bluuebunny/crossref_metadata_2025 huggingface dataset:
The P2X7 ATP Receptor in the Kidney: A Matter of Life or Death?
Authors: Hillman K.A. , Burnstock G. , Unwin R.J.
Published: May 2005

P2X7 is an intriguing membrane receptor for the extracellular nucleotide ATP, which functions as a ligand-gated ion channel; it can activate cell membrane permeabilization and also has a wide range of downstream signaling pathways, including mediation of inflammatory responses and modulation of cell turnover. Despite recent identification of P2X7 receptor protein in the renal tract, the biological and potential pathological functions of this receptor and its signaling cascades in the kidney are not yet fully understood. P2X7 receptor protein is expressed in normal kidney development, predominantly in the condensing mesenchyme, and later in the maturing and adult derivatives of the ureteric bud. Glomerular expression of the molecule is scarce in normal kidney, but is upregulated in chronic and inflammatory conditions, suggesting a role in the inflammatory response or in repair and remodeling in these settings. P2X7 receptor expression in the adult collecting ducts of murine kidney, as well as the collecting duct cysts in autosomal recessive polycystic kidney disease, has been described and agonists of the receptor can modulate the development of renal cysts in an in vitro model of cyst formation derived from the cpk/cpk mouse. Further investigation of the function of the P2X7 receptor in normal and abnormal kidneys might lead to novel therapeutic targets in a wide range of renal diseases.
Control of Hypertension with Captopril Affords Better Renal Protection as Compared with Irbesartan in Salt-Loaded Uremic Rats
Authors: Weissgarten Joshua , Berman Sylvia , Efrati Shai , Rapoport Micha , Modai David , Cohn Mirel , Aladjem Mordechay , Galperin Elena , Averbukh Zhan
Published: May 2005

Background/Aim: Hypertension induced by exaggerated sodium consumption accelerates the progression of renal failure. We investigated the effects of a high-sodium (HS) diet on the progression of renal failure in rats maintained normotensive by angiotensin-converting enzyme inhibition or AT-1 blockade. Methods: In 70 Sprague-Dawley rats, renal failure was induced by five-sixths nephrectomy. They were fed isocaloric normal-sodium (NS), low-sodium (LS), or HS diets. HS rats prone to develop hypertension were divided into three subgroups: treated to normotension by irbesartan (HS-1) or captopril (HS-2) or left untreated (HS-0). Results: All HS animals developed significant proteinuria which strongly correlated with the 24-hour sodium excretion. HS-0 rats demonstrated severe hypertension, rapid deterioration of the renal function, and 100% mortality after 3 weeks. In irbesartan-treated HS-1 rats, mortality and decline of the glomerular filtration rate were similar to those of normal- or low-sodium-fed animals (100% mortality after week 12). In captopril-treated HS-2 rats, glomerular filtration rate decline and mortality were significantly blunted as compared with all other groups (50% mortality after week 12). Conclusions: (1) In five-sixths-nephrectomized uremic rats maintained normotensive by either irbesartan or captopril, the rate of deterioration of the renal function was not aggravated by exaggerated sodium consumption. (2) In this experimental setting, captopril treatment yielded a better survival outcome as compared with irbesartan, despite the similar hypotensive effect.
Do Healthy Potential Kidney Donors in India Have an Average Glomerular Filtration Rate of 81.4 ml/min?
Authors: Barai Sukanta , Bandopadhayaya G.P. , Patel C.D. , Rathi Manish , Kumar R. , Bhowmik D. , Gambhir S. , Gopendro Singh N. , Malhotra A. , Gupta K.D.
Published: May 2005

Background: Until now, a normal reference range for glomerular filtration rate (GFR) in adult Indian potential kidney donors has not been determined and values from a western population are being used as reference. Aim: To determine the reference range of GFR in healthy adult Indian potential kidney donors. Basic Procedures: GFR was measured in 610 (250 male, 360 female, average age 35.16 years) healthy potential kidney donors using the 99mTc-DTPA (diethylenetriamine pentaacetic acid) two-plasma sample method of Russell. Results: The mean body surface area (BSA)-normalized GFR value of a young healthy Indian adult potential kidney donor was calculated as 81.4 ± 19.4 ml/min/1.73 m2 BSA – for males it was 82.3 ± 21.3 ml/min/1.73 m2 BSA and for females 80.8 ± 18.1 ml/min/1.73 m2 BSA. There was no significant difference between derived mean GFR values in males and females with a p value of 0.37. Conclusions: The normal GFR value for the healthy Indian adult potential kidney donor appears to be much lower than the accepted value for a western population. The mean GFR value of a young healthy Indian adult potential kidney donor is 81.4 ± 19.4 ml/min/1.73 m2 BSA, which is significantly different from the normal value of 109–125 ml/min derived from a western population. These findings might be useful in deciding on a suitable kidney donor in an Indian context.
Association of Apolipoprotein J Gene 866C→T Polymorphism with Preeclampsia and Essential Hypertension
Authors: Chen MiaoXin , Yuan ZhuHua , Shan KeRen
Published: May 2005

The etiology of preeclampsia (PE) is unknown, but endothelial cell injury plays a pivotal role. Moreover, there is a significantly positive association between PE and later hypertension. Apolipoprotein J (apo J) plays an important role in stabilizing cell membranes at diverse fluid-tissue interfaces and might protect vascular endothelium against an attack by some factors in plasma such as active complement complexes. This study investigated the prevalence and possible association of apo J gene in PE and essential hypertension (EH). To screen for polymorphisms of apo J gene in a population in Guizhou, China, by employing polymerase chain reaction combined with denaturing gradient gel electrophoresis, we identified 866C→T polymorphism in exon 5 and a rare variant 1061C→T in exon 7. The CT genotype and T-allele frequencies in PE (CT genotype 26%; T allele 13%) and EH (CT genotype 28.57%; T allele 17.14%) were significantly lower than that in the control group (CT geno type 50%; T allele 27%). The results suggested that the 866C→T polymorphism might be associated with PE and EH. It is plausible that apo J may play a certain role in the predisposition to PE and EH.
Assessment of Oxidative Stress in the Early Posttransplant Period: Comparison of Cyclosporine A and Tacrolimus-Based Regimens
Authors: Vural Abdulgaffar , Yilmaz Mahmut Ilker , Caglar Kayser , Aydin Ahmet , Sonmez Alper , Eyileten Tayfun , Acikel Cengizhan , Gulec Bulent , Kozak Orhan , Oner Koksal
Published: May 2005

Background: Oxidative stress is one of the leading causes of cardiovascular morbidity and mortality in chronic kidney disease. Although it is clear that many metabolic abnormalities improve, the effects of kidney transplantation on oxidative state are obscure. Methods: Twenty-three kidney transplant patients were included in the study. Eleven patients (mean age 27.9± 9.1 years) were treated with cyclosporine A (CsA) whereas 12 patients (mean age 22.4 ± 3.4 years) were treated with tacrolimus. Twenty-three healthy subjects served as controls. None of the patients or controls suffered from diabetes mellitus or an acute infection at the time of the study. Plasma malondialdehyde (MDA), plasma selenium (Se), erythrocyte glutathione peroxidase (GSH-Px), erythrocyte superoxide dismutase (SOD), erythrocyte Zn (EZn), and erythrocyte Cu (ECu) levels were studied before and in the 1st,3rd, 7th, 14th and 28th days after the transplantation. Results: The GSH-Px, SOD, ECu, EZn and selenium levels were lower and MDA levels were higher in patients than controls before transplantation (p < 0.001 for all). MDA levels decreased and SOD, GSH-Px, ECu, EZn levels increased in parallel to the decrement of serum creatinine levels following the renal transplantation. No difference was found among the patients regarding the treatment regime. Conclusion: The study data suggest that the improvement in oxidative state parameters begins at the first day of renal transplantation and continues at the 28th posttransplant day in living donor transplantations.
Use of Tissue Doppler to Assess Right Ventricle Function in Hemodialysis Patients
Authors: Arinc Huseyin , Gunduz Huseyin , Tamer Ali , Ozhan Hakan , Akdemir Ramazan , Saglam Hayrettin , Oguzhan Abdurrahman , Uyan Cihangir
Published: May 2005

Aims: Although there are plenty of data about the differences in left ventricular tissue Doppler (TD) velocities by preload reduction, only a few studies regarding right ventricular function are found in the literature. We investigated the effect of intravascular volume reduction on right ventricular function by ultrafiltration in dialysis patients. Methods: 27 end-stage renal failure patients who were hypervolemic and undergoing hemodialysis were included in the study. TD studies of the right ventricle were performed before and 1 h after dialysis. These data were compared. Results: The mean age of the patients was 41 ± 15 years and mean volume of ultrafiltration was 3.8 ± 1.8 liters. Systolic, early and late diastolic lateral annular TD velocities before dialysis were 0.109 ± 0.029, 0.088 ± 0.039, 0.111 ± 0.039 m/s, and after dialysis were 0.099 ± 0.028, 0.078 ± 0.036, 0.106 ± 0.037 m/s, respectively (p = 0.216, p = 0.112, p = 0.350). Myocardial early diastolic velocity decreased significantly (p = 0.049) but systolic and late diastolic velocities did not change significantly (p = 0.579, p = 0.146). Conclusion: Right ventricular systolic and diastolic velocities detected by TD were not or only minimally affected by preload reduction in hemodialysis patients and the TD early/late ratio is the most valuable variable that can predict right ventricular diastolic function. The right ventricular systolic and early diastolic TD velocities were positively correlated with left ventricle ejection fraction.
Mechanisms of Inducible Nitric Oxide Synthase–Mediated Vascular Dysfunction
Authors: Gunnett C.A. , Lund D.D. , McDowell A.K. , Faraci F.M. , Heistad D.D.
Published: June 2005

Objective—

Inducible nitric oxide synthase (iNOS) is expressed in arteries during inflammation and may contribute to vascular dysfunction. Effects of gene transfer of iNOS to carotid arteries were examined in vitro in the absence of systemic inflammation to allow examination of mechanisms by which iNOS impairs contraction and relaxation.

Methods and Results—

After gene transfer of iNOS with an adenovirus (AdiNOS), constrictor responses to phenylephrine (PE) and U46619 were impaired. After AdiNOS, inhibition of soluble guanylate cyclase (sGC) with 1H-[1,2,4]oxadiazolo-[4,3,2]quinoxalin-1-one (ODQ) reduced the EC
50
for PE from 4.33±0.78 μmol/L to 1.15±0.43 μmol/L (mean±SEM). These results imply that iNOS impairs contraction by activation of the NO/cGMP pathway. Relaxation to acetylcholine (ACh) also was impaired after AdiNOS. Sepiapterin (300 μmol/L), the precursor for tetrahydrobiopterin (BH
4
), improved relaxation to Ach. Because BH
4
is an essential cofactor for production of NO by both iNOS and endothelial nitric oxide synthase (eNOS), these results suggest that iNOS may reduce production of NO by eNOS by limiting availability of BH
4
. Next, we examined effects of expression of iNOS in endothelium and adventitia. Selective expression of iNOS in endothelium, but not adventitia, impaired contraction to phenylephrine and relaxation to acetylcholine.

Conclusions—

We conclude that: (1) iNOS may impair contraction in part by activation of sGC; (2) iNOS impairs relaxation, at least in part, by limiting availability of BH
4
; and (3) expression of iNOS in endothelium may be a more important mediator of vascular dysfunction than expression of iNOS in adventitia.
Vitamin E Inhibits Abdominal Aortic Aneurysm Formation in Angiotensin II–Infused Apolipoprotein E–Deficient Mice
Authors: Gavrila Dan , Li Wei Gen , McCormick Michael L. , Thomas Manesh , Daugherty Alan , Cassis Lisa A. , Miller Francis J. , Oberley Larry W. , Dellsperger Kevin C. , Weintraub Neal L.
Published: June 2005

Background—

Abdominal aortic aneurysms (AAAs) in humans are associated with locally increased oxidative stress and activity of NADPH oxidase. We investigated the hypothesis that vitamin E, an antioxidant with documented efficacy in mice, can attenuate AAA formation during angiotensin II (Ang II) infusion in apolipoprotein E–deficient mice.

Methods and Results—

Six-month-old male apolipoprotein E–deficient mice were infused with Ang II at 1000 ng/kg per minute for 4 weeks via osmotic minipumps while consuming either a regular diet or a diet enriched with vitamin E (2 IU/g of diet). After 4 weeks, abdominal aortic weight and maximal diameter were determined, and aortic tissues were sectioned and examined using biochemical and histological techniques. Vitamin E attenuated formation of AAA, decreasing maximal aortic diameter by 24% and abdominal aortic weight by 34% (
P
<0.05, respectively). Importantly, animals treated with vitamin E showed a 44% reduction in the combined end point of fatal+nonfatal aortic rupture (
P
<0.05). Vitamin E also decreased aortic 8-isoprostane content (a marker of oxidative stress) and reduced both aortic macrophage infiltration and osteopontin expression (
P
<0.05, respectively). Vitamin E treatment had no significant effect on the extent of aortic root atherosclerosis, activation of matrix metalloproteinases 2 or 9, serum lipid profile, or systolic blood pressure.

Conclusions—

Vitamin E ameliorates AAAs and reduces the combined end point of fatal+nonfatal aortic rupture in this animal model. These findings are consistent with the concept that oxidative stress plays a pivotal role in Ang II–driven AAA formation in hyperlipidemic mice.
Downregulation of Apoptosis-Inducing Factor in Harlequin Mutant Mice Sensitizes the Myocardium to Oxidative Stress–Related Cell Death and Pressure Overload–Induced Decompensation
Authors: van Empel Vanessa P.M. , Bertrand Anne T. , van der Nagel Roel , Kostin Sawa , Doevendans Pieter A. , Crijns Harry J. , de Wit Elly , Sluiter Wim , Ackerman Susan L. , De Windt Leon J.
Published: June 2005

Apoptosis-inducing factor (AIF), or programmed cell death 8 (Pdcd8), is a highly conserved, ubiquitous flavoprotein localized in the mitochondrial intermembrane space. In vivo, AIF provides protection against neuronal apoptosis induced by oxidative stress. Conversely, in vitro, AIF has been demonstrated to have a proapoptotic role when, on induction of the mitochondrial death pathway, AIF translocates to the nucleus where it facilitates chromatin condensation and large scale DNA fragmentation. To determine the role of AIF in myocardial apoptotic processes, we examined cardiomyocytes from an AIF-deficient mouse mutant, Harlequin (
Hq
).
Hq
mutant cardiomyocytes demonstrated increased sensitivity to H
2
O
2
-induced cell death. Further,
Hq
hearts subjected to ischemia/reperfusion revealed more cardiac damage and, unlike wild-type mice, the amount of damage increased with the age of the animal. Aortic banding caused enhanced hypertrophy, increased cardiomyocyte apoptotic and necrotic cell death, and accelerated progression toward maladaptive left ventricular remodeling in
Hq
mutant mice compared with wild-type counterparts. These findings correlated with a reduced capacity of subsarcolemmal mitochondria from
Hq
mutant hearts to scavenge free radicals. Together, these data demonstrate a critical role for AIF as a cardiac antioxidant in the protection against oxidative stress–induced cell death and development of heart failure induced by pressure overload.
Spatial Nonuniformity of Excitation–Contraction Coupling Causes Arrhythmogenic Ca
2+
Waves in Rat Cardiac Muscle
Authors: Wakayama Yuji , Miura Masahito , Stuyvers Bruno D. , Boyden Penelope A. , ter Keurs Henk E.D.J.
Published: June 2005

Ca
2+
waves underlying triggered propagated contractions (TPCs) are initiated in damaged regions in cardiac muscle and cause arrhythmias. We studied Ca
2+
waves underlying TPCs in rat cardiac trabeculae under experimental conditions that simulate the functional nonuniformity caused by local mechanical or ischemic local damage of myocardium. A mechanical discontinuity along the trabeculae was created by exposing the preparation to a small jet of solution with a composition that reduces excitation–contraction coupling (ECC) in myocytes within that segment. The jet solution contained either caffeine (5 mmol/L), 2,3-butanedione monoxime (BDM; 20 mmol/L), or low Ca
2+
concentration ([Ca
2+
]; 0.2 mmol/L). Force was measured with a silicon strain gauge and sarcomere length with laser diffraction techniques in 15 trabeculae. Simultaneously, [Ca
2+
]
i
was measured locally using epifluorescence of Fura-2. The jet of solution was applied perpendicularly to a small muscle region (200 to 300 μm) at constant flow. When the jet contained caffeine, BDM, or low [Ca
2+
], during the stimulated twitch, muscle-twitch force decreased and the sarcomeres in the exposed segment were stretched by shortening normal regions outside the jet. Typical protocols for TPC induction (7.5 s-2.5 Hz stimulus trains at 23°C; [Ca
2+
]
o
=2.0 mmol/L) reproducibly generated Ca
2+
waves that arose from the border between shortening and stretched regions. Such Ca
2+
waves started during force-relaxation of the last stimulated twitch of the train and propagated (0.2 to 2.8 mm/sec) into segments both inside and outside of the jet. Arrhythmias, in the form of nondriven rhythmic activity, were induced when the amplitude of the Ca
2+
-wave was increased by raising [Ca
2+
]
o
. Arrhythmias disappeared rapidly when uniformity of ECC throughout the muscle was restored by turning the jet off. These results show, for the first time, that nonuniform ECC can cause Ca
2+
waves underlying TPCs and suggest that Ca
2+
dissociated from myofilaments plays an important role in the initiation of Ca
2+
waves.
Endothelin-1–Induced Arrhythmogenic Ca
2+
Signaling Is Abolished in Atrial Myocytes of Inositol-1,4,5-Trisphosphate(IP
3
)–Receptor Type 2–Deficient Mice
Authors: Li Xiaodong , Zima Aleksey V. , Sheikh Farah , Blatter Lothar A. , Chen Ju
Published: June 2005

Recent studies have suggested that inositol-1,4,5-trisphosphate-receptor (IP
3
R)–mediated Ca
2+
release plays an important role in the modulation of excitation–contraction coupling (ECC) in atrial tissue and the generation of arrhythmias, specifically chronic atrial fibrillation (AF). IP
3
R type-2 (IP
3
R2) is the predominant IP
3
R isoform expressed in atrial myocytes. To determine the role of IP
3
R2 in atrial arrhythmogenesis and ECC, we generated IP
3
R2-deficient mice. Our results revealed that endothelin-1 (ET-1) stimulation of wild-type (WT) atrial myocytes caused an increase in basal [Ca
2+
]
i
, an enhancement of action potential (AP)-induced [Ca
2+
]
i
transients, an improvement of the efficacy of ECC (increased fractional SR Ca
2+
release), and the occurrence of spontaneous arrhythmogenic Ca
2+
release events as the result of activation of IP
3
R-dependent Ca
2+
release. In contrast, ET-1 did not alter diastolic [Ca
2+
]
i
or cause spontaneous Ca
2+
release events in IP
3
R2-deficient atrial myocytes. Under basal conditions the spatio-temporal properties (amplitude, rise-time, decay kinetics, and spatial spread) of [Ca
2+
]
i
transients and fractional SR Ca
2+
release were not different in WT and IP
3
R2-deficient atrial myocytes. WT and IP
3
R2-deficient atrial myocytes also showed a significant and very similar increase in the amplitude of AP-dependent [Ca
2+
]
i
transients and Ca
2+
spark frequency in response to isoproterenol stimulation, suggesting that both cell types maintained a strong inotropic reserve. No compensatory changes in Ca
2+
regulatory protein expression (IP
3
R1, IP
3
R3, RyR2, NCX, SERCA2) or morphology of the atria could be detected between WT and IP
3
R2-deficient mice. These results show that lack of IP
3
R2 abolishes the positive inotropic effect of neurohumoral stimulation with ET-1 and protects from its arrhythmogenic effects.
Equilibrative Nucleoside Transporter 1 Expression Is Downregulated by Hypoxia in Human Umbilical Vein Endothelium
Authors: Casanello Paola , Torres Alberto , Sanhueza Felipe , González Marcelo , Farías Marcelo , Gallardo Victoria , Pastor-Anglada Marçal , Martín Rody San , Sobrevia Luis
Published: June 2005

Reduced oxygen level (hypoxia) induces endothelial dysfunction and release of the endogenous nucleoside adenosine. Human umbilical vein endothelium (HUVEC) function in an environment with 3% to 5% O
2
and exhibit efficient adenosine membrane transport via human equilibrative nucleoside transporters 1 (hENT1). We studied whether adenosine transport and hENT1 expression are altered by hypoxia in HUVEC. Hypoxia (0 to 24 hours, 2% and 1% O
2
) reduced maximal hENT1-adenosine transport velocity (
V
max
) and maximal nitrobenzylthionosine (NBMPR, a high-affinity hENT1 protein ligand) binding, but increased extracellular adenosine concentration. Hypoxia also reduced hENT1 protein and mRNA levels, effects unaltered by
N
ω
-nitro-
l
-arginine methyl ester (
l
-NAME, nitric oxide synthase [NOS] inhibitor) or PD-98059 (inhibitor of mitogen-activated protein kinase kinase 1 and 2 [MEK1/2]). Hypoxia reduced endothelial NOS (eNOS) activity and eNOS phosphorylation at Ser
1177
, but increased eNOS protein level. Hypoxia increased (1 to 3 hours), but reduced (24 hours) p42/44
mapk
phosphorylation. Thus, hypoxia-increased extracellular adenosine may result from reduced hENT1-adenosine transport in HUVEC. Hypoxia effect seems not to involve NO, but p42/44
mapk
may be required for the relatively rapid effect (1 to 3 hours) of hypoxia. These results could be important in diseases where the fetus is exposed to intrauterine environments poor in oxygen, such as intrauterine growth restriction, or where adenosine transport is altered, such as gestational diabetes.
A Systematic Review of the Risk Factors for Cervical Artery Dissection
Authors: Rubinstein Sidney M. , Peerdeman Saskia M. , van Tulder Maurits W. , Riphagen Ingrid , Haldeman Scott
Published: June 2005

Background and Purpose—

Cervical artery dissection (CAD) is a recognized cause of ischemic stroke among young and middle-aged individuals. The pathogenesis of dissections is unknown, although numerous constitutional and environmental risk factors have been postulated. To better understand the quality and nature of the research on the pathogenesis of CAD, we performed a systematic review of its risk factors.

Methods—

PubMed [MEDLINE (1966 to February 22, 2005)] and Embase (1980 to February 22, 2005) were searched to identify studies fulfilling the inclusion criteria. Two reviewers independently assessed methodological quality of the primary studies. Relevant data were extracted, including the risk factor(s) investigated, characteristics of the study population, and strength of the association(s).

Results—

Thirty-one case-control studies were included for analysis. Selection bias, lack of control for confounding, and inadequate method of data analysis were the most common identified methodological shortcomings. Strong associations were reported from individual studies for the following risk factors: aortic root diameter >34 mm (odds ratio [OR=14.2; 95% confidence interval [CI], 3.2 to 63.6), migraine (OR
adj
, 3.6; 95% CI, 1.5 to 8.6), relative diameter change (>11.8%) during the cardiac cycle of the common carotid artery (OR
adj
, 10.0; 95% CI, 1.8 to 54.2), and trivial trauma (in the form of manipulative therapy of the neck) (OR
adj
, 3.8; 95% CI, 1.3 to 11). A weak association was found for homocysteine (2 studies: OR
crude
, unknown; 95% CI, 1.05 to 1.52; OR
crude
, 1.3; 95% CI, 1.0 to 1.7), and recent infection (OR
adj
, 1.60; 95% CI, 0.67 to 3.80). Two studies had conflicting findings for low levels of α
1
-antitrypsin, with the methodologically stronger study suggesting no association with CAD.

Conclusions—

CAD is a multi-factorial disease. Many of the reviewed studies contained 2 or more major sources of bias commonly found in case-control studies. Only one study (of homocysteine) used healthy controls, a robust sample size, and had a low risk of biased results. The relationship between atherosclerosis and CAD has been insufficiently examined.
Ischemic Neuroprotection With Selective κ-Opioid Receptor Agonist Is Gender Specific
Authors: Chen Chih-Hung , Toung Thomas J.K. , Hurn Patricia D. , Koehler Raymond C. , Bhardwaj Anish
Published: June 2005

Background and Purpose—

We demonstrated previously that treatment with selective κ-opioid receptor (KOR) agonist
BRL 52537
hydrochloride [(±)-1-(3,4-dichlorophenyl) acetyl-2-(1-pyrrolidinyl) methylpiperidine] (1) has a long therapeutic window for providing ischemic neuroprotection, and (2) attenuates ischemia-evoked NO production in vivo in rats. Neuronally derived NO has been shown to be deleterious in the male but not in the female rodent model of focal ischemic stroke. We tested the hypothesis that
BRL
provides significant neuroprotection from transient focal ischemia in male but not in female rats.

Methods

Halothane-anesthetized adult male and female Wistar rats (250 to 275 g) were subjected to 2 hours of middle cerebral artery occlusion (MCAO) by the intraluminal suture technique. Adequacy of MCAO and reperfusion was monitored with laser-Doppler flowmetry over the ipsilateral parietal cortex. In the first experiment, male and female rats were treated in a blinded randomized fashion with vehicle saline or 1 mg/kg per hour
BRL
infusion started at the onset of reperfusion and continued for 22 hours. In the second experiment, ovariectomized (OVX) female rats were treated with vehicle or
BRL
. Infarct volume in the cortex and caudoputamen (CP) complex was assessed by triphenyl tetrazolium chloride staining at 72 hours after MCAO.

Results

Infarct volume (percentage of ipsilateral structure; mean±SEM) was attenuated significantly in male rats with
BRL
treatment (cortex 23±5%; CP 44±6%; n=15) compared with vehicle-treated male rats (cortex 38±4%; CP 66±4%; n=15) but not in female rats (
BRL
−cortex 26±6; CP 55±8%; vehicle−cortex 26±5; CP 62±5%; n=10 each). Neurologic deficit score was improved in
BRL
-treated male rats but not in female rats. Infarct volume was not different in OVX female rats treated with vehicle or
BRL
.

Conclusions

These data: (1) demonstrate that this dose of selective KOR agonist provides ischemic neuroprotection in male but not female rats, (2) demonstrate that the lack of protection by
BRL
is not attributable to circulating ovarian hormones, and (3) highlight the importance of using animal models of both sexes in preclinical studies of experimental ischemia.
Prognostic Impact of Fibrinogen in Carotid Atherosclerosis
Authors: Sabeti Schila , Exner Markus , Mlekusch Wolfgang , Amighi Jasmin , Quehenberger Peter , Rumpold Helmut , Maurer Gerald , Minar Erich , Wagner Oswald , Schillinger Martin
Published: June 2005

Background—

Fibrinogen is a key factor in the coagulation cascade, it exhibits proinflammatory properties, and it is suggested to play a pivotal role in atherogenesis. We investigated whether fibrinogen predicts future progression of carotid atherosclerosis, analyzing whether fibrinogen levels add to the prognostic information of other inflammatory parameters.

Methods—

We prospectively studied 1268 consecutive patients without recent (12 months) symptoms from cerebrovascular disease. Patients underwent serial ultrasound investigations in 6- to 9-month intervals, categorizing carotid arteries as 0% to 29%, 30% to 49%, 50% to 69%, 70% to 89%, or 90% to 99% stenosed, or occluded. Fibrinogen levels were determined at baseline and follow-up. The risk for progressive carotid atherosclerosis according to fibrinogen levels was calculated, adjusting for traditional risk factors and other inflammatory parameters (C-reactive protein and serum amyloid A).

Results—

Progression of carotid atherosclerosis was found in 117 of 1268 patients (9.2%) after a median of 8 months (range 6 to 18). Adjusted hazard ratios for atherosclerosis progression with increasing quartiles of baseline fibrinogen were 1.83 (
P
=0.037), 2.09 (
P
=0.008), and 2.45 (
P
=0.002), respectively, compared with the lowest quartile. Fibrinogen at follow-up also was associated with progressive disease (
P
=0.004). However, additionally adjusting for other inflammatory parameters diminished these associations to a nonsignificant level.

Conclusion—

Elevated fibrinogen, reflecting the level of inflammatory activity, is associated with progression of carotid atherosclerosis, as it was demonstrated previously for other inflammatory parameters. However, this association seems to be nonspecifically related to the extent of the inflammatory process in atherosclerotic disease rather than to specific properties of fibrinogen.
Folate, Vitamin B
12
, and Risk of Ischemic and Hemorrhagic Stroke
Authors: Van Guelpen Bethany , Hultdin Johan , Johansson Ingegerd , Stegmayr Birgitta , Hallmans Göran , K. Nilsson Torbjörn , Weinehall Lars , Witthöft Cornelia , Palmqvist Richard , Winkvist Anna
Published: June 2005

Background and Purpose—

Folate metabolism has been implicated in stroke. However, the possibility of a role for folate and vitamin B
12
, independent of their effects on homocysteine status, remains to be explored. The aim of this prospective, nested case-referent study was to relate plasma and dietary intake levels of folate and vitamin B
12
to risk of stroke, taking into consideration plasma homocysteine concentrations and methylenetetrahydrofolate reductase polymorphisms.

Methods—

Subjects were 334 ischemic and 62 hemorrhagic stroke cases and matched double referents from the population-based Northern Sweden Health and Disease Cohort.

Results—

Plasma folate was statistically significantly associated with risk of hemorrhagic stroke in an inverse linear manner, both in univariate analysis and after adjustment for conventional risk factors including hypertension (odds ratio [OR] for highest versus lowest quartile 0.21 (95% confidence interval [CI], 0.06 to 0.71;
P
for trend=0.008)). Risk estimates were attenuated by inclusion of homocysteine in the model (OR, 0.34; 95% CI, 0.08 to 1.40;
P
for trend=0.088). A similar pattern was observed for increasing folate intake (multivariate OR, 0.07; 95% CI, 0.01 to 0.55;
P
for trend=0.031 without homocysteine, and OR, 0.16, 95% CI, 0.02 to 1.23;
P
for trend=0.118 with homocysteine in the analysis). We found little evidence of an association between plasma or dietary folate and risk of ischemic stroke. Neither plasma nor dietary vitamin B
12
was associated with risk of either stroke subtype.

Conclusions—

The results of this study suggest a protective role for folate, possibly in addition to its effects on homocysteine status, in hemorrhagic but not ischemic stroke.
Components of the Metabolic Syndrome and Risk for First-Ever Acute Ischemic Nonembolic Stroke in Elderly Subjects
Authors: Milionis Haralampos J. , Rizos Evangelos , Goudevenos John , Seferiadis Konstantinos , Mikhailidis Dimitri P. , Elisaf Moses S.
Published: June 2005

Background and Purpose—

Metabolic syndrome (MetSyn) represents a constellation of lipid and nonlipid risk factors for cardiovascular disease and is a recognized target for increased behavioral therapy.

Objective—

The association between acute ischemic/nonembolic stroke and the MetSyn in elderly individuals was assessed in a population-based case-control study in the prefecture of Ioannina, Greece.

Study Population—

A total of 163 patients aged older than 70 years admitted with first-ever-in-a-lifetime acute ischemic/nonembolic stroke and 166 controls were included.

Results—

The prevalence of MetSyn (defined according to NCEP/ATP III criteria) was high in stroke patients (46.0% versus 15.7%,
P
<0.001). Compared with controls as a group (with and without MetSyn), stroke patients with the MetSyn showed higher concentrations of triglycerides, lipoprotein(a), uric acid, and fibrinogen, and lower high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I levels. In logistic regression analysis, crude and adjusted odd ratios (ORs) for MetSyn were 5.33 (95% confidence interval [CI], 2.91 to 9.79;
P
<0.0001) and 2.59 (95% CI, 1.24 to 5.42;
P
=0.012), respectively. The analysis of interaction between MetSyn and its individual components revealed significant associations with abdominal obesity (adjusted OR, 2.74; 95% CI, 1.15 to 6.50;
P
=0.02), hypertension (OR, 2.03; 95% CI, 0.91 to 4.49;
P
=0.08), high fasting glucose levels (OR, 2.95; 95% CI, 1.19 to 7.35;
P
=0.02), high triglyceride (OR, 5.55; 95% CI, 2.71 to 11.37;
P
<0.0001]), and low HDL cholesterol (OR, 5.42; 95% CI, 2.85 to 10.30;
P
<0.0001). Notably, in stroke patients with the MetSyn the inverse relationship between HDL cholesterol levels and ischemic stroke was negated (OR, 1.04; 95% CI, 1.02 to 1.05;
P
<0.0001).

Conclusions—

MetSyn is associated with an increased risk for acute ischemic/nonembolic stroke in elderly subjects with significant contributions from its individual components. In the presence of MetSyn, HDL cholesterol loses its protective role against ischemic stroke.
Subcortical Aphasia
Authors: de Boissezon Xavier , Démonet Jean-François , Puel Michèle , Marie Nathalie , Raboyeau Gaëlle , Albucher Jean-François , Chollet François , Cardebat Dominique
Published: June 2005

Background and Purpose—

Very few neuroimaging studies have focused on follow-up of subcortical aphasia. Here, overt language production tasks were used to correlate regional cerebral blood flow (rCBF) changes and language performance in patients with vascular subcortical lesions.

Methods—

Seven aphasic patients were scanned twice with positron emission tomography (PET) at 1-year interval during a word-generation task. Using SPM2, Language-Rest contrast at PET1 was correlated to language performance and to time-lag from stroke. The same contrast was performed at PET2 and session effect (PET2–PET1) was correlated with performance improvement.

Results—

At PET1, correlation between rCBF and delay from stroke involved mainly ventral regions of the left temporal cortex and mesial frontal cortex. Correlations between rCBF and performance showed predominantly left dorsal regions in the frontal, temporal, and parietal lobes, but also the left ventral temporal cortex. One year apart, language performance improved and rCBF increased in perisylvian regions bilaterally. Best performers at PET2 showed an increase of activity in left ventral temporal cortex as well as in right middle temporal gyrus.

Conclusions—

On follow-up, expected language improvement and increase of activation in the classical language areas and their counterparts were observed. Moreover, all correlational analyses both at PET1 and on follow-up implicated the anterior part of the left inferior temporal gyrus, suggesting a disconnection between the superior and inferior parts of the left temporal cortex and a specific role for this region in lexical semantic processing.
Multi-Detector Row Computed Tomography Angiography in Diagnosing Spinal Dural Arteriovenous Fistula
Authors: Lai Ping-Hong , Pan Huay-Ben , Yang Chien-Fang , Yeh Lee-Ren , Hsu Shu-Shong , Lee Kwo-Wei , Weng Mei-Jui , Wu Ming-Ting , Liang Huei-Lung , Chen Clement-Kuen
Published: June 2005

Background and Purpose—

Multi-detector computed tomographic (MDCT) angiography is a recently developed imaging technique that can study small vessels such as medullary arteries and veins. The purpose of this study was to evaluate MDCT angiography in diagnosing SDAVF.

Methods—

Eight patients with initial magnetic resonance imaging (MRI) and clinical findings suggestive of spinal dural arteriovenous fistula (SDAVF) and 8 control subjects underwent MDCT angiography. Both MDCT angiography and catheter angiography were performed within 5 days in patients with SDAVFs. The results of MDCT angiography in patients with SDAVFs were compared with those of catheter angiography.

Results—

MDCT angiography detected engorged perimedullary draining veins and correctly localized the fistula of the SDAVFs, and correlated well with catheter angiography. Fistula was at the thoracic level in 7 patients, and sacral level in 1 patient. MDCT angiography did not visualize the engorged perimedullary venous plexus in the control group.

Conclusion—

MDCT angiography correlated well with catheter angiography in diagnosing SDAVFs. It might play a role in shortening the length of the catheter angiography in diagnosing this disease.
How Close Are We to Understanding V1?
Authors: Olshausen Bruno A. , Field David J.
Published: May 2005

A wide variety of papers have reviewed what is known about the function of primary visual cortex. In this review, rather than stating what is known, we attempt to estimate how much is still unknown about V1 function. In particular, we identify five problems with the current view of V1 that stem largely from experimental and theoretical biases, in addition to the contributions of nonlinearities in the cortex that are not well understood. Our purpose is to open the door to new theories, a number of which we describe, along with some proposals for testing them.
Erkundungen Von Gegenwelten: Zur Orientierungsleistung «mythischer» Reisen Am Beispiel Zweier Mesopotamischer Texte Erkundungen Von Gegenwelten: Zur Orientierungsleistung «mythischer» Reisen Am Beispiel Zweier Mesopotamischer Texte
Authors: Pezzoli-Olgiati Daria
Published: May 2005

The present article focuses on the function of mythic journeys with regard to the problem of death and the transience of human life in two selected Mesopotamian literary sources: the Gilgamesh-Epic IX–XI and the Descent of Ishtar to the Underworld. The selected texts are analysed and compared from the perspective of a functionalist definition of religious symbol systems, with particular attention to the transformation involved in travelling through different cosmic regions. The structure of the journey, the characterisation of the different regions visited by the protagonist, and the changes provoked by the mythic travel evince similarities and differences in the strategies employed to produce a religious orientation dealing with the ineluctable limits of life.
Locality and Myth: the Resacralization of Selja and the Cult of St. Sunniva
Authors: Mikaelsson Lisbeth
Published: May 2005

The article demonstrates the merging of contemporary processes of resacralization, retraditionalization, and local identity construction embodied in one particular example, the island of Selja on the west coast of Norway. In Roman-Catholic times, Selja was a major pilgrimage site, famous for its legend of St. Sunniva, an Irish princess who fled from her country and took refuge on the island where she suffered a martyr death. The national conversion to Lutheranism in the 16th century put an end to the official Sunniva cult. In our time, however, the legend has been revived and is celebrated for various purposes by the local Lutheran state church, the tourist business, and individuals who are attracted to the symbolic complex of Selja-Sunniva for spiritual reasons. The article argues that the revival of the legend converts the old site with its ruins and landscape features into a narrative space, re-establishing a sanctuary with a variety of symbolic references. Selja meets the requirements of modern seekers and pilgrims, while its history and myth are excellently fitted to serve local identity construction.
Is “Buddha-Nature” Buddhist?
Authors: King Richard
Published: June 2005

Recent controversies in Japanese Buddhist scholarship have focused upon the Mahāyāna notion of a “Buddha nature” within all sentient beings and whether or not the concept is compatible with traditional Buddhist teachings such as anātman (no-abiding-self). This controversy is not only relevant to Far Eastern Buddhism, for which the notion of a Buddha-nature is a central doctrinal theme, but also for the roots of this tradition in those Indian Mahāyāna sūtras which utilised the notion of tathāgatagarbha (Buddha-embryo or Buddha womb). One of the earliest Buddhist texts to discuss this notion is the Queen Śrīmālā Sūtra (Śrīmālādevīsūtra), which appears to display a transitional and revisionist attitude towards traditional Mahāyāna doctrines such as emptiness (śūnyatā) and no-abiding-self (anātman). These and related issues are examined as they occur in the Śrīmālā Sūtra and as they might relate to the issue of the place of Buddha-nature thought within the Buddhist tradition. Finally some concluding remarks are made about the quest for “true” Buddhism.
SOD polymorphism in the Xiphinema americanum-group (Nematoda: Longidoridae)
Authors: Robbins Robert , Lemos Rui , Nagy Peter , McKenry Michael , Lamberti Franco , Abawi George , Moens Maurice , Kotcon James , Crozzoli Renato , Molinari Sergio , Magunacelaya Juan Carlos , Halbrendt John , Duncan Larry , Brown Derek , Nyczepir Andrew
Published: May 2005

Isoelectrofocusing of superoxide dismutase (SOD) isoforms was carried out on the extracts of 117 nematode populations belonging to the so-called Xiphinema americanum-group. These populations came from the USA (77), Chile (5), Argentina (1), Venezuela (5), Portugal (15), Italy (2), Crete (1), Montenegro (1), Slovakia (4), Hungary (3), Egypt (1) and India (2). A total of 17 bands of enzyme activity were observed in the screening, whilst single enzyme phenotypes showed from two to eight bands. The high degree of SOD polymorphism of this nematode collection was grouped by cluster analysis into seven distinct homogeneous groups characterised by specific combinations of SOD markers. Sub-groups could be discriminated for larger groups. The small Groups 3 and 5 were constituted mostly by populations from USA east coast states (i.e., NY and PA, respectively). The larger Group 1 resulted from the association of populations coming from various and distant North American States. In other large groups, North American populations were associated with South American and European populations. Overall, the data presented here suggest that geographic separation and different hosts do not seem to be the source of genetic diversity for the X. americanum-group. When an adequate number of populations were collected from the same country, the variability expressed by such a sub-sample was comparable to that of the whole nematode collection. For the first time, homogeneous populations of a large collection of X. americanum-group populations were associated by molecular means in order to explore further approaches that may help resolve the recalcitrant taxonomy and phylogeny of this much debated group.
Spirits and Land Reforms: Conflicts About Land in Dande, Northern Zimbabwe
Authors: Spierenburg Marja
Published: May 2005

Despite its present support for the invasion of (mainly white-owned) commercial farms and emphasis on 'fast-track resettlement', most interventions by the post-Independence government of Zimbabwe in agriculture aimed to confine African farmers to the Communal Areas. In Dande, northern Zimbabwe, a land reform programme was introduced in 1987 that sought to 'rationalise' local land use practices and render them more efficient. Such reforms were deemed necessary to reduce the pressure on commercial farms. This article describes how the reforms caused Mhondoro mediums in Dande to challenge the authority of the state over land, thereby referring to the role they and their spirits played in the struggle for Independence. Pressure on the mediums to revoke their criticism resulted in a complex process in which adherents challenged the reputation of mediums who were not steadfast in their resistance to the reforms.
Community Policing: A Preliminary Assessment of Environmental Impact With Panel Data on Program Implementation in U.S. Cities
Authors: He Ni (Phil) , Zhao Jihong (Solomon) , Lovrich Nicholas P.
Published: June 2005

This article examines the environmental impact on the programmatic implementation of community-oriented policing (COP) in large municipal police agencies during the 1990s. Three waves of nationwide surveys (1993, 1996, and 2000) based on a random sample of 281 municipalities and the corresponding police agencies were used for our analysis. Based on one-way generalized least square (GLS) panel data analysis, we found that post-Crime Control Act of 1994federal funding and council-manager forms of government are significant predictors of COP implementation. To the contrary, other environmental factors such as personnel resources, city socioeconomic status, and mechanisms for citizen participation did not yield any statistically significant effects.
A Review of Gender Differences Among Substance Abusers
Authors: Pelissier Bernadette , Jones Nicole
Published: June 2005

This article provides a review of various types of literature on gender differences among substance abusers. The authors begin this literature review by summarizing the literature on the differing treatment needs of men and women. The authors continue with a review of the empirically based literature on gender differences in background characteristics of substance users. They conclude with a review of treatment outcome studies. This review provides a context for identifying the gaps in the literature and identifies a research agenda that will help improve treatment services for women in both community-based and prison settings.
Predicting Offender-Generated Exchange Rates: Implications for a Theory of Sentence Severity
Authors: May David C. , Wood Peter B. , Mooney Jennifer L. , Minor Kevin I.
Published: June 2005

We solicited offender-generated exchange rates between prison and several noncustodial sanctions from a sample of 588 offenders currently serving community-based punishments. We then regressed these exchange rates on demographic, attitudinal, and correctional experience indicators. Males, Blacks, older offenders, offenders with prison experience, and those who agree most strongly with reasons to avoid alternative sanctions are likely to serve less of a given alternative to avoid imprisonment. In addition, offender-generated exchange rates are used to develop a ranking of sanction severity that includes prison and nine intermediate sanctions. Implications of these findings for correctional policy, practice, and a theory of sentence severity are discussed.
Team effectiveness in China: Cooperative conflict for relationship building
Authors: Tjosvold Dean , Poon Margaret , Yu Zi-you
Published: June 2005

Groups are increasingly responsible for accomplishing critical, complex tasks for organizations, but understanding and developing effective teamwork have proved difficult. Findings from groups in Chinese enterprises supported recent theorizing that confidence in the group’s interpersonal relationships promotes team effectiveness. Results also suggested, in contrast to traditional theorizing about Chinese values, that conflict management was an important foundation for this confidence in relationships. Specifically, the structural equation analysis supported the reasoning that cooperative conflict builds confidence in relationships that, in turn, results in team effectiveness. Results were interpreted as providing support for the universalistic aspirations of the theory of cooperation and competition and that managing conflict cooperatively is a foundation for team effectiveness in China as well as in the West.
Objections to evolutionary psychology: Reflections, implications and the leadership exemplar
Authors: Nicholson Nigel
Published: June 2005

A recent exchange of articles in Human Relations debated the validity, philosophical coherence and applicability of the ideas of evolutionary psychology (EP), with specific reference, inter alia, to previous writings where the author has sought to apply EP to the field of organizational behaviour. This article aims to analyse key areas of controversy about the logic and assumptions on both sides of the debate and to explore the possibilities for common ground to be found between them. It is argued that this entails an inter-actionist approach to the analysis of individual agency and action, and a co-evolutionary perspective on the social context. Leadership is taken as an exemplar of how this would be applied.