bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of intermittent hemodialysis on buprenorphine and norbuprenorphine plasma concentrations in chronic pain patients treated with transdermal buprenorphine
Authors: Filitz Jörg , Griessinger Norbert , Sittl Reinhard , Likar Rudi , Schüttler Jürgen , Koppert Wolfgang 
Published: January 2006

AbstractThe present study was designed to study the impact of intermittent hemodialysis on the disposition of the partial agonist buprenorphine and its metabolite norbuprenorphine during therapy with transdermal buprenorphine in chronic pain patients with end‐stage kidney disease. Ten patients (mean age 63 years) who had received transdermal buprenorphine for at least 1 week, were asked to provide blood samples immediately before and after hemodialysis. Blood samples were analysed for buprenorphine and its metabolite norbuprenorphine. The median buprenorphine plasma concentrations were found to be 0.16 ng/ml before and 0.23 ng/ml after hemodialysis. A significant correlation between plasma levels and administered doses was observed (Spearman R = 0.74; P < 0.05). In three patients norbuprenorphine plasma levels were detected. No differences in pain relief before and after hemodialysis were observed. This investigation shows no elevated buprenorphine and norbuprenorphine plasma levels in patients with renal insufficiency receiving transdermal buprenorphine up to 70 μg/h. Furthermore, hemodialysis did not affect buprenorphine plasma levels, leading to stable analgesic effects during the therapy.
Developmental and amyloid plaque‐related changes in cerebral cortical capillaries in transgenic Tg2576 Alzheimer mice
Authors: Kouznetsova Elena , Klingner Margrit , Sorger Dietlind , Sabri Osama , Großmann Udo , Steinbach Jörg , Scheunemann Matthias , Schliebs Reinhard 
Published: January 2006

AbstractThere is experimental evidence that cerebral perfusion is decreased during aging and in Alzheimer's disease. To characterize the temporal relationship between amyloid deposition, plaque size and cerebrovascular abnormalities, a semiquantitative immunohistochemical study was performed in transgenic Tg2576 mice that express the Swedish double mutation of human amyloid precursor protein (APP) and progressively develop Alzheimer‐like β‐amyloid deposits. Cortical cryocut sections, obtained from mice at ages ranging between 4 and 18 months, were immunostained to label glucose transporter type 1 (GLUT1), a marker of vascular endothelial cells, and thioflavine‐S to visualize plaques. Regardless of age and transgene, a laminar distribution of capillaries was observed being highest in cortical layers IV and V. The density of microvessels estimated in cortical regions with high plaque load was found to be significantly lower as compared to areas with low plaque load. Around large thioflavine‐S‐positive senile plaques the capillary density was low, while diffuse plaques demonstrated a close association of capillaries with no signs of any damage.The data suggest that amyloid plaque deposition differentially affects the cerebrovascular system in an age‐ and plaque type‐related manner, and provide further evidence that β‐amyloid, in addition to its well‐described neurotoxic effects, may also contribute to neuronal dysfunction through its actions on the cerebrovasculature.
Recent progress in the ancient lentil
Authors: SARKER A. , ERSKINE W. 
Published: January 2006

Lentil (Lens culinaris Medikus subsp. culinaris) was among the first crops domesticated and has become an important food legume crop in the farming and food systems of many countries globally. Its seed is a rich source of protein, minerals, and vitamins for human nutrition, and the straw is a valued animal feed. Its ability in nitrogen and carbon sequestration improves soil nutrient status, which in turn provides sustainability in production systems. In the current paper, research progress achieved in lentil improvement at national and international levels is reviewed.Since the late 1970s there have been significant national and international lentil improvement programmes, with the main objectives being to develop phenologically adapted, stress resistant and high-yielding cultivars with improved production packages.Systematic research on lentil started recently, compared to other early-domesticated crops. During the last two and a half decades, research progress has been made in various aspects of the crop. Large numbers of germplasm have been collected, evaluated and preserved at national and international levels, with the International Center for Agricultural Research in the Dry Areas (ICARDA) holding the largest collection of cultivated and wild germplasm accessions. A major effort has been made to study the genetic variation in the world germplasm collection, in order to understand local adaptation and to develop specific research programmes. Genotypes with resistance to various biotic and abiotic stresses, particularly resistance to vascular wilt, rust and Ascochyta blight have been identified, and directly exploited or used in breeding programmes. New genotypes have been bred with good standing ability, suitable for mechanical harvest for West Asia and North Africa. Through introduction and hybridization, the genetic base of lentil has been broadened, most particularly in South Asia, by breaking an ancient genetic bottleneck.Agronomic practices, including seeding time, seed rate, tillage requirements, soil type, and weed control, are optimized locally and improved production packages have been developed to realize higher yield. To date, a total of 91 improved cultivars have been released globally, emanating from genetic material supplied by ICARDA. Due to adoption of improved varieties combined with production technologies, the average global productivity has increased from 611 kg/ha to 966 kg/ha, and total production from 1·3 million tonnes to 3·8 million tonnes in the last three decades. Research at the molecular level, including construction of a lentil genetic linkage map, identification of molecular markers, and genetic transformation, has progressed considerably.
Multiple signalling pathways involved in β2‐adrenoceptor‐mediated glucose uptake in rat skeletal muscle cells
Authors: Nevzorova Julia , Evans Bronwyn A , Bengtsson Tore , Summers Roger J 
Published: January 2006

β‐adrenoceptor (AR) agonists increase 2‐deoxy‐[3H]‐D‐glucose uptake (GU) via β2‐AR in rat L6 cells. The β‐AR agonists, zinterol (β2‐AR) and (−)‐isoprenaline, increased cAMP accumulation in a concentration‐dependent manner (pEC50=9.1±0.02 and 7.8±0.02). Cholera toxin (% max increase 141.8±2.5) and the cAMP analogues, 8‐bromo‐cAMP (8Br‐cAMP) and dibutyryl cAMP (dbcAMP), also increased GU (196.8±13.5 and 196.4±17.3%).
The adenylate cyclase inhibitor, 2′,5′‐dideoxyadenosine (50 μM), significantly reduced cAMP accumulation to zinterol (100 nM) (109.7+35.0 to 21.6+4.5 pmol well−1), or forskolin (10 μM) (230.1±58.0 to 107.2±26.3 pmol well−1), and partially inhibited zinterol‐stimulated GU (217±26.3 to 176.1±20.4%). The protein kinase A (PKA) inhibitor, 4‐cyano‐3‐methylisoquinoline (100 nM), did not inhibit zinterol‐stimulated GU. The PDE4 inhibitor, rolipram (10 μM), increased cAMP accumulation to zinterol or forskolin, and sensitised the GU response to zinterol, indicating a stimulatory role of cAMP in GU.
cAMP accumulation studies indicated that the β2‐AR was desensitised by prolonged stimulation with zinterol, but not forskolin, whereas GU responses to zinterol increased with time, suggesting that receptor desensitisation may be involved in GU. Receptor desensitisation was not reversed by inhibition of PKA or Gi.
PTX pretreatment (100 ng ml−1) inhibited insulin or zinterol‐stimulated but not 8Br‐cAMP or dbcAMP‐stimulated GU. The PI3K inhibitor, LY294002 (1 μM), inhibited insulin‐ (174.9±5.9 to 142.7±2.7%) and zinterol‐ (166.9±7.6 to 141.1±8.1%) but not 8 Br‐cAMP‐stimulated GU. In contrast to insulin, zinterol did not cause phosphorylation of Akt.
The results suggest that GU in L6 cells involves three mechanisms: (1) an insulin‐dependent pathway involving PI3K, (2) a β2‐AR‐mediated pathway involving both cAMP and PI3K, and (3) a receptor‐independent pathway suggested by cAMP analogues that increase GU independently of PI3K. PKA appears to negatively regulate β2‐AR‐mediated GU.

British Journal of Pharmacology (2006) 147, 446–454. doi:10.1038/sj.bjp.0706626
Actions of flecainide on susceptibility to phase‐2 ventricular arrhythmias during infarct evolution in rat isolated perfused hearts
Authors: Clements‐Jewery Hugh , Kanaganayagam Gajen Sunthar , Kabra Ruchi , Curtis Michael J 
Published: January 2006

The mechanism of flecainide‐induced unexpected death remains uncertain. Phase‐2 ventricular arrhythmias occur during infarct evolution. We examined whether flecainide (0.74 and 1.48 μM, representing the peak unbound plasma and total blood concentrations, respectively, at ‘therapeutic’ dosage) has proarrhythmic activity on phase‐2 arrhythmia susceptibility during infarct evolution.
To achieve this, we used the Langendorff‐perfused rat heart preparation (n=8 per group) in which baseline phase‐2 arrhythmia susceptibility is low. Left main coronary occlusion evoked phase‐1 (acute ischaemia‐induced) ventricular arrhythmias including fibrillation (VF) in all hearts. By 90 min, hearts were relatively arrhythmia‐free.
Randomized and blinded switch of perfusion to flecainide at 90 min caused no increase over baseline in the incidence of VF, tachycardia (VT) or premature beats (VPB) during the following 150 min of ischaemia, or during reperfusion (begun 240 min after the onset of ischaemia).
In separate hearts, catecholamines (313 nM norepinephrine and 75 nM epinephrine) were co‐perfused with flecainide from 90 min of ischaemia. Catecholamine perfusion increased heart rate, coronary flow and QT interval, and shortened PR interval (all P<0.05), actions that were not altered by flecainide. Catecholamine perfusion caused a weak nonsignificant increase in phase‐2 VPB, VT and VF incidence, but there was no proarrhythmic interaction with flecainide.
In conclusion, the present findings suggest that the increased risk of death associated with clinical use of flecainide is not due to facilitation of phase‐2 ventricular arrhythmias.

British Journal of Pharmacology (2006) 147, 468–475. doi:10.1038/sj.bjp.0706633
Depletion of intracellular Ca2+ stores enhances flow‐induced vascular dilatation in rat small mesenteric artery
Authors: Liu Cuiling , Ngai Ching‐Yuen , Huang Yu , Ko Wing‐Hung , Wu Min , He Guo‐Wei , Garland Christopher J , Dora Kim A , Yao Xiaoqiang 
Published: January 2006

The effect of depleting intracellular Ca2+ stores on flow‐induced vascular dilatation and the mechanism responsible for the vasodilatation were examined in rat isolated small mesenteric arteries.
The arteries were pressurized to 50 mmHg and preconstricted with phenylephrine. Intraluminal flow reversed the effect of phenylephrine, resulting in vasodilatation. Flow dilatation consisted of an initial transient peak followed by a sustained plateau phase. The magnitude of dilatation was markedly reduced by removing Ca2+ from the intraluminal flow medium.
Depletion of intracellular Ca2+ stores with either cyclopiazonic acid (CPA, 2 μM) or 1,4‐dihydroxy‐2,5‐di‐tert‐butylbenzene (BHQ, 10 μM) significantly augmented the magnitude of flow dilatation. Flow‐induced endothelial cell Ca2+ influx was also markedly enhanced in arteries pretreated with CPA or BHQ.
Flow‐induced dilatation was insensitive to Nw‐nitro‐L‐arginine methyl ester (100 μM) plus indomethacin (3 μM) or to oxyhemoglobin (3 μM), but was markedly reduced by 30 mM extracellular K+ or 2 mM tetrabutylammonium (TBA), suggesting an involvement of EDHF.
Catalase at 1200 U ml−1 abolished the flow‐induced dilatation, while the application of exogenous H2O2 (90–220 μM) induced relaxation in phenylephrine‐preconstricted arteries. Relaxation to exogenous H2O2 was blocked in the presence of 30 mM extracellular K+, and H2O2 (90 μM) hyperpolarized the smooth muscle cells, indicating that H2O2 can act as an EDHF.
In conclusion, flow‐induced dilatation in rat mesenteric arteries can be markedly enhanced by prior depletion of intracellular Ca2+ stores. Furthermore, these data are consistent with a role for H2O2 as the vasodilator involved.

British Journal of Pharmacology (2006) 147, 506–515. doi:10.1038/sj.bjp.0706639
Activation of insulin‐like growth factor I receptor‐mediated pathway by ginsenoside Rg1
Authors: Chen Wen‐Fang , Lau Wai‐Sum , Cheung Pik‐Yuen , Guo De‐An , Wong Man‐Sau 
Published: January 2006

Ginsenoside Rg1, an active ingredient in ginseng, was previously shown to be a novel class of potent phytoestrogen. The present study aims at investigating the molecular mechanisms involved in mediating its actions in human breast cancer (MCF‐7) cells.
Rg1 (1 pM) stimulates cell proliferation (P<0.01) and estrogen‐responsive pS2 mRNA expression (P<0.05) without alteration of estrogen receptor alpha (ERα) protein or mRNA expression in MCF‐7 cells. In addition, 10−14–10−4 M of Rg1 does not demonstrate specific binding to ERα.
We hypothesize that Rg1 may exert its actions in MCF‐7 cell via the activation of crosstalk between ER‐ and insulin growth factor I receptor (IGF‐IR)‐dependent pathways.
The results indicate that Rg1 significantly increases IGF‐IR expression and IGF‐IR promoter activity in MCF‐7 cells (P<0.05). Cotreatment of MCF‐7 cells with 1 μM of estrogen antagonist ICI 182,780 completely abolishes the effects of Rg1 on IGF‐IR expression.
Furthermore, Rg1 enhances tyrosine phosphorylation of IRS‐1 in MCF‐7 cells upon IGF‐I stimulation and the activation of IRS‐1 phosphorylation is also ER‐dependent.
Taken together, our results suggest that Rg1 not only increases IGF‐IR expression but also enhances IGF‐IR‐mediated signaling pathways in MCF‐7 cells. The stimulation of IGF‐IR expression by Rg1 in MCF‐7 cells appears to require ER, and its actions might involve ligand‐independent activation of ER.

British Journal of Pharmacology (2006) 147, 542–551. doi:10.1038/sj.bjp.0706640
Endothelium‐dependent relaxation evoked by ATP and UTP in the aorta of P2Y2‐deficient mice
Authors: Guns Pieter‐Jan D F , Van Assche Tim , Fransen Paul , Robaye Bernard , Boeynaems Jean‐Marie , Bult Hidde 
Published: January 2006

Based on pharmacological criteria, we previously suggested that in the mouse aorta, endothelium‐dependent relaxation by nucleotides is mediated by P2Y1(adenosine diphosphate (ADP)), P2Y2(adenosine triphosphate (ATP)) and P2Y6(uridine diphosphate (UDP)) receptors. For UTP, it was unclear whether P2Y2, P2Y6or yet another subtype was involved. Therefore, in view of the lack of selective purinergic agonists and antagonists, we used P2Y2‐deficient mice to clarify the action of UTP.Thoracic aorta segments (width 2 mm) of P2Y2‐deficient and wild‐type (WT) mice were mounted in organ baths to measure isometric force development and intracellular calcium signalling.Relaxations evoked by ADP, UDP and acetylcholine were identical in knockout and WT mice, indicating that the receptors for these agonists function normally.P2Y2‐deficient mice showed impaired ATP‐ and adenosine 5′[γ‐thio] triphosphate (ATPγS)‐evoked relaxation, suggesting that in WT mice, ATP and ATPγS activate predominantly the P2Y2subtype.The ATP/ATPγS‐evoked relaxation and calcium signals in the knockout mice were partially rescued by P2Y1, as they were sensitive to 2′‐deoxy‐N6‐methyladenosine 3′,5′‐bisphosphate (MRS2179), a P2Y1‐selective antagonist.In contrast to ATP, the UTP‐evoked relaxation was not different between knockout and WT mice. Moreover, the action of UTP was not sensitive to MRS2179. Therefore, the action of UTP is probably mediated mainly by a P2Y6(like) receptor subtype.In conclusion, we demonstrated that ATP‐evoked relaxation of the murine aorta is mainly mediated by P2Y2. But this P2Y2receptor has apparently no major role in UTP‐evoked relaxation. The vasodilator effect of UTP is probably mediated mainly by a P2Y6(like) receptor.British Journal of Pharmacology(2006)147, 569–574. doi:10.1038/sj.bjp.0706642
Vasorelaxant effects of oleamide in rat small mesenteric artery indicate action at a novel cannabinoid receptor
Authors: Hoi Pui Man , Hiley C Robin 
Published: January 2006

Oleamide (cis‐9‐octadecenoamide) exhibits some cannabimimetic responses despite its low affinities at the currently known cannabinoid receptors. Here we have investigated whether or not it is a vasorelaxant in rat small mesenteric arteries.Oleamide elicited vasorelaxation (EC50=1.2±0.2 μM,Rmax=99.1±3.9%,n=8) which was reduced by endothelial removal. Nitric oxide synthase inhibition reduced the response (EC50=5.3±1.6 μM,Rmax=59.2±7.7%,n=7;P<0.01) as did blockade of Ca2+‐sensitive K+channels (KCa) with apamin plus charybdotoxin (both 50 nM) (EC50=2.1±0.2 μM,Rmax=58.4±1.9%,n=5;P<0.05). Desensitisation of vanilloid receptors with capsaicin (10 μMfor 30 min) shifted the oleamide concentration–response curve ∼30‐fold to the right (n=7;P<0.01). Pertussis toxin (400 ng ml−1for 2 h) caused a two‐fold shift in the response curve (EC50=2.2±0.4 μM,Rmax=66.8±4.5%,n=6;P<0.01).Rimonabant (CB1cannabinoid receptor antagonist; SR141716A; 3 μM) significantly inhibited relaxation induced by oleamide (EC50=3.5±0.3 μM,Rmax=75.1±1.9%;n=8;P<0.05). In contrast, neither the more selective CB1receptor antagonist, AM251 (1 μM), nor the CB2antagonist, SR144528 (1 μM), had significant effects. O‐1918 (10 μM), a putative antagonist at a novel endothelial cannabinoid receptor (abnormal‐cannabidiol site), markedly reduced the relaxation to oleamide (n=7;P<0.01).It is concluded that oleamide responses in the rat isolated small mesenteric artery are partly dependent on the presence of the endothelium, activation of Ca2+‐sensitive K+channels (KCa) and involve capsaicin‐sensitive sensory nerves. Oleamide may share a receptor (sensitive to rimonabant and O‐1918, and coupled toKCaandGi/o) with anandamide in this vessel. This might be distinct from both of the known cannabinoid receptors and the novel abnormal‐cannabidiol site.British Journal of Pharmacology(2006)147, 560–568. doi:10.1038/sj.bjp.0706643
A3 adenosine receptor antagonists delay irreversible synaptic failure caused by oxygen and glucose deprivation in the rat CA1 hippocampus in vitro
Authors: Pugliese Anna Maria , Coppi Elisabetta , Spalluto Giampiero , Corradetti Renato , Pedata Felicita 
Published: January 2006

The role of adenosine A3 receptor activation during ischaemia‐like conditions produced by oxygen and glucose deprivation (OGD) was evaluated with extracellular recordings from the CA1 region of rat hippocampal slices. In all, 7 min of OGD evoked tissue anoxic depolarisation (AD, peak at ∼7 min from OGD start, n=20) and were invariably followed by irreversible loss of electrically evoked field epsps (fepsps, n=42).
The selective adenosine A3 antagonists 3‐propyl‐6‐ethyl‐5[(ethylthio)carbonyl]‐2‐phenyl‐4‐propyl‐3‐pyridinecarboxylate (MRS 1523, 1–100 nM, n=31), N‐[9‐chloro‐2‐(2‐furanyl)[1,2,4]‐triazolo[1,5‐c]quinazolin‐5‐yl]benzeneacetamide (MRS 1220, 100 nM, n=7), N‐(2‐methoxyphenyl)‐N′‐[2‐(3‐pyrindinyl)‐4‐quinazolinyl]‐urea, (VUF 5574, 100 nM, n=3) and 5‐[[(4‐pyridyl)amino]carbonyl]amino‐8‐methyl‐2‐(2‐furyl)‐pyrazolo[4,3‐e]1,2,4‐triazolo[1,5‐c]pyrimidine hydrochloride (1 nM, n=4), prevented the irreversible failure of neurotransmission induced by 7 min OGD (n=45) and the development of AD in 20 out of 22 monitored slices.
When tested on OGD episodes of longer duration (8–10 min, n=18), 100 nM MRS 1523 prevented or delayed the appearance of AD and exerted a protective effect on neurotransmission for episodes of up to 9 min duration. In the absence of AD, the fepsp recovery was almost total, regardless of OGD episode duration.
These findings support the notion that A3 receptor stimulation is deleterious during ischaemia and suggest that selective A3 receptor block may substantially increase the resistance of the CA1 hippocampal region to ischaemic damage.

British Journal of Pharmacology (2006) 147, 524–532. doi:10.1038/sj.bjp.0706646
On the indices of plant–plant competition and their pitfalls
Authors: Oksanen Lauri , Sammul Marek , Mägi Merike 
Published: January 2006

The index of relative competition intensity (RCI) has serious built‐in biases, due to its asymptotic behavior when competition intensity is high and its tendency to obtain very low values when plants with neighbors intact perform better than neighbor removal plants. These biases have been partially corrected in the index of relative neighbor effect (RNE), but the existence of fixed upper and lower bounds (−1≤RNE≤+1) still creates problems and biases in communities where the average intensity of competition or facilitation is high and plant performance pronouncedly varies in space. The third commonly used index, the logarithm of response ratio (lnRR), is mathematically and statistically sound, but when computed from pair‐wise comparisons between neighbor removal and control plants, this index reflects the geometric mean of the treatment effect. Moreover, linear patterns in lnRR reflect exponential patterns in the intensity of competition. As the interest of ecologists usually focuses on arithmetic means, we propose a corrected index of relative competition intensity, CRCI=arc sin (RNE). This index is fairly linear within the observed ranges of competition and facilitation, and for the range of competition intensities where RNE behaves reasonably, the two indices obtain almost identical values.We compared the performance of the four indices, using both imagined and real data, the latter from systems where the responses of plants to neighbor removal ranged from weak to moderate, so that RNE and CRCI were expected to behave similarly. The indices were computed both from pooled data for each community and as averages of pair‐wise comparisons. lnRR and CRCI were found to behave in a consistent and bias‐free manner, yielding similar results regardless of method of computation. This was, by and large, the case with RNE, too, but as the values of indices grew, the values from pair‐wise comparisons became increasingly smaller than values computed from pooled data. RCI yielded grossly aberrant results in computations based on pair‐wise comparisons. Therefore, the further use of RCI is unadvisable and studies where RCI has been derived from pair‐wise comparisons should be excluded from meta‐analyses.
Long‐term prognosis in Crohn's disease: factors that affect quality of life
Authors: CANAVAN C. , ABRAMS K. R. , HAWTHORNE B. , DROSSMAN D. , MAYBERRY J. F. 
Published: January 2006

SummaryBackgroundThere are many studies investigating quality of life in recently diagnosed patients and following surgery for Crohn's disease, but there are none investigating quality of life changes with disease duration. The response shift model suggests quality of life improves with time following diagnosis.AimTo assess how well the model applies to patients with Crohn's disease.MethodsThe Cardiff Crohn's disease database contains data on all patients diagnosed there since 1934. Three hundred and ninety four patients diagnosed before 1 January 1985 were traced and the mortality status on 31 December 2004 established. Two hundred and eleven still living were sent quality of life questionnaires. Two hundred and eighty five questionnaires were sent to patients with varying disease duration attending out‐patient clinics in Leicester.ResultsEighty‐nine valid replies were received from Cardiff, 63 from Leicester patients diagnosed over 20 years, 69 from Leicester patients diagnosed <10 years. There was no difference in quality of life between newly diagnosed and established patients. Of greatest concern was possible need for ostomy, uncertain nature of disease, and lack of energy. Stepwise regression showed that increased disease severity, older age and smoking adversely affect quality of life.DiscussionQuality of life is equally poor in patients with established disease as in those newly diagnosed, and directly correlates with disease severity. The response shift model may not be applicable in Crohn's disease.