bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated Levels of IL-10 and G-CSF Associated with Asymptomatic Malaria in Pregnant Women
Authors: Wilson Nana O. , Bythwood Tameka , Solomon Wesley , Jolly Pauline , Yatich Nelly , Jiang Yi , Shuaib Faisal , Adjei Andrew A. , Anderson Winston , Stiles Jonathan K.
Published: July 2010

In sub-Saharan Africa, approximately 30 million pregnant women are at risk of contracting malaria annually. Nearly 36% of healthy pregnant women receiving routine antenatal care tested positive forPlasmodium falciparumHRP-II antigen in Ghana. We tested the hypothesis that asymptomatic HRP II positive pregnant women expressed a unique Th1 and Th2 phenotype that differs from healthy controls. Plasma from healthy (n=15) and asymptomatic (n=25) pregnant women were evaluated for 27 biomarkers (IL-1b, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL- 17, Eotaxin, bFGF-2, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-bb, RANTES, TNF, and VEGF) associated with Th1 and Th2 cytokine homeostasis. IL-10 and G-CSF levels were elevated in the asymptomatic group when compared with the healthy group (P=.031and .041, resp.). The median ratios of IL-1β:5, IL-1β:10, IL-1β:G-CSF, IL-1β:Eotaxin, IL-12:G-CSF, IL-15:10, IL-17:G-CSF, IL-17:Eotaxin, TNF:IL-4, TNF:IL-5, and TNF:G-CSF were significantly different among the two groups. Thus, asymptomatic malaria carriage may be linked to circulating levels of IL-10 and G-CSF.
Differences between Goldmann Applanation Tonometry and Dynamic Contour Tonometry following Trabeculectomy
Authors: Detorakis Efstathios T. , Grammenandi Emilia , Pallikaris Ioannis G. , Tsilimbaris Miltiadis K.
Published: July 2010

Background. To evaluate differences between Goldmann Applanation Tonometry (GAT) and Dynamic Controur Tonometry (DCT) following trabeculectomy.Methods. Thirty eight glaucomatous eyes with a history of trabeculectomy (Trabeculectomy group, TG), 20 eyes without a history of trabeculectomy but with a history of latanoprost use (Latanoprost group, LG), and 19 nonglaucomatous eyes (Control group, CG) were included. GAT-IOP, DCT-IOP, the difference between them (dIOP), the central corneal thickness (CCT), the axial length (AL), and the depth of the anterior chamber (ACD) were measured.Results. dIOP was significantly higher in TG (5.19 mmHg) than in LG (4.01 mmHg) and CG (1.98 mmHg). Correlations between AL and dIOP were statistically significant in both TG and LG but not in CG whereas correlations between dIOP and other clinical parameters examined were statistically not significant in all groups.Conclusions. The significantly higher dIOP in TG implies that the bio-mechanical properties of the ocular walls are altered following trabeculectomy.
Experimental Validation of a Coexistence Model of IEEE 802.15.4 and IEEE 802.11b/g Networks
Authors: Yuan Wei , Wang Xiangyu , Linnartz Jean-Paul M. G. , Niemegeers Ignas G. M. M.
Published: July 2010

As IEEE 802.15.4 Wireless Sensor Networks (WSNs) and IEEE 802.11b/g Wireless Local Area Networks (WLANs) are often collocated, coexistence issues arise as these networks share the same 2.4 GHz Industrial, Scientific, and Medical (ISM) band. Consequently, their performance may degrade. We have proposed a coexistence model of IEEE 802.15.4 and IEEE 802.11b/g networks, which addresses their coexistence behavior and explains their coexistence performance. As an extension of the previous work, a compact testbed was developed and experiments on the coexistence issues between these networks were conducted. The experiments not only validated the theoretical model but also provided more information and insights about the coexistence issues in the real-life environment.
DAMPening Inflammation by Modulating TLR Signalling
Authors: Piccinini A. M. , Midwood K. S.
Published: July 2010

Damage-associated molecular patterns (DAMPs) include endogenous intracellular molecules released by activated or necrotic cells and extracellular matrix (ECM) molecules that are upregulated upon injury or degraded following tissue damage. DAMPs are vital danger signals that alert our immune system to tissue damage upon both infectious and sterile insult. DAMP activation of Toll-like receptors (TLRs) induces inflammatory gene expression to mediate tissue repair. However, DAMPs have also been implicated in diseases where excessive inflammation plays a key role in pathogenesis, including rheumatoid arthritis (RA), cancer, and atherosclerosis. TLR activation by DAMPs may initiate positive feedback loops where increasing tissue damage perpetuates pro-inflammatory responses leading to chronic inflammation. Here we explore the current knowledge about distinct signalling cascades resulting from self TLR activation. We also discuss the involvement of endogenous TLR activators in disease and highlight how specifically targeting DAMPs may yield therapies that do not globally suppress the immune system.
Fabrication and Performance Test of Fresnel Zone Plate with 35 nm Outermost Zone Width in Hard X-Ray Region
Authors: Suzuki Yoshio , Takeuchi Akihisa , Takenaka Hisataka , Okada Ikuo
Published: July 2010

A Fresnel zone plate (FZP) with 35 nm outermost zone width has been fabricated and tested in the hard X-ray region. The FZP was made by electron beam lithography and reactive ion etching technique. The performance test of the FZP was carried out by measuring the focused beam profile for coherent hard X-ray beam at the beamline 20XU of SPring-8. The full width at half maximum of the focused beam profile measured by knife-edge scan method is 34.9±2.7 nm, that agrees well with the theoretical value of diffraction-limited resolution. Applications to scanning microscopy were also carried out.
Association of Toll-Like Receptor Signaling and Reactive Oxygen Species: A Potential Therapeutic Target for Posttrauma Acute Lung Injury
Authors: Xiang Meng , Fan Janet , Fan Jie
Published: July 2010

Acute lung injury (ALI) frequently occurs in traumatic patients and serves as an important component of systemic inflammatory response syndrome (SIRS). Hemorrhagic shock (HS) that results from major trauma promotes the development of SIRS and ALI by priming the innate immune system for an exaggerated inflammatory response. Recent studies have reported that the mechanism underlying the priming of pulmonary inflammation involves the complicated cross-talk between Toll-like receptors (TLRs) and interactions between neutrophils (PMNs) and alveolar macrophages (AMϕ) as well as endothelial cells (ECs), in which reactive oxygen species (ROS) are the key mediator. This paper summarizes some novel mechanisms underlying HS-primed lung inflammation focusing on the role of TLRs and ROS, and therefore suggests a new therapeutic target for posttrauma ALI.
Necessary and Sufficient Conditions for the Boundedness of Dunkl‐Type Fractional Maximal Operator in the Dunkl‐Type Morrey Spaces
Authors: Guliyev Emin , Eroglu Ahmet , Mammadov Yagub
Published: July 2010

We consider the generalized shift operator, associated with the Dunkl operator Λα(f)(x) = (d/dx)f(x)+((2α + 1)/x)((f(x) − f(−x))/2), α > −1/2. We study the boundedness of the Dunkl‐type fractional maximal operator Mβ in the Dunkl‐type Morrey space Lp,λ,α(ℝ), 0 ≤ λ < 2α + 2. We obtain necessary and sufficient conditions on the parameters for the boundedness Mβ, 0 ≤ β < 2α + 2 from the spaces Lp,λ,α(ℝ) to the spaces Lq,λ,α(ℝ), 1 < p ≤ q < ∞, and from the spaces L1,λ,α(ℝ) to the weak spaces WLq,λ,α(ℝ), 1 < q < ∞. As an application of this result, we get the boundedness of Mβ from the Dunkl‐type Besov‐Morrey spaces to the spaces , 1 < p ≤ q < ∞, 0 ≤ λ < 2α + 2, 1/p − 1/q = β/(2α + 2 − λ), 1 ≤ θ ≤ ∞, and 0 < s < 1.
Weakly Nonlinear Stability Analysis of a Thin Magnetic Fluid during Spin Coating
Authors: Chen Cha′o-Kuang , Lai Dong-Yu
Published: July 2010

This paper investigates the stability of a thin electrically conductive fluid under an applied uniform magnetic filed during spin coating. A generalized nonlinear kinematic model is derived by the long‐wave perturbation method to represent the physical system. After linearizing the nonlinear evolution equation, the method of normal mode is applied to study the linear stability. Weakly nonlinear dynamics of film flow is studied by the multiple scales method. The Ginzburg‐Landau equation is determined to discuss the necessary conditions of the various critical flow states, namely, subcritical stability, subcritical instability, supercritical stability, and supercritical explosion. The study reveals that the rotation number and the radius of the rotating circular disk generate similar destabilizing effects but the Hartmann number gives a stabilizing effect. Moreover, the optimum conditions can be found to alter stability of the film flow by controlling the applied magnetic field.
Proliferation but Not Migration Is Associated with Blood Vessels during Development of the Rostral Migratory Stream
Authors: Nie Kai , Molnár Zoltán , Szele Francis G.
Published: July 2010

Blood vessels play a critical role in regulating neural stem cell proliferation and migration. We show here that blood vessels became progressively aligned in the direction of the rostral migratory stream (RMS) from embryonic day 14 to postnatal day 4. Dividing cells revealed by phosphohistone H3+ immunoreactivity were statistically closer to isolectin B4+ blood vessels than predicted by chance in the emerging RMS. The close proximity of blood vessels and H3+ cells was consistent regardless of the age of the RMS and was strikingly similar to the embryonic cerebral cortex. In contrast to the adult RMS, we found no evidence for preferential juxtaposition of migratory doublecortin-positive neuroblasts and vasculature in the neonatal RMS. Our work provides an important framework for understanding the precise mechanism behind regulation of proliferation.
Changes of Serum Cytokines in Hyperthyroid Graves’ Disease Patients at Diagnosis and during Methimazole Treatment
Authors: Pedro Ana Beatriz B. , Romaldini João H. , Takei Kyoko
Published: July 2010

Objective: Cytokines are involved in the pathogenesis of Graves’ disease (GD), but ambiguous serum cytokine results have been described. Methods: We studied the changes in serum interleukin (IL)-1β, soluble IL-2 receptor (sIL-2R), IL-5, IL-6 and tumor necrosis factor (TNF)-α concentrations in 29 untreated GD patients before and after restoration of euthyroidism with methimazole (MMI) treatment compared to 25 control subjects. Eleven out of 29 GD patients had active Graves’ ophthalmopathy (GO). Results: Compared to controls, untreated GD patients had significantly higher median levels of serum IL-1β (18.7 vs. 34.0 pg/ml), sIL-2R (292.5 vs. 1,585.0 pg/ml), IL-5 (1.0 vs. 9.0 pg/ml), IL-6 (3.0 vs. 5.0 pg/ml) and TNF-α (8.1 vs. 16.0 pg/ml). In euthyroidism following MMI treatment, concentrations of IL-1β (25.0 pg/ml), sIL-2R (362.0 pg/ml), IL-5 (3.0 pg/ml), IL-6 (3.0 pg/ml) and TNF-α (5.0 pg/ml) declined significantly and were similar to controls. The greatest reductions were noted in sIL-2R (76.9%), TNF-α (68.8%) and IL-5 (66.6%) levels. Serum sIL-2R, IL-5 and TNF-α levels in active GO patients were significantly elevated, but no significant differences were observed in GD patients without GO. Using a multiple linear regression analysis, serum IL-1β was significantly associated with free thyroxine, sIL-2R with triiodothyronine and serum thyrotropin receptor antibody (TRAb) and TNF-α with TRAb. Conclusion: These results support the notion that serum cytokines could be used as a marker of GD activity, and the decrease in cytokine levels might be related to the achievement of euthyroidism and the immunomodulatory effects of MMI treatment.
Dynamics of Functional Heterochromatic Domains in the Plant Interphase Nucleus
Authors: Delgado M. , Frescatada M. , Ribeiro-Varandas E. , Viegas W. , Jones R.N.
Published: July 2010

Biologists have been fascinated for more than 2 centuries about how the nucleus in eukaryotes is organised. Certain of the component parts are well known, but the overall picture is blurred and often confusing. Small genome species have chromosomes in their interphase nuclei disposed in diffuse chromosome territories, without any Rabl arrangement, while in large genomes the chromosomes run string-like through the nucleus with a Rabl orientation following through the cell cycle. What happens in genomes of intermediate size is either a bit of both, depending on the tissue being studied, or still remains to be determined. The centromeres are the most dynamic and least well understood part of the nucleus, subject to rapid evolutionary change and with an epigenetic mark based on a special form of histone CENH3. Nonetheless, the centromere epigenetic mark has been inherited for millions of years by a process that is a complete mystery. Centromeres are involved with the dynamic interactions between chromosomes and other parts of the nuclear environment, such as the nuclear matrix and inner nuclear membrane, and they also engage with the spindle when the order within the nucleus changes during its division. The nucleolus organizer regions have likewise posed tantalising problems about their massive amplification of rDNA sequences, and how they are regulated and expressed. Some of these issues are now becoming clearer with advances in the science and the ongoing development of new molecular tools. These developments are discussed in this contribution, with particular reference to the centromere and the nucleolus organizer.
Reciprocal and Multi-Species Chromosome BAC Painting in Crucifers (Brassicaceae)
Authors: Lysak M.A. , Mandáková T. , Lacombe E.
Published: July 2010

In crucifer cytogenomics, BAC contigs of Arabidopsis thaliana have been used as probes for comparative chromosome painting among species. Here we successfully tested chromosome-specific BAC contigs of A. thaliana (n = 5) and A. halleri (n = 8) as probes for reciprocal BAC painting. Furthermore, BAC contigs of both Arabidopsis species were applied as multi-species painting probes to a third crucifer species, Noccaea caerulescens (n = 7), revealing their shared chromosome homeology. Specifically, we found homeology across portions of chromosomes At2, Ah4, and Nc4, which reflects their shared common origin with chromosome AK4 of the Ancestral Crucifer Karyotype (n = 8). We argue that multi-species and multi-directional painting will significantly expedite comparative cytogenomics in Brassicaceae and other plant families.
Physical Distribution of Homoeologous Recombination in Individual Chromosomes of Festuca pratensis in Lolium multiflorum
Authors: Kopecký D. , Havránková M. , Loureiro J. , Castro S. , Lukaszewski A.J. , Bartoš J. , Kopecká J. , Doležel J.
Published: July 2010

Crossing over-based recombination is a powerful tool for generating new allelic combinations during sexual reproduction. It usually occurs between homologous chromosomes. However, under some conditions, homoeologues may also be capable of crossing over. Whether homologous and homoeologous crossovers are equivalent and governed by the same rules has never been established. Here we report on chromosome distribution of homoeologous crossovers in a unique system of Festuca × Lolium hybrids. Unlike in most other hybrids, in these intergeneric hybrids, homoeologous chromosomes are capable of pairing and crossing over with frequencies approaching that of homologues. At the same time, genome divergence makes cytological detection of chromosome recombination feasible. We analyzed the distribution of homoeologous recombination along individual chromosomes in a complete set of intergeneric single chromosome substitutions fromF. pratensisinto tetraploid L. multiflorum. Homoeologous recombination sites were not evenly distributed along the chromosomes, being concentrated in intercalary regions of the arms and reduced in proximal and distal regions. Several recombination hotspots and cold spots were found along individual chromosomes and the recombination was not affected by the presence of a secondary constriction. Our results indicate that despite the uneven distribution of homoeologous recombination, introgression of any part of the F. pratensis genome into L. multiflorum is feasible.
Neurotoxic Effects of MDMA (Ecstasy) on the Developing Rodent Brain
Authors: Dzietko M. , Sifringer M. , Klaus J. , Endesfelder S. , Brait D. , Hansen H.H. , Bendix I. , Felderhoff-Mueser U.
Published: July 2010

The incidence of methamphetamine abuse is particularly high in adolescents and is a common problem among women of childbearing age, leading to an increasing number of children with prenatal exposure. MDMA (3,4-methylenedioxymethamphetamine, ecstasy) is an amphetamine-like stimulant and is known to induce apoptotic damage to fine serotonergic fibers in the adult rat brain. Little is known about toxic effects of MDMA and potential underlying molecular mechanisms in the developing brain. Here, we investigated whether MDMA exposure during the period of rapid brain growth causes neurodegeneration in the developing rat brain. MDMA significantly enhanced neuronal death in the brains of 6-day-old rat pups at a dose of 60 mg/kg, but no significant toxicity was detected at the ages of 14 and 21 days. Brain regions mainly affected were the cortex, septum, thalamus, hypothalamus and the cornu ammonis 1 region. To explore possible molecular mechanisms involved in this neurodegenerative process, we investigated the impact of MDMA on the expression of the neurotrophins brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor. Neonatal exposure of 6-day-old rats to MDMA triggered a considerable increase in cortical BDNF and NT-3 levels. Moreover, P7 CD1/BDNF knockout mice were noticeably more sensitive to MDMA exposure as compared to their wild-type age-matched littermates. These data suggest that a single injection of MDMA causes neurodegeneration in the neonatal rat brain. The upregulation of BDNF and NT-3 expression may indicate an important compensatory mechanism leading to the survival of neuronal cells in the developing brain.
Interspecific Hybrids of Hordeum marinum ssp. marinum × H. bulbosum Are Mitotically Stable and Reveal No Gross Alterations in Chromatin Properties
Authors: Sanei M. , Pickering R. , Fuchs J. , Banaei Moghaddam A.M. , Dziurlikowska A. , Houben A.
Published: July 2010

Interspecific hybrids between the related wild barley species Hordeum marinum and H. bulbosum were generated and tested regarding their chromosomal stability and chromatin properties. Unlike in H. vulgare × H. bulbosum hybrid embryos, there was no effect of temperature on uniparental chromosome elimination or retention during hybrid seed development and 7 chromosomes from each parent were detected according to genomic in situ hybridization analyses. The centromere-specific histone H3 gene (CENH3) of both parental genomes is active in hybrid plants. Indirect immunostaining of flow-sorted 2C nuclei indicated that no major reorganization of histone H3 methylation (K4, K9 and K27), H3K9 acetylation and histone H2A ubiquitination marks or location of active RNA polymerase II sites occurred after interspecific hybridization.
Structural Differences in Chromosomes Distinguish Species in the Tomato Clade
Authors: Anderson L.K. , Covey P.A. , Larsen L.R. , Bedinger P. , Stack S.M.
Published: July 2010

The tomato clade of Solanaceae is composed of 12 species that are all diploid with the same chromosome number and morphology. Species in the tomato clade are considered to have evolved primarily by genic changes rather than large-scale chromosomal rearrangements because pachytene chromosomes in F1 hybrids synapse normally along their lengths and linkage maps of intra- and inter-specific hybrids are co-linear. However, small inversions have been reported between tomato and some of its wild relatives. Therefore, we reevaluated 5 F1 hybrids using high-resolution, electron microscopic examination of pachytene chromosome (= synaptonemal complex) spreads to determine whether any minor structural changes had occurred among species in the tomato clade, which were not easily visible using light microscopic analysis of conventional chromosome squashes. Our study revealed a number of unexpected synaptic configurations such as mismatched kinetochores, inversion loops and reciprocal translocations. Most of these structural differences were in or close to heterochromatin that has comparatively few genes and little recombination, so they would be expected to have little effect on the evident colinearity of linkage maps, especially in euchromatin. However, these results demonstrate that substantial changes in chromosome structure have occurred among species within the tomato clade.
Fate of Aegilops speltoides-Derived, Repetitive DNA Sequences in Diploid Aegilops Species, Wheat-Aegilops Amphiploids and Derived Chromosome Addition Lines
Authors: Kumar S. , Friebe B. , Gill B.S.
Published: July 2010

The present study reports the cloning and characterization of an Aegilopsspeltoides-derived subtelomeric repeat, designated as pSp1B16. Clone pSp1B16 has 98% sequence homology with the previously isolated Ae. speltoides repeat Spelt1. The distribution of pSp1B16 and another Ae. speltoides repeat, pGc1R1, was analyzed in diploid Aegilops species, tetra- and hexaploid wheats, wheat-Aegilops amphiploids and derived chromosome addition lines by fluorescence in situ hybridization (FISH). Clones pSp1B16 and pGc1R1 revealed FISH sites in Ae. speltoides, Ae. sharonensis and Triticumtimopheevii, whereas additional pGc1R1 FISH sites were observed in Ae. longissima and Ae. caudata. The pSp1B16 and pGc1R1 FISH patterns of the Aegilops chromosomes in the wheat-Aegilops amphiploids and chromosome addition lines are similar to those present in the Aegilops parent accession. We did not observe any evidence of pSp1B16 and pGc1R1 sequence elimination, which is in contrast to previous studies using similar hybrids and repeats. The presented data suggest that the genomic changes in synthetic amphiploids observed in previous studies might be caused by homoeologous recombination, which was suppressed in the amphiploid analyzed in this study.
A Nonsense Mutation in the SCN9A Gene in Congenital Insensitivity to Pain
Authors: Kurban Mazen , Wajid Muhammad , Shimomura Yutaka , Christiano Angela M.
Published: July 2010

Background: Congenital insensitivity to pain (CIP) (OMIM 243000) is a rare autosomal-recessive disorder. Clinically, CIP is characterized by insensitivity to all modalities of pain except neuropathic pain, and recurrent injuries frequently go unnoticed. CIP is caused by mutations in the SCN9A gene encoding for the Na1.7 channel. Methods: We analyzed the DNA from members of a consanguineous Pakistani family for mutations in the SCN9A gene through direct sequencing after performing linkage studies. Results: We identified a novel missense mutation designated R523X in all affected individuals. A screening assay ruled out the possibility of polymorphism. Conclusion: We identified a novel mutation in the Na1.7 channel leading to CIP, extending the spectrum of mutations in the Na1.7 channel, and enhancing our understanding of the physiology of pain.
Evidence for a New Fumarate Hydratase Gene Mutation in a Unilateral Type 2 Segmental Leiomyomatosis
Authors: Parmentier Laurent , Tomlinson Ian , Happle Rudolf , Borradori Luca
Published: July 2010

Background: Multiple cutaneous and uterine leiomyomata syndrome (MCUL; MIM 150800) is a rare condition that sometimes predisposes to renal cancer. It is caused by deleterious mutations in the fumarate hydratase (FH) gene. In many patients, skin leiomyomas have been reported to develop according to a segmental type 1 or type 2 distribution. We report a patient showing multiple leiomyomas distributed according to a segmental type 2 distribution and covering several areas exclusively on the left side of his body. Objective: To search for a specific mutation in the FH gene associated with this phenotype. Methods: Genomic DNA from peripheral blood leucocytes of the proband was sequenced and screened for mutation of the FH gene. Results: Heterozygosity for an as yet undescribed mutation c.695delG, leading to a truncated protein p.Gly232AspfsX24, was found. Conclusion:We report a new mutation in the FH gene and discuss the unusual pattern of purely unilateral distribution in the present case.
Relationship between Tongue Pressure and Dysphagia in Stroke Patients
Authors: Konaka Kuni , Kondo Jugo , Hirota Nobuko , Tamine Kenichi , Hori Kazuhiro , Ono Takahiro , Maeda Yoshinobu , Sakoda Saburo , Naritomi Hiroaki
Published: July 2010

Background: Although poststroke dysphagia is an important issue for determining prognosis, the pathophysiology of oral-phase dysphagia has yet to be clarified due to a lack of adequate devices and protocols. The present study investigated the relationships between swallowing pressure production by the tongue and dysphagia in stroke patients using a newly developed method of tongue pressure measurement with a sensor sheet system. Methods: Subjects were 64 stroke patients, including 30 patients with dysphagia. A T-shaped sensor sheet with 5 measuring points was attached to the hard palate to record tongue pressure while swallowing 5 ml of water. The average maximal magnitude and incidence of abnormalities such as asynchronous and/or polyphasic patterns in tongue pressure waves in 5 locations were compared between patients with and without dysphagia. Results: The average maximal tongue pressure was significantly smaller in patients with dysphagia than in those without dysphagia. Asynchronous and polyphasic patterns showed a sensitivity of 63 and 87%, and a specificity of 91 and 71%, respectively, for identifying patients with dysphagia. Conclusion: Tongue pressure production during swallowing appears closely related to poststroke dysphagia. Tongue pressure measurement appears useful for evaluating the pathophysiology of oral-phase dysphagia in stroke patients.
Postconditioning and Remote Postconditioning of Ischemic Rat Cardiac Grafts
Authors: Tang Y. , Mennander A. , Oksala N. , Atalay M. , Syvala H. , Lagerstedt A. , Kuuslahti M. , Nieminen R. , Anas N. , Moilanen E. , Tarkka M.
Published: July 2010

Background: Global warm ischemia of transplanted cardiac grafts is associated with apoptosis and subsequent tissue necrosis. It is suggested that postconditioning (PostC) may ameliorate the early outcome of cardiac grafts after ischemia-reperfusion. We investigated whether PostC and remote postconditioning (RPostC) have a histopathologic impact after transplantation of warm ischemic rat cardiac grafts. Materials and Methods: Thirteen rats were randomized to undergo either PostC or RPostC after heterotopic transplantation of ischemic cardiac grafts. Six rats without intervention besides transplantation served as controls (control). The recipient rats were sacrificed 24 h after transplantation to evaluate histopathology and apoptotic index. Results: No significant differences were observed between the study groups in terms of graft heat shock protein 70 and oxygen radical absorbing capacity, an indicator of antioxidant capacity. While apoptosis and PCARB, a marker of protein oxidation and oxidative stress, decreased after RPostC (p < 0.05), contraction band necrosis was less prominent in both PostC and RPostC. Conclusion: Both PostC and RPostC have a histopathologic impact after 24 h of reperfusion of warm ischemic rat cardiac grafts.
Spot Urine Osmolality/Creatinine Ratio in Healthy Humans
Authors: Godevithanage Srini , Kanankearachchi Piyumi P. , Dissanayake Mahanama P. , Jayalath Thilak A. , Chandrasiri Nimal , Jinasena Rangani P. , Kumarasiri Ranjith P.V. , Goonasekera Chulananda D.A.
Published: July 2010

Background: Spot urine albumin/creatinine ratio is a reliable estimate of 24-hour urine albumin excretion. In a pilot study, we observed that the spot urine osmolality/creatinine ratio (Uosm/Ucr) in healthy adults is reproducible. Therefore, we postulated that Uosm/Ucr of a spot urine sample may give an overall estimate of urinary excretion of solutes, renal concentrating ability and body hydration status. Method: Early morning spot urine samples were collected from healthy humans, frozen and analyzed in batches to establish spot Uosm/Ucr and its variation in relation to sex, age, body weight and height. Results: Two hundred and twenty-nine healthy volunteers participated. They were stratified into seven age groups: (a) 1.5–5, (b) >5–10, (c) >10–20, (d) >20–30, (e) >30–45, (f) >45–60, and (g) >60 years. Fifteen males and 15 females were allocated to each age category. A spot urine sample was collected from all subjects in the morning after the first void and was analyzed for osmolality and creatinine. The influence of age, sex, body weight and height on spot Uosm/Ucr was investigated using multiple linear regression. Only height showed a significant correlation (R2 = 0.02). Further analysis after excluding the 1.5–5 years age group revealed no significant correlation between age, sex, body weight and height and the Uosm/Ucr ratio. Conclusion: Spot Uosm/ Ucr of healthy humans is a consistent index in steady state and needs no correction for sex, age and body weight above the age of 5 years.
Effects of Anemia and Uremia and a Combination of Both on Cardiovascular Structures
Authors: Jürgensen J.S. , Grimm R. , Benz K. , Philipp S. , Eckardt K.U. , Amann K.
Published: July 2010

Background: Cardiovascular complications are a major cause of morbidity and mortality in chronic renal failure (CRF) patients. Chronic anemia is a complication of CRF and a cardiovascular risk factor per se. It was the aim of the present study to clarify whether uremia and anemia are additive or supra-additive with respect to cardiovascular alterations. Methods: Thirty SD rats were sham operated (sham) or subtotally nephrectomized (SNX). Both groups were subdivided into anemic (target hemoglobin 10 g/dl, by tail artery punctures) and untreated animals. Blood pressure, echocardiographic measurements and morphometric investigations were performed. The study was terminated after 16 weeks. Results: Heart rate and blood pressure were similar in all groups. Anemia was comparable in sham+anemia and SNX+anemia. Left ventricular end-diastolic pressure was significantly higher in untreated SNX and SNX+anemia than in sham. Anemia and SNX caused comparable left ventricular hypertrophy (LVH), which was significantly higher in SNX+anemia. In sham animals, anemia induced thickening of intramyocardial arteries, which was significantly more pronounced in SNX with no additional effect of anemia. Conclusions: Experimentally, anemia and CRF induced LVH and intramyocardial arteriolar thickening. If both are combined, the increase in LVH is even more marked, whereas there are no additional effects on intramyocardial structural alterations.
Comparison of Different Methods to Assess Fistula Flow
Authors: Eloot Sunny , Dhondt Annemieke , Hoeben Heidi , Vanholder Raymond
Published: July 2010

Background: We compared three access flow (AF) monitoring techniques: blood dilution using ultrasound (US), blood temperature monitoring (BTM), and online clearance monitoring (OCM), and investigated the impact of dialyzer blood flow (QB), measurement time point and patient’s position. Methods: US, BTM and OCM were performed in 20 hemodialysis (HD) patients at QB300. OCM was unreliable for measuring AF and was therefore further omitted. US and BTM measurements were repeated in 10 patients at QB200 ml/min, in 15 patients at the first weekly HD start and end and at the midweek HD start, and switching position during midweek HD. Results: AFs of 1,104 ± 607 (US) and 1,264 ± 664 ml/min (BTM) significantly correlated. No differences were found comparing AF at QB300 and QB200. AF decreased from HD start to end, while no difference was found changing patient’s position. Conclusion: AFs by BTM and US correlated well and may be measured at QB200–300 in all measured positions.
Carotid Plaque Inflammation Is Associated With Cerebral Microembolism in Patients With Recent Transient Ischemic Attack or Stroke
Authors: Moustafa Ramez Reda , Izquierdo-Garcia David , Fryer Tim D. , Graves Martin J. , Rudd James H.F. , Gillard Jonathan H. , Weissberg Peter L. , Baron Jean-Claude , Warburton Elizabeth A.
Published: July 2010

Background—

Cerebral infarcts distal to carotid stenoses are thought to be caused by emboli from inflamed, destabilized plaques. We hypothesized that microembolic signals (MES) on transcranial Doppler will be associated with carotid plaque inflammation on
18
F fluorodeoxyglucose positron-emission tomography (FDG PET) in recently symptomatic patients.

Methods and Results—

Sixteen patients presenting with recent (47±31 days) anterior circulation transient ischemic attack or minor stroke and 50% to 99% stenosis of the ipsilateral carotid bifurcation underwent FDG PET, high-resolution black-blood carotid MRI, and transcranial Doppler for detection of MES. Patients with potential cardiac sources of emboli or contralateral MES were excluded. Regions of interest defined on the coregistered MRI were used to measure FDG standardized uptake values (with Rousset partial volume correction) from the index and contralateral carotid plaques and artery. Ipsilateral MES were detected in 7 patients (MES+ group) and absent in 8 (MES− group). There was a significant difference in index-to-contralateral plaque standardized uptake value ratio between MES+ (median, 1.05; first to third quartile, 0.96 to 1.32) and MES− (median, 0.76; first to third quartile, 0.62 to 0.94) patients (
P
=0.005). The interval from symptom onset to PET and percent index carotid stenosis were not different between the 2 groups (
P
=0.68 and
P
=0.48, respectively).

Conclusions—

In this sample of recently symptomatic patients with carotid stenosis, an association was found between in vivo measures of plaque inflammation detected by FDG PET and the presence of transcranial Doppler MES. These findings strengthen the notion that embolic events distal to carotid stenoses are related to plaque inflammation, and FDG PET may be useful in the investigation of culprit carotid lesions.
Ablation of C/EBP Homologous Protein Attenuates Endoplasmic Reticulum–Mediated Apoptosis and Cardiac Dysfunction Induced by Pressure Overload
Authors: Fu Hai Ying , Okada Ken-ichiro , Liao Yulin , Tsukamoto Osamu , Isomura Tadashi , Asai Mitsutoshi , Sawada Tamaki , Okuda Keiji , Asano Yoshihiro , Sanada Shoji , Asanuma Hiroshi , Asakura Masanori , Takashima Seiji , Komuro Issei , Kitakaze Masafumi , Minamino Tetsuo
Published: July 2010

Background—

Apoptosis may contribute to the development of heart failure, but the role of apoptotic signaling initiated by the endoplasmic reticulum in this condition has not been well clarified.

Methods and Results—

In myocardial samples from patients with heart failure, quantitative real-time polymerase chain reaction revealed an increase in messenger RNA for C/EBP homologous protein (CHOP), a transcriptional factor that mediates endoplasmic reticulum–initiated apoptotic cell death. We performed transverse aortic constriction or sham operation on wild-type (WT) and CHOP-deficient mice. The CHOP-deficient mice showed less cardiac hypertrophy, fibrosis, and cardiac dysfunction compared with WT mice at 4 weeks after transverse aortic constriction, although the contractility of isolated cardiomyocytes from CHOP-deficient mice was not significantly different from that in the WT mice. In the hearts of CHOP-deficient mice, phosphorylation of eukaryotic translation initiation factor 2α, which may reduce protein translation, was enhanced compared with WT mice. In the hearts of WT mice, CHOP-increased apoptotic cell death with activation of caspase-3 was observed at 4 weeks after transverse aortic constriction. In contrast, CHOP-deficient mice had less apoptotic cell death and lower caspase-3 activation at 4 weeks after transverse aortic constriction. Furthermore, the Bcl2/Bax ratio was decreased in WT mice, whereas this change was significantly blunted in CHOP-deficient mice. Real-time polymerase chain reaction microarray analysis revealed that CHOP could regulate several Bcl2 family members in failing hearts.

Conclusions—

We propose the novel concept that CHOP, which may modify protein translation and mediate endoplasmic reticulum–initiated apoptotic cell death, contributes to development of cardiac hypertrophy and failure induced by pressure overload.
Efficacy and Safety of Automatic Remote Monitoring for Implantable Cardioverter-Defibrillator Follow-Up
Authors: Varma Niraj , Epstein Andrew E. , Irimpen Anand , Schweikert Robert , Love Charles
Published: July 2010

Background—

Monitoring implantable cardiac device function and patient condition is important. The Lumos-T Safely Reduces Routine Office Device Follow-Up (TRUST) trial tested the hypothesis that remote home monitoring with automatic daily surveillance (HM) is safe and effective for implantable cardioverter-defibrillator follow-up for 1 year and enables rapid physician evaluation of significant events.

Methods and Results—

In total, 1339 patients were randomized 2:1 to HM or conventional follow-up. Follow-up checks occurred at 3, 6, 9, 12, and 15 months after implantation. HM was used before office visits at 3 and 15 months in the HM group. At 6, 9, and 12 months, HM only was used but was followed by office visits if necessary. Conventional patients were evaluated with office visits only. Scheduled office visits and unscheduled evaluations, incidence of morbidity, and time elapsed from first event occurrence in each patient to physician evaluation were tracked for each group. HM and conventional patients were similar (age, 63.3±12.8 versus 64.0±12.1 years; gender, 72.0% versus 73.1% male; New York Heart Association class II, 55.9% versus 60.4%; pathology: left ventricular ejection fraction, 29.0±10.7% versus 28.5±9.8%; coronary artery disease, 64.8% versus 71.7%; primary prevention indication, 72.2% versus 73.8%; and dual-chamber implants, 57.8% versus 56.6%). HM reduced total in-hospital device evaluations by 45% without affecting morbidity. In the HM group, 85.8% of all 6-, 9-, and 12-month follow-ups were performed remotely only, indicating that HM provided sufficient assessment in the majority. Median time to evaluation was <2 days in the HM group compared with 36 days in the conventional group (
P
<0.001) for all arrhythmic events.

Conclusions—

HM is safe and allows more rapid detection of actionable events compared with conventional monitoring in patients with implantable electronic cardiac devices.

Clinical Trials Registration—URL:

http:/www.clinicaltrials.gov. Unique identifier: NCT00336284.
Monitoring Initial Response to Angiotensin-Converting Enzyme Inhibitor–Based Regimens
Authors: Bell Katy J.L. , Hayen Andrew , Macaskill Petra , Craig Jonathan C. , Neal Bruce C. , Fox Kim M. , Remme Willem J. , Asselbergs Folkert W. , van Gilst Wiek H. , MacMahon Stephen , Remuzzi Giuseppe , Ruggenenti Piero , Teo Koon K. , Irwig Les
Published: July 2010

Most clinicians monitor blood pressure to estimate a patient’s response to blood pressure–lowering therapy. However, the apparent change may not actually reflect the effect of the treatment, because a person’s blood pressure varies considerably even without the administration of drug therapy. We estimated random background within-person variation, apparent between-person variation, and true between-person variation in blood pressure response to angiotensin-converting enzyme inhibitors after 3 months. We used meta-analytic mixed models to analyze individual patient data from 28 281 participants in 7 randomized, controlled trials from the Blood Pressure Lowering Trialists Collaboration. The apparent between-person variation in response was large, with SDs for change in systolic blood pressure/diastolic blood pressure of 15.2/8.5 mm Hg. Within-person variation was also large, with SDs for change in systolic blood pressure/diastolic blood pressure of 14.9/8.45 mm Hg. The true between-person variation in response was small, with SDs for change in systolic blood pressure/diastolic blood pressure of 2.6/1.0 mm Hg. The proportion of the apparent between-person variation in response that was attributed to true between-person variation was only 3% for systolic blood pressure and 1% for diastolic blood pressure. In conclusion, most of the apparent variation in response is not because of true variation but is a consequence of background within-person fluctuation in day-to-day blood pressure levels. Instead of monitoring an individual’s blood pressure response, a better approach may be to simply assume the mean treatment effect.
Efficacy of Revascularization For Renal Artery Stenosis Caused by Fibromuscular Dysplasia
Authors: Trinquart Ludovic , Mounier-Vehier Claire , Sapoval Marc , Gagnon Nathalie , Plouin Pierre-François
Published: July 2010

In patients with fibromuscular dysplasia and renal artery stenosis, renal artery revascularization has been used to cure hypertension or to improve blood pressure control. To provide an up-to-date assessment of the benefits and risks associated with revascularization in this condition, we performed a systematic review of studies in which hypertensive patients with fibromuscular dysplasia renal artery stenosis underwent percutaneous transluminal renal angioplasty or surgical reconstruction. We assessed how often periprocedural complications and hypertension cure and improvement occurred. We selected 47 angioplasty studies (1616 patients) and 23 surgery studies (1014 patients). Combined rates of hypertension cure, defined according to the criteria in each study, after angioplasty or surgery were estimated to be 46% (95% CI: 40% to 52%) and 58% (95% CI: 53% to 62%), respectively, with substantial variations across studies. The probability of being cured was negatively associated with patient age and time of publication. Cure rates using current definitions of hypertension cure (blood pressure <140/90 mm Hg without treatment) were only 36% and 54% after angioplasty and surgery, respectively. The combined risks of periprocedural complications were 12% and 17% after angioplasty and surgery, respectively, with less major complications after angioplasty than surgery (6% versus 15%). In conclusion, angioplasty or surgical revascularization yielded moderate benefits in patients with fibromuscular dysplasia renal artery stenosis, with substantial variation across studies. The blood pressure outcome was strongly influenced by patient age.
Angiotensin II Type 1 Receptor-Mediated Augmentation of Urinary Excretion of Endogenous Angiotensin II in Val
5
-Angiotensin II-Infused Rats
Authors: Shao Weijian , Seth Dale M. , Navar L. Gabriel
Published: July 2010

Rats infused chronically with Val
5
-Angiotensin (Ang) II exhibit increased urinary excretion of endogenous Ile
5
-Ang II by the 12th day of infusion, suggesting the stimulation of endogenous Ang II formation by Val
5
-Ang II infusion. The present study determined the time course of increased urinary Ang II excretion and the effects of Ang II type 1 receptor blockade (candesartan, 2 mg/kg per day) on the urinary excretion rates of Ile
5
-Ang II in Val
5
-Ang II-infused (80 ng/min) rats. Ile
5
-Ang II was separated from Val
5
-Ang II by high-performance liquid chromatography and measured by radioimmunoassay. Systolic blood pressure increased progressively (215±2 mm Hg) in Val
5
-Ang II-infused rats (n=5), whereas the candesartan-treated group (n=6) remained normotensive (124±3 mm Hg). Candesartan treatment significantly increased the level of plasma Ile
5
-Ang II (24.0±7.6 versus 156.9±24.6 fmol/mL;
P
<0.01); in contrast, there was a markedly lower intrarenal Ile
5
-Ang II content (357.9±76.6 versus 21.1±2.8 fmol/g;
P
<0.01). Urinary Ile
5
-Ang II excretion rates were elevated by day 9 (2185.7±283.2 fmol/24 hours) in Val
5
-Ang II-infused rats but not in candesartan-treated rats (740.6±110.3 fmol/24 hours). Thus, Ang II type 1 receptor blockade prevents the increase in urinary excretion of endogenous Ang II in rats subjected to chronic Ang II infusion. These data indicate that the increased urinary excretion of endogenous Ang II in Val
5
-Ang II-infused rats is primarily attributed to Ang II type 1 receptor-dependent secretion into and/or de novo formation of Ang II within the tubular lumen.
Chlorthalidone Decreases Platelet Aggregation and Vascular Permeability and Promotes Angiogenesis
Authors: Woodman Ryan , Brown Christina , Lockette Warren
Published: July 2010

Variations in diuretic-mediated inhibition of carbonic anhydrase-dependent chloride transport in platelets and vascular smooth muscle could account for the contrasting efficacy of the thiazide and thiazide-like diuretics in reducing cardiovascular morbidity in patients with hypertension. We assessed platelet carbonic anhydrase activity and catecholamine-induced platelet aggregation in the presence of a thiazide and a “thiazide-like” inhibitor of the sodium-chloride cotransporter. Individual variation in platelet carbonic anhydrase activity correlated with contrasting sensitivity to epinephrine-mediated platelet aggregation. Both chlorthalidone, which potently inhibits platelet carbonic anhydrase, and bendroflumethiazide, which has much less effect on this enzyme, increased the amount of epinephrine needed to induce platelet aggregation when compared with the absence of a diuretic. However, chlorthalidone was significantly more effective than bendroflumethiazide in reducing epinephrine-mediated platelet aggregation. Chlorthalidone also induced marked changes in the number of gene transcripts for two proteins that mediate angiogenesis and vascular permeability, vascular endothelial growth factor C and transforming growth factor-β3; chlorthalidone and bendroflumethiazide had contrasting effects on the expression of vascular endothelial growth factor C. Chlorthalidone and bendroflumethiazide reduced vascular permeability to albumin, but only chlorthalidone increased angiogenesis. Thiazides and thiazide-like diuretics can comparably reduce blood pressure, but the drugs in this class are not all alike. It can be suggested from our findings that thiazide and thiazide-like diuretics vary in their pleiotropic effects on platelets and in the vasculature, and these differences could explain the contrasting ability of these drugs to reduce cardiovascular morbidity despite comparable reduction in blood pressure.
Climate Change and the Common Good: Some Reflections from the South African Context
Authors: M. Conradie Ernst
Published: July 2010

This article is based on the observation that any theological discourse is always from a particular location and a particular point of view, which is immediately recognized by others. At the same time, any (theological) discourse cannot escape the use of universals, of common categories that we need to communicate with others. We make constructions of the whole, of that which is common, albeit that we ineluctably make particular constructions of the whole. This poses particular challenges for discourse on the common good in the context of public theology. On this basis the article investigates a selection of ecclesial statements on climate change produced during the course of the year 2009 alone that are available in English. It focuses on how these statements handle the dilemma of speaking about the universal and the particular, given the moral ambiguities surrounding any Christian discourse on climate change. It argues that most of these documents are plagued with problems of reception; namely, whether the stipulated addressees would actually receive and read the documents, let alone respond to them appropriately.