bluuebunny/crossref_metadata_2025 huggingface dataset:
Adiponectin Cardioprotection After Myocardial Ischemia/Reperfusion Involves the Reduction of Oxidative/Nitrative Stress
Authors: Tao Ling , Gao Erhe , Jiao Xiangying , Yuan Yuexing , Li Shuzhuang , Christopher Theodore A. , Lopez Bernard L. , Koch Walter , Chan Lawrence , Goldstein Barry J. , Ma Xin L.
Published: March 2007

Background—Several clinical studies have demonstrated that levels of adiponectin are significantly reduced in patients with type 2 diabetes and that adiponectin levels are inversely related to the risk of myocardial ischemia. The present study was designed to determine the mechanism by which adiponectin exerts its protective effects against myocardial ischemia/reperfusion.

Methods and Results—Adiponectin−/−or wild-type mice were subjected to 30 minutes of myocardial ischemia followed by 3 hours or 24 hours (infarct size and cardiac function) of reperfusion. Myocardial infarct size and apoptosis, production of peroxynitrite, nitric oxide (NO) and superoxide, and inducible NO synthase (iNOS) and gp91phoxprotein expression were compared. Myocardial apoptosis and infarct size were markedly enhanced in adiponectin−/−mice (P<0.01). Formation of NO, superoxide, and their cytotoxic reaction product, peroxynitrite, were all significantly higher in cardiac tissue obtained from adiponectin−/−than from wild-type mice (P<0.01). Moreover, myocardial ischemia/reperfusion–induced iNOS and gp91phoxprotein expression was further enhanced, but endothelial NOS phosphorylation was reduced in cardiac tissue from adiponectin−/−mice. Administration of the globular domain of adiponectin 10 minutes before reperfusion reduced myocardial ischemia/reperfusion–induced iNOS/gp91phoxprotein expression, decreased NO/superoxide production, blocked peroxynitrite formation, and reversed proapoptotic and infarct-enlargement effects observed in adiponectin−/−mice.

Conclusion—The present study demonstrates that adiponectin is a natural molecule that protects hearts from ischemia/reperfusion injury by inhibition of iNOS and nicotinamide adenine dinucleotide phosphate-oxidase protein expression and resultant oxidative/nitrative stress.
Direct Myocardial Effects of Levosimendan in Humans With Left Ventricular Dysfunction
Authors: Givertz Michael M. , Andreou Costa , Conrad Chester H. , Colucci Wilson S.
Published: March 2007

Background—Enthusiasm for the development of Ca2+sensitizers as inotropic agents for heart failure has been tempered by reports of impaired relaxation. Levosimendan, which increases myofilament Ca2+sensitivity via Ca2+-dependent binding to troponin C, exerts positive inotropic and lusitropic effects in failing human myocardium in vitro. We sought to determine the direct effects of levosimendan on failing human myocardium in vivo, and in particular whether levosimendan exerts heart rate–dependent effects on systolic or diastolic function.

Methods and Results—Ten patients with left ventricular dysfunction caused by nonischemic dilated cardiomyopathy (mean left ventricular ejection fraction, 27±2%) were instrumented with an infusion catheter in the left main coronary artery, a high-fidelity micromanometer-tipped catheter in the left ventricle, and a bipolar pacing wire in the right atrium. Inotropic (peak +dP/dt) and lusitropic (Tau) responses were assessed during continuous intracoronary drug infusion in sinus rhythm followed by atrial pacing at 20, 40, and 60 beats per minute above the sinus rate. Under control conditions (intracoronary 5% dextrose in water), atrial-pacing tachycardia decreased Tau by 13% (P<0.05), but did not increase +dP/dt. Intracoronary levosimendan (3.75 and 12.5 μg/min for 15 minutes each) increased +dP/dt dose-dependently and decreased Tau over a range of heart rates, but did not alter the slope of the force-frequency or relaxation-frequency relationship.

Conclusions—Myocardial calcium sensitization with levosimendan exerts mild inotropic and lusitropic effects in humans with left ventricular dysfunction, but does not alter the force-frequency or relaxation-frequency relationship.
Angiotensin II Induces Angiogenesis in the Hypoxic Adult Mouse Heart In Vitro Through an AT2–B2 Receptor Pathway
Authors: Munk Veronica C. , Sanchez de Miguel Lourdes , Petrimpol Marco , Butz Nicole , Banfi Andrea , Eriksson Urs , Hein Lutz , Humar Rok , Battegay Edouard J.
Published: March 2007

Angiotensin II is a vasoactive peptide that may affect vascularization of the ischemic heart via angiogenesis. In this study we aimed at studying the mechanisms underlying the angiogenic effects of angiotensin II under hypoxia in the mouse heart in vitro. Endothelial sprout formation from pieces of mouse hearts was assessed under normoxia (21% O2) and hypoxia (1% O2) during a 7-day period of in vitro culture. Only under hypoxia did angiotensin II dose-dependently induce endothelial sprout formation, peaking at 10−7mol/L of angiotensin II. Angiotensin II type 1 (AT1) receptor blockade by losartan did not affect angiotensin II–induced sprouting in wild-type mice. Conversely, the angiotensin II type 2 (AT2) receptor antagonist PD 123319 blocked this response. In hearts from AT1−/−mice, angiotensin II–elicited sprouting was preserved but blocked again by AT2receptor antagonism. In contrast, no angiotensin II–induced sprouting was found in preparations from hearts of AT2−/−mice. Angiotensin II–mediated angiogenesis was also abolished by a specific inhibitor of the B2 kinin receptor in both wild-type and AT1−/−mice. Furthermore, angiotensin II failed to induce endothelial sprout formation in hearts from B2−/−mice. Finally, NO inhibition completely blunted sprouting in hearts from wild-type mice, whereas NO donors could restore sprouting in AT2−/−and B2−/−hearts. This in vitro study suggests the obligatory role of hypoxia in the angiogenic effect of angiotensin II in the mouse heart via the AT2receptor through a mechanism that involves bradykinin, its B2 receptor, and NO as a downstream effector.
Disturbed Diurnal Rhythm Alters Gene Expression and Exacerbates Cardiovascular Disease With Rescue by Resynchronization
Authors: Martino Tami A. , Tata Nazneen , Belsham Denise D. , Chalmers Jennifer , Straume Marty , Lee Paul , Pribiag Horia , Khaper Neelam , Liu Peter P. , Dawood Fayez , Backx Peter H. , Ralph Martin R. , Sole Michael J.
Published: March 2007

Day/night rhythms are recognized as important to normal cardiovascular physiology and timing of adverse cardiovascular events; however, their significance in disease has not been determined. We demonstrate that day/night rhythms play a critical role in compensatory remodeling of cardiovascular tissue, and disruption exacerbates disease pathophysiology. We use a murine model of pressure overload cardiac hypertrophy (transverse aortic constriction) in a rhythm-disruptive 20-hour versus 24-hour environment. Echocardiography reveals increased left ventricular end-systolic and -diastolic dimensions and reduced contractility in rhythm-disturbed transverse aortic constriction animals. Furthermore, cardiomyocytes and vascular smooth muscle cells exhibit reduced hypertrophy, despite increased pressure load. Microarray and real-time PCR demonstrate altered gene cycling in transverse aortic constriction myocardium and hypothalamic suprachiasmatic nucleus. With rhythm disturbance, there is a consequent altered cellular clock mechanism (
per2
and
bmal
), whereas key genes in hypertrophic pathways (
ANF, BNP, ACE
, and
collagen
) are downregulated paradoxical to the increased pressure. Phenotypic rescue, including reversal/attenuation of abnormal pathology and genes, only occurs when the external rhythm is allowed to correspond with the animals’ innate 24-hour internal rhythm. Our study establishes the importance of diurnal rhythm as a vital determinant in heart disease. Disrupted rhythms contribute to progression of organ dysfunction; restoration of normal diurnal schedules appears to be important for effective treatment of disease.
Molecular Genetics of Experimental Hypertension and the Metabolic Syndrome
Authors: Pravenec Michal , Kurtz Theodore W.
Published: March 2007

Genetic studies of human and experimental hypertension provide a means to identify key pathways that predispose individuals to increased blood pressure and associated risk factors for cardiovascular and metabolic diseases. The pathways so identified can then serve as targets for therapeutic intervention. This article discusses genetic studies in animal models of hypertension in which specific genes have been identified that regulate blood pressure and biochemical features of the metabolic syndrome. Consistent with studies in humans with monogenic disorders of blood pressure regulation, studies in rat models have demonstrated that naturally occurring genetic variation in pathways regulating sodium chloride transport can contribute to inherited variation in blood pressure. Such studies have also indicated that naturally occurring variation in genes, such as Cd36, that regulate fatty acid metabolism and ectopic accumulation of fat and fat metabolites can influence both biochemical and hemodynamic features of the metabolic syndrome and mediate the antidiabetic effects of drugs that activate the peroxisome proliferator-activated receptor-γ. Angiotensin II receptor blockers with the ability to selectively modulate activity of peroxisome proliferator-activated receptor-γ and expression of genes in these fat metabolism pathways may represent useful prototypes for a new class of transcription modulating drugs aimed at treating patients with hypertension and the metabolic syndrome.
Les Églises de l'Armée Céleste comme Églises de guérison en Haïti: Un développement qui repose sur une double légitimité
Authors: Vonarx Nicolas
Published: March 2007

Pentecostalism is growving in popularity in rural Haiti due to the emergence of Armée Céleste Churches. The popularity of these churches appears to rest upon a dlouble legitimacy. These churches exist, first, in a religious context in which they must present themselves as Christian churches, and, second, a medical context which requires efficient and effective response to medical conditions presented by the Haitian population. To ensure their success, they are organized around these two imperatives and borrow from local medical knowledge to accomplish the mandate they have defined for themselves and is expected of them. This article presents ethnographic data on the Armée Céleste Churches, offers reference points that explain their double legitimacy and, finally, defines them as healing churches. The article submits that the success of Pentecostalism in rural Haiti can be explained primarily by their concern for illness and healing.
Clinical Diagnosis of Dementia, Not Presence of Behavioral and Psychological Symptoms, Is Associated With Psychotropic Use in Community-Dwelling Elders Classified as Having Dementia
Authors: Chan Ding-Cheng , Kasper Judith D. , Black Betty S. , Rabins Peter V.
Published: March 2007

Little is known about the prevalence and correlates of psychotropic use in community-dwelling elders with dementia. Baseline data from 285 community-dwelling elders with a research classification of dementia (based on a neuropsychological battery of 4 tests) and their knowledgeable informants enrolled in the observational Memory and Medical Care Study were analyzed. A total of 33.3% of subjects with a research classification of dementia were clinically diagnosed, 28.8% used at least 1 psychotropic drug, and 61.8% had at least 1 behavioral or psychological symptom of dementia (BPSD). Presence of BPSD was associated with a higher likelihood of a clinical diagnosis of dementia. Multivariate logistic regression showed a clinical diagnosis of dementia, not BPSD, was associated with psychotropic use; clinical recognition of dementia appears to be an intermediate step between presence of BPSD and prescription of psychotropics. In addition, most community-dwelling elders meeting the research criteria for dementia were not clinically diagnosed, despite contact with a physician (89%) in the previous year.
A delayed climatic response to solar forcing at 2800 cal. BP: multiproxy evidence from three Irish peatlands
Authors: Swindles Graeme T. , Plunkett Gill , Roe Helen M.
Published: March 2007

Multiproxy palaeohydrological records from three raised bogs in Northern Ireland indicate that a major shift to wetter/cooler climatic conditions postdated the rapid decrease in solar activity at 2800 cal. BP by ~100 years. This event is bracketed by two wiggle-match radiocarbon-dated cryptotephra layers in each profile, enabling a high degree of chronological precision. These replicated data corroborate previous findings based on Irish peat humification profiles, and may indicate spatial complexity in the climatic response to solar activity between oceanic and continental areas.
Spatial complexity of ‘Little Ice Age’ climate in East Africa: sedimentary records from two crater lake basins in western Uganda
Authors: Russell James M. , Verschuren Dirk , Eggermont Hilde
Published: March 2007

Lithostratigraphic analyses of the sedimentary record from two contrasting crater lake basins in western Uganda, Africa, provide evidence for three major century-scale arid intervals during the last 2000 years. Variations in sedimentation and salt mineralogy of hypersaline Lake Kitagata, and a succession of fine-grained lake sediments and peat in the freshwater Lake Kibengo, suggest century-scale droughts centred on AD 0, ~1100, ~1550 and 1750. These results broadly support data from nearby Lake Edward on the timing of drought in western Uganda, but contrast with lake sediment records from eastern equatorial Africa. In particular, our results suggest regional variability of East African climate during the main phase of the ‘Little Ice Age’ (AD ~1500 to 1800), with westernmost East Africa experiencing drought while areas farther east were wet. This spatial pattern highlights the strongly regional nature of century-scale climate changes over the African continent, and holds implications for the mechanisms governing African rainfall during the ‘Little Ice Age’.
Entrepreneurship, Management Learning and Negotiated Narratives: ‘Making it Otherwise for Us—Otherwise for Them’
Authors: Fletcher Denise E. , Watson Tony J.
Published: March 2007

A dialogic and drama-like narrative is presented. This has resulted from an unexpected circumstance in which a business idea is seen to emerge. This narrative provides a valuable resource for a ‘negotiated narrative’ style of entrepreneurship management learning and it is used to contribute to the theoretical understanding of entrepreneurship itself and to the production of a novel way of conceptualizing entrepreneurial processes generally. Emphasis is given to the emergent and relational processes through which learning occurs and through which entrepreneurial opportunities are realized. Entrepreneurship can thus be seen as a matter of entrepreneurial actors relationally ‘becoming otherwise’ through enabling customers or clients to ‘become otherwise’.
Peacekeeping: Organized Hypocrisy?
Authors: Lipson Michael
Published: March 2007

The UN has been accused of hypocrisy — failing to act in accordance with the ideals it espouses — in post-Cold War peacekeeping missions. This article argues that such inconsistency can arise from ‘organized hypocrisy’, a phenomenon identified by organization theorists in which organizations respond to conflicting pressures in external environments through contradictory actions and statements. Organized hypocrisy may have both positive and negative effects on peacekeeping. On the one hand, it may produce or exacerbate gaps between commitments and resources, undermine reforms if they are decoupled from practice, and impede efforts to mitigate harmful peacekeeping externalities. On the other hand, organized hypocrisy may enable the UN, or regional organizations, to manage irreconcilable pressures that might otherwise render the organization incapable of effective action and threaten its survival. This article explains and develops the concept of organized hypocrisy, and apples it to post-Cold War peace operations.
Effects of proficiency differences and patterns of pair interaction on second language learning: collaborative dialogue between adult ESL learners
Authors: Watanabe Yuko , Swain Merrill
Published: March 2007

This study investigated the effects of second language (L2) proficiency differences in pairs and patterns of interaction on L2 learning, making use of both qualitative and quantitative data. We designed the study in such a way that four different core participants interacted with higher and lower proficiency non-core participants. These learners engaged in a three-stage task involving pair writing, pair comparison (between their original text and a reformulated version of it) and individual writing. The core participants also engaged in a stimulated recall after the task. We analysed each pair's collaborative dialogue in terms of language-related episodes and patterns of pair interaction (Storch, 2002a) as well as each learner's individual post-test score. The findings suggested that the patterns of pair interaction greatly influenced the frequency of LREs and post-test performance. When the learners engaged in collaborative patterns of interaction, they were more likely to achieve higher posttest scores regardless of their partner's proficiency level. It seems that proficiency differences do not necessarily affect the nature of peer assistance and L2 learning.
Condensing Practices
Authors: Hand Martin , Shove Elizabeth
Published: March 2007

In the UK, the majority of households have a freezer and by most criteria it would be fair to say that home freezing and frozen food provisioning reached sociotechnical ‘closure’ some 20 years ago or more. Detailed examination of how people actually live with freezers suggests, by contrast, that associated consumption practices and processes are varied, unstable and subject to change. Interviews with representatives of 40 households provide new insight into the ways in which discursive, material and temporal aspects of daily life condense around the freezer. In analysing these experiences, we suggest that freezing is persistently dynamic because the freezer figures as an orchestrating node around which multiple aspects of consumption and provision converge.We show how different ways of living with a freezer are negotiated and maintained and we discuss the relation between household practices and the systems of provision with which they intersect.We suggest that concepts like those of ‘domestication’ and ‘normalization’ fail to capture the persistently dynamic status of material objects in daily life, or their constitutive role in systems of social order. In response, we argue for an analysis of ‘normalization’ as an ongoing achievement, and for an interpretation of freezing as a surprisingly performative process involving the active integration of materials, ideologies and skills.
Cultural Differences in Distributive and Procedural Justice
Authors: Reithel Scott M. , Baltes Boris B. , Buddhavarapu Swati
Published: March 2007

The purpose of this study was to examine cultural differences in perceptions of distributive and procedural justice. Four different structural equation models of the relationship between distributive and procedural justice and their impact on systemic and individual outcome variables were tested. The models are similar to those tested by Sweeney and McFarlin, who found support for a two-factor model in a sample of employees from the United States. The models in the current study were tested on a sample of full-time employees working in Hong Kong. Support for cultural differences was found, as the two-factor model did not fit for Hong Kong employees. The distributive-halo model was the most appropriate and showed that distributive justice impacted perceptions of both fairness outcomes and procedural justice. In addition, gender did not significantly impact outcomes.
Public Television in the Context of Established and Emerging Democracies: Quo Vadis?
Authors: Rozanova Julia
Published: March 2007

The future of democracy is seen by many as uncertain, particularly in Russia. Consequently, the prospects for the freedom and independence of the media cannot be considered outside this context. This article provides initial insights into the factors that facilitate and constrain the ability of one the most influential media – television – to be an instrument of democracy. Contrasting the original Russian voices with the key perspectives established in the seminal western literature, it points out several common conclusions, namely, that ‘publicness’ is an essential characteristic of free and independent television, that informational pluralism cannot be maintained without combining the market and the non-market regulatory practices in the broadcasting sphere, and that new media, community media, Internet discussion groups and other ‘alternative’ forums may not replace public television but can meaningfully complement its functions.
TLR3 ligand stimulates fully functional memory CD8+ T cells in the absence of CD4+ T-cell help
Authors: Hervas-Stubbs Sandra , Olivier Aurélie , Boisgerault Florence , Thieblemont Nathalie , Leclerc Claude
Published: March 2007

We investigated whether Toll-like receptor ligands (TLR-Ls) can bypass the requirement for CD4+ T-cell help in the induction of fully efficient memory CD8+ T cells (cytotoxic T lymphocytes [CTLs]). “Helpless” CTLs were induced by a synthetic CD8+ T-cell epitope administered with TLR3-L and TLR9-L, but not with TLR2/6-L, TLR4-L, or TLR7-L. The up-regulation of MHC-I and costimulatory molecules by dendritic cells following TLR stimulation was not sufficient for the priming of “helpless” CTLs, which depended essentially on the induction of a strong IFN-α/β response. The “helpless” CTLs induced by TLR-Ls differentiated into fully functional memory CTLs able to proliferate as well as their “helped” counterparts upon challenge, in the absence of CD4+ T-cell help.
Structural and evolutionary bioinformatics of the SPOUT superfamily of methyltransferases
Authors: Tkaczuk Karolina L , Dunin-Horkawicz Stanislaw , Purta Elzbieta , Bujnicki Janusz M
Published: March 2007

Background

SPOUT methyltransferases (MTases) are a large class of S-adenosyl-L-methionine-dependent enzymes that exhibit an unusual alpha/beta fold with a very deep topological knot. In 2001, when no crystal structures were available for any of these proteins, Anantharaman, Koonin, and Aravind identified homology between SpoU and TrmD MTases and defined the SPOUT superfamily. Since then, multiple crystal structures of knotted MTases have been solved and numerous new homologous sequences appeared in the databases. However, no comprehensive comparative analysis of these proteins has been carried out to classify them based on structural and evolutionary criteria and to guide functional predictions.

Results

We carried out extensive searches of databases of protein structures and sequences to collect all members of previously identified SPOUT MTases, and to identify previously unknown homologs. Based on sequence clustering, characterization of domain architecture, structure predictions and sequence/structure comparisons, we re-defined families within the SPOUT superfamily and predicted putative active sites and biochemical functions for the so far uncharacterized members. We have also delineated the common core of SPOUT MTases and inferred a multiple sequence alignment for the conserved knot region, from which we calculated the phylogenetic tree of the superfamily. We have also studied phylogenetic distribution of different families, and used this information to infer the evolutionary history of the SPOUT superfamily.

Conclusion

We present the first phylogenetic tree of the SPOUT superfamily since it was defined, together with a new scheme for its classification, and discussion about conservation of sequence and structure in different families, and their functional implications. We identified four protein families as new members of the SPOUT superfamily. Three of these families are functionally uncharacterized (COG1772, COG1901, and COG4080), and one (COG1756 represented by Nep1p) has been already implicated in RNA metabolism, but its biochemical function has been unknown. Based on the inference of orthologous and paralogous relationships between all SPOUT families we propose that the Last Universal Common Ancestor (LUCA) of all extant organisms contained at least three SPOUT members, ancestors of contemporary RNA MTases that carry out m1G, m3U, and 2'O-ribose methylation, respectively. In this work we also speculate on the origin of the knot and propose possible 'unknotted' ancestors. The results of our analysis provide a comprehensive 'roadmap' for experimental characterization of SPOUT MTases and interpretation of functional studies in the light of sequence-structure relationships.
An efficient grid layout algorithm for biological networks utilizing various biological attributes
Authors: Kojima Kaname , Nagasaki Masao , Jeong Euna , Kato Mitsuru , Miyano Satoru
Published: March 2007

Background

Clearly visualized biopathways provide a great help in understanding biological systems. However, manual drawing of large-scale biopathways is time consuming. We proposed a grid layout algorithm that can handle gene-regulatory networks and signal transduction pathways by considering edge-edge crossing, node-edge crossing, distance measure between nodes, and subcellular localization information from Gene Ontology. Consequently, the layout algorithm succeeded in drastically reducing these crossings in the apoptosis model. However, for larger-scale networks, we encountered three problems: (i) the initial layout is often very far from any local optimum because nodes are initially placed at random, (ii) from a biological viewpoint, human layouts still exceed automatic layouts in understanding because except subcellular localization, it does not fully utilize biological information of pathways, and (iii) it employs a local search strategy in which the neighborhood is obtained by moving one node at each step, and automatic layouts suggest that simultaneous movements of multiple nodes are necessary for better layouts, while such extension may face worsening the time complexity.

Results

We propose a new grid layout algorithm. To address problem (i), we devised a new force-directed algorithm whose output is suitable as the initial layout. For (ii), we considered that an appropriate alignment of nodes having the same biological attribute is one of the most important factors of the comprehension, and we defined a new score function that gives an advantage to such configurations. For solving problem (iii), we developed a search strategy that considers swapping nodes as well as moving a node, while keeping the order of the time complexity. Though a naïve implementation increases by one order, the time complexity, we solved this difficulty by devising a method that caches differences between scores of a layout and its possible updates.

Conclusion

Layouts of the new grid layout algorithm are compared with that of the previous algorithm and human layout in an endothelial cell model, three times as large as the apoptosis model. The total cost of the result from the new grid layout algorithm is similar to that of the human layout. In addition, its convergence time is drastically reduced (40% reduction).
Investigating the cost-effectiveness of videotelephone based support for newly diagnosed paediatric oncology patients and their families: design of a randomised controlled trial
Authors: Bensink Mark , Wootton Richard , Irving Helen , Hallahan Andrew , Theodoros Deborah , Russell Trevor , Scuffham Paul , Barnett Adrian G
Published: March 2007

Background

Providing ongoing family centred support is an integral part of childhood cancer care. For families living in regional and remote areas, opportunities to receive specialist support are limited by the availability of health care professionals and accessibility, which is often reduced due to distance, time, cost and transport. The primary aim of this work is to investigate the cost-effectiveness of videotelephony to support regional and remote families returning home for the first time with a child newly diagnosed with cancer

Methods/design

We will recruit 162 paediatric oncology patients and their families to a single centre randomised controlled trial. Patients from regional and remote areas, classified by Accessibility/Remoteness Index of Australia (ARIA+) greater than 0.2, will be randomised to a videotelephone support intervention or a usual support control group. Metropolitan families (ARIA+ ≤ 0.2) will be recruited as an additional usual support control group. Families allocated to the videotelephone support intervention will have access to usual support plus education, communication, counselling and monitoring with specialist multidisciplinary team members via a videotelephone service for a 12-week period following first discharge home. Families in the usual support control group will receive standard care i.e., specialist multidisciplinary team members provide support either face-to-face during inpatient stays, outpatient clinic visits or home visits, or via telephone for families who live far away from the hospital. The primary outcome measure is parental health related quality of life as measured using the Medical Outcome Survey (MOS) Short Form SF-12 measured at baseline, 4 weeks, 8 weeks and 12 weeks. The secondary outcome measures are: parental informational and emotional support; parental perceived stress, parent reported patient quality of life and parent reported sibling quality of life, parental satisfaction with care, cost of providing improved support, health care utilisation and financial burden for families.

Discussion

This investigation will establish the feasibility, acceptability and cost-effectiveness of using videotelephony to improve the clinical and psychosocial support provided to regional and remote paediatric oncology patients and their families.
A family practice breastfeeding education pilot program: an observational, descriptive study
Authors: Betzold Christine M , Laughlin Kathleen M , Shi Carol
Published: March 2007

Background

The United States Preventive Services Task Force found that effective interventions for extending breastfeeding duration are generally begun during the prenatal period, provide ongoing support for patients and combine information with face-to-face guidance. A 2001 literature review had similar findings but also found that employing a lactation consultant in the clinical setting may increase breastfeeding duration rates. Thus, a program was developed at a family practice office that employed a lactation consultant and followed the American Academy of Pediatrics' "Ten Steps to Support Parents' Choice to Breastfeed Their Baby."

Methods

The program distributed handouts at each prenatal and well-child visit (up to one year). Using questionnaires, a small audit project evaluated the program's impact on breastfeeding goals, duration, in-hospital exclusivity and maternal perception of success. Mothers completed goal surveys at baseline and post-intervention, usually while waiting for prenatal clinic visits. Duration was assessed by surveys completed during well-infant visits, postal mailings or telephone interviews at breastfeeding cessation, 6 months and 1 year. The outcomes measured were increases in goals, maternal perception of success, duration and in-hospital exclusivity.

Results

Participants included 33 women: 48% had a bachelor's or master's degree, 61% were non-Hispanic white, and 67% reported incomes of US$75,000 or higher. At baseline 5/31 planned to exclusively breastfeed for 4–6 months and 5/33 planned to breastfeed for 6–12 months. Post-intervention there was a 200% increase (15/31) in the exclusively breastfeeding 4–6 month group and a 160% increase (13/33) in the 6–12 month duration group. Actual in-hospital exclusivity rates were 61%, 6-month duration rates were 73%, and 12-month rates were 33%. Over 75% of mothers reported feeling successful.

Conclusion

This small pilot educational program may have significant impacts on breastfeeding goals. Setting and meeting goals may increase duration and in-hospital exclusivity rates as well as enhance maternal self-perception and empowerment due to succeeding at their breastfeeding goals and/or experiencing a fulfilling breastfeeding relationship.
Dissociation between the translocation and the activation of Akt in fMLP-stimulated human neutrophils—effect of prostaglandin E2
Authors: Burelout Chantal , Naccache Paul H , Bourgoin Sylvain G
Published: March 2007

PGE2 and other cAMP-elevating agents are known to down-regulate most functions stimulated by fMLP in human polymorphonuclear neutrophils. We reported previously that the inhibitory potential of PGE2 resides in its capacity to suppress fMLP-stimulated PI-3Kγ activation via the PGE2 receptor EP2 and hence, to decrease phosphatidylinositol 3,4,5-triphosphate [PI(3,4,5)P3] formation. Akt activity is stimulated by fMLP through phosphorylation on threonine 308 (Thr308) and serine 473 (Ser473) by 3-phosphoinositide-dependent kinase 1 (PDK1) and MAPK-AP kinase (APK)-APK-2 (MAPKAPK-2), respectively, in a PI-3K-dependent manner. Despite the suppression of fMLP-induced PI-3Kγ activation observed in the presence of PGE2, we show that Akt is fully phosphorylated on Thr308 and Ser473. However, fMLP-induced Akt translocation is decreased markedly in this context. PGE2 does not affect the phosphorylation of MAPKAPK-2 but decreases the translocation of PDK1 induced by fMLP. Other cAMP-elevating agents such as adenosine (Ado) similarly block the fMLP-induced PI-3Kγ activation process but do not inhibit Akt phosphorylation. However, Akt activity stimulated by fMLP is down-regulated slightly by agonists that elevate cAMP levels. Whereas protein kinase A is not involved in the maintenance of Akt phosphorylation, it is required for the inhibition of Akt translocation by PGE2. Moreover, inhibition of fMLP-stimulated PI-3Kδ activity by the selective inhibitor IC87114 only partially affects the late phase of Akt phosphorylation in the presence of PGE2. Taken together, these results suggest that cAMP-elevating agents, such as PGE2 or Ado, are able to induce an alternative mechanism of Akt activation by fMLP in which the translocation of Akt to PI(3,4,5)P3-enriched membranes is not required prior to its phosphorylation.
Eosinophils develop in distinct stages and are recruited to peripheral sites by alternatively activated macrophages
Authors: Voehringer David , van Rooijen N , Locksley Richard M
Published: March 2007

Eosinophils are associated with allergic diseases and helminth infections. Development of these cells and recruitment to peripheral tissues are only partially understood. Distinct stages of eosinophil development in fetal liver, bone marrow, and blood could be identified using IL-4 reporter mice and mAb against FIRE, Siglec-F, and CCR3. Immature eosinophils were present in the fetal liver and could reconstitute the eosinophil compartment in irradiated recipient mice. In adult mice, eosinophil maturation proceeded from CCR3− to CCR3+ cells in the bone marrow and was accompanied with changes in the transcriptional profile. Eosinophils appeared as activated cells in lung, thymus, lymph nodes, and Peyer’s patches but remained in a resting state in bone marrow, blood, and spleen. Mixed bone marrow chimeras revealed that recruitment to lung and peritoneum was dependent on Stat6 expression in noneosinophils. Alternatively activated macrophages contributed substantially to tissue recruitment of eosinophils, providing a novel basis for development of therapeutic approaches to lower tissue eosinophilia.
Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells
Authors: Del Giudice Elda , Rinaldi Luciano , Passarotto Marzia , Facchinetti Fabrizio , D’Arrigo Antonello , Guiotto Adriano , Carbonare Maurizio Dalle , Battistin Leontino , Leon Alberta
Published: March 2007

Cannabidiol (CBD), a prominent psychoinactive component of cannabis with negligible affinity for known cannabinoid receptors, exerts numerous pharmacological actions, including anti-inflammatory and immunosuppressive effects, the underlying mechanisms of which remain unclear. In the current study, we questioned whether CBD modulates activation of mast cells, key players in inflammation. By using the rat basophilic leukemia mast cell line (RBL-2H3), we demonstrate that CBD (3–10 μM) augments β-hexosaminidase release, a marker of cell activation, from antigen-stimulated and unstimulated cells via a mechanism, which is not mediated by Gi/Go protein-coupled receptors but rather is associated with a robust rise in intracellular calcium ([Ca2+]i) levels sensitive to clotrimazole and nitrendipine (10–30 μM). This action, although mimicked by Δ9-tetrahydrocannabinol (THC), is opposite to that inhibitory, exerted by the synthetic cannabinoids WIN 55,212-2 and CP 55,940. Moreover, the vanilloid capsaicin, a full agonist of transient receptor potential channel VR1, did not affect [Ca2+]ilevels in the RBL-2H3 cells, thus excluding the involvement of this receptor in the CBD-mediated effects. Together, these results support existence of yet-to-be identified sites of interaction, i.e., receptors and/or ion channels associated with Ca2+ influx of natural cannabinoids such as CBD and THC, the identification of which has the potential to provide for novel strategies and agents of therapeutic interest.
Oxidative Stress Response in Telomerase‐Immortalized Fibroblasts from a Centenarian
Authors: MONDELLO CHIARA , BOTTONE MARIA GRAZIA , NORIKI SAKON , SOLDANI CRISTIANA , PELLICCIARI CARLO , SCOVASSI ANNA IVANA
Published: March 2007

Abstract:  It has been reported that cells with ectopic expression of telomerase are more resistant to apoptotic cell death than their normal counterpart. However, controversial results were obtained when the cellular response to oxidative stress was analyzed. The present research was therefore aimed at defining the effect of the oxidative stress induced by tert‐butylhydroperoxide (tBOOH) and 2‐deoxy‐d‐ribose (d‐ribose) in human fibroblasts from a centenarian (cen3) and, in parallel, on the same cells after telomerase immortalization (cen3tel cells). By studying different parameters of apoptosis in situ (i.e., chromatin condensation, phosphatidylserine externalization, and DNA fragmentation), we found that both tBOOH and d‐ribose induce apoptosis to a greater extent in cen3 than in cen3tel cells, suggesting a protective role of telomerase toward apoptotic death. However, monitoring the cell number during treatment with the drugs, we found a decrease in cell number; since this reduction was lower in cen3 fibroblasts compared to cen3tel cells, it is likely that telomerase does not fully protect cells from drug toxicity.
Differential Modulation of AMPK Signaling Pathways by Low or High Levels of Exogenous Reactive Oxygen Species in Colon Cancer Cells
Authors: PARK IN‐JA , HWANG JIN‐TAEK , KIM YOUNG MIN , HA JOOHUN , PARK OCK JIN
Published: March 2007

Abstract:  This study was undertaken to examine the effect of low and high concentrations of H2O2 on cancer cell proliferation and apoptosis, and AMPK signaling pathways in HT‐29 human colon cancer cells. Nontoxic doses of H2O2 (10 μM) induced cancer cell proliferation, whereas the toxic level of 1,000 μM H2O2 induced apoptosis. The stimulation of cell proliferation was accompanied with an increase in cyclooxygenase‐2 (COX‐2), and apoptosis induced by high‐dose H2O2 was correlated with the activation of AMPK and negatively correlated with COX‐2 expression. These results suggest that ROS at nontoxic levels can stimulate cancer cell growth by regulating AMP‐activated protein kinase (AMPK) and/or COX‐2, and the abundant exogenous ROS linked to the growth inhibition through modulating AMPK signaling pathways.
Targeting Signal‐Transducer‐and‐Activator‐of‐Transcription‐3 for Prevention and Therapy of Cancer
Authors: AGGARWAL BHARAT B. , SETHI GAUTAM , AHN KWANG SEOK , SANDUR SANTOSH K. , PANDEY MANOJ K. , KUNNUMAKKARA AJAIKUMAR B. , SUNG BOKYUNG , ICHIKAWA HARUYO
Published: March 2007

Abstract:  Recent evidence indicates a convergence of molecular targets for both prevention and therapy of cancer. Signal‐transducer‐and‐activator‐of‐transcription‐3 (STAT3), a member of a family of six different transcription factors, is closely linked with tumorigenesis. Its role in cancer is indicated by numerous avenues of evidence, including the following: STAT3 is constitutively active in tumor cells; STAT3 is activated by growth factors (e.g., EGF, TGF‐α, IL‐6, hepatocyte growth factor) and oncogenic kinases (e.g., Src); STAT3 regulates the expression of genes that mediate proliferation (e.g., c‐myc and cyclin D1), suppress apoptosis (e.g., Bcl‐xL and survivin), or promote angiogenesis (e.g, VEGF); STAT3 activation has been linked with chemoresistance and radioresistance; and chemopreventive agents have been shown to suppress STAT3 activation. Thus inhibitors of STAT3 activation have potential for both prevention and therapy of cancer. Besides small peptides and oligonucleotides, numerous small molecules have been identified as blockers of STAT3 activation, including synthetic molecules (e.g., AG 490, decoy peptides, and oligonucleotides) and plant polyphenols (e.g., curcumin, resveratrol, flavopiridol, indirubin, magnolol, piceatannol, parthenolide, EGCG, and cucurbitacin). This article discusses these aspects of STAT3 in more detail.
Atrial Appendage Transcriptional Profile in Patients with Atrial Fibrillation with Structural Heart Diseases
Authors: KHARLAP MARIA S. , TIMOFEEVA ANGELICA V. , GORYUNOVA LUDMILA E. , KHASPEKOV GEORGE L. , DZEMESHKEVICH SERGEY L. , RUSKIN VLADIMIR V. , AKCHURIN RENAT S. , GOLITSYN SERGEY P. , BEABEALASHVILLI ROBERT SH.
Published: March 2007

Abstract:  During the last few years DNA microarray studies of gene expression changes in human atrial tissues from patients with and without atrial fibrillation (AF) have been performed. For this purpose, tissue samples are usually collected from AF patients undergoing open heart surgery. These investigations have limitations associated with the unavoidable heterogeneity of compared groups which is due to the presence of various structural changes accompanying different sets of underlying heart diseases in both groups. It is thus reasonable to compare the atrial tissue samples from AF patients with those from individuals without signs of cardiovascular disease. To address this, we selected the atrial tissue samples from 12 AF patients (who underwent open heart surgery) and compared them with control atrial tissue samples from 10 individuals with no signs of cardiovascular diseases (those who died due to street accident). cDNA microarray method and reverse transciption–polymerase chain reaction (RT‐PCR) analysis were used to identify genes which can discriminate between control and pathologically altered atrial tissues. Thirty‐nine genes were found to be differentially expressed in pathologically altered tissues samples independently of the type of the underlying structural heart disease. These genes are involved in signal transduction, gene transcription regulation, cell proliferation, and apoptosis. The greatest alterations were observed for NOR1, DEC1, MSF, and Bcl2A1 genes (5 to 28‐fold decrease, P < 0.05). Additional studies are needed to determine the specific role of each selected gene in pathophysiological changes leading to AF.
Update in Osteoporosis and Metabolic Bone Disorders
Authors: Shoback Dolores
Published: March 2007

Considerable progress has been made in the development and testing of agents to treat osteoporosis. Most impressive are reports on new antiresorptive agents—both bisphosphonates (ibandronate and zoledronic acid) and monoclonal antibodies (MAbs) (denosumab) directed against receptor activator of nuclear factor κB-ligand, a key molecule in the control of commitment and activation of osteoclasts. Bisphosphonates promise convenience and potency at slowing bone loss, whereas denosumab offers powerful suppression of resorption and rapid offset of action. Attention is also shifting from the osteoclast as a target for new therapies to the osteoblast and the osteocyte, with its complex network within the depths of bone. Wnt signaling through the frizzled receptor and its coreceptor, the low-density lipoprotein receptor related protein-5, appears from both molecular and in vivo evidence to be a pivotal pathway for modulating osteoblastic activity, bone formation, and bone strength. The recently identified product of the SOST gene or sclerostin has also been shown to block Wnt signaling. Sclerostin is produced by the osteocytes buried in the bone and is a new target to treat bone loss. Clinical trial reports indicate that the calcimimetic cinacalcet can effectively treat PTH hypersecretion due to primary and secondary hyperparathyroidism and parathyroid carcinoma. Lastly, it is now recognized that the matrix protein dentin matrix protein-1 enhances the release of the phosphate-regulating factor fibroblast growth factor 23 and that mutations in dentin matrix protein-1 play a causative role in a form of hypophosphatemic rickets.
Application and Evaluation of Solvent-Free Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry for the Analysis of Derivatized Fullerenes
Authors: Kotsiris Sotirios G. , Vasil'ev Yury V. , Streletskii Alexey V. , Han Ming , Mark Lewis P. , Boltalina Olga V. , Chronakis Nikos , Orfanopoulos Michael , Hungerbühler Hartmut , Drewello Thomas
Published: March 2007

A variety of derivatized fullerenes have been studied by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. Of particular emphasis has been the evaluation of a recently introduced solvent-free sample/target preparation method. Solvent-free MALDI is particularly valuable in overcoming adverse solvent-related effects, such as insolubility and/or degradation of the sample. The method was applied to fullerene derivatives susceptible to decomposition under insufficiently “soft” MALDI conditions. Analytes included the hydrofullerene: C60H36, fluorofullerenes: C60F x where x = 18, 36, 46, 48 and C70F x where x = 54, 56, methano-bridged amphiphilic ligand adducts to C60 and the [4 + 2] cycloadduct of tetracene to C60. The new solvent-free sample preparation is established as an exceedingly valuable addition to the repertoire of preparation protocols within MALDI. The MALDI mass spectra were of very high quality throughout, providing a testimony that “soft” MALDI conditions could be achieved. Using the [4 + 2] cycloadduct of tetracene to C60 as the model analyte for direct comparison with solvent-based MALDI, the solvent-free approach led to less fragmentation and more abundant analyte ions. Applying solvent-free sample preparation, different matrix compounds have been examined for use in the MALDI of derivatized fullerenes, including sulfur, tetracyanoquinodimethane (TCNQ), 9-nitroanthracene (9-NA) and trans-2-[3-(4- tert-butylphenyl)-2-methyl-2-propenylidene]malononitrile (DCTB). DCTB was confirmed as the best performing matrix, reducing unwanted decomposition and suppression effects.