bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exogenous factors influencing the human erythrocyte sodium–lithium countertransport system
Authors: BEUCKELMANN DIRK , ERDMANN ERLAND 
Published: March 2008

Abstract. It has recently been found that the Na+–Li+ countertransport across the human erythrocyte membrane is increased in patients with essential hypertension. We investigated the influence of hypokalaemia, oral contraceptives, diabetes mellitus and essential hypertension on the activity of this transport system.Normal values for the maximal Na+–Li+ transport rate were 0·25pL0·08 mmol l‐1 h‐1 (males, n= 18) and 0·23pL0·06 (females, n= 14). We found elevated values in women taking oral contraceptives (0·34pL0·07, n= 10, P<0·001), in patients with chronic hypokalaemia due to diuretic or laxative abuse (0·41pL0·16, n= 13, P<0·005) and in those with essential hypertension (0·32pL0·08, n= 24, P<0·001) (all data meanpLSD).Thus our results with hypertensive patients support the findings of other investigators. However, oral contraceptives and drug‐induced hypokalaemia greatly modify this system, indicating a regulation of the Na+–Li+ countertransport by hormones. Thus the transport rate does not seem to be an appropriate test for the diagnosis of essential hypertension.
Abnormal intestinal motility in diabetics with the gastroparesis syndrome
Authors: CAMILLERI MICHAEL , MALAGELADA JUAN‐R. 
Published: March 2008

Abstract. Gastroparesis syndrome is a recognized complication of longstanding diabetes mellitus and is attributed to reduced gastric contractility due to ‘autovagotomy’. However, motor abnormalities associated with this syndrome may not be limited to the stomach. To test this hypothesis we have studied the fasting and fed manometric profiles of the proximal small intestine of fourteen patients with the clinical diagnosis of gastroparesis. Abnormal intestinal manometric patterns were observed in twelve out of the fourteen patients. In four patients there was reduced duodenojejunal phasic pressure activity, whereas in nine there were non‐propagated long bursts of powerful contractions. Furthermore, while the majority of patients (eleven out of fourteen) exhibited the expected reduction in antral pressure activity and gastric phase III, a small subgroup of three patients exhibited a peculiar continuous 3 min‐1 antral contractile activity.Our findings show that the small intestine is frequently affected in patients with diabetic gastroparesis, and that the motility disorder both in the stomach and the small bowel is not invariably of a ‘paretic’ type. The occurrence of incoordinated intestinal long bursts and continuous antral activity suggests that disturbed sympathetic innervation participates in the aetiopathogenesis of their upper‐gut dysfunction.
Effect of long‐term starvation on acetate and ketone body metabolism in obese patients
Authors: SEUFERT C. D. , MEWES W. , SOELING H. D. 
Published: March 2008

Abstract. The turnover of ketone bodies and acetate was evaluated as well from the disappearance rate of (3‐14C)acetoacetate or (1‐14C)acetate respectively as from the conversion of FFA into these metabolites in normal weight and obese overnight‐fasted and in obese long‐term starved patients. The disappearance rate of (1‐14C)oleate was the same in all three groups.Long‐term starvation enhanced ketone body turnover almost 10‐fold, whereas the disappearance rate for ketone bodies decreased from 0·035 to 0·015 min‐1. Under the same circumstances the turnover of acetate was about 1 μmol g‐1 min‐1 accounting for about 5% of FFA turnover.Long‐term starvation decreased the conversion of (1‐14C)oleate into triglycerides by almost 50% and increased the (2‐C)‐(4‐C)/(1‐C) ratio of radioactivity in ketone bodies. The reincorporation of radioactivity from the (1‐C)position of (1‐14C)oleate into the ((2‐C)‐(n‐C)) position of FFA, which is a measure of the reutilization of acetyl‐CoA for FFA synthesis decreased significantly during long‐term starvation.
Stimulation of peritoneal synthesis of vasoactive prostaglandins during peritonitis in patients on continuous ambulatory peritoneal dialysis
Authors: STEINHAUER H. B. , GÜNTER B. , SCHOLLMEYER P. 
Published: March 2008

Abstract. The peritoneal generation of arachidonic acid metabolites was studied in eight patients with end‐stage renal disease undergoing continuous ambulatory peritoneal dialysis (CAPD) during infection‐free periods and during bacterial peritonitis. The prostacyclin metabolite 6‐keto‐PGF1α was found to be the major prostanoid generated by human peritoneal mesothelium (1090 ng(6h)‐1, SEM 86, n= 8) followed by lesser amounts of PGE2 (142 ng (6 h)‐1, SEM 26, n= 8), PGF2α (162ng(6h)‐1, SEM 27, n= 8) and TXB2 (59 ng (6 h)‐1, SEM 5, n= 8). During peritonitis a significant increase of all prostaglandins and TXB2 occurred (P < 0·001). The ratio of the vasodilating prostaglandins and their metabolites (PGE2 and 6‐keto‐PGF1α) to the vasoconstrictors and their metabolites (PGF2α and TXB2) increased from 6·6 to 10·5 during peritoneal inflammation. Augmented peritoneal clearances of creatinin and urea and increased losses of proteins during peritonitis as well as the enhanced peritoneal generation of prostanoids were reduced to basal values by adequated antibiotic therapy.The present results suggest that the increased peritoneal blood flow during peritonitis, probably responsible for the observed changes of peritoneal transport properties, may be induced by a change in the ratio of vasoactive prostaglandins generated by peritoneal mesothelial cells.
Adrenergic regulation of lipolysis in abdominal adipocytes of obese subjects during caloric restriction: reversal of catecholamine action caused by relief of endogenous inhibition
Authors: KATHER H. , WIELAND E. , FISCHER B. , WIRTH A. , SCHLIERF G. 
Published: March 2008

Abstract. The effects of adrenaline, noradrenaline, and of the α2‐ and β‐selective agonists clonidine and isoproterenol were studied in fifteen obese subjects before and after 4 weeks of caloric restriction (300 cal day‐1). Basal glycerol release averaged 1·4 μmol (106 cells)‐1 (180 min)‐1 before starvation and 2·8 μmol (106 cells)‐1 (180 min)‐1 during starvation (P≤ 0·1). Before starvation adrenaline and noradrenaline caused a 2–3‐fold increase of glycerol release. This lipolytic effect disappeared during starvation. An inhibitory effect of adrenaline was observed instead which was maximal at an adrenaline concentration of 1 μmol 1‐1 (P≤ 0·05). The dose‐response relationships of the α2 and β‐selective agents clonidine and isoproterenol were not appreciably changed by caloric restriction.The increase of basal lipolytic rate and the reversal of adrenaline action seen during caloric restriction could be mimicked by removal of endogenous adenosine using adenosine deaminase (1·6 μg ml‐1). In addition, inclusion of N6‐phenylisopropyladenosine (1 μmol 1‐1) into the medium reverted the adrenaline‐induced inhibition seen during caloric restriction.The results suggest that local modulators such as adenosine are of primary importance for the apparent change of responsiveness to adrenaline and noradrenaline seen during starvation of human fat cells in vitro.
Effect of sympathetic stimulation and intrarenal alpha‐blockade on the secretion of renin by the human kidney
Authors: LEEUW P. W. DE , BOS R. DE , ES P. N. VAN , BIRKENHÄGER W. H. 
Published: March 2008

Abstract. This study was initiated to explore the possible involvement of renal alpha‐adrenoceptors in the regulation of active and inactive renin. In fifteen hypertensive patients who proved not to have vascular abnormalities on diagnostic renal arteriography, blood samples were collected simultaneously from the renal artery and vein before and during an intrarenal infusion of either saline (n= 5), or the alpha‐1 blocker doxazosin (n= 5) or the non‐selective alpha‐blocker phentolamine (n= 5). Subsequently, responses of renal blood flow and renin secretion were assessed following 3 min of handgrip exercise. In none of the experiments secretion of inactive renin could be detected. Release of active renin increased from 580 (SEM 170) to 650 (SEM 220) μU min‐1 (100 g)‐1 during infusion of doxazosin (P < 0·05)and from 760(SEM 100)to 1000 (SEM 340) μU min‐1 (100 g)‐1 during infusion of phentolamine (P < 0·01). Saline infusion had no effect on secretion of active renin. While handgrip exercise had no significant effect on active renin secretion in the saline and in the doxazosin group, it enhanced secretion from 1000 (SEM 340) to 1280 (SEM 390) μU min‐1 (100 g)‐1 in the phentolamine group (P < 0·01).The results indicate that mainly alpha‐2 adrenoceptors exert an inhibitory effect on release of active renin, although alpha‐1 receptors participate to some degree. There is no evidence that the kidney secretes inactive renin.
Bioavailability, gastrointestinal transit, solubilization and faecal excretion of ursodeoxycholic acid in man
Authors: PARQUET M. , METMAN E. H. , RAIZMAN A. , RAMBAUD J. C. , BERTHAUX N. , INFANTE R. 
Published: March 2008

Abstract. The bioavailability of ursodeoxycholic acid (UDCA), a cholesterolic gallstone dissolving agent, has been analysed in seven healthy human volunteers. After absorption of a capsule containing a 500 mg dose, the time course of plasma concentrations of the drug presented a double peak profile over a 240 min period. In order to explain this result, a second group of five subjects bearing a four‐way jejunal catheter fitted with an occluding balloon, received an oral dose of 250, 500 or 750 mg of the drug. Simultaneous analyses of plasma UDCA concentrations and jejunal UDCA contents were carried out.UDCA is poorly soluble in the gastro‐duodeno‐jejunal contents of fasted subjects since 21–50% of the ingested doses were recovered in solid form. The profile of plasma concentration paralleled the amount of soluble UDCA present in intestinal lumen. When jejunal contents were infused below the balloon a second plasma peak appeared in cases corresponding to ingestion of higher doses of UDCA. In conclusion, pharmacological doses of UDCA are not readily soluble in the stomach and intestine of a healthy fasting man. In consequence, the bioavailability of the drug varies with its progressive solubilization in the gastrointestinal tract. The present results suggest that repeated daily doses of UDCA should improve its bioavailability in treated gallstone patients.
Age related changes of platelet prostacyclin receptors in humans
Authors: MODESTI P. A. , FORTINI A. , ABBATE R. , GENSINI G. F. 
Published: March 2008

Abstract. Platelet receptors for PGI2 were investigated in eighteen healthy volunteers divided in two classes of age: nine were 18–40 years old and nine were 41–65 years old.PGI2 platelet receptors were found to decrease significantly with age; the young subjects had 106 ± 16 (mean ± SD) high affinity receptors/platelet and 3509 ± 529 low affinity receptors/platelet whereas the old subjects had 86 ± 14 high affinity receptors/platelet (P<0·02) and 2471 ± 640 low affinity receptors/platelet (P<0·005). The cumulated data from all the subjects yielded a significant negative correlation with age(r= ‐0·71, P< 0·001 for the high affinity class and r=‐0·65, P<0·01 for the low affinity class). The affinity of receptor sites for the ligand did not statistically change with aging (P<0·30 and P<0·90 respectively for high and low affinity receptors).
Haemodynamic and hormonal responses to exercise: Studies in patients with diabetes mellitus and adrenomedullary deficiency
Authors: BARNETT A. , MASLOWSKI A. , LIVESEY J. , NICHOLLS G. , IKRAM H. , ESPINER E. 
Published: March 2008

Abstract. The haemodynamic and hormonal responses of patients with autonomic neuropathy and others with adrenomedullary deficiency were compared with mild hypertensives (range of blood pressure 90–100 mmHg diastolic and 140–160 mmHg systolic) and uncomplicated diabetics during standard exercise and postural manoeuvres using continuous arterial blood pressure monitoring. There was no difference in these parameters between the groups when at rest or on standing. During exercise there was no significant difference in blood pressure and heart rate between the groups and all showed significant increases in plasma noradrenaline (mean rise for all groups 2730–22105 pm l‐1, P<0·03) and (in all but the adrenalectomized subjects) adrenaline (mean rise for remaining three groups 946–3384 pm l‐1, P<0·03; adrenalectomized group showed no rise). The group with autonomic neuropathy showed a significant rise in plasma cortisol from basal 450 ± 40 to 845 ± 72 nm l‐1, P < 0·005 after exercise, but the other groups showed no significant change. The maximum level attained for plasma cortisol in the adrenalectomized subjects after exercise was significantly less (260 ± 41 nm l‐1) than in the diabetic groups (696 ± 68 nm l‐1 (non‐neuropaths), 845 ± 72 nm l‐1 (neuropaths), P<0·01).We have demonstrated normal blood pressure and pulse responses to posture and sustained exercise in diabetics with autonomic neutropathy. The findings of similarly normal responses in patients with adrenomedullary deficiency suggest that circulating adrenaline is not obligatory to a normal haemodynamic response to exercise.
Differing attitudes of industry and academia towards controlled clinical trials
Authors: BLUM A. L. , CHALMERS T. C. , DEUTSCH E. , KOCH‐WESER J. , LANGMAN M. , ROSEN A. , TYGSTRUP N. , ZENTGRAF R. 
Published: March 2008

Abstract. A consensus conference was held in 1984 on controversial issues concerning controlled clinical trials. Thirty‐six individuals working in academic institutions, forty‐six in industry and twelve in regulatory authorities participated. Academics accepted and industrial representatives rejected the following:

existing regulations cannot cope with the rate at which new treatments develop;
drug companies may be reluctant to undertake surveillance programmes because sales will fall if adverse reactions are detected;
novel remedies should not be promoted before extensive post‐marketing surveillance;
third parties should finance trials promising to reduce the costs of illness and
trialists should be separated from sponsors in data analysis and interpretation, the investigator owning the data unless stated otherwise.

Industrial representatives supported and academics rejected the following:

government price control inhibits drug development and
a multicentre trial can be justified simply by the wish to speed drug registration.
Relationship between growth hormone and Somatomedin‐C levels in untreated acromegaly, after surgery and radiotherapy and during medical therapy with Sandostatin (SMS 201–995)
Authors: LAMBERTS S. W. J. , UITTERLINDEN P. , VERLEUN T. 
Published: March 2008

Abstract. Several conflicting reports have been published with regard to the relationships between circulating growth hormone (GH), Somatomedin‐C (SM‐C) levels and clinical activity during different stages of therapy of acromegaly. We did not find a significant correlation between (fasting, post‐prandial and mean 24‐h) plasma GH and SM‐C concentrations in twenty‐two untreated acromegalic patients. There was a statistical significant correlation, however, if only the GH levels below 100 μg l‐1 were considered (n=18 patients, P<0·01). The distribution of molecular forms of GH (‘little’, ‘big’ and ‘big‐big’) did not differ between the four patients with GH levels above 100 μg l‐1 and in four patients with levels between 40 μg l‐1 and 80 μg l‐1. Therefore, it is suggested that GH levels of 80–100 μg l‐1 maximally activate Somatomedin‐C production in man and that further increases in GH in general will not result in a further increase in SM‐C generation. There was a significant correlation between GH and SM‐C levels in forty‐nine acromegalic patients after surgery and/or radiotherapy (P<0·001). In twenty‐three of thirty‐one patients with elevated SM‐C levels the disease was subjectively still active, while this was the case in none of the patients with normal SM‐C levels. In eight patients the disease was considered not to be clinically active any more, despite slightly increased SM‐C levels. During long‐term therapy of ten acromegalic patients for 16–108 weeks (mean 66±10) with 200–300 μg Sandostatin subcutaneously, clinical activity of the disease disappeared well before mean 24–h GH and SM‐C levels reached the normal levels. There was a close correlation between mean 24‐h GH and SM‐C levels during Sandostatin therapy (P<0·001). ‘Clinical cure’ during this medical treatment was reached in five patients, as reflected by disappearance of subjective complaints, normalization of SM‐C levels and 24‐h mean GH levels of 2·8±0·2 μg l‐1.Conclusions: (i) in untreated acromegaly, circulating GH and SM‐C levels correlate well up to GH concentrations of 100 μg l‐1. A further increase in GH does not result in a corresponding further increase in SM‐C levels, suggesting a maximally activated production, without further GH‐dependent capacity. (ii) Clinical ‘cure’ of acromegaly often occurs before normalization of the circulating SM‐C levels. (iii) The measurement of plasma SM‐C concentrations can be used well to adjust the dose and frequency of Sandostatin administration in acromegaly. This avoids the need of measuring extensive 24‐h GH profiles.
Monocyte C1‐inhibitor synthesis in patients with C1‐inhibitor deficiency
Authors: LAPPIN D. F. , McPHADEN A. R. , YAP PENG‐LEE , CARTER P. E. , BIRNIE G. D. , FOTHERGILL J. E. , WHALEY K. 
Published: March 2008

Abstract. Monocytes of seven out of eight patients with type 1 C1‐inhibitor (C1‐inh) deficiency (HAE) produced 40% as much C1‐inh as monocytes from normal donors (controls). In contrast, monocytes from three patients with type 2 and three patients with acquired C1‐inh deficiency produced similar amounts of Cl‐inh as controls. Recombinant γ‐interferon (γ ‐interferon 10 ng/ml) stimulated C1‐inh production of C1‐inh (eight‐10‐fold) by control and patients' monocytes. Monocytes from patients with type 1 HAE contained 40% the level of C1‐inh messenger ribonucleic acid (mRNA) found in control monocytes, γ ‐interferon increased the abundance of Cl‐inh mRNA by the same extent in both control and patients' monocytes. C1‐inh protein and mRNA were undetectable in the monocytes of one patient, unless stimulated by γ‐interferon. Under these conditions, his monocytes produced comparable amounts of C1‐inh (protein and mRNA) as γ‐interferon‐stimulated monocytes of the other type 1 HAE patients.The data suggest that in most type 2 HAE patients there is a lesion in the C1‐inh gene such that mRNA is transcribed by a single allele.
Analysis of cysteinyl leukotrienes in human urine: enhanced excretion in patients with liver cirrhosis and hepatorenal syndrome*
Authors: HUBER M. , KÄSTNER S. , SCHÖLMERICH J. , GEROK W. , KEPPLER D. 
Published: March 2008

Abstract. The cysteinyl leukotrienes, comprising leuk‐otriene C4 and its metabolites, are biologically most active mediators, eliminated from the blood circulation by the liver and the kidneys. The urine of normal subjects and of patients with hepatic and/or renal failure was analysed for endogenous cysteinyl leukotrienes. The leukotriene metabolites were separated by reversed‐phase high‐performance liquid chromatography and subsequently quantified by radioimmunoassay.Leukotreine E4 was detected in all urine samples analysed. Its mean concentration increased from 0.3 nmol I‐1 in healthy subjects to 0.8 nmol 1‐1in patients with liver cirrhosis. In patients with hepatorenal syndrome leukotriene E4 averaged 7.8 nmol I‐1; in addition, N‐acetyl‐leukotriene E4 was detected in an average amount of 1.5 nmol ‐1. The mean leukotriene E4/creatinine ratio in urine increased from 0.02 in healthy subjects to 0.11 in patients with liver cirrhosis and to 1.2 μmol leukotriene E4 mol‐1 creatinine in patients with hepatorenal syndrome. These results indicate that cysteinyl leukotrienes may play an important role in the mediator network responsible for the development of the hepatorenal syndrome in patients with severe liver disease.
Adenosine receptor mediated stimulation of ventilation in man
Authors: JONZON B. , SYLVÉN C. , BEERMANN B. , BRANDT R. 
Published: March 2008

Abstract. We wanted to examine how adenosine stimulates ventilation in man. Bolus doses of adenosine were given i.v. in an antebrachial vein in multiples of 2.65 mg. The minute ventilation was increased by adenosine 5.3 to 15.9 mg (median values) from control 12.6 ± 1.9 1 min‐1 to 42.5 ± 4.7 1 min‐1 in a dose‐dependent manner. The adenosine receptor antagonist theophylline, 58.3 ± 3.3 (mean±SEM) μniol 1‐1 plasma, inhibited the response by approximately 25%. Dipyridamole 10 mg, an adenosine uptake blocker, enhanced the effect of adenosine by approximately 60%. The ventilation was not affected by metoprolol, atropine, naloxone or cromolyn sodium but was attenuated by hyperventilation.The respiratory stimulation started before chest pain and cardiovascular effects such as AV‐block were encountered. It is concluded that this respiratory stimulation shows characteristics of adenosine receptor mediated responses but the location of such adenosine receptors is uncertain. The findings are compatible with a stimulatory or facilitating effect of adenosine on afferent pathways.
Increased number of ouabain binding sites in lymphocytes from borderline hypertensives
Authors: NIELSEN J. ROKKEDAL , PEDERSEN K. E. , KLITGAARD N. A. , JOHANSEN T. 
Published: March 2008

Abstract. Lymphocytes were used as a cellular model for the in vitro measurements of maximal ouabain binding sites in order to assess any changes in young men at increased risk of developing essential hypertension, and to analyse whether any such changes were associated to borderline hypertension and/or heredity.Four groups were evaluated; 28 normotensive (NTO) and 20 borderline hypertensive (BHO) offspring of hypertensives. Twelve borderline hypertensives (BH) and 28 normotensive subjects (NT) with normotensive parents.The number of ouabain binding sites were significantly increased in the borderline hypertensives irrespective of heredity.The borderline hypertensives were heavier than the normotensives. A stepwise multiple regression model was therefore used in order to control confoundings by body mass index (BMI) and other factors such as age, gamma glutamyl transferase, 24 h sodium excretion, serum triglyceride, and serum cholesterole, which may influence the number of ouabain binding sites. Only BMI entered the stepwise model.These results indicate the presence of an increased number of sodium‐potassium pumps in lymphocytes from borderline hypertensives. This difference may be attributed to the blood pressure disease or increased body mass.