bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro maturation, in vitro fertilization and embryonic development of canine oocytes
Authors: Lee S.R. , Kim B.S. , Kim J-W. , Kim M.O. , Kim S.H. , Yoo D.H. , Shin M-J. , Park Y.S. , Lee S. , Park Y.B. , Ha J.H. , Ryoo Z.Y. 
Published: October 2007

SummaryIn this study we have investigated the efficiency of in vitro maturation (IVM) as a basic way to study the development of canine oocytes after in vitro fertilization (IVF). We decided, therefore, to perform two-part experiments. Firstly, experiment I compared the effects of TCM199 without fetal bovine serum (FBS) with TCM199 supplemented with 5% FBS on the in vitro nuclear maturation rate of canine oocytes. For the efficiency of meiotic development to the metaphase II (MII) stage, we found that 4.7% (4/64) of all oocytes grown in TCM199 without FBS developed to the MII stage compared with only 1.7% (1/59) of those grown in TCM199 with 5% FBS for 48 h. Therefore, FBS did not increase in vitro nuclear maturation. In experiment II, the cleavage rate of canine oocytes used for IVF was investigated following heparin treatment. Canine oocytes were fertilized in four groups: Fert–TALP medium without heparin (Fert I) or Fert–TALP medium supplemented with 10, 20 or 30 µg/ml heparin (Fert II, Fert III, Fert IV, respectively). Oocytes that were grown for 24 h in Fert I following fertilization showed the highest rate of all of the groups, 6.5% (5/77) and developed to the early morula stage. Markedly, the oocytes cultured in Fert I for 24 h following insemination had a higher rate of embryonic development than other groups. We can assert that, unlike findings in other mammals, heparin treatment in canine IVF does not increase the efficiency of the fertilization rate and is therefore not an important factor.
Long-term follow-up of porcine male germ cells transplanted into mouse testes
Authors: Choi Y-J. , Park J-K. , Lee M-S. , Ahn J.D. , Hwang K-C. , Song H. , Kim J-H. 
Published: October 2007

SummaryThis study investigated the effect of increased phylogenetic distance on the outcome of spermatogonial transplantation, with porcine donors and mice recipients. It was designed to develop a technique for detecting foreign donor cells in recipient animals. Porcine male germ cells were harvested from postnatal male testes and incubated with the lipophilic membrane dye PKH-26. For transplantation, approximately 106PKH-26-labelled porcine male germ cells were injected into the efferent ducts of mouse testes. Animals were sacrificed at post-graft days 1, 10, 30, 45, 60 and 150 (n= 5 each). Serial frozen sections of explanted testes were prepared for detecting labelled cells. Transplanted porcine donor cells were easily detected in the recipient tubules for 8 weeks. After transplantation, we could detect both incorporation into the basement membrane and differentiation of grafted porcine donor cells by our double detection system, using PKH staining and slide PCR. However, our RT-PCR and apoptosis results revealed that most of the grafted porcine male donor cells could not differentiate past early-meiotic spermatocytes. We could induce partial differentiation of xenografted porcine donor cells in mouse testes, but not full induction of spermatogenesis. We have developed a very reliable technique for detecting foreign donor cells in recipient animals using a combination of PKH staining and slide PCR methods. Our results provide a valuable experimental model for applying and evaluating this technology in other species.
Bisphosphonates and prevention of metastases: the AZURE study
Authors: Burkinshaw R. , Thorpe H. , Coleman R. 
Published: October 2007

AbstractMost patients present with disease that appears to be confined to the breast. However, a significant proportion of women will go on to develop metastatic breast cancer with bone being the most frequent site of distant relapse. The bone microenvironment provides a fertile soil for circulating metastatic cells as resorbing bone releases growth factors that are thought to attract circulating cancer cells to the bone surface and facilitate their growth and proliferation. These infiltrating tumour cells in turn produce bone cell-activating factors, which lead to increased bone resorption and further release of growth factors in a ‘vicious cycle’. The third-generation bisphosphonate zoledronic acid is a potent inhibitor of osteoclast-mediated bone resorption. It also has effects on numerous processes in the metastatic cascade, with in vitro and animal studies showing synergistic antitumour effects with a range of cytotoxic and endocrine treatments. The addition of zoledronic acid to adjuvant therapy could therefore be a therapeutic strategy of potential importance.To investigate this, the AZURE trial was designed to determine whether adjuvant zoledronic acid improves the disease-free and bone metastasis-free survival of women with stage II/III breast cancer. Recruitment of 3300 subjects was completed in January 2006. First efficacy data are expected in 2008. There is a potential for synergistic action with chemotherapy to manifest as enhanced toxicity. Reassuringly, initial safety data show that zoledronic acid is well tolerated and can be safely combined with adjuvant chemotherapy without any increase in myelotoxicity or effect on dose intensity.
A model of the French pension reserve fund: what could be the optimal contribution path rate?
Authors: BERGER CHARLIE , LAVIGNE ANNE 
Published: October 2007

AbstractCurrent and expected demographic and economic trends are likely to jeopardize the financial sustainability of the French retirement pension scheme, which mainly operates on a pay-as-you-go basis. In 1999, the French government set up a Pension Reserve Fund (Fonds de réserve pour les retraites, FRR) the main objective of which was to introduce some public funding in the PAYG basic pension scheme to cope with its expected financial unsustainability within the next decade. This paper presents some simulation results on the projected evolution of the French Pension Reserve Fund under various assumptions. The main idea is to optimize the profile of the trend in contribution rates needed to meet the objective of a balanced basic pension scheme over the period 2006–2050. Our simulations show that under plausible assumptions the amount of funding is likely to be less important than the Government expected at the FRR set up, about 100 billion euros. Some stress tests show that severe shocks on financial markets may dramatically affect the funding profile of the FRR beyond 2045.
Demography and investment behavior of pension funds: evidence for Switzerland
Authors: GERBER DAVID S. , WEBER RENÉ 
Published: October 2007

AbstractThis paper focuses on the nexus between pension funds' balance sheet liabilities, reflecting their age profile and payments obligations, and the investment behavior and costs of these funds. The context of the analysis is the stringent regulatory framework and the highly fragmented and heterogeneous pension fund landscape in Switzerland. Detailed data from the Swiss Pension Statistic are analyzed using multivariate OLS-regressions. The evidence shows that a younger age structure and lower short-term benefits payouts are related to a higher share of equities and lower real estate holdings. Legal form, pension plan type, and size are important for administrative costs. The findings support the view that aging may lead to increased risk aversion and thus to a lower engagement of institutional investors in equities.
An analysis of money's worth ratios in Chile
Authors: THORBURN CRAIG , ROCHA ROBERTO , MORALES MARCO 
Published: October 2007

AbstractEmpirical analyses of annuities markets have been limited to a few developed countries and restricted by data limitations. Chile provides excellent conditions for research on annuities due to the depth of its market and the availability of data. The paper utilizes an extensive dataset on individual annuities to examine econometrically a measure of market performance – money's worth ratios (MWRs), or the ratio of the expected present value of annuity payments to the premium. The results show that annuitants in Chile have generally got a good deal for their premiums, as indicated by MWRs higher than one and also higher than those estimated for other countries. The difference between Chile and other countries is striking considering that annuities in Chile are indexed to prices. The wide range of indexed instruments in Chile, allowing providers to hedge their risks while extracting higher returns, helps explain the difference. The high degree of market competition has also contributed to this outcome. Efforts to improve market transparency through a new electronic quotation system have decreased the dispersion of MWRs. Finally, MWRs tend to decrease for contracts with longer durations, reflecting pricing for higher longevity and reinvestment risks. These results are consistent with separate research on the annuity rate, and indicate the need to ensure competition and market transparency, as well as to develop appropriate financial instruments for providers in order to ensure good outcomes for annuitants.
The roles of the prostaglandin D2receptors DP1and CRTH2 in promoting allergic responses
Authors: Pettipher R 
Published: October 2007

Prostaglandin D2(PGD2) is produced by mast cells, Th2 lymphocytes and dendritic cells and has been detected in high concentrations at sites of allergic inflammation. PGD2exerts its inflammatory effects through high affinity interactions with the G protein coupled receptors DP1and chemoattractant‐homologous receptor expressed on Th2 cells (CRTH2, also known as DP2). DP1and CRTH2 act in concert to promote a number of biological effects associated with the development and maintenance of the allergic response. During the process of allergen sensitization, DP1activation may enhance polarization of Th0 cells to Th2 cells by inhibiting production of interleukin 12 by dendritic cells. Upon exposure to allergen in sensitized individuals, activation of DP1may contribute to the long lasting blood flow changes in the target organ. CRTH2 is expressed by Th2 lymphocytes, eosinophils and basophils and may mediate the recruitment of these cell types during the late phase allergic response. The role played by CRTH2 in promoting the production of Th2 cytokines and IgE make antagonism of this receptor a particularly attractive approach to the treatment of chronic allergic disease.British Journal of Pharmacology(2008)153, S191–S199; doi:10.1038/sj.bjp.0707488; published online 29 October 2007
Intermedin (adrenomedullin‐2): a novel counter‐regulatory peptide in the cardiovascular and renal systems
Authors: Bell D , McDermott B J 
Published: October 2007

Intermedin (IMD) is a novel peptide related to calcitonin gene‐related peptide (CGRP) and adrenomedullin (AM). Proteolytic processing of a larger precursor yields a series of biologically active C‐terminal fragments, IMD1–53, IMD1–47 and IMD8–47. IMD shares a family of receptors with AM and CGRP composed of a calcitonin‐receptor like receptor (CALCRL) associated with one of three receptor activity modifying proteins (RAMP). Compared to CGRP, IMD is less potent at CGRP1 receptors but more potent at AM1 receptors and AM2 receptors; compared to AM, IMD is more potent at CGRP1 receptors but less potent at AM1 and AM2 receptors. The cellular and tissue distribution of IMD overlaps in some aspects with that of CGRP and AM but is distinct from both. IMD is present in neonatal but absent or expressed sparsely, in adult heart and vasculature and present at low levels in plasma. The prominent localization of IMD in hypothalamus and pituitary and in kidney is consistent with a physiological role in the central and peripheral regulation of the circulation and water‐electrolyte homeostasis. IMD is a potent systemic and pulmonary vasodilator, influences regional blood flow and augments cardiac contractility. IMD protects myocardium from the deleterious effects of oxidative stress associated with ischaemia‐reperfusion injury and exerts an anti‐growth effect directly on cardiomyocytes to oppose the influence of hypertrophic stimuli. The robust increase in expression of the peptide in hypertrophied and ischaemic myocardium indicates an important protective role for IMD as an endogenous counter‐regulatory peptide in the heart.British Journal of Pharmacology (2008) 153, S247–S262; doi:10.1038/sj.bjp.0707494; published online 29 October 2007
Differential effects of cannabinoid receptor agonists on regional brain activity using pharmacological MRI
Authors: Chin C‐L , Tovcimak A E , Hradil V P , Seifert T R , Hollingsworth P R , Chandran P , Zhu C Z , Gauvin D , Pai M , Wetter J , Hsieh G C , Honore P , Frost J M , Dart M J , Meyer M D , Yao B B , Cox B F , Fox G B 
Published: October 2007

Background and purpose:Activation of cannabinoid CB1 and/or CB2 receptors mediates analgesic effects across a broad spectrum of preclinical pain models. Selective activation of CB2 receptors may produce analgesia without the undesirable psychotropic side effects associated with modulation of CB1 receptors. To address selectivity in vivo, we describe non‐invasive, non‐ionizing, functional data that distinguish CB1 from CB2 receptor neural activity using pharmacological MRI (phMRI) in awake rats.Experimental approach:Using a high field (7 T) MRI scanner, we examined and quantified the effects of non‐selective CB1/CB2 (A‐834735) and selective CB2 (AM1241) agonists on neural activity in awake rats. Pharmacological specificity was determined using selective CB1 (rimonabant) or CB2 (AM630) antagonists. Behavioural studies, plasma and brain exposures were used as benchmarks for activity in vivo.Key results:The non‐selective CB1/CB2 agonist produced a dose‐related, region‐specific activation of brain structures that agrees well with published autoradiographic CB1 receptor density binding maps. Pretreatment with a CB1 antagonist but not with a CB2 antagonist, abolished these activation patterns, suggesting an effect mediated by CB1 receptors alone. In contrast, no significant changes in brain activity were found with relevant doses of the CB2 selective agonist.Conclusion and implications:These results provide the first clear evidence for quantifying in vivo functional selectivity between CB1 and CB2 receptors using phMRI. Further, as the presence of CB2 receptors in the brain remains controversial, our data suggest that if CB2 receptors are expressed, they are not functional under normal physiological conditions.British Journal of Pharmacology (2008) 153, 367–379; doi:10.1038/sj.bjp.0707506; published online 29 October 2007
Potentiation of E‐4031‐induced torsade de pointes by HMR1556 or ATX‐II is not predicted by action potential short‐term variability or triangulation
Authors: Michael G , Dempster J , Kane K A , Coker S J 
Published: October 2007

Background and purpose:Torsade de pointes (TdP) can be induced by a reduction in cardiac repolarizing capacity. The aim of this study was to assess whether I
Ks blockade or enhancement of I
Na could potentiate TdP induced by I
Kr blockade and to investigate whether short‐term variability (STV) or triangulation of action potentials preceded TdP.Experimental approach:Experiments were performed in open‐chest, pentobarbital‐anaesthetized, α1‐adrenoceptor‐stimulated, male New Zealand White rabbits, which received three consecutive i.v. infusions of either the I
Kr blocker E‐4031 (1, 3 and 10 nmol kg−1 min−1), the I
Ks blocker HMR1556 (25, 75 and 250 nmol kg−1 min−1) or E‐4031 and HMR1556 combined. In a second study rabbits received either the same doses of E‐4031, the I
Na enhancer, ATX‐II (0.4, 1.2 and 4.0 nmol kg−1) or both of these drugs. ECGs and epicardial monophasic action potentials were recorded.Key results:HMR1556 alone did not cause TdP but increased E‐4031‐induced TdP from 25 to 80%. ATX‐II alone caused TdP in 38% of rabbits, as did E‐4031; 75% of rabbits receiving both drugs had TdP. QT intervals were prolonged by all drugs but the extent of QT prolongation was not related to the occurrence of TdP. No changes in STV were detected and triangulation was only increased after TdP occurred.Conclusions and implications:Giving modulators of ion channels in combination substantially increased TdP but, in this model, neither STV nor triangulation of action potentials could predict TdP.British Journal of Pharmacology (2007) 152, 1215–1227; doi:10.1038/sj.bjp.0707513; published online 29 October 2007
Δ9‐Tetrahydrocannabinol (THC) and AM 404 protect against cerebral ischaemia in gerbils through a mechanism involving cannabinoid and opioid receptors
Authors: Zani A , Braida D , Capurro V , Sala M 
Published: October 2007

Background and purpose:It has been suggested that the endocannabinoid system elicits neuroprotection against excitotoxic brain damage. In the present study the therapeutic potential of AM 404 on ischaemia‐induced neuronal injury was investigatedin vivoand compared with that of the classical cannabinoid receptor type 1 (CB1) agonist, Δ9‐tetraydrocannabinol (THC), using a model of transient global cerebral ischaemia in the gerbil.Experimental approach:The effects of AM 404 (0.015–2 mg kg−1) and THC (0.05–2 mg kg−1), given 5 min after ischaemia, were measured from 1 h to 7 days in terms of electroencephalographic (EEG) total spectral power, spontaneous motor activity, memory function, rectal temperature and hippocampal CA1neuronal count.Key results:Over the dose range tested, AM 404 (2 mg kg−1) and THC (1 mg kg−1) completely reversed the ischaemia‐induced behavioural, EEG and histological damage. Only THC (1 and 2 mg kg−1) induced a decrease of body temperature. Pretreatment with the selective CB1receptor antagonist, AM 251 (1 mg kg−1) and the opioid antagonist, naloxone (2 mg kg−1) reversed the protective effect induced by both AM 404 and THC while the TRPV1vanilloid antagonist, capsazepine (0.01 mg kg−1), was ineffective.Conclusions and implications:Our findings demonstrate that AM 404 and THC reduce neuronal damage caused by bilateral carotid occlusion in gerbils and that this protection is mediated through an interaction with CB1and opioid receptors. Endocannabinoids might form the basis for the development of new neuroprotective drugs useful for the treatment of stroke and other neurodegenerative pathologies.British Journal of Pharmacology(2007)152, 1301–1311; doi:10.1038/sj.bjp.0707514; published online 29 October 2007
The endothelin system as a therapeutic target in cardiovascular disease: great expectations or bleak house?
Authors: Kirkby N S , Hadoke P W F , Bagnall A J , Webb D J 
Published: October 2007

There is considerable evidence that the potent vasoconstrictor endothelin‐1 (ET‐1) contributes to the pathogenesis of a variety of cardiovascular diseases. As such, pharmacological manipulation of the ET system might represent a promising therapeutic goal. Many clinical trials have assessed the potential of ET receptor antagonists in cardiovascular disease, the most positive of which have resulted in the licensing of the mixed ET receptor antagonist bosentan, and the selective ETAreceptor antagonists, sitaxsentan and ambrisentan, for the treatment of pulmonary arterial hypertension (PAH). In contrast, despite encouraging data fromin vitroand animal studies, outcomes in human heart failure have been disappointing, perhaps illustrating the risk of extrapolating preclinical work to man. Many further potential applications of these compounds, including resistant hypertension, chronic kidney disease, connective tissue disease and sub‐arachnoid haemorrhage are currently being investigated in the clinic. Furthermore, experience from previous studies should enable improved trial design and scope remains for development of improved compounds and alternative therapeutic strategies. Although ET‐converting enzyme inhibitors may represent one such alternative, there have been relatively few suitable compounds developed, and consequently, clinical experience with these agents remains extremely limited. Recent advances, together with an increased understanding of the biology of the ET system provided by improved experimental tools (including cell‐specific transgenic deletion of ET receptors), should allow further targeting of clinical trials to diseases in which ET is involved and allow the therapeutic potential for targeting the ET system in cardiovascular disease to be fully realized.British Journal of Pharmacology(2008)153, 1105–1119; doi:10.1038/sj.bjp.0707516; published online 29 October 2007
Cannabinoid receptors in acute and chronic complications of atherosclerosis
Authors: Mach F , Montecucco F , Steffens S 
Published: October 2007

Atherosclerosis is a chronic inflammatory disease that is the primary cause of myocardial infarction and stroke, which occur after sudden thrombotic occlusion of an artery. A growing body of evidence suggests that cannabinoid signalling plays a fundamental role in atherosclerosis development and its clinical manifestations. Thus, CB2 receptors are protective in myocardial ischaemia/reperfusion and implicated in the modulation of chemotaxis, which is crucial for the recruitment of leukocytes during inflammation. Delta‐9‐Tetrahydrocannabinol (THC)‐mediated activation has been shown to inhibit atherosclerotic plaque progression in a CB2 dependent manner. Although CB1 and CB2 expression has been reported on platelets, their involvement in thrombus formation is still controversial. While several reports suggest that CB1 receptors may have a relevant role in neuroprotection after ischaemic stroke, recent studies show the protective effects in various forms of neuroprotection are not related to CB1 stimulation, and a protective role of CB1 blockade has also been reported. In addition, vascular and myocardial CB1 receptors contribute to the modulation of blood pressure and heart rate. It is tempting to suggest that pharmacological modulation of the endocannabinoid system is a potential novel therapeutic strategy in the treatment of atherosclerosis. For these purposes, it is important to better understand the complex mechanisms of endocannabinoid signalling and potential consequences of its pharmacological modulation, as it may have both pro‐ and anti‐atherosclerotic effects.British Journal of Pharmacology (2008) 153, 290–298; doi:10.1038/sj.bjp.0707517; published online 29 October 2007