bluuebunny/crossref_metadata_2025 huggingface dataset:
Quit smoking advice from health professionals in Taiwan: the role of funding policy and smoker socioeconomic status
Authors: Chang Fong-ching , Hu Teh-wei , Lo Shu-ying , Yu Po-tswen , Chao Kun-yu , Hsiao Mei-ling
Published: December 2009

Objectives

In 2002, Taiwan launched a program to encourage doctors to provide brief cessation counselling to their patients during routine outpatient visits. This study is to compare and analyse the annual prevalence rate of receiving advice to quit smoking from health professionals before (2004) and after (2005, 2006) the increase in funding and the withdrawal of additional funding (2007).

Methods

We analysed pooled data from 2004 to 2007 Taiwan Adult Tobacco Survey, an annual random digit dialling telephone survey, to estimate the prevalence of receiving quit advice among ever smokers across these years. Smoking characteristics and the socioeconomic factors of smokers associated with receipt of advice to quit smoking were also examined.

Results

The prevalence rate of receiving quit advice increased from 21.1% in 2004 to 28.2% in 2006, and then decreased slightly to 27.6% in 2007 after the funds were cut. Multivariate analyses results indicated that increasing financing for smoking cessation services in 2005, being male, older, a daily cigarette user, having previously attempted to quit, perceiving oneself as having poor health and being aware of the benefits of smoking cessation services were significantly positively associated with receiving quit advice from health professionals. In contrast, smokers who were younger, female and occasional cigarette users were less likely to receive quit advice. Also, smokers with socioeconomic disadvantages were not less likely to receive quit advice.

Conclusions

During the period of increased funding for smoking cessation services, the rates of receiving quit advice increased among all smokers and across different socioeconomic groups.
Awareness and impact of the ‘Bubblewrap’ advertising campaign among Aboriginal smokers in Western Australia
Authors: Boyle Terry , Shepherd Carrington C J , Pearson Glenn , Monteiro Heather , McAullay Daniel , Economo Kristina , Stewart Susan
Published: December 2009

Background

Antismoking mass media campaigns have been shown to reduce smoking prevalence in the mainstream community, however there is little published research on their effect on Aboriginal Australian smokers.

Objectives

To evaluate the awareness and impact of a mainstream mass media advertising campaign (the ‘Bubblewrap’ campaign) on Aboriginal smokers in the state of Western Australia.

Methods

A personal intercept survey was conducted in July 2008 across three sites (the Perth metropolitan area and the non-metropolitan towns of Kalgoorlie and Broome). An opportunity or convenience sampling strategy was used to recruit Aboriginal participants, and face-to-face interviews were conducted with 198 Aboriginal smokers to ascertain awareness of the campaign advertisements, whether they were seen as believable and relevant, and the impact the advertisements had on smoking behaviour.

Results

The majority of the participants interviewed had seen and/or heard the ‘Bubblewrap’ campaign advertisements, although there was considerably greater awareness of the television advertisement than the radio advertisements. Both forms of advertising were considered to be believable and relevant by the majority of Aboriginal smokers. Most of the smokers interviewed thought about cutting down and/or quitting after seeing or hearing the advertisements.

Conclusions

Our findings suggest that mainstream antismoking mass media campaigns can positively influence the thoughts and behaviours that Aboriginal smokers have, and exhibit, towards quitting smoking. Notwithstanding this, advertisers should continue to look for better ways to incorporate Aboriginal themes in campaign messages. Future mainstream antismoking campaigns should source sufficient funds to ensure that advertising messages reach the large Aboriginal populations in regional and remote Australia.
Smoking estimates from around the world: data from the first 17 participating countries in the World Mental Health Survey Consortium
Authors: Storr Carla L , Cheng Hui , Alonso Jordi , Angermeyer Matthias , Bruffaerts Ronny , de Girolamo Giovanni , de Graaf Ron , Gureje Oye , Karam Elie G , Kostyuchenko Stanislav , Lee Sing , Lepine Jean-Pierre , Medina Mora Maria Elena , Myer Landon , Neumark Yehuda , Posada-Villa Jose , Watanabe Makoto , Wells J Elisabeth , Kessler Ronald C , Anthony James C
Published: December 2009

Objective

To contribute new multinational findings on basic descriptive features of smoking and cessation, based upon standardised community surveys of adults residing in seven low-income and middle-income countries and 10 higher-income countries from all regions of the world.

Methods

Data were collected using standardised interviews and community probability sample survey methods conducted as part of the WHO World Mental Health Surveys Initiative. Demographic and socioeconomic correlates of smoking are studied using cross-tabulation and logistic regression approaches. Within-country sample weights were applied with variance estimation appropriate for complex sample survey designs.

Results

Estimated prevalence of smoking experience (history of ever smoking) and current smoking varied across the countries under study. In all but four countries, one out of every four adults currently smoked. In higher-income countries, estimated proportions of former smokers (those who had quit) were roughly double the corresponding estimates for most low-income and middle-income countries. Characteristics of smokers varied within individual countries, and in relation to the World Bank's low-medium-high gradient of economic development. In stark contrast to a sturdy male-female difference in the uptake of smoking seen in each country, there is no consistent sex-associated pattern in the odds of remaining a smoker (versus quitting).

Conclusion

The World Mental Health Surveys estimates complement existing global tobacco monitoring efforts. The observed global diversity of associations with smoking and smoking cessation underscore reasons for implementation of the Framework Convention on Tobacco Control provisions and prompt local adaptation of prevention and control interventions.
Tobacco coverage in print media: the use of timing and themes by tobacco control supporters and opposition before a failed tobacco tax initiative
Authors: Harris Jenine K , Shelton Sarah C , Moreland-Russell Sarah , Luke Douglas A
Published: December 2009

Objective

Tobacco control policies gained ground nationwide in 2006, with voters in nine states approving legislation to strengthen clean indoor air policies and increase tobacco excise taxes. Despite having the second lowest cigarette tax rate in the nation, Missouri was unsuccessful in passing its 2006 ballot initiative to raise the tax. An important way to encourage health-related policy change such as increasing tobacco taxes is through media coverage of tobacco issues. We examined how tobacco issues were presented in Missouri's print media leading up to the 2006 election.

Methods

This study analysed 1263 articles with tobacco content published in 187 Missouri newspapers in the year before the election. Articles were coded for general and tobacco-related characteristics including article type (news story, editorial, letter to the editor), tobacco control position (pro, neutral, anti) and article theme (economic, health, political).

Results

Most articles were news stories (73.6%) and pro-tobacco control (63.8%). The proportion of anti-tobacco control articles increased significantly (χ2=104.9, p<0.001) the month before the election, driven by an increase in economically themed articles. Economic articles were published more often in counties with less voter support for the tax (F=5.68, p<0.01). Finally, tobacco control position varied significantly across article types (χ2=148.3, p<0.01), with letters to the editor being anti-tobacco control most often.

Conclusion

The media have a critical role in promoting public health goals and presenting health issues which influences formation of health policies. Tobacco control advocates must consider public opinion, opposition pressure, timing and themes in tobacco-related media coverage when promoting policy change.
Beyond Drosophila: RNAi In Vivo and Functional Genomics in Insects
Authors: Bellés Xavier
Published: December 2009

The increasing availability of insect genomes has revealed a large number of genes with unknown functions and the resulting problem of how to discover these functions. The RNA interference (RNAi) technique, which generates loss-of-function phenotypes by depletion of a chosen transcript, can help to overcome this challenge. RNAi can unveil the functions of new genes, lead to the discovery of new functions for old genes, and find the genes for old functions. Moreover, the possibility of studying the functions of homologous genes in different species can allow comparisons of the genetic networks regulating a given function in different insect groups, thereby facilitating an evolutionary insight into developmental processes. RNAi also has drawbacks and obscure points, however, such as those related to differences in species sensitivity. Disentangling these differences is one of the main challenges in the RNAi field.
Causes and Consequences of Cannibalism in Noncarnivorous Insects
Authors: Richardson Matthew L. , Mitchell Robert F. , Reagel Peter F. , Hanks Lawrence M.
Published: December 2009

We review the primary literature to document the incidence of cannibalism among insects that typically are not carnivorous. Most of the cannibalistic species were coleopterans and lepidopterans, and the cannibals often were juveniles that aggregate or that overlap in phenology with the egg stage. Cannibalism can be adaptive by improving growth rate, survivorship, vigor, longevity, and fecundity. It also can play an important role in regulating population density and suppressing population outbreaks, stabilizing host plant–insect relationships, and reducing parasitism rates. Cannibalism often was favored by density-dependent factors for herbivores that feed in concealed feeding situations (such as stem borers, leafminers), but also by density-independent factors (such as high ambient temperature) for herbivores that feed in exposed feeding situations.
Feeding Mechanisms of Adult Lepidoptera: Structure, Function, and Evolution of the Mouthparts
Authors: Krenn Harald W.
Published: December 2009

The form and function of the mouthparts in adult Lepidoptera and their feeding behavior are reviewed from evolutionary and ecological points of view. The formation of the suctorial proboscis encompasses a fluid-tight food tube, special linking structures, modified sensory equipment, and novel intrinsic musculature. The evolution of these functionally important traits can be reconstructed within the Lepidoptera. The proboscis movements are explained by a hydraulic mechanism for uncoiling, whereas recoiling is governed by the intrinsic proboscis musculature and the cuticular elasticity. Fluid uptake is accomplished by the action of the cranial sucking pump, which enables uptake of a wide range of fluid quantities from different food sources. Nectar-feeding species exhibit stereotypical proboscis movements during flower handling. Behavioral modifications and derived proboscis morphology are often associated with specialized feeding preferences or an obligatory switch to alternative food sources.
Insect Biodiversity and Conservation in Australasia
Authors: Cranston Peter S.
Published: December 2009

Australasia, which consists of Australia and the adjacent islands of the southwestern Pacific Ocean, has an insect diversity approximately proportional to the land mass. This diversity is distinctive, with some major groups missing and others having radiated. Iconic species are familiar to most people living in Australia and New Zealand, and a range of insects once contributed to Aboriginal Australian culture and diet. Conservation of Australasian entomological biodiversity is an increasing challenge for contemporary scientists. Examples are provided of insect conservation schemes from New Guinea, New Zealand, and Australia. Funding for insect biodiversity studies beyond flagship species is needed.
Ecology of Herbivorous Arthropods in Urban Landscapes
Authors: Raupp Michael J. , Shrewsbury Paula M. , Herms Daniel A.
Published: December 2009

Urbanization affects communities of herbivorous arthropods and provides opportunities for dramatic changes in their abundance and richness. Underlying these changes are creation of impervious surfaces; variation in the density, diversity, and complexity of vegetation; and maintenance practices including pulsed inputs of fertilizers, water, and pesticides. A rich body of knowledge provides theoretical underpinnings for predicting and understanding impacts of urbanization on arthropods. However, relatively few studies have elucidated mechanisms that explain patterns of insect and mite abundance and diversity across urbanization gradients. Published accounts suggest that responses to urbanization are often taxon specific, highly variable, and linked to properties of urbanization that weaken top-down and/or bottom-up processes, thereby destabilizing populations of herbivores and their natural enemies. In addition to revealing patterns in diversity and abundance of herbivores across urbanization gradients, a primary objective of this review is to examine mechanisms underlying these patterns and to identify potential hypotheses for future testing.
Integrated Management of Sugarcane Whitegrubs in Australia: An Evolving Success
Authors: Allsopp Peter G.
Published: December 2009

Canegrubs, larvae of a complex of endemic melolonthine scarabs, are the key pests in Australian sugarcane. In the early 1990s, following the withdrawal of organochlorines, the Australian sugarcane industry faced a crisis with increasing canegrub damage. A comprehensive integrated pest management strategy was developed on the basis of research on a wide range of topics such as basic taxonomy, species identification, ecology and biology of the different species within the sugarcane system, development of new insecticides and new formulations of insecticides, potential development of genetically modified pest-resistant canes, and methods for predicting risk of infestations. The value of the research depended on a wide-ranging extension program that saw broadscale adoption of the new strategies. However, the cropping system is not static, and recent changes have the potential to alter plant architecture and phenology and therefore could affect canegrub biology, canegrub feeding, the impact of natural controls on canegrubs, and the accessibility to soil for sampling and insecticide application. Growers also demand cheaper, easier-to-use options.
The Developmental, Molecular, and Transport Biology of Malpighian Tubules
Authors: Beyenbach Klaus W. , Skaer Helen , Dow Julian A.T.
Published: December 2009

Molecular biology is reaching new depths in our understanding of the development and physiology of Malpighian tubules. In Diptera, Malpighian tubules derive from ectodermal cells that evaginate from the primitive hindgut and subsequently undergo a sequence of orderly events that culminates in an active excretory organ by the time the larva takes its first meal. Thereafter, the tubules enlarge by cell growth. Just as modern experimental strategies have illuminated the development of tubules, genomic, transcriptomic, and proteomic studies have uncovered new tubule functions that serve immune defenses and the breakdown and renal clearance of toxic substances. Moreover, genes associated with specific diseases in humans are also found in flies, some of which, astonishingly, express similar pathophenotypes. However, classical experimental approaches continue to show their worth by distinguishing between -omic possibilities and physiological reality while providing further detail about the rapid regulation of the transport pathway through septate junctions and the reversible assembly of proton pumps.
The Making of a Medical Entomologist
Authors: Service Mike W.
Published: December 2009

This article describes the childhood of Mike Service, his very early interest in insects, his time at Imperial College, London University, and his career in Nigeria studying the taxonomy and biology of anopheline malaria vectors. On his return to England he became increasingly interested in the ecology and population dynamics of hematophagous insects. After almost eight years undertaking only research, he joined the Liverpool School of Tropical Medicine, where he was involved in lecturing as well as research and engaged in frequent overseas travel mainly to Africa, Central and South America, and Asia. On retirement he retains an active interest in medical entomology. Although he undertook a considerable amount of taxonomic work on mosquitoes, he believes his most important, and possibly influential, work was introducing ecological methods that were used by agricultural scientists to the study of mosquitoes. For example, the construction of life tables, calculating the percentage mortality of pre-adult mosquitoes, and the identification of predators by serological methods.
Ekbom Syndrome: The Challenge of “Invisible Bug” Infestations
Authors: Hinkle Nancy C.
Published: December 2009

Ekbom Syndrome is synonymous with delusory parasitosis, a belief that one's body is infested by invisible bugs. Persons suffering from this syndrome often claim to feel dermal sensations and to visualize the bugs, although no one else can see them. Ekbom Syndrome is a delusional condition; it is intractable and cannot be corrected by argument or evidence. Ekbom Syndrome sufferers exhibit a range of predictable behaviors in their attempts to eliminate their infestations, including seeking identifications and treatment from physicians and entomologists. Frequently they also experience comorbid psychological conditions. Because this is a delusional affliction, successful treatment typically requires neuroleptic medications, necessitating intervention by medical professionals.
Bayesian Phylogenetics and Its Influence on Insect Systematics
Authors: Ronquist Fredrik , Deans Andrew R.
Published: December 2009

Bayesian inference and Markov chain Monte Carlo techniques have enjoyed enormous popularity since they were introduced into phylogenetics about a decade ago. We provide an overview of the field, with emphasis on recent developments of importance to empirical systematists. In particular, we describe a number of recent advances in the stochastic modeling of evolution that address major deficiencies in current models in a computationally efficient way. These include models of process heterogeneity across sites and lineages, as well as alignment-free models and model averaging approaches. Many of these methods should find their way into standard analyses in the near future. We also summarize the influence of Bayesian methods on insect systematics, with particular focus on current practices and how they could be improved using existing and emerging techniques.
Age-associated changes in excitation-contraction coupling are more prominent in ventricular myocytes from male rats than in myocytes from female rats
Authors: Howlett Susan E.
Published: December 2009

We evaluated effects of age on components of excitation-contraction (EC) coupling in ventricular myocytes from male and female rats to examine sex differences in mechanisms responsible for age-related contractile dysfunction. Myocytes were isolated from anesthetized young adult (∼3 mo) and aged (∼24 mo) Fischer 344 rats. Ca2+ concentrations and contractions were measured simultaneously (37°C, 2 Hz). Fractional shortening declined with age in males (6.7 ± 0.6% to 2.4 ± 0.4%; P < 0.05), as did peak Ca2+ transients (47.7 ± 4.6 to 28.1 ± 2.1 nM; P < 0.05) and Ca2+ current densities (−7.7 ± 0.7 to −6.2 ± 0.5 pA/pF; P < 0.05). Although sarcoplasmic reticulum (SR) Ca2+ content was similar regardless of age in males, EC coupling gain declined significantly with age to 55.8 ± 7.8% of values in younger males. In contrast with results in males, contraction and Ca2+ transient amplitudes were unaffected by age in females. Ca2+ current density declined with age in females (−7.5 ± 0.5 to −5.1 ± 0.7 pA/pF; P < 0.05), but SR Ca2+ content actually increased dramatically (49.0 ± 7.5 to 147.3 ± 28.5 nM; P < 0.05). Even so, EC coupling gain was not affected by age in female myocytes. Age also promoted hypertrophy of male myocytes more than female myocytes. Age and sex differences in EC coupling were largely maintained when conditioning pulse frequency was increased to 4 Hz. Contractions, Ca2+ transients, and EC coupling gain were also smaller in young females than in young males. Thus age-dependent changes are more prominent in myocytes from males than females. Increased SR Ca2+ content may compensate for reduced Ca2+ current to preserve contractile function in aged females, which may limit the detrimental effects of age on cardiac contractile function.
Intercellular calcium waves are associated with the propagation of vasomotion along arterial strips
Authors: Seppey Dominique , Sauser Roger , Koenigsberger Michèle , Bény Jean-Louis , Meister Jean-Jacques
Published: December 2009

Vasomotion consists of cyclic arterial diameter variations induced by synchronous contractions and relaxations of smooth muscle cells. However, the arteries do not contract simultaneously on macroscopic distances, and a propagation of the contraction can be observed. In the present study, our aim was to investigate this propagation. We stimulated endothelium-denuded rat mesenteric arterial strips with phenylephrine (PE) to obtain vasomotion and observed that the contraction waves are linked to intercellular calcium waves. A velocity of ∼100 μm/s was measured for the two kinds of waves. To investigate the calcium wave propagation mechanisms, we used a method allowing a PE stimulation of a small area of the strip. No calcium propagation could be induced by this local stimulation when the strip was in its resting state. However, if a low PE concentration was added on the whole strip, local PE stimulations induced calcium waves, spreading over finite distances. The calcium wave velocity induced by local stimulation was identical to the velocity observed during vasomotion. This suggests that the propagation mechanisms are similar in the two cases. Using inhibitors of gap junctions and of voltage-operated calcium channels, we showed that the locally induced calcium propagation likely depends on the propagation of the smooth muscle cell depolarization. Finally, we proposed a model of the propagation mechanisms underlying these intercellular calcium waves.
Arterial pulsatile hemodynamic load induced by isometric exercise strongly predicts left ventricular mass in hypertension
Authors: Chirinos Julio A. , Segers Patrick , Raina Amresh , Saif Hassam , Swillens Abigail , Gupta Amit K. , Townsend Raymond , Emmi Anthony G. , Kirkpatrick James N. , Keane Martin G. , Ferrari Victor A. , Wiegers Susan E. , St. John Sutton Martin G.
Published: December 2009

Although resting hemodynamic load has been extensively investigated as a determinant of left ventricular (LV) hypertrophy, little is known about the relationship between provoked hemodynamic load and the risk of LV hypertrophy. We studied central pressure-flow relations among 40 hypertensive and 19 normotensive adults using carotid applanation tonometry and Doppler echocardiography at rest and during a 40% maximal voluntary forearm contraction (handgrip) maneuver. Carotid-femoral pulse wave velocity (CF-PWV) was measured at rest. Hypertensive subjects demonstrated various abnormalities in resting and induced pulsatile load. Isometric exercise significantly increased systemic vascular resistance, aortic characteristic impedance (Zc), induced earlier wave reflections, increased augmentation index, and decreased total arterial compliance (TAC; all P ≤ 0.01). In hypertensive subjects, CF-PWV was the strongest resting predictor of LV mass index (LVMI) and remained an independent predictor after adjustment for age, gender, systemic vascular resistance, reflection magnitude, aortic Zc, and TAC (β = 2.52 m/s; P < 0.0001). Age, sex, CF-PWV, and resting hemodynamic indexes explained 48% of the interindividual variability in LVMI. In stepwise regression, TAC (β = −17.85; P < 0.0001) during handgrip, Zc during handgrip (β = −150; P < 0.0001), and the change in the timing of wave reflections during handgrip (β = −0.63; P = 0.03) were independent predictors of LVMI. A model that included indexes of provoked hemodynamic load explained 68% of the interindividual variability in LVMI. Hemodynamic load provoked by isometric exercise strongly predicts LVMI in hypertension. The magnitude of this association is far greater than for resting hemodynamic load, suggesting that provoked testing captures important arterial properties that are not apparent at rest and is advantageous to assess dynamic arterial load in hypertension.
Morphine prevents the mitochondrial permeability transition pore opening through NO/cGMP/PKG/Zn2+/GSK-3β signal pathway in cardiomyocytes
Authors: Xi Jinkun , Tian Wei , Zhang Lei , Jin Yulan , Xu Zhelong
Published: December 2009

The aim of this study was to test whether morphine prevents the mitochondrial permeability transition pore (mPTP) opening through Zn2+and glycogen synthase kinase 3β (GSK-3β). Fluorescence dyes including Newport Green Dichlorofluorescein (DCF), 4-amino-5-methylamino-2′,7′-difluorofluorescein (DAF-FM), and tetramethylrhodamine ethyl ester (TMRE) were used to image free Zn2+, nitric oxide (NO), and mitochondrial membrane potential (ΔΨm), respectively. Fluorescence images were obtained with confocal microscopy. Cardiomyocytes treated with morphine for 10 min showed a significant increase in Newport Green DCF fluorescence intensity, an effect that was reversed by the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME), indicating that morphine mobilizes Zn2+via NO. Morphine rapidly produced NO. ODQ and NS2028, the inhibitors of guanylyl cyclase, prevented Zn2+release by morphine, implying that cGMP is involved in the action of morphine. The effect of morphine on Zn2+release was also abolished by KT5823, a specific inhibitor of protein kinase G (PKG). Morphine prevented oxidant-induced loss of ΔΨm, indicating that morphine can modulate the mPTP opening. The effect of morphine on the mPTP was reversed by KT5823 and the Zn2+chelator N, N, N′, N′-tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN). The action of morphine on the mPTP was lost in cells transfected with the constitutively active GSK-3β mutant, suggesting that morphine may prevent the mPTP opening by inactivating GSK-3β. In support, morphine significantly enhanced phosphorylation of GSK-3β at Ser9, and this was blocked by TPEN. GSK-3β small interfering RNA prevented the pore opening in the control cardiomyocytes but failed to enhance the effect of morphine on the mPTP opening. In conclusion, morphine mobilizes intracellular Zn2+through the NO/cGMP/PKG signaling pathway and prevents the mPTP opening by inactivating GSK-3β through Zn2+.
Enhanced apoptotic propensity in diabetic cardiac mitochondria: influence of subcellular spatial location
Authors: Williamson Courtney L. , Dabkowski Erinne R. , Baseler Walter A. , Croston Tara L. , Alway Stephen E. , Hollander John M.
Published: December 2009

Cardiovascular complications, such as diabetic cardiomyopathy, account for the majority of deaths associated with diabetes mellitus. Mitochondria are particularly susceptible to the damaging effects of diabetes mellitus and have been implicated in the pathogenesis of diabetic cardiomyopathy. Cardiac mitochondria consist of two spatially distinct subpopulations, termed subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM). The goal of this study was to determine whether subcellular spatial location is associated with apoptotic propensity of cardiac mitochondrial subpopulations during diabetic insult. Swiss Webster mice were subjected to intraperitoneal injection of streptozotocin or citrate saline vehicle. Ten weeks following injection, diabetic hearts displayed increased caspase-3 and caspase-9 activities, indicating enhanced apoptotic signaling ( P < 0.05, for both). Mitochondrial size (forward scatter) and internal complexity (side scatter) were decreased in diabetic IFM ( P < 0.05, for both) but not in diabetic SSM. Mitochondrial membrane potential (ΔΨm) was lower in diabetic IFM ( P < 0.01) but not in diabetic SSM. Mitochondrial permeability transition pore (mPTP) opening was increased in diabetic compared with control IFM ( P < 0.05), whereas no differences were observed in diabetic compared with control SSM. Examination of mPTP constituents revealed increases in cyclophilin D in diabetic IFM. Furthermore, diabetic IFM possessed lower cytochrome c and BcL-2 levels and increased Bax levels ( P < 0.05, for all 3). No significant changes in these proteins were observed in diabetic SSM compared with control. These results indicate that diabetes mellitus is associated with an enhanced apoptotic propensity in IFM, suggesting a differential apoptotic susceptibility of distinct mitochondrial subpopulations based upon subcellular location.
Exercise-induced brachial artery vasodilation: effects of antioxidants and exercise training in elderly men
Authors: Donato Anthony J. , Uberoi Abhimanyu , Bailey Damian M. , Walter Wray D. , Richardson Russell S.
Published: December 2009

Aging, vascular function, and exercise are thought to have a common link in oxidative stress. Of the 28 subjects studied (young, 26 ± 2 yr; old, 71 ± 6 yr), 12 took part in a study to validate an antioxidant cocktail (AOC: vitamins C, E, and α-lipoic acid), while the remaining 8 young and 8 old subjects performed submaximal forearm handgrip exercise with placebo or AOC. Old subjects repeated forearm exercise with placebo or AOC following knee-extensor (KE) exercise training. Brachial arterial diameter and blood velocity (Doppler ultrasound) were measured at rest and during exercise. During handgrip exercise, brachial artery vasodilation in the old subjects was attenuated compared with that in young subjects following placebo (maximum = ∼3.0 and ∼6.0%, respectively). In contrast to the previously documented attenuation in exercise-induced brachial artery vasodilation in the young group with AOC, in the old subjects the AOC restored vasodilation (maximum = ∼7.0%) to match the young. KE training also improved exercise-induced brachial artery vasodilation. However, in the trained state, AOC administration no longer augmented brachial artery vasodilation in the elderly, but rather attenuated it. These data reveal an age-related pro-/antioxidant imbalance that impacts vascular function and show that exercise training is capable of restoring equilibrium such that vascular function is improved and the AOC-mediated reduction in free radicals now negatively impacts brachial artery vasodilation, as seen in the young.
Glutamate regulates Ca2+ signals in smooth muscle cells of newborn piglet brain slice arterioles through astrocyte- and heme oxygenase-dependent mechanisms
Authors: Xi Qi , Umstot Edward , Zhao Guiling , Narayanan Damodaran , Leffler Charles W. , Jaggar Jonathan H.
Published: December 2009

Glutamate is the principal cerebral excitatory neurotransmitter and dilates cerebral arterioles to match blood flow to neural activity. Arterial contractility is regulated by local and global Ca2+ signals that occur in smooth muscle cells, but modulation of these signals by glutamate is poorly understood. Here, using high-speed confocal imaging, we measured the Ca2+ signals that occur in arteriole smooth muscle cells of newborn piglet tangential brain slices, studied signal regulation by glutamate, and investigated the physiological function of heme oxygenase (HO) and carbon monoxide (CO) in these responses. Glutamate elevated Ca2+ spark frequency by ∼188% and reduced global intracellular Ca2+ concentration ([Ca2+]i) to ∼76% of control but did not alter Ca2+ wave frequency in brain arteriole smooth muscle cells. Isolation of cerebral arterioles from brain slices abolished glutamate-induced Ca2+ signal modulation. In slices treated with l-2-α-aminoadipic acid, a glial toxin, glutamate did not alter Ca2+ sparks or global [Ca2+]i but did activate Ca2+ waves. This shift in Ca2+ signal modulation by glutamate did not occur in slices treated with d-2-α-aminoadipic acid, an inactive isomer of l-2-α-aminoadipic acid. In the presence of chromium mesoporphyrin, a HO blocker, glutamate inhibited Ca2+ sparks and Ca2+ waves and did not alter global [Ca2+]i. In isolated arterioles, CORM-3 [tricarbonylchloro(glycinato)ruthenium(II)], a CO donor, activated Ca2+ sparks and reduced global [Ca2+]i. These effects were blocked by 1 H-(1,2,4)-oxadiazolo-(4,3-a)-quinoxalin-1-one, a soluble guanylyl cyclase inhibitor. Collectively, these data indicate that glutamate can modulate Ca2+ sparks, Ca2+ waves, and global [Ca2+]i in arteriole smooth muscle cells via mechanisms that require astrocytes and HO. These data also indicate that soluble guanylyl cyclase is involved in CO activation of Ca2+ sparks in arteriole smooth muscle cells.
Cardioprotective effects of a novel calpain inhibitor SNJ-1945 for reperfusion injury after cardioplegic cardiac arrest
Authors: Yoshikawa Yoshiro , Zhang Guo-Xing , Obata Koji , Ohga Yoshimi , Matsuyoshi Hiroko , Taniguchi Shigeki , Takaki Miyako
Published: December 2009

We have previously indicated that calpain inhibitor-1 prevents the heart from ischemia- reperfusion injury associated with the impairment of total Ca2+ handling by inhibiting the proteolysis of α-fodrin. However, this inhibitor is insoluble with water and inappropriate for clinical application. The aim of the present study was to investigate the protective effect of a newly developed calpain inhibitor, SNJ-1945 (SNJ), with good aqueous solubility on left ventricular (LV) mechanical work and energetics in the cross-circulated rat hearts. SNJ (150 μM) was added to KCl (30 meq) cardioplegia (CP). Mean end-systolic pressure at midrange LV volume (ESPmLVV) and systolic pressure-volume area (PVA) at mLVV (PVAmLVV; a total mechanical energy per beat) were hardly changed after CP plus SNJ arrest-reperfusion (post-CP + SNJ), whereas ESPmLVV and PVAmLVV in post-CP group were significantly ( P < 0.01) decreased. Mean myocardial oxygen consumption for the total Ca2+ handling in excitation-contraction coupling did not significantly decrease in post-CP + SNJ group, whereas it was significantly ( P < 0.01) decreased in post-CP group. The mean amounts of 145- and 150-kDa fragments of α-fodrin in the post-CP group were significantly larger than those in normal and post-CP + SNJ groups. In contrast, the mean amounts of L-type Ca2+ channel and sarcoplasmic reticulum Ca2+-ATPase were not significantly different among normal, post-CP, and post-CP + SNJ groups. Our results indicate that soluble SNJ attenuates cardiac dysfunction due to CP arrest-reperfusion injury associated with the impairment of the total Ca2+ handling in excitation-contraction coupling by inhibiting the proteolysis of α-fodrin.
TRPV4-mediated endothelial Ca2+ influx and vasodilation in response to shear stress
Authors: Mendoza Suelhem A. , Fang Juan , Gutterman David D. , Wilcox David A. , Bubolz Aaron H. , Li Rongshan , Suzuki Makoto , Zhang David X.
Published: December 2009

The transient receptor potential vallinoid type 4 (TRPV4) channel has been implicated in the endothelial shear response and flow-mediated dilation, although the precise functions of this channel remain poorly understood. In the present study, we investigated the role of TRPV4 in shear stress-induced endothelial Ca2+ entry and the potential link between this signaling response and relaxation of small resistance arteries. Using immunohistochemical analysis and RT-PCR, we detected strong expression of TRPV4 protein and mRNA in the endothelium in situ and endothelial cells freshly isolated from mouse small mesenteric arteries. The selective TRPV4 agonist GSK1016790A increased endothelial Ca2+ and induced potent relaxation of small mesenteric arteries from wild-type (WT) but not TRPV4−/− mice. Luminal flow elicited endothelium-dependent relaxations that involved both nitric oxide and EDHFs. Both nitric oxide and EDHF components of flow-mediated relaxation were markedly reduced in TRPV4−/− mice compared with WT controls. Using a fura-2/Mn2+ quenching assay, shear was observed to produce rapid Ca2+ influx in endothelial cells, which was markedly inhibited by the TRPV4 channel blocker ruthenium red and TRPV4-specific short interfering RNA. Flow elicited a similar TRPV4-mediated Ca2+ entry in HEK-293 cells transfected with TRPV4 channels but not in nontransfected cells. Collectively, these data indicate that TRPV4 may be a potential candidate of mechanosensitive channels in endothelial cells through which the shear stimulus is transduced into Ca2+ signaling, leading to the release of endothelial relaxing factors and flow-mediated dilation of small resistance arteries.
Progressive muscle metaboreflex activation gradually decreases spontaneous heart rate baroreflex sensitivity during dynamic exercise
Authors: Sala-Mercado Javier A. , Ichinose Masashi , Coutsos Matthew , Li Zhenhua , Fano Dominic , Ichinose Tomoko , Dawe Elizabeth J. , O'Leary Donal S.
Published: December 2009

Ischemia of active skeletal muscle elicits a pressor response termed the muscle metaboreflex. We tested the hypothesis that in normal dogs during dynamic exercise, graded muscle metaboreflex activation (MMA) would progressively attenuate spontaneous heart rate baroreflex sensitivity (SBRS). The animals were chronically instrumented to measure heart rate (HR), cardiac output (CO), mean and systolic arterial pressure (MAP and SAP), and left ventricular systolic pressures (LVSP) at rest and during mild or moderate treadmill exercise before and during progressive MMA [via graded reductions of hindlimb blood flow (HLBF)]. SBRS [slopes of the linear relationships (LRs) between HR and LVSP or SAP during spontaneous sequences of ≥3 consecutive beats when HR changed inversely vs. pressure] decreased during mild exercise from the resting values (−5.56 ± 0.86 vs. −2.67 ± 0.50 beats·min−1·mmHg−1, P <0.05), and in addition, these LRs were shifted upward. Progressive MMA gradually and linearly increased MAP, CO, and HR; linearly decreased SBRS; and shifted LRs upward and rightward to higher HR and pressures denoting baroreflex resetting. Moderate exercise caused a substantial reduction in SBRS (−1.57 ± 0.38 beats·min−1·mmHg−1, P <0.05) and both an upward and rightward resetting. Gradual MMA at this higher workload also caused significant progressive increases in MAP, CO, and HR and progressive decreases in SBRS, and the LRs were shifted to higher MAP and HR. Our results demonstrate that gradual MMA during mild and moderate dynamic exercise progressively decreases SBRS. In addition, baroreflex control of HR is progressively reset to higher blood pressure and HR in proportion to the extent of MMA.
Mechanisms of myocardium-coronary vessel interaction
Authors: Algranati Dotan , Kassab Ghassan S. , Lanir Yoram
Published: December 2009

The mechanisms by which the contracting myocardium exerts extravascular forces (intramyocardial pressure, IMP) on coronary blood vessels and by which it affects the coronary flow remain incompletely understood. Several myocardium-vessel interaction (MVI) mechanisms have been proposed, but none can account for all the major flow features. In the present study, we hypothesized that only a specific combination of MVI mechanisms can account for all observed coronary flow features. Three basic interaction mechanisms (time-varying elasticity, myocardial shortening-induced intracellular pressure, and ventricular cavity-induced extracellular pressure) and their combinations were analyzed based on physical principles (conservation of mass and force equilibrium) in a realistic data-based vascular network. Mechanical properties of both vessel wall and myocardium were coupled through stress analysis to simulate the response of vessels to internal blood pressure and external (myocardial) mechanical loading. Predictions of transmural dynamic vascular pressure, diameter, and flow velocity were determined under each MVI mechanism and compared with reported data. The results show that none of the three basic mechanisms alone can account for the measured data. Only the combined effect of the cavity-induced extracellular pressure and the shortening-induced intramyocyte pressure provides good agreement with the majority of measurements. These findings have important implications for elucidating the physical basis of IMP and for understanding coronary phasic flow and coronary artery and microcirculatory disease.
Molecular biological effects of selective neuronal nitric oxide synthase inhibition in ovine lung injury
Authors: Saunders Fiona D. , Westphal Martin , Enkhbaatar Perenlei , Wang Jianpu , Pazdrak Konrad , Nakano Yoshimitsu , Hamahata Atsumori , Jonkam Collette C. , Lange Matthias , Connelly Rhykka L. , Kulp Gabriela A. , Cox Robert A. , Hawkins Hal K. , Schmalstieg Frank C. , Horvath Eszter , Szabo Csaba , Traber Lillian D. , Whorton Elbert , Herndon David N. , Traber Daniel L.
Published: December 2009

Neuronal nitric oxide synthase is critically involved in the pathogenesis of acute lung injury resulting from combined burn and smoke inhalation injury. We hypothesized that 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor, blocks central molecular mechanisms involved in the pathophysiology of this double-hit insult. Twenty-five adult ewes were surgically prepared and randomly allocated to 1) an uninjured, untreated sham group ( n = 7), 2) an injured control group with no treatment ( n = 7), 3) an injury group treated with 7-nitroindazole from 1-h postinjury to the remainder of the 24-h study period ( n = 7), or 4) a sham-operated group subjected only to 7-nitroindazole to judge the effects in health. The combination injury was associated with twofold increased activity of neuronal nitric oxide synthase and oxidative/nitrosative stress, as indicated by significant increases in plasma nitrate/nitrite concentrations, 3-nitrotyrosine (an indicator of peroxynitrite formation), and malondialdehyde lung tissue content. The presence of systemic inflammation was evidenced by twofold, sixfold, and threefold increases in poly(ADP-ribose) polymerase, IL-8, and myeloperoxidase lung tissue concentrations, respectively (each P < 0.05 vs. sham). These molecular changes were linked to tissue damage, airway obstruction, and pulmonary shunting with deteriorated gas exchange. 7-Nitroindazole blocked, or at least attenuated, all these pathological changes. Our findings suggest 1) that nitric oxide formation derived from increased neuronal nitric oxide synthase activity represents a pivotal reactive agent in the patho-physiology of combined burn and smoke inhalation injury and 2) that selective neuronal nitric oxide synthase inhibition represents a goal-directed approach to attenuate the degree of injury.
Targeted disruption of NF-κB1 (p50) augments cigarette smoke-induced lung inflammation and emphysema in mice: a critical role of p50 in chromatin remodeling
Authors: Rajendrasozhan Saravanan , Chung Sangwoon , Sundar Isaac K. , Yao Hongwei , Rahman Irfan
Published: December 2009

NF-κB-mediated proinflammatory response to cigarette smoke (CS) plays a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD). The heterodimer of RelA/p65-p50 (subunits of NF-κB) is involved in transactivation of NF-κB-dependent genes, but interestingly p50 has no transactivation domain. The endogenous role of p50 subunit, particularly in regulation of CS-mediated inflammation in vivo, is not known. We therefore hypothesized that p50 subunit plays a regulatory role on RelA/p65, and genetic ablation of p50 (p50−/−) leads to increased lung inflammation and lung destruction in response to CS exposure in mouse. To test this hypothesis, p50-knockout and wild-type (WT) mice were exposed to CS for 3 days to 6 mo, and inflammatory responses as well as air space enlargement were assessed. Lungs of p50-deficient mice showed augmented proinflammatory response to acute and chronic CS exposures as evidenced by increased inflammatory cell influx and proinflammatory mediators release such as monocyte chemoattractant protein-1 (MCP-1) and interferon-inducible protein-10 (IP-10) compared with WT mice. IKK2 inhibitor (IMD-0354), which reduces the nuclear translocation of RelA/p65, attenuated CS-mediated neutrophil influx in bronchoalveolar lavage fluid and cytokine (MCP-1 and IP-10) levels in lungs of WT but not in p50-deficient mice. Importantly, p50 deficiency resulted in increased phosphorylation (Ser276 and Ser536), acetylation (Lys310), and DNA binding activity of RelA/p65 in mouse lung, associated with increased chromatin remodeling evidenced by specific phosphoacetylation of histone H3 (Ser10/Lys9) and acetylation of H4 (Lys12) in response to CS exposure. Surprisingly, p50-null mice showed spontaneous air space enlargement, which was further increased after CS exposure compared with WT mice. Thus our data showed that p50 endogenously regulates the activity of RelA/p65 by decreasing its phosphoacetylation and DNA binding activity and specific histone modifications and that genetic ablation of p50 leads to air space enlargement in mouse.
Mechanisms of Ca2+-stimulated fluid secretion by porcine bronchial submucosal gland serous acinar cells
Authors: Lee Robert J. , Foskett J. Kevin
Published: December 2009

The serous acini of airway submucosal glands are important for fluid secretion in the lung. Serous cells are also sites of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl−channel. However, the mechanisms of serous cell fluid secretion remain poorly defined. In this study, serous acinar cells were isolated from porcine bronchi and studied using optical techniques previously used to examine fluid secretion in rat parotid and murine nasal acinar cells. When stimulated with the cholinergic agonist carbachol, porcine serous cells shrank by ∼20% (observed via DIC microscopy) after a profound elevation of intracellular [Ca2+] ([Ca2+]i; measured by simultaneous fura 2 fluorescence imaging). Upon removal of agonist and relaxation of [Ca2+]ito resting levels, cells swelled back to resting volume. Similar results were observed during stimulation with histamine and ATP, and elevation of [Ca2+]iwas found to be necessary and sufficient to activate shrinkage. Cell volume changes were associated with changes in [Cl−]i(measured using SPQ fluorescence), suggesting that shrinkage and swelling are caused by loss and gain of intracellular solute content, respectively, likely reflecting changes in the secretory state of the cells. Shrinkage was inhibited by niflumic acid but not by GlyH-101, suggesting Ca2+-activated secretion is mediated by alternative non-CFTR Cl−channels, possibly including Ano1 (TMEM16A), expressed on the apical membrane of porcine serous cells. Optimal cell swelling/solute uptake required activity of the Na+K+2Cl−cotransporter and Na+/H+exchanger, both of which are expressed on the basolateral membrane of serous acini and likely contribute to sustaining transepithelial secretion.