bluuebunny/crossref_metadata_2025 huggingface dataset:
The monosialosyl ganglioside GM-1 reduces the vagolytic efficacy of δ2-opioid receptor stimulation
Authors: Davis Shavsha , Deo Shekhar H. , Barlow Matthew , Yoshishige Darice , Farias Martin , Caffrey James L.
Published: July 2006

The cardiac enkephalin, methionine-enkephalin-arginine-phenylalanine (MEAP), alters vagally induced bradycardia when introduced by microdialysis into the sinoatrial (SA) node. The responses to MEAP are bimodal; lower doses enhance bradycardia and higher doses suppress bradycardia. The opposing vagotonic and vagolytic effects are mediated, respectively, by δ1and δ2phenotypes of the same receptor. Stimulation of the δ1receptor reduced the subsequent δ2responses. Experiments were conducted to test the hypothesis that the δ-receptor interactions were mediated by the monosialosyl ganglioside GM-1. When the mixed agonist MEAP was evaluated after nodal GM-1 treatment, δ1-mediated vagotonic responses were enhanced, and δ2-mediated vagolytic responses were reduced. Prior treatment with the δ1-selective antagonist 7-benzylidenaltrexone (BNTX) failed to prevent attrition of the δ2-vagolytic response or restore it when added afterward. Thus the GM-1-mediated attrition was not mediated by δ1receptors or increased competition from δ1-mediated vagotonic responses. When GM-1 was omitted, deltorphin produced a similar but less robust loss in the vagolytic response. In contrast, however, to GM-1, the deltorphin-mediated attrition was prevented by pretreatment with BNTX, indicating that the decline in response after deltorphin alone was mediated by δ1receptors and that GM-1 effectively bypassed the receptor. Whether deltorphin has intrinsic δ1activity or causes the release of an endogenous δ1-agonist is unclear. When both GM-1 and deltorphin were omitted, the subsequent vagolytic response was more intense. Thus GM-1, deltorphin, and time all interact to modify subsequent δ2-mediated vagolytic responses. The data support the hypothesis that δ1-receptor stimulation may reduce δ2-vagolytic responses by stimulating the GM-1 synthesis.
Cardioprotection by postconditioning in conscious rats is limited to coronary occlusions <45 min
Authors: Tang Xian-Liang , Sato Hiroshi , Tiwari Sumit , Dawn Buddhadeb , Bi Qiuli , Li Qianhong , Shirk Gregg , Bolli Roberto
Published: July 2006

Objectives: Brief episodes of ischemia and reperfusion after a lethal ischemic insult confer cardioprotection, a phenomenon termed “ischemic postconditioning.” However, all studies reported to date have been conducted in open-chest animal models. We sought to determine whether postconditioning occurs in conscious animals and whether it protects against severe myocardial injury. Methods: Chronically instrumented rats were assigned to a 30- ( Subset 1), 45- ( Subset 2), or 60-min ( Subset 3) coronary occlusion followed by 24 h of reperfusion. In each subset, rats received no further intervention (control), were preconditioned with 12 cycles of 2-min occlusion/2-min reperfusion immediately (early preconditioning; EPC) or 24 h (late preconditioning; LPC) before myocardial infarction, or were postconditioned with 20 cycles of 10-s occlusion/10-s reperfusion immediately after myocardial infarction (20-10 PostC). Results: With a 30-min occlusion, infarct size (54.4 ± 2.3% of risk region in control-30) was significantly reduced in EPC-30, LPC-30, and 20-10 PostC-30 groups (by 72, 70, and 47%, respectively; all P < 0.05 vs. control-30). With a 45-min occlusion, infarct size (62.2 ± 2.4% in control-45) was reduced in EPC-45 and LPC-45 groups (by 47 and 41%, respectively; all P < 0.05 vs. control-45) but not in the 20-10 PostC-45 group [55.4 ± 2.3%, P = not significant (NS) vs. control-45]. With a 60-min occlusion, infarct size (72.7 ± 2.2% in control-60) was reduced in the EPC-60 (by 20%, P < 0.05) but not in the LPC-60 (63.6 ± 2.5%, P = NS) or in the 20-20 PostC group (71.5 ± 3.4%, P = NS). Conclusions: Both early and late ischemic preconditioning as well as ischemic postconditioning confer protection in conscious rats; however, unlike early preconditioning, postconditioning protects only against coronary occlusions <45 min. In the conscious rat, the cardioprotection afforded by postconditioning is limited to mild to moderate myocardial injury.
Endothelial coordination of cerebral vasomotion via myoendothelial gap junctions containing connexins 37 and 40
Authors: Haddock Rebecca E. , Grayson T. Hilton , Brackenbury Therese D. , Meaney Kate R. , Neylon Craig B. , Sandow Shaun L. , Hill Caryl E.
Published: July 2006

Control of cerebral vasculature differs from that of systemic vessels outside the blood-brain barrier. The hypothesis that the endothelium modulates vasomotion via direct myoendothelial coupling was investigated in a small vessel of the cerebral circulation. In the primary branch of the rat basilar artery, membrane potential, diameter, and calcium dynamics associated with vasomotion were examined using selective inhibitors of endothelial function in intact and endothelium-denuded arteries. Vessel anatomy, protein, and mRNA expression were studied using conventional electron microscopy high-resolution ultrastructural and confocal immunohistochemistry and quantitative PCR. Membrane potential oscillations were present in both endothelial cells and smooth muscle cells (SMCs), and these preceded rhythmical contractions during which adjacent SMC intracellular calcium concentration ([Ca2+]i) waves were synchronized. Endothelium removal abolished vasomotion and desynchronized adjacent smooth muscle cell [Ca2+]iwaves. NG-nitro-l-arginine methyl ester (10 μM) did not mimic this effect, and dibutyryl cGMP (300 μM) failed to resynchronize [Ca2+]iwaves in endothelium-denuded arteries. Combined charybdotoxin and apamin abolished vasomotion and depolarized and constricted vessels, even in absence of endothelium. Separately,37,43Gap27 and40Gap27 abolished vasomotion. Extensive myoendothelial gap junctions (3 per endothelial cell) composed of connexins 37 and 40 connected the endothelial cell and SMC layers. Synchronized vasomotion in rat basilar artery is endothelium dependent, with [Ca2+]iwaves generated within SMCs being coordinated by electrical coupling via myoendothelial gap junctions.
Adenosine A2Areceptor modulation of juvenile female rat skeletal muscle microvessel permeability
Authors: Wang Jianjie , Huxley Virginia H.
Published: July 2006

Little is known of the regulation of skeletal muscle microvascular exchange under resting or stimulating conditions. Adenosine (ADO) levels in skeletal muscle increase during physiological (exercise) and pathological (hypoxia, inflammation, and ischemia) conditions. Later stages of these pathologies are characterized by the loss of vascular barrier integrity. This study focused on determining which ADO receptor mediates the robust reduction in microvessel permeability to rat serum albumin ( PsRSA) observed in juvenile female rats. In microvessels isolated from abdominal skeletal muscle, ADO suffusion induced a concentration-dependent reduction in arteriolar [log(IC50) = −9.8 ± 0.2 M] and venular [log(IC50) = −8.4 ± 0.2 M] PsRSA. RT-PCR and immunoblot analysis demonstrated mRNA and protein expression of ADO A1, A2A, A2B, and A3receptors in both vessel types, and immunofluorescence assay revealed expression of the four subtype receptors in the microvascular walls (endothelium and smooth muscle). PsRSAresponses of arterioles and venules to ADO were blocked by 8-( p-sulphophenyl)theophylline, a nonselective A1and A2antagonist. An A2Aagonist, CGS21680 , was more potent than the A1agonist, cyclopentyladenosine, or the most-selective A2Bagonist, 5′-( N-ethylcarboxamido)adenosine. The ability of CGS21680 or ADO to reduce PsRSAwas abolished by the A2Aantagonist, ZM241385. An adenylyl cyclase inhibitor, SQ22536, blocked the permeability response to ADO. In aggregate, these results demonstrate that, in juvenile females (before the production of the reproductive hormones), ADO enhances skeletal muscle arteriole and venule barrier function predominantly via A2Areceptors using activation of adenylyl cyclase-signaling mechanisms.
Molecular and electrophysiological characteristics of K+conductance sensitive to acidic pH in aortic smooth muscle cells of WKY and SHR
Authors: Kiyoshi Hidekazu , Yamazaki Daiju , Ohya Susumu , Kitsukawa Mika , Muraki Katsuhiko , Saito Shin-ya , Ohizumi Yasushi , Imaizumi Yuji
Published: July 2006

Changes in K+conductances and their contribution to membrane depolarization in the setting of an acidic pH environment have been studied in myocytes from aortic smooth muscle cells of spontaneously hypertensive rats (SHR) compared with those from Wistar-Kyoto (WKY) rats. The resting membrane potential (RMP) of aortic smooth muscle at extracellular pH (pHo) of 7.4 was significantly more depolarized in SHR than in WKY rats. Acidification to pHo6.5 made this difference in RMP between SHR and WKY rats more significant by further depolarizing the SHR myocytes. Large-conductance Ca2+-activated K+(BK) currents, which were markedly suppressed by acidification, were larger in aortic myocytes of SHR than in those of WKY rats. In contrast, acid-sensitive, non-BK currents were smaller in SHR. Western blot analyses showed that expression of BK-α- and -β1subunits in SHR aortas was upregulated and comparable with those in WKY rats, respectively. Additional electrophysiological and molecular studies showed that pH- and halothane-sensitive two-pore domain weakly inward rectifying K+channel (TWIK)-like acid-sensitive K+(TASK) channel subtypes were functionally expressed in aortas, and TASK1 expression was significantly higher in WKY than in SHR. Although the background current through TASK channels at normal pHo(7.4) was small and may not contribute significantly to the regulation of RMP, TASK channel activation by halothane or alkalization (pHo8.0) induced significant hyperpolarization in WKY but not in SHR. In conclusion, the larger depolarization and subsequent abnormal contractions after acidification in aortic myocytes in the setting of SHR hypertension are mainly attributable to the larger contribution of BK current to the total membrane conductance than in WKY aortas.
Loss of α2B-adrenoceptors increases magnitude of hypertension following nitric oxide synthase inhibition
Authors: Duling Laura C. , Cherng Tom W. , Griego Jason R. , Perrine Michael F. , Kanagy Nancy L.
Published: July 2006

Vascular α2B-adrenoceptors (α2B-AR) may mediate vasoconstriction and contribute to the development of hypertension. Therefore, we hypothesized that blood pressure would not increase as much in mice with mutated α2B-AR as in wild-type (WT) mice following nitric oxide (NO) synthase (NOS) inhibition with Nω-nitro-l-arginine (l-NNA, 250 mg/l in drinking water). Mean arterial pressure (MAP) was recorded in heterozygous (HET) α2B-AR knockout mice and WT littermates using telemetry devices for 7 control and 14 l-NNA treatment days. MAP in HET mice was increased significantly on treatment days 1 and 4 to 14, whereas MAP did not change in WT mice ( days 0 and 14 = 113 ± 3 and 114 ± 4 mmHg in WT, 108 ± 0.3 and 135 ± 13 mmHg in HET, P < 0.05). MAP was significantly higher in HET than in WT mice days 10 through 14 ( P < 0.05). Thus blood pressure increased more rather than less in mice with decreased α2B-AR expression. We therefore examined constrictor responses to phenylephrine (PE, 10−9 to 10−4 M) with and without NOS inhibition to determine basal NO contributions to arterial tone. In small pressurized mesenteric arteries (inner diameter = 177 ± 5 μm), PE constriction was decreased in untreated HET arteries compared with WT ( P < 0.05). l-NNA (100 μM) augmented PE constriction more in HET arteries than in WT arteries, and responses were not different between groups in the presence of l-NNA. Acetylcholine dilated preconstricted arteries from HET mice more than arteries from WT mice. Endothelial NOS expression was increased in HET compared with WT mesenteric arteries by Western analysis. Griess assay showed increased NOx concentrations in HET plasma compared with those in WT plasma. These data demonstrate that diminished α2B-AR expression increases the dependence of arterial pressure and vascular tone on NO production and that vascular α2B-AR either directly or indirectly regulates vascular endothelial NOS function.
ATP and norepinephrine contributions to sympathetic vasoconstriction of tail artery are altered in streptozotocin-diabetic rats
Authors: Speirs Lynne , Donnelly Aisling , Lynch Joanne , Scholfield C. Norman , Johnson Christopher
Published: July 2006

Sympathetic vasoconstriction is susceptible to diabetes, but contributions made by purinergic neurotransmission in this state have not been investigated. We aimed to evaluate sympathetic vasoconstriction contributions by ATP and norepinephrine in the tail artery from streptozotocin-diabetic rats by using isometric vascular rings. Tail arteries were isolated from rats made diabetic 3 mo earlier with streptozotocin (diabetic group), age-matched nondiabetic rats (nondiabetic injected), age-matched untreated animals (noninjected normal), and age-matched untreated animals in high glucose control Krebs solution (high glucose control). Responses to KCl (60 mM) or nerve stimulus trains of 1–100 impulses were identical in all groups. Electrical stimulation produced progressively greater contractions with increasing impulse numbers. These were partially reduced by suramin (100 μM, P2 antagonist), NF-279 (1 μM, P2X blocker), and phentolamine (2 μM, α-blocker). For purinergic antagonists, blockade was greater in diabetic vessels compared with that in others. No differential effect could be detected for phentolamine between groups. Bath-applied ATP (1 nM–1 mM) and norepinephrine (0.1 nM–100 μM) showed increased potency with diabetic group vessels. Desipramine (1 μM, norepinephrine reuptake inhibitor) potentiated neurally evoked responses in all groups equally and increased sensitivity to exogenous norepinephrine in a similar fashion. Histochemical labeling of sympathetic nerves with neuronal marker protein PGP-9.5 and a sympathetic nerve-specific antibody for tyrosine hydroxylase showed no reduction in diabetic innervation density. We demonstrate, for the first time, changes in contributions of ATP and norepinephrine in sympathetic responses of rat tail artery in diabetes, which cannot be accounted for by axonal degeneration or by changes in norepinephrine reuptake.
Bone morphogenetic protein-2 upregulates expression and function of voltage-gated K+channels in human pulmonary artery smooth muscle cells
Authors: Fantozzi Ivana , Platoshyn Oleksandr , Wong Ada H. , Zhang Shen , Remillard Carmelle V. , Furtado Manohar R. , Petrauskene Olga V. , Yuan Jason X.-J.
Published: July 2006

Activity of voltage-gated K+(KV) channels in pulmonary artery smooth muscle cells (PASMC) plays an important role in control of apoptosis and proliferation in addition to regulating membrane potential and pulmonary vascular tone. Bone morphogenetic proteins (BMPs) inhibit proliferation and induce apoptosis in normal human PASMC, whereas dysfunctional BMP signaling and downregulated KVchannels are involved in pulmonary vascular medial hypertrophy associated with pulmonary hypertension. This study evaluated the effect of BMP-2 on KVchannel function and expression in normal human PASMC. BMP-2 (100 nM for 18–24 h) significantly (>2-fold) upregulated mRNA expression of KCNA5, KCNA7, KCNA10, KCNC3, KCNC4, KCNF1, KCNG3, KCNS1, and KCNS3 but downregulated (at least 2-fold) KCNAB1, KCNA2, KCNG2, and KCNV2. The most dramatic change was the >10-fold downregulation of KCNG2 and KCNV2, two electrically silent γ-subunits that form heterotetramers with functional KVchannel α-subunits (e.g., KCNB1–2). Furthermore, the amplitude and current density of whole cell KVcurrents were significantly increased in PASMC treated with BMP-2. It has been demonstrated that K+currents generated by KCNB1 and KCNG1 (or KCNG2) or KCNB1 and KCNV2 heterotetramers are smaller than those generated by KCNB1 homotetramers, indicating that KCNG2 and KCNV2 (2 subunits that were markedly downregulated by BMP-2) are inhibitors of functional KVchannels. These results suggest that BMP-2 divergently regulates mRNA expression of various KVchannel α-, β-, and γ-subunits and significantly increases whole cell KVcurrents in human PASMC. Finally, we present evidence that attenuation of c-Myc expression by BMP-2 may be involved in BMP-2-mediated increase in KVchannel activity and regulation of KVchannel expression. The increased KVchannel activity may be involved in the proapoptotic and/or antiproliferative effects of BMP-2 on PASMC.
Rho kinase activation maintains high pulmonary vascular resistance in the ovine fetal lung
Authors: Parker Thomas A. , Roe Gates , Grover Theresa R. , Abman Steven H.
Published: July 2006

Mechanisms that maintain high pulmonary vascular resistance (PVR) in the fetal lung are poorly understood. Activation of the Rho kinase signal transduction pathway, which promotes actin-myosin interaction in vascular smooth muscle cells, is increased in the pulmonary circulation of adult animals with experimental pulmonary hypertension. However, the role of Rho kinase has not been studied in the fetal lung. We hypothesized that activation of Rho kinase contributes to elevated PVR in the fetus. To address this hypothesis, we studied the pulmonary hemodynamic effects of brief (10 min) intrapulmonary infusions of two specific Rho kinase inhibitors, Y-27632 (15–500 μg) and HA-1077 (500 μg), in chronically prepared late-gestation fetal lambs ( n = 9). Y-27632 caused potent, dose-dependent pulmonary vasodilation, lowering PVR from 0.67 ± 0.18 to 0.16 ± 0.02 mmHg·ml−1·min−1 ( P < 0.01) at the highest dose tested without lowering systemic arterial pressure. Despite brief infusions, Y-27632-induced pulmonary vasodilation was sustained for 50 min. HA-1077 caused a similar fall in PVR, from 0.39 ± 0.03 to 0.19 ± 0.03 ( P < 0.05). To study nitric oxide (NO)-Rho kinase interactions in the fetal lung, we tested the effect of Rho kinase inhibition on pulmonary vasoconstriction caused by inhibition of endogenous NO production with nitro-l-arginine (l-NA; 15–30 mg), a selective NO synthase antagonist. l-NA increased PVR by 127 ± 73% above baseline under control conditions, but this vasoconstrictor response was completely prevented by treatment with Y-27632 ( P < 0.05). We conclude that the Rho kinase signal transduction pathway maintains high PVR in the normal fetal lung and that activation of the Rho kinase pathway mediates pulmonary vasoconstriction after NO synthase inhibition. We speculate that Rho kinase plays an essential role in the normal fetal pulmonary circulation and that Rho kinase inhibitors may provide novel therapy for neonatal pulmonary hypertension.
3-Deazaadenosine mitigates arterial remodeling and hypertension in hyperhomocysteinemic mice
Authors: Ovechkin Alexander V. , Tyagi Neetu , Sen Utpal , Lominadze David , Steed Mesia M. , Moshal Karni S. , Tyagi Suresh C.
Published: July 2006

Chronic hyperhomocysteinemia (HHcy) is an important factor in development of arterial hypertension. HHcy is associated with activation of matrix metalloproteinases (MMPs); however, it is unclear whether HHcy-dependent extracellular matrix (ECM) accumulation plays a role in arterial hypertrophy and hypertension. We tested the hypothesis that in HHcy the mechanism of arterial hypertension involves arterial dysfunction in response to ECM accumulation between endothelial and arterial smooth muscle cells and subsequent endothelium-myocyte (E-M) uncoupling. To decrease plasma Hcy, dietary supplementation with 3-deazaadenosine (DZA), the S-adenosylhomocysteine hydrolase inhibitor, was administered to cystathionine β-synthase (CBS) knockout (KO) mice. Mice were grouped as follows: wild type (WT; control), WT+DZA, CBSKO, and CBSKO+DZA ( n = 4/group). Mean aortic blood pressure and heart rate were monitored in real time with a telemetric system before, during, and after DZA treatment (6 wk total). In vivo aorta function and morphology were analyzed by M-mode and Doppler echocardiography in anesthetized mice. Aorta MMP activity in unfixed cryostat sections was measured with DQ gelatin. Aorta MMP-2, MMP-9, and connexin 43 expression were measured by RT-PCR and Western blot analyses, respectively. HHcy caused increased aortic blood pressure and resistance, tachycardia, and increased wall thickness and ECM accumulation in aortic wall vs. control groups. There was a linear correlation between aortic wall thickness and plasma Hcy levels. MMP-2, MMP-9, and connexin 43 expression were increased in HHcy. In the CBSKO+DZA group, aortic blood pressure and levels of MMP and connexin 43 were close to those found in control groups. However, removal of DZA reversed the aortic lumen-to-wall thickness ratio in CBSKO mice, suggesting, in part, a role of vascular remodeling in the increase in blood pressure in HHcy. The results show that arterial hypertension in HHcy mice is, in part, associated with arterial remodeling and E-M uncoupling in response to MMP activation.
Effect of Imatinib Mesylate Combined with Granulocyte Colony-Stimulating Factor on Leukaemic Blast Cells Derived from Advanced-Stage Chronic Myelogenous Leukaemia Patients
Authors: Ota Shuichi , Musashi Manabu , Kondo Keiichi , Toyoshima Nobuyasu , Toubai Tomomi , Onozawa Masahiro , Mori Akio , Hashino Satoshi , Tanaka Junji , Matsuno Kazuhiko , Imamura Masahiro , Asaka Masahiro
Published: July 2006

Neutropenia is a severe adverse effect that can occur when treating patients with imatinib mesylate for advanced-stage chronic myelogenous leukaemia (CML). Therefore, we evaluated in vitro the combined effect of imatinib and granulocyte colony-stimulating factor (G-CSF) on proliferation and apoptosis of Bcr-Abl-expressing leukaemic cells to infer the safety of G-CSF administration. In KU812 and K562 cell lines, G-CSF neither stimulated their proliferation nor abolished the suppressive effect of imatinib. However, it stimulated the proliferation of blast cells in 2 out of the 5 cases with advanced-stage CML. These in vitro studies appear to provide data for the decision of G-CSF administration in combination with imatinib in the treatment of neutropenic patients with advanced-stage CML.
Amantadine Resistance among Porcine H1N1, H1N2, and H3N2 Influenza A Viruses Isolated in Germany between 1981 and 2001
Authors: Schmidtke Michaela , Zell Roland , Bauer Katja , Krumbholz Andi , Schrader Christina , Suess Jochen , Wutzler Peter
Published: July 2006

This study was designed to gain insight into amantadine susceptibility of porcine influenza A viruses isolated in Germany between 1981 and 2001. The 12 studied H1N1, H1N2, and H3N2 porcine influenza virus strains were isolated in chicken eggs and passaged once in MDCK cells. Plaque reduction assays were applied to examine virus susceptibility to amantadine. Genotyping was used to confirm drug resistance. In the results of these antiviral studies, only 3 of the 12 isolates were shown to be amantadine-susceptible. All resistant strains contained the AA substitutions G16E, S31N, and R77Q in the membrane protein 2 (M2). Additionally, L27A was detected in two H1N1 strains. S31N and/or L27A are well-known amino acid substitutions in M2 that confer amantadine resistance. The role of the pig as an intermediate host of avian and human influenza A viruses, the possible involvement of genetic reassortment, and the high incidence of naturally amantadine-resistant porcine influenza A viruses suggest a real risk of emergence of amantadine resistant human viruses. Therefore, drug susceptibility monitoring appears to be warranted for effective application of those drugs.
Adolescence: A Critical Period for Long-Term Tracking of Risk for Coronary Heart Disease?
Authors: Ovesen Lars
Published: July 2006

Tracking of dietary and physical activity patterns throughout adolescence into adulthood is low, which indicates that risk patterns for coronary heart disease are not maintained. Biological risk factors for heart disease, particularly obesity and clusters of nutritionally modifiable risk factors (e.g. the metabolic syndrome), display somewhat higher tracking correlations. Tracking gives little guidance as to how to use this information for screening purposes. For behavioral and biological risk factors predictive values and sensitivities and specificities are generally low, suggesting that population-based approaches are likely to be more effective than targeting only the high-risk subset for reducing the risk of coronary heart disease.
Analysis of Retinol Concentrations in Bovine Liver and Its Habitual Consumption by Pregnant Women
Authors: Praxedes de Aquino Rose Cléia , Pereira de Melo Illana Louise , da Silva Lourenço Raquel Maria , Dimenstein Roberto
Published: July 2006

Aims: The objectives of this study were to analyze retinol concentrations in two groups of bovine liver, to estimate the habitual consumption of bovine liver among pregnant women, and, based on these data, to evaluate the women’s ingestion of vitamin A. Method: 60 samples of bovine liver, 30 of the Nelore breed and 30 of undefined breed (UB), were analyzed using the high-performance liquid chromatography (HPLC) method for retinol dosage. 100 women under care at the University Maternity Hospital Januário Cicco, UFRN, in Natal, RN, Brazil, completed the Frequency of Nourishment Questionnaire. Results: The mean ± SD values for the retinol concentrations in the liver samples of the Nelore breed and the UB groups were 16,947.8 ± 6,866.9 and 5,213.1 ± 2,517.2 µg of retinol/100 g, respectively. A high number of women consumed liver (73%) and in 71% of the cases the advice for the consumption of this food was provided by qualified professionals. Conclusion: It is concluded that the daily consumption of the bovine liver is not recommended for pregnant women, regardless of the genetic origin of the animal. The study alert health professionals of the danger of recommending the ingestion of bovine liver during pregnancy.
Differences in Measured and Self-Reported Height and Weight in Dutch Adolescents
Authors: Jansen W. , van de Looij-Jansen P.M. , Ferreira I. , de Wilde E.J. , Brug J.
Published: July 2006

Background/Aims: Monitoring overweight prevalence and its trends in Dutch youth is frequently based on self-reported data. The validity of self-reported data especially in young adolescents is not sufficiently known. The purpose of this study is to study the validity of self-reported height and weight in 12- to 13-year-olds, to identify sociodemographic correlates and to explore whether correction factors can be developed to estimate the prevalence of overweight in youth. Methods: 5,525 12- to 13-year-old pupils in the Rotterdam area filled in a confidential questionnaire on health topics, including their height and weight. In a sub-sample of 499 pupils both self-reported and measured height and weight were available. Results: Self-reported data led to a considerable underestimation of Body Mass Index and consequently the prevalence of overweight. Underestimation was higher in pupils who regarded themselves as more fat, were of non-Dutch origin and in lower education levels. Conclusion: Self-reported height and weight appeared to be inappropriate to estimate the overweight prevalence in 12- to 13-year-olds, unless the figures were adjusted. Using adjusted self-reported BMI on an individual level is questionable. Actual measurements of height and weight are necessary to draw up valid correction formulas in new samples.
Aspects of Protein and Amino Acid Metabolism in a Model of Severe Glutamine Deficiency in Sepsis
Authors: Safranek Roman , Holecek Milan , Sispera Luděk , Muthný Tomáš
Published: July 2006

Background/Aims: Growth hormone (GH) could have the potential to improve protein metabolism in sepsis but glutamine deficiency has been reported after GH treatment. The aim was to investigate the effects of glutamine deficiency in sepsis with and without GH treatment on protein and amino acid metabolism. Methods: Cecal ligation and puncture (CLP) was used as a model of sepsis. Serious glutamine deficiency was induced by administration of glutamine synthetase inhibitor, methionine sulfoximine (MSO). Young Wistar rats were divided into 5 groups: control; CLP; CLP+MSO; CLP+GH, and CLP+MSO+GH. Parameters of protein metabolism were measured on incubated soleus and extensor digitorum longus muscles: [1-14C]leucine was used to estimate protein synthesis and leucine oxidation, tyrosine release was used to evaluate protein breakdown. Amino acid concentrations in plasma, skeletal muscle and incubation media were measured by HPLC. Results/Conclusions: A reduced muscle glutamine concentration after MSO treatment is not associated with changes in the rates of protein synthesis or breakdown. MSO treatment decreased glutamine release from skeletal muscle and plasma glutamine concentration. Severe glutamine deficiency in GH-treated septic rats resulted in increased release of branched-chain amino acids from skeletal muscle.
Serum Retinol, α-Tocopherol, and β-Carotene Levels Are Not Altered by Excess Ingestion of Diacylglycerol-Containing Plant Sterol Esters
Authors: Saito Shinichiro , Tomonobu Kazuichi , Kudo Naoto , Shiiba Daisuke , Hase Tadashi , Tokimitsu Ichiro
Published: July 2006

Background: Diacylglycerol (DAG) suppresses the postprandial increase in serum triglycerides, and has antiobesity effects. On the other hand, plant sterol esters (PSE) lower serum cholesterol levels in hypercholesterolemia. Thus, DAG-containing PSE (PSE/DAG) would be expected to maintain an appropriate serum cholesterol level and decrease the risk of arteriosclerotic disorders. Several recent studies, however, report negative effects of PSE on serum fat-soluble (pro)vitamin levels. The objective of this study was to investigate the effect of PSE/DAG on serum retinol, β-carotene, and α-tocopherol levels using a threefold excess of the effective dose obtained in our previous study. Methods: A randomized placebo-controlled double-blind parallel study was performed in healthy and mildly hypercholesterolemic subjects, in which the subjects ingested 1.2 g PSE/30 g DAG for 2 weeks in the form of mayonnaise-type products. Triacylglycerol (TAG) mayonnaise was used as a control. Result: There were no subjective adverse effects or changes in serum retinol, α-tocopherol, and β-carotene levels, abdominal symptoms, hematologic values, or blood biochemical values. Conclusion: Ingestion of a threefold excess of PSE/DAG for 2 weeks had no adverse effects compared to ingestion of conventional TAG mayonnaise.
Oral Administration of Hot Water Extracts of Chlorella vulgaris Increases Physical Stamina in Mice
Authors: An Hyo-Jin , Choi Hyun-Myung , Park Hyeung-Suk , Han Jae-Gab , Lee Eun-Hee , Park Young-Sig , Um Jae-Young , Hong Seung-Heon , Kim Hyung-Min
Published: July 2006

Background/Aims: A unicellular algae, Chlorella vulgaris, was used as a biological response modifier. Although hot water extracts of C. vulgaris (CVE) are thought to augment immune responses, the effect of CVE on fatigue and physical stamina has not been studied. Methods: In the present study, we investigated the effect of CVE on forced swimming test and blood biochemical parameters related to fatigue, blood urea nitrogen (BUN), creatine kinase (CK), lactic dehydrogenase (LDH), glucose (Glc), and total protein (TP). CVE (0.05–0.15 g/kg/day) was orally administered to mice. Results: After 7 days, the immobility time was decreased in the 0.1- and 0.15-g/kg CVE-treated groups (179 ± 8.3 and 175 ± 2.1 s) in comparison with the control group (223 ± 5.4 s). In addition, the contents of BUN, CK, and LDH in the blood serum were decreased in the CVE-fed group. However, they had no effect on the elevation of Glc and TP level. Conclusions: The results predict a potential benefit of CVE for enhancing immune function and improving physical stamina.
Influence of Daily Consumption of Probiotic and Conventional Yoghurt on the Plasma Lipid Profile in Young Healthy Women
Authors: Fabian Elisabeth , Elmadfa Ibrahim
Published: July 2006

Background: A number of studies have found conflicting results concerning the modulation of plasma lipids induced by probiotics. Therefore, the aim of this study was to verify and compare the effects of probiotic and conventional yoghurt on the plasma lipid profile of normocholesterolemic women. Methods: In this study, female volunteers consumed 100 g/day of probiotic (n = 17) or conventional yoghurt (n = 16) for 2 weeks (T1–T2) and 200 g/day for further 2 weeks (T2–T3). A washout phase lasting 2 weeks followed (T4). Total and HDL cholesterol and triglycerides were determined by enzymatic methods; LDL cholesterol was calculated using the Friedewald formula. Results: The average concentration of total cholesterol was consistent throughout the whole study in the control group, but decreased significantly (p < 0.01) in the probiotic group consuming 200 g yoghurt/day (T2–T3). During the period of daily yoghurt intake (T1–T3) the mean HDL cholesterol level increased significantly (p < 0.05) in the probiotic group, resulting in a significant (p < 0.05) improvement of the total/HDL cholesterol ratio. The significant (p < 0.01) reduction of the average plasma LDL cholesterol values found in this period (T1–T3) in the probiotic and the control groups was associated with a significant (p < 0.05) improvement of the LDL/HDL cholesterol ratios in both tested groups. Conclusion: Although several lipid parameters changed during the study in both the probiotic and the control group, no significant differences between the groups were observed. Therefore, it can be concluded that the regular consumption of both probiotic and conventional yoghurt for 4 weeks had a positive effect on the lipid profile in plasma of healthy women.
Psychometric Evaluation of the Brief Cancer Impact Assessment among Breast Cancer Survivors
Authors: Alfano Catherine M. , McGregor Bonnie A. , Kuniyuki Alan , Reeve Bryce B. , Bowen Deborah J. , Wilder Smith Ashley , Baumgartner Kathy B. , Bernstein Leslie , Ballard-Barbash Rachel , Malone Kathleen E. , Ganz Patricia A. , McTiernan Anne
Published: July 2006

Objectives: The increasing number of cancer survivors brings greater attention to the biopsychosocial impact of surviving cancer. Instruments exist that measure quality of life (QOL), symptoms, and specific types of functioning after cancer; however, a reliable and valid assessment of the perceived impact of cancer (IOC) on the life plans and activities of cancer survivors has been missing. This study evaluated the psychometric properties of the 16-item Brief Cancer Impact Assessment (BCIA). Methods: Factor analysis with Promax oblique rotation established the factor structure of the BCIA in 783 ethnically diverse breast cancer survivors, ≧2 years after diagnosis. Construct validity was assessed by comparing factor-based scale means by demographic and treatment characteristics, and correlating scales with psychosocial and health-related QOL scales. Results: Factor analysis revealed four factors measuring the IOC on caregiving and finances, exercise and diet behaviors, social and emotional functioning, and religiosity. Scale scores differed by demographic and treatment characteristics according to expectations, and the pattern of correlations with psychosocial and health-related QOL generally supported the construct validity of the scales. Conclusion: Including the BCIA with measures of QOL, symptoms, and functioning will allow researchers to gain a more comprehensive assessment of the biopsychosocial IOC in survivors.
Combined Detection of CEA, CK-19 and c-met mRNAs in Peripheral Blood: A Highly Sensitive Panel for Potential Molecular Diagnosis of Non-Small Cell Lung Cancer
Authors: Sheu Chau-Chyun , Chang Mei-Yin , Chang Huang-Chou , Tsai Jong-Rung , Lin Shiu-Ru , Chang Shun-Jen , Hwang Jhi-Jhu , Huang Ming-Shyan , Chong Inn-Wen
Published: July 2006

Objective: Detection of tumor-related mRNA in blood has become a potential cancer diagnostic approach. However, the sensitivity of single-marker assays is not high enough for clinical applications. The present study was aimed to evaluate the efficacy of a multimarker panel for molecular diagnosis of non-small cell lung cancer (NSCLC). Methods: Carcinoembryonic antigen (CEA), cytokeratin 19 (CK-19), c-met and heterogeneous nuclear ribonucleoprotein (hnRNP) B1 mRNAs were quantified by quantitative real-time reverse transcriptase polymerase chain reaction in 34 tumor tissues and 69 peripheral blood samples of NSCLC patients. Results: All four markers displayed high overexpression rates (range 82.3–97.1%) in NSCLC tumors. When used as single markers in blood for NSCLC diagnosis, CEA, CK-19, c-met and hnRNP B1 could only reach sensitivities of 52.2, 50.7, 42 and 17.4%, respectively. However, the sensitivity was enhanced up to 85.5% when CEA, CK-19 and c-met were combined in a 3-marker panel. Moreover, the expression of c-met and hnRNP B1 in blood was significantly correlated with patients’ pathological stages. Conclusions:The combined detection of CEA, CK-19 and c-met mRNAs in blood provided a valuable tool for molecular diagnosis of NSCLC. In addition, our results also suggested that hnRNP B1 was not a valuable diagnostic marker but a potential prognostic marker for NSCLC.
Glucagon-Like Peptide-1 Is Involved in Sodium and Water Homeostasis in Humans
Authors: Gutzwiller Jean-Pierre , Hruz Petr , Huber Andreas R. , Hamel Christian , Zehnder Carlos , Drewe Juergen , Gutmann Heike , Stanga Zeno , Vogel Daniel , Beglinger Christoph
Published: July 2006

In previous studies with glucagon-like peptide-1 (GLP-1) we have observed that this peptide modulates fluid intake and increases renal sodium excretion in healthy volunteers and in patients with diabetes mellitus type 2. The effect of GLP-1 on thirst, water intake and on osmoregulation has, however, not been examined in detail in humans. Methods: Seventeen healthy male subjects were enrolled in two double-blind, placebo-controlled studies. In study part A, 8 volunteers participated in a protocol with an intravenous salt load of 26.7 ± 0.9 g comparing the effect of an infusion of GLP-1 (1.5 pmol/kg × min) to isotonic saline (placebo). Sodium excretion and water intake were measured. In part B, 9 volunteers were challenged with an oral salt load of 27.7 ± 0.5 g; sodium excretion and water intake were determined comparing an infusion of GLP-1 (1.5 pmol/kg × min) to isotonic saline (placebo). In part C, intestinal biopsies along the gastrointestinal tract were obtained from 14 healthy subjects. Expression of human GLP-1 receptor mRNA was measured by real-time polymerase chain reaction. Results: In study part A, an increase in renal sodium excretion was demonstrated: FeNa rose from 1.6 ± 0.3 (placebo) to 2.7 ± 0.2% (GLP-1; p = 0.0005). There was no difference in water consumption between the two treatments: 1,291 ± 69 (saline) vs. 1,228 ± 74 ml (GLP-1; p = 0.49). In part B, an oral salt challenge of 27.7 ± 0.5 g led to an increased renal excretion of sodium during GLP-1: FeNa increased from 1.6 ± 0.2% (placebo) to 2.0 ± 0.2% (GLP-1; p = 0.012). In contrast to part A, oral water intake was reduced by 36% under GLP-1 treatment: 1,848 ± 331 ml (placebo) vs. 1,181 ± 177 ml (GLP-1; p = 0.0414). Three subjects in part B did not finish treatment with GLP-1 because of diarrhea. Human GLP-1 receptor mRNA expression was highest in the proximal human small intestine compared to terminal ileum and colon (p < 0.02). Conclusions: GLP-1 acts on renal tissue reducing sodium absorption, probably via similar sodium transporters, which also may be localized in the gastrointestinal tract. This hypothesis needs to be confirmed by further studies.
Non-Transferrin-Bound Iron Is Associated with Enhanced Staphylococcus aureus Growth in Hemodialysis Patients Receiving Intravenous Iron Sucrose
Authors: Barton Pai Amy , Pai Manjunath P. , Depczynski Joseph , McQuade Charles R. , Mercier Renee-Claude
Published: July 2006

Background: Hemodialysis vascular access infections are most frequently caused by Staphylococcus spp. The purpose of this study was to determine if S. aureus growth is enhanced after administration of IV iron sucrose and to establish a relationship between the appearance of non-transferrin-bound iron (NTBI) and S. aureus growth. Methods: Serum samples were obtained from 12 hemodialysis patients receiving maintenance doses of 100 mg of iron sucrose at baseline and 5, 30, 90, 220 min and 48 h after iron administration. Assays for NTBI and transferrin saturation were performed. S. aureus isolates were used to inoculate patient serum samples. Bacterial growth was determined by optical density. Results: Six of 12 patients had NTBI present within 30 min of the iron dose. NTBI was present more frequently in patients with baseline transferrin saturation values >30% (p < 0.05). Bacterial growth was significantly greater in patients who had NTBI present at 5, 90 and 220 min after iron administration compared to those who did not have NTBI present. Conclusions: Doses of 100 mg of iron sucrose are associated with the presence of NTBI and enhanced S. aureus growth.
Effect of Chronic Renal Failure on Arginase and Argininosuccinate Synthetase Expression
Authors: Moradi Hamid , Kwok Vincent , Vaziri Nosratola D.
Published: July 2006

Background:L-arginine (L-arg) participates in numerous biological functions including urea and nitric oxide synthesis. Sources of L-arg include dietary proteins and endogenous synthesis by argininosuccinate synthetase and argininosuccinate lyase. L-arg is converted to urea by arginase I in the liver and arginase II in the kidney. Normally, the liver fully consumes L-arg for urea generation and does not contribute to its circulating pool. Instead, much of the circulating L-arg is produced by the kidney. If true, plasma L-arg should be severely reduced in chronic renal failure (CRF); however, plasma L-arg is frequently unchanged in CRF. We hypothesized that preservation of plasma L-arg in CRF may be, partly, due to downregulation/inhibition of arginase. Methods: Argininosuccinate synthetase, arginase I and II protein abundance and activity were measured in the liver and kidneys of rats 6 weeks after 5/6 nephrectomy or sham operation. In addition, arginase activity was measured in the presence of different urea concentrations to simulate azotemia in vitro. Results: Arginases I and II protein abundance as well as arginase activity in the liver, measured in the physiological buffer, were similar among the CRF and control groups. However, in vitro experiments simulating a uremic milieu revealed a marked concentration-dependent inhibition of arginase activity by urea in the tissue lysates. CRF had no significant effect on argininosuccinate synthetase abundance in the kidney, liver, spleen or intestine. Conclusions: Although CRF does not change the abundance or intrinsic properties of arginase, the inherent rise in urea concentration inhibits its enzymatic activity. The latter, in turn, attenuates L-arg catabolism and urea production and, thereby, mitigates the fall in plasma L-arg.
Nutritional Support after Open Liver Resection: A Systematic Review
Authors: Richter B. , Schmandra T.C. , Golling M. , Bechstein W.O.
Published: July 2006

Background: Perioperative nutrition in patients with limited liver function after partial hepatic resection is still controversial. In particular, the significance of perioperative total enteral nutrition remains unresolved. The aim of this review is to investigate the impact of early postoperative total enteral nutrition on convalescence after partial liver resection. Materials and Methods: In an internet-based Medline-Search (time course: 1960–08/2005) a total of five prospective, randomized controlled trials were found comparing the impact of enteral and parenteral nutrition after liver resection. After study validity had been established, a systematic review was undertaken (odds ratio, 95% confidence interval, p < 0.05 level of significance; Review Manager 4.2®, The Cochrane Collaboration). Primary endpoints were complication rate (infection, organ malfunction) and mortality. Standardized immune parameters were also surveyed. Results: Statistical analysis showed that enteral nutrition resulted in a significantly lower rate (p = 0.04) of wound infection and catheter-related complications than parenteral nutrition did. No statistically significant differences in mortality due to enteral or parenteral nutrition could be found. Patients receiving enteral nutrition showed better postoperative immune competence. Conclusion: Early enteral nutrition after liver resection is a safe procedure. Compared to parenteral nutrition it is associated with a decreased incidence of postoperative complications. Facing the inhomogeneity of these trials, especially in nutrition protocols and end points, this first systematic review stresses the need for an update of the importance of early enteral nutrition after liver resection within randomized controlled multicenter trials.
Delayed Closure of Complex Duodenal Injuries by a Foley Balloon Catheter Duodenostomy
Authors: van Ginhoven T. , Schepers T. , Obertop H. , van Eijck C.H.J.
Published: July 2006

Less than 5% of abdominal injuries comprise the duodenum. Treatment is complex with high mortality and morbidity rates. These injuries are usually treated surgically and complications frequently occur. Three cases are presented in this communication in which the injury of the duodenum could not be repaired tension-free. In these cases a Foley balloon catheter was used to close the rupture. After a few weeks, patients were fed through the Foley catheter duodenostomy until a fistular track was formed. On removal of the catheter the fistular track closed spontaneously including the perforation of the duodenum.
Randomised Trial Comparing Three Different Schedules of Infusional 5FU and Raltitrexed Alone as First-Line Therapy in Metastatic Colorectal Cancer
Authors: Ducreux M. , Bouche O. , Pignon J.P. , Mousseau M. , Raoul J.L. , Cassan P. , Leduc B. , Berger C. , Dunant A. , Fournet J. , Bedenne L.
Published: July 2006

LV5FU2 with high-dose leucovorin (LV), weekly infusional 5-fluorouracil (5FU) (AIO schedule) and raltitrexed have been demonstrated to be active agents in first-line treatment of colorectal cancer. We performed a 4-arm randomised trial to compare (1) a low-dose intravenous bolus of LV (20 mg/m2), followed by an intravenous bolus of 5FU (400 mg/m2), followed by a 22-hour continuous infusion of 5FU (600 mg/m2) on day 1 and day 2/2 weeks (ldLV5FU2 arm), (2) a weekly continuous infusion of high-dose 5FU (2.6 g/m2/week) for 6 weeks followed by a rest week (HD-FU arm) and (3) raltitrexed (Tomudex® arm; 3 mg/m2/3 weeks) to standard LV5FU2. From 1997 to 2001, 294 patients were included. The 4 arms were well balanced for sex ratio, age, WHO performance status, the primary tumour site and prior adjuvant chemotherapy. Treatment was stopped due to low accrual. Two toxicity-related deaths were observed in the Tomudex arm. The treatments gave rise to different rates of grade 3–4 neutropenia (3, 4, 11 and 14% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively, p = 0.028), leucopenia and vomiting. At least one episode of grade 3–4 toxicity was observed in 27, 25, 38 and 47% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively (p = 0.016). An objective response was observed in 28, 21, 22 and 10% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively (p = 0.04). Progression-free survival (PFS) of the patients in the Tomudex arm was statistically lower compared to that of patients treated with LV5FU2 or ldLV5FU2 (combined group; p = 0.013, log rank test). In conclusion, Tomudex is more toxic and yields shorter PFS than infusional 5FU. Despite the early closure of the study and the lack of power of the comparison, it seems that ldLV5FU2 could be considered as an active, easier and less expensive option for the treatment of metastatic colorectal cancer compared to classic LV5FU2 or weekly HD-FU.