bluuebunny/crossref_metadata_2025 huggingface dataset:
DOCA-salt treatment enhances responses to endothelin-1 in murine corpus cavernosumThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.
Authors: Carneiro Fernando S. , Giachini Fernanda R.C. , Lima Victor V. , Carneiro Zidonia N. , Nunes Kênia P. , Ergul Adviye , Leite Romulo , Tostes Rita C. , Webb R. Clinton
Published: May 2008

The penis is kept in the flaccid state mainly via a tonic activity of norepinephrine and endothelins (ETs). ET-1 is important in salt-sensitive forms of hypertension. We hypothesized that cavernosal responses to ET-1 are enhanced in deoxycorticosterone acetate (DOCA)-salt mice and that blockade of ETAreceptors prevents abnormal responses of the corpus cavernosum in DOCA-salt hypertension. Male C57BL/6 mice were unilaterally nephrectomized and treated for 5 weeks with both DOCA and water containing 1% NaCl and 0.2% KCl. Control mice were uninephrectomized and received tap water with no added salt. Animals received either the ETAantagonist atrasentan (5 mg·day−1·kg−1body weight) or vehicle. DOCA-salt mice displayed increased systolic blood pressure (SBP), and treatment with atrasentan decreased SBP in DOCA-salt mice. Contractile responses in cavernosal strips from DOCA-salt mice were enhanced by ET-1, phenylephrine, and electrical field stimulation (EFS) of adrenergic nerves, whereas relaxations were not altered by IRL-1620 (an ETBagonist), acetylcholine, sodium nitroprusside, and EFS of nonadrenergic noncholinergic nerves. PD59089 (an ERK1/2 inhibitor), but not Y-27632 (a Rho-kinase inhibitor), abolished enhanced contractions to ET-1 in cavernosum from DOCA-salt mice. Treatment of DOCA-salt mice with atrasentan did not normalize cavernosal responses. In summary, DOCA-salt treatment in mice enhances cavernosal reactivity to contractile, but not to relaxant, stimuli, via ET-1/ETAreceptor-independent mechanisms.
Oxidative stress-induced, poly(ADP-ribose) polymerase-dependent upregulation of ET-1 expression in chronic diabetic complicationsThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.
Authors: Chiu Jane , Xu Bing Ying , Chen Shali , Feng Biao , Chakrabarti Subrata
Published: May 2008

Hyperglycemia in diabetes induces increased endothelin-1 (ET-1) production in the retina, kidney, and heart that may lead to hemodynamic impairment, permeability alteration, and increased extracellular matrix (ECM) protein production. Chronically elevated blood glucose levels may cause oxidative stress in these target tissues of diabetic complications. Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme activated by DNA strand breaks due to oxidative stress. We investigated the role of PARP in regulating ET-1 expression and ET-1-induced abnormalities in the targets organs of diabetic complications. Male Sprague–Dawley rats were injected with streptozotocin to induce diabetes. Once diabetes was established, half of the diabetic rats were randomly chosen to receive PARP inhibitor 3-aminobenzamide for 4 months. In a second set of experiments, PARP−/− mice and their controls were fed for 2 months with either a normal rodent diet or a 30% galactose diet to induce a normoinsulinemic hyperhexosemic state. Tissues harvested at the conclusion of both experiments were then subjected to real-time RT-PCR analysis for mRNA expression and immunohistochemical assessment of oxidative stress. In both experiments, the hyperhexosemic state upregulated expression of ET-1 mRNA in the retina, kidney, and heart. Furthermore, upregulation of ET-1-dependent ECM transcripts, such as fibronectin and extradomain B-containing fibronectin, was noted in all tissues. These tissues also demonstrated oxidative stress, as evidenced by the presence of nuclei positive for 8-hydroxy-2′-deoxyguanosine. In contrast, inhibition of PARP, either through a chemical means in the diabetic rats or by genetic manipulation in the galactose-fed animals, prevented both oxidative stress and hyperhexosemia-induced upregulation of these genes. These results suggest that, in diabetes, oxidative stress and PARP activation may produce their effects through ET-1. Hence, blockade of such pathways may constitute potential adjuvant treatment modalities in chronic diabetic complications.
Impaired insulin-mediated vasorelaxation in a nonobese model of type 2 diabetes: role of endothelin-1This article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.
Authors: Elgebaly Mostafa M. , Kelly Aisha , Harris Alex K. , Elewa Hazem , Portik-Dobos Vera , Ketsawatsomkron Pimonrat , Marrero Mario , Ergul Adviye
Published: May 2008

Insulin resistance involves decreased phosphorylation of insulin receptor substrate (IRS) proteins and (or) Akt. In the vasculature, modulated Akt phosphorylation may cause impaired vasorelaxation via decreased eNOS activation. Diet-induced insulin resistance enhances endothelin-1(ET-1)-mediated vasoconstriction and prevents vasodilatation to insulin. Presently, we evaluated insulin-mediated vascular relaxation, assessed molecular markers of the insulin signaling pathway, and determined the involvement of ET-1 in response to insulin by using selective ETA- or ETB-receptor blockade in a lean model of type 2 diabetes. Dose–response curves to insulin (0.01–100 ng/mL) were generated with wire myograph using thoracic aorta rings from control Wistar or diabetic Goto–Kakizaki (GK) rats (n = 3–11). Maximal relaxation (Rmax) to insulin was significantly impaired and insulin sensitivity was decreased in the GK group. Preincubation with 1 μmol/L BQ-123 or BQ-788 for ETA- and ETB-receptor blockade, respectively, resulted in improved insulin sensitivity. Immunoblotting for native and phosphorylated Akt and IRS-1 revealed a decrease in Akt activation in the GK group. In vivo hyperinsulinemic euglycemic clamp studies showed decreased glucose utilization in GK rats, indicative of insulin resistance. These findings provide evidence that vascular insulin resistance occurs in a nonobese model of diabetes and that both ET receptor subtypes are involved in vascular relaxation to insulin.
SOFTWARE ENGINEERING FOR WEB SERVICES WORKFLOW SYSTEMS
Authors: BLAKE M. BRIAN , SINGH LISA
Published: May 2008

Service-oriented computing (SOC) suggests that many open, network-accessible services will be available over the Internet for organizations to incorporate into their own processes. Developing new software systems by composing an organization's local services and externally-available web services is conceptually different from system development supported by traditional software engineering lifecycles. Consumer organizations typically have no control over the quality and/or consistency of the external services that they incorporate, thus top-down software development lifecycles are impractical. Software architects and designers will require agile, lightweight processes to evaluate tradeoffs in system design based on the "estimated" responsiveness of external services coupled with known performance of local services. We introduce a model-driven software engineering approach for designing systems (i.e. workflows of web services) under these circumstances and a corresponding simulation-based evaluation tool.
A LOOSELY COUPLED ASPECT LANGUAGE FOR SOA APPLICATIONS
Authors: MENDONÇA NABOR C. , SILVA CLAYTON F. , MAIA IAN G. , RODRIGUES MARIA ANDRÉIA F. , VALENTE MARCO TÚLIO O.
Published: May 2008

The aspect-oriented programming (AOP) paradigm offers software developers with powerful modularization abstractions to help them explicitly separate design concerns at the source code level. However, the impact of AOP in the service-oriented architecture (SOA) paradigm has been dwarfed by the fact that existing AOP solutions are tightly coupled to a particular programming language, middleware system or execution platform. Clearly, this not only restricts the implementation choices available to application developers, but it also clashes with the heterogeneous and loosely coupled nature of SOA. This paper presents the Web Service Aspect Language (WSAL) that seamlessly integrates AOP and SOA concepts, thus avoiding the drawbacks of existing solutions. In WSAL, aspects themselves are freely specified, implemented and executed as loosely coupled web services. This characteristic allows WSAL aspects to be easily woven into the message flow exchanged between service consumers and service providers, in a way that is completely independent from any particular implementation technology. This paper also reports on the implementation and preliminary evaluation of a prototype aspect weaver for WSAL, which is based on an existing web intermediary technology.
DYNAMIC SERVICE COMPOSITION: A DISCOVERY-BASED APPROACH
Authors: LEE JONATHAN , MA SHANG-PIN , LIN YING-YAN , LEE SHIN-JIE , WANG YAO-CHIANG
Published: May 2008

Service-Orientated Computing (SOC) has become a main trend in software engineering that promotes the construction of applications based on the notion of services. SOC has recently attracted the researchers' attention and has been adopted industry-wide. However, service composition that enables one to aggregate existing services into a new composite service is still a highly complex and critical task in service-oriented technology. To enhance availability of composite services, we propose a discovery-based service composition framework to better integrate component services in both static and dynamic manner, including (1) to devise a notion of service availability especially for composition; (2) to develop a dynamic service composition (DSC) pattern for addressing the issues of service availability; and (3) to extend Contract Net Protocol (ECNP) to coordinate service discovery, composition and invocation based on the composite pattern. The main benefit of the proposed approach is better availability through attaching multiple candidate services for future binding.
Lötschberg tunnel disaster, 100 years ago
Authors: Waltham T.
Published: May 2008

The older of Switzerland's Lötschberg tunnels presented a classic case of an engineering geology disaster, which is surprisingly little known. The tunnel heading breached rockhead into a buried valley that had a depth greater than anything perceived as possible at that time. It demonstrates the need for engineers to understand the geological processes behind ground conditions.
Engineering geology and geotechnics: the role of higher education with particular reference to the undergraduate programme at Portsmouth
Authors: Duncan N. , Poulsom A.J. , Browning G.R.J.
Published: May 2008

The Honours degree in Engineering Geology and Geotechnics, founded at the (then) Portsmouth College of Technology in 1967, is the only UK full undergraduate programme in Engineering Geology to have been in continuous operation since the founding of the
Quarterly Journal of Engineering Geology and Hydrogeology
in that year. Now part of the portfolio of the University of Portsmouth, the vocational nature of the programme is made clear and the evolution of the curriculum over the years discussed in the light of the changes in Higher Education more generally in the UK and the EU. The student context is reviewed and the fulfilment of the intention to prepare graduates for immediate employment in engineering geology and geotechnology explored.
The historical record as a basis for assessing interactions between geology and civil engineering
Authors: Turner A.K.
Published: May 2008

Engineering construction dates from the dawn of civilization. Although both geology and civil engineering have existed in a reasonably modern form for only about 250 years, for thousands of years some individuals with an awareness of rock and soil conditions offered counsel on excavations, site conditions, and construction materials. The closeness of partnerships between geologists and engineers has varied over time and reflects a natural tension between the inductive approach of geological investigations and the deductive approach of engineering design. Both science and engineering have periods in which their governing paradigms, the generally accepted set of practices that define a discipline during a particular period of time, are subject to rapid change. Some of these ‘paradigm shifts’ have fostered closer collaborations between geologists and engineers; others have resulted in a weakening of such interactions. Society now demands that both geologists and engineers increasingly undertake complex predictions. Engineering projects have become much more complex; bridges and tunnels have become longer and larger, and high-speed transportation links have become common. Population growth has pushed developments into more complex geological locations where site conditions are less than optimal and geohazards more likely. New and ever more challenging environmental and economic issues make the design of new facilities increasingly dependent on accurate predictions of geological conditions. Decision-making under uncertainty (prediction) requires an increasingly multi-disciplinary approach, and thus continued close interactions between geologists and civil engineers.
William Robert Dearman: Britain's first Professor of engineering geology
Authors: Reeves G.M.
Published: May 2008

Professor William Robert (‘Bill’) Dearman was the first British Professor of Engineering Geology. He played a significant role in the development of the subject in construction and land-use planning in the UK, and development of engineering geology mapping as a practical technique for ground engineering. He became the first permanent scientific editor of the
Quarterly Journal of Engineering Geology
(from 1972 to 1977) and his contributions to IAEG and UNESCO publications and guidelines on engineering geology mapping are still in use today.
Regulation of direct transintestinal cholesterol excretion in mice
Authors: van der Velde Astrid E. , Vrins Carlos L. J. , van den Oever Karin , Seemann Ingar , Oude Elferink Ronald P. J. , van Eck Miranda , Kuipers Folkert , Groen Albert K.
Published: May 2008

Biliary secretion is generally considered to be an obligate step in the pathway of excess cholesterol excretion from the body. We have recently shown that an alternative route exists. Direct transintestinal cholesterol efflux (TICE) contributes significantly to cholesterol removal in mice. Our aim was to investigate whether the activity of this novel pathway can be influenced by dietary factors. In addition, we studied the role of cholesterol acceptors at the luminal side of the enterocyte. Mice were fed a Western-type diet (0.25% wt/wt cholesterol; 16% wt/wt fat), a high-fat diet (no cholesterol; 24% wt/wt fat), or high-cholesterol diet (2% wt/wt), and TICE was measured by isolated intestinal perfusion. Bile salt-phospholipid mixtures served as cholesterol acceptor. Western-type and high-fat diet increased TICE by 50 and 100%, respectively. In contrast, the high-cholesterol diet did not influence TICE. Intestinal scavenger receptor class B type 1 (Sr-B1) mRNA and protein levels correlated with the rate of TICE. Unexpectedly, although confirming a role for Sr-B1, TICE was significantly increased in Sr-B1-deficient mice. Apart from the long-term effect of diets on TICE, acute effects by luminal cholesterol acceptors were also investigated. The phospholipid content of perfusate was the most important regulator of TICE; bile salt concentration or hydrophobicity of bile salts had little effect. In conclusion, TICE can be manipulated by dietary intervention. Specific dietary modifications might provide means to stimulate TICE and, thereby, to enhance total cholesterol turnover.
Effects of buspirone on posthypoxic ventilatory behavior in the C57BL/6J and A/J mouse strains
Authors: Yamauchi Motoo , Dostal Jesse , Kimura Hiroshi , Strohl Kingman P.
Published: May 2008

Buspirone, a partial agonist of the serotonergic 5-HT1Areceptor, improves breathing irregularities in humans with Rett syndrome or brain stem injury. The purpose of this study was to examine whether buspirone alters posthypoxic ventilatory behavior in C57BL/6J (B6) and A/J mouse strains. Measurements of ventilatory behavior were collected from unanesthetized adult male mice ( n = 6 for each strain) using the plethysmographic method. Mice were given intraperitoneal injections of vehicle or several doses of buspirone and exposed to 2 min of hypoxia (10% O2) followed by rapid reoxygenation (100% O2). Twenty minutes later, mice were tested for hypercapnic response (8% CO2-92% O2). On a separate day, mice were injected with the 5-HT1Areceptor antagonist 4-iodo- N-{2-[4-(methoxyphenyl)-1-piperazinyl] ethyl}- N-2-pyridinylbenzamide ( p-MPPI) before the injection of buspirone, and measurements were repeated. In separate studies, arterial blood-gas analysis was performed for each strain ( n = 12 in B6 and 10 in A/J) with buspirone or vehicle. In both strains, buspirone stimulated ventilation at rest. In the B6 mice, the hypoxic response was unchanged, but the response to hypercapnia was reduced with buspirone (5 mg/kg; P < 0.05). With reoxygenation, vehicle-treated B6 exhibited periodic breathing and greater variation in ventilation compared with A/J ( P < 0.01). In B6 animals, ≥3 mg/kg of buspirone reduced variation and prevented the occurrence of posthypoxic periodic breathing. Both effects were reversed by p-MPPI. Treatment effect of buspirone was not explained by a difference in resting arterial blood gases. We conclude that buspirone improves posthypoxic ventilatory irregularities in the B6 mouse through its agonist effects on the 5-HT1Areceptor.
Habitual physical activity in daily life correlates positively with markers for mitochondrial capacity
Authors: den Hoed Marcel , Hesselink Matthijs K. C. , van Kranenburg Gerrit P. J. , Westerterp Klaas R.
Published: May 2008

Physical exercise training is a powerful tool to maintain or improve mitochondrial density and function (mitochondrial capacity). This study aims to determine whether mitochondrial capacity is also associated with habitual physical activity in daily life (PADL). The capacity of classic markers for mitochondrial density, i.e., the capacity of citrate synthase (CS) and succinate dehydrogenase (SDH), as well the capacity of cytochrome c oxidase (COX) and β-hydroxyacyl-CoA dehydrogenase (HAD), was determined in homogenized muscle biopsy samples obtained from the vastus lateralis muscle of nonexercising healthy young (age 20 ± 2 yr) subjects (31 women, 7 men). PADL was measured during two periods of 14 days using a triaxial accelerometer for movement registration. CS, SDH, and COX were positively associated with PADL [ P < 0.05, R = 0.36, 95% confidence interval (CI): 1.3·10−4 to 2.2·10−3; P < 0.05, R = 0.39, 95% CI: 1.1·10−5 to 9.9·10−5; and P < 0.05, R = 0.33, 95% CI: 7.5·10−6 to 3.6·10−4, respectively], and HAD tended to correlate positively with PADL ( P = 0.06, R = 0.31, 95% CI: −2.2·10−5 to 1.1·10−3). The population was subsequently stratified based on the intensity of the activities performed. CS was only associated with PADL in subjects spending more time on high-intensity physical activity, whereas HAD was only associated with PADL in subjects spending less time on low intensity physical activity. We are the first to report that even within the range of normal daily life activities, mitochondrial capacity is positively associated with the level of habitual physical activity in daily life. Thus an active lifestyle may help to maintain or improve mitochondrial capacity.
FKBP12 deficiency reduces strength deficits after eccentric contraction-induced muscle injury
Authors: Corona Benjamin T. , Rouviere Clement , Hamilton Susan L. , Ingalls Christopher P.
Published: May 2008

Strength deficits associated with eccentric contraction-induced muscle injury stem, in part, from excitation-contraction uncoupling. FKBP12 is a 12-kDa binding protein known to bind to the skeletal muscle sarcoplasmic reticulum Ca2+ release channel [ryanodine receptor (RyR1)] and plays an important role in excitation-contraction coupling. To assess the effects of FKBP12 deficiency on muscle injury and recovery, we measured anterior crural muscle (tibialis anterior and extensor digitorum longus muscles) strength in skeletal muscle-specific FKBP12-deficient and wild-type (WT) mice before and after a single bout of 150 eccentric contractions, as well as before and after the performance of six injury bouts. Histological damage of the tibialis anterior muscle was assessed after injury. Body weight and peak isometric and eccentric torques were lower in FKBP12-deficient mice compared with WT mice. There were no differences between FKBP12-deficient and WT mice in preinjury peak isometric and eccentric torques when normalized to body weight, and no differences in the relative decreases in eccentric torque with a single or multiple injury bouts. After a single injury bout, FKBP12-deficient mice had less initial strength deficits and recovered faster (especially females) than WT mice, despite no differences in the degree of histological damage. After multiple injury bouts, FKBP12-deficient mice recovered muscle strength faster than WT mice and exhibited significantly less histological muscle damage than WT mice. In summary, FKBP12 deficiency results in less initial strength deficits and enhanced recovery from single (especially females) and repeated bouts of injury than WT mice.
Modulation of β-adrenoceptor signaling in the hearts of 4-wk simulated weightlessness rats
Authors: Yin Wen , Liu Jin-Cheng , Fan Rong , Sun Xi-Qing , Ma Jin , Feng Na , Zhang Quan Yu , Yin Zhao , Zhang Shu-Miao , Guo Hai-Tao , Bi Hui , Wang Yue-Min , Sun Xin , Cheng Liang , Cui Qin , Yu Shi-Qiang , Yi Ding-Hua , Pei Jian-Ming
Published: May 2008

The modulation of β-adrenoceptor signaling in the hearts of hindlimb unweighting (HU) simulated weightlessness rats has not been reported. In the present study, we adopted the rat tail suspension for 4 wk to simulate weightlessness; then the effects of simulated microgravity on β-adrenoceptor signaling were studied. Mean arterial blood pressure (ABP), left ventricular pressure (LVP), systolic function (+dP/d tmax), and diastolic function (−dP/d tmax) were monitored in the course of the in vivo experiment. Single rat ventricular myocyte was obtained by the enzymatic dissociation method. Hemodynamics, myocyte contraction, and cAMP production in response to β-adrenoceptor stimulation with isoproterenol or adenylyl cyclase stimulation with forskolin were measured, and Gs protein was also determined. Compared with the control group, no significant changes were found in heart weight, body weight and ABP, while LVP and ±dP/d tmaxwere significantly reduced. The ABP decrease, LVP increase, and ±dP/d tmaxin response to isoproterenol administration were significantly attenuated in the HU group. The effects of isoproterenol on electrically induced single-cell contraction and cAMP production in myocytes of ventricles in the HU rats were significantly attenuated. The biologically active isoform, Gsα (45 kDa) in the heart, was unchanged. Both the increased electrically induced contraction and cAMP production in response to forskolin were also significantly attenuated in the simulated weightlessness rats. Above results indicated that impaired function of adenylyl cyclase causes β-adrenoceptor desensitization, which may be partly responsible for the depression of cardiac function.
Glutamate availability is important in intramuscular amino acid metabolism and TCA cycle intermediates but does not affect peak oxidative metabolism
Authors: Mourtzakis M. , Graham T. E. , González-Alonso J. , Saltin B.
Published: May 2008

Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops ∼40–80% with the onset of exercise and 2-oxoglutarate declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained (T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption (V̇o2peak) in the T thigh was greater than that in the UT thigh ( P < 0.05); V̇o2peak was not different between the T and UT thighs with glutamate infusion. Peak exercise under control conditions revealed a greater glutamate uptake in the T thigh compared with rest (7.3 ± 3.7 vs. 1.0 ± 0.1 μmol·min−1·kg wet wt−1, P < 0.05) without increase in TCA cycle intermediates. In the UT thigh, peak exercise (vs. rest) induced an increase in fumarate (0.33 ± 0.07 vs. 0.02 ± 0.01 mmol/kg dry wt (dw), P < 0.05) and malate (2.2 ± 0.4 vs. 0.5 ± 0.03 mmol/kg dw, P < 0.05) and a decrease in 2-oxoglutarate (12.2 ± 1.6 vs. 32.4 ± 6.8 μmol/kg dw, P < 0.05). Overall, glutamate infusion increased arterial glutamate ( P < 0.05) and maintained this increase. Glutamate infusion coincided with elevated fumarate and malate ( P < 0.05) and decreased 2-oxoglutarate ( P < 0.05) at peak exercise relative to rest in the T thigh; there were no further changes in the UT thigh. Although glutamate may have a role in the expansion of the TCA cycle, glutamate and TCA cycle intermediates do not directly affect V̇o2peak in either trained or untrained muscle.
Acid Susceptibility at Various Depths of pH-Cycled Enamel and Dentine Specimens
Authors: Lagerweij M.D. , ten Cate J.M.
Published: May 2008

pH-cycling and in situ studies have shown that fluctuations in de-/remineralisation conditions or in fluoride usage can lead to laminations inside enamel or dentine lesions. Layers with different mineral content are thought to reflect the history of fluoride administrations. Studying the dissolution properties of such lesions at various depths – using bulk specimens – is presumably hampered by limited diffusion of acids through the lesion pores. Therefore, in this study the acid susceptibility of enamel and dentine lesions and the underlying sound tissues was studied by exposing sections to acid buffers from the cut rather than from the external surface. Specimens were obtained from a previous study of the effects of high-fluoride (0, 1,000, 2,000, 3,000/5,000 ppm F) toothpastes on enamel and dentine de-/remineralisation. Sections were subjected to acid buffers for 3 and 7 days and the changes in mineral content were monitored by contact microradiography. For enamel lesions a significant difference in dissolution over depth was observed between the groups subjected to the different fluoride schemes. At 7 days a dose response was found between the different fluoride groups and the lesion parameters. In the no-fluoride group dissolution in the original lesion and the sound tissue were similar. All dentine lesions which had been treated with fluoride showed inhibition of dissolution, but the inhibition did not increase with higher fluoride concentrations. Deeper into the dentine tissue there was some protection, but it was not statistically significant. We conclude that penetration of fluoride through the lesion pores determines the dissolution pattern of a lesion at various depths.
An in vitro Study of Affected Dentin as a Risk Factor for the Development of Secondary Caries
Authors: Borczyk Dariusz , Piątowska Danuta , Krzemiński Zbigniew
Published: May 2008

The objective of the study was to investigate the association between the presence of residual caries (inner affected dentin) on the cavity walls of cavity preparations and the further development of secondary caries lesions. Two 2 × 5 × 2 mm cavities, one in the apical portion (A) and one in the cervical portion (C) of the root, were prepared on both the lingual (L) and buccal (B) surfaces of 18 extracted human roots. The apical cavities (AB and AL) were artificially demineralized for 30 min using a decalcifying solution, followed by staining with a caries detector dye and then excavation of irreversibly demineralized dentin, leaving behind a layer of inner carious dentin. The cervical cavities (CB and CL) remained intact with sound dentin on the cavity walls. All cavities were then restored with composite resin. Following restoration, lingual specimens (AL and CL) were completely covered by an acid-resistant varnish to prevent further demineralization. All specimens were then incubated in an in vitro microbial artificial mouth model for 3 days in order to develop secondary carious lesions. At the end of the study all specimens were processed for energy-dispersive X-ray analysis of Ca concentration adjacent to the border between dentin and restoration. Statistical analysis of Ca concentrations revealed that the presence of affected inner dentin does not increase the susceptibility to secondary caries. Therefore, it was concluded that conservative cavity preparations leaving behind affected dentin do not increase the risk of secondary caries development.
How Bartter’s and Gitelman’s Syndromes, and Dent’s Disease Have Provided Important Insights into the Function of Three Renal Chloride Channels: ClC-Ka/b and ClC-5
Authors: Briet Marie , Vargas-Poussou Rosa , Lourdel Stephane , Houillier Pascal , Blanchard Anne
Published: May 2008

Chloride channels are expressed in almost all cell membranes and are potentially involved in a wide variety of functions. The kidney expresses 8 of the 9 chloride channels of the ClC family that have been cloned so far to date in mammals. This review focuses on the pathophysiology of two renal disorders that have contributed recently to our understanding of the physiological role of chloride channels belonging to the ClC family. First are the related syndromes of Bartter’s and Gitelman’s, in which inactivating mutations of the genes encoding either of the ClC-Ks, or their regulatory β-subunit barttin, have shown the important contribution of these chloride channels to renal tubular sodium and chloride (NaCl) transport along the loop of Henle and distal tubule. Second is the renal Fanconi syndrome known as Dent’s disease, in which ClC-5 disruption has revealed the key role of this endosomal chloride channel in the megalin-mediated endocytotic pathway in the proximal tubule. The underlying pathophysiology of this inherited disorder demonstrates how ClC-5 is directly or indirectly required for the reabsorption of filtered low-molecular-weight proteins and bioactive peptides, also expression of membrane transporters, and clearance of calcium-based stone-forming crystals.
Transient Body Fluid Accumulation and Enhanced NKCC2 Expression in Gerbils with Brain Infarction
Authors: Ejima Yutaka , Nakamura Yohsuke , Michimata Mari , Hatano Ryo , Kazama Itsuro , Sanada Satoru , Arata Tomohiro , Suzuki Michiko , Miyama Noriyuki , Sato Akira , Satomi Susumu , Fushiya Shinji , Sasaki Sei , Matsubara Mitsunobu
Published: May 2008

Background: Enhanced expression of a kidney-specific sodium co-transporter (NKCC2: Na-K-2Cl co-transporter) in the thick ascending limb of Henle has been identified in rat models of congestive heart failure and liver cirrhosis, suggesting that high NKCC2 expression underlies edema formation. An increased abundance of NKCC2, however, has also been noted in rats with the syndrome of inappropriate secretion of antidiuretic hormone; hyponatremia without edema. In the present study, we examined NKCC2 expression in non-edematous disease, such as a brain infarction, and investigated the physiological and/or pathological characterization of NKCC2 expression. Methods:We initially examined NKCC2 expression in an animal model of brain infarction. Mongolian gerbils (around 60 g body weight) underwent bilateral clamping of the common carotid arteries for 5 min for the induction of brain infarction. NKCC2 and apical water channel (AQP2) protein levels in the collecting duct were examined by Western blotting in kidney tissues 2, 7, and 14 days after the brain infarction. Gerbils with brain infarction were then fed either a normal low-sodium diet (0.3 g/kg/day) or a high-sodium diet (3.0 g/kg/day), and body weight, urine volume and urinary osmolality were examined daily. Blood parameters were measured on day 14 after the brain infarction. Results: Histochemical examination of the brain confirmed the presence of brain infarction, as manifested by altered cresyl violet staining in the hippocampus. Protein levels of NKCC2 were significantly increased in gerbils with brain infarction on days 2 and 7 after brain infarction, whereas AQP2 protein signals remained unaltered. However, the increased NKCC2 intensity disappeared on day 14. Body weight gain was slightly, but significantly greater in gerbils with brain infarction than in sham-operated gerbils up to 7 days after the brain infarction. The high-sodium diet resulted in significant urinary concentration and enhanced weight gain in infarcted gerbils. Conclusion: We noted increased NKCC2 abundance in non-edematous disease, which enhanced body fluid accumulation, likely via the sodium loading-dependent concentration of the urine. These results suggest that the physiological process of edema formation is based on specific NKCC2 expression. The transient duration of these findings in the present animal model suggests two different characteristics of specific NKCC2 expression, an immediate, transient appearance as a common response in serious conditions and more chronic expression that leads to edema formation.
The Uremic Environment and Muscle Dysfunction in Man and Rat
Authors: Harrison A.P. , Nielsen A.H. , Eidemak I. , Molsted S. , Bartels E.M.
Published: May 2008

Background: Patients reaching end-stage renal disease experience debilitating fatigue, with progression of this disease, rendering patients dysfunctional in their everyday lives. Methods: In vivomeasurements of muscle function, assessed using surface electromyography (EMG), were made on 25 patients prior to and after a session of hemodialysis (HD) treatment, alongsidein vitro measurements of muscle function in isolated rat muscles incubated in normal or uremic conditions approximating to those found in uremic rats (rat uremic: RU) or uremic humans (human uremic: HU). Results: HD significantly affected plasma values, e.g. reducing urea (69%), creatinine (62%), potassium (23%) and phosphate (48%) concentrations in patients (all p < 0.01). Treatment also improved the EMG frequency of 2nd dorsal interosseous (fast-twitch) (p < 0.01), although no change was noted for vastus lateralis (slow-twitch). In isolated rat muscles, a uremic environment had no significant effect on slow-twitch soleus during field stimulation, however, in fast-twitch extensor digitorum longus, a significant 23% (RU) and 22% (HU) faster rate of decline in force was measured, compared to controls (p < 0.001 and p < 0.01, respectively). Conclusion: It is concluded that (1) muscle weakness and its electrophysiological correlates may be rapidly induced by uremic solutes and rapidly reversed when the solutes are removed by dialysis, and (2) fast-twitch muscles are more readily affected by uremic conditions than slow-twitch muscles.
Engineering Transport Protein Function: Theoretical and Technical Considerations Using the Sugar-Transporting Phosphotransferase System of Escherichia coli as a Model System
Authors: Soberón Xavier , Saier Jr. Milton H.
Published: May 2008

Potential experimental approaches for developing and applying protein-engineering protocols to transmembrane transport systems are described. We specifically consider procedures designed to alter protein function. These procedures are designed for the specific purposes of (1) changing protein interaction specificities and (2) changing a protein’s catalytic function. We use sugar-transporting bacterial phosphotransferase systems as model systems to illustrate the proposed approaches. These and other similar procedures are likely to prove to be of utility for biotechnological manipulation of proteins as well as for elucidating potential evolutionary pathways taken for the appearance of novel functions within a protein family.
Sleep Disorders Are Underdiagnosed in Patients on Maintenance Hemodialysis
Authors: Jurado-Gamez B. , Martin-Malo A. , Alvarez-Lara M.A. , Muñoz L. , Cosano A. , Aljama P.
Published: May 2008

Background: Sleep apnea-hypopnea syndrome (SAHS) is a cardiovascular risk factor. The aim of this study was to evaluate sleep disorders using polysomnography on a non-selected population of patients on maintenance hemodialysis. Methods: Overnight polysomnography was performed on 32 hemodialysis patients (24 men/8 women, 54 ± 16 years), and on 19 healthy subjects of similar age, sex and body mass index who were used as controls. Results: In hemodialysis patients, the most frequent sleep disorder was SAHS in 44% (14/32), followed by insomnia in 41% (13/32). Compared to healthy controls, patients on hemodialysis showed less slow-wave sleep and rapid eye movement sleep (23 vs. 36%, p = 0.001), less sleep efficiency (71 vs. 87%, p = 0.0079) and a higher periodic limb movement index (39.7 vs. 9.1; p = 0.003). An increase in apnea-hypopnea index (18.9 vs. 4.3; p = 0.007) and dips in the SaO2 (≧4%) per hour of sleep (22.6 vs. 6.4; p = 0.021) were also significantly greater in hemodialysis patients than controls. 72% of the cases of SAHS were diagnosed solely by means of polysomnography. Conclusions: The patients on hemodialysis showed poor sleep quality with a significant increase in the apnea-hypopnea index and in the number of dips in SaO2. SAHS was underdiagnosed in a large percentage of the hemodialysis patients.
Backward Genotype-Trait Association (BGTA)-Based Dissection of Complex Traits in Case-Control Designs
Authors: Zheng Tian , Wang Hui , Lo Shaw-Hwa
Published: May 2008

Background: The studies of complex traits project new challenges to current methods that evaluate association between genotypes and a specific trait. Consideration of possible interactions among loci leads to overwhelming dimensions that cannot be handled using current statistical methods. Methods: In this article, we evaluate a multi-marker screening algorithm – the backward genotype-trait association (BGTA) algorithm for case-control designs, which uses unphased multi-locus genotypes. BGTA carries out a global investigation on a candidate marker set and automatically screens out markers carrying diminutive amounts of information regarding the trait in question. To address the ‘too many possible genotypes, too few informative chromosomes’ dilemma of a genomic-scale study that consists of hundreds to thousands of markers, we further investigate a BGTA-based marker selection procedure, in which the screening algorithm is repeated on a large number of random marker subsets. Results of these screenings are then aggregated into counts that the markers are retained by the BGTA algorithm. Markers with exceptional high counts of returns are selected for further analysis. Results and Conclusion: Evaluated using simulations under several disease models, the proposed methods prove to be more powerful in dealing with epistatic traits. We also demonstrate the proposed methods through an application to a study on the inflammatory bowel disease.
Antithrombotic Therapy and Predilection for Cerebellar Hemorrhage
Authors: Toyoda Kazunori , Okada Yasushi , Ibayashi Setsuro , Inoue Tooru , Yasumori Kotaro , Fukui Daisuke , Uwatoko Takeshi , Makihara Noriko , Minematsu Kazuo
Published: May 2008

Background: With the recent increase in the use of antithrombotic therapy, intracerebral hemorrhage (ICH) has been found to be a common complication. We determined whether the use of oral antithrombotic therapy and the patients’ preexisting comorbidities were predictive of cerebellar hemorrhage (CH; previously reported to be associated with anticoagulants) as compared to other ICH, and whether antithrombotic therapy affected the clinical severity of CH. Methods: A study of 327 consecutive patients hospitalized in our institute within 3 days after the onset of ICH, including 38 patients with a CH. Results: CH accounted for 12% of all ICH, 75% of which occurred in patients on warfarin therapy with an international normalized ratio (INR) for prothrombin time >2.5 (p < 0.0001), and 33% of which occurred in patients on ticlopidine therapy (p = 0.017). Warfarin therapy with an INR >2.5 and high blood glucose on admission were independently predictive of CH as compared to other ICH. In addition, previous ischemic stroke (p = 0.002) and heart diseases (p = 0.018) were more prevalent in patients with CH than in those with other ICH. The number of major arteriosclerotic comorbidities and risk factors was also independently predictive of CH risk. Conclusions: We confirmed that warfarin therapy with an INR >2.5 is associated with CH. Patients with CH frequently had arteriosclerotic comorbidities requiring antithrombotic therapy that can complicate their acute management.
Recurrence after Ischemic Stroke in Chinese Patients: Impact of Uncontrolled Modifiable Risk Factors
Authors: Xu Gelin , Liu Xinfeng , Wu Wentao , Zhang Renliang , Yin Qin
Published: May 2008

Background: Data concerning stroke occurrence and recurrence in China are extremely rare. This study was designed to analyze determinants of stroke recurrence in a cohort of Chinese patients. Methods: Subjects were patients with ischemic stroke registered in the Nanjing Stroke Registry Program. Modifiable risk factors for stroke were identified and stratified into 3 levels: without, controlled and uncontrolled. Cox proportional hazard model was used to detect influence factors for stroke recurrence. Results: First-year recurrence rate was 11.2% in the registered patients. Hypertension, atrial fibrillation (AF) and smoking were associated with increased risk of recurrence. Controlling hypertension and AF each halved recurrent risk (p < 0.001). Ceasing smoking for more than 1 year reduced hazard ratio of recurrence from 1.71 to 1.39 (p < 0.05). Controlling blood sugar level in diabetics did not significantly change recurrent risk (hazard ratio, 1.69 vs. 1.64, p > 0.05). Conclusions: The recurrence rate is higher in Chinese patients with ischemic stroke compared with the one reported in western populations. Failure to control some modifiable risk factors in Chinese patients may be responsible for this discrepancy.
The Ruler Is Dead: An Analysis of Carotid Plaque Motion
Authors: Lenzi Gian Luigi , Vicenzini Edoardo
Published: May 2008

Factors involved in atherosclerotic plaque progression are still a topic of hot debate. With the advance of new ultrasound techniques it has been possible to identify atherosclerotic plaque characteristics that may reflect a higher risk of vulnerability. Among the various proposed mechanisms, one of the least investigated is plaque motion, i.e. plaque stability in respect to the arterial wall. We report here two asymptomatic patients with internal carotid stenosis that showed differences in plaque motion, a finding that could determine a change in their future treatment.
Trends in the Incidence of Transient Ischemic Attacks, Premorbid Risk Factors and the Use of Preventive Treatments in the Population of Dijon, France from 1985 to 2004
Authors: Bejot Yannick , Rouaud Olivier , Benatru Isabelle , Durier Jérôme , Caillier Marie , Couvreur Grégory , Fromont Agnès , Falvo Nicolas , Osseby Guy-Victor , Cottin Yves , Zeller Marianne , Millerot Emilie , Marie Christine , Moreau Thibault , Giroud Maurice
Published: May 2008

Background: We describe the epidemiological trends of transient ischemic attack (TIA) in a 20-year population-based pilot study. Methods: Trends in the incidence, risk factors and pre-TIA use of preventive treatments for TIA were observed from 1985 to 2004 according to the classic definition in the population of the city of Dijon, France (150,000 inhabitants). Results: The raw and standardized incidence of TIA were stable over time. We observed a significant increase in the mean age at TIA onset in women only. The prevalence of hypercholesterolemia and diastolic blood pressure ≧90 mm Hg among patients with TIA increased significantly. This contrasts with falls in smoking and in history of previous myocardial infarction. Conclusion: The stability of classic TIA incidence, despite the rise in the proportion of elderly people, and the increase in the mean age at onset in women may be considered as a medical progress.
The Khorasan Stroke Registry: Results of a Five-Year Hospital-Based Study
Authors: Ghandehari Kavian , Izadi Zahra
Published: May 2008

The hospital-based stroke registry is useful for understanding the diverse clinical characteristics of stroke related to geographical, racial or environmental differences. The Khorasan Stroke Registry (KSR) was established for the evaluation of incidence, clinical manifestations, risk factors, topography and etiology of ischemic stroke in Southern Khorasan, Iran, during 2001–2005. Consecutive stroke patients underwent a standard battery of diagnostic investigations by a stroke neurologist. The topography and etiology of brain infarction were determined by the Practical Iranian Criteria classification. The incidence of ischemic stroke in the Persian population is 43.17 cases per 100,000 people per year. A total of 1,392 ischemic stroke patients (738 females, 654 males) were evaluated in the KSR. The etiologies included atherosclerosis (53.6%), followed by uncertain causes (19.9%), cardioembolism (11.8%) and miscellaneous etiologies (2.9%). Of our patients, 11.7% had both atherosclerosis and cardioembolic mechanisms. Rheumatic valvular disease was present in 44.8% of cardioembolic stroke patients and caused 4.31 preventable stroke cases per 100,000 Persian people per year. Hypertension and history of ischemic cerebrovascular events were the most frequent risk factors, 53.1 and 22.3%, respectively. The in-hospital mortality of our ischemic stroke patients was 7.3%. A total of 336 patients with intracerebral hemorrhage (189 females, 147 males) were evaluated in the KSR. The incidence of intracerebral hemorrhage in the Persian population is 10.43 cases per 100,000 people per year. The high frequency of atherosclerotic etiology in the KSR is due to its classification criteria, which do not separate small vessel territory infarcts as a different etiologic subtype. Rheumatic valvular disease is an important cause of stroke in the Persian population.
How Good Is the Management of Vascular Risk after Stroke, Transient Ischaemic Attack or Carotid Endarterectomy?
Authors: Johnson Paul , Rosewell Mary , James Martin A.
Published: May 2008

Background: Patients remain at high risk of vascular events after stroke, transient ischaemic attack or carotid endarterectomy. We studied how well this risk is addressed by the effective treatment of modifiable risk factors. Methods: A total of 198 consecutive attenders at a rapid access stroke clinic and 98 consecutive patients undergoing carotid endarterectomy were studied. Treatment of hypertension and hyperlipidaemia, smoking status and the use of antithrombotic therapy were assessed at baseline and 6 months later. The findings were compared with targets from the UK National Clinical Guidelines for Stroke. Results: Baseline and follow-up data were available on 284 patients. The rates of control of vascular risk factors improved only slightly during follow-up. Blood pressure was below target levels in only 69 (24%) at baseline and 79 (28%) at 6 months, and serum cholesterol was below target levels in only 55 (19%) at baseline and 63 (22%) at 6 months. At baseline, 55 (19%) were smokers, of whom 12 (22%) had quit at 6 months. Anticoagulant therapy was prescribed in 19 of 37 patients (51%) in atrial fibrillation at 6 months. Antiplatelet therapy was prescribed in 90% of patients in sinus rhythm. Conclusions: Despite the identification of vascular risk factors at the time of clinic or surgery, 6 months later these risk factors remain poorly addressed. More effective methods of managing vascular risk in these patients are needed.