bluuebunny/crossref_metadata_2025 huggingface dataset:
Pressure overload-induced hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes
Authors: Yan Xinhua , Schuldt Adam J. T. , Price Robert L. , Amende Ivo , Liu Fen-Fen , Okoshi Katashi , Ho Kalon K. L. , Pope Adèle J. , Borg Thomas K. , Lorell Beverly H. , Morgan James P.
Published: January 2008

The role of the angiotensin II type 2 (AT2) receptor in cardiac hypertrophy remains controversial. We studied the effects of AT2 receptors on chronic pressure overload-induced cardiac hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes. Left ventricular (LV) hypertrophy was induced by ascending aorta banding (AS). Transgenic mice overexpressing AT2 (AT2TG-AS) and nontransgenic mice (NTG-AS) were studied after 70 days of aortic banding. Nonbanded NTG mice were used as controls. LV function was determined by catheterization via LV puncture and cardiac magnetic resonance imaging. LV myocyte diameter and interstitial collagen were determined by confocal microscopy. Atrial natriuretic polypeptide (ANP) and brain natriuretic peptide (BNP) were analyzed by Northern blot. Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2, inducible nitric oxide synthase (iNOS), endothelial NOS, ERK1/2, p70S6K, Src-homology 2 domain-containing protein tyrosine phosphatase-1, and protein serine/threonine phosphatase 2A were analyzed by Western blot. LV myocyte diameter and collagen were significantly reduced in AT2TG-AS compared with NTG-AS mice. LV anterior and posterior wall thickness were not different between AT2TG-AS and NTG-AS mice. LV systolic and diastolic dimensions were significantly higher in AT2TG-AS than in NTG-AS mice. LV systolic pressure and end-diastolic pressure were lower in AT2TG-AS than in NTG-AS mice. ANP, BNP, and SERCA2 were not different between AT2TG-AS and NTG-AS mice. Phospholamban (PLB) and the PLB-to-SERCA2 ratio were significantly higher in AT2TG-AS than in NTG-AS mice. iNOS was higher in AT2TG-AS than in NTG-AS mice but not significantly different. Our results indicate that AT2 receptor overexpression modified the pathological hypertrophic response to aortic banding in transgenic mice.
Epithelial expression of TIMP-1 does not alter sensitivity to bleomycin-induced lung injury in C57BL/6 mice
Authors: Fattman Cheryl L. , Gambelli Federica , Hoyle Gary , Pitt Bruce R. , Ortiz Luis A.
Published: January 2008

Matrix metalloproteinases (MMPs) are mediators of lung injury, and their activity has been associated with the development of pulmonary fibrosis. To understand how MMPs regulate the development of pulmonary fibrosis, we examined MMP expression in two strains of mice with differing sensitivities to the fibrosis-inducing drug bleomycin. After a single intratracheal injection of the drug, bleomycin-sensitive C57BL/6 mice showed increased expression for MMPs (-2, -7, -9, -13) at both 7 and 14 days posttreatment compared with the bleomycin-resistant BALB/c strain. In addition, TIMP-1, an endogenous inhibitor of MMPs, was upregulated in the lungs of C57BL/6 mice but not BALB/c mice. We designed two strategies to decrease MMP expression to potentially decrease sensitivity of C57BL/6 mice: 1) we engineered C57BL/6 mice that overexpressed TIMP-1 in their lungs via surfactant protein C (SP-C) promoter; and 2) we inhibited expression of MMPs independent of TIMP-1 by knocking out metallothionein (MT), a critical zinc binding protein. SP-C-TIMP-1 mice reduced MMP expression in response to bleomycin. However, they were equally sensitive to bleomycin as their wild-type counterparts, displaying similar levels of hydroxyproline in the lung tissue. MT null mice displayed decreased lung activity of MMPs with no change in TIMP-1. Nonetheless, there was no difference between the MT null and wild-type control littermates with regards to any of the lung injury parameters measured. We conclude that although TIMP-1 expression is differentially regulated in fibrosis-sensitive and fibrosis-resistant strains, epithelial overexpression of TIMP-1 does not appear to substantially alter fibrotic lung disease in mice.
Mechanism of ischemic tolerance induced by hyperbaric oxygen preconditioning involves upregulation of hypoxia-inducible factor-1α and erythropoietin in rats
Authors: Gu Guo-Jun , Li Yun-Ping , Peng Zao-Yun , Xu Jia-Jun , Kang Zhi-Min , Xu Wei-Gang , Tao Heng-Yi , Ostrowski Robert P. , Zhang John H. , Sun Xue-Jun
Published: January 2008

We studied the effect of hyperbaric oxygen (HBO) preconditioning on the molecular mechanisms of neuroprotection in a rat focal cerebral ischemic model. Seventy-two male Sprague-Dawley rats were pretreated with HBO (100% O2, 2 atmospheres absolute, 1 h once every other day for 5 sessions) or with room air. In experiment 1, HBO-preconditioned rats and matched room air controls were subjected to focal cerebral ischemia or sham surgery. Postinjury motor parameters and infarction volumes of HBO-preconditioned rats were compared with those of controls. In experiment 2, HBO-preconditioned rats and matched room air controls were killed at different time points. Brain levels of hypoxia-inducible factor-1α (HIF-1α) and its downstream target gene erythropoietin (EPO) analyzed by Western blotting and RT-PCR as well as HIF-1α DNA-binding and transcriptional activities were determined in the ipsilateral hemisphere. HBO induced a marked increase in the protein expressions of HIF-1α and EPO and the activity of HIF-1α, as well as the expression of EPO mRNA. HBO preconditioning dramatically improved the neurobehavioral outcome at all time points (3.0 ± 2.1 vs. 5.6 ± 1.5 at 4 h, 5.0 ± 1.8 vs. 8.8 ± 1.4 at 8 h, 6.4 ± 1.8 vs. 9.7 ± 1.3 at 24 h; P < 0.01, respectively) and reduced infarction volumes (20.7 ± 4.5 vs. 12.5 ± 3.6%, 2,3,5-Triphenyltetrazolium chloride staining) after cerebral ischemia. This observation indicates that the neuroprotection induced by HBO preconditioning may be mediated by an upregulation of HIF-1α and its target gene EPO.
Hesperidin inhibits ovariectomized-induced osteopenia and shows differential effects on bone mass and strength in young and adult intact rats
Authors: Horcajada M. N. , Habauzit V. , Trzeciakiewicz A. , Morand C. , Gil-Izquierdo A. , Mardon J. , Lebecque P. , Davicco M. J. , Chee W. S. S. , Coxam V. , Offord E.
Published: January 2008

The main aim of this study was to investigate the bone-sparing effect of hesperidin, one of the main flavonoid present in oranges, in two age groups of ovariectomized female rats, compared with their intact controls. Young (3 mo) and adult (6 mo) female Wistar rats were sham operated (SH) or ovariectomized (OVX) and then pair-fed for 90 days a casein-based diet supplemented or not with 0.5% hesperidin (Hp; n = 10/group). In older rats, Hp intake led to a partial inhibition of OVX-induced bone loss, whereas a complete inhibition was obtained in younger animals. At both ages, while plasma osteocalcin concentrations were unchanged, urinary excretion of deoxypyridinoline was reduced by Hp intake, suggesting that Hp was able to slow down bone resorption. Unexpectedly, in intact young rats, Hp consumption resulted in a significant increase in bone mineral density (BMD). Indeed, 6-mo-old HpSH rats had a similar BMD to 9-mo-old nontreated SH adult rats, suggesting an accelerated bone mass gain in the young rats. In contrast, in intact adult rats, Hp did not further increase BMD but did improve their bone strength. The results of this study show a protective effect of Hp on bone loss in OVX rats of both ages without uterine stimulation and accompanied by a lipid-lowering effect. The unexpected and intriguing findings obtained in intact rats showing improved BMD in young rats and improved femoral load in adult rats merit further investigation. The bone and lipid benefits of hesperidin make it an attractive dietary agent for the management of the health of postmenopausal women.
Declining US Stroke Hospitalization since 1997: National Hospital Discharge Survey, 1988–2004
Authors: Fang Jing , Alderman Michael H. , Keenan Nora L. , Croft Janet B.
Published: January 2008

Background and Purpose: While age-adjusted stroke mortality in the United States has declined consistently during the last century, trends in stroke incidence and hospitalization are less known. This study examines trends in stroke hospitalization from 1988 to 2004. Methods: Stroke hospitalizations were estimated from the annual National Hospital Discharge Survey, 1988–2004. Stroke was defined as a first-listed diagnosis of ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification) code 430–434 or 436–438. Trends in hospitalization rates were compared for groups defined by selected patient characteristics. Results: Stroke hospitalizations totaled 603,000 in 1988, peaked at 833,000 in 1997, then declined to 726,000 in 2004, a figure still higher than in 1988. Age-adjusted stroke hospitalization rates for men (per 100,000 population) increased from 287 in 1988 to 352 in 1997, but declined to 265 in 2004, and for women, rates were 252, 293 and 223 in the corresponding years. The majority of stroke hospitalizations in 2004 occurred at ages ≧65 years (69% in men and 78% in women). Decline in rates after 1997 occurred at ages 65–74 and ≧75 years. In 2004, 64% of strokes were classified as ischemic, 16% as hemorrhagic and 16% as ill-defined. Decline in hospitalization rates after 1997 were observed for ischemic and ill-defined, but not for hemorrhagic stroke. Between 1988 and 2004, the reporting of hypertension, diabetes and coronary heart disease as secondary diagnoses among stroke hospitalizations increased. Conclusions: Decline in stroke hospitalizations since 1997 was observed among men and women >65 years, who suffered ischemic or ill-defined stroke. Although long-term observation is needed to confirm this finding, the decline in stroke hospitalizations after 1997 suggests treatment of hypertension may have resulted in stroke prevention.
Optic Neuritis among National Health Insurance Enrollees in Taiwan, 2000–2004
Authors: Woung Lin-Chung , Lin Ching-Heng , Tsai Ching-Yao , Tsai Ming-Tsu , Jou Jieh-Ren , Chou Pesus
Published: January 2008

Background: The objective was to examine the incidence of optic neuritis in Taiwan. A 5-year longitudinal, nationwide, population-based study was conducted. The participants were a random sample of 191,761 subjects, or about 1% of the enrollees in the National Health Insurance program of Taiwan. Methods: We identified subjects who had at least 1 service claim for ambulatory or inpatient care with a principal diagnosis of optic neuritis between 2000 and 2004. We calculated and statistically analyzed the rates of optic neuritis. The main outcome measures were the incidence rates of optic neuritis. Results: From 2000 to 2004, the total cumulative incidence was 1.33 per 1,000 (1.00 vs. 1.67 for male vs. female subjects; p < 0.001, χ2 test). The cumulative incidence rates for the age groups of 0–19, 20–39, 40–59 and ≧60 years were 0.33, 1.05, 2.16 and 2.81 cases per 1,000, respectively. Among the subjects aged 40–59 years, the cumulative incidence was higher in women than in men (p < 0.001, χ2 test). The incidence density of developing multiple sclerosis after optic neuritis was 0.41% per person-year, and the cumulative incidence of multiple sclerosis after a new diagnosis of optic neuritis was 0.78%. Conclusions: We believe our study is the first nationwide investigation of the incidence rates of optic neuritis in Taiwan. In our investigation, the cumulative incidence peaked among the subjects aged 40–59 years, especially in women. In Taiwan, patients with optic neuritis have a notably low rate of conversion to multiple sclerosis.
The Tasmanian Epilepsy Register – A Community-Based Cohort
Authors: D’Souza Wendyl J. , Fryer Jayne L. , Quinn Stephen J. , Taylor Bruce V. , Ficker David M. , O’Brien Terence J. , Pearce Neil E. , Cook Mark J.
Published: January 2008

Background/Aims: Centralized prescription databases may provide an efficient mechanism for recruitment of community-treated disease. Methods: The Australian federal government agency, the Health Insurance Commission (HIC), invited patients to participate in the Tasmanian Epilepsy Register (TER). Eligible patients included those who received at least one anticonvulsant above a ‘reportable’ price threshold between July 1, 2001 and June 30, 2002. Patients were asked to disclose their medical indication for anticonvulsant treatment with additional demographic and prescription information obtained from the HIC. Results: 7,541 were eligible for recruitment. After two mail invitations over 6 months, 3,375 (46.6%) had responded, but TER enrollment amongst those indicating treatment for epilepsy was 1,180 (78.3%). TER participants were more likely to obtain their prescriptions exclusively from their general practitioner (70.9%) or from combined sources (19.1%) rather than from pediatrician (4.2%), neurologist (1.4%) or general physician (1.0%) sources. Patients were more likely to respond with increasing age (linear trend p < 0.001), when from a higher socioeconomic area (linear trend p < 0.001), or if their prescription was obtained from a neurologist (p < 0.001). Conclusion: The national Australian prescription database represents community-treated epilepsy and provides an effective and efficient method for patient recruitment for clinical epidemiological research.
Spatial Memory during Foraging in Prosimian Primates: Propithecus edwardsi and Eulemur fulvus rufus
Authors: Erhart Elizabeth M. , Overdorff Deborah J.
Published: January 2008

A variety of anthropoids travel efficiently from one food source to another, although there is disagreement over how this is accomplished over large-scale space. Mental maps, for example, require that animals internally represent space, geometrically locate landmarks, use true distance and direction, and generate novel shortcuts to resources. Alternately, topological or route-based maps are based on a network of fixed points, landmarks and routes so that one food patch can be linked with another. In this study we describe travel patterns between food sources for two prosimian species found in southeastern Madagascar, Propithecus edwardsi and Eulemur fulvus rufus. Both species are dependent on fruit and have large home range sizes. By comparing interpatch distances, patch size and turning angles, we found that both species prefer nearest neighbor food patches and P. edwardsi travels in relatively straight lines. The amount of backtracking seen in E. f. rufus may be linked to their large group size and dependence on large-crowned fruit trees. We suggest that the goal-oriented foraging of both prosimian species is dependent on a topological or route-based map. These are rare behavioral data relevant to ecological and social contexts of primate cognitive evolution.
Cell Adhesion Mechanisms in Platelets
Authors: Varga-Szabo David , Pleines Irina , Nieswandt Bernhard
Published: January 2008

At sites of vascular injury, platelets come into contact with the subendothelial extracellular matrix which triggers their activation and the formation of a hemostatic plug. This process is crucial for normal hemostasis, but may also lead to pathological thrombus formation causing diseases such as myocardial infarction or stroke. The initial capture of flowing platelets is mediated by the interaction of the glycoprotein (GP) Ib-V-IX complex with von Willebrand factor (vWF) immobilized on exposed collagens. This interaction allows the binding of the collagen receptor GPVI to its ligand and to initiate cellular activation, a process that is reinforced by locally produced thrombin and soluble mediators released from platelets. These events lead to the shift of β1 and β3 integrins on the platelet surface from a low to a high affinity state, thereby enabling them to bind their ligands and to mediate firm adhesion, spreading, coagulant activity, and aggregation. This review summarizes the most important structural and functional properties of these adhesion receptors and briefly discusses their potential as targets for antithrombotic therapy.
Association Between
ADAMTS1
Matrix Metalloproteinase Gene Variation, Coronary Heart Disease, and Benefit of Statin Therapy
Authors: Sabatine Marc S. , Ploughman Lynn , Simonsen Katy L. , Iakoubova Olga A. , Kirchgessner Todd G. , Ranade Koustubh , Tsuchihashi Zenta , Zerba Kim E. , Long Diane U. , Tong Carmen H. , Packard Christopher J. , Pfeffer Marc A. , Devlin James J. , Shepherd James , Campos Hannia , Sacks Frank M. , Braunwald Eugene
Published: January 2008

Objective—

The purpose of this study was to investigate the association between the
Ala
227
Pro
polymorphism in the
ADAMTS1
metalloproteinase gene and coronary heart disease and benefit from statin therapy in 2 independent cohorts.

Methods and Results—

The frequency of the
ADAMTS1
227
Pro
minor allele was 0.24 in 2421 male subjects from CARE, a randomized trial of pravastatin versus placebo. In the placebo arm, homozygotes (6.3% of study population) had a significantly increased risk of fatal coronary disease or nonfatal myocardial infarction (D/MI) compared with noncarriers (OR 2.12, 95% CI 1.07 to 4.19,
P
=0.03), and in the entire study the benefit of pravastatin in reducing the risk of D/MI was greater in these subjects (OR 0.21, 95% CI 0.06 to 0.69) than in heterozygotes (OR 0.74, 95% CI 0.48 to 1.14) or noncarriers (OR 0.99, 95% CI 0.68 to 1.42;
P
interaction
=0.044). Results were tested in 1565 male subjects from WOSCOPS, also a randomized trial of pravastatin versus placebo. Similar to the results in CARE, in the placebo arm subjects homozygous for the minor allele were at increased risk of D/MI (OR 1.72,
P
=0.052) and in the entire study the benefit of pravastatin in reducing D/MI was greater in these subjects (OR 0.24, 95% CI 0.09 to 0.68) than in heterozygotes (OR 0.73, 95% CI 0.48 to 1.11) or noncarriers (OR 0.65, 95% CI 0.20 to 2.09) (
P
interaction
=0.029).

Conclusions—

In men not on pravastatin, those homozygous for the 227
Pro
allele of
ADAMTS1
have a nearly 2-fold increased risk of coronary heart disease events compared with noncarriers. In this high-risk group, treatment with pravastatin is highly efficacious, reducing the odds of fatal coronary disease or nonfatal MI by approximately 75%, as compared with 25% in noncarriers or heterozygotes.
Wnt5A/CaMKII Signaling Contributes to the Inflammatory Response of Macrophages and Is a Target for the Antiinflammatory Action of Activated Protein C and Interleukin-10
Authors: Pereira Claudia , Schaer Dominik J. , Bachli Esther B. , Kurrer Michael O. , Schoedon Gabriele
Published: January 2008

Objective—

Sepsis is a major cause of death for intensive care patients. High concentrations of inflammatory cytokines are characteristic of severe systemic inflammation and activated monocytes are their predominant cellular source. To identify targets for antiinflammatory intervention, we investigated the response of human macrophages to inflammatory and antiinflammatory mediators.

Methods and Results—

We profiled gene expression in human macrophages exposed to lipopolysaccharide (LPS) and interferon (IFN)-γ in the presence or absence of recombinant activated protein C (APC) or IL-10 and identified Wnt5A as one of the transcripts most highly induced by LPS/IFN-γ and suppressed by APC and IL-10. We confirmed regulation of Wnt5A protein in macrophages and detected it in sera and bone marrow macrophages of patients with severe sepsis. We established that a functional Wnt5A/frizzled-5/CaMKII signaling pathway was essential for macrophage inflammatory activation. To prove the essential contribution of Wnt5A we measured inflammatory cytokines after stimulation with Wnt5A, silenced Wnt5A by siRNA, and blocked receptor binding with soluble Frizzled–related peptide-1 (sFRP1).

Conclusion—

Wnt5A is critically involved in inflammatory macrophage signaling in sepsis and is a target for antiinflammatory mediators like APC or antagonists like sFRP1.
Platelets: Inflammatory Firebugs of Vascular Walls
Authors: May Andreas E. , Seizer Peter , Gawaz Meinrad
Published: January 2008

Atherosclerosis is an inflammatory disease. Platelets can “inflame” the vascular wall by various mechanisms and thereby initiate and support the development of atherosclerosis. Platelet interaction with leukocytes, endothelial cells, and circulating progenitor cells triggers autocrine and paracrine activation processes, leading to inflammatory and atherogenic cascades at the vascular wall. This review highlights the molecular key components and pathways used by platelets to trigger and accelerate inflammation at the vascular wall and, thereby, atherosclerosis.
Oxidative Stress and Platelets
Authors: Freedman Jane E.
Published: January 2008

Platelet-dependent thrombus formation may be influenced by alteration of platelet or vascular redox state, the presence of endogenous or exogenous antioxidants, as well as the formation of reactive oxygen and nitrogen species. Specifically, settings and pathways that influence the formation of superoxide and nitric oxide, as well as their metabolism, may influence platelet function and thrombus formation. Although some antioxidant regimens have been associated with bleeding and hemorrhagic stroke, the therapeutic value of antioxidants in clinical syndromes that lead to platelet-dependent thrombosis is not clear, as supplemental antioxidants have not been generally associated with better cardiovascular outcome.
Protein Modification by O-Linked GlcNAc Reduces Angiogenesis by Inhibiting Akt Activity in Endothelial Cells
Authors: Luo Bai , Soesanto Yudi , McClain Donald A.
Published: January 2008

Objective—Glucose flux through the hexosamine biosynthesis pathway (HBP) has been implicated in the development of diabetic vascular complications. O-linked N-acetylglucosamine (O-GlcNAc) modification on protein is the major mechanism mediating the actions of the HBP. Impaired angiogenesis is well-recognized in diabetes; however, the mechanisms are not completely defined. Here, we investigated the role of protein O-GlcNAc modification in angiogenesis.

Methods and Results—In a mouse aortic ring assay, elevated O-GlcNAc levels induced by high-fat diet, streptozotocin-induced diabetes, or in vitro glucosamine treatment were associated with impaired angiogenesis. In cultured human umbilical vein endothelial cells and EA.hy926 endothelial cells, glucosamine increased protein O-GlcNAc modification and inhibited cell migration and capillary-like structure formation. Conversely, removal of O-GlcNAc by adenoviral-mediated overexpression of O-GlcNAcase improved these steps of angiogenesis. Also, high concentrations of glucose reduced capillary-like structure formation of human umbilical vein endothelial cells. Akt was recognized by an O-GlcNAc specific lectin, and glucosamine increased the amounts of Akt protein in these lectin precipitates. Increased glycosylation paralleled reduced Akt activity in endothelial cells.

Conclusion—These results suggest that elevated protein O-GlcNAc modification through the HBP impairs angiogenesis in endothelial cells, possibly by inhibiting Akt signaling.
P2Y
12
Antagonism
Authors: Michelson Alan D.
Published: January 2008

The P2Y
12
antagonist clopidogrel has a well-established role as an antithrombotic agent in the settings of percutaneous coronary intervention and acute coronary syndromes. However, several challenges remain, including the relatively slow onset of action of clopidogrel and the phenomenon of clopidogrel response variability or “resistance”. Novel P2Y
12
antagonists, including prasugrel, AZD6140, and cangrelor, have a faster onset of action, as well as more potent, and less variable, inhibition of platelet function ex vivo. Whether this promise will be translated into clinical benefit for patients will be determined by the results of ongoing phase 3 clinical trials.
Novel Therapeutic Targets at the Platelet Vascular Interface
Authors: Brass Lawrence F. , Zhu Li , Stalker Timothy J.
Published: January 2008

Platelet activation in vivo can be part of the hemostatic response to injury or a pathological response to disease. In either setting, platelets adhere to the vessel wall and to each other, forming a closely packed mass interspersed with fibrin. Recent studies have identified new molecules on the platelet surface and within platelets that support and regulate thrombus growth and stability, ensuring that platelet accumulation after injury is sufficient to stop bleeding, but not so exuberant that vascular occlusion occurs. An understanding of how this balance is achieved helps to illuminate the events of platelet activation and, at the same time, provides potential targets for new classes of antiplatelet agents.
AKAP150 Is Required for Stuttering Persistent Ca
2+
Sparklets and Angiotensin II–Induced Hypertension
Authors: Navedo Manuel F. , Nieves-Cintrón Madeline , Amberg Gregory C. , Yuan Can , Votaw V. Scott , Lederer W. Jonathan , McKnight G. Stanley , Santana Luis F.
Published: January 2008

Hypertension is a perplexing multiorgan disease involving renal primary pathology and enhanced angiotensin II vascular reactivity. Here, we report that a novel form of a local Ca
2+
signaling in arterial smooth muscle is linked to the development of angiotensin II–induced hypertension. Long openings and reopenings of L-type Ca
2+
channels in arterial myocytes produce stuttering persistent Ca
2+
sparklets that increase Ca
2+
influx and vascular tone. These stuttering persistent Ca
2+
sparklets arise from the molecular interactions between the L-type Ca
2+
channel and protein kinase Cα at only a few subsarcolemmal regions in resistance arteries. We have identified AKAP150 as the key protein, which targets protein kinase Cα to the L-type Ca
2+
channels and thereby enables its regulatory function. Accordingly, AKAP150 knockout mice (AKAP150
−/−
) were found to lack persistent Ca
2+
sparklets and have lower arterial wall intracellular calcium ([Ca
2+
]
i
) and decreased myogenic tone. Furthermore, AKAP150
−/−
mice were hypotensive and did not develop angiotensin II–induced hypertension. We conclude that local control of L-type Ca
2+
channel function is regulated by AKAP150-targeted protein kinase Cα signaling, which controls stuttering persistent Ca
2+
influx, vascular tone, and blood pressure under physiological conditions and underlies angiotensin II–dependent hypertension.
Effects of Magnesium Treatment in a Model of Internal Capsule Lesion in Spontaneously Hypertensive Rats
Authors: Lecrux Clotilde , McCabe Christopher , Weir Christopher J. , Gallagher Lindsay , Mullin Jim , Touzani Omar , Muir Keith W. , Lees Kennedy R. , Macrae I. Mhairi
Published: January 2008

Background and Purpose—

The study aim was to assess the effects of magnesium sulfate (MgSO
4
) administration on white matter damage in vivo in spontaneously hypertensive rats.

Methods—

The left internal capsule was lesioned by a local injection of endothelin-1 (ET-1; 200 pmol) in adult spontaneously hypertensive rats. MgSO
4
was administered (300 mg/kg SC) 30 minutes before injection of ET-1, plus 200 mg/kg every hour thereafter for 4 hours. Infarct size was measured by T2-weighted magnetic resonance imaging (day 2) and histology (day 11), and functional recovery was assessed on days 3 and 10 by the cylinder and walking-ladder tests.

Results—

ET-1 application induced a small, localized lesion within the internal capsule. Despite reducing blood pressure, MgSO
4
did not significantly influence infarct volume (by magnetic resonance imaging: median, 2.1 mm
3
; interquartile range, 1.3 to 3.8, vs 1.6 mm
3
and 1.2 to 2.1, for the vehicle-treated group; by histology: 0.3 mm
3
and 0.2 to 0.9 vs 0.3 mm
3
and 0.2 to 0.5, respectively). Significant forelimb and hindlimb motor deficits were evident in the vehicle-treated group as late as day 10. These impairments were significantly ameliorated by MgSO
4
in both cylinder (left forelimb use,
P
<0.01 and both-forelimb use,
P
<0.03 vs vehicle) and walking-ladder (right hindlimb score,
P
<0.02 vs vehicle) tests.

Conclusions—

ET-1–induced internal capsule ischemia in spontaneously hypertensive rats represents a good model of lacunar infarct with small lesion size, minimal adverse effects, and a measurable motor deficit. Despite inducing mild hypotension, MgSO
4
did not significantly influence infarct size but reduced motor deficits, supporting its potential utility for the treatment of lacunar infarct.
Posturography in Patients With Stroke
Authors: Genthon Nicolas , Gissot Anne-Sophie , Froger Jérôme , Rougier Patrice , Pérennou Dominic
Published: January 2008

Background and Purpose—

Posturography in patients with stroke is widely based on the use of a single force platform and the weightbearing asymmetry quantified from the lateral shift of the center of pressure toward the sound leg. Because the percentage of body weight on each side is a more concrete variable, the present study analyzed the possibility of inferring percentage of body weight from center of pressure.

Methods—

Forty-five hemiparetic subjects were asked to stand on a dual platform in a standardized position 3 months after a hemispheric stroke. First, the relationship between the %BW on each foot and the lateral shift of center of pressure was established. Second, the model was tested with a healthy subject standing on a single force platform.

Results—

The percentage of body weight may be simply modeled from the center of pressure shift, a center of pressure displacement of 10 mm corresponding to a 5% increase in body weight on this side (
r
=0.97,
P
<0.001). This linear model is reliable, accurate, and may be generalized to other stand widths.

Conclusions—

This finding should be useful for constructors and users of single force platforms, especially those involved in posturographic assessments of asymmetric conditions such as hemiparesis.
Identification of Variations in Blood-Brain Barrier Opening After Cerebral Ischemia by Dual Contrast-Enhanced Magnetic Resonance Imaging and T
1sat
Measurements
Authors: Nagaraja Tavarekere N. , Karki Kishor , Ewing James R. , Croxen Richard L. , Knight Robert A.
Published: January 2008

Background and Purpose—

Variations in blood-brain barrier (BBB) opening after ischemia have been suggested by some tracer and magnetization transfer studies, although direct in vivo proof is still lacking. Contrast-enhanced magnetic resonance imaging (MRI) is also often used to visualize BBB damage in stroke. We hypothesized that MR contrast agents of different sizes enhance differently when BBB openings vary in size and that magnetization transfer alterations, measured by T
1
in the presence of off-resonance radiofrequency saturation (T
1sat
), in these regions reflect such differences.

Methods—

Male Wistar rats (≈300 g, n=7) were subjected to 3 hours of suture occlusion of the middle cerebral artery followed by reperfusion. Status of the BBB at 24 hours after the ictus was assessed first by Gd-DTPA (554 Da) MRI and then by Gd–bovine serum albumin linked to Evans blue (Gd-BSA-EB; ≈68 kDa) MRI for contrast enhancement; T
1sat
changes, cerebral blood flow, and blood-to-brain transfer constants (

K
i

s) for the 2 contrast agents were measured. After MRI, rats were injected with fluorescent dextran and brains were studied by fluorescence microscopy.

Results—

The Gd-BSA-EB–enhancing areas were always smaller (147±80 pixels) than those for Gd-DTPA (308±204 pixels) and were contained within the latter. The difference between the 2 areas was significant (
P
=0.024). Changes in T
1sat
were larger in Gd-BSA-EB–enhancing areas (ipsilateral to contralateral [I/C]=1.53±0.20) than in Gd-DTPA–enhancing areas (I/C=1.40±0.24,
P
=0.005). The differences in cerebral blood flow values between the 2 regions were not significant (
P
=0.62), but those for the

K
i

values of the 2 tracers were different (
P
=0.01 to 0.02). Excellent agreement between regions of Gd-BSA-EB enhancement and EB fluorescence was also observed.

Conclusions—

These results substantiate earlier reports of regional differences in BBB opening after stroke and provide the first in vivo evidence for this phenomenon. They also support the possible use of T
1sat
in quantifying stroke-induced graded BBB damage in the absence of contrast-enhanced MRI.
The Effect of Activated Factor VII for Intracerebral Hemorrhage Beyond 3 Hours Versus Within 3 Hours
Authors: Hallevi Hen , Gonzales Nicole R. , Barreto Andrew D. , Martin-Schild Sheryl , Albright Karen C. , Noser Elizabeth A. , Illoh Kachi , Khaja Aslam M. , Allison Teresa , Escobar Miguel A. , Shaltoni Hashem M. , Grotta James C.
Published: January 2008

Background and Purpose—

Recombinant-activated factor VII (rFVIIa) is an investigational treatment for intracerebral hemorrhage (ICH). We have evaluated the drug’s treatment effect based on time to treatment.

Methods—

ICH patients treated up to 4 hours from symptom onset were divided based on time to treatment: ≤3 hours (3H) and 3 to 4 hours (4H). Head CT was done at baseline and 24 hours. Outcome measures included: ICH growth at 24 hours, mortality, favorable outcome and discharge disposition. A cohort of nontreated matched ICH patients was used to asses the clinical efficacy.

Results—

Forty-six patients were treated with rFVIIa: 24 in the 3H group (range 70 to 180 minutes), 22 in the 4H group (range 181 to 300). One hundred and forty-eight patients formed the control group. Mean baseline ICH volume was 8.8 mL for 3H and 10.1 mL for 4H. Mean 24-hour volume was 9.3 mL for 3H (absolute increase 1.05 mL, relative increase 11.9%) and 11.5 mL for 4H (absolute increase 1.1 mL, relative increase 10.9%);
P
=0.47 is for the difference in relative increase. Mortality was 12.5% for 3H group, 13.6% for 4H, and 13.1% for the control. In the 3H group, 58.3% were discharged with a poor outcome, compared with 54.5% in 4H and 54.1% in the control. Thrombotic adverse events occurred in 11.1% of patients treated with rFVIIa.

Conclusions—

In our off-label with rFVIIa, we did not find evidence of a treatment effect based on time to treatment. Other criteria should be sought to identify patients who might benefit clinically from rFVIIa.
Middle Cerebral Artery Infarcts Encompassing the Insula Are More Prone to Growth
Authors: Ay Hakan , Arsava E. Murat , Koroshetz Walter J. , Sorensen A. Gregory
Published: January 2008

Background and Purpose—

Based on previous observations that infarcts encompassing the insula were linked to unfavorable clinical outcome, we hypothesized that insular damage was directly associated with worsened infarction in ischemic but potentially viable neighboring brain tissue.

Methods—

Using acute diffusion- and perfusion-weighted MRI within the first 12 hours of symptom onset and a follow-up MRI on day 5 or later, we calculated the percentage of mismatch lost (PML) in 61 consecutive patients with ischemic stroke within the middle cerebral artery territory. PML denoted the percentage of mismatch tissue between diffusion-weighted imaging and mean transit time maps that eventually underwent infarction. We explored the relationship between PML and insular location using a regression model.

Results—

The median PML was 17.7% (interquartile range, 3.5% to 54.2%) in insular and 2.5% (0.0% to 12.7%) in noninsular infarcts (
P
<0.01). The PML correlated with the volume of abnormal regions on diffusion-weighted imaging (
P
<0.01), mean transit time (
P
<0.01), cerebral blood flow maps (
P
<0.01), and cerebral blood volume maps (
P
<0.01). A linear regression model with PML as response and with acute MRI volumes, age, and the site of vascular occlusion as covariates showed that insular involvement was an independent predictor of PML (
P
=0.01). The regression model predicted an approximately 3.2-fold increase in PML with insular involvement.

Conclusions—

Infarction of the insula is associated with increased conversion of ischemic but potentially viable neighboring tissues into infarction. The unfavorable tissue outcome in insular infarcts may not be a mere bystander effect from proximal middle cerebral artery occlusions.
An Ivory Plaque from Mele Hairam, Turkmenistan
Authors: Kornacka Maja
Published: December 2007

The exploration works at the Partho-Sassanian fire temple at Mele Hairam, southern Turkmenistan, have yielded a fragmentarily preserved double-faced ivory plaque in relief. Although the secular character of scenes depicted excludes the possibility of the plaque playing any role in the fire cult, it might have served as a valuable donation to the temple. The alien nature of the scenes indicates a foreign provenience of the plaque and may be linked to the ivory and bone items belonging to the so-called Begram Treasure or Hoard, and, more specifically, to local Bactrian workshops. Neither the exact dating of the plaque nor the date of its depositing at the temple can be precisely established. The piece could, however, have easily arrived to the temple due to the latter's unique location in the immediate vicinity of the Silk Road.
Stress above Wind-Plus-Paddle Waves: Modeling of a Laboratory Experiment
Authors: Makin V. K. , Branger H. , Peirson W. L. , Giovanangeli J. P.
Published: January 2008

A model based on wind-over-waves coupling (WOWC) theory is used to simulate a laboratory experiment and to explain the observed peculiarities of the surface stress distribution above a combined wave field: wind-generated-plus-monochromatic-paddle waves. Observations show the systematic and significant decrease in the stress as the paddle wave is introduced into the pure wind-wave field. As the paddle-wave steepness is further increased, the stress level returns to the stress level characteristic of the pure wind waves. Further increase in the paddle-wave steepness augments the stress further. The WOWC model explains this peculiarity of the stress distribution by the fact that the paddle waves significantly damp the wind waves in the spectral peak. The stress supported by these dominant waves rapidly falls when the paddle wave is introduced, and this decrease is not compensated by the stress induced by the paddle wave. With further increase in the steepness of the paddle wave, the stress supported by dominant wind waves stays at a low level while the stress supported by the paddle waves continues to grow proportional to the square of the steepness, finally exceeding the stress level characteristic of the pure wind-wave field.
Buoyant Eddies Entering the Labrador Sea Observed with Gliders and Altimetry
Authors: Hátún Hjálmar , Eriksen Charles C. , Rhines Peter B.
Published: January 2008

Intense, buoyant anticyclonic eddies spawned from the west Greenland boundary current were observed with high-resolution autonomous Seaglider hydrography and satellite altimetry as they entered the Labrador Sea interior. Surveys of their internal structure establish the transport of both low-salinity water in the upper ocean and warm, saline Irminger water at depth. The observed eddies can contribute significantly to the rapid restratification of the Labrador Sea interior following wintertime deep convection. These eddies have saline cores between 200 and 1000 m, low-salinity cores above 200 m, and a velocity field that penetrates to at least 1000 m, with 0–1000-m average speeds exceeding 40 cm s−1. Their trajectory, together with earlier estimates of the gyre circulation, suggests why the observed region of deep convection is so small and does not occur where wintertime cooling by the atmosphere is most intense. The cyclostrophic surface velocity field of the anticylones from satellite altimetry matched well with in situ dynamic height baroclinic velocity calculations.
Interannual Sea Level Variations in the South Pacific from 5° to 28°S
Authors: Li Jianke , Clarke Allan J.
Published: January 2008

Ocean Topography Experiment (TOPEX)/Poseidon/Jason-1 satellite altimeter observations for the 11-yr period from January 1993 to December 2003 show that in the South Pacific Ocean most of the interannual sea level variability in the region 5°–28°S is west of 160°W. This interannual variability is largest from about 5° to 15°S and from 155°E to 160°W, reaching a root-mean-square value of over 11 cm. Calculations show that this interannual sea level signal can be described by first and second baroclinic vertical mode Rossby waves forced by the curl of the interannual Ekman transport. This curl, which tends to be positive during El Niño and negative during La Niña, generates positive (negative) sea level anomalies during El Niño (La Niña) that increase westward in amplitude in accordance with Rossby wave dynamics. The sea level anomalies are not exactly in phase with the curl forcing because Sverdrup balance does not hold—vortex stretching also contributes to the response. East of 160°W is a large “quiet” region of low interannual sea level variability, especially south of about 15°S. This is surprising because there is no flow into the coast, so the interannual sea level amplitude of equatorial origin should be constant along the coast, resulting in a source of westward-propagating Rossby waves of considerable amplitude. The large low-variability region results because coastal sea level amplitude falls between 5° and 15°S, so the Rossby wave source south of 15°S is weak. During El Niño the sea level is higher than normal at the coast, so the southward fall in anomalous sea level implies, by geostrophy, that there is an anomalous onshore flow. This flow feeds an anomalous southward El Niño current of up to 20 cm s−1 above the 30–50-km-wide shelf edge. During La Niña the sea level is lower than normal at the coast and the flows reverse: a narrow anomalously northward shelf-edge flow feeding a broad offshore flow between 5° and 15°S. South of 16°S the coastal flow is much weaker.
Maintaining the Role of Humans in the Forecast Process: Analyzing the Psyche of Expert Forecasters
Authors: Stuart Neil A. , Schultz David M. , Klein Gary
Published: January 2008

The Second Forum on the Future Role of the Human in the Forecast Process occurred on 2–3 August 2005 at the American Meteorological Society's Weather Analysis and Forecasting Conference in Washington, D.C. The forum consisted of three sessions. This paper discusses the second session, featuring three presentations on the cognitive and psychological aspects of expert weather forecasters. The first presentation discussed the learning gap between students (goal seekers) and teachers (knowledge seekers)—a similar gap exists between forecasters and researchers. In order to most effectively train students or forecasters, teachers must be able to teach across this gap using some methods described within. The second presentation discussed the heuristics involved in weather forecasting and decision making under time constraints and uncertainty. The final presentation classified the spectrum of forecasters from intuitive scientists to the disengaged. How information technology can best be adapted so as not to inhibit intuitive scientists from their mental modeling of weather scenarios is described. Forecasters must continuously refine their skills through education and training, and be aware of the heuristic contributions to the forecast process, to maintain expertise and have the best chance of ensuring a dynamic role in the future forecast process.
In the Driver's Seat: Rico and Education
Authors: Rauber Robert M. , Stevens Bjorn , Davison Jennifer , Goke Sabine , Mayol-Bracero Olga L. , Rogers David , Zuidema Paquita , Ochs Harry T. , Knight Charles , Jensen Jorgen , Bereznicki Sarah , Bordoni Simona , Caro-Gautier Humberto , Colón-Robles Marilé , Deliz Maylissa , Donaher Shaunna , Ghate Virendra , Grzeszczak Ela , Henry Colleen , Hertel Anne Marie , Jo Ieng , Kruk Michael , Lowenstein Jason , Malley Judith , Medeiros Brian , Méndez-Lopez Yarilis , Mishra Subhashree , Morales-García Flavia , Nuijens Louise A. , O'Donnell Dennis , Ortiz-Montalvo Diana L. , Rasmussen Kristen , Riepe Erin , Scalia Sarah , Serpetzoglou Efthymios , Shen Haiwei , Siedsma Michael , Small Jennifer , Snodgrass Eric , Trivej Panu , Zawislak Jonathan
Published: January 2008

The Rain in Cumulus over the Ocean (RICO) field campaign carried out a wide array of educational activities, including a major first in a field project—a complete mission, including research flights, planned and executed entirely by students. This article describes the educational opportunities provided to the 24 graduate and 9 undergraduate students who participated in RICO.
Prevalence and Correlates of Suicidal Behaviour Among Adolescents in Southwest Nigeria
Authors: Omigbodun Olayinka , Dogra Nisha , Esan Oluyomi , Adedokun Babatunde
Published: January 2008

Background: Despite being recognized by the World Health Organization as a significant social and health concern, information on suicidal behaviours in Nigerian adolescents is unknown.

Aims: To establish the prevalence and associated psychosocial correlates of suicidal ideation and attempts in Nigerian youth.

Methods: Stratified sampling was used to identify youth aged 10—17 years who completed the Nigeria version of the Global School Health Questionnaire (GSHQ) and the Diagnostic Predictive Scale (DPS) for youths (suicidal behaviour questions) in a classroom setting.

Results: A total of 1429 youth completed the instruments. Over 20% reported suicidal ideation and approximately 12% reported that they had attempted suicide in the last year. Adolescents living in urban areas, from polygamous or disrupted families, had higher rates of suicidal behaviour. Multiple psychosocial factors such as sexual abuse, physical attack and involvement in physical fights were significant predictors of suicidal behaviour.

Conclusion: Factors associated with suicidal ideation and behaviours are similar to those found in other studies but the rates of both suicidal ideation and attempts are towards the upper limit of rates for youth. This study suggests that there is an urgent need for Nigerian policymakers and health providers to review and address this issue.
The Relationship Between Past Traumatic Experience and Sickness Absence
Authors: Izutsu Takashi , Shibuya Mihoko , Tsutsumi Atsuro , Konishi Takako , Kawamura Noriyuki
Published: January 2008

Background: Past traumatic experiences have been reported to lower stress tolerance, thereby increasing job strain. However, the relationship between past traumatic experiences and employee sickness absence is poorly understood.

Aims: This study explores the relationship between sickness absence and past traumatic experience with regard to the amount of time lapsed after the experience, job strain and other mental health states such as depression and anxiety.

Methods: A total of 3238 workers were assessed for levels of traumatic stress, depressive status, anxiety and job stress.

Results: Odds ratios of the presence of traumatic experiences to sickness absence, adjusted for sex, age and depressive and anxiety states, were presented according to the length of time that had passed since the traumatic events. The odds ratio in the 0—1 Years Group was 1.75 ( p < 0.05), and the odds ratio for the 19+ Years Group was 1.46 ( p < 0.1).

Conclusions: Past traumatic events are related to sickness absence. Sickness absence resulting from a past traumatic experience is important with respect to industrial health.
Intimacy with Outlaws
Authors: Jacques Scott , Wright Richard
Published: January 2008

The past quarter century has witnessed the emergence of a substantial literature devoted to the mechanics of recruiting, paying, and interviewing currently active offenders. Absent from that literature, however, is a theoretical framework within which to understand, test, modify, and further develop efforts to locate such offenders and gain their cooperation. This note, based on the authors' research with active drug sellers in Atlanta and St. Louis, explores the ways in which relational distance, that is, the nature and degree of intimacy between recruiter, interviewee, and researcher, affects the behavior of active offender research. The note concludes with theoretically situated, practical advice for (1) recruiting active criminals, (2) cost containment, and (3) maximizing the quantity and validity of data produced in interviews.