bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical and Experimental Study of Heat Transfer in a BIPV-Thermal System
Authors: Liao L. , Athienitis A. K. , Candanedo L. , Park K.-W. , Poissant Y. , Collins M.
Published: October 2007

This paper presents a computational fluid dynamics (CFD) study of a building-integrated photovoltaic thermal (BIPV∕T) system, which generates both electricity and thermal energy. The heat transfer in the BIPV∕T system cavity is studied with a two-dimensional CFD model. The realizable k‐ε model is used to simulate the turbulent flow and convective heat transfer in the cavity, including buoyancy effect and long-wave radiation between boundary surfaces is also modeled. A particle image velocimetry (PIV) system is employed to study the fluid flow in the BIPV∕T cavity and provide partial validation for the CFD model. Average and local convective heat transfer coefficients are generated with the CFD model using measured temperature profile as boundary condition. Cavity temperature profiles are calculated and compared to the experimental data for different conditions and good agreement is obtained. Correlations of convective heat transfer coefficients are generated for the cavity surfaces; these coefficients are necessary for the design and analysis of BIPV∕T systems with lumped parameter models. Local heat transfer coefficients, such as those presented, are necessary for prediction of temperature distributions in BIPV panels.
Theoretical Comparison of Solar Water/Space-Heating Combi Systems and Stratification Design Options
Authors: Andersen E. , Furbo S.
Published: October 2007

A theoretical analysis of differently designed solar combi systems is performed with weather data from the Danish Design Reference Year (55 deg N). Three solar combi system designs found on the market are investigated. The investigation focuses on the influence of stratification on the thermal performance under different operation conditions with different domestic hot water and space heating demands. The solar combi systems are initially equipped with heat exchanger spirals and direct inlets to the tank. A step-by-step investigation is performed demonstrating the influence on the thermal performance of using inlet stratification pipes at the different inlets. Also, how the design of the space heating system, the control system of the solar collectors, and the system size influence the thermal performance of solar combi systems are investigated. The work is carried out within the Solar Heating and Cooling Programme of the International Energy Agency (IEA SHC), Task 32.
An Analysis of Nonovercast Sky Luminance Models Against Hong Kong Data
Authors: Li Danny H. W. , Lau Chris C. S.
Published: October 2007

Daylighting is an important issue in modern architecture that has been characterized by the use of curtain walls in buildings. Nonovercast skies, including clear and partly cloudy days, are essential because they may occur more frequently for places such as in equatorial regions and the tropics. Better understanding of nonovercast sky luminance distribution is vital to estimate the dynamic variation in daylight illuminance as sky condition and solar position change. This paper presents the work on the evaluation of six clear sky and three partly cloudy sky models against three-year (1999–2001) measured Hong Kong sky luminance data. The general features and characteristics for the models were described and assessed. The nonovercast sky conditions were identified using the ratio of zenith luminance (Lz) to diffuse illuminance (Dv) and the ratio of global illuminance (Gv) to the extraterrestrial illuminance (Ev). Subsequent interpretations of the clear skies into high and low turbid types were conducted in conjunction with the cloud cover (CLD) and the luminous turbidity (Tv), and partly cloudy skies were further subdivided into thin and thick cloud modes using sunshine hour (SH) and global irradiance (GSI). A statistical analysis of the models revealed that the Gusev model (i.e., CIE (Internal Commission on Illumination) polluted sky No. 13) and the model by Chen et al. (1999, “Luminance Distribution Model of Intermediate Skies,” Zhaom Ing Gong Chen Xuebao, 10(1), pp. 59–63 (in Chinese)) developed using artificial neural network (ANN) theory with the measured data in Chongqing, China (29.6degN and 106.5degE) showed the best predictions for sky luminance at this location under the clear and partly cloudy sky conditions, respectively.
Involvement of cAMP response element-binding protein in the regulation of cell proliferation and the prolactin promoter of lactotrophs in primary culture
Authors: Ishida Maho , Mitsui Tetsuo , Yamakawa Koji , Sugiyama Nobuhiro , Takahashi Wakaba , Shimura Hiroki , Endo Toyoshi , Kobayashi Tetsurou , Arita Jun
Published: October 2007

Hypothalamic hormones, including dopamine, regulate critical functions of pituitary cells via the cAMP-protein kinase A (PKA) pathway. The PKA-downstream transcription factor cAMP response element (CRE)-binding protein (CREB) is an integrating molecule that is also activated by many other protein kinase pathways. We investigated the involvement of CREB in the regulation of cell proliferation and the PRL promoter of rat lactotrophs in primary cell culture. Recombinant adenoviruses were used for efficient gene delivery into pituitary cells. Bromocriptine, a dopaminergic agonist known to decrease intracellular cAMP concentrations, caused inhibition of PRL promoter activity and lactotroph proliferation, which was accompanied by decreases in CRE-mediated transcription and CREB phosphorylation in lactotrophs. Expression of a dominant-negative form of CREB (MCREB), which was effective in suppressing CRE-mediated transcription induced by the adenylate cyclase activator forskolin, inhibited basal and forskolin-induced PRL promoter activity and PRL mRNA expression. MCREB expression lowered basal proliferative levels and blocked forskolin-induced proliferation of lactotrophs. Insulin-like growth factor I (IGF-I), a potent mitogen in lactotrophs, did not affect intracellular cAMP concentrations but transiently increased lactotroph CREB phosphorylation. MCREB expression also inhibited IGF-I-induced lactotroph proliferation. These results suggest that CREB is involved in the regulation of cell proliferation and the PRL promoter in normal lactotrophs and that dopamine inhibition of these lactotroph functions is at least in part due to inhibition of the cAMP-PKA-CREB pathway.
Interaction between murinespf-ashmutation and genetic background yields different metabolic phenotypes
Authors: Marini Juan C. , Erez Ayelet , Castillo Leticia , Lee Brendan
Published: October 2007

The spf-ash mutation in mice results in reduced hepatic and intestinal ornithine transcarbamylase. However, a reduction in enzyme activity only translates in reduced ureagenesis and hyperammonemia when an unbalanced nitrogen load is imposed. Six-week-old wild-type control and spf-ash mutant male mice from different genetic backgrounds (B6 and ICR) were infused intravenously with [13C18O]urea, l-[15N2]arginine, l-[5,5 D2]ornithine, l-[6-13C, 4,4,5,5, D4]citrulline, and l-[ring-D5]phenylalanine to investigate the interaction between genetic background and spf-ash mutation on ureagenesis, arginine metabolism, and nitric oxide production. ICRspf-ashmice maintained ureagenesis (5.5 ± 0.3 mmol·kg−1·h−1) and developed mild hyperammonemia (145 ± 19 μmol/l) when an unbalanced nitrogen load was imposed; however, B6spf-ashmice became hyperammonemic (671 ± 15 μmol/l) due to compromised ureagenesis (3.4 ± 0.1 mmol·kg−1·h−1). Ornithine supplementation restored ureagenesis and mitigated hyperammonemia. A reduction in citrulline entry rate was observed due to the mutation in both genetic backgrounds (wild-type: 128, spf-ash: 60; SE 4.0 μmol·kg−1·h−1). Arginine entry rate was only reduced in B6spf-ashmice (B6spf-ash: 332, ICRspf-ash: 453; SE 20.6 μmol·kg−1·h−1). Genetic background and mutation had an effect on nitric oxide production (B6: 3.4, B6spf-ash: 2.8, ICR: 9.0, ICRspf-ash: 4.6, SE 0.7 μmol·kg−1·h−1). Protein breakdown was the main source of arginine during the postabsorptive state and was higher in ICRspf-ashthan in B6spf-ashmice (phenylalanine entry rate 479 and 327, respectively; SE 18 μmol·kg−1·h−1). Our results highlight the importance of the interaction between mutation and genetic background on ureagenesis, arginine metabolism, and nitric oxide production. These observations help explain the wide phenotypic variation of ornithine transcarbamylase deficiency in the human population.
In vitro simulation of calorie restriction-induced decline in glucose and insulin leads to increased insulin-stimulated glucose transport in rat skeletal muscle
Authors: Arias Edward B. , Cartee Gregory D.
Published: October 2007

In vivo calorie restriction [CR; consuming 60% of ad libitum (AL) intake] induces elevated insulin-stimulated glucose transport (GT) in skeletal muscle. The mechanisms triggering this adaptation are unknown. The aim of this study was to determine whether physiological reductions in extracellular glucose and/or insulin, similar to those found with in vivo CR, were sufficient to elevate GT in isolated muscles. Epitrochlearis muscles dissected from rats were incubated for 24 h in media with glucose (8 mM) and insulin (80 μU/ml) at levels similar to plasma values of AL-fed rats and compared with muscles incubated with glucose (5.5 mM) and/or insulin (20 μU/ml) at levels similar to plasma values of CR rats. Muscles incubated with CR levels of glucose and insulin for 24 h had a subsequently greater ( P < 0.005) GT with 80 μU/ml insulin and 8 mM [3H]-3- O-methylglucose but unchanged GT without insulin. Reducing only glucose or insulin for 24 h or both glucose and insulin for 6 h did not induce altered GT. Increased GT after 24-h incubation with CR levels of glucose and insulin was not attributable to increased insulin receptor tyrosine phosphorylation, Akt serine phosphorylation, or Akt substrate of 160 kDa phosphorylation. Nor did 24-h incubation with CR levels of glucose and insulin alter the abundance of insulin receptor, insulin receptor substrate-1, GLUT1, or GLUT4 proteins. These results provide the proof of principle that reductions in extracellular glucose and insulin, similar to in vivo CR, are sufficient to induce an increase in insulin-stimulated glucose transport comparable to the increase found with in vivo CR.
Positive and Negative Modulation of Motor Response in Primate Superior Colliculus by Reward Expectation
Authors: Ikeda Takuro , Hikosaka Okihide
Published: October 2007

Expectation of reward is crucial for goal-directed behavior of animals. However, little is known about how reward information is used in the brain at the time of action. We investigated this question by recording from single neurons in the macaque superior colliculus (SC) while the animal was performing a memory-guided saccade task with an asymmetrical reward schedule. The SC is an ideal structure to ask this question because it receives inputs from many brain areas including the prefrontal cortex and the basal ganglia where reward information is thought to be encoded and sends motor commands to the brain stem saccade generators. We found two groups of SC neurons that encoded reward information in the presaccadic period: positive reward-coding neurons that showed higher activity when reward was expected and negative reward-coding neurons that showed higher activity when reward was not expected. The positive reward-coding usually started even before a cue for target position was presented, whereas the negative reward-coding was largely restricted to the presaccadic period. The two kinds of reward-coding may be useful for the animal to select an appropriate behavior in a complex environment.
Targeting Altered Calcium Physiology in the Heart: Translational Approaches to Excitation, Contraction, and Transcription
Authors: Seidler Tim , Hasenfuss Gerd , Maier Lars S.
Published: October 2007

Calcium (Ca) is essential for excitation-contraction coupling. At the same time, Ca is of pivotal importance as a second messenger in cardiac signal transduction, where it regulates cardiac growth and function by activation of kinases and phosphatases, ultimately driving transcriptional responses and feeding back on Ca handling proteins, a phenomenon termed excitation-transcription coupling. Cardiac Ca homeostasis thus needs to be maintained via a delicate interplay of proteins to allow physiological function and adaptation, whereas disturbed Ca-handling and Ca-dependent signaling are hallmarks of heart failure. In this review, we will discuss the most recent mechanistic findings in Ca-handling and Ca-signaling proteins in the development of cardiac pathology with a focus on translational aspects.
Renin Release
Authors: Schweda Frank , Friis Ulla , Wagner Charlotte , Skott Ole , Kurtz Armin
Published: October 2007

The aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in salt, volume, and blood pressure homeostasis of the body. Renin is mainly produced and released into circulation by the so-called juxtaglomerular epithelioid cells, located in the walls of renal afferent arterioles at the entrance of the glomerular capillary network. It has been known for a long time that renin synthesis and secretion are stimulated by the sympathetic nerves and the prostaglandins and are inhibited in negative feedback loops by angiotensin II, high blood pressure, salt, and volume overload. In contrast, the events controlling the function of renin-secreting cells at the organ and cellular level are markedly less clear and remain mysterious in certain aspects. The unravelling of these mysteries has led to new and interesting insights into the process of renin release.
PADGE: analysis of heterogeneous patterns of differential gene expression
Authors: Li Li , Chaudhuri Amitabha , Chant John , Tang Zhijun
Published: October 2007

We have devised a novel analysis approach, percentile analysis for differential gene expression (PADGE), for identifying genes differentially expressed between two groups of heterogeneous samples. PADGE was designed to compare expression profiles of sample subgroups at a series of percentile cutoffs and to examine the trend of relative expression between sample groups as expression level increases. Simulation studies showed that PADGE has more statistical power than t-statistics, cancer outlier profile analysis (COPA) (Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, Varambally S, Cao X, Tchinda J, Kuefer R, Lee C, Montie JE, Shah RB, Pienta KJ, Rubin MA, Chinnaiyan AM. Science 310: 644–648, 2005), and kurtosis (Teschendorff AE, Naderi A, Barbosa-Morais NL, Caldas C. Bioinformatics 22: 2269–2275, 2006). Application of PADGE to microarray data sets in tumor tissues demonstrated its utility in prioritizing cancer genes encoding potential therapeutic targets or diagnostic markers. A web application was developed for researchers to analyze a large gene expression data set from heterogeneous biological samples and identify differentially expressed genes between subsets of sample classes using PADGE and other available approaches. Availability: http://www.cgl.ucsf.edu/Research/genentech/padge/ .
Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function
Authors: Spinale Francis G.
Published: October 2007

It is now becoming apparent that dynamic changes occur within the interstitium that directly contribute to adverse myocardial remodeling following myocardial infarction (MI), with hypertensive heart disease and with intrinsic myocardial disease such as cardiomyopathy. Furthermore, a family of matrix proteases, the matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs), has been recognized to play an important role in matrix remodeling in these cardiac disease states. The purpose of this review is fivefold: 1) to examine and redefine the myocardial matrix as a critical and dynamic entity with respect to the remodeling process encountered with MI, hypertension, or cardiomyopathic disease; 2) present the remarkable progress that has been made with respect to MMP/TIMP biology and how it relates to myocardial matrix remodeling; 3) to evaluate critical translational/clinical studies that have provided a cause-effect relationship between alterations in MMP/TIMP regulation and myocardial matrix remodeling; 4) to provide a critical review and analysis of current diagnostic, prognostic, and pharmacological approaches that utilized our basic understanding of MMP/TIMPs in the context of cardiac disease; and 5) most importantly, to dispel the historical belief that the myocardial matrix is a passive structure and supplant this belief that the regulation of matrix protease pathways such as the MMPs and TIMPs will likely yield a new avenue of diagnostic and therapeutic strategies for myocardial remodeling and the progression to heart failure.
The Physiology of Glucagon-like Peptide 1
Authors: Holst Jens Juul
Published: October 2007

Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon, the gene which is expressed in these cells. The current knowledge regarding regulation of proglucagon gene expression in the gut and in the brain and mechanisms responsible for the posttranslational processing are reviewed. GLP-1 is released in response to meal intake, and the stimuli and molecular mechanisms involved are discussed. GLP-1 is extremely rapidly metabolized and inactivated by the enzyme dipeptidyl peptidase IV even before the hormone has left the gut, raising the possibility that the actions of GLP-1 are transmitted via sensory neurons in the intestine and the liver expressing the GLP-1 receptor. Because of this, it is important to distinguish between measurements of the intact hormone (responsible for endocrine actions) or the sum of the intact hormone and its metabolites, reflecting the total L-cell secretion and therefore also the possible neural actions. The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions. It also inhibits gastrointestinal motility and secretion and thus acts as an enterogastrone and part of the “ileal brake” mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake. Because of these actions, GLP-1 or GLP-1 receptor agonists are currently being evaluated for the therapy of type 2 diabetes. Decreased secretion of GLP-1 may contribute to the development of obesity, and exaggerated secretion may be responsible for postprandial reactive hypoglycemia.
Life and Death: Metabolic Rate, Membrane Composition, and Life Span of Animals
Authors: Hulbert A. J. , Pamplona Reinald , Buffenstein Rochelle , Buttemer W. A.
Published: October 2007

Maximum life span differences among animal species exceed life span variation achieved by experimental manipulation by orders of magnitude. The differences in the characteristic maximum life span of species was initially proposed to be due to variation in mass-specific rate of metabolism. This is called the rate-of-living theory of aging and lies at the base of the oxidative-stress theory of aging, currently the most generally accepted explanation of aging. However, the rate-of-living theory of aging while helpful is not completely adequate in explaining the maximum life span. Recently, it has been discovered that the fatty acid composition of cell membranes varies systematically between species, and this underlies the variation in their metabolic rate. When combined with the fact that 1) the products of lipid peroxidation are powerful reactive molecular species, and 2) that fatty acids differ dramatically in their susceptibility to peroxidation, membrane fatty acid composition provides a mechanistic explanation of the variation in maximum life span among animal species. When the connection between metabolic rate and life span was first proposed a century ago, it was not known that membrane composition varies between species. Many of the exceptions to the rate-of-living theory appear explicable when the particular membrane fatty acid composition is considered for each case. Here we review the links between metabolic rate and maximum life span of mammals and birds as well as the linking role of membrane fatty acid composition in determining the maximum life span. The more limited information for ectothermic animals and treatments that extend life span (e.g., caloric restriction) are also reviewed.
In and Out of the ER: Protein Folding, Quality Control, Degradation, and Related Human Diseases
Authors: Hebert Daniel N. , Molinari Maurizio
Published: October 2007

A substantial fraction of eukaryotic gene products are synthesized by ribosomes attached at the cytosolic face of the endoplasmic reticulum (ER) membrane. These polypeptides enter cotranslationally in the ER lumen, which contains resident molecular chaperones and folding factors that assist their maturation. Native proteins are released from the ER lumen and are transported through the secretory pathway to their final intra- or extracellular destination. Folding-defective polypeptides are exported across the ER membrane into the cytosol and destroyed. Cellular and organismal homeostasis relies on a balanced activity of the ER folding, quality control, and degradation machineries as shown by the dozens of human diseases related to defective maturation or disposal of individual polypeptides generated in the ER.
Severe Fetal Hydrocephalus with and without Neural Tube Defect: A Comparative Study
Authors: Schlatter D. , Sanseverino M.T.V. , Schmitt J.M.R. , Fritsch A. , Kessler R.G. , Barrios P.M.M. , Palma-Dias R.S. , Magalhães J.A.
Published: October 2007

Objective: To describe the main perinatal and 1-year outcomes in babies with a prenatal ultrasonographic diagnosis of severe hydrocephalus according to the presence or absence of a neural tube defect (NTD) in a country where abortion is illegal. Method: The study population consisted of cases referred to and delivered at Hospital de Clínicas de Porto Alegre, diagnosed between January 1993 and December 2001. The diagnosis of severe hydrocephalus was based on a lateral ventricular atrium diameter ≧15 mm in at least one hemisphere. Results: Sixty cases were ascertained: 28 with NTD (group 1) and 32 without NTD (group 2). The groups were similar in terms of maternal and child variables at birth and hospitalization days during the 1st year of life. The mortality (including intrauterine deaths and deaths of babies with malformations incompatible with life that characterize a very poor prognosis) until 1 year of age was 36% in group 1 and 59% in group 2 (p = 0.077). The rate of cardiac malformations was higher in the group without NTD (p = 0.015). The length of hospital stay after birth (1st admission) was significantly higher in the group with NTD (p = 0.007). Conclusions: The morbidity was higher in the group with NTD, possibly due to the higher number of surgical interventions in the central nervous system. However, the mortality was higher in the group without NTD, possibly due to the presence of other associated malformations, especially congenital heart disease. Further studies should focus on neurological function and quality of life of the children and their families at the end of the 1st year and after 2 or 6 years of age.
Fetal Adrenal Haemorrhage – Two-Dimensional and Three-Dimensional Imaging
Authors: Schrauder M.G. , Hammersen G. , Siemer J. , Goecke T.W. , Meurer B. , Hart N. , Beckmann M.W. , Schild R.L.
Published: October 2007

A case of prenatal adrenal haemorrhage first detected by 2-dimensional and 3-dimensional sonography at 27 weeks’ gestation is reported. Ultrasound examination showed a large cystic mass (32 × 27 × 27 mm) in the right suprarenal region of the fetus. Two weeks later, the mass had slightly increased in size demonstrating hyperechoic areas within the cyst. Further serial ultrasound examinations revealed a progressive organisation of the cystic mass associated with a moderate reduction in size. The diagnosis of adrenal haemorrhage was confirmed by postnatal follow-up sonograms as the mass decreased in size from 28 × 21 × 21 mm on day 1 to 23 × 18 × 17 mm on day 42. Course and sonographic signs were typical for adrenal haemorrhage and the neonate was therefore managed without surgical exploration. The child is developing normally at 6 months of age.
Free Radicals, Antioxidants and Diabetes: Embryopathy, Retinopathy, Neuropathy, Nephropathy and Cardiovascular Complications
Authors: Aruoma Okezie I. , Neergheen Vidushi S. , Bahorun Theeshan , Jen Ling-Sun
Published: October 2007

The metabolic disturbances in the insulin-dependent diabetes mellitus or type 1 and noninsulin-dependent diabetes mellitus or type 2 are associated with a number of complications including cardiovascular diseases, nephropathy, neuropathy, retinopathy leading to blindness and embryopathy or congenital malformations. Maternal diabetes is associated with a high incidence of congenital malformations and fetal abortions. Heart and kidney anomalies, along with central nervous system defects are frequent manifestations of a maternal diabetic environment. Glycation products from excess glucose can chemically modify DNA causing mutations and complex DNA rearrangements. Therefore, DNA damage in fetal tissues as a result of maternal diabetes may reflect a level of genomic injury sufficient to affect embryonic development. The formation of advanced glycation end products can accelerate vascular occlusion by quenching the vasodilating agent nitric oxide. Interaction with high-affinity receptors located on monocytes and macrophages can enhance the production of free radicals and reactive oxygen/nitrogen species, the secretion of tumor necrosis factor-α, interleukin-1 and insulin-like growth factor 1 which can proliferate endothelial, mesangial and smooth muscle cells and hence contribute significantly to the pathogenesis of cardiovascular complications. Retinopathy is characterized by increased vascular permeability, by vascular closure, together with the growth of new blood vessels on the retina and posterior surface of the vitreous. Reactive oxygen species are involved in decreased retinal blood flow, increased vascular permeability and disruption of blood-retinal barrier. The involvement of oxidative stress in the pathology of diabetes from its associated cardiovascular dysfunctions, nephropathy, neuropathy, retinopathy (leading to blindness) and embryopathy or congenital malformations, suggests that potential management of diabetes could benefit from use of dietary biofactors in medicinal and food plants. There is therefore a requirement for research to focus on the molecular mechanisms of action of extracts and/or the biofactors flavonoids, proanthocyanidins, alkaloids, etc. derived from these plants.
B-Type Natriuretic Peptide in Patients with Systemic Right Ventricle
Authors: Koch Andreas M.E. , Zink Stefan , Singer Helmut
Published: October 2007

Objective: To examine the diagnostic value of B-type natriuretic peptide (BNP) in patients with systemic right ventricle. Methods: Plasma BNP levels were measured in 48 outpatients with D-transposition of the great arteries after atrial switch procedure or congenitally corrected transposition of the great arteries. Results: Plasma BNP was ≤20 pg/ml in 52% and <200 pg/ml in all patients, significantly higher in females compared to males (p = 0.004), and positively correlated with age (r = 0.3, p = 0.04). New York Heart Association class I patients had significantly lower BNP than class II patients (p = 0.03). A positive correlation was found between BNP and severity of tricuspid regurgitation (r = 0.5, p < 0.001). Plasma BNP was weakly, negatively correlated to maximum exercise capability, peak oxygen uptake, maximum heart rate during exercise testing and minimal heart rate in the 24-hour Holter monitoring. Additionally, BNP was negatively correlated with flow velocity across the pulmonary valve in patients with congenitally corrected transposition of the great arteries (r = –0.81, p = 0.03). Conclusion: Plasma BNP is normal in patients with systemic right ventricle, but increases with deterioration of clinical status and decreasing exercise capability. BNP is positively correlated with severity of tricuspid regurgitation, a prognostic factor for survival.
Long-Term Survival and Causes of Death After Stroke
Authors: Brønnum-Hansen Henrik , Davidsen Michael , Thorvaldsen Per
Published: October 2007

Background and Purpose
—

As part of the Danish contribution to the World Health Organization (WHO) MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Project, a register of patients with stroke was established in 1982. The purpose of the present study was to analyze long-term survival and causes of death after a first stroke and to compare them with those of the background population.

Methods
—

The study population comprised all subjects aged 25 years or older who were resident in a geographically defined region in Copenhagen County. All stroke events in the study population during 1982–1991 were ascertained and validated according to standardized criteria outlined for the WHO MONICA Project. After completion of the stroke registry at the end of 1991, all patients were followed up by record linkage to official registries. Standardized mortality ratios were calculated for various causes of death and periods after the stroke.

Results
—

The estimated cumulative risks for death at 28 days, 1 year, and 5 years after onset were 28%, 41%, and 60%, respectively. Compared with the general population, nonfatal stroke was associated with an almost 5-fold increase in risk for death between 4 weeks and 1 year after a first stroke and a 2-fold increase in the risk for death subsequent to 1 year. The excess mortality rate in stroke patients was due mainly to cardiovascular diseases but also to cancer, other diseases, accidents, and suicide. The probability for long-term survival improved significantly during the observation period for patients with ischemic or ill-defined stroke.

Conclusions
—

Stroke is a medical emergency associated with a very high risk for death in the acute and subacute phases and with a continuous excess risk of death. Better prevention and management of strokes may improve the long-term survival rate.
Dysphagia in Lateral Medullary Infarction (Wallenberg’s Syndrome)
Authors: Aydogdu Ibrahim , Ertekin Cumhur , Tarlaci Sultan , Turman Bulent , Kiylioglu Nefati , Secil Yaprak
Published: October 2007

Background and Purpose

—

We have investigated the pathophysiological mechanisms of dysphagia in Wallenberg’s syndrome (WS) that are due to lateral medullary infarction (LMI).

Methods

—

Twenty patients with WS were evaluated by means of clinical and electrophysiological methods that measured the oropharyngeal phase of voluntarily initiated swallowing. For comparison, 22 patients with unilateral hemispheric infarction were investigated during the acute stage of stroke, and 4 patients with unilateral peripheral 9th and 10th cranial nerve palsies were studied. Age-matched 30 healthy control subjects were also included in the study.

Results

—

It was found that dysphagia was clinically more severe in WS patients than in the patients in the other groups. The pharyngeal phase of swallowing was predominantly impaired, whereas in patients with hemispheric stroke, dysphagia was related only to the delay of triggering of the voluntarily induced swallowing. In WS patients, the swallowing reflex was extremely slow in spite of the unilateral involvement due to LMI, whereas the pharyngeal phase of reflex swallowing remained within normal limits in patients with unilateral hemispheric stroke and patients with unilateral peripheral 9th and 10th cranial nerve palsies.

Conclusions

—

Although in WS the lesion due to LMI is unilateral, its effect on oropharyngeal swallowing is bilateral. In LMI, primarily the premotor neurons in the nucleus ambiguus and their connections seem to be affected. Consequently, a disruption and/or disconnection of their linkage to swallowing-related cranial motor neuron pools bilaterally and to the contralateral nucleus ambiguus could produce the swallowing disorders in WS. However, the remaining intact ipsilateral premotor neurons and the contralateral center in the medulla oblongata may eventually begin to operate and overcome the severity and long-term persistence of dysphagia.
Collateral Growth and Angiogenesis Around Cortical Stroke
Authors: Wei Ling , Erinjeri Joseph P. , Rovainen Carl M. , Woolsey Thomas A.
Published: October 2007

Background and Purpose

—

We tested the hypothesis that there are significant long-term local vascular changes after ministroke that could form a basis for functional recovery.

Methods

—

A 6- to 8-mm cranial window was opened over the barrel cortex, which was identified by an intrinsic optical signal during mechanical stimulation of the whiskers in anesthetized female Wistar rats. Branches of the middle cerebral artery (MCA) to this region were ligated. Fluorescein isothiocyanate (FITC) transits were recorded by videomicroscopy in each rat just before, immediately after, and 30 days after ligation. Changes in surface vessels and parenchymal perfusion were measured. In similarly prepared rats, angiogenesis was identified by 5-bromo-2-deoxyuridine labeling and immunohistochemistry for the integrin family member α
v
β
3
.

Results

—

The intrinsic optical signal disappeared immediately after MCA ligations. FITC injection just after ligation demonstrated 3 concentric regions: 1 region of unchanged perfusion, surrounding 1 region of reduced perfusion (the ischemic border) surrounding a central core with little observable perfusion. At 30 days, the following had taken place: (1) diameters and lengths of surface collaterals in the ischemic border had grown significantly, but no new surface vessels were detected, (2) FITC entered occluded MCA segments, (3) arteriocapillary latencies in the ischemic border were shortened compared with latencies just after ligation, and (4) small infarcts were virtually identical to the poorly perfused core. Angiogenesis was confined to the ischemic border.

Conclusions

—

Arteriolar collateral growth and new capillaries support restored perfusion in the ischemic border after ministroke and could support long-term functional recovery.
Simvastatin Protects Against Long-Lasting Behavioral and Morphological Consequences of Neonatal Hypoxic/Ischemic Brain Injury
Authors: Balduini Walter , De Angelis Valerio , Mazzoni Erika , Cimino Mauro
Published: October 2007

Background and Purpose

—

Recent studies suggest that statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) not only reduce the incidence of stroke by lowering cholesterol levels but may also exert neuroprotective effects via a mechanism not related to their lipid-lowering effect. Despite the growing body of evidence, however, the neuroprotective effect of statins in stroke is still controversial. Herein, we studied whether a prophylactic administration of simvastatin (Sim) provides significant protection against brain damage, and we sought to determine its long-lasting behavioral consequences in a neonatal model of hypoxia/ischemia.

Methods

—

Newborn male rats were injected daily from postnatal days 1 to 7 with activated Sim (20 mg/kg) or an equivalent volume of vehicle. On postnatal day 7, the rats were subjected to ligation of the right common carotid artery, followed by 3 hours of hypoxia or by sham operation. The neuroprotective effect of Sim was evaluated after the rats had achieved adulthood by using a battery of behavioral tests and histological analysis.

Results

—

Sim-treated ischemic rats performed the circular water maze, the radial arm maze, and the multiple-choice water maze significantly better than did vehicle-treated ischemic rats. Furthermore, in contrast to the ischemic rats, hypoxia/ischemia-injured rats pretreated with Sim were not hyperactive at weaning and showed less behavioral asymmetry. Consistently, it was found that brain damage was significantly attenuated.

Conclusions

—

These findings indicate that prophylactic administration of statins may provide a potential neuroprotective strategy leading to an improvement in functional outcome in ischemic stroke. However, toxicity concern must be addressed before these agents can be directed to the asphyxiated fetus or newborn.
Apolipoprotein E and Carotid Artery Atherosclerosis
Authors: Slooter A.J.C. , Bots M.L. , Havekes L.M. , del Sol A. Iglesias , Cruts M. , Grobbee D.E. , Hofman A. , Van Broeckhoven C. , Witteman J.C.M. , van Duijn C.M.
Published: October 2007

Background and Purpose

—

Carotid artery atherosclerosis is a strong predictor for future stroke. It is yet unclear whether the apolipoprotein E polymorphism (
APOE
) is related to atherosclerosis in the carotid arteries. The aim of the present study was to investigate the role of
APOE
in carotid artery atherosclerosis.

Methods

—

A population-based cross-sectional study was performed on 5401 subjects. Atherosclerosis was noninvasively assessed by the common carotid artery intima-media wall thickness and the presence of plaques in the carotid arteries. The relationship of the 6
APOE
genotypes with these 2 indicators was studied with linear and logistic regression analysis, respectively, with adjustments for age and sex.

Results

—

Carriers of the
E2E3
genotype had a thinner intima-media wall thickness (mean difference, −0.02 mm; 95% CI, −0.03 to −0.01 mm) and fewer plaques (odds ratio for >3 plaques at 6 sites, 0.6; 95% CI, 0.4 to 0.8) than the most common group,
E3E3
. The
E4E4
group had slightly more atherosclerosis, but this was not statistically significant. Adjusting for the level of the apolipoprotein E protein (apoE) in serum or total or HDL cholesterol did not essentially change these findings.

Conclusions

—

Our results suggest that APOE*4 is not an important risk factor for carotid artery atherosclerosis. The inverse relationship of
E2E3
with carotid artery atherosclerosis seems to be independent of serum apoE and total and HDL cholesterol levels. However, the low frequency, together with the small effects, implies that any protective effect of
E2E3
on carotid artery atherosclerosis is limited.
Polymorphisms in Matrix Metalloproteinase-1, -3, -9, and -12 Genes in Relation to Subarachnoid Hemorrhage
Authors: Zhang Baiping , Dhillon Sahar , Geary Irene , Howell W. Martin , Iannotti Fausto , Day Ian N.M. , Ye Shu
Published: October 2007

Background and Purpose

—

Intracranial aneurysm, which underlies the vast majority of subarachnoid hemorrhage incidences, has a multifactorial etiology, and the importance of genetic factors is increasingly recognized. Development and rupture of intracranial aneurysms involve degradation and remodeling of the vascular wall matrix in which the matrix metalloproteinases (MMPs) play an important role. The possible impact of MMP gene polymorphisms on susceptibility to intracranial aneurysms is still controversial, with conflicting data from different reported studies.

Methods

—

In this study we analyzed 5 different functional promoter polymorphisms in the MMP-1, MMP-3, MMP-9, and MMP-12 genes in a sample of 92 patients with aneurysmal subarachnoid hemorrhage and 158 healthy control subjects, all from southern England.

Results

—

No significant difference was detected between the patient and control groups in genotype distribution of any of the polymorphisms studied.

Conclusions

—

The data do not support the hypothesis that MMP gene variations influence the development of intracranial aneurysms in the population studied.
Systolic Blood Pressure Response to Exercise Stress Test and Risk of Stroke
Authors: Kurl S. , Laukkanen J.A. , Rauramaa R. , Lakka T.A. , Sivenius J. , Salonen J.T.
Published: October 2007

Background and Purpose

—

Systolic blood pressure (SBP) during exercise has been found to predict a future diagnosis of hypertension, coronary heart disease, and cardiovascular disease death. No studies have been conducted to show a relationship between SBP during exercise test and stroke. The aim of the present study was to study the associations between SBP rise, percent maximum SBP at 2 minutes after exercise, and the risk of stroke in a population-based sample of men with no prior coronary heart disease.

Methods

—

SBP was measured every 2 minutes during and after the exercise test. The subjects were a population-based sample of 1026 men without clinical coronary heart disease, antihypertensive medication, or prior stroke at baseline. During an average follow-up of 10.4 years, there were 46 cases of stroke (38 ischemic strokes).

Results

—

Men with SBP rise >19.7 mm Hg per minute of exercise duration had a 2.3-fold increased risk of any stroke and a 2.3-fold increased risk of ischemic stroke compared with men whose SBP rise was <16.1 mm Hg/min. Similarly, percent maximum SBP at 2 minutes after exercise (SBP at 2 minutes’ recovery divided by maximum SBP) was associated (highest tertile) with a 4.6-fold increased risk of any stroke and a 5.2-fold increased risk of ischemic stroke.

Conclusions

—

SBP rise during exercise and percent maximum SBP at 2 minutes after exercise were directly and independently associated with the risk of all stroke and ischemic stroke. Exercise SBP testing may be recommended as an additional tool in the prediction of future stroke.
Influence of Positive End-Expiratory Pressure on Intracranial Pressure and Cerebral Perfusion Pressure in Patients With Acute Stroke
Authors: Georgiadis D. , Schwarz S. , Baumgartner R.W. , Veltkamp R. , Schwab S.
Published: October 2007

Background and Purpose

—

We undertook this study to evaluate the influence of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in patients with acute stroke.

Methods

—

A total of 20 ventilated patients of a neurological intensive care unit were examined under a protocol entailing variation of PEEP to 4, 8, 12, and 4 mm Hg; mean arterial blood pressure (MAP), ICP, heart rate, and mean velocity of the middle cerebral arteries (V
m
MCA) were recorded.

Results

—

CPP significantly changed depending on the various PEEP levels. No significant differences in remaining parameters were evident. Three distinct reaction patterns of the parameters monitored were observed: (1) All parameters remained stable through the various PEEP levels (15 patients, 40 examinations). (2) Increase in PEEP resulted in a significant decrease of MAP, while V
m
MCA remained unchanged, indicating an intact cerebral autoregulation. A slight (statistically insignificant) increase in ICP, which was significantly related to the MAP changes, was evident (7 patients, 16 examinations). (3) Increase in PEEP resulted in a decrease of MAP and V
m
MCA; ICP remained unchanged or demonstrated a slight decline (3 patients, 6 examinations).

Conclusions

—

PEEP increase up to 12 mm Hg does not significantly influence ICP. The observed marked changes in CPP are mediated through the MAP. Thus, PEEP application should be safe, provided that MAP is maintained.
Acute Tissue Damage After Injections of Thrombin and Plasmin into Rat Striatum
Authors: Xue Mengzhou , Del Bigio Marc R.
Published: October 2007

Background and Purpose

—

Extravasation of blood is associated with intracerebral hemorrhage and head trauma. The mechanism of brain cell injury associated with hemorrhage differs from that due to pure ischemia. The purpose of this study was to investigate the acute changes after intracerebral injections of proteins that are involved in blood clotting and clot lysis.

Methods

—

Sixty-eight adult rats were subjected to stereotaxic intrastriatal injections of normal saline (5 μL), low- (2.5 U/5 μL) and high-dose (25 U/5 μL) thrombin, low- (0.1 μg/5 μL) and high-dose (1 μg/5 μL) tissue plasminogen activator, low- (0.05 U/5 μL) and high-dose (0.5 U/5 μL) plasminogen, and low- (0.335 U/5 μL) and high-dose (3.35 U/5 μL) plasmin. Forty-eight hours later rats were perfusion fixed. Brain damage area, eosinophilic neurons, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL)-positive cells, infiltrating neutrophils, CD8a immunoreactive leukocytes, and reactive microglia were quantified.

Results

—

Damage area in striatum, dying cells, inflammatory cells, and microglial reaction were significantly greater after the high-dose plasminogen, plasmin, and thrombin injections. Tissue plasminogen activator injections were associated with mild inflammation.

Conclusions

—

These results suggested that thrombin and plasmin are harmful to brain cells in vivo. Although the doses required to cause damage are relatively great in consideration of the plasma content of these proteins, their pathological effect might be enhanced through synergism with other mechanisms.
Site-Specific Atherosclerotic Plaques in the Carotid Arteries of Middle-Aged Women From Southern Italy
Authors: Rubba Paolo , Panico Salvatore , Bond M. Gene , Covetti Giuseppe , Celentano Egidio , Iannuzzi Arcangelo , Galasso Rocco , Belisario M. Antonietta , Pastinese Antonella , Sacchetti Lucia , Mancini Mario , Salvatore Francesco
Published: October 2007

Background and Purpose

—

Studies on cardiovascular disease have preferentially involved men because of the lower frequency of the disease in preelderly women. The aim of this analysis was to examine, with the use of a standardized ultrasound protocol, a cohort of women to differentiate early atherosclerotic lesions in different carotid segments in relation to traditional (lipoprotein abnormalities, high blood pressure, cigarette smoking) and nontraditional (oxidation markers) cardiovascular risk factors.

Methods

—

More than 5000 clinically healthy, middle-aged women (n=5062; age range, 30 to 69 years) living in the area of Naples in southern Italy participated in the Progetto Atena, a population-based study on the etiology of cardiovascular disease and cancer in the female population. A subsample of 310 participants underwent high-resolution B-mode ultrasound to assess intima-media thickness of common carotid artery and carotid bifurcation.

Results

—

Early atherosclerotic plaques (intima-media thickness >1.2 mm) were detected within the common carotid arteries in 37 women, in the carotid bifurcations in 77 women, and in both sites in 91 women. After age adjustment, common carotid plaques were found to be associated with higher systolic blood pressure (143 versus 138 mm Hg;
P
<0.05) and higher body mass index (29 versus 27 kg/m
2
;
P
<0.01), while lesions at the carotid bifurcations were associated with higher LDL cholesterol (4.3 versus 3.8 mmol/L;
P
<0.01) and with smoking habit. Multivariate odds ratios for the presence of common carotid plaques were related to antibodies against oxidized LDL (odds ratio, 2.72; 95% CI, 1.46 to 5.07), and those for plaques at the bifurcation were related to lipid peroxides (odds ratio, 1.90; 95% CI, 1.04 to 3.47), and both relationships were independent of age, LDL cholesterol concentrations, body mass index, smoking habit, and systolic blood pressure.

Conclusions

—

In a cohort of clinically healthy, middle-aged women, we found a site-specific association of traditional risk factors and oxidation markers with early atherosclerotic lesions in arterial segments differing in geometry, shear stress, extracellular matrix composition, and cell type populations.