bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased tissue protein synthesis during spontaneous inflammatory bowel disease in HLA-B27 rats
Authors: YOUSFI Mimoun EL , BREUILLÉ Denis , PAPET Isabelle , BLUM Stéphanie , ANDRÉ Marc , MOSONI Laurent , DENIS Philippe , BUFFIÈRE Caroline , OBLED Christiane
Published: October 2003

Inflammatory bowel diseases (IBDs) are associated with an increased whole-body protein turnover. In certain drug-induced experimental models of IBD, disturbances of protein synthesis in tissues have been reported recently, but it is unclear if similar disturbances occur in other chronic intestinal diseases. Therefore we investigated changes in protein synthesis in different tissues of HLA-B27 (human leucocyte antigen B27) transgenic rats that develop spontaneously chronic inflammation, with major involvement of the colon. Protein synthesis rate in HLA-B27 rats was shown to be higher in nine different tissues compared with control (Fisher 344) rats. The absolute rate of protein synthesis was highly stimulated at the main inflammatory site (+290% in the colon). However, liver, muscle and skin appeared to be major contributors to the increased protein synthesis observed at the whole-body level. Despite the increased protein synthesis, HLA-B27 rats presented a marked atrophy of muscles, which suggests an increased proteolysis. These results contrast with metabolic disturbances described in acute inflammation and colitis induced by drugs (i.e. dextran sodium sulphate). The present study suggests that the modifications of protein metabolism are strongly influenced by the type of the inflammatory diseases and thus by the underlying mechanisms, which result in different metabolic adaptations and specific nutritional requirements.
Association between the cholesteryl ester transfer protein TaqI-detectable B polymorphism and low high-density lipoprotein cholesterol concentration in Saudis
Authors: AL-DAGHRI Nassr M. , AL-ATTAS Omer , PATEL Ashok , BELYAEV Nikolai D. , BARTLETT William A. , JONES Alan F. , KUMAR Sudesh , BAIN Steve C.
Published: October 2003

Plasma concentrations of HDL (high-density lipoprotein) cholesterol are low in the Saudi Arabian population. A B polymorphism at the CETP (cholesteryl ester protein transfer) locus that is detectable with the restriction enzyme TaqI is a genetic determinant of the plasma HDL cholesterol concentration. We assessed the relationship between the TaqI B CETP polymorphism and lipid and apolipoprotein concentrations in a study sample of 335 Saudi residents. The TaqI B1 and B2 allele frequencies were 0.54 and 0.46 respectively, similar to those in other populations. HDL cholesterol levels in B2B2 homozygotes were significantly higher than in B1B1 homozygotes [1.01 (0.3) compared with 0.92 (0.2) mmol/l; mean (S.D.); P=0.03]. There was also a significant difference between the B2B2 and B1B1 homozygotes with regard to apolipoprotein AI concentration [123.6 (16.4) compared with 113.7 (13.9) mg/dl; P=0.04]. This genetic variation was independent of metabolic risk factors known to influence HDL cholesterol levels. The allele frequency of the TaqI B CETP polymorphism and its relatively modest impact on HDL cholesterol concentrations argue against an important role for this allele, or for strongly linked loci, in determining the low levels of HDL cholesterol seen in the Saudi population.
Labour-associated changes in adrenomedullin content in human placenta and fetal membranes
Authors: AL-GHAFRA A. , GUDE N. M. , BRENNECKE S. P. , KING R. G.
Published: October 2003

The aim of the present study was to determine the effects of labour and mode of delivery on human placental and fetal membrane content of adrenomedullin (AdM). Placentas and fetal membranes were collected either at term or pre-term gestation from women either in labour or not in labour, and AdM was measured in tissue extracts by specific RIA. There were significant increases in AdM concentrations in amnion and choriodecidua for the in-labour group compared with the not-in-labour group for both pre-term and term gestations. There was no difference in AdM concentration in placental tissue between labour groups. This study provides evidence that fetal membrane AdM is increased in amniotic and choriodecidual tissues in response to labour, and suggests that it may play a role during human labour.
Differential expression of Flk-1 and Flt-1 in rat skeletal muscle in response to chronic ischaemia: favourable effect of muscle activity
Authors: MILKIEWICZ Malgorzata , HUDLICKA Olga , VERHAEG Julie , EGGINTON Stuart , BROWN Margaret D.
Published: October 2003

To determine the involvement of vascular endothelial growth factor (VEGF) and its receptors Flk-1 and Flt-1 in capillary growth in ischaemic skeletal muscle, extensor digitorum longus muscles from hindlimbs of Sprague—Dawley rats were studied at 1, 2 and 5 week intervals after iliac artery ligation. Muscle VEGF protein levels (as determined by Western-blot analysis) increased only after 2 (60%) and 5 (80%) weeks, with more capillaries positively immunostained for VEGF than in control muscles. Ischaemia-induced angiogenesis was gradual, with capillary proliferation at 1 and 2 weeks and capillary:fibre ratio increased 20% after 5 weeks. This was associated with an initial doubling of Flk-1 protein after 1 week that declined below control levels by 5 weeks, whereas Flt-1 expression was elevated more than 40% at all time points. During more sustained ischaemia (femoral ligation 3 weeks after iliac ligation), VEGF protein level at 5 weeks was even higher, but Flt-1 and Flk-1 were unchanged from control levels and no capillary growth occurred. Intermittent electrical stimulation (10 Hz, 7×15 min/day) of these ischaemic muscles between weeks 3–5 did not elevate VEGF further, but increased Flk-1 by 32%, decreased Flt-1 by 71%, and led to significant capillary growth. These results demonstrate that during chronic muscle ischaemia Flk-1 and Flt-1 are regulated differentially and that electrical stimulation of ischaemic muscles can promote angiogenesis via Flk-1 up-regulation. Even when ischaemic muscle VEGF levels are high, capillary growth appears to be dependent on the presence of Flk-1.
Decreased HLA (human leucocyte antigen)-DR expression on peripheral blood monocytes predicts the development of organ failure in patients with acute pancreatitis
Authors: MENTULA Panu , KYLÄNPÄÄ-BÄCK Marja-Leena , KEMPPAINEN Esko , TAKALA Annika , JANSSON Sten-Erik , KAUTIAINEN Hannu , PUOLAKKAINEN Pauli , HAAPIAINEN Reijo , REPO Heikki
Published: October 2003

Immune suppression plays an important role in the pathogenesis of acute pancreatitis. Monocyte expression of HLA (human leucocyte antigen)-DR, a cellular marker of immune suppression, was determined in relation to the development of organ dysfunction in patients with acute pancreatitis. A total of 310 consecutive patients with acute pancreatitis, admitted to a university hospital within 72 h of pain onset, were studied; 194 (63%) had mild disease (group I), 87 (28%) had severe disease without organ dysfunction (group II), and 29 (9%) had severe disease with organ dysfunction (group III). HLA-DR expression, defined both as the proportion of monocytes that were HLA-DR-positive and as monocyte HLA-DR fluorescence intensity, was determined at admission, using whole-blood flow cytometry. Of the patients in group III, 13 (45%) developed organ dysfunction within 24 h of admission. The proportion of HLA-DR-positive monocytes and monocyte HLA-DR density were both related to the severity of pancreatitis (P<0.001 for linear trend). In predicting organ dysfunction, the sensitivity, specificity and positive-likelihood ratio for the proportion of HLA-DR-positive monocytes were 83% [95% CI (confidence interval) 64–94%], 72% (67–77%) and 3.0 respectively, and for monocyte HLA-DR density the respective values were 69% (49–85%), 84% (79–88%) and 4.3. In conclusion, monocyte HLA-DR expression predicts the development of organ dysfunction that occurs early in patients with acute pancreatitis.
Effect of preload reduction by haemodialysis on new indices of diastolic function
Authors: GRAHAM Richard J. , GELMAN John S. , DONELAN Lesley , MOTTRAM Philip M. , PEVERILL Roger E.
Published: October 2003

Assessment of mitral annular motion diastolic velocities by M-mode or tissue Doppler imaging and the propagation velocity of early diastolic filling (Vp) by colour M-mode have been proposed as preload-independent indices of diastolic function. The aim of the present study was to determine the effects of preload reduction by haemodialysis on these new echocardiographic indices and to assess the relationship between these indices. The study group comprised 17 patients with chronic renal failure in sinus rhythm with normal left ventricular systolic function who underwent echocardiography 30 min prior to and 30 min following haemodialysis. Following dialysis there were significant reductions in weight (P<0.001), left atrial diameter (P=0.001), the peak Doppler velocity of early diastolic transmitral flow (P=0.005) and the ratio of Doppler velocities of early to late diastolic transmitral flow (P=0.02), consistent with a reduction in intravascular volume. There was no change after dialysis in early diastolic mitral annular velocity using M-mode (P=0.19) or tissue Doppler imaging from either the septal or lateral walls (P=0.88 and P=0.15 respectively), but there was a reduction in Vp after dialysis (55 to 49 cm/s; P=0.04). There were only weak correlations between Vp and the early diastolic mitral annular velocities (r<0.6 for all). We conclude that the assessment of diastolic function by the mitral annular early diastolic velocity appears to be preload-independent, that Vp may be affected by preload and that there is only a weak relationship between Vp and the early diastolic mitral annular velocity.
Hypertensive response to chronic NG-nitro-l-arginine methyl ester (l-NAME) treatment is similar in immature and adult Wistar rats
Authors: ZICHA Josef , PECHÁŇOVÁ Olga , DOBEŠOVÁ Zdena , KUNEŠ Jaroslav
Published: October 2003

The aim of our study was to evaluate whether the blood pressure (BP) response to chronic inhibition of NO synthase (NOS) is exaggerated in young rats, which were reported to develop a more pronounced salt hypertension than the adult ones. The enhanced BP rise in immature rats subjected to excess salt intake might be due either to a generally increased reactivity in immature organisms to these stimuli or to a greater impairment of NO bioavailability that accompanies the development of salt hypertension. To determine between the two alternatives, we have compared the hypertensive response and the extent of NOS inhibition in immature (4-week-old) and adult (12-week-old) male Wistar rats which were treated with NG-nitro-L-arginine methyl ester (L-NAME, 40 mg/kg of body mass per day) for 4 weeks. BP and NOS activity in the aorta, left ventricle and kidney were determined at the end of the experiment. It should be noted that chronic L-NAME treatment caused a similar degree of NOS inhibition in both age groups (irrespective of tissue examined). There was no significant difference in BP elevation between young and adult animals chronically treated with L-NAME. A strong negative correlation between NOS activity and BP level was observed in separate groups of normotensive controls and L-NAME hypertensive rats. Thus the BP of both normotensive and hypertensive animals seems to be inversely proportional to the production of NO. It can be concluded that there was the same BP rise in both age groups of L-NAME-treated rats in which a similar degree of NOS inhibition was disclosed. This suggests that the altered NO bioavailability (but not the generally exaggerated reactivity to hypertensive stimuli) is the cause of exaggerated hypertensive response observed in immature rats exposed to excess salt intake.
Respiratory-related arterial pressure variability as an indicator of graded blood loss: involvement of the autonomic nervous system
Authors: LAI Hsien Yong , YANG Cheryl C. H. , HUANG Fan-Yen , LEE Yi , KUO Yu Ling , KUO Terry B. J.
Published: October 2003

During positive pressure mechanical ventilation, percentile systolic pressure variation (%SPV) or respiratory-related arterial pressure variability (RAPV) have both been used in assessment of graded haemorrhage. We aimed to investigate whether changes in %SPV and RAPV are correlated during graded haemorrhage (by 5, 10 or 20% of the estimated blood volume) in anaesthetized positive pressure ventilated rats and to investigate the involvement of autonomic regulation. Saline vehicle or atropine produced no discernible effect on baseline %SPV or RAPV but, thereafter, %SPV and RAPV increased progressively with graded haemorrhage. Propranolol significantly decreased baseline %SPV and RAPV and changes induced in %SPV and RAPV by graded haemorrhage. Phentolamine significantly enhanced baseline %SPV and RAPV, and further enhancement of %SPV and RAPV by graded haemorrhage did not occur until 20% of the estimated blood volume was removed. RAPV was significantly correlated with %SPV in all experimental groups. We conclude that RAPV is comparable with%SPV as an indicator of graded haemorrhage and that, in anaesthetized and positive pressure ventilated rats, both are dependent on autonomic function, especially β-adrenoceptors.
Regulation of hypoxia-inducible factor-1α by cyclical mechanical stretch in rat vascular smooth muscle cells
Authors: CHANG Hang , SHYU Kou-Gi , WANG Bao-Wei , KUAN Peiliang
Published: October 2003

Vascular smooth muscle cells (VSMCs) are exposed to hormonal and mechanical stress in vivo. Hormonal factors have been shown to affect hypoxia-inducible factor-1α (HIF-1α). How mechanical stress affects the regulation of HIF-1α in VSMCs has not been reported previously, and therefore we sought to investigate the regulation of HIF-1α by cyclical mechanical stretch in cultured rat VSMCs. Rat VSMCs grown on a flexible membrane base were stretched by vacuum to 20% of the maximum elongation at 60 cycles/min. The levels of HIF-1α protein began to increase as early as 2 h after stretch was applied and reached a maximum of 2.8-fold over the control by 4 h. Real-time PCR showed that the levels of HIF-1α mRNA increased 2.1-fold after cyclical stretch for 4 h. Cyclical mechanical stretch also increased the immunohistochemical labelling of HIF-1α in VSMCs after cyclical stretch for 4 h. The phosphorylation of p42/p44 mitogen-activated protein kinase (MAP kinase) increased after stretch and this was inhibited by the MAP kinase kinase inhibitors PD98059 and U0126. PD98059 and U0126 also blocked HIF-1α gene expression induced by cyclical stretch. In conclusion, cyclical mechanical stretch activates the gene expression of HIF-1α in cultured VSMCs and this mechanical effect is possibly mediated by the p42/p44 MAP kinase kinase pathway.
A fat-enriched, glucose-enriched diet markedly attenuates adiponectin mRNA levels in rat epididymal adipose tissue
Authors: NADERALI Ebrahim K. , ESTADELLA Debora , ROCHA Milagros , PICKAVANCE Lucy C. , FATANI Sameer , DENIS Raphael G. P. , WILLIAMS Gareth
Published: October 2003

Adiponectin levels are decreased in subjects with obesity, diabetes and coronary artery disease. In the present study, we have investigated whether the decrease in the levels and mRNA expression of adiponectin is due to obesity or to the diet itself. Wistar rats were either fed standard laboratory chow throughout (controls) or given a fat-enriched, glucose-enriched diet (diet-fed) for 2 days or 16 weeks. After 2 days of diet feeding, total body weight, fat pad masses and the plasma levels of glucose, insulin and leptin were all comparable between the two groups, while plasma NEFA (non-esterified fatty acid) and triacylglycerol levels were increased in the diet-fed animals (P<0.01 for both). There was a marked (P<0.01) decrease in plasma adiponectin levels. After 16 weeks of diet feeding, diet-fed rats had significantly higher body weight, fat pad mass and plasma levels of leptin, adiponectin, NEFA and triacylglycerol (P<0.001 for all) compared with chow-fed controls, whereas plasma levels of glucose and insulin were similar in the two groups. After 2 days of diet feeding, there were no significant changes in Ob mRNA levels in epididymal fat, whereas there was a marked decrease in adiponectin mRNA levels. After 16 weeks of diet feeding, rats had significantly increased levels of Ob mRNA, but decreased adiponectin mRNA levels, in epididymal fat compared with the chow-fed group (P<0.001 for both). These findings suggest that obesity per se is not a factor in the decreased adiponectin levels observed in obese subjects. We propose that the lipid profile of the plasma and/or the constituents of the diet consumed by rats may contribute to adiponectin levels more than obesity per se.
Baseline blood flow and bradykinin-induced vasodilator responses in the human forearm are insensitive to the cytochrome P450 2C9 (CYP2C9) inhibitor sulphaphenazole
Authors: PASSAUER Jens , BÜSSEMAKER Eckhart , LÄSSIG Grit , PISTROSCH Frank , FAULER Joachim , GROSS Peter , FLEMING Ingrid
Published: October 2003

A substantial portion of the vasodilator response elicited by bradykinin in the human forearm is unaffected by the combined inhibition of nitric oxide (NO) synthases and cyclo-oxygenases. The cytochrome P450 (CYP) 2C9 inhibitor sulphaphenazole was recently identified as a potent inhibitor of NO- and prostacyclin (PGI2)-independent relaxation in porcine coronary arteries. The aim of the present study was to determine the effect of sulphaphenazole on basal and bradykinin-induced NO/PGI2-independent changes in the forearm blood flow (FBF) of healthy subjects. Eleven healthy male volunteers participated in this placebo-controlled study. Test agents were infused into the brachial artery and FBF was measured by bilateral venous occlusion plethysmography. Sulphaphenazole (0.02–2 mg/min) alone did not affect basal blood flow. Inhibition of the NO synthases by NG-monomethyl-L-arginine (L-NMMA; 4 μmol/min) and cyclo-oxygenases by ibuprofen (1200 mg, orally) reduced FBF to 48±7% in the absence and 50±8% in the presence of sulphaphenazole (2 mg/min; P=not significant). After pretreatment with L-NMMA (16 μmol/min) and ibuprofen (1200 mg, orally), sulphaphenazole (6 mg/min) did not substantially inhibit bradykinin-induced vasodilation. We conclude that CYP2C9-derived metabolites (i) are not involved in the regulation of baseline blood flow, and (ii) do not mediate bradykinin-induced NO/PGI2-independent vasorelaxation in the human forearm. However, determining the contribution of this enzyme to regulation of blood flow in pathological conditions associated with endothelial dysfunction requires further studies.
Exaggerated postprandial lipaemia and lower post-heparin lipoprotein lipase activity in middle-aged men
Authors: JACKSON Kim G. , KNAPPER-FRANCIS Jacky M. E. , MORGAN Linda M. , WEBB Diane H. , ZAMPELAS Antonis , WILLIAMS Christine M.
Published: October 2003

An exaggerated postprandial lipaemic response is thought to play a central role in the development of an atherogenic lipoprotein phenotype, a recognized lipid risk factor for coronary heart disease. A small number of limited studies have compared postprandial lipaemia in subjects of varying age, but have not investigated mechanisms underlying age-associated changes in postprandial lipaemia. In order to test the hypothesis that impaired lipaemia in older subjects is associated with loss of insulin sensitivity, the present study compared the postprandial lipaemic and hormone responses for 9 h following a standard mixed meal in normolipidaemic healthy young and middle-aged men. Lipoprotein lipase (LPL) and hepatic lipase (HL) activities were determined in post-heparin plasma 9 h postprandially and on another occasion under fasting conditions. Postprandial plasma glucose (P<0.02), retinyl ester (indirect marker for chylomicron particles; P<0.005) and triacylglycerol (TAG)-rich lipoprotein (density<1.006 g/ml fraction of plasma) TAG (P<0.05) and retinyl ester (P<0.005) responses were higher in middle-aged men, whereas plasma insulin responses were lower in this group (P<0.001). Fasting and 9 h postprandial LPL and HL activities were also significantly lower in the middle-aged men compared with the young men (P<0.006). In conclusion, the higher incremental postprandial TAG response in middle-aged men than young men was attributed to the accumulation of dietary-derived TAG-rich lipoproteins (density<1.006 g/ml fraction of plasma) and occurred in the absence of marked differences in fasting TAG levels between the two groups. Fasting and postprandial LPL and HL activities were markedly lower in middle-aged men, but lack of statistical associations between measures of insulin response and post-heparin lipase activities, as well as between insulin and measures of postprandial lipaemia, suggest that this lower activity cannot be attributed to lack of sensitivity of lipases to activation by insulin. Alternatively, post-heparin lipase activities may not be good markers for the insulin-sensitive component of lipase that is activated postprandially.
Uric acid reduces exercise-induced oxidative stress in healthy adults
Authors: WARING W. S. , CONVERY A. , MISHRA V. , SHENKIN A. , WEBB D. J. , MAXWELL S. R. J.
Published: October 2003

Uric acid (UA) possesses free-radical-scavenging properties, and systemic administration is known to increase serum antioxidant capacity. However, it is not known whether this protects against oxidative stress. The effects of raising UA concentration were studied during acute aerobic physical exercise in healthy subjects, as a model of oxidative stress characterized by increased circulating 8-iso-prostaglandin F2α (8-iso-PGF2α) concentrations. Twenty healthy subjects were recruited to a randomized double-blind placebo-controlled crossover study, and underwent systemic administration of 0.5 g of UA in 250 ml of 0.1% lithium carbonate/4% dextrose vehicle or vehicle alone as control. subjects performed high-intensity aerobic exercise for 20 min to induce oxidative stress. Plasma 8-iso-PGF2α concentrations were determined at baseline, after exercise and after recovery for 20 min. A single bout of high-intensity exercise caused a significant increase in plasma 8-iso-PGF2α concentrations from 35.0±4.7 pg/ml to 45.6±6.7 pg/ml (P<0.01). UA administration raised serum urate concentration from 293±16 to 487±16 μmol/l (P<0.001), accompanied by increased serum antioxidant capacity from 1786±39 to 1899±45 μmol/l (P<0.01). UA administration abolished the exercise-induced elevation of plasma 8-iso-PGF2α concentrations. High UA concentrations are associated with increased serum antioxidant capacity and reduced oxidative stress during acute physical exercise in healthy subjects. These findings indicate that the antioxidant properties of UA are of biological importance in vivo.
Neither carvedilol nor bisoprolol in maximally tolerated doses has any specific advantage in lowering chronic heart failure oxidant stress: implications for β-blocker selection
Authors: CHIN Bernard S. P. , GIBBS Christopher R. , BLANN Andrew D. , LIP Gregory Y. H.
Published: October 2003

We hypothesized that abnormal oxidative stress in chronic heart failure (CHF) could be related to endothelial damage and platelet activation, and that the vasodilating β-blocker carvedilol would have beneficial effects on these processes compared with a selective non-vasodilating cardioselective β-blocker, bisoprolol. We therefore assessed the effects of introducing carvedilol and bisoprolol in a prospective manner on indices of oxidative stress [lipid hydroperoxides (LHP)], endothelial damage [von Willebrand factor (vWf)], platelet activation (soluble P-selectin) and coagulation (fibrinogen) and their inter-relationships in stable outpatients with CHF in sinus rhythm. We recruited 46 patients [23 male; age 64±13 years (mean±S.D.); range 38–85 years] with CHF. Baseline levels of serum LHP (P<0.002), plasma vWf (P<0.001) and soluble P-selectin (P=0.02), but not fibrinogen (P=0.16), were higher in CHF patients compared with 22 age- and sex-matched healthy controls. After treatment for 2 months, systolic blood pressure fell in both arms of the study (both P<0.01), but there were no statistically significant (defined as P<0.01) decreases in LHP, vWf, fibrinogen or soluble P-selectin levels with either carvedilol or bisoprolol. In conclusion, patients with CHF have increased levels of plasma LHP and vWf, indicating increased oxidative stress and endothelial damage respectively. Contrary to the proposed antioxidative effects of carvedilol, initiating and titrating such therapy did not result in a reduction in levels of LHP in CHF.
Cardiovascular and hormonal effects of subcutaneous administration of ghrelin, a novel growth hormone-releasing peptide, in healthy humans
Authors: ENOMOTO Mitsunobu , NAGAYA Noritoshi , UEMATSU Masaaki , OKUMURA Hiroyuki , NAKAGAWA Eiichiroh , ONO Fumiaki , HOSODA Hiroshi , OYA Hideo , KOJIMA Masayasu , KANMATSUSE Katsuo , KANGAWA Kenji
Published: October 2003

Ghrelin is a novel GH (growth hormone)-releasing peptide isolated from the stomach. The cardiovascular and hormonal effects of the subcutaneous administration of ghrelin in humans remain unknown. Six healthy volunteers each received subcutaneous administration of three doses of ghrelin (1, 5 or 10 μg/kg) and placebo; the order of administration was randomized, and separate doses were given at least 24 h apart. The serum GH level dose-dependently increased from 0.5±0.4 to 3.6±2.1 ng/ml (1 μg/kg ghrelin; P=0.99 compared with baseline), 27.1±12.0 ng/ml (5 μg/kg; P<0.01 compared with baseline) and 45.4±12.8 ng/ml (10 μg/kg; P<0.01 compared with baseline) 30 min after ghrelin administration. Subcutaneous administration of ghrelin did not significantly alter circulating levels of corticotropin, cortisol, insulin-like growth factor-1, noradrenaline or adrenaline, although 10 μg/kg ghrelin slightly increased the prolactin level. No significant changes in heart rate or mean arterial pressure were observed. In contrast, the left ventricular ejection fraction, as assessed by echocardiography, increased dose-dependently from 63.5±0.6% to 65.1±0.9% (1 μg/kg ghrelin; P=0.97 compared with baseline), 69.6±1.3% (5 μg/kg; P<0.01 compared with baseline) and 71.5±0.9% (10 μg/kg; P<0.01 compared with baseline) 30 min after ghrelin administration. These haemodynamic and hormonal changes were still apparent 60 min after ghrelin injection. In conclusion, subcutaneous administration of ghrelin dose-dependently induced relatively specific GH release and enhanced cardiac performance in humans.
HIF, stretching to get control of VEGF
Authors: WARNER Timothy D. , MITCHELL Jane A.
Published: October 2003

Mechanical forces are key regulators of cell function, particularly of cells within the arterial wall that are exposed to the shear stress and pulsatile pressure of flowing blood. The finding by Chang and colleagues in this issue of Clinical Science that cell stretch can up-regulate the expression of hypoxia-inducible factor-1α and vascular endothelial growth factor, which is a key regulator of blood vessel remodelling, provides us with further insight into the mechanisms underlying remodelling at sites of occlusive disease within the cardiovascular system.
Search for non-invasive load-independent indices of left ventricular relaxation
Authors: NAGUEH Sherif F.
Published: October 2003

Echocardiography is an invaluable tool for the routine evaluation of patients with congestive heart failure. A number of Doppler modalities are now available. In this comment, the haemodynamic determinants and the clinical application of the more recent indices of left ventricular relaxation, namely tissue Doppler imaging of the mitral annulus and the flow propagation velocity by colour M-mode, and the importance of the study by Graham et al. in this issue of Clinical Science are discussed.
To b'EET or not to b'EET? That is the question!
Authors: AHLUWALIA Amrita
Published: October 2003

Since the discovery of endothelium-derived hyperpolarizing factor (EDHF), several different candidates and pathways have been proposed as mediators of endothelium-dependent hyperpolarization of vascular smooth muscle. In particular, there has been considerable support for a role for the cytochrome P450 metabolites, the epoxyeicosatrienoic acids (EETs). However, more recently, this hypothesis has come under severe scrutiny. In this issue of Clinical Science, Passauer et al. demonstrate that an EET cannot be EDHF in the human forearm, and add further to the growing belief that an EET is not a candidate for a ubiquitous EDHF.
Effects of stem fraction on the optimization of biomass allocation and maximum photosynthetic capacity
Authors: Osone Y. , Tateno M.
Published: October 2003

A model was developed to examine effects of the stem biomass fraction on the optimal responses of plants to soil nitrogen availability.

Our model predicts that the optimal leaf : root ratio and optimal photosynthetic capacity (Pmax) increase with soil N availability. For a given N availability, the optimal leaf : root ratio decreases and the optimalPmaxincreases with increasing stem fraction. As a result, the increase in optimal leaf : root ratio is smaller, and that in optimalPmaxis greater, in response to increasing N availability when stem fraction is large.

To test these predictions we grew two herbs with different stem fractions:Polygonum cuspidatumSieb. et Zucc. andChenopodium albumL.Showing excellent agreement with the simulation results, the leaf N concentration and leaf : root ratio of the two herbs increased with increasing N availability, and leaf N concentration was larger forC. albumwith higher stem fraction thanP. cuspidatum.

The general tendency for plants with larger stem fractions also to have greater leaf N concentrations andPmaxwas demonstrated for a wide range of temperate herbs. This suggests that stem fraction may be a source of variation inPmaxamong plants in the same functional group.
Effects of inbreeding on immune response and body size in a social insect, Bombus terrestris
Authors: Gerloff C. U. , Ottmer B. K. , Schmid‐Hempel P.
Published: October 2003

Inbreeding can negatively affect various fitness components. Here we examine how immune response and body size of a social insect are affected by inbreeding, sex and ploidy.

In the bumble‐bee, Bombus terrestris (L.), the offspring of colonies resulting from brother–sister matings were compared with that of outbred colonies. Immune response was measured as the degree of encapsulation of a novel antigen, body size as the length of the radial cell in the forewings.

Inbreeding affected neither immune response nor body size in either workers or haploid males under laboratory conditions. However, fitness characteristics varied significantly among maternal families and colonies. The lack of detectable inbreeding depression for two fitness components might help explain why B. terrestris is a good colonizer in nature.

In addition, sex and ploidy strongly affected the fitness components studied: diploid males had a significantly lower immune response than haploid males, who in turn had a significantly lower immune response than workers of the same colony. The body size of diploid males was intermediate between the body size of workers and haploid males.
Detection of serum immunoglobulins in wild birds by direct ELISA: a methodological study to validate the technique in different species using antichicken antibodies
Authors: Martínez J. , Tomás G. , Merino S. , Arriero E. , Moreno J.
Published: October 2003

This study presents an easy protocol to measure the amount of immunoglobulins from the blood serum of different bird species in the wild (Ficedula hypoleuca Pallas, Parus caeruleus L., Lanius meridionalis Temminkck, Lanius collurio L., Athene noctua Scopoli and Falco tinnunculus L.) by direct enzyme‐linked immunosorbent assay, ELISA using commercial antichicken antibodies.

Additionally, the ELISA technique is validated for detecting serum immunoglobulins by means of other electrophoretic (sodium dodecyl sulphate polyacrylamide gel electrophoresis, SDS‐PAGE, and native electrophoresis) and immunological (Western blot) methods.

The results by Western blot show that the commercial antibody recognized proteins with apparent molecular weight according to heavy and light chains of immunoglobulins.

Both ELISA and Western blot data were correlated, implying that the commercial antibody bound to immunoglobulins and not to other proteins or ELISA plates. Densitometric data achieved by SDS‐PAGE and native electrophoresis were only correlated in some species indicating a problem in detecting clearly the heavy and light chains, and γ‐globulin fraction, respectively.

It is concluded that the proposed protocol is easy to carry out and may be used to detect total serum immunoglobulins from most bird species.
Seed set and gene flow patterns in an experimental population of an endangered heterostylous herb with controlled local opposite‐morph density
Authors: Ishihama F. , Nakano C. , Ueno S. , Ajima M. , Tsumura Y. , Washitani I.
Published: October 2003

Seed reproduction of a plant species is strongly affected by the spatial structures of its population through gene flow patterns. We assessed the effects of the spatial arrangement of genetically compatible mates on the seed set and gene flow of a heterostylous perennial species,Primula sieboldiiE. Morren (Primulaceae), using a patchy experimental population.

Seed set was significantly higher in patches containing opposite‐morph genets than in patches without opposite‐morph genets. Pollen flow within patches explained 76·9% of total pollen flow, while 13·5% was ascribed to pollen flow between patches. Mean and maximum pollen dispersal distances within the experimental population were 7·23 and 89 m, respectively.

Mean and maximum seed dispersal distances were 10·4 and 23·0 cm, respectively.

Our results suggest a profound effect of the spatial arrangement of compatible mates within the patchy population on seed set and gene flow. Investigations using experimental populations in combination with molecular markers will provide highly effective means for evaluating the influences of spatial structures on plant gene flow and reproduction, and will also provide valuable information for conservation efforts.
Does morphology or the size of the internal nitrogen store determine how Vaccinium spp. respond to spring nitrogen supply?
Authors: Grelet G.‐A. , Alexander I. J. , Millard P. , Proe M. F.
Published: October 2003

Vaccinium myrtillus (deciduous) and V. vitis‐idaea (evergreen) are ericaceous shrubs adapted to low‐nitrogen environments. Their comparative responsiveness to N supply was determined in relation to both N storage and developmental constraints.

Plants were grown with high or low N in sand culture to condition their N storage, and their growth measured during the first flush of a second year when plants from each treatment were again supplied either high or low N. 15N‐labelling was used to quantify remobilization of N taken up in the first year for growth in the second.

In both species, the growth response to external N availability was mediated through a change in the number of buds, initially present, which produced shoots, with no alteration of the number of leaves per shoot; but the magnitude of the response was smaller in the evergreen species. The second flush of growth took place more rapidly in V. myrtillus than in V. vitis‐idaea, and depended on both external and internal N supply, in terms of the number of shoots produced and the number of leaves per shoot.

The amount of labelled N remobilized by both species depended on the level of N reserves, and on the number of initial buds which produced shoots. In V. myrtillus, the total amount of N remobilized to new growth was significantly affected by external N supply. Since the total amount of N remobilized is independent of external N availability during spring growth, this result implies that the age of the N remobilized depended on the number of buds that produced shoots. We explain this result by the perennial nature of N storage in V. myrtillus and the age range of the pool of buds coming into growth each year on an individual plant.

Nitrogen remobilization and the growth response to N supply were closely linked with the pattern of bud activation. Species‐specific growth responses to N supply in spring were better explained by developmental constraints on growth than by the ability to store and re‐use N.
Quantifying individual feeding variability: implications for mollusc feeding experiments
Authors: Hanley M. E. , Bulling M. T. , Fenner M.
Published: October 2003

In order to quantify the level of variability in seedling consumption displayed by individual molluscs, we placed one snail (Helix aspersa) in each of 51 trays containing (7‐day‐old) Taraxacum officinale seedlings for 7 days.

Initially, individual snails displayed considerable variability in their consumption of seedlings; however, this variability declined with time. The consumption of seedlings was not related to individual snail mass.

A second grazing experiment, using five different snail densities in similar experimental conditions to the first, showed that increasing snail number reduced variability within treatment groups.

A computer simulation, based on data from the first experiment correctly predicted the basic form of the decline in feeding variability with increasing snail density found in the second. Post hoc changes to the model, based on empirical analysis of the second experiment to account for mutual interference, reduced discrepancies between empirical and model results.

This study highlights the consequences that individual feeding behaviour has on feeding trials with molluscs, and provides a simple method by which this variability can be quantified and accommodated within experimental design.
Influence of acclimation and incubation medium on supercooling by hatchling painted turtles, Chrysemys picta
Authors: Packard G. C. , Packard M. J.
Published: October 2003

Baby Painted Turtles, Chrysemys picta (Schneider 1783), ingest soil and fragments of eggshell as they are hatching from their eggs. The ingested soil typically contains bacterial nucleating agents that can cause water in the gut to freeze at high subzero temperatures. If ice forms in the gut, however, the crystals penetrate the wall of that organ and cause water in body compartments to freeze. Thus, newly hatched turtles freeze spontaneously at high subzero temperatures owing to the nucleation of ice by bacteria in the gut.

Painted Turtles purge their gut of soil in the weeks after hatching, but removing particulate material from the GI tract does not, by itself, result in elimination of the bacterial nucleating agents. The purging of nucleating agents requires that hatchlings also be exposed to low (but non‐freezing) temperatures. The response to low temperature is completed in little more than 1 month; a longer exposure does not elicit a demonstrable improvement in the capacity for supercooling.

The limit of supercooling does not vary significantly among turtles hatching on different kinds of soil, despite the fact that different soils typically harbour different concentrations of nucleating agents. Thus, the risk of heterogeneous nucleation probably does not vary appreciably among turtles hatching and overwintering in different kinds of soil in the field.

Hatchling Painted Turtles that have become acclimatized to low temperatures in the field presumably have acquired a high resistance to freezing by inoculation (as shown by prior study) and an enhanced capacity for supercooling (current study), thereby enabling many animals to withstand exposure to ice and cold during winter by remaining unfrozen and supercooled.
A critique of the Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation (DC‐LD) chapter on non‐affective psychotic disorders
Authors: Melville Craig A.
Published: October 2003

Background  There has been a longstanding interest in the study of psychotic disorders in adults with intellectual disability. The DC‐LD chapter for non‐affective psychotic disorders provides operationalised criteria for use with this population.

Methods  A detailed, structured review of the literature was carried out. Relevant papers were reviewed to provide a framework for a critique of the DC‐LD criteria.

Results  Most of the research literature focuses on psychotic disorders in adults with mild intellectural disability and suggests that this group experience clinical symptoms similar to those experienced by adults with average abilities. Although the DC‐LD criteria for non‐affective psychotic disorders are derived from the ICD‐10 equivalent categories they are broader than other classification systems, which may affect their reliability, validity and utility.

Conclusions  At this stage, it is important that the DC‐LD criteria are used alongside established systems to gather information about their use for clinical and research purposes.
Psychiatric diagnosis, intellectual disabilities and Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation (DC‐LD)
Authors: Cooper Sally‐Ann , Melville Craig A. , Einfeld Stewart L.
Published: October 2003

Background  Classification of psychopathology using operationalized diagnostic criteria is one component of psychiatric assessment. Previous literature has demonstrated that there are limitations in the International Classification of Diseases−10 (ICD‐10) and the Diagnostic and Statistical Manual–IV (DSM‐IV) when used with adults with intellectual disabilities.

Methods  A literature search using Medline, PsychLIT and hand searching of key journals identified the existing literature, which was reviewed by the Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation (DC‐LD) Development Working Group. Key findings are integrated into this paper. This, together with expert consensus led to the development of DC‐LD, a new psychiatric classificatory system devised specifically for use with adults with intellectual disabilities. The new diagnostic criteria and classification within DC‐LD were piloted with 52 field investigators drawing on 709 clinical cases. Validity of DC‐LD classification was measured by comparison between the criteria providing DC‐LD diagnosis and the gold standard of learning disabilities psychiatric assessment.

Results  In 96.3% of cases, the DC‐LD diagnosis was fully concordant with that of clinical opinion. The few discrepancies related to level of detail.

Conclusion  DC‐LD accommodates the pathoplastic effect of intellectual disabilities on psychopathology. Its use will hopefully improve clinical practice and facilitate research, but further work to determine its usefulness and limitations is required.
Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation(DC‐LD) and the diagnosis of anxiety disorders: a review
Authors: Bailey N. M. , Andrews T. M.
Published: October 2003

Background/Methods During the development ofDiagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities[DC‐LD] a literature review of diagnostic issues in anxiety disorders in adults with intellectual disability (ID) was undertaken using electronic and hand searching of journals.

Results Relevant general concepts in the general population are reviewed briefly before those related specifically to adults with ID. The literature relating to the diagnosis of specific anxiety disorders is reviewed, although with the exception of obsessive compulsive disorder this consists mainly of case reports. Difficulties in the use of diagnostic systems developed for the general population for the diagnosis of anxiety disorders in adults with ID are frequently commented upon.

Conclusions It is concluded that anxiety disorders are well recognized in adults with ID, although their prevalence is uncertain, and that the use of modified diagnostic criteria may aid further research in this area.
Intellectual disabilities, depressive episode, diagnostic criteria and Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation (DC‐LD)
Authors: Smiley Elita , Cooper Sally‐Ann
Published: October 2003

Background  Depressive episode is one of the most common types of psychiatric illness that occurs in adults with intellectual disabilities.

Methods  A comprehensive literature search was undertaken using Medline, PsychLIT and hand‐searching of key journals. This paper reviews the evidence and integrates findings, to report how evidence relates to the development of the new Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation[DC‐LD] depressive episode criteria.

Results  This area is better researched than many others, providing evidence on clinical symptomatology and presentation. In view of the lack of utility of standard diagnostic criteria developed for use with the general population, and set within the historical context, there are clearly identified reasons for the introduction of DC‐LD. The depressive episode category has been informed by the evidence, and field trials showed excellent validity compared with the gold standard of learning disabilities psychiatric assessment.

Conclusions  The DC‐LD depressive episode category may improve clinical diagnosis and facilitate research. Its usefulness and limitations are yet to be determined in detail.
Attention deficit hyperactivity disorder: review of ADHD in learning disability: the Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation[DC‐LD] criteria for diagnosis
Authors: Seager Marian C. , O'Brien Gregory
Published: October 2003

Background  Attention deficit hyperactivity disorder [ADHD)]is believed to be common among people with learning disabilities. Classification systems in current use have presented diagnostic difficulties in this area, when used for people with learning disability (particularly adults).

Methods  A literature search using electronic databases was undertaken, and journals were hand‐searched for articles relevant to the diagnosis of mental disorders in adults with intellectual disabilities.

Results  There is preliminary evidence that ADHD is more common in this population than among the non‐learning‐disabled population, and indeed that rates of hyperactivity increase with increasing severity of learning disability. There are also associations between ADHD and certain causal syndromes of learning disability.

Conclusion  While available evidence suggests that ADHD may be common among children and adults with learning disabilities, research has been hindered by deficits in currently used diagnostic classification systems. With the recent development of criteria for the diagnosis of ADHD in learning‐disabled adults, and the publication of these in Diagnostic Criteria for Learning Disabilities/Mental Retardation[DC‐LD] there is scope for an increase in the level of interest in the study of ADHD among adults with learning disabilities.
The classification of problem behaviour in Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation (DC‐LD)
Authors: O'Brien Gregory
Published: October 2003

Background Problem behaviour is common among adults with learning disabilities, often to an extent that it impacts upon the functioning and social inclusion of the individual, and of the individual's family and immediate social network.

Methods/Results However, most approaches to the classification and diagnosis of psychiatric disorder among people with learning disability do not deal with problem behaviour as a diagnosis. The recent innovation of the Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation (DC‐LD) includes diagnostic criteria for problem behaviour. The background and the thinking behind these criteria are reviewed.

Conclusions It is proposed that the adoption of such criteria offers the possibility of improved services for the individuals concerned, with resultant improvements in their adaptation and social inclusion.