively monitoring granulocyte migration to sites of inflammation using indium‐111‐labelled granulocytes, and have used this technique in fifteen patients with ulcerative colitis. In all fifteen cases there was rapid migration of indium‐111‐labelled granulocytes to inflamed bowel within 10 min of return of the labelled cells. This study provides no support for a significant granulocyte migration defect in ulcerative colitis.
Bactericidal activity of ascitic fluid in patients with nephrotic syndrome
Authors: AKALIN H. E. , FISHER K. A. , LALELI YAHYA , CAGLAR SALI
Published: March 2008

Abstract. Patients with nephrotic syndrome are unusually susceptible to infections, including primary peritonitis. In this study, we have evaluated nine adult patients with nephrotic syndrome and ascites for ascitic fluid bactericidal activity, complement and immunoglobulin concentrations. Eight of nine patients had diminished ascitic fluid bactericidal activity while twelve control peritoneal fluids had normal bactericidal activity. Complement (C3 and C4) and immunoglobulin (IgG and IgM) concentrations were significantly lower in nephrotic syndrome ascitic fluid than peritoneal fluid from normal subjects. These findings may explain the high occurrence rate of primary peritonitis in nephrotic patients with ascites.
Reduced tubular reabsorption of phosphate during post‐operative glucose infusions in humans
Authors: RASMUSSEN ALLAN , JESPERSEN LAWS
Published: March 2008

Abstract. It is well‐known that serum phosphate concentration decreases considerably during postoperative glucose infusions. The purpose of this study was to elucidate whether the renal handling of phosphate could be responsible for this fall. Twelve patients were studied during glucose and saline infusions on the 2 first post‐operative days. The maximal tubular capacity for reabsorption of phosphate per litre of glomerulus filtrate (TmP/GFR) was significantly reduced during glucose infusions in relation to saline infusions. The glucose induced fall in serum phosphate concentration was correlated to the change in TmP/GFR (r2= 0·71). This study did not explain the reduced TmP/GFR during the glucose infusions, but a high correlation was found between TmP/GFR and the changes in plasma glucose concentration during the infusions (r=–0·91).
Fibrinolytic study in plasma and ascitic fluid of cirrhotic patients before and after ascites concentration; reinfusion technique
Authors: PATRASSI G. M. , MARTINELLI S. , STURNIOLO G. C. , CAPPELLATO M. G. , VICARIOTTO M. , GIROLAMI A.
Published: March 2008

Abstract. Management of cirrhosis with massive ascites involves particular difficulties. The introduction of a peritoneovenous shunt and reinfusion of concentrated ascitic fluid techniques allows increased diuresis and improves renal function. However, these procedures have frequently been associated with disseminated intravascular coagulation and/or activation of fibrinolysis. Factor VIII activity, antigen and ristocetin cofactor, plasminogen, antiplasmin, plasminogen activator activity and plasmin‐antiplasmin complex were investigated both in the ascitic fluid and plasma of cirrhotic patients before and after the concentration‐reinfusion technique. Our results indicated that no hyperfibrinolysis was seen in the plasma of cirrhotic patients and that activation of fibrinolysis exists in ascites. Significantly higher levels of plasmin‐antiplasmin complex and plasminogen activator activity were found in ascitic fluid than in plasma. In post‐reinfusion much higher levels of all three Factor VIII components were observed in cirrhotic plasma than in normal plasma. In conclusion, activation of fibrinolysis could explain coagulation complications occurring after ascites reinfusion. Antifibrinolytic treatment could render the concentration‐reinfusion technique more acceptable.
Relationship of brain glutamine and brain neutral amino acid concentrations after portacaval anastomosis in rats
Authors: JEPPSSON B. , JAMES J. HOWARD , EDWARDS LAURA L. , FISCHER J. E.
Published: March 2008

Abstract. Evidence from several sources suggest that blood‐brain transport of the large neutral amino acids (NAA) is abnormal in animals with a portacaval anastomosis (PCA) and in patients with liver cirrhosis and portal‐systemic shunting and encephalopathy, but the underlying mechanisms are unknown. After PCA, the concentration of glutamine (Gin) in brain is markedly increased as a by‐product of cerebral ammonia detoxification, and the rate of efflux of Gin from brain is also increased. The following studies were undertaken to clarify the relationships among plasma and brain concentrations of NAA after PCA in rats and to examine the relationship of brain Gin concentration to plasma and brain NAA concentrations.

After PCA plasma phenylalanine, tyrosine and histidine were elevated and leucine, isoleucine and valine were lowered. In brain, phenylalanine, tyrosine, histidine and methionine were markedly elevated after PCA and their concentrations in brain far exceeded the concentrations in plasma.

Analyses of single, partial and multiple correlations of plasma NAA ratios expressed as plasma competitor function (PCF), brain NAA and brain Gin showed significant correlations between PCF and brain NAA in shunted rats. A better correlation was found between brain NAA and brain Gin.

Correlation coefficients obtained from multiple correlation analysis equalled or exceeded those obtained in the partial correlation or in the single correlation, suggesting that the effects of PCF and brain Gin on brain NAA were separate and additive. Gin was shown to compete with other NAA for blood brain transport by inhibiting brain 14C phenylalanine uptake. This in combination with the relationship demonstrated between brain Gin concentration and brain NAA concentrations suggests that Gin exerts some effect on blood‐brain NAA transport. This has therapeutic implications in patients with liver failure and encephalopathy.
Effect of heparin and aspirin on platelet and clotting activation during leukapheresis
Authors: FABRIS F. , CASONATO A. , RANDI M. L. , BELLONI M. , QUAINO V. , ONGARO G. , GIROLAMI A.
Published: March 2008

Abstract. β‐thromboglobulin (βTG), serotonin (5HT) and fibrinopeptide A (FPA) were assessed in twenty‐two normal donors before, during, and at the end of leukapheresis. Seven procedures were carried out adding heparin to the circuit, and seven adding acetyl salicylic acid (ASA). The remaining eight procedures were carried out using only citrate and served as controls. Plasma βTG increased both during and after the apheresis, together with a significant decrease of the intra‐platelet content. Platelet 5HT did not show significant changes whereas FPA increased significantly. Using heparin, we obtained a complete prevention of FPA cleavage during the entire procedure, while βTG increased at the middle of the procedure. No significant effects were observed using ASA both on βTG and FPA levels. These features clearly indicate the activation of platelets and the thrombin generation in the apheresis circuit. Nevertheless, the activation of the clotting system seems to be predominant, as supported by the improved effect of heparin on βTG and FPA amounts.
Metabolic response to different forms of physical exercise in type I diabetics and the duration of the glucose lowering effect
Authors: HÜBINGER A. , RIDDERSKAMP I. , LEHMANN E. , GRIES F. ARNOLD
Published: March 2008

Abstract. In order to analyse the metabolic effects of exercise nine well‐controlled type I diabetics took part in four series of tests: (i) a short exercise with maximal work load, (ii) a 30 min exercise with half maximal work load, (iii) a 3 × 10 min interval exercise and (iv) control without exercise. Exercises were performed on a bicycle ergometer starting at 09.00 h. On the test days, only two thirds of the normal insulin dose was given.

Blood glucose, free insulin, glucagon, catecholamines, growth hormone, Cortisol, lactate and pyruvate were measured during the exercise and the following 60 min. Glucose profiles were taken until 17.15 h.

The short exercise with maximal work load did not affect blood glucose, the half maximal exercise and the interval exercise resulted in a decrease. Short rest phases did not modify the glucose lowering effect nor the overall response of counterregulatory hormones. A snack following exercise resulted in a total compensation of the glucose lowering effect.
Pharmacokinetic and pharmacodynamic interaction between furosemide and metolazone in man
Authors: MARONE C. , MUGGLI F. , LAHN W. , FREY F. J.
Published: March 2008

Abstract. In various clinical situations a poor diuretic response to furosemide may be improved by the addition of metolazone. The mechanism of this additive effect is unclear. The purpose of the present investigation was to establish whether metolazone changes the pharmacokinetics of furosemide and by this mechanism enhances the diuretic effect. Eight volunteers were given an intravenous infusion of 4 mg h‐1 of furosemide for 12 h. After 6 h 2middot;5 mg metolazone were administered orally. The addition of metolazone increased diuresis, urinary excretion of sodium and chloride (P<0middot;01), but decreased urinary excretion of calcium (P<0middot;01), while furosemide excretion remained unchanged. Total body clearance and renal clearance values of furosemide were similar before and after administration of metolazone. Our data confirm the additive diuretic effect of the combination treatment metolazone‐furosemide and show for the first time a distinct hypocalciuric action of metolazone, similar to thiazides. Moreover metolazone does not affect the pharmacokinetics of furosemide.
B complex vitamins activate rat guanylate cyclase and increase cyclic GMP levels
Authors: VESELY D. L.
Published: March 2008

Abstract. Since B complex vitamins and the intracellular messenger cyclic guanosine monophosphate (GMP) have similar effects of promoting growth, DNA and protein synthesis, the present investigation was designed to determine if the B complex vitamins' mechanism of action might involve cyclic GMP. All of the B complex vitamins increased rat cyclic GMP tissue levels. The cause of these increased cyclic GMP levels was activation of the enzyme guanylate cyclase [E.C.4.6.1.2.] which was increased significantly (P<0·001) in a variety of tissues at the 1 nmol 1‐1 concentration of these vitamins. The maximal activation of this enzyme required the presence of manganese ion. The present investigation suggests that the guanylate cyclase‐cyclic GMP system may play a role in the mechanism of action of B complex vitamins at the cellular level.
Naloxone inhibits sulpiride‐induced hyperprolactinaemia in man
Authors: BERNINI G. P. , PEDRINELLI R. , SALVETTI A. , FRANCHI F. , LUISI M.
Published: March 2008

Abstract. In order to evaluate the interaction between the opiate‐like peptidergic pathways and the dopaminergic system in modulating prolactin (PRL) secretion, ten normal volunteers were studied according to a double‐blind, cross‐over, randomized experimental design. A group of five subjects was given a fixed dose of sulpiride (a selective antidopaminergic agent, 25 mg i.v.) plus either placebo or three different doses of naloxone (a selective opioid antagonist, 02,0–4,0‐8 mg i.v.) while a second group of five subjects received the same drugs in a ‘reverse’ protocol, i.e. a fixed dose of naloxone (0–4 mg i.v.) plus either placebo or increasing doses of sulpiride (25, 50, 100 mg i.v.). In both groups, the drugs were injected simultaneously and blood samples for PRL determination were taken at various intervals during the 15 min preceding drug injections and then over the following 4 h. Naloxone (0–4 mg i.v.) per se did not induce any modification of plasma PRL levels, but reduced to a significant extent sulpiride‐induced hyperprolactinaemia (P<0·02). However, a higher dose of naloxone (0–8 mg i.v.) did not cause significant changes in sulpiride‐stimulated PRL levels. Increasing dosages of sulpiride (up to 100 mg i.v.) reversed the blunted response of PRL after sulpiride, 25 mg, in presence of naloxone. Our data show that naloxone, at a dose of 0–4 mg i.v. inactive per se on basal PRL levels, is able to blunt significantly sulpiride‐induced hyperprolactinaemia. This suggests that, in man, opioid peptides are able to influence PRL release after antidopaminergic stimuli.
Antibodies to human T‐cell lymphotropic virus type III in promiscuous healthy homosexual men. Relation to immunological and clinical findings
Authors: GERSTOFT J. , LINDHARDT B. ØRSKOV , PETERSEN C. S. , KROON S. , ULLMAN S. , MØLLER S. , NIELSEN J. OLE , DICKMEISS E.
Published: March 2008

Abstract. Antibodies to human T‐cell lymphotropic virus type III (HTLV‐III Ab) were present in twenty‐one out of sixty‐four asymptomatic promiscuous homosexual men from Copenhagen. The presence of HTLV‐III Ab was associated with lymphadenopathy (P<0·0005), cytomegalovirus isolation (P<0·01), low skin test reactivity (P<0·01) and episodes of fever within the 2 month period prior to investigation (P<0·05). No significant differences occurred in the total number of T‐cells, T‐suppressor cytotoxic cells, T‐helper cells or helper to suppressor ratio (H/S ratio) between HTLV‐III Ab positive and negative homosexuals. An H/S ratio ≤1·0 was significantly more frequent in homosexual men who both had HTLV‐III Ab and excreted cytomegalovirus (P<0·01).

The H/S ratio of HTLV‐III negative homosexuals were significantly lower than that of the controls suggesting that a non‐HTLV‐III related immunosuppression occurs among homosexuals. Within 2 years after the investigation AIDS or the AIDS related complex developed in three of the men, who at the first investigation all had HTLV‐III Ab, alterations in T‐lymphocyte subsets and cutaneous anergy. It is suggested that a combination of T‐cell subset determination and determination of HTLV‐III Ab may provide more valuable prognostic information than isolated determintion of HTLV‐III Ab.
Neutral steroid metabolites in patients with uraemia and after renal transplantation: a quantitative and qualitative study in body fluids
Authors: LUDWIG‐KÖHN HELGA , HENNING H. V. , SZIEDAT ASTRID , KLUG P. , ALEXANDER H. , SCHELER F.
Published: March 2008

Abstract. Steroid metabolites enriched from urine, haemofiltrate, and CAPD‐dialysate (Continous Ambulatory Peritoneal Dialysis) were identified by gas chromatography‐mass spectrometry and quantified by capillary gas chromatography. The study included twenty healthy controls, twenty‐six non‐dialysed urae‐mics, thirty‐nine patients on regular dialysis treatment, and twenty‐two allograft recipients.

Compared to the 24 h urinary excretion rates of controls the excretion rates of androsterone and etiocholanolone were in the lower normal range up to significantly decreased in the body fluids of all patients, and those of the corticoid metabolites were also significantly decreased. 11‐Oxygenated androstano‐lones in urine from non‐dialysed uraemics correlated significantly decreased. 11‐oxygenated androstano‐levels and were significantly increased, but normal in haemofiltrate and CAPD‐dialysate, while in urine of allograft recipients the values were significantly lower.
Effect of captopril infusion on systemic and renal haemodynamics in conscious hypertensive rats with chronic, progressive aortic ligation
Authors: GONZALEZ‐PEREZ LUIS M. , MARTIN‐PAREDERO VICENTE , CASADO SANTOS , LOPEZ‐NOVOA JOSE M.
Published: March 2008

Abstract. The effect of the converting enzyme inhibitor captopril (5 mg (kg bwt)‐1) on systemic and renal haemodynamics has been studied in conscious rats in which a progressive hypertension has been induced by progressive aortic ligation (AL) between the renal arteries, and in a sham‐operated (SO) group.

Cardiac output (CO), organ blood flow and vascular resistances have been measured using radioactive microsphaeres.

Captopril infusion caused increases in CO in both groups of rats, but the increase was higher in SO (9±2 ± 0±7%) than in AL rats (5±2 ± 0±6%; P<0±005). Plasma renin concentrations were similar in both groups but increased more in AL (10±3 μIU ± 1±0) than in SO (5±81 μIU ± 0±62; P<0±05) after captopril. Captopril induced also a larger decrease in arterial pressure (36 ± 4 mmHg), and of the pressure gradient across the stenosis (19 ± 3) mmHg in AL than in SO rats (5±6 ± 1±4 and 1±1 ± 1±3 mmHg, P < 0±005 for both cases). Vascular resistance of the kidney above the ligature decreased more in AL than in SO rats, but this difference was not observed in the other kidney.

From these data it can be concluded that captopril has an acute hypotensive effect despite the normal renin levels of this model of chronic hypertension. In addition, blood flow to the high‐pressure perfused kidney seems to be dependent on the increased renin production by the contralateral kidney.
On the mechanism of renin release during experimental myocardial ischaemia
Authors: ERTL GEORG , MEESMANN MALTE , KOCHSIEK KURT
Published: March 2008

Abstract. An increase in plasma renin activity (PRA) following experimental coronary occlusion has previously been demonstrated in anaesthetized and conscious dogs. The purpose of the present study was to analyse the mechanism of this renin release. In two distinct models of myocardial ischaemia in anaesthetized dogs–i.e. occlusion of the left‐anterior descending coronary artery (model A, n= 21) and atrial pacing in the presence of stenosis of the left‐anterior descending coronary artery (model B, n= 23), an increase in arterial PRA was found from 1±68 ± 0±43 to 3±06 ± 0±63 ng ml‐1 h‐1 (model A, ±± SEM, P<0±025) and from 9±87 ± 3±59 to 14±96 ± 4±06 ng ml‐1 h‐1 (model B, P<0±05), respectively. The increase in PRA following coronary occlusion was not blunted by adrenergic beta‐receptor blockade with propranolol (3 mg kg‐1 i.v.; n= 4). Coronary sinus PRA was lower than arterial PRA and the increase in PRA did not occur in nephrectomized dogs (n= 5). The data suggest that myocardial ischaemia induces a release of renin from the kidney which is not mediated by adrenergic beta receptors.
Platelet alpha2 adrenoceptors in Parkinson's disease: decreased number in untreated patients and recovery after treatment
Authors: VILLENEUVE ALAIN , BERLAN MICHEL , LAFONTAN MAX , CARANOBE CLAUDINE , BONEU BERNARD , RASCOL ANDRÉ , MONTASTRUC JEAN‐LOUIS
Published: March 2008

Abstract. [3H]‐yohimbine binding sites were quantified in platelets from Parkinsonians with no clinical signs of dysautonomia. Never‐treated Parkinsonians had a lower specific binding than control subjects. This alteration was associated with decreased epinephrine‐induced platelet aggregation. Treatment with dopaminergic agents induced a significant increment of [3H]‐yohimbine binding sites. These results show that Parkinson's disease is associated with a reduced number of peripheral alpha2 adrenoceptors and that dopaminergic agents induce partial recovery.
Hepatic regeneration and metabolism after partial hepatectomy in normal rats: effects of insulin therapy
Authors: JOHNSTON D. G. , JOHNSON G. A. , ALBERTI K. G. M. M. , MILLWARD‐SADLER G. H. , MITCHELL J. , WRIGHT R.
Published: March 2008

Abstract The effect of insulin therapy on liver regeneration has been studied in normal fed rats 12, 24 and 48 h after partial hepatectomy. Dry weight of regenerating liver increased between 12 and 48 h after partial hepatectomy and was unaffected by insulin therapy. [6‐3H] Thymidine uptake peaked at 24‐h (24·7 ± 2·4% of total liver cells) and insulin treatment had no additional effect. At 12‐h after partial hepatectomy, hepatic [ATP] was decreased 15%, while [ADP] and [AMP] were increased 47% and 83% respectively compared with sham‐operated animals. Partial hepatectomy also caused an increase in hepatic [triglyceride], a decrease in hepatic [glycogen] and an increase in the levels of glucose and several glycolytic intermediates. The hepatic redox ratios, [lactate]:[pyruvate] and [3‐hydroxybutryate]:[acetoacetate], were elevated. Insulin therapy had only minor effects on hepatic adenine nucleotide levels, intermediary metabolite concentrations or intrahepatic redox ratios after partial hepatectomy. These findings suggest a decreased hepatic intracellular energy state in regenerating liver; insulin therapy in normal rats does not influence this metabolic change nor the regenerative response.
Nephrotoxicity of cyclosporin A. A lithium clearance and micropuncture study in rats
Authors: DIEPERINK HANS , LEYSSAC PAUL P. , STARKLINT HENRIK , KEMP EJVIND
Published: March 2008

Abstract.Renal function was studied in rats treated with cyclosporin A (CyA). Peroral CyA 25 mg kg‐1day‐1depressed glomerular filtration rate (GFR) from 1284 ± 429 to 500 ± 228μl min‐1g‐1kidney weight (KW) (P< 0·01). Absolute rate of proximal tubular reabsorption (APR) decreased from 1075 ± 437 to 468 ± 203μl min gKW‐1(P< 0·01). Proximal tubular fractional reabsorption (PFR) was 67·7 and 68·5% measured with the TT/OT and fractional lithium‐clearance methods, respectively. Amiloride had no effect on lithium‐clearance in CyA treated rats. Acute isotonic volume expansion increased GFR and APR towards normal, while PFR remained increased. Increased sodium clearance did not normalize renal function. CyA intravenously (12·5 mg kg‐1) depressed GFR and APR acutely, while PFR increased. Proximal intratubular pressures were low normal (mean 11·6 mmHg). Proximal transit times were prolonged (mean 25·2 s,P< 0·01). Renal morphology was normal. The data are evidence against a primary tubular damage of CyA, and makes it less likely that the major lesion is located to the glomerular membrane. The results suggest that CyA nephrotoxicity mainly is due to a haemodynamic effect.
Renal prostaglandins E2 and F2α throughout normal human pregnancy
Authors: BERNHEIM J. , SHAPIRA J. , DAVID F. , BEHARI C. , GELERNTNER I. , RATHAUS M.
Published: March 2008

Abstract. Twenty‐five normal pregnant women were studied sequentially at 4‐week intervals, beginning from weeks 8–16 until delivery. In eighteen women the study was repeated 6 weeks after delivery. The 24‐h urinary excretion of PGE2 and PGF2α plasma renin activity (PRA), plasma aldosterone and fractional excretion of sodium (FENa) were measured at each visit. PGE2 and PGF2α, increased progressively throughout pregnancy (867 ± 81 and 1048 ± 94 ng 24 h‐1 respectively, before week 15 and 1581 ± 175 and 2625 ± 305 ng 24 h‐1, respectively, after week 35) and returned to normal values 6 weeks after delivery (748 ± 107 and 1503 ± 165 ng 24 h‐1, respectively). PRA and aldosterone increased in a similar fashion, but values of prostaglandins did not correlate with those of PRA or aldosterone. PGE2 correlated directly with FENa but this correlation was weak. These results may suggest that tubulo‐interstitial prostaglandins play a role in the regulation of sodium homeostasis during pregnancy.
Renin, aldosterone and arginine vasopressin in patients with liver cirrhosis: the influence of ascites retransfusion
Authors: BURMEISTER P. , SCHÖLMERICH J. , DIENER W. , GEROK W.
Published: March 2008

Abstract. Plasma renin activity (PRA), and concentrations of aldosterone (PAL) and arginine vasopressin (AVP) in plasma were determined in 15 patients with ascites due to cirrhosis. The concentrations in ascites were analyzed simultaneously. Six patients were studied during extracorporeal ascites retransfusion. All but one patient with ascites showed elevated PAL (642 ± 255 pg ml‐1) and PRA (43 ± 26 ng ml‐1 h‐1); all had increased AVP (7·3 ± 5·1 pg ml‐1). A low ascites to plasma ratio was found for aldosterone (0·023 ± 0·023), but not for AVP (0·71 ± 0·82), Retransfusion resulted in a normalization of central venous pressure (CVP), urinary volume, sodium/potassium ratio in urine, PAL and PRA, but not of AVP, serum sodium concentration and urinary sodium excretion. PRA and PAL increased again after cessation of treatment, while urinary output, CVP and sodium/potassium ratio in urine decreased. The results support the ‘underfilling’ concept, but give evidence that, in addition, other factors must be involved in the impaired natriuresis in cirrhotic patients. They further support the concept of volume expansion and increased renal perfusion as reason for the therapeutic efficacy of ascites retransfusion. Previous diuretic treatment seems not to be of importance for altered hormone metabolism in liver cirrhosis. Storage in a third compartment may be a factor in the persistently elevated AVP levels.
Osteoporosis of the slender smoker revisited by epidemiologic approach
Authors: JENSEN G. FINN
Published: March 2008

Abstract. A representative sample of 285 70‐year‐old Danish women were examined by case history, 125I photon absorptiometry of both forearms (BMC), and lateral X‐rays of the spine. Fat mass was calculated from height (H), weight (W) and estimated lean body mass (LBM) as W‐LBM/H kg m‐1. Seventy‐five participants with previous or present disease or treatment known to influence the calcium metabolism were excluded. The remaining 210 women included the final study groups of seventy‐seven long‐term smokers and 103 non‐smokers. Within both groups BMC correlated positively to fat mass, r= 0·447 and 0·560, respectively (P < 0·001). The slopes of the regression lines and their positions were similar (P > 0·05). Hence, for a certain degree of overweight smoking per se does not influence BMC to a significant degree. Although the smokers were less obese (P < 0·005) and tended to have lower BMC (P < 0·10) their frequency of non‐violent post‐menopausal fractures, 40·3%, was the same as for non‐smokers, 44·7%. The respective frequencies of definite osteoporotic fractures (i.e., spinal crush and fractures of the hip, proximal humerus and distal forearm) were comparable as well. In conclusion, the influence of smoking on the female skeleton seems mainly to be caused by the associated slenderness.
Evidence for capillary leakage during chemotherapy in man
Authors: VRIES E. G. E. DE , BEEKHUIS H. , JONG R. DE , MULDER N. H. , PIERS D. A.
Published: March 2008

Abstract. The influence of intensive chemotherapy with high dose VP 16–213, cyclophosphamide and autologous bone marrow transplantation on transcapillary escape rate of albumin was evaluated. Transcapillary escape rate and plasma volume were measured with 131I‐labelled albumin. Measurements were performed 1 day before (T0), 1 week after (T1) and 2 weeks after (T2) start of chemotherapy. Before therapy TER (n= 7, x̄= 7·1% h‐1) was already raised in patients compared to controls (n= 5, x̄= 3·8% h‐1, P < 0·025). No difference was found for transcapillary escape rate on T1 (n= 9, x̄= 7·6% h‐1) compared to T0. There was an increase of transcapillary escape rate from T0 to T2 (n= 8, x̄= 9·5% h‐1, P < 0·05). Plasma volume did not change during therapy. Serum albumin concentrations were reduced before chemotherapy (x̄= 38 g l‐1) compared to controls (x̄= 44 g l‐1). After 1 (x̄= 34 g l‐1) and 2 weeks (x̄= 31 g l‐1) these concentrations decreased further. The same was found for intravascular mass of albumin related to body weight. The intravascular mass of albumin/bodyweight and the transcapillary escape rate are related in the patients (r=–0·477, P < 0·01) and the patients plus controls r=–0·585, P < 0·001). This means the higher the transcapillary escape rate the lower the intravascular mass of albumin. No correlation between transcapillary escape rate and presence of fever was found. It can be concluded that intensive chemotherapy leads to further increase of an already elevated transcapillary escape rate for albumin.
Effects of atriopeptin III on renal function, regional blood flows and left ventricular function in conscious dogs in presence or absence of hypovolaemia
Authors: HABIB B. R. , HANET C. , MECHELEN H. VAN , KEYEUX A. , CHARLIER A. A. , POULEUR H.
Published: March 2008

Abstract. The effects of atriopeptin III (AP III) on the left ventricular and renal functions were studied in thirteen chronically instrumented conscious dogs and compared to those of the solvent (saline). In the normovolaemic state, an AP III infusion (1 μg kg‐1 min‐1 i.v.) had no effects on heart rate, on mean arterial or left ventricular pressure, on (dP/dt) Max (2989±119 vs. 3007±155 mmHg s‐1; NS) or on the relaxation rate. The left ventricular endocardial and epicardial coronary blood flows (radioactive microspheres) and the renal flow in the outer cortex (707–683 ml (min‐1 100 g‐1); NS) or in the inner cortex (563–570; NS) were also insignificantly affected by AP III infusion. However, AP III increased urinary flow from 24±6 to 36±7 ml h‐1 (P<0·025) and the Na+ and Cl‐ excretions by 92 and 98%, respectively, (P<0·025 and P<0·05 vs. saline group) without altering significantly K+, urea and creatinine eliminations. In the moderately hypovolaemic state (mean reduction in renal flow: outer cortex ‐15%; P<0·05, inner cortex ‐5%; NS), AP III infusion at two doses (1 and 3 μg kg‐1 min‐1) still had no effects on arterial pressure and on the indexes of left ventricular inotropic state and relaxation but in this setting, the diuretic effect of AP III became variable. Five dogs markedly increased their excretion of water, Na+ and Cl‐ whereas no change was noted in the seven remaining dogs. Regional renal blood flows and urinary output before infusion were similar in the responders and non‐responders but the mean arterial pressure (81±2 vs. 73±3 mmHg; P<0·01) was lower in the non‐responders. It is concluded that AP III has no effect on left ventricular contractility or on the coronary vasculature; at small doses, its diuretic effects appear independent of a renal vasodilation and are rapidly blunted in the presence of hypotension.
Stimulation of hepatic efflux and turnover of glutathione by methionine in the rat
Authors: LAUTERBURG B. H. , SMITH C. V.
Published: March 2008

Abstract. The effect on hepatic glutathione (GSH) turnover of transpeptidation of substrate amino acids by γ‐glutamyl transferase (GGT) was evaluated in intact rats. The infusion of 5 mmol kg‐1 of L‐methionine, L‐cysteine and glycylglycine promptly stimulated hepatic GSH turnover as measured by acetaminophen probe analysis. This stimulation was abolished by pretreatment of the animals with inhibitors of GGT. Glycine and phenylalanine, two amino acids that are poor substrates for transpeptidation by GGT, had no effect on GSH turnover. A methionine load led to a decrease in hepatic GSH from 6·40±0·6 to 4·1±0·4 μmol g‐1 and significantly increased the plasma clearance of GSH from 4·76 ± 0·09 to 6·05 ± 0·36 ml min‐1 100g bw‐1. In the in situ perfused rat liver increasing concentrations of methionine in the perfusate stimulated the efflux of GSH from 19·5 nmol min‐1 g liver‐1 without added methionine to 34·1 and 56·3 nmol min‐1 g liver‐1 at 0·1 and 1·0 mM methionine, respectively. We conclude that the administration of amino acids or dipeptides that are good substrates for transpeptidation by GGT increases hepatic turnover of GSH. The stimulation of sinusoidal efflux of GSH by methionine indicates that an increased efflux is responsible for the increased rate of turnover of hepatic GSH. The associated increase in the plasma clearance of GSH suggests that by increasing the efflux of GSH the liver may provide more GSH for the extracellular transpeptidation of substrate amino acids.
Maximal oxygen consumption and pulmonary circulation in patients with chronic bronchitis
Authors: HENRIQUEZ A. , SCHRIJEN F. , POINCELOT F. , GIMENEZ M. , POLU J. M. , SADOUL P.
Published: March 2008

Abstract. In order to study the relations between maximal oxygen consumption during exercise (V̇O2max) and the pulmonary circulation when pulmonary artery pressure (PPA) and pulmonary vascular resistance (PVR) are normal or close to normal, we evaluated twenty‐three patients with chronic bronchitis, in stable clinical condition. All these patients performed a progressive exercise test on a bicycle ergometer until exhaustion (V̇O2max); they were also subjected to right heart catheterization at rest and during light exercise at constant load. In these patients with moderate functional impairment, we observed on average a significant, although weak, correlation (r=‐0·52, P<0·01) between pulmonary vascular resistance at rest and V̇O2max. When V̇O2max exceeded 2 l min‐1, PVR was below 210 dyn s cm‐5. From the heart rate during maximal exercise we computed the oxygen pulse (O2Pmax). In eight patients O2Pmax was reduced (≤ 11 ml) with maximal heart rate close to its predicted value; in seven of these subjects PVR was abnormal and P̄PA at rest was at least 20 mmHg.

Thus it seems that in chronic obstructive bronchitis mild disturbances in pulmonary circulation may be a contributory factor in the limitation of exercise performance, and a maximal exercise test may help to detect pulmonary hypertension in these patients.