bluuebunny/crossref_metadata_2025 huggingface dataset:
Fusarium head blight resistance derived from Lophopyrum elongatum chromosome 7E and its augmentation with Fhb1 in wheat
Authors: Shen X. , Ohm H.
Published: September 2006

The objective of this study was to assess the effectiveness of Fusarium head blight (FHB) resistance derived from wheatgrass Lophopyrum elongatum chromosome 7E and to determine whether this resistance can augment resistance in combination with other FHB resistance quantitative trait loci (QTL) or genes in wheat. The ‘Chinese Spring’–Lophopyrum elongatum disomic substitution line 7E(7B) was crossed to three wheat lines: ‘Ning 7840’, L3, and L4. F2 populations were evaluated for type II resistance with the single‐floret inoculation method in the greenhouse. Simple sequence repeat markers associated with Fhb1 in ‘Ning 7840’ and L4 and markers located on chromosome 7E were genotyped in each population. Marker–trait association was analysed with one‐way or two‐way analysis of variance. The research showed that, in the three populations, the average number of diseased spikelets (NDS) in plants with chromosome 7E is 1.2, 3.1 and 3.2, vs. NDS of 3.3, 7.2 and 9.1 in plants without 7E, a reduction in NDS of 2.1, 4.1 and 5.9 in the respective populations. The QTL on 7E and the Fhb1 gene augment disease resistance when combined. The effect of the QTL on 7E was greater than that on 3BS in this experiment. Data also suggest that the FHB resistance gene derived from L. elongatum is located on the long arm of 7E.
Use of cDNA‐AFLP for transcript profiling in narrow genetic pools; for example, cucumber (Cucumis sativusL.)
Authors: Bae K. M. , Kwon Y. S. , Cho I. H. , Yi S. I.
Published: September 2006

A cDNA‐AFLP transcript profiling was employed to examine three representative tissues (seedling, ovary and leaf) of nine Korean cucumber (Cucumis sativusL.) F1hybrids. Differential accumulation of transcript‐derived fragments (TDFs) was detected in 92 profiles. Genetic distance‐based cluster analysis partitioned these hybrids into four main groupings, consistent with their phenotypic relationships. Although several polymorphic profiles were confirmed by reverse transcriptase polymerase chain reaction (RT‐PCR) analysis, many were not reproducible, indicating that a large portion of the observed polymorphisms were based on sequence variation of transcripts rather than expression of variation. Thus, it is proposed that cDNA‐AFLP profiling be based on a dual descriptor system (sequence and expression). Data indicate that such a system would provide an efficient genetic marker system for identifying polymorphisms in narrow genetic pools.
Anther culture response of F1 durum × bread wheat hybrids after colchicine application
Authors: Tersi M. , Xynias I. N. , Gouli‐Vavdinoudi E. , Roupakias D. G.
Published: September 2006

The effect of colchicine on the androgenic response of durum × bread wheat F1 hybrids was studied. For this, three Greek durum wheat cultivars, exhibiting good yield and pasta quality, were crossed to two bread wheat cultivars with good response to anther culture. Spikes of the resulting hybrids, containing microspores in the mid to late uninucleate stage, were selected and cultured on two different media (W14 and solid potato‐2) with and without colchicine. A negative effect on anther culture response was observed when colchicine was added to the W14 induction medium. A similar effect was observed in two of the hybrids when they were cultured on to potato‐2 induction medium. In both induction media, green plant production was influenced negatively by colchicine treatment. The same was observed in albino plant production. The results of the present study support the view that anther culture response is strongly genotype dependent. Finally, potato‐2 induction medium was the most suitable one for the material studied.
Microbial colonization of nebulizers used by asthmatic children
Authors: COHEN HERMAN A , KAHAN ERNESTO , COHEN ZEEV , SARRELL MICHAEL , BENI SARA , GROSMAN ZAHI , ASHKENAZI SHAI
Published: September 2006

Background: The aim of the present study was to determine the microbial colonization of nebulizers used at home by asthmatic children, and to investigate their parents’ cleaning and maintenance routines.

Methods: The nebulizer equipment used at home by 39 asthmatic children was examined. Swabs taken from the inner surface of the reservoir cups, face masks and filters were cultured. Results were recorded as mean number of colony‐forming units per cultured surface. Parents were interviewed regarding their cleaning and disinfection routines.

Results: Twenty‐six reservoir cups (66.7%), 24 face masks (61.5%), and 18 filters (78.3%) were found to be contaminated. Pseudomonas aeruginosa was isolated from 17 reservoir cups (43.6%) and 12 face masks (30.8%), and Staphylococcus aureus from two face masks (5.1%). None of the parents knew that the nebulizer has a filter and that it requires periodic cleaning or changing; only eight of the parents (20.5%) received maintenance instructions from the medical staff, and only 19 (48.7%) cleaned the nebulizer equipment after use.

Conclusion: Home nebulizers are frequently colonized with microorganisms. As recommended, nebulizers should be washed after each use and air‐blown dry. Nebulizer maintenance should be emphasized in educational programs for managing asthma.
Determinants of birthweight inequalities: Population‐based study
Authors: DUBOIS LISE , GIRARD MANON
Published: September 2006

Background: The aim of this paper is to study the whole spectrum of birthweight in a population‐based birth cohort in order to document the role played by social factors, which complement physiological and behavioural factors, in the development of birthweight inequalities at the population level.

Methods: The analyses were performed with data from the ‘Quebec Longitudinal Study of Child Development 1998–2002 (QLSCD)’. The study follows a representative sample (n = 2103) of the children born in 1998 in the Canadian province of Québec.

Results: Multivariate analyses adjusted for gestational age and mother’s age indicate that mean birthweight was higher for boys than girls; improved with birth rank, mother’s body mass index (BMI), and family socioeconomic status; and was lower for children of smoking mothers. Compared with children born to non‐smoking mothers of higher socioeconomic status, the odds of having a low birthweight were between 6 and 12 times higher for children born to smoking mothers of lower or middle socioeconomic status. When maternal smoking status and mother’s BMI are combined, socioeconomic status could still be seen to have a positive effect on mean birthweight except for overweight or obese smoking mothers, among whom the relationship between socioeconomic status and mean birthweight was reversed. In families of lower socioeconomic status, maternal smoking was the most important factor in birthweight inequalities, and in families of higher socioeconomic status, mother’s BMI was the most important factor in birthweight inequalities.

Conclusion: This research is not only important for children in developed nations, but also for those in developing countries, where high birthweight and obesity are becoming more prevalent.
Lipid peroxidation in cord blood and neonatal outcome
Authors: WEINBERGER BARRY , NISAR SALMAN , ANWAR MUJAHID , OSTFELD BARBARA , HEGYI THOMAS
Published: September 2006

Background: Periventricular–intraventricular hemorrhage, necrotizing enterocolitis, chronic lung disease and retinopathy of prematurity have been referred to as oxygen radical diseases (ORD) because they are thought to be related to excess oxidant stress relative to anti‐oxidant defenses in premature infants. 8‐Isoprostane is a product of lipid peroxidation that can be used as a measure of free radical exposure or injury. The aim of the present study was to determine whether fetal oxidant stress is associated with adverse effects in preterm infants.

Methods: Mothers delivering at gestational age <37 weeks were recruited. Umbilical arterial and venous cord blood samples were collected and 8‐isoprostane levels measured. Levels of 8‐isoprostane in cord blood were correlated with maternal and perinatal variables, neonatal mortality, and the development of one or more ORD.

Results: Umbilical cord venous, but not arterial, 8‐isoprostane levels were associated with mortality and the development of one or more of the ORD. After controlling for gestational age, for each unit change in the log value of 8‐isoprostane in venous cord blood the odds of mortality were 12 (95% confidence interval [CI]: 1–223) and oxygen radical disease were 2.7 (95%CI: 1–7.2). Isoprostane levels were not related to gender, method of delivery, use of maternal magnesium or steroids, pregnancy‐induced hypertension, or delivery room resuscitation.

Conclusion: Oxidant stress in utero may be an important determinant of mortality and morbidity in preterm infants. Elevated umbilical venous isoprostane levels suggest that oxidative injury to maternal and placental tissues predispose to adverse neonatal outcomes.
Assessing the ecology in ecotoxicology: a review and synthesis in freshwater systems
Authors: Relyea Rick , Hoverman Jason
Published: September 2006

The field of ecotoxicology is experiencing a surge in attention among ecologists as we gain a deeper appreciation for how contaminants can impact natural ecosystems. This interest is particularly strong in aquatic systems where many non‐target organisms experience pesticides. In this article, we assess how pesticides affect freshwater systems by applying the conceptual framework of density‐ and trait‐mediated indirect effects from the field of basic ecology. We demonstrate the utility of this framework for understanding the conditions under which pesticides affect species interactions, communities and ecosystems. Through the integration of laboratory toxicity tests and this ecological framework, ecotoxicologists should be better able to identify the mechanisms through which pesticides affect communities and ecosystems. We also identify several areas of research that are in critical need of empirical attention including synergistic effects between pesticides and natural stressors, the importance of pesticides on community assembly via habitat preferences and oviposition effects, the timing and frequency of pesticide applications, pesticide effects on population dynamics, the evolution of pesticide resistance in non‐target organisms and ecosystem recovery. With this knowledge, one can improve upon management decisions and help protect non‐target species that are of conservation concern.
The ecology of virulence
Authors: Lively Curtis M.
Published: September 2006

Theoretical work has shown that parasites should evolve intermediate levels of virulence. Less attention has been given to the ecology of virulence. Here I explore population‐dynamic models of infection in an annual host. The infection does not kill the host; but it can decrease the number of offspring produced by the host, and the magnitude of this effect depends on host population size. Hence, ‘virulence’ is density dependent, and is defined here as the difference in birth rates between uninfected and infected hosts, divided by the birth rate of uninfected hosts. The results suggest that infection can be highly virulent at the host's equilibrium density, even though the parasite has no effect on the host's intrinsic birth rate. The results also suggest that parasites may help to stabilize host population dynamics. In general, the impact of infection may be underestimated in natural populations.
Tumour‐associated angiogenesis in human colorectal cancer
Authors: Rmali K. A. , Puntis M. C. A. , Jiang W. G.
Published: September 2006

Tumour angiogenesis is a critical step in the growth, metastatic spread and regrowth of colorectal cancer. Angiogenesis specific to tumour is a complicated process, the mechanisms of which remain unclear. Metastasis of colorectal cancer may result from passive entry into the circulation secondary to the effect of angiogenic factors. The survival and growth of colorectal tumour and thus their metastases are dependent on the balance of endogenous angiogenic and anti‐angiogenic factors such that the outcome favours increased angiogenesis. Angiogenesis has become an attractive target for anticancer drug development, based on its important roles in tumour growth, invasion and metastasis. Several growth factors have been identified that regulate angiogenesis in colorectal cancer; the most important of these are vascular endothelial growth factors (VEGF), and of the several angiogenic factors, VEGF expression at the deepest invasive site of tumour is the most statistically significant prognostic indicator in advanced colorectal carcinoma. In this review article, we provide an overview on angiogenic factors and their receptors, and discuss the role of newly identified tumour endothelial markers (TEMs) that are involved in tumour‐associated angiogenesis in colorectal cancer.
Influence of caseload and surgical speciality on outcome following surgery for colorectal cancer: a review of evidence Part 2: Long‐term outcome
Authors: Iversen L. H. , Harling H. , Laurberg S. , Wille‐Jørgensen P. ,   the Danish Colorectal Cancer Group
Published: September 2006

Objective  We reviewed recent literature to assess the impact of hospital caseload, surgeon's caseload and education on long‐term outcome following colorectal cancer surgery.

Method  We searched the MEDLINE and Cochrane Library databases for relevant literature starting from 1992. We selected hospital caseload, surgeon's caseload and surgeon's education, type of hospital, and surgeon's experience as variables of interest. Measures of outcome were recurrence‐free survival and overall survival, and for rectal cancer frequency of permanent stoma. We reviewed the 34 studies according to tumour location: colonic cancer, rectal cancer, or colorectal cancer. We described the studies individually and performed a meta‐analysis whenever it was considered appropriate.

Results  For colonic cancer, overall survival improved with increasing hospital caseload, odds ratio (OR) 1.22 [95% confidence interval (CI) 1.16–1.28], and surgeon's education. For rectal cancer, overall survival improved with increasing hospital caseload, OR 1.38 (95% CI 1.19–1.60), and, possibly by surgeon’ education and experience. Cancer‐free survival was strongly influenced by surgeon's education. The colostomy rate was less in high caseload hospitals, OR 0.76 (95% CI 0.68–0.85). For colorectal cancer, overall survival improved with surgeon's education.

Conclusion  The data have provided evidence that long‐term survival following colorectal cancer surgery in general improved significantly with increasing hospital caseload and surgeon's education.
Minor gene effect of leptin receptor variant on the body weight in KK/Ta mice
Authors: Gohda T. , Tanimoto M. , Kaneko S. , Shibata T. , Funabiki K. , Horikoshi S. , Tomino Y.
Published: September 2006

Objective:  Leptin is an adipocyte‐derived hormone involved in body weight regulation that acts through the leptin receptor. Previous studies exploring potential association between the leptin receptor (Lepr) variant and obesity have reported conflicting results. The objectives of the present study are to evaluate (1) whether the Lepr variant contributes to type 2 diabetes and its related disorders such as obesity and (2) whether the gene interaction between Lepr and Zn‐α2 glycoprotein1 (Azgp1) genes is recognized using genetically homogeneous type 2 diabetic KK/Ta mice.

Methods:  The levels of leptin (Lep) and Lepr mRNA in adipose tissues and brain were measured by relative quantitative RT‐PCR. The levels of leptin protein in sera were measured by enzyme‐linked immunosorbent assay. Genotyping of backcross mice was performed using a mismatch primer.

Results:  Leptin protein and its mRNA levels were increased in KK/Ta mice. Lepr mRNA levels of KK/Ta mice did not differ from those of BALB/c mice. Sequence analysis revealed that the coding region of Lep in KK/Ta mice was identical to that in BALB/c mice. Six nucleotide polymorphisms were observed in the coding region of Lepr. In KK/Ta × (BALB/c × KK/Ta) F1 backcross mice, the Lepr variant of KK/Ta mice failed to alter any of the variables of obesity except for body weight at 20 weeks of age. However, it enhanced the effect of Azgp1 on body weight.

Conclusion:  It is concluded that the Lepr variant contributes to obesity to some degree in KK/Ta mice.
Insulin sensitivity during oral glucose tolerance test and its relations to parameters of glucose metabolism and endothelial function in type 2 diabetic subjects under metformin and thiazolidinedione
Authors: Kautzky‐Willer A. , Tura A. , Winzer C. , Wagner O. F. , Ludvik B. , Hanusch‐Enserer U. , Prager R. , Pacini G.
Published: September 2006

Aim:  This study was designed to assess the usefulness of a model‐based index of insulin sensitivity during an oral glucose tolerance test (OGTT) in the identification of possible changes in this metabolic parameter produced by pharmacological agents known to be potent insulin sensitizers, that is metformin (M) and thiazolidinedione (T). The association of these agents with several other factors related to glucose metabolism was also investigated, as well as the relation of insulin sensitivity and secretion with markers of endothelial function such as different adhesion molecules (cAMs), that is vascular cell adhesion molecule‐1, intercellular adhesion molecule‐1 and E‐Selectin.

Methods:  Twenty type 2 diabetic patients treated with diet only underwent a 3‐h OGTT for measurement of plasma glucose, insulin, proinsulin, C‐peptide and cAMs before and after administration of randomly given M (n = 9; 1700 mg/day) or T (n = 11; 600 mg/day). After 16 weeks of treatment, a second OGTT was performed. Insulin sensitivity was calculated with homeostasis model assessment and with oral glucose insulin sensitivity (OGIS), which quantifies dynamic glucose clearance per unit change of insulin. Insulin secretion was assessed by modelling technique. Differences in these parameters before and after treatment, as well as possible relationships with cAMs, were assessed.

Results:  Basal and stimulated plasma glucose decreased after therapy in both the groups by approximately 20%. Basal insulin resistance also decreased. Insulin sensitivity in dynamic conditions (OGIS: ml/min/m2) increased with M (289.3 ± 18.8 vs. 234.7 ± 18.1, p < 0.02) and tended to improve with T (323.5 ± 18.1 vs. 286.8 ± 22.1, p = 0.09). Total insulin secretion over the OGTT [TIS: nmol/l(3 h)] tended to decrease with M (17.1 ± 2.5 vs. 27.3 ± 0.3, p = 0.08) but not with T (23.6 ± 3.5 vs. 22.5 ± 2.7). Plasma concentrations of E‐Selectin decreased in T (38.0 ± 2.3 vs. 51.2 ± 6.1 ng/ml, p < 0.05). No correlation was found between insulin sensitivity and cAMs.

Conclusions:  Model‐based indices of insulin sensitivity and secretion during an OGTT can be able to detect changes observed in patients under treatment with pharmacological agents such as M or T. Both the drugs improved glucose control similarly. Decreased plasma E‐Selectin concentrations were seen in patients on T therapy only.
Personality Reflected in a Coherent Idiosyncratic Interplay of Intra‐ and Interpersonal Self‐Regulatory Processes
Authors: Morf Carolyn C.
Published: September 2006

ABSTRACT
This article discusses a framework that conceptualizes personality in terms of a unique pattern of interacting intra‐ and interpersonal self‐regulatory mechanisms employed in the service of constructing and maintaining a desired self. These personal goals motivate the individuals' self‐construction efforts and give direction, organization, and coherence to the self‐regulatory dynamics—both within the person and in the social world in which they play out. The framework is illustrated through research on construct validation of the narcissistic personality type and extended by brief applications to dependency and rejection sensitivity to show how it may help us understand the complex signatures that are the expressions of a personality type. It offers a guide for where to look for and how to organize the unique features and idiosyncratic dynamics of different self‐construction types and to make sense of their otherwise often seemingly paradoxical expressions. In so doing, the framework speaks to basic goals of personality psychology by providing an approach for capturing trait‐like individual differences while simultaneously shedding light on the psychological mechanism that underlies them.
Children's Conscience and Self‐Regulation
Authors: Kochanska Grazyna , Aksan Nazan
Published: September 2006

ABSTRACT
We focus on children's conscience, an inner guiding system responsible for the gradual emergence and maintenance of self‐regulation. Drawing from our research program that has encompassed three large longitudinal studies cumulatively covering the first 6 years of life, we discuss two major components of conscience: moral emotions (guilt, discomfort following transgressions) and moral conduct compatible with rules and standards. We discuss the organization of young children's conscience, focusing on relations between moral emotions and moral conduct, and the development of conscience, focusing on its early form: the child's eager, willing stance toward parental socialization. We also review research on two major sets of influences that predict individual differences in moral emotions and moral conduct: biologically based temperament and socialization in the family. We discuss two inhibitory systems of temperament—fearfulness and effortful control—and several features of socialization, including the style of parental discipline and the quality of the parent‐child relationship. Early conscience is an important early personality system, coherently organized, relatively stable over time, and subject to individual differences that emerge as a result of a complex interplay between children's temperamental individuality and socialization in the family.
The Development of Children's Ideal and Ought Self‐Guides: Parenting, Temperament, and Individual Differences in Guide Strength
Authors: Manian Nanmathi , Papadakis Alison A. , Strauman Timothy J. , Essex Marilyn J.
Published: September 2006

ABSTRACT
Regulatory focus theory (RFT; Higgins, 1997) predicts that individual differences in the strength of promotion (ideal) and prevention (ought) orientations emerge from patterns of parent/child interactions that emphasize making good things happen versus keeping bad things from happening. This article examines the development of individual differences in the strength of children's promotion and prevention goals and presents selected findings from three studies exploring the origins of regulatory focus. We found a three‐factor structure for parenting behaviors that differentiated between the presence/absence of positive outcomes versus the presence/absence of negative outcomes in two different data sets and validated that factor structure by examining its associations with maternal temperament. In turn, the parenting factors predicted individual differences in children's orientations to ideal and ought guides, and those associations were moderated by individual differences in child temperament.
Strength and Safety in Numbers: Considering the Social Implications of Regulatory Focus
Authors: Brazy Paige C. , Shah James Y.
Published: September 2006

ABSTRACT
The present article examines how individual and situational differences in individuals' regulatory focus on nurturance and gain (promotion) and on security and safety (prevention) may have significant, and distinct, social and interpersonal implications. We first review recent research examining how significant others affect goal pursuit and how individual differences in regulatory focus may moderate the various behavioral, evaluative, and experiential manifestations of social identification. We then consider how regulatory focus moderates the way in which people “size up” their social world in terms of the efficiency in which they identify and appraise motivationally relevant aspects of their social environment. Finally, we explore how regulatory focus moderates people's deliberate and automatic reactions to the beliefs, expectations, behavior, and emotions of other individuals and social groups.
Dynamic Prediction by Landmarking in Event History Analysis
Authors: VAN HOUWELINGEN HANS C.
Published: September 2006

Abstract.  This article advocates the landmarking approach that dynamically adjusts predictive models for survival data during the follow up. This updating is achieved by directly fitting models for the individuals still at risk at the landmark point. Using this approach, simple proportional hazards models are able to catch the development over time for models with time‐varying effects of covariates or data with time‐dependent covariates (biomarkers). To smooth the effect of the landmarking, sequences of models are considered with parametric effects of the landmark time point and fitted by maximizing appropriate pseudo log‐likelihoods that extend the partial log‐likelihood to cover the landmarking approach.
The Determinants of Contract Length in Temporary Help Employment
Authors: Nannicini Tommaso
Published: September 2006

Abstract.  This paper investigates the determinants of labor contract duration in the case of temporary help employment. A simple theoretical model is developed, in order to depict the choice of contract length made by a firm that recruits temporary agency workers to deal with activity peaks. Assuming that the hiring of a new worker is associated with selection and training costs, longer contracts have an option value in face of a greater persistence of positive shocks. The model has two testable implications. First, the degree of serial correlation in market demand positively affects contract length. Second, the shortage of alternative employment opportunities negatively affects contract length. Using data on Italian temporary agency workers, both implications are confirmed by the econometric analysis.
MATHESIS AND ANALYSIS: FINITUDE AND THE INFINITE IN THE MONADOLOGY OF LEIBNIZ
Authors: LUCHTE JAMES
Published: September 2006

There is an infinity of figures and of movements, present and past, which enter into the efficient cause of my present writing, and in its final cause, there are an infinity of slight tendencies and dispositions of my soul, present and past.1
THE LIGHTNING AND THE EARTHQUAKE: KIERKEGAARD ON THE ANFECHTUNG OF LUTHER
Authors: PODMORE SIMON D.
Published: September 2006

By focusing discussion through Søren Kierkegaard's view of Martin Luther's initiation into the monastery (the lightning strike), it is suggested that an analogy can be discerned for Kierkegaard's own sense of divine vocation (the portentous ‘earthquake’ which he makes enigmatic reference to) and the ensuing self‐mortification of melancholy and religious scrupulosity which commentators have suspected in both figures. Kierkegaard's often ambivalent critique of Luther's Anfechtung is thus read as bearing ironic significance for his own struggles with ‘spiritual trial’ [Anfægtelse]. In this reading, Luther's Anfechtung is taken to signify for Kierkegaard both the anguish inherent to the authentic God‐relationship and also the dangerous possibility of the individual imagination's [Phantasi] capitulation into the precariously embellished realm of ‘the fantastic’ [Phantastiske]. It is here that Kierkegaard's emphasis upon individual responsibility – contrasted with Luther's concentration upon the role of the devil – demonstrates the fundamental differentiation between Kierkegaard's anatomy of Anfægtelse and Luther's Anfechtung.
Blockade of noradrenaline transport abolishes 4‐methylthioamphetamine‐induced contraction of the rat aortain vitro
Authors: Quinn S. T. , Guiry P. J. , Schwab T. , Keenan A. K. , McBean G. J.
Published: September 2006

1 The aim of this study was to characterize the effects of 4‐methylthioamphetamine (4‐MTA) on contractility and noradrenaline (NA) transport and release in the isolated rat aorta.

2 Descending thoracic aortic rings were isolated from male Wistar rats (220–240 g) and the effect of 4‐MTA on contractility was measured by isometric force displacement. 4‐MTA (0.1 μm–1 mm) induced a concentration‐dependent contraction of aortic rings, with a pD2of 4.40 ± 0.38, and anEmaxof 0.80 ± 0.05 g tension.

3 Theα1‐adrenoceptor antagonist, prazosin (1 μm) andα2antagonist, yohimbine (1 μm) inhibited maximal contraction to 100 μm4‐MTA by 45.0 ± 6.7% and 53.5 ± 7.1% of control values respectively, whereas the 5‐hydroxytryptamine (5‐HT) antagonist, ketanserin (100 nm) had no effect on the 4‐MTA‐mediated contraction. The specific NA transport inhibitor, nisoxetine (1 μm) abolished contraction of the aorta by 4‐MTA.

4 Nisoxetine‐sensitive [3H]‐NA transport in aortic rings was measured over a concentration range of 0–5 μm[3H]‐NA, and had a maximal rate of transport (Vmax) of 0.77 ± 0.07 pmol [3H]‐NA min−1 mg−1protein and a Michaelis affinity constant (KM) of 2.3 ± 0.5 μm. 4‐MTA inhibited nisoxetine‐sensitive [3H]‐NA transport with a pIC50of 6.16 ± 0.18 and the pIC50for inhibition of nisoxetine‐sensitive [3H]‐NA transport by 3,4‐methylenedioxymethamphetamine (MDMA) was 6.83 ± 0.13. 4‐MTA (1–100 μm) significantly stimulated release of pre‐loaded [3H]‐NA from aortic rings and 4‐MTA‐induced [3H]‐NA release was inhibited by 1 μmnisoxetine.

5 These data suggest that 4‐MTA causes contraction of the rat aortain vitroby a mechanism that is consistent with an ability to cause release of NA at the level of the NA transporter. It is concluded that 4‐MTA has the potential to increase the extracellular concentration of NA peripherally as well as centrally, and that this may cause adverse cardiovascular effects in its users.
Alpha1A/L‐adrenoceptors mediate contraction of the circular smooth muscle of the pig urethra
Authors: Bagot K. , Chess‐Williams R.
Published: September 2006

1 Sympathetically mediated urethral tone is essential for the maintenance of continence and involves the activation of postjunctional α1‐adrenoceptors. This study characterizes the α1‐adrenoceptor subtypes responsible for mediating contraction of the urethral circular smooth muscle of the pig.

2 The potency order of a number of agonists and the affinities of several receptor selective antagonists were determined on pig‐isolated circular smooth muscle strips in the presence of cocaine (1 μm) and corticosterone (10 μm) to inhibit amine uptake and propranolol (1 μm) to antagonize β‐adrenoceptors.

3 The potency order for agonists was N‐[5‐(4,5‐dihydro‐1H‐imidazol‐2yl)‐2‐hydroxy‐5,6,7,8‐tetrahydronaphthalen‐1‐yl]methanesulphonamide (A61603) > noradrenaline = phenylephrine = M6434 > methoxamine with pEC50 values of 7.3, 5.8, 5.7, 5.6 and 5.0 respectively.

4 The α1D‐adrenoceptor‐selective antagonist 8‐[2‐[4‐(2‐methoxyphenyl)‐1‐piperazinyl]ethyl]‐8‐azaspiro[4,5]decane‐7,9‐dione (BMY7378) caused rightward shifts of the concentration–response curves to noradrenaline, yielding a low affinity estimate (6.6) for the urethral receptor. The α1A‐adrenoceptor‐selective antagonists, RS100329 and 5‐methylurapidil, gave relatively high affinity estimates (9.6 and 8.8 respectively) for this receptor. All three antagonists produced Schild plots with slopes close to unity but did reduce maximum responses at higher concentrations. Prazosin antagonized responses of the urethra to noradrenaline, yielding a mean affinity estimate of 9.0. Although the Schild plot for prazosin again had a slope of unity, this drug also reduced maximum responses to noradrenaline at all concentrations examined (10–100 nm). N‐[2‐(2‐cyclopropylmethoxyphenoxy)ethyl]‐5‐chloro‐α,α‐dimethyl‐1H‐indole‐3‐ethanamide (RS17053), which discriminates between responses mediated via α1A (high affinity) and α1L‐adrenoceptors (low affinity) at concentrations up to 3 μm, failed to antagonize responses of the urethra.

5 These results suggest that contraction of urethral circular smooth muscle in the pig is mediated via a single population of adrenoceptors with the pharmacological characteristics of the α1A/L‐adrenoceptor, most probably the α1L‐adrenoceptor.
Dopamine receptor subtypes in the human pulmonary arterial tree
Authors: Ricci A. , Mignini F. , Tomassoni D. , Amenta F.
Published: September 2006

1 Dopamine induces vasorelaxation of pulmonary artery primarily through an endothelium‐dependent mechanism, but dopamine receptor subtypes involved in these mechanisms have not been identified yet. The expression and localization of dopamine D1‐like (D1 and D5) and D2‐like (D2, D3 and D4) receptors were investigated in hilar, lobar and intrapulmonary branches of human pulmonary artery by immunoblotting and immunohistochemistry.

2 Pulmonary artery expresses dopamine D1, D2, D4 and D5 receptor subtypes, but not the D3 receptor subtype. Dopamine D1 and to a lesser extent D5 receptors were accumulated primarily in the endothelium of extrapulmonary branches of pulmonary artery. A faint dopamine D1 and D5 receptor immunoreactivity was found in the inner media of extrapulmonary and of large sized intrapulmonary branches of pulmonary artery, but not in medium‐ or small‐sized intrapulmonary artery branches.

3 Dopamine D2 and to a lesser extent D4 receptor immunoreactivity co‐localized with the tyrosine hydroxylase‐immunoreactive sympathetic plexus supplying pulmonary artery was found in the adventitia and in the adventitia‐media of both extra‐ and different‐sized intrapulmonary branches of pulmonary artery.

4 These findings suggest the possible role of dopamine receptors in the pulmonary endothelium‐dependent vasorelaxing activity. The D1 receptor subtype seems to be the most involved in this mechanism. Dopamine D2‐like receptors are prejunctional and are located at the level of sympathetic neuroeffector plexus. The heterogeneous distribution and density of dopamine receptor subtypes along the human pulmonary arterial tree may be related to the different functional roles of dopamine at various levels of the pulmonary circulation.
Editorials: The Cardiovascular Effects of Arteriovenous Fistulas in Chronic Kidney Disease: A Cause for Concern?
Authors: MacRae Jennifer M. , Levin Adeera , Belenkie Israel
Published: September 2006

Arteriovenous fistulas (AVFs) are the preferred type of vascular access, but relatively little is known regarding their effects on cardiovascular remodeling and cardiac function. The following is a review regarding the immediate and long‐term complications associated with AVF creation, including the development of left ventricular hypertrophy, high‐output cardiac failure, exacerbation of coronary ischemia, and the possible contribution to the development of central vein stenosis.
Pulmonary Hypertension in Hemodialysis Patients: An Unrecognized Threat
Authors: Yigla Mordechai , Abassi Zaid , Reisner Shimon A. , Nakhoul Farid
Published: September 2006

Pulmonary hypertension (PH) is a progressive, fatal pulmonary circulatory disease that accompanies many conditions (including left to right side shunt) with compensatory elevated cardiac output. PH also complicates chronic hemodialysis (HD) therapy immediately after the creation of an arteriovenous (AV) access, even before starting HD therapy. It tends to regress after temporary AV access closure and after successful kidney transplantation. Affected patients have significantly higher cardiac output. This syndrome is associated with a statistically significant survival disadvantage. The laboratory hallmark of this syndrome is reduced basal and stimulatory nitric oxide (NO) levels. It appears that patients with end‐stage renal disease (ESRD) acquire endothelial dysfunction that reduces the ability of their pulmonary vessels to accommodate the AV access‐mediated elevated cardiac output, exacerbating the PH. Doppler echocardiographic screening of ESRD patients scheduled for HD therapy for the occurrence of PH is indicated. Early diagnosis enables timely intervention, currently limited to changing dialysis modality or referring for kidney transplantation.
Three Controversial Issues in Extracorporeal Toxin Removal
Authors: Feinfeld Donald A. , Rosenberg Jeffrey W. , Winchester James F.
Published: September 2006

The optimal method of extracorporeal removal of many toxic compounds is often a matter of debate. Due to the lack of well‐designed studies, we are often left with circumstantial evidence, and we must exercise our best clinical judgment as to whether extracorporeal drug removal is beneficial and if so, by what method. It is clear, however, that rapidity in toxin removal is beneficial. We present three issues dealing with extracorporeal removal of toxins for which there is no definitive answer but which may arise in clinical practice. The first is whether continuous renal replacement therapy (CRRT) is better at removing dialyzable toxins than classic hemodialysis. The second is whether charcoal hemoperfusion is at all useful in treating paraquat poisoning. Finally, is any modality of extracorporeal treatment useful in the treatment of amatoxin poisoning? After a thorough literature review, it is evident that definitive answers are not strikingly apparent. However, extracorporeal treatment in the latter two instances may have potential benefit and may be the only hope for patient survival. Due to the urgent nature of treatment for poisoning, as well as the somewhat obscure nature of these issues, there may never be well‐designed evidence‐based studies to help guide us. In the meantime, we must continue to use less than ideal evidence and our own experience in dealing with these controversial issues to guide our decision‐making process.
Use of Antiepileptic Drugs in Patients with Kidney Disease
Authors: Israni Rubeen K. , Kasbekar Nishaminy , Haynes Kevin , Berns Jeffrey S.
Published: September 2006

The number of medications used to treat different types of seizures has increased over the last 10–15 years. Most of the newer antiepileptic drugs (AEDs) are likely to be unfamiliar to many nephrologists. For both the older and newer AEDs, basic pharmacokinetic information, recommendations for drug dosing in patients with reduced kidney function or who are on dialysis, and adverse renal and fluid‐electrolyte effects are reviewed. Newer AEDs are less likely to have significant drug–drug interactions than older agents, but are more likely to need dosage adjustment in patients with reduced kidney function. The most common renal toxicities of these drugs include metabolic acidosis, hyponatremia, and nephrolithiasis; interstitial nephritis and other adverse effects are less common. Little is known about the clearance of most of the newer AEDs with high‐efficiency hemodialyzers or with peritoneal dialysis. Monitoring of drug levels when available, careful clinical assessment of patients taking AEDs, and close collaboration with neurologists is essential to the management of patients taking AEDs.
ASDIN Original Investigation: Successful Treatment of the Chronically Thrombosed Dialysis Access Graft: Resuscitation of Dead Grafts
Authors: Beathard Gerald A.
Published: September 2006

The most common contributing cause of thrombosis of an arteriovenous graft (AVG) in the hemodialysis patient is the presence of venous stenosis. In the face of a recovery of renal function either spontaneously or as a result of renal transplantation, an AVG commonly thromboses. In cases in which the AVG was recently placed, it is unlikely to have had a significant anatomic lesion at the time function was lost. Even though the access that has been left untreated has become a “dead” AVG, it offers an opportunity for “resuscitation.” Thirteen cases that met the specific criteria of being placed only a short period of time prior to thrombosis (3 weeks to 6 months), thrombosing after a return of renal function and having been left untreated (3 months to 8 years) were attempted over a 12 year period. The technique applied was modified from the one routinely used based on the presumption that very little or no thrombus was present. The effort was met with success in 8 of the 13 patients. After being opened, the AVG appeared to follow the same patency pattern as other AVGs. It appears that attempting restoration of function of an AVG meeting these criteria may be indicated. Limited experience using this approach in AVGs that do not meet these specific criteria has uniformly met with failure.
Fellows' Forum in Dialysis: Interdialytic Weight Gain: Implications in Hemodialysis Patients
Authors: Sarkar Shubho R. , Kotanko Peter , Levin Nathan W.
Published: September 2006

Interdialytic weight gain (IDWG) is an easily measurable parameter in the dialysis unit, routinely assessed at the beginning of the dialysis session. It is used along with clinical symptoms and signs and predialysis blood pressure readings to make decisions regarding the amount of fluid removal during a dialysis session. IDWG is also used as a basis for fluid and salt intake recommendations. However, advising fluid and salt restriction based solely on IDWG may not be appropriate because of its status as a nutritional indicator, as well. Very few studies have been designed to determine the direct effect of IDWG on morbidity and mortality. Any such effect is confounded by residual renal function and various comorbidities, the effects of which might be difficult to separate from those of IDWG. Most attempts to control IDWG have concentrated on requiring patients to reduce fluid and dietary salt intake. Although there does not seem to be a consensus at this point, it is likely that within the lower values of IDWG (less than 5.7% of dry weight), tighter control of fluid and salt intake might not be warranted since these values may reflect higher protein and calorie intake, indicating better nutritional status.
A Dialysis Case Presentation and Discussion: A Case of Fatal Cardiac Tamponade During Hemodialysis
Authors: Schmiege Lorenz M. , Wolf Dwayne A.
Published: September 2006

A 27‐year‐old Hispanic man with a history of hypertension and end‐stage renal disease for 4 years became unresponsive, apneic, and pulseless during hemodialysis. During his 4 year period on dialysis, vascular access had become increasingly difficult and ultimately a transhepatic catheter had been placed 9 months prior to this event. Resuscitation was unsuccessful. At autopsy, death was determined to be due to cardiac tamponade secondary to perforation of the right atrium by the transhepatic catheter. Cardiac tamponade is a rare cause of sudden death during hemodialysis with a long‐standing catheter.
Monoamine Metabolism and Behavioral Responses to Ethanol in Mitochondrial Aldehyde Dehydrogenase Knockout Mice
Authors: Fernandez Elizabeth , Koek Wouter , Ran Qitao , Gerhardt Greg A. , France Charles P. , Strong Randy
Published: September 2006

Background: It is widely accepted that, in addition to removing acetaldehyde produced during the metabolism of ethanol, mitochondrial aldehyde dehydrogenase (ALDH2) functions in the pathway by which aldehyde metabolites of the monoamines dopamine (DA) and serotonin (5‐HT) are converted to their acidic metabolites. Moreover, studies of ALDH2 inhibitors used for treating alcoholism suggest that their antidipsotropic effects may be related to inhibition of monoamine metabolism. Therefore, we examined the hypothesis that altered brain monoamine metabolism is related to the influence of ALDH2 on behavioral responses to ethanol.

Methods: Mice were generated with a gene‐trap mutation of the ALDH2 gene. ALDH2 mRNA was absent in ALDH2−/− mice. Western blot analysis of liver mitochondria confirmed the absence of ALDH2 protein in the ALDH2−/− mice. Wild‐type and ALDH2‐deficient mice were tested for the effects of different doses of ethanol on locomotor activity, ataxia, and a 2‐bottle ethanol–water preference test.

Results: Wild‐type and ALDH2+/− mice preferred ethanol to water. However, ALDH2−/− mice drank significantly less ethanol than wild‐type or ALDH2+/− mice. Locomotor activity and ataxia were significantly more affected by ethanol in ALDH2−/− mice than in wild‐type or ALDH2+/− mice. There was no effect of genotype on levels of 5‐HT, DA, or their precursors or metabolites in several brain regions, as measured by HPLCec.

Conclusions: The results indicate that: (1) the effect of the mutant genotype on behavioral responses to ethanol is unrelated to altered brain monoamine metabolism and (2) ALDH2 is not required for the metabolism of brain monoamines in vivo.
Gene Array Profiles of Alcohol and Aldehyde Metabolizing Enzymes in Brains of C57BL/6 and DBA/2 Mice
Authors: Bhave Sanjiv V. , Hoffman Paula L. , Lassen Natalie , Vasiliou Vasilis , Saba Laura , Deitrich Richard A. , Tabakoff Boris
Published: September 2006

Background: Differences in ethanol metabolizing enzymes expressed in brain have been suggested to contribute to the significant differences in ethanol (alcohol) preference between inbred C57BL/6 and DBA/2 mouse strains.

Methods: We have utilized 2 different platforms of oligonucleotide microarray technology (CodeLink UniSet I BioArray from G.E. Healthcare and MG U74A v2.0 from Affymetrix) to simultaneously assess expression of alcohol and acetaldehyde metabolizing enzymes in the whole brain of naïve (no exposure to alcohol) C57BL/6 and DBA/2 mice.

Results: There were no significant differences between the 2 strains of mice in gene expression intensity for alcohol dehydrogenases (ADH), catalase, and a number of the cytochrome P450 family of genes, which can be involved in ethanol catabolism. However, significantly higher expression of mRNA for aldehyde dehydrogenase 2 (ALDH2), an isoform mainly responsible for the catabolism of acetaldehyde, was observed in whole brains of DBA/2 mice with both platforms. Aldehyde dehydrogenase 2 protein was also higher in DBA/2 brain. Expression of aldehyde dehydrogenase 1A1 (ALDH1A1) mRNA was found to be higher in brains of DBA/2 mice, when measured with the CodeLink platform, but not when measured with Affymetrix arrays or quantitative reverse transcriptase–real‐time polymerase chain reaction (qRT‐PCR). The ALDH1A1 protein, however, reflected the results obtained with the CodeLink arrays and was higher in DBA/2 brain, compared with brains of C57BL/6 mice. In contrast, the expression intensity for the aldehyde dehydrogenase 7A1 (ALDH7A1) mRNA and protein was significantly higher in C57BL/6 mice than DBA/2 mice. These expression differences are consistent with more rapid metabolism of acetaldehyde in brains of DBA/2 mice.

Conclusions: The use of 2 different microarray platforms provides important cross‐validation of many results, and some discrepancies can be resolved with qRT‐PCR and immunoblotting. The expression differences that were validated may affect alcohol/aldehyde metabolism in brain and/or alcohol preference in the 2 strains of mice.