bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Potyvirus Effective Population Size in Inoculated Leaves on Viral Accumulation and the Onset of Symptoms
Authors: Zwart Mark P. , Daròs José-Antonio , Elena Santiago F.
Published: June 2012

Effective population size (

N
e

) is a key parameter for understanding evolutionary processes, but it is generally not considered in epidemiological studies or in studying infections of individual hosts. Whether

N
e

has an effect on the onset of symptoms and viral accumulation in
Tobacco etch virus
(TEV) infection of
Nicotiana tabacum
plants is considered here. Using mixtures of TEV variants carrying fluorescent markers, the dose dependence of

N
e

was confirmed, and the inoculation procedure was found to be the main source of variation in these experiments. Whereas the onset of symptoms was independent of

N
e

, there was less and more variable accumulation at 6 days postinoculation for small

N
e

values (

N
e

< 5). The observed variation in accumulation was not heritable, however, suggesting that this variation was not due to the fixation of deleterious mutations in the small founder populations. On the other hand, virus-induced fluorescence and accumulation in the inoculated leaf were strongly

N
e

dependent. Systemic accumulation was independent of

N
e

, although removal of the inoculated leaf led to a small reduction in systemic accumulation for small

N
e

values. For whole plants,

N
e

-dependent effects on accumulation were no longer observed at 9 days postinoculation. Therefore, the effects of

N
e

on accumulation are due mainly to limited expansion in the inoculated leaf and are transient. In this system,

N
e

-dependent effects will be strongest at low doses and early in infection. We conclude that

N
e

can have implications for epidemiology and infection at the individual host level, beyond determining the rate of mixed-genotype infection.
Effects of Auricular Acupressure Combined with Low-Calorie Diet on the Leptin Hormone in Obese and Overweight Iranian Individuals
Authors: Darbandi Mahsa , Darbandi Sara , Mobarhan Majid Ghayor , Owji Ali Akbar , Zhao Baxiao , Iraji Kambiz , Abdi Hamid , Saberfiroozi Mehdi , Nematy Mohsen , Safarian Mohammad , Parizadeh Mohammad Reza , Abbasi Parisa , Salehmoghadam Masoud , Fardaei Majid , Dabbaghmanesh Mohammad Hossein , Ferns Gordon , Mokarram Pooneh
Published: June 2012

Background

Human leptin is a peptide hormone that is released from white adipocytes. The absence of leptin or its receptor leads to uncontrolled food intake, leading to obesity. In the present work, the effects of auricular acupressure combined with low-calorie diet on the leptin hormone level were investigated.

Methods

Volunteers (n=86) with body mass indices (BMI) between 25 and 45 kg/m2 were randomised into a case (n=43) or a control (n=43) group. Participants in each group received a low-calorie diet for 6 weeks. The case group was treated with auricular acupressure and the control group received a sham procedure. Plasma leptin levels, body fat mass, body weight and BMI were measured before and after treatment.

Results

Participants who received auricular acupressure showed significant reductions in their plasma leptin levels (18.57%, p<0.01) as well as in their body fat mass (4%, p<0.05). These changes were not observed in the control group. The reduction in leptin was significantly greater in the acupressure group than the controls.

Conclusions

Auricular acupressure combined with a low-calorie diet significantly reduced plasma levels of leptin. However, the mechanism of this reduction is not clear.
Influence of Acupuncture on Leptin, Ghrelin, Insulin and Cholecystokinin in Obese Women: A Randomised, Sham-Controlled Preliminary Trial
Authors: Güçel Funda , Bahar Burak , Demirtas Canan , Mit Setenay , Çevik Cemal
Published: June 2012

Background

Obesity is an energy balance problem caused by overeating. Obesity treatment includes diet, exercise, behaviour treatment, pharmacotherapy and surgery; in addition, acupuncture is also an option.

Objective

To investigate the effect of acupuncture on weight loss and whether a brief acupuncture treatment of 5 weeks can change circulating levels of leptin, ghrelin, insulin and cholecystokinin (CCK) in obese women.

Methods

40 women with a body mass index (BMI)>30 kg/m2 were equally randomised to either an acupuncture group or a sham (non-penetrating) acupuncture group and received treatment at LI4, HT7, ST36, ST44 and SP6 bilaterally. Both groups had two sessions of 20 min/week for a total of 10 sessions. Serum insulin, leptin, plasma ghrelin and CCK levels were measured by ELISA.

Results

Acupuncture treatment decreased insulin and leptin levels and induced weight loss, together with a decrease in BMI compared with sham acupuncture. Furthermore, between-group analyses demonstrated increases in plasma ghrelin and CCK levels in subjects who received acupuncture treatment.

Conclusion

These findings suggest that acupuncture may help to regulate weight owing to its beneficial effects on hormones such as insulin, leptin, ghrelin and CCK in obese subjects even after a few weeks of treatment.
Anaemia and Skin Pigmentation after Excessive Cupping Therapy by An Unqualified Therapist in Korea: A Case Report
Authors: Kim Kun Hyung , Kim Tae-Hun , Hwangbo Min , Yang Gi Young
Published: June 2012

A case is reported of skin pigmentation and associated anemia resulting from persistently repeated cupping therapies performed by an unqualified practitioner in South Korea. Almost 30 sessions of excessive cupping therapies with blood loss over two months yielded little benefit but led the patient to admit a hospital and receive blood transfusion for acquired iron deficiency anemia. Skin pigmentation on the cupping-attached region remained without any subjective discomfort. We suggest the importance of qualified health professionals when receiving cupping treatments.
‘Is he awake?’: dialogues between callers and call handlers about consciousness during emergency calls for suspected acute stroke
Authors: Gibson Josephine M E , Bullock Mike , Ford Gary A , Jones Stephanie P , Leathley Michael J , McAdam Joanna J , Quinn Tom , Watkins Caroline L ,   on behalf of the ESCORTT group
Published: June 2012

Background

Altered consciousness is an important symptom of acute stroke but assessment may be challenging when cognitive or language deficits are present. Callers are routinely questioned about conscious level by emergency medical services (EMS) call handlers for any presenting problem.

Objective

This study aimed to identify and compare how patients' conscious level was questioned, described and interpreted by callers and call handlers during acute stroke calls.

Method

Audio recordings of 643 EMS calls for patients with suspected or confirmed acute stroke, admitted to one hospital in North West England over a 12-month period were retrieved from EMS recordings. Calls from primary care physicians were excluded. The caller's response to two standard questions was coded: ‘Is the patient conscious?’ and ‘Is he/she completely awake?’, and other relevant dialogue. Responses which suggested misinterpretation of terms relating to conscious level, or where the call handler used additional clarifying questions, were analysed in detail.

Results

109/643 (17%) of the calls had an altered level of consciousness recorded on the ambulance report form. Calls often contained unscripted, protracted dialogue about conscious level. Conscious level was difficult for the caller to determine, miscommunicated, or conflated with breathing difficulties.

Conclusion

Ambiguities and contradictions in dialogue about conscious level arise during ambulance calls for suspected and confirmed stroke. Further study is needed to identify whether these issues also arise in non-stroke calls, and which terms are best understood by the public in describing conscious level.
Pedestrian crossing location influences injury severity in urban areas
Authors: Rothman Linda , Howard Andrew William , Camden Andi , Macarthur Colin
Published: June 2012

Background

Pedestrian incidents represent an increasing proportion of serious injuries resulting from motor vehicle collisions in Canada. However, few studies have examined the effect of pedestrian crossing location in urban areas on injury severity. The objective of this study was to investigate the relationship between pedestrian–motor vehicle collision injury severity and crossing location.

Methods

This study was a population-based analysis of police-reported pedestrian collision data. The study group was pedestrian collisions from 1 January 2000 to 31 December 2009 in Toronto. Main outcome measures were a binary indicator of severe injury, and a four-level categorical variable of injury severity. The exposure variable was crossing at mid-block with no traffic control compared to signalised intersection. Analysis was via binary and multinomial logistic regression models to estimate ORs of injury severity with 95% CIs.

Results

The analysis included 9575 pedestrian–motor vehicle collisions, of which 7325 occurred at signalised intersections when crossing and 2230 occurred at uncontrolled mid-block locations when crossing without right of way. Uncontrolled mid-block collisions resulted in greater injury severity when controlling for road type. The odds of severe injury were 1.75 (95% CI 1.07 to 2.86) for children, 2.55 (95% CI 2.13 to 3.05) for adults and 1.68 (95% CI 1.23 to 2.28) for older adults. The odds of death at uncontrolled mid-block crossings were 4.97 (95% CI 3.11 to 7.94) in adults and 3.49 (95% CI 2.07 to 5.89) in older adults.

Conclusions

Crossing at uncontrolled mid-block locations resulted in greater injury severity compared with crossing at signalised intersections. This has important implications for pedestrian behaviour and traffic environment design and emphasises the need for safe pedestrian crossings on urban roads.
Translating road safety into health outcomes using a quantitative impact assessment model
Authors: Dhondt Stijn , Pirdavani Ali , Macharis Cathy , Bellemans Tom , Putman Koen
Published: June 2012

Introduction

The majority of traffic safety policies are limited to preventing mortality. However, non-fatal injuries also impose a significant risk of adverse health. Therefore, both mortality and morbidity outcomes should be included in the evaluation of traffic safety policies. The authors propose a method to evaluate different policy options taking into account both fatalities and serious injuries.

Methods

A health impact model was developed and aligned with a transport and road safety model, calculating the health impact of fatalities and seriously injured traffic victims for two transport scenarios in Flanders and Brussels (Belgium): a base scenario and a fuel price increase of 20% as an alternative. Victim counts were expressed as disability adjusted life years, using a combination of police and medical data. Seriously injured victims were assigned an injury, using injury distributions derived from hospital data, to estimate the resulting health impact from each crash. Health impact of fatalities was taken as the remaining life expectancy at the moment of the fatal crash.

Results

The fuel price scenario resulted in a decrease of health impact due to fatalities of 5.53%–5.85% and 3.37%–3.88% for severe injuries. This decrease was however not equal among all road users.

Conclusions

With this method, the impact of traffic polices can be evaluated on both mortality and morbidity, while taking into account the variability of different injuries following a road crash. This model however still underestimates the impact due to non-fatal injuries.
Transarterial balloon assisted Onyx embolization of pericallosal arteriovenous malformations
Authors: Orozco Ludwig D , Luzardo Gustavo D , Buciuc Razvan F
Published: June 2012

Preliminary experience using a balloon assisted technique (BAT) for embolization of arteriovenous malformations (AVM) is reported. Two patients with large pericallosal AVMs were successfully embolized with Onyx under Scepter C balloon catheter flow arrest.

Clinical presentation

One patient presented with a large intraventricular hemorrhage and hydrocephalus. The second patient presented with a long history of seizures and a small intracerebral hemorrhage. Both patients demonstrated extensive interhemispheric AVMs with multiple arterial feeders, predominantly from the pericallosal arteries.

Intervention

A Marathon microcatheter was navigated into the target arterial feeders and a Scepter C occlusion balloon catheter was inflated immediately proximal. Under flow arrest, Onyx was injected via the microcatheter with excellent nidal penetration. In both cases, there was complete angiographic obliteration of the treated component of the AVM.

Conclusions

Onyx embolization under balloon catheter flow arrest allows for greater nidal penetration of embolic material and improved reflux control. The technique is limited by the current deliverability of balloon catheters and the potential risk for earlier embolization of dangerous anastomosis.
Thermonuclear Burst Oscillations
Authors: Watts Anna L.
Published: June 2012

Burst oscillations, a phenomenon observed in a significant fraction of Type I (thermonuclear) X-ray bursts, involve the development of highly asymmetric brightness patches in the burning surface layers of accreting neutron stars. Intrinsically interesting as nuclear phenomena, they are also important as probes of dense matter physics and the strong gravity, high magnetic field environment of the neutron star surface. Burst oscillation frequency is also used to measure stellar spin, and doubles the sample of rapidly rotating (above 10 Hz) accreting neutron stars with known spins. Although the mechanism remains mysterious, burst oscillation models must take into account thermonuclear flame spread, nuclear processes, rapid rotation, and the dynamical role of the magnetic field. This review provides a comprehensive summary of the observational properties of burst oscillations, an assessment of the status of the theoretical models that are being developed to explain them, and an overview of how they can be used to constrain neutron star properties such as spin, mass, and radius.
Microlensing Surveys for Exoplanets
Authors: Gaudi B. Scott
Published: June 2012

Unlike most other planet-detection techniques, gravitational microlensing does not rely on detection of photons from either the host or the planet. Rather, planets are discovered by their gravitational perturbation of light from a more distant source. I review the fundamental concepts of microlensing planet searches and discuss their practical application. I show how the strengths and peculiarities of the method flow from the basic manner in which planets are discovered. In particular, microlensing is sensitive to very low-mass planets on wide orbits and free-floating planets, and can be used to search for planets orbiting host stars with a broad range of masses and Galactocentric distances. However, microlensing events are rare and cannot be predicted in advance, the majority of the host stars are extremely faint, and the planetary signals typically last less than a day. These strengths motivate microlensing searches as powerful, complementary probes of unexplored parameter space that have already provided important constraints on the demographics of planets beyond the “snow line.” However, the real-world challenges associated with the practical application of the method have driven the organization and evolution of the microlensing field and will continue to drive future developments from next-generation ground-based experiments through possible future space-based missions.
Observational Evidence of Active Galactic Nuclei Feedback
Authors: Fabian A.C.
Published: June 2012

Radiation, winds, and jets from the active nucleus of a massive galaxy can interact with its interstellar medium, and this can lead to ejection or heating of the gas. This terminates star formation in the galaxy and stifles accretion onto the black hole. Such active galactic nuclei (AGN) feedback can account for the observed proportionality between the central black hole and the host galaxy mass. Direct observational evidence for the radiative or quasar mode of feedback, which occurs when AGN are very luminous, has been difficult to obtain but is accumulating from a few exceptional objects. Feedback from the kinetic or radio mode, which uses the mechanical energy of radio-emitting jets often seen when AGN are operating at a lower level, is common in massive elliptical galaxies. This mode is well observed directly through X-ray observations of the central galaxies of cool core clusters in the form of bubbles in the hot surrounding medium. The energy flow, which is roughly continuous, heats the hot intracluster gas and reduces radiative cooling and subsequent star formation by an order of magnitude. Feedback appears to maintain a long-lived heating/cooling balance. Powerful, jetted radio outbursts may represent a further mode of energy feedback that affects the cores of groups and subclusters. New telescopes and instruments from the radio to X-ray bands will come into operation over the next several years and lead to a rapid expansion in observational data on all modes of AGN feedback.
Gaseous Galaxy Halos
Authors: Putman M.E. , Peek J.E.G. , Joung M.R.
Published: June 2012

Galactic halo gas traces inflowing star-formation fuel and feedback from a galaxy's disk and is therefore crucial to our understanding of galaxy evolution. In this review, we summarize the multiwavelength observational properties and origin models of Galactic and low-redshift spiral galaxy halo gas. Galactic halos contain multiphase gas flows that are dominated in mass by the ionized component and extend to large radii. The densest, coldest halo gas observed in neutral hydrogen (Hi) is generally closest to the disk (<20 kpc), and absorption line results indicate warm and warm-hot diffuse halo gas is present throughout a galaxy's halo. The hot halo gas detected is not a significant fraction of a galaxy's baryons. The disk-halo interface is where the multiphase flows are integrated into the star-forming disk, and there is evidence for both feedback and fueling at this interface from its temperature and kinematic gradients, and Hi structures.

The origin and fate of halo gas are considered in the context of cosmological and idealized local simulations. Accretion along cosmic filaments occurs in both hot (>105.5 K) and cold modes in simulations, with the compressed material close to the disk being the coldest and densest, in agreement with observations. There is evidence in halo gas observations for radiative and mechanical feedback mechanisms, including escaping photons from the disk, supernova-driven winds, and a galactic fountain. Satellite accretion also leaves behind abundant halo gas. This satellite gas interacts with the existing halo medium, and much of this gas will become part of the diffuse halo before it reaches the disk. The accretion rate from cold and warm halo gas is generally below a galaxy disk's star-formation rate, but gas at the disk-halo interface and stellar feedback may be important additional fuel sources.
Microbial Population and Community Dynamics on Plant Roots and Their Feedbacks on Plant Communities
Authors: Bever James D. , Platt Thomas G. , Morton Elise R.
Published: June 2012

The composition of the soil microbial community can be altered dramatically due to association with individual plant species, and these effects on the microbial community can have important feedbacks on plant ecology. Negative plant-soil feedback plays primary roles in maintaining plant community diversity, whereas positive plant-soil feedback may cause community conversion. Host-specific differentiation of the microbial community results from the trade-offs associated with overcoming plant defense and the specific benefits associated with plant rewards. Accumulation of host-specific pathogens likely generates negative feedback on the plant, while changes in the density of microbial mutualists likely generate positive feedback. However, the competitive dynamics among microbes depends on the multidimensional costs of virulence and mutualism, the fine-scale spatial structure within plant roots, and active plant allocation and localized defense. Because of this, incorporating a full view of microbial dynamics is essential to explaining the dynamics of plant-soil feedbacks and therefore plant community ecology.
Plant Defense Compounds: Systems Approaches to Metabolic Analysis
Authors: Kliebenstein Daniel J.
Published: June 2012

Systems biology attempts to answer biological questions by integrating across diverse genomic data sets. With the increasing ability to conduct genomics experiments, this integrative approach is being rapidly applied across numerous biological research communities. One of these research communities investigates how plants utilize secondary metabolites or defense metabolites to defend against attack by pathogens and other biotic organisms. This use of systems biology to integrate across transcriptomics, metabolomics, and genomics is significantly enhancing the rate of discovery of genes, metabolites, and bioactivities for plant defense compounds as well as extending our knowledge of how these compounds are regulated. Plant defense compounds are also providing a unique proving platform to develop new approaches that enhance the ability to conduct systems biology with existing and previously unforseen genomics data sets. This review attempts to illustrate both how systems biology is helping the study of plant defense compounds and vice versa.
Plant Immunity to Necrotrophs
Authors: Mengiste Tesfaye
Published: June 2012

Plants inhabit environments crowded with infectious microbes that pose constant threats to their survival. Necrotrophic pathogens are notorious for their aggressive and wide-ranging virulence strategies that promote host cell death and acquire nutrients for growth and reproduction from dead cells. This lifestyle constitutes the axis of their pathogenesis and virulence strategies and marks contrasting immune responses to biotrophic pathogens. The diversity of virulence strategies in necrotrophic species corresponds to multifaceted host immune response mechanisms. When effective, the plant immune system disarms the infectious necrotroph of its pathogenic arsenal or attenuates its effect, restricting further ingress and disease symptom development. Simply inherited resistance traits confer protection against host-specific necrotrophs (HSNs), whereas resistance to broad host-range necrotrophs (BHNs) is complex. Components of host genetic networks, as well as the molecular and cellular processes that mediate host immune responses to necrotrophs, are being identified. In this review, recent advances in our understanding of plant immune responses to necrotrophs and comparison with responses to biotrophic pathogens are summarized, highlighting common and contrasting mechanisms.
Minimal effect of collateral flow on coronary microvascular resistance in the presence of intermediate and noncritical coronary stenoses
Authors: Verhoeff Bart-Jan , van de Hoef Tim P. , Spaan Jos A. E. , Piek Jan J. , Siebes Maria
Published: June 2012

Depending on stenosis severity, collateral flow can be a confounding factor in the determination of coronary hyperemic microvascular resistance (HMR). Under certain assumptions, the calculation of HMR can be corrected for collateral flow by incorporating the wedge pressure (Pw) in the calculation. However, although Pw > 25 mmHg is indicative of collateral flow, Pw does in part also reflect myocardial wall stress neglected in the assumptions. Therefore, the aim of this study was to establish whether adjusting HMR by Pw is pertinent for a diagnostically relevant range of stenosis severities as expressed by fractional flow reserve (FFR). Accordingly, intracoronary pressure and Doppler flow velocity were measured a total of 95 times in 29 patients distal to a coronary stenosis before and after stepwise percutaneous coronary intervention. HMR was calculated without (HMR) and with Pw-based adjustment for collateral flow (HMRC). FFR ranged from 0.3 to 1. HMR varied between 1 and 5 and HMRC between 0.5 and 4.2 mmHg·cm−1·s. HMR was about 37% higher than HMRC for stenoses with FFR < 0.6, but for FFR > 0.8, the relative difference was reduced to 4.4 ± 3.4%. In the diagnostically relevant range of FFR between 0.6 and 0.8, this difference was 16.5 ± 10.4%. In conclusion, Pw-based adjustment likely overestimates the effect of potential collateral flow and is not needed for the assessment of coronary HMR in the presence of a flow-limiting stenosis characterized by FFR between 0.6 and 0.8 or for nonsignificant lesions.
Vascular effects of maternal alcohol consumption
Authors: Ramadoss Jayanth , Magness Ronald R.
Published: June 2012

Maternal alcohol consumption during pregnancy is a significant field of scientific exploration primarily because of its negative effects on the developing fetus, which is specifically defined as fetal alcohol spectrum disorders. Though the effects on the mother are less explored compared with those on the fetus, alcohol produces multiple effects on the maternal vascular system. Alcohol has major effects on systemic hemodynamic variables, endocrine axes, and paracrine factors regulating vascular resistance, as well as vascular reactivity. Alcohol is also reported to have significant effects on the reproductive vasculature including alterations in blood flow, vessel remodeling, and angiogenesis. Data presented in this review will illustrate the importance of the maternal vasculature in the pathogenesis of fetal alcohol spectrum disorders and that more studies are warranted in this field.
Soluble guanylyl cyclase is a target of angiotensin II-induced nitrosative stress in a hypertensive rat model
Authors: Crassous Pierre-Antoine , Couloubaly Samba , Huang Can , Zhou Zongmin , Baskaran Padmamalini , Kim David D. , Papapetropoulos Andreas , Fioramonti Xavier , Durán Walter N. , Beuve Annie
Published: June 2012

Nitric oxide (NO) by activating soluble guanylyl cyclase (sGC) is involved in vascular homeostasis via induction of smooth muscle relaxation. In cardiovascular diseases (CVDs), endothelial dysfunction with altered vascular reactivity is mostly attributed to decreased NO bioavailability via oxidative stress. However, in several studies, relaxation to NO is only partially restored by exogenous NO donors, suggesting sGC impairment. Conflicting results have been reported regarding the nature of this impairment, ranging from decreased expression of one or both subunits of sGC to heme oxidation. We showed that sGC activity is impaired by thiol S-nitrosation. Recently, angiotensin II (ANG II) chronic treatment, which induces hypertension, was shown to generate nitrosative stress in addition to oxidative stress. We hypothesized that S-nitrosation of sGC occurs in ANG II-induced hypertension, thereby leading to desensitization of sGC to NO hence vascular dysfunction. As expected, ANG II infusion increases blood pressure, aorta remodeling, and protein S-nitrosation. Intravital microscopy indicated that cremaster arterioles are resistant to NO-induced vasodilation in vivo in anesthetized ANG II-treated rats. Concomitantly, NO-induced cGMP production decreases, which correlated with S-nitrosation of sGC in hypertensive rats. This study suggests that S-nitrosation of sGC by ANG II contributes to vascular dysfunction. This was confirmed in vitro by using A7r5 smooth muscle cells infected with adenoviruses expressing sGC or cysteine mutants: ANG II decreases NO-stimulated activity in the wild-type but not in one mutant, C516A. This result indicates that cysteine 516 of sGC mediates ANG II-induced desensitization to NO in cells.
Reverse remodeling and recovery from cachexia in rats with aldosteronism
Authors: Cheema Yaser , Zhao Wenyuan , Zhao Tieqiang , Khan M. Usman , Green Kelly D. , Ahokas Robert A. , Gerling Ivan C. , Bhattacharya Syamal K. , Weber Karl T.
Published: June 2012

The congestive heart failure (CHF) syndrome with soft tissue wasting, or cachexia, has its pathophysiologic origins rooted in neurohormonal activation. Mechanical cardiocirculatory assistance reveals the potential for reverse remodeling and recovery from CHF, which has been attributed to device-based hemodynamic unloading whereas the influence of hormonal withdrawal remains uncertain. This study addresses the signaling pathways induced by chronic aldosteronism in normal heart and skeletal muscle at organ, cellular/subcellular, and molecular levels, together with their potential for recovery (Recov) after its withdrawal. Eight-week-old male Sprague-Dawley rats were examined at 4 wk of aldosterone/salt treatment (ALDOST) and following 4-wk Recov. Compared with untreated, age-/sex-/strain-matched controls, ALDOST was accompanied by 1) a failure to gain weight, reduced muscle mass with atrophy, and a heterogeneity in cardiomyocyte size across the ventricles, including hypertrophy and atrophy at sites of microscopic scarring; 2) increased cardiomyocyte and mitochondrial free Ca2+, coupled to oxidative stress with increased H2O2 production and 8-isoprostane content, and increased opening potential of the mitochondrial permeability transition pore; 3) differentially expressed genes reflecting proinflammatory myocardial and catabolic muscle phenotypes; and 4) reversal to or toward recovery of these responses with 4-wk Recov. Aldosteronism in rats is accompanied by cachexia and leads to an adverse remodeling of the heart and skeletal muscle at organ, cellular/subcellular, and molecular levels. However, evidence presented herein implicates that these tissues retain their inherent potential for recovery after complete hormone withdrawal.
Remote ischemic preconditioning prevents reduction in brachial artery flow-mediated dilation after strenuous exercise
Authors: Bailey Tom G. , Birk Gurpreet K. , Cable N. Timothy , Atkinson Greg , Green Daniel J. , Jones Helen , Thijssen Dick H. J.
Published: June 2012

Strenuous exercise is associated with an immediate decrease in endothelial function. Repeated bouts of ischemia followed by reperfusion, known as remote ischemic preconditioning (RIPC), is able to protect the endothelium against ischemia-induced injury beyond the ischemic area. We examined the hypothesis that RIPC prevents the decrease in endothelial function observed after strenuous exercise in healthy men. In a randomized, crossover study, 13 healthy men performed running exercise preceded by RIPC of the lower limbs (4 × 5-min 220-mmHg bilateral occlusion) or a sham intervention (sham; 4 × 5-min 20-mmHg bilateral occlusion). Participants performed a graded maximal treadmill running test, followed by a 5-km time trial (TT). Brachial artery endothelial function was examined before and after RIPC or sham, as well as after the 5-km TT. We measured flow-mediated dilation (FMD), an index of endothelium-dependent function, using high-resolution echo-Doppler. We also calculated the shear rate area-under-the-curve (from cuff deflation to peak dilatation; SRAUC). Data are described as mean and 95% confidence intervals. FMD changed by <0.6% immediately after both ischemic preconditioning (IPC) and sham interventions ( P > 0.30). In the sham trial, FMD changed from 5.1 (4.4–5.9) to 3.7% (2.6–4.8) following the 5-km TT ( P = 0.02). In the RIPC trial, FMD changed negligibly from 5.4 (4.4–6.4) post-IPC and 5.7% (4.6–6.8) post 5-km TT ( P = 0.60). Baseline diameter, SRAUC, and time-to-peak diameter were all increased following the 5-km TT ( P < 0.05), but these changes did not influence the IPC-mediated maintenance of FMD. In conclusion, these data indicate that strenuous lower-limb exercise results in an acute decrease in brachial artery FMD of ∼1.4% in healthy men. However, we have shown for the first time that prior RIPC of the lower limbs maintains postexercise brachial artery endothelium-dependent function at preexercise levels.
Interferon-γ ablation exacerbates myocardial hypertrophy in diastolic heart failure
Authors: Garcia Anthony G. , Wilson Richard M. , Heo Joline , Murthy Namita R. , Baid Simoni , Ouchi Noriyuki , Sam Flora
Published: June 2012

Diastolic heart failure (HF) accounts for up to 50% of all HF admissions, with hypertension being the major cause of diastolic HF. Hypertension is characterized by left ventricular (LV) hypertrophy (LVH). Proinflammatory cytokines are increased in LVH and hypertension, but it is unknown if they mediate the progression of hypertension-induced diastolic HF. We sought to determine if interferon-γ (IFNγ) plays a role in mediating the transition from hypertension-induced LVH to diastolic HF. Twelve-week old BALB/c (WT) and IFNγ-deficient (IFNγKO) mice underwent either saline ( n = 12) or aldosterone ( n = 16) infusion, uninephrectomy, and fed 1% salt water for 4 wk. Tail-cuff blood pressure, echocardiography, and gene/protein analyses were performed. Isolated adult rat ventricular myocytes were treated with IFNγ (250 U/ml) and/or aldosterone (1 μM). Hypertension was less marked in IFNγKO-aldosterone mice than in WT-aldosterone mice (127 ± 5 vs. 136 ± 4 mmHg; P < 0.01), despite more LVH (LV/body wt ratio: 4.9 ± 0.1 vs. 4.3 ± 0.1 mg/g) and worse diastolic dysfunction (peak early-to-late mitral inflow velocity ratio: 3.1 ± 0.1 vs. 2.8 ± 0.1). LV ejection fraction was no different between IFNγKO-aldosterone vs. WT-aldosterone mice. LV end systolic dimensions were decreased significantly in IFNγKO-aldosterone vs. WT-aldosterone hearts (1.12 ± 0.1 vs. 2.1 ± 0.3 mm). Myocardial fibrosis and collagen expression were increased in both IFNγKO-aldosterone and WT-aldosterone hearts. Myocardial autophagy was greater in IFNγKO-aldosterone than WT-aldosterone mice. Conversely, tumor necrosis factor-α and interleukin-10 expressions were increased only in WT-aldosterone hearts. Recombinant IFNγ attenuated cardiac hypertrophy in vivo and modulated aldosterone-induced hypertrophy and autophagy in cultured cardiomyocytes. Thus IFNγ is a regulator of cardiac hypertrophy in diastolic HF and modulates cardiomyocyte size possibly by regulating autophagy. These findings suggest that IFNγ may mediate adaptive downstream responses and challenge the concept that inflammatory cytokines mediate only adverse effects.
Electroporation induced by internal defibrillation shock with and without recovery in intact rabbit hearts
Authors: Wang Yves T. , Efimov Igor R. , Cheng Yuanna
Published: June 2012

Defibrillation shocks from implantable cardioverter defibrillators can be lifesaving but can also damage cardiac tissues via electroporation. This study characterizes the spatial distribution and extent of defibrillation shock-induced electroporation with and without a 45-min postshock period for cell membranes to recover. Langendorff-perfused rabbit hearts ( n = 31) with and without a chronic left ventricular (LV) myocardial infarction (MI) were studied. Mean defibrillation threshold (DFT) was determined to be 161.4 ± 17.1 V and 1.65 ± 0.44 J in MI hearts for internally delivered 8-ms monophasic truncated exponential (MTE) shocks during sustained ventricular fibrillation (>20 s, SVF). A single 300-V MTE shock (twice determined DFT voltage) was used to terminate SVF. Shock-induced electroporation was assessed by propidium iodide (PI) uptake. Ventricular PI staining was quantified by fluorescent imaging. Histological analysis was performed using Masson's Trichrome staining. Results showed PI staining concentrated near the shock electrode in all hearts. Without recovery, PI staining was similar between normal and MI groups around the shock electrode and over the whole ventricles. However, MI hearts had greater total PI uptake in anterior ( P < 0.01) and posterior ( P < 0.01) LV epicardial regions. Postrecovery, PI staining was reduced substantially, but residual staining remained significant with similar spacial distributions. PI staining under SVF was similar to previously studied paced hearts. In conclusion, electroporation was spatially correlated with the active region of the shock electrode. Additional electroporation occurred in the LV epicardium of MI hearts, in the infarct border zone. Recovery of membrane integrity postelectroporation is likely a prolonged process. Short periods of SVF did not affect electroporation injury.
Differential effect of central command on aortic and carotid sinus baroreceptor-heart rate reflexes at the onset of spontaneous, fictive motor activity
Authors: Matsukawa Kanji , Ishii Kei , Kadowaki Akito , Liang Nan , Ishida Tomoko
Published: June 2012

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in conscious cats and spontaneous contraction in decerebrate cats. The purpose of this study was to examine whether central command attenuates the sensitivity of the carotid sinus baroreceptor-HR reflex at the onset of spontaneous, fictive motor activity in paralyzed, decerebrate cats. We confirmed that aortic nerve (AN)-stimulation-induced bradycardia was markedly blunted to 26 ± 4.4% of the control (21 ± 1.3 beats/min) at the onset of spontaneous motor activity. Although the baroreflex bradycardia by electrical stimulation of the carotid sinus nerve (CSN) was suppressed ( P < 0.05) to 86 ± 5.6% of the control (38 ± 1.2 beats/min), the inhibitory effect of spontaneous motor activity was much weaker ( P < 0.05) with CSN stimulation than with AN stimulation. The baroreflex bradycardia elicited by brief occlusion of the abdominal aorta was blunted to 36% of the control (36 ± 1.6 beats/min) during spontaneous motor activity, suggesting that central command is able to inhibit the cardiomotor sensitivity of arterial baroreflexes as the net effect. Mechanical stretch of the triceps surae muscle never affected the baroreflex bradycardia elicited by AN or CSN stimulation and by aortic occlusion, suggesting that muscle mechanoreflex did not modify the cardiomotor sensitivity of aortic and carotid sinus baroreflex. Since the inhibitory effect of central command on the carotid baroreflex pathway, associated with spontaneous motor activity, was much weaker compared with the aortic baroreflex pathway, it is concluded that central command does not force a generalized modulation on the whole pathways of arterial baroreflexes but provides selective inhibition for the cardiomotor component of the aortic baroreflex.
Free hemoglobin induction of pulmonary vascular disease: evidence for an inflammatory mechanism
Authors: Buehler Paul W. , Baek Jin Hyen , Lisk Christina , Connor Ian , Sullivan Tim , Kominsky Douglas , Majka Susan , Stenmark Kurt R. , Nozik-Grayck Eva , Bonaventura Joe , Irwin David C.
Published: June 2012

Cell-free hemoglobin (Hb) exposure may be a pathogenic mediator in the development of pulmonary arterial hypertension (PAH), and when combined with chronic hypoxia the potential for exacerbation of PAH and vascular remodeling is likely more pronounced. We hypothesized that Hb may contribute to hypoxia-driven PAH collectively as a prooxidant, inflammatory, and nitric oxide (NO) scavenger. Using programmable micropump technology, we exposed male Sprague-Dawley rats housed under room air or hypoxia to 12 or 30 mg per day Hb for 3, 5, and 7 wk. Blood pressure, cardiac output, right ventricular hypertrophy, and indexes of pulmonary vascular remodeling were evaluated. Additionally, markers of oxidative stress, NO bioavailability and inflammation were determined. Hb increased pulmonary arterial (PA) pressure, pulmonary vessel wall stiffening, and right heart hypertrophy with temporal and dose dependence in both room air and hypoxic cohorts. Hb induced a modest increase in plasma oxidative stress markers (malondialdehyde and 4-hydroxynonenal), no change in NO bioavailability, and increased lung ICAM protein expression. Treatment with the antioxidant Tempol attenuated Hb-induced pulmonary arterial wall thickening, but not PA pressures or ICAM expression. Chronic exposure to low plasma Hb concentrations (range = 3–10 μM) lasting up to 7 wk in rodents induces pulmonary vascular disease via inflammation and to a lesser extent by Hb-mediated oxidation. Tempol demonstrated a modest effect on the attenuation of Hb-induced pulmonary vascular disease. NO bioavailability was found to be of minimal importance in this model.
Effect of length oscillations on airway smooth muscle reactivity and cross-bridge cycling
Authors: Al-Jumaily Ahmed M. , Mbikou Prisca , Redey Prachi R.
Published: June 2012

Excessive airway narrowing due to airway smooth muscle (ASM) hyperconstriction is a major symptom in many respiratory diseases. In vitro imposition of length oscillations similar to those produced by tidal breathing on contracted ASM have shown to reduce muscle active forces, which is usually attributed to unconfirmed disruption of actomyosin cross-bridges. This research focuses on an in vitro investigation of the effect of mechanical oscillations on ASM reactivity and actomyosin cross-bridges. A computerized organ bath system was used to test maximally precontracted bovine ASM subjected to length oscillations at frequencies in the range of 10–100 Hz superimposed on tidal breathing oscillation. Using an immunofluorescence technique, two specific antibodies against the phospho-serine19 myosin light chain and the α-smooth muscle actin were used to analyze the colocalization between these two filaments. Data were processed using the plug-in “colocalization threshold” of ImageJ 1.43m software. The results demonstrate that both tidal and superimposed length oscillations reduce the active force in contracted ASM for a relatively long term and that the latter enhances the force reduction of the former. This reduction was also found to be frequency and time dependent. Additionally colocalization analysis indicates that length oscillations cause the detachment of the actomyosin connections and that this condition is sustained even after the cessation of the length oscillations.
TNFR1-dependent pulmonary apoptosis during ischemic acute kidney injury
Authors: White Laura E. , Santora Rachel J. , Cui Yan , Moore Frederick A. , Hassoun Heitham T.
Published: June 2012

Despite advancements in renal replacement therapy, the mortality rate for acute kidney injury (AKI) remains unacceptably high, likely due to remote organ injury. Kidney ischemia-reperfusion injury (IRI) activates cellular and soluble mediators that incite a distinct pulmonary proinflammatory and proapoptotic response. Tumor necrosis factor receptor 1 (TNFR1) has been identified as a prominent death receptor activated in the lungs during ischemic AKI. We hypothesized that circulating TNF-α released from the postischemic kidney induces TNFR1-mediated pulmonary apoptosis, and we aimed to elucidate molecular pathways to programmed cell death. Using an established murine model of kidney IRI, we characterized the time course for increased circulatory and pulmonary TNF-α levels and measured concurrent upregulation of pulmonary TNFR1 expression. We then identified TNFR1-dependent pulmonary apoptosis after ischemic AKI using TNFR1−/− mice. Subsequent TNF-α signaling disruption with Etanercept implicated circulatory TNF-α as a key soluble mediator of pulmonary apoptosis and lung microvascular barrier dysfunction during ischemic AKI. We further elucidated pathways of TNFR1-mediated apoptosis with NF-κB (Complex I) and caspase-8 (Complex II) expression and discovered that TNFR1 proapoptotic signaling induces NF-κB activation. Additionally, inhibition of NF-κB (Complex I) resulted in a proapoptotic phenotype, lung barrier leak, and altered cellular flice inhibitory protein signaling independent of caspase-8 (Complex II) activation. Ischemic AKI activates soluble TNF-α and induces TNFR1-dependent pulmonary apoptosis through augmentation of the prosurvival and proapoptotic TNFR1 signaling pathway. Kidney-lung crosstalk after ischemic AKI represents a complex pathological process, yet focusing on specific biological pathways may yield potential future therapeutic targets.
Microparticles and acute lung injury
Authors: McVey Mark , Tabuchi Arata , Kuebler Wolfgang M.
Published: June 2012

The pathophysiology of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), is characterized by increased vascular and epithelial permeability, hypercoagulation and hypofibrinolysis, inflammation, and immune modulation. These detrimental changes are orchestrated by cross talk between a complex network of cells, mediators, and signaling pathways. A rapidly growing number of studies have reported the appearance of distinct populations of microparticles (MPs) in both the vascular and alveolar compartments in animal models of ALI/ARDS or respective patient populations, where they may serve as diagnostic and prognostic biomarkers. MPs are small cytosolic vesicles with an intact lipid bilayer that can be released by a variety of vascular, parenchymal, or blood cells and that contain membrane and cytosolic proteins, organelles, lipids, and RNA supplied from and characteristic for their respective parental cells. Owing to this endowment, MPs can effectively interact with other cell types via fusion, receptor-mediated interaction, uptake, or mediator release, thereby acting as intrinsic stimulators, modulators, or even attenuators in a variety of disease processes. This review summarizes current knowledge on the formation and potential functional role of different MPs in inflammatory diseases with a specific focus on ALI/ARDS. ALI has been associated with the formation of MPs from such diverse cellular origins as platelets, neutrophils, monocytes, lymphocytes, red blood cells, and endothelial and epithelial cells. Because of their considerable heterogeneity in terms of origin and functional properties, MPs may contribute via both harmful and beneficial effects to the characteristic pathological features of ALI/ARDS. A better understanding of the formation, function, and relevance of MPs may give rise to new promising therapeutic strategies to modulate coagulation, inflammation, endothelial function, and permeability either through removal or inhibition of “detrimental” MPs or through administration or stimulation of “favorable” MPs.
Lipid Storage Myopathy in Behçet's Disease: A Rare Cause of Elevated Serum Creatine Kinases Levels
Authors: Yilmaz Sedat , Cinar Muhammet , Karslioglu Yıldırım , Simsek Ismail , Erdem Hakan , Pay Salih , Dinc Ayhan
Published: June 2012

Muscular involvement in Behçet’s disease is rare and there are only a few case reports in the literature. The causes of elevated muscle enzymes in a patient with Behcet’s disease are many, including myositis, drug-induced myopathy, metabolic myopathy, and the disease itself. We herein have defined an algorithmic approach to a patient with Behcet’s disease and elevated muscle enzymes and report a case of coexisting of lipid storage myopathy.
Stat3 Inhibition Augments the Immunogenicity of B-cell Lymphoma Cells, Leading to Effective Antitumor Immunity
Authors: Cheng Fengdong , Wang Hongwei , Horna Pedro , Wang Zi , Shah Bijal , Sahakian Eva , Woan Karrune V. , Villagra Alejandro , Pinilla-Ibarz Javier , Sebti Said , Smith Mitchell , Tao Jianguo , Sotomayor Eduardo M.
Published: June 2012

Mantle cell lymphoma (MCL) is an aggressive and incurable subtype of B-cell non–Hodgkin lymphomas. Although patients often respond initially to first-line treatment with chemotherapy plus monoclonal antibodies, relapse and decreased response to further lines of treatment eventually occurs. Harnessing the immune system to elicit its exquisite specificity and long-lasting protection might provide sustained MCL immunity that could potentially eradicate residual malignant cells responsible for disease relapse. Here, we show that genetic or pharmacologic disruption of Stat3 in malignant B cells augments their immunogenicity leading to better activation of antigen-specific CD4+ T cells and restoration of responsiveness of tolerized T cells. In addition, treatment of MCL-bearing mice with a specific Stat3 inhibitor resulted in decreased Stat3 phosphorylation in malignant B cells and anti-lymphoma immunity in vivo. Our findings therefore indicate that Stat3 inhibition may represent a therapeutic strategy to overcome tolerance to tumor antigens and elicit a strong immunity against MCL and other B-cell malignancies. Cancer Res; 72(17); 4440–8. ©2012 AACR.