ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.00292.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.1780527.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Application of compressive forces to osteoblastic cells is known to cause specific cellular responses. We report that hydrostatic pressure increased c‐fosmRNA expression in MC3T3‐E1 cells after 15, 30 and 60min. This effect was absent when 5×10−7molL−1indomethacin, an inhibitor of prostaglandin synthesis, was present in the culture medium during pressurization. Using radioimmunoassays, a significant increase in the concentrations of 6‐keto‐PGF1α, the stable conversion product of prostacyclin (PGI2), in the conditioned medium of pressurized cells, was measured after 60min. In contrast, PGE2levels were not significantly changed and we therefore assume that under these experimental conditions PGE2is not responsible for the transduction of the hydrostatic force. However, we also found that PGE2has the capacity to induce c‐fosmRNA in MC3T3‐E1 cells. Furthermore, we show for the first time that the stable prostacyclin analogue, Iloprost‐Trometamol (Ilomedin), is a potent activator of c‐fosgene transcription. Our data suggest that prostacyclin is a likely candidate in mediating the effect of hydrostatic compressive stress on bone cells by regulating the level of c‐fosmRNA, a member of the activator protein (AP)‐1 complex and potent regulator of osteoblastic prolifer

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.165312.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Cardiac transplantation has become a successful therapy for end‐stage heart disease. However, increased bone loss has been observed in heart transplant recipients, sometimes being responsible for osteoporotic fractures. Glucocorticoids cause dose‐related bone loss, particularly in the first 6–12 months of use, but cyclosporine might play a role as well. The evolution of bone mineral density (BMD) and biochemical parameters was prospectively assessed in 24 patients (mean age 52 years) from cardiac transplantation. All patients received cyclosporin A (CsA) and prednisone, the latter at decreasing dosage. The mean current daily dose of CsA was 321 mg and serum levels of CsA were constant. All patients received calcium (500 mg day−1) and vitamin D (1000 U day−1) for prevention of bone loss. BMD (g cm−2) was measured in 17 patients at the lumbar spine, femoral neck and total hip with dual energy X‐ray absorptiometry every 6 months. Spinal BMD as well as neck and total hip BMD decreased at 6 and 12 months after transplantation, being statistically significant at the three sites: −5.6 and −3.4% for the lumbar spine, −9.3 and−8.5% for the femoral neck, −4.8% and −6.0% for the total hip respectively. Parathyroid hormone (PTH) and osteocalcin (BGP) increased by 90% and 800% respectively between pretransplantation values and 18 months after transplantation. BGP levels measured every 2 months from transplantation increased continuously from 8.7 μg L−1(mean ± SEM) before transplantation to 31.3 ± 10.1 (P<0.05) at 4 months, to 59.1 ± 8.8 (P<0.01) at 6 months and to 72.2 ± 9.9 (P<0.01) at 18 months (Kruskal–Wallis analysis: P<0.0001). PTH showed a biphasic pattern with an initial decrease from 39.3 ± 4.1 ng L−1at baseline to 22.0 ± 2.8 ng L−1at 2 months, but increasing thereafter to 45.9 ± 5.7 at 6 months and 74.2 ± 8.9 at 18 months (Kruskal–Wallis analysis: P<0.001). These variations represent a biochemical profile remarkably different from that of glucocorticoid‐induced osteoporosis. In summary, cardiac transplant patients lose bone immediately after transplantation at the spine and the hip. Later on, the loss in BMD discontinues at all sites of the skeleton, but predominantly at the spine, and a few patients still lose bone at the hip. This is probably a re

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.00170.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

We tested the hypothesis that the status of the renin–angiotensin–aldosterone system affects insulin sensitivity. Insulin sensitivity (by the euglycaemic insulin clamp technique) was measured in eight patients with angiographically proven renovascular hypertension and in eight normotensive subjects matched for age, gender, body mass index and glucose tolerance. In the patients, insulin sensitivity was measured both at baseline and following 7 days of ACE inhibition. Following glucose ingestion, patients and controls showed similar insulin and glucose responses. Insulin infusion (7 pmol min−1 kg−1) promoted similar glucose utilization in the hypertensives and normotensives: 24.8±2.3 vs. 26.0±3.0μmol min−1kg−1respectively. One week of ACE inhibition caused a 20±4 mmHg decrease in mean blood pressure and a 20±6% decrease in peripheral vascular resistance. Plasma angiotensin II concentrations dropped from 24.6±6.3 to 13.5±5.0 pg mL−1(P<0.05) and plasma aldosterone from 17<4 to 92 ng dL−1(P<0.05), and plasma renin activity doubled (from 1.6±0.3 to 3.4±1.7 ng mL−1h−1P<0.02). Nevertheless, insulin sensitivity was unchanged (before, 24.8±2.3; after, 25.8±2.2μmol min−1kg−1P=Ns). During insulin infusion, forearm blood flow did not change from baseline in either set of studies. Also, the antinatriuretic (before, −26±18; after, −22±14%) and antikaliuretic (before: −36±13%, after: −39±11%) action of the hormone was unaffected by the therapy. In conclusion, human renovascular hypertension is not associated with insulin resistance. Furthermore, a selective, drastic reduction of the renin–angiotensin‐aldosterone system activity and vascular tone does

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.1740521.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

This cross‐sectional study was aimed at investigating the association between eating behaviour and current glycaemic control, body mass or autonomic nervous function in patients with type I and type II diabetes mellitus (DM). In 72 patients (31 type I DM, 41 type II DM) we investigated body mass index (BMI), serum cholesterol, serum triglycerides, haemoglobin A1c (HbA1c) and autonomic nervous function (seven standardized tests). The three‐factor eating questionnaire was used to investigate cognitive control of eating behaviour (CC) and susceptibility to eating problems (SEP). The mathematical product of CC and SEP provides information about disinhibition of eating control (DEC). In type I DM, there was a correlation between SEP and age (r=−0.536,P<0.01), SEP and duration (−0.441,P<0.05), SEP and HbA1c (0.438,P<0.05), and between DEC and duration (−0.371,P<0.05) and DEC and HbA1c (0.376,P<0.05). In type II DM, there was a correlation between SEP and BMI (0.401,P<0.01) and between DEC and BMI (0.429,P<0.01). Low CC was associated with autonomic nervous dysfunction in type I DM (P=0.022). In type II DM, autonomic nervous dysfunction was associated with high SEP (P=0.044). In conclusion, the correlation between eating behaviour and HbA1c or triglycerides in type I DM indicates that the questionnaire is able to address current parameters of diabetes control. Self‐assessment of eating behaviour in type I and type II diabetic patients reveals associations between eating behaviour and autonomic nervo

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.1720529.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Plasma membrane lipid dynamics and cellular morphology were evaluated in endothelial cells obtained from umbilical cords of five women affected by insulin‐dependent diabetes mellitus (IDDM) and six healthy pregnant women of similar age and gestational age. Endothelial cells were prepared by an adaptation of the method of Jaffeet al.Membrane fluidity was studied by means of the steady‐state fluorescence anisotropy (r) of 1‐(4‐trimethylaminophenyl)‐6‐phenyl‐1,3,5‐hexatriene (TMA‐DPH), a fluorescent probe specifically anchoring at the membrane surface. Fluid phase endocytosis was evaluated by the measurement of the changes in fluorescence intensity of TMA‐DPH at various times, owing to the internalization of the fluorescent marker in endocytic vesicles. The morphological and morphometric studies were performed by means of transmission electron microscopy (TEM). Endothelial cells obtained from IDDM women showed: (a) increased fluidity of the superficial region of the plasma membrane; (b) a more active fluid phase endocytosis compared with cells from healthy women; (c) increase in mitochondrial area, Weibel–Palade bodies and rough reticulum with wide cisternae. No statistically significant correlation was found between metabolic control and membrane fluidity and endocytosis. All the observed modifications suggest the presence of endothelial cell activation with membrane reshaping during IDDM. These alterations might play a central role in the pathophysiology of atherosclerosis and microangiopathy associated w

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.1750526.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

In this study the muscarinic receptor antagonist atropine and the cholecystokinin (CCK)‐A receptor antagonist loxiglumide were used to investigate the relative importance of cholinergic and CCK‐mediated regulation of intestinal phase antro‐pyloro‐duodenal motility. Plasma levels of gastrointestinal hormones [pancreatic polypeptide (PP), gastrin, CCK] were concomitantly determined to estimate biological potency of the doses of the receptor antagonists. In eight healthy male volunteers, a 30‐min basal interdigestive period was followed by duodenal perfusion of a mixed liquid meal for 150 min at 2.6 kcal min−1against a background of saline or atropine (5 μg kg−1h−1) or loxiglumide (10 mg kg−1h−1). Antro‐pyloro‐duodenal motility was continuously monitored with a sleeve straddling the pylorus. Against a background of saline, duodenal nutrients persistently stimulated isolated pyloric pressure waves. After 60 min, the initially low antral and duodenal contraction rates increased. In the fed state, atropine reduced total number of antral contractions and integrated motility index by 73% (P<0.01) and 76% (P<0.005), total number of pyloric contractions and integrated motility index by 43% and 50% (P<0.05) with inhibition increasing over time. It did not alter duodenal contraction frequency but diminished duodenal motility index by 39% (P<0.05) owing to a reduction in amplitude and duration of contractions. Loxiglumide decreased total numbers of antral, pyloric and duodenal contractions by 44% (P<0.05), 74% (P<0.005) and 41% (P<0.005) respectively. It reduced cumulative antral, pyloric and duodenal motility indexes by 60% (P<0.01), 80% (P<0.01) and 61% (P<0.05) respectively. Atropine fully abolished PP release to duodenal nutrients whereas loxiglumide reduced it by 60% (P<0.05). Both atropine and loxiglumide enhanced gastrin release whereas only loxiglumide markedly stimulated CCK release. We conclude that both cholinergic input and endogenous CCK are major stimulatory regulators of antro‐pyloroduodenal motility in the intestinal phase. There appears to be a regional heterogeneity of cholinergic and CCK control. Cholinergic input predominates in the antrum. Both systems are equipotent at the pylorus. CCK predominates in the duodenum. We suggest that CCK primarily interacts with receptors on cholinergic neurons in the antropyloric region and primarily affects smo

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.1790522.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

In order to study the renal and hormonal actions of atrial natriuretic peptide (ANP) during background infusions with angiotensin II (ANG II) or noradrenaline (NA), 69 healthy subjects were examined in three main groups receiving a 90‐min infusion with either placebo, ANG II (1.5 ng kg−1 min−1), or NA (25 ng kg−1 min−1). Each of these three main groups were subdivided into two groups receiving an infusion with either placebo or ANP (10 ng kg−1 min−1) for the last 60 min of the background infusion. Lithium clearance was used to evaluate segmental tubular reabsorption. ANG II alone caused a decrease in glomerular filtration rate (GFR), renal plasma flow, urinary absolute and fractional excretion of sodium, both proximal and distal fractional tubular sodium reabsorption, and urinary flow. NA alone caused a decrease in renal plasma flow. ANP alone caused a decrease in renal plasma flow. Urinary absolute and fractional excretion of sodium were increased and the distal fractional tubular reabsorption of sodium decreased, whereas the proximal fractional tubular reabsorption was unchanged by ANP. ANG II + ANP: during a background ANG II infusion, ANP still increased fractional excretion of sodium. Proximal fractional reabsorption was decreased, whereas distal fractional reabsorption of sodium was unchanged by ANP during ANG II infusion. The ANP‐induced decreases in proximal absolute (−147 vs. +714 μmol min−11.73 m−2P = 0.05) and fractional (−1.7% vs. +0.6%,P<0.01) tubular sodium reabsorption were more pronounced, and the decrease in distal fractional tubular reabsorption of sodium (−0.1% vs. −1.4%,P<0.05) less pronounced compared with when ANP was given alone. NA + ANP: during a background NA infusion, ANP still increased urinary sodium excretion and decreased distal fractional reabsorption. None of the ANP‐induced absolute changes seen during background infusion with NA were significantly different from the ANP‐induced changes seen during placebo background infusion. It is concluded that the natriuretic action of low‐dose ANP seems to be preserved during background infusions with ANG II and NA in man. Net sodium excretion during the combined infusion with ANG II and ANP seems to reflect the sum of the opposing influences of each peptide. Low‐dose ANP had a very modest but significant inhibitory eff

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.00180.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

A kinetic chromogenic limulus test was carried out in order to investigate the possibility of a sensitive and specific detection of circulating endotoxin during the first 24 h of septic shock or severe sepsis in 76 patients. Two commercial kits, Whittaeker (W) and Chromogenix (C), were used. Blood culture was taken as a reference. At 1 : 10 plasma dilution (a currently used dilution in the end point limulus test) abnormal reaction kinetics were found in 13% and 41% of tests, for C and W respectively (P = 0.0008), resulting in unreliable results. Retesting plasma at a greater dilution, until the reaction kinetic was identical to calibration curve control values, gave similar results between the two kits and a better accuracy. Beyond a 0.5 EU mL−1endotoxin level, the probability of Gram‐negative bacteraemia was high (sensitivity = 0.53 and 0.47; specificity = 0.95 and 0.93 for C and W respectively). This kinetic limulus amoebocyte lysate (LAL) test may be useful in therapeutic decisions for tr

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.1810531.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY