bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of long‐term treatment with fluoxetine and venlafaxine on rat isolated vas deferens
Authors: Göçmez S. S. , Utkan T. , Ulak G. , Gacar N. , Erden F. 
Published: June 2010

Summary 1 Antidepressant therapy is considered as one of the factors leading to male infertility. 2 In this study, the effects of long‐term treatment with fluoxetine or venlafaxine were investigated on electrical field stimulation (EFS, 1–64 Hz), noradrenaline (10−8 to 10−4 m), serotonin (10−8 to 10−4 m), adenosine 5′‐triphosphate [ATP (10−8 to 10−4 m)] and 80 mm KCl‐induced contractile responses in the epididymal and prostatic portions of rat isolated vas deferens strips. 3 Serotonin‐induced contractile responses were significantly increased in the epididymal portion of the vas deferens obtained from the fluoxetine‐treatment group, whereas in the prostatic portion there was no change. However, venlafaxine treatment had no effect on serotonin responses in the either portion of the vas deferens. Both fluoxetine and venlafaxine treatment significantly inhibited ATP‐evoked contractions of the prostatic and epididymal portions of the rat vas deferens, but had no effect on EFS, noradrenaline‐ and KCl‐evoked contractions of the vas deferentia in both portions. 4 In conclusion, these results suggest that chronic treatment with fluoxetine and venlafaxine affects vas deferens motility. Purinoceptors may, at least in part, responsible for the impaired motility in chronic treatment of venlafaxine and fluoxetine.
Acetyl‐l‐carnitine protects yeast cells from apoptosis and aging and inhibits mitochondrial fission
Authors: Palermo Vanessa , Falcone Claudio , Calvani Menotti , Mazzoni Cristina 
Published: June 2010

SummaryIn this work we report that carnitines, in particular acetyl‐l‐carnitine (ALC), are able to prolong the chronological aging of yeast cells during the stationary phase. Lifespan extension is significantly reduced in yca1 mutants as well in rho0 strains, suggesting that the protective effects pass through the Yca1 caspase and mitochondrial functions. ALC can also prevent apoptosis in pro‐apoptotic mutants, pointing to the importance of mitochondrial functions in regulating yeast apoptosis and aging. We also demonstrate that ALC attenuates mitochondrial fission in aged yeast cells, indicating a correlation between its protective effect and this process. Our findings suggest that ALC, used as therapeutic for stroke, myocardial infarction and neurodegenerative diseases, besides the well‐known anti‐oxidant effects, might exert protective effects also acting on mitochondrial morphology.
Pharmacokinetic interaction between itraconazole and metformin in rats: competitive inhibition of metabolism of each drug by each other via hepatic and intestinal CYP3A1/2
Authors: Choi YH , Lee U , Lee BK , Lee MG 
Published: June 2010

BACKGROUND AND PURPOSE Fungal infection is prevalent in patients with diabetes mellitus. Thus, we investigated whether a pharmacokinetic interaction occurs between the anti‐fungal agent itraconazole and the anti‐glycaemic drug metformin, as both drugs are commonly administered together to diabetic patients and are metabolized via hepatic CYP3A subfamily in rats.EXPERIMENTAL APPROACH Itraconazole (20 mg·kg−1) and metformin (100 mg·kg−1) were simultaneously administered i.v. and p.o. to rats. Concentrations (I) of each drug in the liver and intestine, maximum velocity (Vmax), Michaelis–Menten constant (Km) and intrinsic clearance (CLint) for the disappearance of each drug, apparent inhibition constant (Ki) and [I]/Ki ratios of each drug in the liver and intestine were determined. Also the metabolism of each drug in rat and human CYPs was measured in vitro.KEY RESULTS After simultaneous administration of both drugs, either i.v. or p.o., the total area under the plasma concentration–time curve from time zero to infinity (AUC)s of itraconazole and metformin were significantly greater than that of either drug administered alone. The metabolism of itraconazole and metformin was significantly inhibited by each other via CYP3A1 and 3A2 in rat and 3A4 in human microsomes.CONCLUSIONS AND IMPLICATIONS The significantly greater AUCs of itraconazole and metformin after i.v. administration of both drugs are probably due to competitive inhibition of the metabolism of each drug by each other via hepatic CYP3A1/2. Whereas after oral administration of both drugs, the significantly greater AUCs of each drug administered together than that of either drug alone is mainly due to competitive inhibition of intestinal metabolism of each drug by each other via intestinal CYP3A1/2.
Reversal of acid‐induced and inflammatory pain by the selective ASIC3 inhibitor, APETx2
Authors: Karczewski Jerzy , Spencer Robert H , Garsky Victor M , Liang Annie , Leitl Michael D , Cato Matthew J , Cook Sean P , Kane Stefanie , Urban Mark O 
Published: June 2010

BACKGROUND AND PURPOSE Inflammatory pain is triggered by activation of pathways leading to the release of mediators such as bradykinin, prostaglandins, interleukins, ATP, growth factors and protons that sensitize peripheral nociceptors. The activation of acid‐sensitive ion channels (ASICs) may have particular relevance in the development and maintenance of inflammatory pain. ASIC3 is of particular interest due to its restricted tissue distribution in the nociceptive primary afferent fibres and its high sensitivity to protons.EXPERIMENTAL APPROACH To examine the contribution of ASIC3 to the development and maintenance of muscle pain and inflammatory pain, we studied the in vivo efficacy of a selective ASIC3 inhibitor, APETx2, in rats.KEY RESULTS Administration of APETx2 into the gastrocnemius muscle prior to the administration of low pH saline prevented the development of mechanical hypersensitivity, whereas APETx2 administration following low‐pH saline was ineffective in reversing hypersensitivity. The prevention of mechanical hypersensitivity produced by acid administration was observed whether APETx2 was applied via i.m. or i.t. routes. In the complete Freund's adjuvant (CFA) inflammatory pain model, local administration of APETx2 resulted in a potent and complete reversal of established mechanical hypersensitivity, whereas i.t. application of APETx2 was ineffective.CONCLUSIONS AND IMPLICATIONS ASIC3 contributed to the development of mechanical hypersensitivity in the acid‐induced muscle pain model, whereas ASIC3 contributed to the maintenance of mechanical hypersensitivity in the CFA inflammatory pain model. The contribution of ASIC3 to established hypersensitivity associated with inflammation suggests that this channel may be an effective analgesic target for inflammatory pain states.
Late Holocene climatic variability reconstructed from incremental data from pines and pearl mussels – a multi‐proxy comparison of air and subsurface temperatures
Authors: HELAMA SAMULI , LÄÄNELAID ALAR , TIETÄVÄINEN HANNA , FAURIA MARC MACIAS , KUKKONEN ILMO T. , HOLOPAINEN JARI , NIELSEN JAN K. , VALOVIRTA ILMARI 
Published: June 2010

Helama, S., Läänelaid, A., Tietäväinen, H., Macias Fauria, M., Kukkonen, I. T., Holopainen, J., Nielsen, J. K. & Valovirta, I. 2010: Late Holocene climatic variability reconstructed from incremental data from pines and pearl mussels – a multi‐proxy comparison of air and subsurface temperatures. Boreas, Vol. 39, pp. 734–748. 10.1111/j.1502‐3885.2010.00165.x. ISSN 0300‐9483.Dendrochronological and sclerochronological records are mean series of arboreal and molluscan increments that are correctly aligned in time by rigorous dating. These records of tree rings and annual shell‐growth increments exhibit climate signals that can be used to reconstruct fluctuations and trends in past climates. Here we present a multi‐proxy reconstruction of temperature histories using a combination of dendrochronological and sclerochronological evidence. Regional curve standardization (RCS) was used to remove the non‐climatic variations from dendrochronological and sclerochronological series prior to palaeoclimatic interpretation. Conventional and signal‐free methods of RCS were compared. It was found that the signal‐free methods produced more reliable chronologies and systematically higher climate–proxy correlations. Consequently, the temperature reconstructions were derived using the chronologies constructed by this method. Proxy‐based histories of summer (July–August) temperatures were reconstructed from AD 1767 onwards. The compound use of proxies resulted in reconstructions that were of higher quality than single‐proxy reconstructions. Further improvement of reconstructions was accomplished by the inclusion of lagging increment values in the transfer functions. The final multi‐proxy model explained 58% of the temperature variance over the instrumental period. The multi‐proxy temperature reconstruction correlated well with the long records of instrumental temperatures from Tornedalen, St. Petersburg, Uppsala and Stockholm. Overall, the reconstruction for the past 250 years agreed reasonably well with borehole temperature reconstructions obtained in northern Finland. In general, this study demonstrates the benefits of the compound use of several proxies in reconstructing climate histories. In particular, the study emphasizes the so far largely unexploited advantages of multi‐proxy data sets obtained by rigorously cross‐dated incremental chronologies to produce more robust palaeoclimatic reconstructions.
Air Removal Efficiency of a Venous Bubble Trap in a Minimal Extracorporeal Circuit During Coronary Artery Bypass Grafting
Authors: Roosenhoff Tamara P.A. , Stehouwer Marco C. , De Vroege Roel , Butter René P. , Van Boven Wim‐Jan , Bruins Peter 
Published: June 2010

AbstractThe use of minimized extracorporeal circuits (MECC) in cardiac surgery is expanding. These circuits eliminate volume storage and bubble trap reservoirs to minimize the circuit. However, this may increase the risk of gaseous micro emboli (GME). To reduce this risk, a venous bubble trap was designed. This study was performed to evaluate if incorporation of a venous bubble trap in a MECC system as compared to our standard minimized extracorporeal circuit without venous bubble trap reduces gaseous micro emboli during cardiopulmonary bypass (CPB). Forty patients were randomly assigned to be perfused either with or without an integrated venous bubble trap. After preliminary evaluation of the data of 23 patients, the study was terminated prior to study completion. The quantity and volume of GME were significantly lower in patients perfused with a venous bubble trap compared to patients perfused without a venous bubble trap. The present study demonstrates that a MECC system with a venous bubble trap significantly reduces the volume of GME and strongly reduces the quantity of large GME (>500 µm). Therefore, the use of a venous bubble trap in a MECC system is warranted.
Effect of slice thickness on liver lesion detection and characterisation by multidetector CT
Authors: Smith JT , Hawkins RM , Guthrie JA , Wilson DJ , Arnold PM , Boyes S , Robinson PJ 
Published: June 2010

SummaryThe purpose of our study was to compare the effectiveness of 3.2 mm, 5 mm and 7.5 mm slice thicknesses in the detection and characterisation of liver lesions found on CT in patients with known or suspected malignant disease. 110 patients underwent portal phase imaging using four‐slice MDCT. Two blinded observers independently read hard copy images at each slice thickness. The size and location of each lesion detected was recorded by each observer on a diagram of liver segmental anatomy. Each lesion was characterised as benign, malignant or indeterminate in nature. A diagnostic confidence score was allocated for each lesion on a scale of 1–4. The pathology or behaviour of lesions was assessed using surgery with intra‐operative ultrasound (IOUS) and histology, or interval imaging with MRI, CT, or sonography. 294 lesions were detected, 64 (22%) of which were malignant. Both observers detected significantly more lesions on the 3.2 mm versus 7.5 mm slice thickness (p < 0.0001). Both observers detected more malignant lesions on 3.2 mm and 5 mm slice thicknesses versus 7.5 mm. As slice thickness decreased there was a significant increase in the sensitivity of malignant lesion detection for observer 1 (p < 0.001) and borderline significance for observer 2 (p = 0.07). As slice thickness decreased the proportion of lesions characterised as indeterminate by both observers fell. With thinner slices, both detection and characterisation of liver lesions were improved. A slice thickness no greater than 5 mm should be used to maximise both detection and correct characterisation of liver lesions.
Diffusion‐weighted MRI for tumour volume delineation: Comparison with morphological MRI
Authors: Wolf G , Schindler S , Koch A , Abolmaali N 
Published: June 2010

SummaryDiffusion‐weighted magnetic resonance imaging (dwMRI) is sensitive to tissue microstructure on the cellular level and may therefore help to define biological tumour subvolumes and add complementary information to morphology‐based cancer treatment protocols and therapy monitoring. The purpose of this study was therefore to evaluate the potential of dwMRI as compared with morphological MRI (mMRI) for tumour volume delineation using a nude rat human tumour xenograft model. Sixteen tumour‐bearing rats (10 H1299, six FaDu) were examined with mMRI (T2‐weighted true fast imaging with steady precession (TrueFISP), T1‐weighted fast low angle shot (FLASH), T2‐weighted dual echo steady state (DESS)) and echo‐planar dwMRI in a clinical scanner at 1.5 T. For each method, we compared tumour volume and intra‐ and inter‐observer variability of tumour outer edge delineation (disregarding intra‐tumoural structure) as well as tumour signal‐to‐noise ratio (SNR) and tumour‐to‐muscle contrast‐to‐noise ratio (CNR). Tumours were visualised with significantly higher SNR and CNR in dwMRI. Median tumour volumes as measured by dwMRI (3.5 cm3) and mMRI (TrueFISP: 3.3 cm3; FLASH: 3.3 cm3; DESS: 3.2 cm3) were not significantly different and significantly correlated. Related to partial volume effects, the intra‐ and inter‐observer variability of dwMRI (intra/inter: 12%/12%) was larger than for mMRI (TrueFISP: 4%/4%; FLASH: 5%/5%; DESS: 5%/5%). In conclusion, dwMRI allows tumour delineation with overall volume estimation comparable with mMRI approaches but slightly higher observer variability. Thus, besides tumour outline, it may potentially supplement morphology‐based therapy planning and monitoring with additional biological information.
Hypofractionated Whole‐Breast Radiotherapy: Impact on Departmental Waiting Times and Cost
Authors: Dwyer P , Hickey B , Burmeister E , Burmeister B 
Published: June 2010

SummaryConventionally fractionated breast radiation therapy is delivered over 5–6 weeks. Randomised evidence has shown that hypofractionated whole‐breast radiotherapy (HWBRT) over 3 weeks results in similar local control without increased toxicity. HWBRT is not standard practice in Australia for all eligible women. We examined the effect of using HWBRT (for eligible patients) on waiting lists and monetary costs. We identified factors associated with prescribing HWBRT. The Princess Alexandra Hospital Radiation Oncology Database was searched for all women with breast cancer treated with adjuvant radiotherapy in 2008. Included patients had undergone breast conserving surgery and had T1‐2N0 tumours with negative margins. Women with large breasts and those receiving nodal irradiation were excluded. The outcome evaluated was fractionation schedule. Patient, tumour and treatment factors associated with the use of HWBRT were examined. The impact on departmental resources and health‐care costs were calculated assuming the entire cohort received HWBRT. Two hundred seventy‐nine patients met the inclusion criteria. Sixty‐seven (24%) of these patients were treated with HWBRT. Compared with the conventionally fractionated breast radiation therapy group, the HWBRT group were older (median 69 vs. 54 years; P < 0.001) and more likely to have smaller tumours (12 mm vs. 15 mm; P = 0.02). Had all eligible patients received HWBRT an extra 14 patients each month could be treated and health‐care costs would be reduced by 24%. HWBRT was more frequently prescribed in older women with small tumours. More widespread use of HWBRT would allow significantly more patients to be treated each month with considerable cost savings.
Rectal dose reduction with IMRT for prostate radiotherapy
Authors: Hardcastle N , Davies A , Foo K , Miller A , Metcalfe PE 
Published: June 2010

SummaryDose escalation in radiation therapy has led to increased control rates with some clinical trial evidence that rectal toxicity may be reduced when using intensity‐modulated radiotherapy (IMRT) over 3D conformal radiotherapy (3DCRT) for dose‐escalated prostate radiotherapy. However, IMRT for prostate patients is not yet standard in many Australian radiation oncology centres. This study investigates dosimetric changes that can be observed between IMRT and 3DCRT in prostate radiotherapy. Fifteen patients were selected for analysis. Two target definitions were investigated – prostate‐only and prostate plus seminal vesicles (p + SVs). A five‐field 3DCRT and seven‐field IMRT plan were created for each patient and target definition. The planning target volume coverage was matched for both plans. Doses to the rectum, bladder and femoral heads were compared using dose volume histograms. The rectal normal tissue complication probabilities (NTCPs) were calculated and compared for the 3DCRT and IMRT plans. The delivery efficiency was investigated. The IMRT plans resulted in reductions in the V25, V50, V60, V70 and V75 Gy values for both the prostate‐only and p + SVs targets. Rectal NTCP was reduced with IMRT for three different sets of model parameters. The reductions in rectal dose and NTCP were much larger for the p + SVs target. Delivery of IMRT plans was less efficient than for 3DCRT plans. IMRT resulted in superior plans based on dosimetric and biological endpoints. The dosimetric gains with IMRT were greater for the more complex p + SVs target. The gains made came at the cost of decreased delivery efficiency.
Management of skin toxicity during radiation therapy: A review of the evidence
Authors: Kumar S , Juresic E , Barton M , Shafiq J 
Published: June 2010

SummaryAcute skin toxicity occurs in the majority of the patients undergoing radical radiotherapy. While a variety of topical agents and dressing are used to ameliorate side effects, there is minimal evidence to support their use. The aims of this study were to systematically review evidence on acute skin toxicity management and to assess the current practices in ANZ. A systematic review of the literature was conducted on studies published between 1980 and 2008. A meta‐analysis was performed on articles on clinical trials reporting grade II or greater toxicity. Analyses were divided into breast (the most common site) and other sites. A survey of Radiation Oncology departments across ANZ was conducted to identify patterns of practices and compare these with the published evidence. Twenty‐nine articles were reviewed. Only seven articles demonstrated statistically significant results for management of side‐effects. These were for topical corticosteroids, hyaluronic acid, sucralfate, calendula, Cavilon cream (3M, St Paul, Minnesota, USA) and silver leaf dressing. Meta‐analysis demonstrated statistical significance for the prophylactic use of topical agents in the management acute toxicity. The survey of departments had a low response rate but demonstrated variation in skin care practices across ANZ. A considerable number of these practices were based only on anecdotal evidence. Lack of evidence in the literature for the care of radiation skin reactions was associated with variation in practice. Only a limited number of studies have demonstrated a significant benefit of specific topical agents. There is a need for objective and prospective recording of skin toxicity to collect meaningful comparative data on which to base recommendations for practice.
Interleukin-7 Permits Th1/Tc1 Maturation and PromotesEx vivoExpansion of Cord Blood T Cells: A Critical Step toward Adoptive Immunotherapy after Cord Blood Transplantation
Authors: Davis Craig C. , Marti Luciana C. , Sempowski Gregory D. , Jeyaraj Durairaj A. , Szabolcs Paul 
Published: June 2010

AbstractDonor leukocyte infusions (DLI) in the allogeneic hematopoietic transplant setting can provide a clinically relevant boost of immunity to reduce opportunistic infections and to increase graft-versus-leukemia activity. Despite significant advances in applicability, DLI has not been available for single-unit recipients of unrelated cord blood transplant. Ex vivo expansion of cord blood T cells can be achieved with interleukin (IL)-2 and CD3/CD28 costimulatory beads. However, significant apoptosis occurs in proliferating T cells, diminishing the yield and skewing the CD4/CD8 ratio in the T-cell population, jeopardizing the potential efficacy of DLI. In this study, we show that interleukin (IL)-7 not only reduces apoptosis of activated T lymphocytes and enhances their proliferation but also promotes functional maturation, leading to secretion of IFN-γ and other key cytokines. Recognizing that infused T lymphocytes will need to meet microbial antigens in secondary lymphoid organs to generate effectors, we also show that expansion with IL-7 promotes the preservation of a polyclonal broad T-cell receptor repertoire and a surface phenotype that favors lymph node homing. Expanded lymphocytes lack alloreactivity against recipient and other allogeneic cells, indicating a favorable safety profile from graft-versus-host disease. Nevertheless, expanded T cells can be primed subsequently against lymphoid and myeloid leukemia cells to generate tumor-specific cytotoxic T cells. Taken together, our findings offer a major step in fulfilling critical numerical and biological requirements to quickly generate a DLI product ex vivo using a negligible fraction of a cord blood graft that provides a flexible adoptive immunotherapy platform for both children and adults. Cancer Res; 70(13); 5249–58. ©2010 AACR.
Angiopoietin-2 Regulates Gene Expression in TIE2-Expressing Monocytes and Augments Their Inherent Proangiogenic Functions
Authors: Coffelt Seth B. , Tal Andrea O. , Scholz Alexander , De Palma Michele , Patel Sunil , Urbich Carmen , Biswas Subhra K. , Murdoch Craig , Plate Karl H. , Reiss Yvonne , Lewis Claire E. 
Published: June 2010

Abstract
TIE2-expressing monocytes/macrophages (TEM) are a highly proangiogenic subset of myeloid cells in tumors. Here, we show that circulating human TEMs are already preprogrammed in the circulation to be more angiogenic and express higher levels of such proangiogenic genes as matrix metalloproteinase-9 (MMP-9), VEGFA, COX-2, and WNT5A than TIE2− monocytes. Additionally, angiopoietin-2 (ANG-2) markedly enhanced the proangiogenic activity of TEMs and increased their expression of two proangiogenic enzymes: thymidine phosphorylase (TP) and cathepsin B (CTSB). Three “alternatively activated” (or M2-like) macrophage markers were also upregulated by ANG-2 in TEMs: interleukin-10, mannose receptor (MRC1), and CCL17. To investigate the effects of ANG-2 on the phenotype and function of TEMs in tumors, we used a double-transgenic (DT) mouse model in which ANG-2 was specifically overexpressed by endothelial cells. Syngeneic tumors grown in these ANG-2 DT mice were more vascularized and contained greater numbers of TEMs than those in wild-type (WT) mice. In both tumor types, expression of MMP-9 and MRC1 was mainly restricted to tumor TEMs rather than TIE2− macrophages. Furthermore, tumor TEMs expressed higher levels of MRC1, TP, and CTSB in ANG-2 DT tumors than WT tumors. Taken together, our data show that although circulating TEMs are innately proangiogenic, exposure to tumor-derived ANG-2 stimulates these cells to exhibit a broader, tumor-promoting phenotype. As such, the ANG-2–TEM axis may represent a new target for antiangiogenic cancer therapies. Cancer Res; 70(13); 5270–80. ©2010 AACR.