bluuebunny/crossref_metadata_2025 huggingface dataset:
Is there a gender difference in concussion incidence and outcomes?
Authors: Dick R W
Published: May 2009

Objective:

To determine if there is a gender difference in the incidence and outcomes of sport concussion.

Design:

Critical literature review of sport concussion by gender.

Intervention:

PubMed and major sports medicine journals were reviewed using the keywords concussion and gender. Articles included in this paper were English prospective surveillance that included concussion as an injury option conducted over the past 10 years, involved data collected by qualified medical personnel (athletic trainers/therapists or medical doctors) and used injury rates as opposed to raw counts. Only data from sports (soccer, basketball and ice hockey) where actions, equipment and most rules were similar between genders were reviewed.

Results:

For the PubMed search, using “concussion” and “gender” as keywords, there were 51 articles. Ten studies (four in football (soccer), four in basketball and two in ice hockey, including high school, college and professional athletes) were included in the incidence portion of the paper. Nine of the studies showed higher absolute injury rates for female concussion compared to their male counterparts with four of them reaching statistical significance. Five of the studies (two football (soccer), two basketball and one ice hockey) examined concussion mechanism and in all cases, males had a higher absolute percent of player contact concussions while females had a higher absolute percentage of surface or ball contact concussion episodes. Two brain injury and four sport concussion outcome papers were reviewed. Traumatic brain injury outcome was shown to be worse in females than in males for a majority of measured variables; females also are shown to have different baseline and post-concussion outcomes on neuropsychological testing.

Conclusions:

After evaluating multiple years of concussion data in comparable sports, the evidence indicates that female athletes may be at greater risk for concussion than their male counterparts. There also is some evidence that gender differences exist in outcomes of traumatic brain injury and concussions. Because concussion is a clinical diagnosis often depending on self reporting and with no established biological marker or consistent symptoms/definitions, and because there is evidence that females are more honest in reporting general injuries than males, it is unclear whether the concussion incidence data, while generally consistent in showing a higher risk in females as compared to males in similar sports, is a true difference or is influenced by a reporting bias.
Knowledge transfer principles as applied to sport concussion education
Authors: Provvidenza C F , Johnston K M
Published: May 2009

Objective:

To (a) examine knowledge transfer literature and optimal learning needs as applied to healthcare professionals, coaches and student athletes; (b) apply the practice of knowledge transfer to sport concussion education resources; and (c) identify needs and make recommendations for optimising concussion education.

Design:

Qualitative literature review of knowledge transfer and concussion education literature.

Intervention:

Pubmed, Medline, Psych Info and Sport Discus databases were reviewed. 52 journal articles, 20 websites and 2 books were reviewed.

Results:

The methods in which individuals experience optimal learning varies and should be considered when developing effective concussion education strategies. Physician knowledge and performance are impacted by education outreach, interaction and reminder messages. Educational strategies associated with optimal learning for physio and athletic therapists include problem and evidence-based practice, socialisation and peer-assisted learning. From a coaching perspective, research supports the reflective process as a learning modality. Student athletes have strengths and weaknesses in different areas and so perform differently on activities requiring distinct strategies. Knowing the impact of sport concussion resources on knowledge enhancement and modifying attitudes and behaviours toward concussion requires evaluation strategies. Review of concussion resources using the perspective of knowledge transfer and methods for improvement is discussed.

Conclusions:

Knowledge transfer is a relatively new concept in sports medicine and its influence on enhancing concussion education is not well known. The needs and optimal learning styles of target audiences coupled with evaluation need to be a piece of the overall concussion education puzzle to effectively impact knowledge of and attitudes and behaviours towards sport concussion.
Effect of household passive smoking exposure on the risk of ischaemic heart disease in never-smoke female patients in Hong Kong
Authors: Ding D , Wing-Hong Fung J , Zhang Q , Wai-Kwok Yip G , Chan C-K , Yu C-M
Published: May 2009

Objective:

To investigate the relation between household passive smoking exposure and risk of ischaemic heart disease (IHD) among never-smoke female patients by a retrospective case-control analysis.

Methods:

This study recruited 314 patients with IHD who had never smoked and 319 controls who were admitted for other reasons in the same hospital during the same period. Subjects were interviewed about their exposure to household passive smoking. The dose metrics of passive smoking exposure were evaluated by using “pack years” and “hour years”, which indicated the cumulative amount and duration of exposure. The ORs and 95% CIs were computed by unconditional logistic regression, adjusted for other risk factors.

Results:

Subjects with passive smoking exposure were associated with higher risk of IHD (OR 1.51, 95% CI 1.01 to 2.27, p = 0.043) when compared to non-exposed subjects. Subjects exposed to an average of ⩾1 pack of cigarette per day had an OR of 1.69 (95% CI 1.07 to 2.68, p = 0.025). The OR was 1.52 for those exposed for ⩾5 years (95% CI 1.01 to 2.29, p = 0.043) and was 1.82 for those exposed ⩾4 h per day (95% CI 1.05 to 3.15, p = 0.032). Similarly, the risk of IHD increased with cumulative exposure duration, with an OR of 1.53 (95% CI 1.01 to 2.32, p = 0.043) at the exposure level ⩾5 pack years, and an OR of 1.61 (95% CI 1.03 to 2.52, p = 0.037) at the exposure level ⩾20 hour years. There was a significant dose-response association between the exposure measures and risk of IHD (p<0.01 for trend).

Conclusion:

Our data suggested an increased risk of IHD from passive household smoking in female never-smoke subjects, and demonstrated a dose-response association.
LORENTZ BOOSTED NUCLEON-NUCLEON T-MATRIX AND THE TRITON BINDING ENERGY
Authors: KAMADA H. , GLÖCKLE W. , WITAŁA H. , GOLAK J. , SKIBIŃSKI R. , POLYZOU W. N. , ELSTER CH.
Published: May 2009

The phase equivalent relativistic NN potential, which is related by a nonlinear equation to the original nonrelativistic potential, is used to construct the mass operator (rest Hamiltonian) of the 3-nucleon system. Employing the CD Bonn NN potential, the solution of the relativistic 3N Faddeev equation for 3 H shows slightly less binding energy than the corresponding nonrelativistic result. The effect of the Wigner spin rotation on the binding is very small.
FEW-NUCLEON STUDIES AT INTERMEDIATE ENERGIES
Authors: MESSCHENDORP J. G.
Published: May 2009

Observables in proton-deuteron scattering are sensitive probes of the nucleon-nucleon interaction and three-nucleon force effects. Several facilities, including the KVI, allow a detailed study of few-nucleon interactions below the pion-production threshold exploiting polarized proton and deuteron beams. In this contribution, some recent results are discussed and interpreted exploiting rigorous Faddeev calculations. Furthermore, experimental inconsistencies between two measurements of the cross section in elastic proton-deuteron scattering at 135 MeV/nucleon are reviewed.
PARITY VIOLATION IN $d\vec \gamma \to np$ WITH PIONLESS EFFECTIVE THEORY
Authors: HYUN CHANG HO , SHIN JAE WON , ANDO SHUNG-ICHI
Published: May 2009

We consider a pionless effective theory with dibaryon fields for the description of the weak process involving two nucleons. We construct leading order Lagrangians that contain nucleon-dibaryon weak coupling constants. We calculate the physical observable in the photodisintegration of the deuteron at threshold and obtain the result in terms of the nucleon-dibaryon weak coupling constants. Relation to existing calculations is discussed.
MEASUREMENT AND RE-ANALYSIS OF TENSOR ANALYZING POWER OF pd RADIATIVE CAPTURE AT RCNP
Authors: SAGARA KENSHI , TAMESHIGE Y. , HATANAKA K. , KUROITA S. , MATSUBARA H. , FUJITA K. , SHIMIZU Y. , KAWABATA T. , MAEDA Y. , SAKEMI Y. , OKAMURA H. , SEKIGUCHI K. , TAMII A. , WAKASA T.
Published: May 2009

We made again an experiment of pd radiative capture at [Formula: see text], and obtained Axx, Ayy and Azz (= -Axx - Ayy) data using a newly-developed data-analysis method of high detection efficiency. Re-analysis of previous data on Axx and Ayy was also made using a new method. All the new and previous data at 197 MeV agree to each other, and Axx anomaly has been confirmed.
OFF-SHELL EFFECTS IN FEW-BODY SYSTEMS WITH COULOMB FORCE
Authors: ORYU SHINSHO , HIRATSUKA YASUHISA , NISHINOHARA SATOSHI , CHIBA SATOSHI
Published: May 2009

The exact treatment of the two-body problem in momentum space in the presence of Coulomb forces is discussed. Convergence of the traditionally used renormalization approximation is investigated with respect to increasing ranges of the screened Coulomb potentials. The permissible energy range for this approximation is obtained for the first time in this work.
PRODUCTION OF DOUBLE STRANGENESS HYPERNUCLEI IN 12C(K-,K+) REACTION AT 1.67 GeV/c
Authors:   FOR THE KEK-PS E522 COLLABORATION, CHOI B. H. , KIM S. J. , AHN J. K. , MIWA K. , YOON C. J. , IMAI K.
Published: May 2009

We have measured (K-,K+) reaction at 1.67 GeV/cK- at the KEK proton synchrotron. A scintillating fiber active target was employed to view both secondary interactions and decays of particles produced in the (K-,K+) reaction. This tracking capability for the vertex region provides us for studying the fate of Ξ- hypernuclei, which is advantageous over the previous two experiments. We present a preliminary result on the production cross sections for [Formula: see text], and also on the branching fractions into the decay modes with charged particles and/or Λ hyperon(s).
3He(K-, n) REACTION SPECTRUM NEAR THE $\bar KN \to \pi \sum $ DECAY THRESHOLD AND THE DEEPLY-BOUND K-pp STATE
Authors: KOIKE TAKAHISA , HARADA TORU
Published: May 2009

The formation of a deeply-bound K-pp state by the 3 He ( in - flight K-, n) reaction is investigated theoretically in a distorted-wave impulse approximation using the Green's function method. The expected inclusive and semi-exclusive spectra at pK- = 1.0 GeV / c and θn = 0° are calculated for the forthcoming J-PARC E15 experiment. We discuss these spectra with some K--"pp" optical potentials, taking into account the energy-dependence of the imaginary part of the potentials by a phase space suppression factor.
NUCLEAR CLUSTERS WITH HALO EFFECTIVE FIELD THEORY
Authors: HIGA RENATO
Published: May 2009

After a brief discussion of effective field theory applied to nuclear clusters, I present the aspect of Coulomb interactions, with applications to low-energy alpha-alpha and nucleon-alpha scattering.
ELECTROMAGNETIC PROCESSES IN χEFT
Authors: PASTORE S. , SCHIAVILLA R. , GOITY J. L.
Published: May 2009

Nuclear electromagnetic currents derived in a chiral-effective-field-theory framework including explicit nucleons, Δ isobars, and pions up to N2LO, i.e. ignoring loop corrections, are used in a study of neutron radiative captures on protons and deuterons at thermal energies, and of A=2 and 3 nuclei magnetic moments. With the strengths of the Δ-excitation currents determined to reproduce the n-p cross section and isovector combination of the trinucleon magnetic moments, we find that the cross section and photon circular polarization parameter, measured respectively in n-d and [Formula: see text] processes, are significantly underpredicted by theory.
ANALYSIS OF PION WEAK-PRODUCTION NEAR THRESHOLD BY MULTIPOLE AMPLITUDES
Authors: CHEOUN MYUNG-KI , KIM K. S.
Published: May 2009

By exploiting the chiral Ward identities based on the QCD Lagrangian for pion weak production, we derive a transition amplitude by the weak current and show analytical results of relevant multipole amplitudes without any expansion. Their physical implications and numerical results are also discussed.
πK INTERACTION EFFECTS ON CP VIOLATION IN B → Kπ+π- DECAYS
Authors: LOISEAU B. , EL-BENNICH B. , FURMAN A. , KAMIŃSKI R. , LEŚNIAK L. , MOUSSALLAM B.
Published: May 2009

We apply QCD factorization to the quasi two-body B → (Kπ)π decays where the (Kπ)-pair effective mass is limited to 1.8 GeV. Our strong interaction phases constrained by theory and πK experimental data yield useful information for studies of CP violation.
PROGRESS ON FEW-BODY CALCULATIONS: THE ROLE OF TENSOR FORCE
Authors: HORIUCHI WATARU , SUZUKI YASUYUKI
Published: May 2009

One of the methods to obtain a precise solution of a few-body equation is to expand the orbital part of the wave function into the correlated Gaussian with double global vectors. In this contribution, we report our recent studies applying this method to light nuclei, (i) excited states of 4 He and (ii) two-nucleon momentum distribution in 6 He and 6 Li , especially focusing on the importance of the tensor force.
A NEW HYPERCENTERAL POTENTIAL TO STUDY A NONRELATIVISTIC N-BODY SYSTEM
Authors: HASSANABADI H. , RAJABI A. A.
Published: May 2009

The Hyperspherical coordinates method (HCM), allows one to obtain the spectrum of the system and develop the classification of excited states. We have solved the radial Schrödinger wave equation exactly in three dimensions for an N -body problem. Using the obtained results, we have studied the N family baryon masses.
NEUTRINO ENERGY LOSS AT MATTER-RADIATION DECOUPLING PHASE
Authors: IBRAHIM UNGKU FERWANI SALWA UNGKU , AHMAD NOR SOFIAH , YUSOF NORHASLIZA , KASSIM HASAN ABU
Published: May 2009

Neutrinos are produced copiously in the early universe. Neutrinos and antineutrinos ceased to be in equilibrium with radiation when the weak interaction rate becomes slower than the rate expansion of the universe. The ratio of the temperature of the photon to the temperature of the neutrino at this stage is Tγ/Tν = (11/4)1/3. We investigate the neutrino energy loss due to the oscillation of the electron neutrino into a different flavor in the charged-current interaction of νe-e- based on the work of Sulaksono and Simanjuntak. The energy loss from the neutrinos ΔEν during the decoupling of the neutrinos with the rest of the matter would be a gain in the energy of the electrons and can be obtained from the integration of stopping power equation ΔEν = (dEν/dT-1)dT-1 where Eν and T are the energy of the neutrinos and the temperature respectively. When the universe expands and matter-radiation decouples, an extra energy will be transferred to the photons via the annihilation of the electron-positron pairs, e++e-→γ+γ. This consequently will increase the temperature of the photons. The net effect to the lowest order is an increase in the ratio of the photon temperature to the neutrino temperature. The magnitude of energy loss of the neutrino is ∼10-4-10-5 MeV for the probability of conversion of νe → νi (i = μ,τ) between 0 to 1.0.
Women in Parliaments: Descriptive and Substantive Representation
Authors: Wängnerud Lena
Published: May 2009

This essay reviews two research programs. The first focuses on variations in the number of women elected to national parliaments in the world (descriptive representation), and the second focuses on effects of women's presence in parliament (substantive representation). The theory of the politics of presence (Phillips 1995) provides reasons for expecting a link between descriptive and substantive representation. The safest position would be to say that results are “mixed” when it comes to empirical support for the theory of the politics of presence. However, when a large number of studies covering a wide set of indicators on the importance of gender in the parliamentary process are piled together, the picture that emerges shows that female politicians contribute to strengthening the position of women's interests.
Experiments on Racial Priming in Political Campaigns
Authors: Hutchings Vincent L. , Jardina Ashley E.
Published: May 2009

Since the first half of the twentieth century, whites have become much more accepting of the principle of racial equality even as they have continued to endorse negative racial stereotypes about African-Americans. Some scholars argue that this ambivalence has been exploited by contemporary political elites who have learned to fashion subtle racial appeals that activate these latent attitudes without appearing to violate widely held norms of racial equality. This strategy has been dubbed racial priming. In this brief article, we summarize and evaluate the work in this area, with a particular emphasis on studies that employ experimental research designs.
Sepiapterin reductase regulation of endothelial tetrahydrobiopterin and nitric oxide bioavailability
Authors: Gao Ling , Pung Yuh-Fen , Zhang Jun , Chen Peng , Wang Ting , Li Min , Meza Miguel , Toro Ligia , Cai Hua
Published: May 2009

Sepiapterin reductase (SPR) catalyzes the final step of tetrahydrobiopterin (H4B) biosynthesis and the first step of H4B regeneration from an exogenous precursor sepiapterin. Despite the potential significance of SPR in regulating H4B-dependent nitric oxide (NO•) production, the endothelium-specific sequence and functions of SPR remain elusive. We first cloned endothelial SPR cDNA from bovine aortic endothelial cells (Genebank: DQ978331). In cells transiently transfected with SPR gene, SPR activity (HPLC) was dramatically increased by 19-fold, corresponding to a significant increase in endothelial H4B content (HPLC) and NO•production (electron spin resonance). In vivo delivery of SPR gene significantly increased vascular SPR protein expression (mouse vs. bovine antibodies to differentiate endogenous vs. exogenous), activity, H4B content, and NO•production, as well as NO•-dependent vasorelaxation. In endothelial cells transfected with small interfering RNA specific for SPR, ∼87% of mRNA were attenuated (real-time quantitative RT-PCR), corresponding to a significant reduction in SPR protein expression and activity, which was associated with decreases in both intracellular H4B content and NO•level. Exogenous administration of sepiapterin to endothelial cells significantly upregulated H4B and NO•levels, which were attenuated by SPR RNA interference (RNAi). H4B-stimulated increase in NO•production, however, was SPR RNAi independent. GTP cyclohydrolase 1 expression and activity, as well as dihydrofolate reductase expression, were not affected by SPR RNAi, whereas dihydrofolate reductase activity was significantly downregulated. These data represent the first to study endothelial SPR functionally and clearly demonstrate an important role of endothelial SPR in modulating H4B and NO•bioavailability.
NO production and eNOS phosphorylation induced by epinephrine through the activation of β-adrenoceptors
Authors: Figueroa Xavier F. , Poblete Inés , Fernández Ricardo , Pedemonte Cristóbal , Cortés Víctor , Huidobro-Toro J. Pablo
Published: May 2009

Epinephrine plays a key role in the control of vasomotor tone; however, the participation of the NO/cGMP pathway in response to β-adrenoceptor activation remains controversial. To evaluate the involvement of the endothelium in the vascular response to epinephrine, we assessed NO production, endothelial NO synthase phosphorylation, and tissue accumulation of cGMP in the perfused arterial mesenteric bed of rat. Epinephrine elicited a concentration-dependent increase in NO (EC50of 45.7 pM), which was coupled to cGMP tissue accumulation. Both NO and cGMP production were blocked by either endothelium removal (saponin) or NO synthase inhibition ( Nω-nitro-l-arginine). Blockade of β1- and β2-adrenoceptors with 1 μM propranolol or β3-adrenoceptor with 10 nM SR 59230A displaced rightward the concentration-NO production curve evoked by epinephrine. Selective stimulation of β1-, β2-, or β3-adrenoceptors also resulted in NO and cGMP production. Propranolol (1 μM) inhibited the rise in NO induced by isoproterenol or the β2-adrenoceptor agonists salbutamol, terbutaline, or fenoterol. Likewise, 10 nM SR 59230A reduced the effects of the β3-adrenoceptor agonists BRL 37344, CGP 12177, SR 595611A, or pindolol. The NO production induced by epinephrine and BRL 37344 was associated with the activation of the phosphatidylinositol 3-kinase/Akt pathway and phosphorylation of eNOS in serine 1177. In addition, in anaesthetized rats, bolus administration of isoproterenol, salbutamol, or BRL 37344 produced NO-dependent reductions in systolic blood pressure. These findings indicate that β1-, β2-, and β3-adrenoceptors are coupled to the NO/cGMP pathway, highlighting the role of the endothelium in the vasomotor action elicited by epinephrine and related β-adrenoceptor agonists.
Role of store-operated Ca2+entry in adenosine-induced vasodilatation of rat small mesenteric artery
Authors: Wang Shengpeng , Zhang Yan , Wier W. Gil , Yu Xiaojiang , Zhao Ming , Hu Hao , Sun Lei , He Xi , Wang Youhua , Wang Bing , Zang Weijin
Published: May 2009

Store-operated Ca2+entry (SOCE) has recently been proposed to contribute to Ca2+influx in vascular smooth muscle cells (VSMCs). Adenosine is known for its protective role against hypoxia and ischemia by increasing nutrient and oxygen supply through vasodilation. This study was designed to examine the hypothesis that SOCE have a functional role in adenosine-induced vasodilation. Small mesenteric resistance arteries and mesenteric VSMCs were obtained from rats. Isometric tensions of isolated artery rings were measured by a sensitive myograph system. Laser-scanning confocal microscopy was used to determine the intracellular Ca2+concentration of fluo 3-loaded VSMCs. Adenosine (0.1–100 μM) relaxed artery rings that were precontracted by phenylephrine in a concentration-dependent manner. In cultured mesenteric VSMCs, passive store depletion by thapsigargin and active store depletion by phenylephrine both induced Ca2+influx due to SOCE. Adenosine inhibited SOCE-mediated increases in cytosolic Ca2+levels evoked by the emptying of the stores. In isolated artery rings, adenosine inhibited SOCE-induced contractions due to store depletion. A2Areceptor antagonism with SCH-58261 and adenylate cyclase inhibition with SQ-22536 largely attenuated adenosine responses. The cAMP analog 8-bromo-cAMP mimicked the effects of adenosine on SOCE. Our results indicate a novel mechanism of vasodilatation by adenosine that involves regulation of SOCE through the cAMP signaling pathway due to activation of adenosine A2Areceptors.
Role of coupled gating between cardiac ryanodine receptors in the genesis of triggered arrhythmias
Authors: Chen Wei , Wasserstrom J. Andrew , Shiferaw Y.
Published: May 2009

Mutations in the ryanodine receptor (RyR) have been linked to exercise-induced sudden cardiac death. However, the precise sequence of events linking RyR channel mutations to a whole heart arrhythmia is not completely understood. In this paper, we apply a detailed, mathematical model of subcellular calcium (Ca) release, coupled to membrane voltage, to study how defective RyR channels can induce arrhythmogenic-triggered activity. In particular, we show that subcellular Ca activity, such as spontaneous Ca sparks and Ca waves, is highly sensitive to coupled gating between RyR channels in clusters. We show that small changes in coupled gating can induce aberrant Ca release activity, which, under Ca overload conditions, can induce delayed afterdepolarization (DAD). We systematically investigate the properties of subcellular Ca during DAD induction and show that the voltage time course during a DAD is dependent on the timing and number of spontaneous Ca sparks that transition to Ca waves. These results provide a detailed mechanism for the role of coupled gating in the genesis of triggered arrhythmias.
Targeted disruption of the voltage-dependent calcium channel α2/δ-1-subunit
Authors: Fuller-Bicer Geraldine A. , Varadi Gyula , Koch Sheryl E. , Ishii Masakazu , Bodi Ilona , Kadeer Nijiat , Muth James N. , Mikala Gabor , Petrashevskaya Natalia N. , Jordan Michael A. , Zhang Sui-Po , Qin Ning , Flores Christopher M. , Isaacsohn Idit , Varadi Maria , Mori Yasuo , Jones W. Keith , Schwartz Arnold
Published: May 2009

Cardiac L-type voltage-dependent Ca2+channels are heteromultimeric polypeptide complexes of α1-, α2/δ-, and β-subunits. The α2/δ-1-subunit possesses a stereoselective, high-affinity binding site for gabapentin, widely used to treat epilepsy and postherpetic neuralgic pain as well as sleep disorders. Mutations in α2/δ-subunits of voltage-dependent Ca2+channels have been associated with different diseases, including epilepsy. Multiple heterologous coexpression systems have been used to study the effects of the deletion of the α2/δ-1-subunit, but attempts at a conventional knockout animal model have been ineffective. We report the development of a viable conventional knockout mouse using a construct targeting exon 2 of α2/δ-1. While the deletion of the subunit is not lethal, these animals lack high-affinity gabapentin binding sites and demonstrate a significantly decreased basal myocardial contractility and relaxation and a decreased L-type Ca2+current peak current amplitude. This is a novel model for studying the function of the α2/δ-1-subunit and will be of importance in the development of new pharmacological therapies.
Comparative investigation of the left ventricular pressure-volume relationship in rat models of type 1 and type 2 diabetes mellitus
Authors: Radovits Tamás , Korkmaz Sevil , Loganathan Sivakkanan , Barnucz Enikő , Bömicke Timo , Arif Rawa , Karck Matthias , Szabó Gábor
Published: May 2009

Diabetes mellitus (DM) is associated with characteristic structural and functional changes of the myocardium, termed diabetic cardiomyopathy. As a distinct entity independent of coronary atherosclerosis, diabetic cardiomyopathy is an increasingly recognized cause of heart failure. A detailed understanding of diabetic cardiac dysfunction, using relevant animal models, is required for the effective prevention and treatment of cardiovascular complications in diabetic patients. We investigated and compared cardiac performance in rat models of type 1 DM (streptozotocin induced) and type 2 DM (Zucker diabetic fatty rats) using a pressure-volume (P-V) conductance catheter system. Left ventricular (LV) systolic and diastolic function was evaluated in vivo at different preloads, including the slope of the end-systolic P-V relation (ESPVR) and end-diastolic P-V relationship (EDPVR), preload recruitable stroke work (PRSW), maximal slope of the systolic pressure increment (dP/d tmax), and its relation to end-diastolic volume (dP/d tmax-EDV) as well as the time constant of LV relaxation and maximal slope of the diastolic pressure decrement. Type 1 DM was associated with decreased LV systolic pressure, dP/d tmax, slope of ESPVR and dP/d tmax-EDV, PRSW, ejection fraction, and cardiac and stroke work indexes, indicating marked systolic dysfunction. In type 2 DM rats, systolic indexes were altered only to a lower extent and the increase of LV stiffness was more pronounced, as indicated by the higher slopes of EDPVR. Our data suggest that DM is characterized by decreased systolic performance and delayed relaxation (mainly in type 1 DM), accompanied by increased diastolic stiffness of the heart (more remarkably in type 2 DM). Based on the sophisticated method of P-V analysis, different characteristics of type 1 and type 2 diabetic cardiac dysfunction can be demonstrated.
Long-acting phosphodiesterase-5 inhibitor, tadalafil, induces sustained cardioprotection against lethal ischemic injury
Authors: Ahmad Nauman , Wang Yigang , Ali Ailia K. , Ashraf Muhammad
Published: May 2009

The ability of pharmacological preconditioning mimetics to confer long-lasting and sustained cardioprotection may be a logical criterion to develop a drug that can be used clinically for cardioprotection. We propose here that the use of long-acting phosphodiesterase-5 inhibitor, tadalafil, may confer sustained cardioprotection against ischemia. Tadalafil (5 mg/kg) was administered orally to male C57B/6J mice ( n = 6 in each treatment subgroup at each time point studied). Hearts were isolated and subjected to 40 min of ischemia and 30 min of reperfusion on Langendorff's apparatus at 1, 12, 24, 36, 48, 60, 72, and 108 h after tadalafil administration. In 1- to 48-h subgroups, tadalafil was given once at 0 h only. In 60- and 72-h subgroups, tadalafil was given twice at 0 and 36 h. Similarly, in the 108-h subgroup, tadalafil was administered at 0, 36, and 72 h. In the same subgroups, wortmannin (15 μg/kg ip), an inhibitor of phosphatidylinositol 3-kinase or 5-hydroxydecanoic acid (5 mg/kg ip), an inhibitor of mitochondrial ATP-sensitive K+ channels, was given together with tadalafil, and the hearts were subjected to ischemia-reperfusion at 36 h to determine whether the effect of tadalafil on ischemia-reperfusion injury was abolished. As a result, tadalafil treatment reduced left ventricular end-diastolic pressure and increased left ventricular developed pressure as well as reduced lactate dehydrogenase release. This protection remained till 36–40 h, and thereafter it vanished. The readministration of tadalafil at 36 and 72 h restored the protection till 108 h. Tadalafil treatment accelerated Akt phosphorylation in cardiac tissue and decreased myocyte apoptosis. The administration of wortmannin abolished the beneficial effects of tadalafil on hemodynamic parameters and myocyte apoptosis, together with significantly reduced Akt phosphorylation. 5-Hydroxydecanoic acid also abolished the antiapoptotic effect of tadalafil. It is concluded that tadalafil treatment induces the long-term protection of ischemic myocardium via phosphatidylinositol 3-kinase/Akt signaling pathway.
Catecholaminergic automatic activity in the rat pulmonary vein: electrophysiological differences between cardiac muscle in the left atrium and pulmonary vein
Authors: Doisne Nicolas , Maupoil Véronique , Cosnay Pierre , Findlay Ian
Published: May 2009

Ectopic activity in cardiac muscle within pulmonary veins (PVs) is associated with the onset and the maintenance of atrial fibrillation in humans. The mechanism underlying this ectopic activity is unknown. Here we investigate automatic activity generated by catecholaminergic stimulation in the rat PV. Intracellular microelectrodes were used to record electrical activity in isolated strips of rat PV and left atrium (LA). The resting cardiac muscle membrane potential was lower in PV [−70 ± 1 (SE) mV, n = 8] than in LA (−85 ± 1 mV, n = 8). No spontaneous activity was recorded in PV or LA under basal conditions. Norepinephrine (10−5 M) induced first a hyperpolarization (−8 ± 1 mV in PV, −3 ± 1 mV in LA, n = 8 for both) then a slowly developing depolarization (+21 ± 2 mV after 15 min in PV, +1 ± 2 mV in LA) of the resting membrane potential. Automatic activity occurred only in PV; it was triggered at approximately −50 mV, and it occurred as repetitive bursts of slow action potentials. The diastolic membrane potential increased during a burst and slowly depolarized between bursts. Automatic activity in the PV was blocked by either atenolol or prazosine, and it could be generated with a mixture of cirazoline and isoprenaline. In both tissues, cirazoline (10−6 M) induced a depolarization (+37 ± 2 mV in PV, n = 5; +5 ± 1 mV in LA, n = 5), and isoprenaline (10−7 M) evoked a hyperpolarization (−11 ± 3 mV in PV, n = 7; −3 ± 1 mV in LA, n = 6). The differences in membrane potential and reaction to adrenergic stimulation lead to automatic electrical activity occurring specifically in cardiac muscle in the PV.
A numerical study on the flow of blood and the transport of LDL in the human aorta: the physiological significance of the helical flow in the aortic arch
Authors: Liu Xiao , Pu Fang , Fan Yubo , Deng Xiaoyan , Li Deyu , Li Shuyu
Published: May 2009

It has been proposed that a mass transfer phenomenon called concentration polarization of low-density lipoproteins (LDLs) may occur in the arterial system and is likely involved in the localization of atherogenesis. To test the hypothesis that concentration polarization of LDL may be suppressed by the helical flow pattern in the human aorta, hence sparing the ascending aorta from atherosclerosis, the effects of aortic torsion, branching, curvature, and taper on blood flow and LDL transport in the lumen were simulated numerically under steady-state flow conditions using four aorta models constructed based on in vivo MRI slices. The results showed that it was the aortic torsion that induced the helical flow in the aortic arch, stabilizing the flow of blood in the aorta, and compensated the adverse effects of the aortic curvature on blood flow and LDL transport. The helical flow reduced the luminal surface LDL concentration in the aortic arch and probably played a role in suppressing severe polarization of LDL at the entrances of the three branches on the arch, hence, protecting them from atherogenesis. The taper of the aorta was another important feature of the aorta that further stabilized the flow of blood and delayed the attenuation of the helical flow, making it move beyond the arch and into the beginning part of the descending aorta. The results therefore may account for why the ascending aorta and the arch are relatively free of atherosclerosis.
An internal domain of β-tropomyosin increases myofilament Ca2+sensitivity
Authors: Jagatheesan Ganapathy , Rajan Sudarsan , Schulz Emily M. , Ahmed Rafeeq P. H. , Petrashevskaya Natalia , Schwartz Arnold , Boivin Greg P. , Arteaga Grace M. , Wang Tao , Wang Yi-Gang , Ashraf Muhammad , Liggett Stephen B. , Lorenz John , Solaro R. John , Wieczorek David F.
Published: May 2009

Tropomyosin (TM) is involved in Ca2+-mediated muscle contraction and relaxation in the heart. Striated muscle α-TM is the major isoform expressed in the heart. The expression of striated muscle β-TM in the murine myocardium results in a decreased rate of relaxation and increased myofilament Ca2+sensitivity. Replacing the carboxyl terminus (amino acids 258–284) of α-TM with β-TM (a troponin T-binding region) results in decreased rates of contraction and relaxation in the heart and decreased myofilament Ca2+sensitivity. We hypothesized that the putative internal troponin T-binding domain (amino acids 175–190) of β-TM may be responsible for the increased myofilament Ca2+sensitivity observed when the entire β-TM is expressed in the heart. To test this hypothesis, we generated transgenic mice that expressed chimeric TM containing β-TM amino acids 175–190 in the backbone of α-TM (amino acids 1–174 and 191–284). These mice expressed 16–57% chimeric TM and did not develop cardiac hypertrophy or any other morphological changes. Physiological analysis showed that these hearts exhibited decreased rates of contraction and relaxation and a positive response to isoproterenol. Skinned fiber bundle analyses showed a significant increase in myofilament Ca2+sensitivity. Biophysical experiments demonstrated that the exchanged amino acids did not influence the flexibility of the TM. This is the first study to demonstrate that a specific domain within TM can increase the Ca2+sensitivity of the thin filament and affect sarcomeric performance. Furthermore, these results enhance the understanding of why TM mutations associated with familial hypertrophic cardiomyopathy demonstrate increased myofilament sensitivity to Ca2+.
Resveratrol induces mitochondrial biogenesis in endothelial cells
Authors: Csiszar Anna , Labinskyy Nazar , Pinto John T. , Ballabh Praveen , Zhang Hanrui , Losonczy Gyorgy , Pearson Kevin , de Cabo Rafael , Pacher Pal , Zhang Cuihua , Ungvari Zoltan
Published: May 2009

Pathways that regulate mitochondrial biogenesis are potential therapeutic targets for the amelioration of endothelial dysfunction and vascular disease. Resveratrol was shown to impact mitochondrial function in skeletal muscle and the liver, but its role in mitochondrial biogenesis in endothelial cells remains poorly defined. The present study determined whether resveratrol induces mitochondrial biogenesis in cultured human coronary arterial endothelial cells (CAECs). In CAECs resveratrol increased mitochondrial mass and mitochondrial DNA content, upregulated protein expression of electron transport chain constituents, and induced mitochondrial biogenesis factors (proliferator-activated receptor-coactivator-1α, nuclear respiratory factor-1, mitochondrial transcription factor A). Sirtuin 1 (SIRT1) was induced, and endothelial nitric oxide (NO) synthase (eNOS) was upregulated in a SIRT1-dependent manner. Knockdown of SIRT1 (small interfering RNA) or inhibition of NO synthesis prevented resveratrol-induced mitochondrial biogenesis. In aortas of type 2 diabetic (db/db) mice impaired mitochondrial biogenesis was normalized by chronic resveratrol treatment, showing the in vivo relevance of our findings. Resveratrol increases mitochondrial content in endothelial cells via activating SIRT1. We propose that SIRT1, via a pathway that involves the upregulation of eNOS, induces mitochondrial biogenesis. Resveratrol induced mitochondrial biogenesis in the aortas of type 2 diabetic mice, suggesting the potential for new treatment approaches targeting endothelial mitochondria in metabolic diseases.
Effect of early versus late AT1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits
Authors: González Germán E. , Seropian Ignacio M. , Krieger Maria Laura , Palleiro Jimena , Lopez Verrilli Maria A. , Gironacci Mariela M. , Cavallero Susana , Wilensky Luciana , Tomasi Victor H. , Gelpi Ricardo J. , Morales Celina
Published: May 2009

To characterize the temporal activation of the renin-angiotensin system after myocardial infarction (MI) in rabbits, we examined cardiac ANG II type 1 receptor (AT1R) expression and ANG II levels from 3 h to 35 days. The effects of losartan (12.5 mg·kg−1·day−1) on functional and histomorphometric parameters when treatment was initiated early (3 h) and late ( day 15) post-MI and maintained for different periods of time [short term (4 days), midterm (20 days), and long term (35 days)] were also studied. AT1R expression increased in the MI zone at 15 and 35 days ( P < 0.05). ANG II levels increased ( P < 0.05) in the non-MI zone at 24 h and in the MI zone as well as in plasma at 4 days and then progressively decreased until 35 days. The survival rate was significantly lower in untreated MI and early long-term-treated animals. Diastolic pressure-volume curves in MI at 35 and 56 days shifted to the right ( P < 0.05). This shift was even more pronounced in long-term-treated groups ( P < 0.05). Contractility decreased ( P < 0.05 vs. sham) in the untreated and long-term-treated groups and was attenuated in the midterm-treated group. The early administration of losartan reduced RAM 11-positive macrophages from 4.15 ± 0.05 to 3.05 ± 0.02 cells/high-power field (HPF; P < 0.05) and CD45 RO-positive lymphocytes from 2.23 ± 0.05 to 1.48 ± 0.01 cells/HPF ( P < 0.05) in the MI zone at 4 days. Long-term treatment reduced the scar collagen (MI: 70.50 ± 2.35% and MI + losartan: 57.50 ± 2.48, P < 0.05), determined the persistency of RAM 11-positive macrophages (3.02 ± 0.13 cells/HPF) and CD45 RO-positive lymphocytes (2.77 ± 0.58 cells/HPF, P < 0.05 vs. MI), and reduced the scar thinning ratio at 35 days ( P < 0.05). Consequently, the temporal expressions of cardiac AT1R and ANG II post-MI in rabbits are different from those described in other species. Long-term treatment unfavorably modified post-MI remodeling, whereas midterm treatment attenuated this harmful effect. The delay in wound healing (early reduction and late persistency of inflammatory infiltrate) and adverse remodeling observed in long-term-treated animals might explain the unfavorable effect observed in rabbits.
ETAselective receptor antagonism prevents ventricular remodeling in volume-overloaded rats
Authors: Murray David B. , McMillan Ronald , Brower Gregory L. , Janicki Joseph S.
Published: May 2009

The objective of this study was to investigate the ability of selective endothelin receptor subtype A (ETA) endothelin receptor antagonism (ETA) to prevent the acute myocardial remodeling process secondary to volume overload. Left ventricular tissue from sham-operated (Sham) and untreated (Fist), and TBC-3214 (Fist + ETA, 25 mg·kg−1·day−1)-treated fistula animals was analyzed for mast cell density, matrix metalloproteinase (MMP) activity, and extracellular collagen volume fraction (CVF) 1 and 5 days following the initiation of volume overload. Compared with Fist, ETA treatment prevented the increase in left ventricular mast cell density at 1 day and 5 days. Additionally, at 1 day postfistula, a substantial decrease in MMP-2 activity below Sham levels was observed following endothelin receptor antagonism (1.7 ± 0.7 vs. 0.3 ± 0.3 vs. 0.9 ± 0.2 arbitrary activity units, Fist vs. Fist + ETA vs. Sham, P ≤ 0.05). This same effect was also seen at 5 days postfistula (1.9 ± 0.3 vs. 0.5 ± 0.1 arbitrary activity units, Fist vs. Fist + ETA, P ≤ 0.05). The marked decrease in myocardial CVF seen in Fist hearts (0.7 ± 0.1 vs. 1.6 ± 0.1% myocardial area, Fist vs. Sham, P ≤ 0.05) was prevented by ETA (1.7 ± 0.1% Fist + ETA, P < 0.05 vs. Fist). This preservation of the collagen matrix was also present on day 5 in the TBC-treated group vs. the Fist group (1.0 ± 0.1 vs. 1.4 ± 0.1%, Fist vs. Fist + ETA, P ≤ 0.01). Furthermore, an 8-wk preventative treatment with ETA significantly attenuated the increase in left ventricular end systolic and diastolic volumes compared with untreated fistula hearts. In conclusion, the novel findings of this study indicate that the activation of cardiac mast cells and subsequent MMP activation/collagen degradation during the acute stages of volume overload are prevented by blockade of the ETAreceptor subtype. Furthermore, by preventing these events, ET-1 antagonism was efficacious in attenuating ventricular dilatation and limiting the development of structural and functional deficits.
Overexpression of CYP2J2 provides protection against doxorubicin-induced cardiotoxicity
Authors: Zhang Yunfang , El-Sikhry Haitham , Chaudhary Ketul R. , Batchu Sri Nagarjun , Shayeganpour Anooshirvan , Jukar Taibeh Orujy , Bradbury J. Alyce , Graves Joan P. , DeGraff Laura M. , Myers Page , Rouse Douglas C. , Foley Julie , Nyska Abraham , Zeldin Darryl C. , Seubert John M.
Published: May 2009

Human cytochrome P-450 (CYP)2J2 is abundant in heart and active in biosynthesis of epoxyeicosatrienoic acids (EETs). Recently, we demonstrated that these eicosanoid products protect myocardium from ischemia-reperfusion injury. The present study utilized transgenic (Tr) mice with cardiomyocyte-specific overexpression of human CYP2J2 to investigate protection toward toxicity resulting from acute (0, 5, or 15 mg/kg daily for 3 days, followed by 24-h recovery) or chronic (0, 1.5, or 3.0 mg/kg biweekly for 5 wk, followed by 2-wk recovery) doxorubicin (Dox) administration. Acute treatment resulted in marked elevations of serum lactate dehydrogenase and creatine kinase levels that were significantly greater in wild-type (WT) than CYP2J2 Tr mice. Acute treatment also resulted in less activation of stress response enzymes in CYP2J2 Tr mice (catalase 750% vs. 300% of baseline, caspase-3 235% vs. 165% of baseline in WT vs. CYP2J2 Tr mice). Moreover, CYP2J2 Tr hearts exhibited less Dox-induced cardiomyocytes apoptosis (measured by TUNEL) compared with WT hearts. After chronic treatment, comparable decreases in body weight were observed in WT and CYP2J2 Tr mice. However, cardiac function, assessed by measurement of fractional shortening with M-mode transthoracic echocardiography, was significantly higher in CYP2J2 Tr than WT hearts after chronic Dox treatment (WT 37 ± 2%, CYP2J2 Tr 47 ± 1%). WT mice also had larger increases in β-myosin heavy chain and cardiac ankryin repeat protein compared with CYP2J2 Tr mice. CYP2J2 Tr hearts had a significantly higher rate of Dox metabolism than WT hearts (2.2 ± 0.25 vs. 1.6 ± 0.50 ng·min−1·100 μg protein−1). In vitro data from H9c2 cells demonstrated that EETs attenuated Dox-induced mitochondrial damage. Together, these data suggest that cardiac-specific overexpression of CYP2J2 limited Dox-induced toxicity.
Superoxide production by NAD(P)H oxidase and mitochondria is increased in genetically obese and hyperglycemic rat heart and aorta before the development of cardiac dysfunction. The role of glucose-6-phosphate dehydrogenase-derived NADPH
Authors: Serpillon Sabrina , Floyd Beverly C. , Gupte Rakhee S. , George Shimran , Kozicky Mark , Neito Venessa , Recchia Fabio , Stanley William , Wolin Michael S. , Gupte Sachin A.
Published: May 2009

Increased oxidative stress is a known cause of cardiac dysfunction in animals and patients with diabetes, but the sources of reactive oxygen species [e.g., superoxide anion (O2−)] and the mechanisms underlying O2−production in diabetic hearts are not clearly understood. Our aim was to determine whether NADPH oxidase (Nox) is a source of O2−and whether glucose-6-phosphate dehydrogenase (G6PD)-derived NADPH plays a role in augmenting O2−generation in diabetes. We assessed cardiac function, Nox and G6PD activities, NADPH levels, and the activities of antioxidant enzymes in heart homogenates from young (9–11 wk old) Zucker lean and obese (fa/fa) rats. We found that myocardial G6PD activity was significantly higher in fa/fa than in lean rats, whereas superoxide dismutase and glutathione peroxidase activities were decreased ( P < 0.05). O2−levels were elevated (70–90%; P < 0.05) in the diabetic heart, and this elevation was blocked by the Nox inhibitor gp-91ds-tat(50 μM) or by the mitochondrial respiratory chain inhibitors antimycin (10 μM) and rotenone (50 μM). Inhibition of G6PD by 6-aminonicotinamide (5 mM) and dihydroepiandrosterone (100 μM) also reduced ( P < 0.05) O2−production. Notably, the activities of Nox and G6PD in the fa/fa rat heart were inhibited by chelerythrine, a protein kinase C inhibitor. Although we detected no changes in stroke volume, cardiac output, or ejection fraction, left ventricular diameter was slightly increased during diastole and systole, and left ventricular posterior wall thickness was decreased during systole ( P < 0.05) in Zucker fa/fa rats. Our findings suggest that in a model of severe hyperlipidema and hyperglycemia Nox-derived O2−generation in the myocardium is fueled by elevated levels of G6PD-derived NADPH. Similar mechanisms were found to activate O2−production and induce endothelial dysfunction in aorta. Thus G6PD may be a useful therapeutic target for treating the cardiovascular disease associated with type 2 diabetes, if second-generation drugs specifically reducing the activity of G6PD to near normal levels are developed.