bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Exhaled Nitric Oxide and Breath pH during Fluticasone Wean in Asthma
Authors: Liu Lei , Urban Peter , Hunt John F. , Wilkinson Patricia , Laning Kappy , Gaston Benjamin
Published: September 2009

Background: Inhaled corticosteroid (ICS) therapy improves asthma outcome. Both the anti-inflammatory efficacy and toxicities of ICS therapy are dose dependent. Therefore, there is interest in monitoring airway inflammation during ICS dose adjustments. Objective: Fraction of expired nitric oxide (FENO) and exhaled breath condensate (EBC) pH were studied as noninvasive, corticosteroid-responsive markers of airway inflammation. Methods:We prospectively studied the effect of stepwise ICS wean on FENO and EBC pH over 6 months in otherwise healthy adults with moderate persistent asthma. Results:Eighteen subjects completed the initial dose titration and 13 completed the protocol. Of these, 7 weaned off ICS completely and 6 had exacerbations. FENO rose significantly with ICS withdrawal, though there was heterogeneity in the starting level and the degree of rise. EBC pH was collected at home in all subjects and fell more in subjects who had an exacerbation than in those who did not. The decrease in pH was associated with hazard of exacerbation. Conclusion: FENO can be a patient-specific index of airway inflammation during ICS dose titration; change in EBC pH is one home marker that might possibly be used during ICS dose titration. However, additional studies are required.
Quality of Spirometry in Primary Care for Case Finding of Airway Obstruction in Smokers
Authors: Leuppi J.D. , Miedinger D. , Chhajed P.N. , Buess C. , Schafroth S. , Bucher H.C. , Tamm M.
Published: September 2009

Background: Diagnosis of chronic obstructive pulmonary disease (COPD) and its severity determination is based on spirometry. The quality of spirometry is crucial. Objectives: Our aim was to assess the quality of spirometry performed using a spirometer with automated feedback and quality control in a general practice setting in Switzerland and to determine the prevalence of airflow limitation in smokers aged ≧40 years. Method: Current smokers ≧40 years of age were consecutively recruited for spirometry testing by general practitioners. General practitioners received spirometry training and were provided with an EasyOne™ spirometer. Spirometry tests were assigned a quality grade from A to D and F, based on the criteria of the National Lung Health Education Program. Only spirometry tests graded A–C (reproducible measurements) were included in the analysis of airflow limitation. Results: A total of 29,817 spirometries were analyzed. Quality grades A–D and F were assigned to 33.9, 7.1, 19.4, 27.8 and 11.8% of spirometries, respectively. 95% required ≤5 trials to achieve spirometries assigned grade A. The prevalence of mild, moderate, severe and very severe airway obstruction in individuals with spirometries graded A–C was 6, 15, 5 and 1%, respectively. Conclusion: Spirometries in general practice are of acceptable quality with reproducible spirometry in 60% of measurements. Airway obstruction was found in 27% of current smokers aged ≧40 years. Office spirometry provides a simple and quick means of detecting airflow limitation, allowing earlier diagnosis and intervention in many patients with early COPD.
High Factor VIII Levels Independently Predict Venous Thromboembolism in Cancer Patients
Authors: Vormittag R. , Simanek R. , Ay C. , Dunkler D. , Quehenberger P. , Marosi C. , Zielinski C. , Pabinger I.
Published: September 2009

Objective—

Patients with cancer are at an increased risk for venous thromboembolism (VTE). Clotting factor VIII activity (FVIII) has been established as risk factor of primary and recurrent VTE. We investigated FVIII as predictive parameter of VTE in cancer patients.

Methods and Results—

The prospective observational Cancer and Thrombosis Study (CATS) includes patients with newly diagnosed cancer or disease progression, study end point is symptomatic VTE. FVIII was measured on a Sysmex CA 7000 analyzer. Data on 840 patients (median age: 62 years, 25th to 75th percentile 53 to 68, 378 women) were available for analyses, of these 111 patients had hematologic malignancies and 729 solid cancer. During a median observation time of 495 days 62 events occurred. Cumulative probability of VTE after 6 months was 14% in patients with elevated FVIII-levels and 4% in those with normal levels (
P
=0.001). The association was strongest in younger patients: whereas in 40-year-old patients a 2-fold VTE risk per factor VIII increase of 20% was observed (HR=2.0 [95% CI: 1.5 to 2.7],
P
<0.0001), this association was still present but attenuated in older patients.

Conclusions—

FVIII is independently associated with an increased risk of VTE in cancer patients. The association between FVIII and VTE risk declines with increasing age.
Eotaxin Increases Monolayer Permeability of Human Coronary Artery Endothelial Cells
Authors: Jamaluddin Md Saha , Wang Xinwen , Wang Hao , Rafael Cubas , Yao Qizhi , Chen Changyi
Published: September 2009

Objective—

The objective of this study was to determine the effects and molecular mechanisms of eotaxin, a newly discovered chemokine (CCL11), on endothelial permeability in the human coronary artery endothelial cells (HCAECs).

Methods and Results—

Cells were treated with eotaxin, and the monolayer permeability was studied by using a costar transwell system with a Texas Red–labeled dextran tracer. Eotaxin significantly increased monolayer permeability in a concentration-dependent manner. In addition, eotaxin treatment significantly decreased the mRNA and protein levels of endothelial junction molecules including zonula occludens-1 (ZO-1), occludin, and claudin-1 in a concentration-dependent manner as determined by real-time RT-PCR and Western blot analysis, respectively. Increased oxidative stress was observed in eotaxin-treated HCAECs by analysis of cellular glutathione levels. Furthermore, eotaxin treatment substantially activated the phosphorylation of MAPK p38. HCAECs expressed CCR3. Consequently, antioxidants (ginkgolide B and MnTBAP), specific p38 inhibitor SB203580, and anti-CCR3 antibody effectively blocked the eotaxin-induced permeability increase in HCAECs. Eotaxin also increased the phosphorylation of Stat3 and nuclear translocation of NF-κB in HCAECs.

Conclusions—

Eotaxin increases vascular permeability through CCR3, the downregulation of tight junction proteins, increase of oxidative stress, and activation of MAPK p38, Stat3, and NF-kB pathways in HCAECs.
Cardio-Renal Effects of the A1 Adenosine Receptor Antagonist SLV320 in Patients With Heart Failure
Authors: Mitrovic Veselin , Seferovic Petar , Dodic Slobodan , Krotin Mirjana , Neskovic Aleksander , Dickstein Kenneth , de Voogd Hanka , Böcker Christiane , Ziegler Dieter , Godes Michael , Nakov Roumen , Essers Hans , Verboom Cees , Hocher Berthold
Published: September 2009

Background—Blocking the tubuloglomerular feedback mechanism with adenosine A1 receptor antagonists seems to improve diuresis and sodium excretion without compromising the glomerular filtration rate in patients with heart failure. However, the direct cardiac effects of this compound class have not been investigated to date.

Methods and Results—In total, 111 patients (109 men and 2 women) received a 1-hour infusion of 5, 10, and 15 mg SLV320, an adenosine A1 receptor antagonist, placebo, or 40 mg furosemide. Mean age was 57.9 years, mean ejection fraction was 28.1%, 82 patients were of New York Heart Association class II, and 29 patients were of New York Heart Association class III. Hemodynamic parameters (heart rate, blood pressure, pulmonary capillary wedge pressure, mean pulmonary arterial pressure, systemic vascular resistance, right atrial pressure, and cardiac output) were determined. Kidney function was assessed by cystatin C measurements and by analysis of urine output and urine electrolytes. In addition, pharmacokinetics of SLV320 and ex vivo inhibition of adenosine A1 receptor activity were performed. SLV320 was well tolerated, and no serious adverse events were observed. Heart rate, blood pressure, pulmonary capillary wedge pressure, mean pulmonary arterial pressure, right atrial pressure, and cardiac output were not altered by any dose of SLV320. Pulmonary capillary wedge pressure was significantly (P=0.04) decreased by furosemide (−6.2�5.9 mm Hg). Systemic vascular resistance was significantly (P=0.04) increased in the furosemide group (+166.70�261.87 dynes � s−1� cm−5), whereas all SLV320 groups showed no significant alterations of systemic vascular resistance. Changes from baseline cystatin C plasma concentrations decreased after 10 mg SLV320 (−0.093�0.137 mg/L,P=0.046), whereas furosemide resulted in a significant (P=0.03) increase of cystatin C (+0.052�0.065 mg/L) versus baseline. All values represent mean changes�SD from baseline at 3 hours postdosing: SLV320 (10 and 15 mg) increased significantly sodium excretion and diuresis compared with placebo during the 0- to 6-hour collection period postdosing.

Conclusions—SLV320 infusion shows no immediate effects on cardiac hemodynamics. SLV320 might improve glomerular filtration rate while simultaneously promoting natriuresis and diuresis.

Clinical Trial Registration—clinicaltrials.gov Indentifier: NCT00160134.
Development of Left Ventricular Diastolic Dysfunction With Preservation of Ejection Fraction During Progression of Infant Right Ventricular Hypertrophy
Authors: Kitahori Kazuo , He Huamei , Kawata Mitsuhiro , Cowan Douglas B. , Friehs Ingeborg , del Nido Pedro J. , McGowan Francis X.
Published: September 2009

Background—

Progressive left ventricular (LV) dysfunction can be a major late complication in patients with chronic right ventricular pressure overload (eg, tetralogy of Fallot). Therefore, we examined LV function (serial echocardiography and ex vivo Langendorff) and histology in a model of infant pressure-load right ventricular hypertrophy (RVH).

Methods and Results—

Ten-day-old rabbits (n=6 per time point, total n=48) that underwent pulmonary artery banding were euthanized at 2 to 8 weeks after pulmonary artery banding, and comparisons were made with age-matched sham controls. LV performance (myocardial performance index) decreased during the progression of RVH, although the LV ejection fraction was maintained. In addition, RVH caused significant septal displacement, reduced septal contractility, and decreased LV end-systolic and end-diastolic dimensions, resulting in LV diastolic dysfunction with the appearance of preserved ejection fraction. Significant septal and LV free-wall apoptosis (myocyte-specific TUNEL and activated caspase-3), fibrosis (Masson trichrome stain), and reduced capillary density (CD31 immunostaining) occurred in the pulmonary artery banding group after 6 to 8 weeks (all
P
<0.05).

Conclusion—

This is the first study showing that pressure overload of the right ventricular resulting in RVH causes LV diastolic dysfunction while preserving ejection fraction through mechanical and molecular effects on the septum and LV myocardium. In particular, the development of RVH is associated with septal and LV apoptosis and reduced LV capillary density.
Role of Ca
2+
/Calmodulin-Stimulated Cyclic Nucleotide Phosphodiesterase 1 in Mediating Cardiomyocyte Hypertrophy
Authors: Miller Clint L. , Oikawa Masayoshi , Cai Yujun , Wojtovich Andrew P. , Nagel David J. , Xu Xiangbin , Xu Haodong , Florio Vince , Rybalkin Sergei D. , Beavo Joseph A. , Chen Yiu-Fai , Li Jian-Dong , Blaxall Burns C. , Abe Jun-ichi , Yan Chen
Published: September 2009

Rationale:

Cyclic nucleotide phosphodiesterases (PDEs) through the degradation of cGMP play critical roles in maintaining cardiomyocyte homeostasis. Ca
2+
/calmodulin (CaM)-activated cGMP-hydrolyzing PDE1 family may play a pivotal role in balancing intracellular Ca
2+
/CaM and cGMP signaling; however, its function in cardiomyocytes is unknown.

Objective:

Herein, we investigate the role of Ca
2+
/CaM-stimulated PDE1 in regulating pathological cardiomyocyte hypertrophy in neonatal and adult rat ventricular myocytes and in the heart in vivo.

Methods and Results:

Inhibition of PDE1 activity using a PDE1-selective inhibitor, IC86340, or downregulation of PDE1A using siRNA prevented phenylephrine induced pathological myocyte hypertrophy and hypertrophic marker expression in neonatal and adult rat ventricular myocytes. Importantly, administration of the PDE1 inhibitor IC86340 attenuated cardiac hypertrophy induced by chronic isoproterenol infusion in vivo. Both PDE1A and PDE1C mRNA and protein were detected in human hearts; however, PDE1A expression was conserved in rodent hearts. Moreover, PDE1A expression was significantly upregulated in vivo in the heart and myocytes from various pathological hypertrophy animal models and in vitro in isolated neonatal and adult rat ventricular myocytes treated with neurohumoral stimuli such as angiotensin II (Ang II) and isoproterenol. Furthermore, PDE1A plays a critical role in phenylephrine-induced reduction of intracellular cGMP- and cGMP-dependent protein kinase (PKG) activity and thereby cardiomyocyte hypertrophy in vitro.

Conclusions:

These results elucidate a novel role for Ca
2+
/CaM-stimulated PDE1, particularly PDE1A, in regulating pathological cardiomyocyte hypertrophy via a cGMP/PKG-dependent mechanism, thereby demonstrating Ca
2+
and cGMP signaling cross-talk during cardiac hypertrophy.
Dystroglycan Matrix Receptor Function in Cardiac Myocytes Is Important for Limiting Activity-Induced Myocardial Damage
Authors: Michele Daniel E. , Kabaeva Zhyldyz , Davis Sarah L. , Weiss Robert M. , Campbell Kevin P.
Published: September 2009

Rationale:

Genetic mutations in a number of putative glycosyltransferases lead to the loss of glycosylation of dystroglycan and loss of its laminin-binding activity in genetic forms of human muscular dystrophy. Human patients and glycosylation defective
myd
mice develop cardiomyopathy with loss of dystroglycan matrix receptor function in both striated and smooth muscle.

Objective:

To determine the functional role of dystroglycan in cardiac muscle and smooth muscle in the development of cardiomyopathy in muscular dystrophies.

Methods and Results:

Using cre/lox–mediated gene targeting, we show here that loss of dystroglycan function in ventricular cardiac myocytes is sufficient to induce a progressive cardiomyopathy in mice characterized by focal cardiac fibrosis, increase in cardiac mass, and dilatation ultimately leading to heart failure. In contrast, disruption of dystroglycan in smooth muscle is not sufficient to induce cardiomyopathy. The specific loss of dystroglycan function in cardiac myocytes causes the accumulation of large, clustered patches of myocytes with membrane damage, which increase in number in response to exercise-induced cardiac stress, whereas exercised mice with normal dystroglycan expression accumulate membrane damage limited to individual myocytes.

Conclusions:

Our findings suggest dystroglycan function as an extracellular matrix receptor in cardiac myocytes plays a primary role in limiting myocardial damage from spreading to neighboring cardiac myocytes, and loss of dystroglycan matrix receptor function in cardiac muscle cells is likely important in the development of cardiomyopathy in glycosylation-deficient muscular dystrophies.
Deletion of Protein Tyrosine Phosphatase 1b Improves Peripheral Insulin Resistance and Vascular Function in Obese, Leptin-Resistant Mice via Reduced Oxidant Tone
Authors: Ali M. Irfan , Ketsawatsomkron Pimonrat , Belin de Chantemele Eric J. , Mintz James D. , Muta Kenjiro , Salet Christina , Black Stephen M. , Tremblay Michel L. , Fulton David J. , Marrero Mario B. , Stepp David W.
Published: September 2009

Rationale:

Obesity is a risk factor for cardiovascular dysfunction, yet the underlying factors driving this impaired function remain poorly understood. Insulin resistance is a common pathology in obese patients and has been shown to impair vascular function. Whether insulin resistance or obesity, itself, is causal remains unclear.

Objective:

The present study tested the hypothesis that insulin resistance is the underlying mediator for impaired NO-mediated dilation in obesity by genetic deletion of the insulin-desensitizing enzyme protein tyrosine phosphatase (PTP)1B in
db/db
mice.

Methods and Results:

The
db/db
mouse is morbidly obese, insulin-resistant, and has tissue-specific elevation in PTP1B expression compared to lean controls. In
db/db
mice, PTP1B deletion improved glucose clearance, dyslipidemia, and insulin receptor signaling in muscle and fat. Hepatic insulin signaling in
db/db
mice was not improved by deletion of PTP1B, indicating specific amelioration of peripheral insulin resistance. Additionally, obese mice demonstrate an impaired endothelium dependent and independent vasodilation to acetylcholine and sodium nitroprusside, respectively. This impairment, which correlated with increased superoxide in the
db/db
mice, was corrected by superoxide scavenging. Increased superoxide production was associated with increased expression of NAD(P)H oxidase 1 and its molecular regulators, Noxo1 and Noxa1.

Conclusions:

Deletion of PTP1B improved both endothelium dependent and independent NO-mediated dilation and reduced superoxide generation in
db/db
mice. PTP1B deletion did not affect any vascular function in lean mice. Taken together, these data reveal a role for peripheral insulin resistance as the mediator of vascular dysfunction in obesity.
TRPC1 Channels Are Critical for Hypertrophic Signaling in the Heart
Authors: Seth Malini , Zhang Zhu-Shan , Mao Lan , Graham Victoria , Burch Jarrett , Stiber Jonathan , Tsiokas Leonidas , Winn Michelle , Abramowitz Joel , Rockman Howard A. , Birnbaumer Lutz , Rosenberg Paul
Published: September 2009

Rationale:

Cardiac muscle adapts to increase workload by altering cardiomyocyte size and function resulting in cardiac hypertrophy. G protein–coupled receptor signaling is known to govern the hypertrophic response through the regulation of ion channel activity and downstream signaling in failing cardiomyocytes.

Objective:

Transient receptor potential canonical (TRPC) channels are G protein–coupled receptor operated channels previously implicated in cardiac hypertrophy. Our objective of this study is to better understand how TRPC channels influence cardiomyocyte calcium signaling.

Methods and Results:

Here, we used whole cell patch clamp of adult cardiomyocytes to show upregulation of a nonselective cation current reminiscent of TRPC channels subjected to pressure overload. This TRPC current corresponds to the increased TRPC channel expression noted in hearts of mice subjected to pressure overload. Importantly, we show that mice lacking TRPC1 channels are missing this putative TRPC current. Moreover,
Trpc1
−
/
−
mice fail to manifest evidence of maladaptive cardiac hypertrophy and maintain preserved cardiac function when subjected to hemodynamic stress and neurohormonal excess. In addition, we provide a mechanistic basis for the protection conferred to
Trpc1
−
/
−
mice as mechanosensitive signaling through calcineurin/NFAT, mTOR and Akt is altered in
Trpc1
−
/
−
mice.

Conclusions:

From these studies, we suggest that TRPC1 channels are critical for the adaptation to biomechanical stress and TRPC dysregulation leads to maladaptive cardiac hypertrophy and failure.
Whole Body UVA Irradiation Lowers Systemic Blood Pressure by Release of Nitric Oxide From Intracutaneous Photolabile Nitric Oxide Derivates
Authors: Opländer Christian , Volkmar Christine M. , Paunel-Görgülü Adnana , van Faassen Ernst E. , Heiss Christian , Kelm Malte , Halmer Daniel , Mürtz Manfred , Pallua Norbert , Suschek Christoph V.
Published: September 2009

Rationale:

Human skin contains photolabile nitric oxide derivates like nitrite and
S
-nitroso thiols, which after UVA irradiation, decompose and lead to the formation of vasoactive NO.

Objective:

Here, we investigated whether whole body UVA irradiation influences the blood pressure of healthy volunteers because of cutaneous nonenzymatic NO formation.

Methods and Results:

As detected by chemoluminescence detection or by electron paramagnetic resonance spectroscopy in vitro with human skin specimens, UVA illumination (25 J/cm
2
) significantly increased the intradermal levels of free NO. In addition, UVA enhanced dermal
S
-nitrosothiols 2.3-fold, and the subfraction of dermal
S
-nitrosoalbumin 2.9-fold. In vivo, in healthy volunteers creamed with a skin cream containing isotopically labeled
15
N-nitrite, whole body UVA irradiation (20 J/cm
2
) induced significant levels of
15
N-labeled
S
-nitrosothiols in the blood plasma of light exposed subjects, as detected by cavity leak out spectroscopy. Furthermore, whole body UVA irradiation caused a rapid, significant decrease, lasting up to 60 minutes, in systolic and diastolic blood pressure of healthy volunteers by 11±2% at 30 minutes after UVA exposure. The decrease in blood pressure strongly correlated (
R
2
=0.74) with enhanced plasma concentration of nitrosated species, as detected by a chemiluminescence assay, with increased forearm blood flow (+26±7%), with increased flow mediated vasodilation of the brachial artery (+68±22%), and with decreased forearm vascular resistance (−28±7%).

Conclusions:

UVA irradiation of human skin caused a significant drop in blood pressure even at moderate UVA doses. The effects were attributed to UVA induced release of NO from cutaneous photolabile NO derivates.
Effect of Telmisartan on Functional Outcome, Recurrence, and Blood Pressure in Patients With Acute Mild Ischemic Stroke
Authors: Bath Philip M. W. , Martin Reneé H. , Palesch Yuko , Cotton Daniel , Yusuf Salim , Sacco Ralph , Diener Hans-Christoph , Toni Danilo , Estol Conrado , Roberts Robin
Published: September 2009

Background and Purpose—

High blood pressure (BP) is common in acute ischemic stroke and associated independently with a poor functional outcome. However, the management of BP acutely remains unclear because no large trials have been completed.

Methods—

The factorial PRoFESS secondary stroke prevention trial assessed BP-lowering and antiplatelet strategies in 20 332 patients; 1360 were enrolled within 72 hours of ischemic stroke, with telmisartan (angiotensin receptor antagonist, 80 mg/d, n=647) vs placebo (n=713). For this nonprespecified subgroup analysis, the primary outcome was functional outcome at 30 days; secondary outcomes included death, recurrence, and hemodynamic measures at up to 90 days. Analyses were adjusted for baseline prognostic variables and antiplatelet assignment.

Results—

Patients were representative of the whole trial (age 67 years, male 65%, baseline BP 147/84 mm Hg, small artery disease 60%, NIHSS 3) and baseline variables were similar between treatment groups. The mean time from stroke to recruitment was 58 hours. Combined death or dependency (modified Rankin scale: OR, 1.03; 95% CI, 0.84–1.26;
P
=0.81; death: OR, 1.05; 95% CI, 0.27–4.04; and stroke recurrence: OR, 1.40; 95% CI, 0.68–2.89;
P
=0.36) did not differ between the treatment groups. In comparison with placebo, telmisartan lowered BP (141/82 vs 135/78 mm Hg, difference 6 to 7 mm Hg and 2 to 4 mm Hg;
P
<0.001), pulse pressure (3 to 4 mm Hg;
P
<0.002), and rate-pressure product (466 mm Hg.bpm;
P
=0.0004).

Conclusion—

Treatment with telmisartan in 1360 patients with acute mild ischemic stroke and mildly elevated BP appeared to be safe with no excess in adverse events, was not associated with a significant effect on functional dependency, death, or recurrence, and modestly lowered BP.
Silent Cerebral Infarcts in Patients With Pulmonary Embolism and a Patent Foramen Ovale
Authors: Clergeau Marie-Rose , Hamon Michèle , Morello Rémy , Saloux Eric , Viader Fausto , Hamon Martial
Published: September 2009

Background and Purpose—

Pulmonary embolism is thought to be associated with a small but definite risk of paradoxical embolism in patients with a patent foramen ovale (PFO). Although neurological complications are infrequent, the incidence of clinically silent brain infarction is unknown. We assessed the rate of clinically apparent and silent cerebral embolism in patients with pulmonary embolism in relation to the presence or not of a PFO.

Methods—

We used diffusion-weighted MRI in patients hospitalized for a pulmonary embolism to assess cerebral embolic events. Sixty consecutive patients were evaluated at diffusion-weighted MRI. All patients underwent neurological assessment before diffusion-weighted MRI and a contrast echocardiography to detect PFO the next day.

Results—

Diffusion-weighted MRI showed bright lesions in 6 patients among the 60 consecutive patients with pulmonary embolism in a pattern consistent with embolic events. There was only one patient with a neurological deficit. After contrast echocardiography, a PFO was diagnosed in 15 patients (25%). The frequency of silent brain infarcts in patients with a PFO was significantly higher than in patients without PFO (5 [33.3%] of 15 versus one [2.2%] of 45 patients,
P
=0.003). By logistic regression analysis, PFO was identified as an independent predictor of silent brain infarcts (OR, 34.9 [3.1 to 394.3];
P
=0.004).

Conclusions—

In pulmonary embolism, cerebral embolic events are more frequent than the apparent neurological complication rate. The prevalence of silent brain infarcts is closely related to the presence of a PFO suggesting a high incidence of unsuspected paradoxical emboli in those patients.
Hemodynamic Compromise as a Cause of Internal Border-Zone Infarction and Cortical Neuronal Damage in Atherosclerotic Middle Cerebral Artery Disease
Authors: Yamauchi Hiroshi , Nishii Ryuichi , Higashi Tatsuya , Kagawa Shinya , Fukuyama Hidenao
Published: September 2009

Background and Purpose—

Hemodynamic compromise due to atherosclerotic middle cerebral artery (MCA) disease may induce internal border-zone infarction and cortical neuronal damage. This study aimed to determine whether internal border-zone infarction is associated with increased oxygen extraction fraction (OEF) and a decrease in central benzodiazepine receptors (BZRs) in the overlying cerebral cortex in atherosclerotic MCA disease.

Methods—

We measured the OEF by using positron emission tomography and
15
O gas in 100 nondisabled patients with atherosclerotic MCA disease in the chronic stage. On MRI, the infarcts were categorized as territorial, border-zone (external or internal), deep perforator, and superior perforator infarcts. In 62 patients, BZRs were measured using
11
C-flumazenil. By using 3-dimensional stereotactic surface projections, the abnormally decreased BZR index (“BZR index”) [(the extent of the pixels with Z score more than 2 compared with controls)×(average Z score in those pixels)] was calculated. In the hemisphere affected by MCA disease, the type of infarcts was correlated with the value of OEF or BZR index in the cerebral cortex of the MCA distribution.

Results—

Compared with patients without internal border-zone infarcts, those with these infarcts (n=18) had significantly increased OEF and significantly high BZR index. Multivariate analysis revealed that internal border-zone infarction was independently associated with increased OEF and high BZR index.

Conclusions—

In atherosclerotic MCA disease, internal border-zone infarction is associated with increased OEF and a decrease in BZRs in the overlying cerebral cortex, suggesting that hemodynamic compromise may induce internal border-zone infarction and cortical neuronal damage.
Child Rearing in a Group Setting
Authors: Huijbregts Sanne K. , Tavecchio Louis , Leseman Paul , Hoffenaar Peter
Published: September 2009

Child care centers in Western countries are becoming increasingly culturally diverse, regarding both professional caregivers, children, and their parents. Child-rearing beliefs, which differ between cultures, are found to affect process quality and children’s developmental outcomes. The first aim of this study is to investigate cultural differences in caregivers’ cultural child-rearing beliefs through a semistructured interview. The second aim is to explore the relation between the centers’ cultural context and caregivers’ beliefs. Participants are 61 caregivers (20 Dutch, 20 Caribbean Dutch, and 21 Mediterranean Dutch) working in Dutch child care centers with 2- to 4-year-olds. Cultural differences between Dutch and immigrant caregivers are evident. Dutch caregivers mentioned independence as a socialization goal most, whereas Mediterranean Dutch caregivers stressed collectivistic child-rearing goals most. More years of experience and a positive orientation toward the Dutch society made caregivers value individualistic child-rearing goals more. Working in an ethnically diverse context made both immigrant and Dutch caregivers express collectivistic beliefs more. The results further demonstrate that all cultural groups valued dimensions of both individualism and collectivism, providing further support for the multidimensionality of child-rearing beliefs.
Acquiring an Artificial Logographic Orthography
Authors: Ehrich John F. , Meuter Renata F. I.
Published: September 2009

To date, studies have focused on the acquisition of alphabetic second languages in alphabetic first language (L1) users, demonstrating significant transfer effects. The present study examines the process from a reverse perspective, comparing logographic (Mandarin-Chinese) and alphabetic (English) L1 users in the acquisition of an artificial logographic script to determine whether similar language-specific advantageous transfer effects occurred. Chinese-English bilinguals, English-French bilinguals, and English monolinguals learned a small set of symbols (six nouns and six verbs) in an artificial logographic script. A lexical decision task on the artificial symbols revealed markedly faster response times in the Chinese-English bilinguals, indicating a logographic transfer effect suggestive of a language experience— specific advantage. A syntactic decision task evaluated the degree to which the new language was mastered beyond the single word level. No L1-specific transfer effects were found for artificial language strings. However, when carrying out the same task in the native language, both the Chinese-English and the English-French bilinguals outperformed the English monolinguals, indicative of a bilingual processing advantage. The results are discussed in relation to possible differences in processing styles relating to logographic versus alphabetic languages, variably involving visual versus phonological coding.
Literacy, Negotiable Fate, and Thinking Style Among Low Income Women in India
Authors: Chaturvedi Avinish , Chiu Chi-yue , Viswanathan Madhubalan
Published: September 2009

Few studies have examined how cultural models of agency and literacy are related to thinking styles. The present study fills this gap by examining these links among 180 low-income women with low to moderate levels of literacy. Among these women, those with lower literacy levels believed more strongly in negotiable fate—the belief that although one lacks direct control over one’s fate, one can negotiate control with it. More importantly, among the low-literate participants, the belief in negotiable fate was linked to a greater tendency to exhibit decontextualized judgment and rule-based categorization. This result suggests that thinking style may grow out of an adaptive process whereby people with limited resources negotiate control with the harsh environment they face. This result also highlights the theoretical contribution of a sociocultural perspective to thinking style.
Role of Purinergic Receptor in Alpha Fodrin Degradation in Par C5 Cells
Authors: Hwang S.-M. , Li J. , Koo N.-Y. , Choi S.-Y. , Lee S.J. , Oh S.-B. , Castro R. , Kim J.-S. , Park K.
Published: September 2009

Autoantibodies specific for alpha-fodrin fragments are found in the tissues of persons afflicted with Sjögren’s syndrome (SS). However, the mechanism for alpha-fodrin degradation remains elusive. The following experiments utilized Par C5 cells to examine the role of P2X7 receptor (P2X7R) in apoptosis, particularly in the cleavage and release of alpha-fodrin, an apparent SS autoantigen. Five mM ATP stimulation induced apoptotic cell death with a sustained Ca2+ influx, which was mimicked in HEK cells transfected with P2X7R. ATP also induced cleavage of alpha-fodrin mediated by caspase-3 and calpain, releasing alpha-fodrin fragments through membrane blebs. However, both apoptotic cell death and alpha-fodrin cleavage were inhibited in the presence of 300 μM oxidized-ATP (ox-ATP), an irreversible blocker of P2X7R, or in Ca2+-free solution. We concluded that P2X7R plays an important role in apoptosis and alpha-fodrin degradation in salivary epithelial cells, providing an important clue elucidating the presence of alpha-fodrin fragments in SS tissues.
Influence of Luting Material Filler Content on Post Cementation
Authors: Ferrari M. , Carvalho C.A. , Goracci C. , Antoniolli F. , Mazzoni A. , Mazzotti G. , Cadenaro M. , Breschi L.
Published: September 2009

Luting of fiber posts to intra-radicular dentin represents the worst-case scenario in terms of control of polymerization shrinkage. This study tested the hypothesis that filler content of resin cements does not influence luting of fiber posts to intra-radicular dentin, by assaying polymerization stress, push-out bond strength, and nanoleakage expression. The polymerization stress of experimental cements containing 10%, 30%, 50%, or 70% in filler content was investigated. Post spaces were prepared in endodontically treated teeth, and fiber posts were cemented with the experimental cements. A push-out test was performed, and interfacial nanoleakage expression was analyzed. Results showed that luting cements with higher filler content were related to increased polymerization stress (p < 0.05), decreased push-out bond strength (p < 0.05), and increased interfacial nanoleakage expression (p < 0.05). Conversely, lower-stress luting materials increased bonding of fiber posts to intra-radicular dentin. Further in vivo studies are needed to investigate the long-term clinical performance of these materials.
Runx2, Osx, and Dspp in Tooth Development
Authors: Chen S. , Gluhak-Heinrich J. , Wang Y.H. , Wu Y.M. , Chuang H. H. , Chen L. , Yuan G.H , Dong J. , Gay I. , MacDougall M.
Published: September 2009

The transcription factors Runx2 and Osx are necessary for osteoblast and odontoblast differentiation, while Dspp is important for odontoblast differentiation. The relationship among Runx2, Osx, and Dspp during tooth and craniofacial bone development remains unknown. In this study, we hypothesized that the roles of Runx2 and Osx in the regulation of osteoblast and odontoblast lineages may be independent of one another. The results showed that Runx2 expression overlapped with Osx in dental and osteogenic mesenchyme from E12 to E16. At the later stages, from E18 to PN14, Runx2 and Osx expressions remained intense in alveolar bone osteoblasts. However, Runx2 expression was down-regulated, whereas Osx expression was clearly seen in odontoblasts. At later stages, Dspp transcription was weakly present in osteoblasts, but strong in odontoblasts where Osx was highly expressed. In mouse odontoblast-like cells, Osx overexpression increased Dspp transcription. Analysis of these data suggests differential biological functions of Runx2, Osx, and Dspp during odontogenesis and osteogenesis.
Increased Oral Fibroblast Lifespan Is Telomerase-independent
Authors: Enoch S. , Wall I. , Peake M. , Davies L. , Farrier J. , Giles P. , Baird D. , Kipling D. , Price P. , Moseley R. , Thomas D. , Stephens P.
Published: September 2009

Oral mucosal wound-healing is characterized by rapid re-epithelialization and remodeling, with minimal scar formation. This may be attributed to the distinct phenotypic characteristics of the resident fibroblasts. To test this hypothesis, we investigated patient-matched oral mucosal and skin fibroblasts. Compared with skin fibroblasts, oral mucosal fibroblasts had longer proliferative lifespans, underwent more population doublings, and experienced senescence later, which was directly related to longer telomere lengths within oral mucosal fibroblasts. The presence of these longer telomeres was independent of telomerase expression, since both oral oral mucosal fibroblasts and skin fibroblasts were negative for active telomerase, as assessed according to the Telomeric Repeat Amplification Protocol. This study has demonstrated that, compared with skin fibroblasts, oral mucosal fibroblasts are ‘younger’, with a more embryonic/fetal-like phenotype that may provide a notable advantage for their ability to repair wounds in a scarless fashion.
The Impact of Fluoride on Ameloblasts and the Mechanisms of Enamel Fluorosis
Authors: Bronckers A.L.J.J. , Lyaruu D.M. , DenBesten P.K.
Published: September 2009

Intake of excess amounts of fluoride during tooth development cause enamel fluorosis, a developmental disturbance that makes enamel more porous. In mild fluorosis, there are white opaque striations across the enamel surface, whereas in more severe cases, the porous regions increase in size, with enamel pitting, and secondary discoloration of the enamel surface. The effects of fluoride on enamel formation suggest that fluoride affects the enamel-forming cells, the ameloblasts. Studies investigating the effects of fluoride on ameloblasts and the mechanisms of fluorosis are based on in vitro cultures as well as animal models. The use of these model systems requires a biologically relevant fluoride dose, and must be carefully interpreted in relation to human tooth formation. Based on these studies, we propose that fluoride can directly affect the ameloblasts, particularly at high fluoride levels, while at lower fluoride levels, the ameloblasts may respond to local effects of fluoride on the mineralizing matrix. A new working model is presented, focused on the assumption that fluoride increases the rate of mineral formation, resulting in a greater release of protons into the forming enamel matrix.
Micro-organism and Cell Viability on Antimicrobially Modified Titanium
Authors: Omori S. , Shibata Y. , Arimoto T. , Igarashi T. , Baba K. , Miyazaki T.
Published: September 2009

When titanium is anodized by discharge in NaCl solution, both antimicrobial activity and osteoconductivity are conferred. The viability of adherent micro-organisms and cells on antimicrobial titanium remains uncertain. We hypothesized that a thin peroxidation barrier would efficiently destroy adherent bacteria, whereas adherent osteoblastic cells would be viable, since these cells adhere to the surface indirectly though serum proteins. The efficacy of antimicrobial titanium appears to be based on peroxidation, since peroxidation products were detected in parallel with the destruction of bacterial cell-surface structures. The peroxidation effect of antimicrobial titanium was confined to the surface within narrow limits. The viability of osteoblastic cells on the surface was strongly dependent on the presence of serum protein, whereas that of adherent Streptococcus mutans was not affected by the presence of serum proteins. Therefore, differences in the adherent systems used by bacteria and osteoblastic cells are important determinants of their viability on antimicrobial titanium.
Missing Posterior Teeth and Risk of Temporomandibular Disorders
Authors: Wang M.Q. , Xue F. , He J.J. , Chen J.H. , Chen C.S. , Raustia A.
Published: September 2009

There is disagreement about the association between missing posterior teeth and the presence of temporomandibular disorders (TMD). Here, the purpose was to investigate whether the number of missing posterior teeth, their distribution, age, and gender are associated with TMD. Seven hundred and forty-one individuals, aged 21–60 years, with missing posterior teeth, 386 with and 355 without TMD, were included. Four variables—gender, age, the number of missing posterior teeth, and the number of dental quadrants with missing posterior teeth—were analyzed with a logistic regression model. All four variables—gender (OR = 1.59, men = 1, women = 2), age (OR = 0.98), the number of missing posterior teeth (OR = 0.51), and the number of dental quadrants with missing posterior teeth (OR = 7.71)—were entered into the logistic model (P < 0.01). The results indicate that individuals who lose posterior teeth, with fewer missing posterior teeth but in more quadrants, have a higher prevalence of TMD, especially young women.
Impact of Hydrodynamics on Oral Biofilm Strength
Authors: Paramonova E. , Kalmykowa O.J. , van der Mei H.C. , Busscher H.J. , Sharma P.K.
Published: September 2009

Mechanical removal of oral biofilms is ubiquitously accepted as the best way to prevent caries and periodontal diseases. Removal effectiveness strongly depends on biofilm strength. To investigate the influence of hydrodynamics on oral biofilm strength, we grew single- and multi-species biofilms of Streptococcus oralis J22, Actinomyces naeslundii TV14-J1, and full dental plaque at shear rates ranging from 0.1 to 50 1/sec and measured their compressive strength. Subsequently, biofilm architecture was evaluated by confocal laser scanning microscopy. Multi-species biofilms were stronger than single-species biofilms, with strength values ranging from 6 to 51 Pa and from 5 to 17 Pa, respectively. In response to increased hydrodynamic shear, biofilm strength decreased, and architecture changed from uniform carpet-like to more “fluffy” with higher thickness. S. oralis biofilms grown under variable shear of 7 and 50 1/sec possessed properties intermediate of those measured at the respective single shears.
Examination of the Effect of Increasing Doses of Etoricoxib on Oral Methotrexate Pharmacokinetics in Patients With Rheumatoid Arthritis
Authors: Schwartz Jules I. , Agrawal Nancy G. B. , Wong P. H. , Miller Jutta , Bachmann Kenneth , Marbury Thomas , Hoelscher David , Cavanaugh Paul F. , Gottesdiener Keith
Published: September 2009

The authors designed 2 randomized controlled studies to examine the effects of etoricoxib 60 to 120 mg daily on methotrexate pharmacokinetics in 50 rheumatoid arthritis (RA) patients on stable doses of methotrexate (7.5–20 mg). Patients received oral methotrexate at baseline and on days 7 and 14. In study 1, patients received etoricoxib 60 mg (days 1–7) and then 120 mg (days 8–14); in study 2, patients received etoricoxib 90 mg (days 1–7) and then 120 mg (days 8–14). For study 1, the AUC0‐∞ geometric mean ratio (GMR) (90% confidence interval [CI]) for day 7 versus baseline was 1.01 (0.91, 1.12) for etoricoxib 60 mg; the area under the plasma concentration‐time curve from zero to infinity (AUC0‐∞) GMR (90% CI) for day 14 was 1.28 (1.15, 1.42) for etoricoxib 120 mg. For study 2, the AUC0‐∞ GMR (90% CI) for day 7 versus baseline was 1.07 (1.01, 1.13) for etoricoxib 90 mg; the AUC0‐∞ GMR (90% CI) for day 14 was 1.05 (0.99, 1.11) for etoricoxib 120 mg. In summary, etoricoxib 60 and 90 mg had no effect on methotrexate plasma concentrations. Although no effect on methotrexate pharmacokinetics was observed with etoricoxib 120 mg in study 2, GMR AUC0‐∞ fell outside the prespecified bounds in study 1. Standard monitoring of methotrexate‐related toxicity should be continued when etoricoxib and methotrexate are administered concurrently, especially with doses >90 mg etoricoxib.
Multiple Doses of Sitagliptin, a Selective DPP‐4 Inhibitor, Do Not Meaningfully Alter Pharmacokinetics and Pharmacodynamics of Warfarin
Authors: Wright D. Hamish , Herman Gary A. , Maes Andrea , Liu Qi , Johnson‐Levonas Amy O. , Wagner John A.
Published: September 2009

Sitagliptin is an orally active, highly selective dipeptidyl peptidase IV (DPP‐4) inhibitor for treatment of type 2 diabetes mellitus. This randomized, open‐label, 2‐part, 2‐period crossover study assessed pharmacokinetics/pharmacodynamics of warfarin in the presence/absence of multiple‐dose sitagliptin. Twelve participants received treatments A and B separated by >7‐day washout: treatment A involved coadministration of sitagliptin 200 mg/d for 11 days (days 1–11) and warfarin 30 mg on day 5, and treatment B involved warfarin 30 mg alone on day 1. R(+) warfarin, S(−) warfarin, and international normalized ratio (INR) were assayed predose and up to 168 hours postdose. The geometric mean ratios (GMRs; warfarin + sitagliptin/warfarin alone) (90% confidence intervals [CIs]) were 0.99 (0.95, 1.03) and 0.95 (0.90, 1.02) for the AUC0‐∞of R(+) and S(−) warfarin, respectively. GMRs (warfarin + sitagliptin/warfarin alone) (90% CIs) were 0.89 (0.86, 0.93) and 0.89 (0.86, 0.92) for the Cmaxof R(+) and S(−) warfarin, respectively. INR AUC0–168 hand INRmaxGMRs were 1.01 (0.96, 1.06) and 1.08 (1.00, 1.17), respectively. Coadministration of sitagliptin and warfarin was generally well tolerated. Pharmacokinetics (AUC for R(+) and S(−) warfarin) and pharmacodynamics (INR of R(+) or S(−) warfarin) were not meaningfully altered following coadministration of multiple‐dose sitagliptin and single‐dose warfarin, indicating that no dosage adjustment for warfarin is necessary when coadministered with sitagliptin.
Pharmacokinetics and Safety of Sunitinib Malate in Subjects With Impaired Renal Function
Authors: Khosravan Reza , Toh Melvin , Garrett May , La Fargue JoAnn , Ni Grace , Marbury Thomas C. , Swan Suzanne K. , Lunde Norman M. , Bello Carlo L.
Published: September 2009

This phase I, open‐label, single‐dose study evaluates the effects of severe renal impairment and end‐stage renal disease (ESRD) requiring hemodialysis on the pharmacokinetics, safety, and tolerability of sunitinib and its primary active metabolite, SU12662. Subjects with normal renal function (creatinine clearance > 80 mL/min), severe renal impairment (creatinine clearance < 30 mL/min), and ESRD requiring hemodialysis receive a single dose of sunitinib 50 mg. Serial blood samples are collected for quantification of plasma concentrations using a validated liquid chromatography with tandem mass spectrometry assay. Safety is monitored. Twenty‐four subjects complete the study. Pharmacokinetics in subjects with severe renal impairment appear similar to those with normal renal function. Plasma exposure to sunitinib and SU12662 appears lower in subjects with ESRD compared with subjects with normal renal function or severe renal impairment. Single‐dose sunitinib 50 mg is well tolerated regardless of renal function. The currently approved starting dose of sunitinib 50 mg on Schedule 4/2 is expected to be appropriate for patients with renal impairment; any subsequent dose modifications should be based on patients' ability to tolerate treatment.
Soldiers as Police Officers/ Police Officers as Soldiers: Role Evolution and Revolution in the United States
Authors: Campbell Donald J. , Campbell Kathleen M.
Published: September 2009

The military and police professions share a number of common facets, but in spite of surface similarities, the two professions are significantly different. Consequently, the evidence indicating a convergence of primary aspects of the two roles presages an important societal development, with substantial implications on several levels. Thus, this article has several objectives. First, it reviews the evidence indicating role convergence, that is, evidence that significant segments of police operations in the United States have taken on military characteristics; and evidence indicating that many U.S. military initiatives have taken on policing characteristics. Next, using the notion of internal and external role-change “drivers,” it examines how such role shifts occur and considers some political and legal implications of the shift. Third, the article compares the role orientations and job demands of both professions, identifying the important differences inherent in the two roles and presenting an analysis of the occupational implications of role convergence for job holders, job evaluators, and job “clients” (i.e., ordinary citizens). The last section considers the implications of role convergence for role management.