bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient‐reported outcomes following islet cell or pancreas transplantation (alone or after kidney) in Type 1 diabetes: a systematic review
Authors: Speight J. , Reaney M. D. , Woodcock A. J. , Smith R. M. , Shaw J. A. M. 
Published: May 2010

Diabet. Med. 27, 812–822 (2010)AbstractAims  For selected individuals with complex Type 1 diabetes, pancreatic islet transplantation (IT) offers the potential of excellent glycaemic control without significant hypoglycaemia, balanced by the need for ongoing systemic immunosuppression. Increasingly, patient‐reported outcomes (PROs) are considered alongside biomedical outcomes as a measure of transplant success. PROs in IT have not previously been compared directly with the closest alternate treatment option, pancreas transplant alone (PTA) or pancreas after kidney (PAK).Methods  We used a Population, Intervention, Comparisons, Outcomes (PICO) strategy to search Scopus and screened 314 references for inclusion.Results  Twelve studies [including PRO assessment of PAK, PTA, islet‐after kidney (IAK) and islet transplant alone (ITA); n = 7–205] used a total of nine specified and two unspecified PRO measures. Results were mixed but identified some benefits which remained apparent up to 36 months post‐transplant, including improvements in fear of hypoglycaemia, as well as some aspects of diabetes‐specific quality of life (QoL) and general health status. Negative outcomes included short‐term pain associated with the procedure, immunosuppressant side effects and depressed mood associated with loss of graft function.Conclusions  The mixed results may be attributable to limited sample sizes. Also, some PRO measures may lack sensitivity to detect actual changes, as they exclude issues and domains of life likely to be important for QoL post‐transplantation and when patients may no longer perceive themselves to have diabetes. Thus, the full impact of islet/pancreas transplantation (alone or after kidney) on QoL is unknown. Furthermore, no studies have assessed patient satisfaction, which may highlight further advantages and disadvantages of transplantation.
WHO'S ARGUING? A CALL FOR REFLEXIVITY IN BIOETHICS
Authors: IVES JONATHAN , DUNN MICHAEL 
Published: May 2010

ABSTRACTIn this paper we set forth what we believe to be a relatively controversial argument, claiming that ‘bioethics’ needs to undergo a fundamental change in the way it is practised. This change, we argue, requires philosophical bioethicists to adopt reflexive practices when applying their analyses in public forums, acknowledging openly that bioethics is an embedded socio‐cultural practice, shaped by the ever‐changing intuitions of individual philosophers, which cannot be viewed as a detached intellectual endeavour. This said, we argue that in order to manage the personal, social and cultural embeddedness of bioethics, philosophical bioethicists should openly acknowledge how their practices are constructed and should, in their writing, explicitly deal with issues of bias and conflict of interest, just as empirical scientists are required to do.
THE FUTURE OF BIOETHICS: THREE DOGMAS AND A CUP OF HEMLOCK
Authors: DAWSON ANGUS 
Published: May 2010

ABSTRACTIn this paper I argue that bioethics is in crisis and that it will not have a future unless it begins to embrace a more Socratic approach to its leading assumptions. The absence of a critical and sceptical spirit has resulted in little more than a dominant ideology. I focus on three key issues. First, that too often bioethics collapses into medical ethics. Second, that medical ethics itself is beset by a lack of self‐reflection that I characterize here as a commitment to three dogmas. Third, I offer a more positive perspective by suggesting how bioethics may benefit from looking towards public health ethics as a new source of inspiration and direction.
Ownership and the Value of Political Connections: Evidence from China
Authors: Wu Wenfeng , Wu Chongfeng , Rui Oliver M. 
Published: May 2010

AbstractResearch has found that political connectedness can have both positive and negative effects on firm value. To resolve these mixed findings, we investigate the impact of political ties conditional on ownership for a sample of Chinese firms over the period 1999–2006. We find that private firms with politically connected managers have a higher value and obtain more government subsidies than those without connected managers, whereas local state‐owned enterprises with connected managers have a lower value and employ more surplus labour than those without connected managers. Our results indicate that the effect of political ties is subject to firm ownership.
High concentrations of dexmedetomidine inhibit compound action potentials in frog sciatic nerves without α2adrenoceptor activation
Authors: Kosugi Toshifumi , Mizuta Kotaro , Fujita Tsugumi , Nakashima Mikio , Kumamoto Eiichi 
Published: May 2010

BACKGROUND AND PURPOSEDexmedetomidine, an α2‐adrenoceptor agonist, exhibits anti‐nociceptive actions at the spinal cord and enhances the effect of local anaesthetics in the peripheral nervous system. Although the latter action may be attributed in part to inhibition of nerve conduction produced by dexmedetomidine, this has not been fully examined yet.EXPERIMENTAL APPROACHWe examined the effects of various adrenoceptor agonists including dexmedetomidine, and tetracaine, a local anaesthetic, on compound action potentials (CAPs) recorded from the frog sciatic nerve, using the air‐gap method.KEY RESULTSDexmedetomidine reversibly and concentration‐dependently reduced the peak amplitude of CAPs (IC50= 0.40 mmol·L−1). This action was not antagonized by two α2‐adrenoceptor antagonists, yohimbine and atipamezole; the latter antagonist itself reduced CAP peak amplitude. Clonidine and oxymetazoline, two other α2‐adrenoceptor agonists, also inhibited CAPs; the maximum effect of clonidine was only 20%, while oxymetazoline was less potent (IC50= 1.5 mmol·L−1) than dexmedetomidine. On the other hand, (±)‐adrenaline, (±)‐noradrenaline, α1‐adrenoceptor agonist (‐)‐phenylephrine and β‐adrenoceptor agonist (‐)‐isoprenaline (each 1 mmol·L−1) had no effect on CAPs. Tetracaine reversibly reduced CAP peak amplitude (IC50of 0.014 mmol·L−1).CONCLUSIONS AND IMPLICATIONSDexmedetomidine reduced CAP peak amplitude without α2‐adrenoceptor activation (at concentrations >1000‐fold higher than those used as α2adrenoceptor agonist), with a lower potency than tetracaine. CAPs were inhibited by other α2adrenoceptor agonists, oxymetazoline and clonidine, and also an α2adrenoceptor antagonist atipamezole. Thus, some drugs acting on α2adrenoceptors are able to block nerve conduction.
Irbesartan treatment up‐regulates hepatic expression of PPARα and its target genes in obese Koletsky (fak/fak) rats: a link to amelioration of hypertriglyceridaemia
Authors: Rong X , Li Y , Ebihara K , Zhao M , Kusakabe T , Tomita T , Murray M , Nakao K 
Published: May 2010

BACKGROUND AND PURPOSEHypertriglyceridaemia is associated with an increased risk of cardiovascular disease. Irbesartan, a well‐established angiotensin II type 1 receptor (AT1) blocker, improves hypertriglyceridaemia in rodents and humans but the underlying mechanism of action is unclear.EXPERIMENTAL APPROACHMale obese Koletsky (fak/fak) rats, which exhibit spontaneous hypertension and metabolic abnormalities, received irbesartan (40 mg·kg−1·day−1) or vehicle by oral gavage over 7 weeks. Adipocyte‐derived hormones in plasma were measured by ELISA. Gene expression in liver and other tissues was assessed by real‐time PCR and Western immunoblotting.KEY RESULTSIn Koletsky (fak/fak) rats irbesartan lowered plasma concentrations of triglycerides and non‐esterified fatty acids, and decreased plasma insulin concentrations and the homeostasis model assessment of insulin resistance index. However, this treatment did not affect food intake, body weight, epididymal white adipose tissue weight, adipocyte size and plasma leptin concentrations, although plasma adiponectin was decreased. Irbesartan up‐regulated hepatic expression of mRNAs corresponding to peroxisome proliferator‐activated receptor (PPAR)α and its target genes (carnitine palmitoyltransferase‐1a, acyl‐CoA oxidase and fatty acid translocase/CD36) that mediate hepatic fatty acid uptake and oxidation; the increase in hepatic PPARα expression was confirmed at the protein level. In contrast, irbesartan did not affect expression of adipose PPARγ and its downstream genes or hepatic genes that mediate fatty acid synthesis.CONCLUSIONS AND IMPLICATIONSThese findings demonstrate that irbesartan treatment up‐regulates PPARα and several target genes in liver of obese spontaneously hypertensive Koletsky (fak/fak) rats and offers a novel insight into the lipid‐lowering mechanism of irbesartan.
Stimulatory effects of the multi‐kinase inhibitor sorafenib on human bladder cancer cells
Authors: Rose A , Grandoch M , vom Dorp F , Rübben H , Rosenkranz A , Fischer JW , Weber A‐A 
Published: May 2010

BACKGROUND AND PURPOSESorafenib is an inhibitor of several intracellular signalling kinases with anti‐proliferative, anti‐angiogenic and pro‐apoptotic effects in tumour cells. Sorafenib is used in the therapy of advanced renal cell carcinoma, and several phase II clinical trials are being carried out in patients with urothelial carcinomas.EXPERIMENTAL APPROACHUsing a panel of human bladder cancer cell lines (RT4, T24, J82), we characterized systematically the effects of sorafenib on intracellular signalling, migration, proliferation and apoptosis.KEY RESULTSWe demonstrated that at low concentrations (<1 µM), sorafenib is capable of significantly stimulating migration and proliferation of the bladder cancer cells. We hypothesize that these stimulatory effects on tumour cell functions might be explained by an activation of the Ras/ERK‐1/2 signal transduction pathway. In addition, the comparison of different bladder cancer cell lines not only revealed a different biology (e.g. cell migration), but also a differential susceptibility to the anti‐apoptotic effects of sorafenib. Finally, we confirmed in different bladder cancer cell lines the known inhibitory actions of sorafenib in pharmacological concentrations (≥3 µM) on ERK‐1/2 phosphorylation, migration and proliferation, as well as the pro‐apoptotic effects of the compound.CONCLUSIONS AND IMPLICATIONSTaken together, these findings suggest that although sorafenib has the potential to be used in the treatment of urothelial carcinoma, this compound might also activate bladder cancer cells at low concentrations. This should be relevant for dosing regiments to optimize the treatment with this promising anti‐tumour drug.
Inhibition of choriodecidual cytokine production and inflammatory gene expression by selective I‐κB kinase (IKK) inhibitors
Authors: De Silva D , Mitchell MD , Keelan JA 
Published: May 2010

BACKGROUND AND PURPOSEInflammation of the extraplacental membranes plays a key role in the pathogenesis of preterm labour. The aim of this study was to screen a number of commercially available small molecule nuclear factor‐kappa B inhibitors to identify candidates suitable for clinical evaluation as anti‐inflammatory agents for the prevention of preterm birth.EXPERIMENTAL APPROACHNine inhibitors were evaluated across a range of concentrations for their ability to inhibit lipopolysaccharide (LPS)‐stimulated cytokine production in primary term choriodecidual cells in culture without affecting cell viability. Expression of 112 inflammation‐ and apoptosis‐related genes was evaluated using boutique oligonucleotide arrays.KEY RESULTSTwo IKKβ inhibitors were found to be highly effective and non‐toxic inhibitors of choriodecidual cytokine production: parthenolide and [5‐(p‐fluorophenyl)‐2‐ureido] thiophene‐3‐carboxamide (TPCA‐1). Both compounds also inhibited LPS‐stimulated nuclear translocation of p65/RelA. Expression of 38 genes on the arrays (34%) was significantly (P < 0.05) inhibited by TPCA‐1 or parthenolide. Of the 14 genes significantly stimulated by LPS, all were inhibited by TPCA‐1 and 12 were inhibited by parthenolide. Overall, gene expression was more robustly inhibited by TPCA‐1 than parthenolide; however, expression of two genes was only inhibited by parthenolide. Neither compound significantly altered the expression profile of anti‐apoptosis genes on the arrays.CONCLUSIONS AND IMPLICATIONSThese studies provide evidence that pharmacological inhibition of IKKβ activity holds promise as a potential strategy for the prevention and/or treatment of inflammation‐driven preterm birth. TPCA‐1 appeared the most promising compound among those tested in this study. Different inhibitors may have subtly different effect profiles despite having similar modes of action.
Investigation of the distribution and function of α‐adrenoceptors in the sheep isolated internal anal sphincter
Authors: Rayment SJ , Eames T , Simpson JAD , Dashwood MR , Henry Y , Gruss H , Acheson AG , Scholefield JH , Wilson VG 
Published: May 2010

BACKGROUND AND PURPOSEWe have investigated the distribution of α‐adrenoceptors in sheep internal anal sphincter (IAS), as a model for the human tissue, and evaluated various imidazoline derivatives for potential treatment of faecal incontinence.EXPERIMENTAL APPROACHSaturation and competition binding with3H‐prazosin and3H‐RX821002 were used to confirm the presence and density of α‐adrenoceptors in sheep IAS, and the affinity of imidazoline compounds at these receptors. A combination ofin vitroreceptor autoradiography and immunohistochemistry was used to investigate the regional distribution of binding sites. Contractile activity of imidazoline‐based compounds on sheep IAS was assessed by isometric tension recording.KEY RESULTSSaturation binding confirmed the presence of both α1‐ and α2‐adrenoceptors, and subsequent characterization with sub‐type‐selective agents, identified them as α1A‐ and α2D‐adrenoceptor sub‐types. Autoradiographic studies with3H‐prazosin showed a positive association of α1‐adrenoceptors with immunohistochemically identified smooth muscle fibres. Anti‐α1‐adrenoceptor immunohistochemistry revealed similar distributions of the receptor in sheep and human IAS. The imidazoline compounds caused concentration‐dependent contractions of the anal sphincter, but the maximum responses were less than those elicited byl‐erythro‐methoxamine, a standard non‐imidazoline α1‐adrenoceptor agonist. Prazosin (selective α1‐adrenoceptor antagonist) significantly reduced the magnitude of contraction tol‐erythro‐methoxamine at the highest concentration used. Both prazosin and RX811059 (a selective α2‐adrenoceptor antagonist) reduced the potency (pEC50) of clonidine.CONCLUSIONS AND IMPLICATIONSThis study shows that both α1‐ and α2‐adrenoceptors are expressed in the sheep IAS, and contribute (perhaps synergistically) to contractions elicited by various imidazoline derivatives. These agents may prove useful in the treatment of faecal incontinence.
Anti‐glycophorin C induces mitochondrial membrane depolarization and a loss of extracellular regulated kinase 1/2 protein kinase activity that is prevented by pretreatment with cytochalasin D: implications for hemolytic disease of the fetus and newborn caused by anti‐Ge3
Authors: Micieli Jonathan A. , Wang Duncheng , Denomme Gregory A. 
Published: May 2010

BACKGROUND: Anti‐glycophorin C (GPC), blood group antibodies of which cause hemolytic disease of the fetus and newborn (HDFN), is a potent inhibitor of erythroid progenitor cell growth. The cellular mechanism for growth inhibition has not been characterized.STUDY DESIGN AND METHODS: K562 cells were incubated in the presence of either anti‐GPC, an immunoglobulin G isotype control, an inhibitor of actin polymerization called cytochalasin D with anti‐GPC, or cytochalasin D alone. The JC‐1 cationic dye was used to detect mitochondrial depolarization and the activity of the mitogen‐activated protein kinases was assessed by Western blotting.RESULTS: Anti‐GPC inhibits the activity of extracellular regulated kinase (ERK)1/2 within 10 minutes but does not alter the activity of p38 or c‐Jun N‐terminal kinase. After 24 hours there was a significant loss of mitochondrial membrane potential compared to isotype control–treated cells. Both the ERK1/2 inhibition and the loss of mitochondrial potential were prevented by pretreatment with cytochalasin D.CONCLUSION: A cell surface antibody can cause anemia by altering the signaling pathways in erythroid cells by promoting depolarization of mitochondria via cytoskeletal rearrangement. The observation that neonates with anti‐GPC HDFN are unresponsive to erythropoietin can be explained by the antibody inhibiting a protein kinase through which this hematopoietic growth factor achieves its effects.
Physiological trade‐offs between flight muscle and reproductive development in the wing‐dimorphic cricket Velarifictorus ornatus
Authors: Zhao Lv‐Quan , Zhu Dao‐Hong , Zeng Yang 
Published: May 2010

AbstractMorphology, flight muscles, and reproductive development were compared between long‐winged (LW) and short‐winged (SW) morphs of the cricket Velarifictorus ornatus (Shiraki) (Orthoptera: Gryllidae). There was no difference in body weight and pre‐oviposition between the two morphs, but LW individuals had better‐developed flight muscles than SW individuals during and after emergence of the adult. The flight muscles at adult emergence represented 11.9% of the total body weight in the LW female and 4.9% in the SW female. In addition, the weight of the flight muscle of LW females increased by 50% during the first 5 days, whereas the flight muscle of the SW variant increased only slightly after adult emergence. The process of oviposition in LW, SW, and de‐alated females varied: SW females produced more eggs at the early stage than LW females, but de‐alation could shorten the time until the peak of egg laying and caused histolysis of flight muscles of LW females. There was no significant difference in total egg production between the above three groups. In the male, unlike the female, the accessory glands of the two wing morphs enlarged continuously at the same rate. There was no difference between the two wing morphs in the mass of the testes during the first 7 days after adult emergence.
Stimuli associated with viburnum leaf beetle (Pyrrhalta viburni) aggregative oviposition behavior
Authors: Desurmont Gaylord A. , Weston Paul A. 
Published: May 2010

AbstractViburnum leaf beetle, Pyrrhalta viburni (Paykull) (Coleoptera: Chrysomelidae), oviposits in terminal twigs of Viburnum spp. shrubs (Caprifoliaceae). Twigs react to oviposition by producing neoplasm that overgrows the egg mass. Pyrrhalta viburni oviposition behavior is aggregative: females prefer to lay egg masses on twigs previously infested by other females and to position their egg masses adjacent to existing ones. Female oviposition preferences were studied in a series of choice tests under laboratory conditions. The three components of the egg mass (cavity, eggs, and egg cap) were not sufficient to elicit complete aggregation oviposition response when presented separately. Cavity and egg cap elicited positional preference, but not the artificial cavity, artificial egg cap, or frass, suggesting that stimulatory cues might be associated with insect saliva and egg cap secretion. Females preferred to lay eggs on twigs that had produced wound tissue in response to previous oviposition. We conclude that twig choice and positional preference for oviposition are likely to be dissociated, and that twig wound response might be used by P. viburni females to locate twigs already infested and possibly less defended against subsequent oviposition. Pyrrhalta viburni females preferred to lay egg masses on heavily infested twigs rather than on lightly infested twigs. Females did not show preference for twigs infested with their own egg masses, but laid more egg masses on twigs infested by multiple females than on twigs infested by single females. We conclude that both egg mass and conspecific density affect oviposition preferences of P. viburni and discuss the possible ecological implications of this behavior.
Larval crowding effects on the mosquito Culex quinquefasciatus: physical or chemical?
Authors: Roberts Derek , Kokkinn Michael 
Published: May 2010

Abstract Culex quinquefasciatus Say (Diptera: Culicidae) is an abundant urban mosquito that is the vector of filariasis. Breeding in septic tanks, where there are very high levels of bacterial food, it is likely to have a different reaction to crowding compared with other mosquitoes. To test for the presence and type of crowding effects, four larval densities of C. quinquefasciatus varying from 0.4 to 3.2 larvae ml−1 of water were reared in tubes. Mortality was found to greatly increase at densities above 0.8 larvae, whereas larval duration increased even above 0.4 larvae ml−1. Changing the water in the tubes daily gave a small (but significant) response in reducing mortality and larval duration. However, when larvae kept at a low density shared the same water with larvae at high density, there was no chemical influence on their growth rate and mortality. The effect of crowding was primarily due to physical disturbances between larvae. When larvae were kept at a high density in the same volume of water, but in shallow trays with a large surface area and therefore much less contact between them, mortality was the same as for the lowest density. There was still, however, a significant increase in larval duration from 8.6 days at 0.4 larvae ml−1 to 12.1 days at 3.2 larvae ml−1. It is therefore concluded that the larvae respond to physical rather than chemical factors by prolonging larval development and having some increase in mortality.
Mi‐mediated aphid resistance in tomato: tissue localization and impact on the feeding behavior of two potato aphid clones with differing levels of virulence
Authors: Pallipparambil Godshen R. , Reese John C. , Avila Carlos A. , Louis Joe M. , Goggin Fiona L. 
Published: May 2010

AbstractThe Mi‐1.2 gene in tomato, Solanum lycopersicum L. (Solanaceae), confers resistance against several herbivores, including the potato aphid, Macrosiphum euphorbiae (Thomas) (Hemiptera: Sternorrhyncha: Aphididae) and the sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Sternorrhyncha: Aleyrodidae). Previous studies on the tissue localization of resistance have given varying results; whitefly resistance was attributed to factors localized in the mesophyll or epidermis, whereas aphid resistance was attributed to factors localized in the phloem. Our study utilizes the direct current electrical penetration graph (DC‐EPG) technique to compare aphid feeding behavior on resistant (Mi‐1.2+) and susceptible (Mi‐1.2−) tomato plants. This study also compares the impact of resistance on the feeding behavior of two aphid clones that vary in their virulence, or their ability to survive and reproduce on resistant plants. Previous work had shown that the avirulent WU11 clone is almost completely inhibited by resistance, whereas the semi‐virulent WU12 clone can colonize resistant hosts. Here, DC‐EPG analysis shows that both aphid clones take longer to initiate cell sampling and to establish a confirmed sieve element phase on resistant plants than on susceptible hosts, and have shorter ingestion periods on resistant plants. However, the magnitude of these deterrent effects is far less for the semi‐virulent clone than for the avirulent aphids. In particular, the WU12 clone is less sensitive to factors that limit sieve element ingestion, showing shorter non‐probe duration and rapidly establishing sustained phloem ingestion on resistant plants when compared to the WU11 clone. We conclude that, in addition to previously described factors in the phloem that inhibit ingestion, Mi‐mediated aphid resistance also involves factors (possibly in the mesophyll and/or epidermis) that delay initiation of phloem salivation, and that act in the intercellular spaces to deter the first cell sampling. Furthermore, the relative effectiveness of these components of resistance differs among insect populations.