bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Bupropion a More Specific Substrate for Porcine CYP2E than Chlorzoxazone andp‐Nitrophenol?
Authors: Skaanild Mette T. , Friis Christian 
Published: June 2007

Abstract:  Porcine microsomes are able to hydroxylate chlorzoxazone andp‐nitrophenol, the most commonly used human test substrates for CYP2E1. However, in pigs, CYP2E appears not to be the only enzyme involved in the hydroxylation of chlorzoxazone andp‐nitrophenol, as the enzyme capacity and immunochemical level of the apoprotein do not correlate. The present study shows that the hydroxylation of chlorzoxazone andp‐nitrophenol is inhibited 50–65% by anti‐human CYP2A6, suggesting that these substrates are metabolized almost equally well by CYP2A and CYP2E in pigs. To find an alternative probe to porcine CYP2E, bupropion, another human substrate, was examined. Incubation with bupropion concentrations ranging from 0.05 to 20 mM and with various inhibitors revealed that this substrate is metabolized by both CYP2A and CYP2E. At the high substrate concentration (5 mM), however, the CYP2A6 inhibition decreased compared to inhibition percentages found using the low substrate concentration (0.5 mM). The opposite was found for CYP2E, as inhibition studies with antibodies and diethyldithiocarbamate indicate that it catalysed a negligible part of the reaction at the low substrate concentration and up to 84% at the high concentration. Thus, hydroxylation of bupropion follows the same pattern in pigs as in human beings and the activity measured in pigs is comparable with the human counterpart. Furthermore, bupropion is a more specific substrate for CYP2E than chlorzoxazone andp‐nitrophenol although not perfect.
External World Skepticism
Authors: Greco John 
Published: June 2007

AbstractRecent literature in epistemology has focused on the following argument for skepticism (SA): I know that I have two hands only if I know that I am not a handless brain in a vat. But I don't know I am not a handless brain in a vat. Therefore, I don't know that I have two hands. Part I of this article reviews two responses to skepticism that emerged in the 1980s and 1990s: sensitivity theories and attributor contextualism. Part II considers the more recent ‘neo‐Moorean’ response to skepticism and its development in ‘safety’ theories of knowledge. Part III argues that the skeptical argument set out in SA is not of central importance. Specifically, SA is parasitic on skeptical reasoning that is more powerful and more fundamental than that displayed by SA itself. Finally, Part IV reviews a Pyrrhonian argument for skepticism that is not well captured by SA, and considers a promising strategy for responding to it.
Spirituality and the Body in Late Modernity
Authors: Dziuban Agata 
Published: June 2007

AbstractThe aim of this article is to examine the role of the body in contemporary spirituality. The body is understood here as being simultaneously individual and social, a corporeal phenomenon, that is, on one hand, a ‘lived experience’ that forms the basis of self‐identity and, on the other, an entity affected by the social system. As such, the body plays an important role in mediating the relationship between one's self‐identity and one's social identity. This article focuses on three particular contemporary phenomena: the conceptualizations of the body presented by both the New Age movements and feminism (especially ecofeminism), as well as the trend towards modifying the body in particular ways, primarily through tattooing and piercing. These movements are understood in terms of Anthony Giddens’ broader conceptualization of the conditions of life in late modernity, in particular his discussion of the reflexive project of identity, and his and other theorists’ speculations on the new grounds for spirituality in the face of heightened ontological uncertainty of our times. I will show that, during the processes of both autonomous self‐expression and identity (trans)formation, the body (as well as the self) is being sacralized, in the sense that it is treated as the subject, rather than an object, through which an individual undertakes the quest for spiritual development.
Endothelium‐dependent relaxation of isolated splanchnic arteries from cirrhotic patients: Role of reactive oxygen species
Authors: Salcedo Adely , Garijo Jesús , Monge Luis , Sánchez Ana , Fernández Nuria , García‐Villalón Angel L. , Turrión Víctor S. , Cuervas‐Mons Valentín , Diéguez Godofredo 
Published: June 2007

Aim:  To examine the endothelium‐dependent relaxation of splanchnic arteries during cirrhosis as well as the role of reactive oxygen species in this relaxation using hepatic arteries from cirrhotic patients undergoing liver transplantation and mesenteric arteries from liver donors.Methods:  Arterial segments 3 mm long were mounted in organ baths for isometric tension recording and precontracted with the thromboxane A2 analog U46619 (10−7−10−6 M).Results:  The relaxation to acetylcholine (10−8−10−4 M), but not to sodium nitroprusside (10−8−10−4 M) was lower in hepatic arteries. The inhibitor of nitric oxide synthesis, Nω‐nitro‐l‐arginine methyl ester (l‐NAME, 10−4 M), the inhibitor of cyclooxygenase, meclofenamate (10−5 M), or l‐NAME (10−4 M) + meclofenamate (10−5 M) diminished the relaxation to acetylcholine only in mesenteric arteries. l‐NAME (10−4 M) + meclofenamate (10−5 M) combined with charybdotoxin (10−7 M) + apamine (10−6 M) inhibited the relaxation toacetylcholine in both types of arteries, and this inhibition was greater than with l‐NAME + meclofenamate. The scavenger of hydrogen peroxide, catalase (1000 U/mL), the superoxide dismutase mimetic, tiron (10−2 M) or the inhibitor of NAD(P)H oxidase, diphenyleneiodonium (5 × 10−6 M), but not the inhibitor of superoxide dismutase, diethyldithiocarbamate (10−3 M) potentiated the acetylcholine‐induced relaxation only in hepatic arteries. l‐NAME did inhibit the relaxation to acetylcholine in hepatic arteries pretreated with catalase or tiron.Conclusions:  Cirrhosis may decrease endothelial release and/or bioavailability of nitric oxide and prostacyclin in splanchnic arteries, which might be caused partly by increased production of reactive oxygen species.
Changes in circulating cytokine levels and lymphocyte subsets in healthy liver donors after partial hepatectomy
Authors: Nakashima Sayori , Katano Yoshiaki , Nakano Isao , Hirooka Yoshiki , Ito Akihiro , Ishigami Masatoshi , Hayashi Kazuhiko , Honda Takashi , Goto Hidemi 
Published: June 2007

Aim:  Studies of animal models have determined that liver regeneration after partial hepatectomy is mediated by a various cytokines. The aim of the present study was to evaluate the levels of these cytokines and subsets of circulating lymphocytes in healthy humans after partial hepatectomy.Methods:  Four individuals underwent partial hepatectomy for living‐related donor liver transplantation. We also evaluated for comparison, three patients with myoma uteri who underwent hysterectomy. Blood samples were obtained before surgery and on postoperative days (PD) 1, 3, and 7. Serum levels of hepatocyte growth factor, interleukin (IL)‐6, ‐10, and plasma levels of transforming growth factor beta were measured.Results:  Increased circulating levels of hepatocyte growth factor and transforming growth factor beta were observedafter hepatectomy. The levels of IL‐6 and IL‐10 peaked on PD 1. Circulating white blood cell counts increased remarkably, whereas lymphocyte count decreased particularly on PD 1 and 3. CD4/CD8 and T‐helper cell (Th)1/Th2 ratios were still decreased on PD 7. The percentage of natural killer cells was increased on PD 1. Partial hepatectomy in healthy humans leads not only to decreased lymphocyte counts, but also to remarkable changes in lymphocyte subsets.Conclusion:  These findings suggest that immune suppression after partial hepatectomy involves decreases in CD4+ helper T cells, particularly Th1 cells.
Alterations of DNA methylation and histone modifications contribute to gene silencing in hepatocellular carcinomas
Authors: Kondo Yutaka , Shen Lanlan , Suzuki Seiji , Kurokawa Tsuyoshi , Masuko Kazuo , Tanaka Yasuhito , Kato Hideaki , Mizuno Yoshiki , Yokoe Masamichi , Sugauchi Fuminaka , Hirashima Noboru , Orito Etsuro , Osada Hirotaka , Ueda Ryuzo , Guo Yi , Chen Xinli , Issa Jean‐Pierre J. , Sekido Yoshitaka 
Published: June 2007

Aim:  The aim of the present study was to examine DNA methylation and histone modification changes in hepatocellular carcinomas (HCC).Methods:  DNA methylation in the P16, RASSF1a, progesterone receptor (PGR) and estrogen receptor α (ERα) promoters was determined by quantitative bisulfite‐pyrosequencing technique in HCC patients. Histone H3‐lysine (K) 4, H3‐K9 and H3‐K27 modifications in all these four genes were examined by chromatin immunoprecipitation (ChIP) assay in HCC cell lines. Expression of two DNA methyltransferases (DNMT1 and DNMT3b) and three histone methyltransferases (SUV39H1, G9a and EZH2) in HCC patients was measured by real‐time polymerase chain reaction.Results:  Aberrant DNA methylation was detected in all the HCC. Patients with DNA methylation in the RASSF1a, PGR andERα promoters in cancers also had substantial DNA methylation in their non‐cancerous liver tissues, whereas DNA methylation in the P16 promoter was cancer specific. Epigenetic states in HCC cell lines showed that silencing of P16 and RASSF1a depended on DNA methylation and histone H3‐K9 methylation. However, silencing of the PGR and ERα genes was more closely related to H3‐K27 methylation rather than DNA methylation. Consistent with the alteration of histone status, higher expression of G9a and EZH2 was found in HCC than in non‐cancerous liver tissues (P < 0.01).Conclusion:  These data suggest that multiple epigenetic silencing mechanisms are inappropriately active in HCC cells.
The fraction of long-term sickness absence attributable to work environmental factors: prospective results from the Danish Work Environment Cohort Study: Table 1
Authors: Bang Christensen Karl , Lund Thomas , Labriola Merete , Villadsen Ebbe , Bültmann Ute 
Published: June 2007

Objective:To examine the fraction of long-term sickness absence periods attributable to physical and psychosocial work environmental risk factors.Method:A random population sample was followed for 18 months in a national register of social transfer payments. Mutually adjusted hazard ratios for onset of long-term sickness absence and aetiological fractions were computed.Results:After mutual adjustment, no significant effect of psychosocial work environment factors remained. In men, 23% and 28% of long-term sickness absence were attributable to working mainly standing or squatting, and lifting or carrying loads, respectively. In women, 27% of long-term sickness absence was attributable to bending or twisting of the neck or back.Conclusions:Physical work environment exposures explained between 10% and 30% of long-term sickness absence. The potential for reducing long-term sickness absence is substantial.
The Incidence and Characteristics of Shoulder Instability at the United States Military Academy
Authors: Owens Brett D. , Duffey Michele L. , Nelson Bradley J. , DeBerardino Thomas M. , Taylor Dean C. , Mountcastle Sally B. 
Published: June 2007

Background The literature provides little information detailing the incidence of traumatic shoulder instability in young, healthy athletes. Hypothesis Shoulder instability is common in young athletes. Study Design Descriptive epidemiologic study. Methods We prospectively captured all traumatic shoulder instability events at the United States Military Academy between September 1, 2004, and May 31, 2005. Throughout this period, all new traumatic shoulder instability events were evaluated with physical examination, plain radiographs, and magnetic resonance imaging. Instability events were classified according to direction, chronicity, and type (subluxation or dislocation). Subject demographics, mechanism of injury, and sport were evaluated. Results Among 4141 students, 117 experienced new traumatic shoulder instability events during the study period; 11 experienced multiple events. The mean age of these 117 subjects was 20.0 years; 101 students were men (86.3%), and 16 were women (13.7%). The 1-year incidence proportion was 2.8%. The male incidence proportion was 2.9% and the female incidence proportion was 2.5%. Eighteen events were dislocations (15.4%), and 99 were subluxations (84.6%). Of the 99 subluxations, 45 (45.5%) were primary events, while 54 (54.5%) were recurrent. Of the 18 dislocations, 12 (66.7%) were primary events, while 6 (33.3%) were recurrent. The majority of the 117 events were anterior in nature (80.3%), while 12 (10.3%) were posterior, and 11 (9.4%) were multidirectional. Forty-four percent (43.6%) of the instability events experienced were as a result of contact injuries, while 41.0% were a result of noncontact injuries, including 9 subluxations caused by missed punches during boxing; information was unavailable for the remaining 15%. Conclusion Glenohumeral instability is a common injury in this population, with subluxations comprising 85% of instability events.
Endothelial Cell Seeding onto Various Biomaterials Causes Superoxide-induced Cell Death
Authors: Coyle Christian H. , Mendralla Scott , Lanasa Stephanie , Kader Khalid N. 
Published: June 2007

The seeding and/or in-growth of endothelial cells on a number of blood-contacting implants are a concern for both biomaterials and tissue engineering. While endothelialization has been viewed positively, owing to their ability to regulate both smooth muscle and blood, there is evidence which suggests that endothelial cells on a nonoptimized surface may be counterproductive. The present study describes the experimentation designed to elucidate the effect of culture substrate on intracellular superoxide (SO) levels, a marker for endothelial cell dysfunction. The adaptation of the use of dihydroethidium under physiologically relevant shearing conditions is also reported.The present study describes a standardized method for the use of dihydroethidium as a marker for intracellular oxidative stress under physiologic shear. Levels of hydrogen peroxide (oxidative stress producing agent) are optimized to a minimum of 60 μM (under static conditions) to allow for the detection of SO within the free radical scavenging environment. A flow rate of 24.4 mL/min is applied and found to produce physiologically relevant shear stress (8.2 dynes/cm2) within the system under study. Dihydroethidium is a useful marker for assessing intracellular oxidative stress in studies that require shear.
A novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding groove
Authors: Percy Melanie J. , Furlow Paul W. , Beer Philip A. , Lappin Terence R. J. , McMullin Mary Frances , Lee Frank S. 
Published: June 2007

AbstractThe molecular basis of the erythrocytosis group of red cell disorders is incompletely defined. Some cases are due to dysregulation of erythropoietin (Epo) synthesis. The hypoxia inducible transcription factor (HIF) tightly regulates Epo synthesis. HIF in turn is regulated through its α subunit, which under normoxic conditions is hydroxylated on specific prolines and targeted for degradation by the von Hippel Lindau (VHL) protein. Several mutations in VHL have been reported in erythrocytosis, but only 1 mutation in the HIF prolyl hydroxylase PHD2 (prolyl hydroxylase domain protein 2) has been described. Here, we report a novel PHD2 mutation, Arg371His, which causes decreased HIF binding, HIF hydroxylase, and HIF inhibitory activities. In the tertiary structure of PHD2, Arg371 lies close to the previously described Pro317Arg mutation site. These findings substantiate PHD2 as a critical enzyme controlling HIF and therefore Epo in humans, and furthermore suggest the location of an active site groove in PHD2 that binds HIF.
Mouse oocytes fertilised by ICSI during in vitro maturation retain the ability to be activated after refertilisation in metaphase II and can generate Ca2+oscillations
Authors: Jędrusik Agnieszka , Ajduk Anna , Pomorski Paweł , Maleszewski Marek 
Published: June 2007

Abstract

Background
At fertilisation, mammalian oocytes are activated by oscillations of intracellular Ca2+ ([Ca2+]i). Phospholipase Cζ, which is introduced by fertilising spermatozoon, triggers [Ca2+]i oscillations through the generation of inositol 1,4,5-triphosphate (IP3), which causes Ca2+ release by binding to IP3 receptors located on the endoplasmic reticulum (ER) of the oocyte. Ability to respond to this activating stimulus develops during meiotic maturation of the oocyte. Here we examine how the development of this ability is perturbed when a single spermatozoon is introduced into the oocyte prematurely, i.e. during oocyte maturation.

Results
Mouse oocytes during maturation in vitro were fertilised by ICSI (intracytoplasmic sperm injection) 1 – 4 h after germinal vesicle break-down (GVBD) and were subsequently cultured until they reached metaphase II (MII) stage. At MII stage they were fertilised in vitro for the second time (refertilisation). We observed that refertilised oocytes underwent activation with similar frequency as control oocytes, which also went through maturation in vitro, but were fertilised only once at MII stage (87% and 93%, respectively). Refertilised MII oocytes were able to develop [Ca2+]i oscillations in response to penetration by spermatozoa. We found however, that they generated a lower number of transients than control oocytes. We also showed that the oocytes, which were fertilised during maturation had a similar level of MPF activity as control oocytes, which were not subjected to ICSI during maturation, but had reduced level of IP3 receptors.

Conclusion
Mouse oocytes, which were experimentally fertilised during maturation retain the ability to generate repetitive [Ca2+]i transients, and to be activated after completion of maturation.
Selective stimulation of catecholamine release from bovine adrenal chromaffin cells by an ionotropic purinergic receptor sensitive to 2-methylthio ATP
Authors: Tomé Ângelo R , Castro Enrique , Santos Rosa M , Rosário Luís M 
Published: June 2007

AbstractBackground2-Methylthioadenosine 5'-triphosphate (2-MeSATP), formerly regarded as a specific P2Y (metabotropic) purinergic receptor agonist, stimulates Ca2+influx and evokes catecholamine release from adrenal chromaffin cells. These cells express P2Y and P2X (ionotropic) purinoceptors, with the latter providing an important Ca2+influx pathway. Using single cell calcium imaging techniques, we have determined whether 2-MeSATP might be a specific P2X receptor agonist in bovine chromaffin cells and assessed the relative role of P2X and P2Y receptors on catecholamine secretion from these cells.ResultsATP raised the [Ca2+]iin ~50% of the cells. Removing extracellular Ca2+suppressed the [Ca2+]i-raising ability of 2-MeSATP, observed in ~40% of the ATP-sensitive cells. This indicates that 2-MeSATP behaves as a specific ionotropic purinoceptor agonist in bovine chromaffin cells. The 2-MeSATP-induced [Ca2+]i-rises were suppressed by PPADS. UTP raised the [Ca2+]iin ~40% of the ATP-sensitive cells, indicating that these expressed Ca2+-mobilizing P2Y receptors. UTP-sensitive receptors may not be the only P2Y receptors present, as suggested by the observation that ~20% of the ATP-sensitive pool did not respond to either 2-MeSATP or UTP. The average sizes of the ATP- and 2-MeSATP-evoked [Ca2+]iresponses were identical in UTP-insensitive cells. 2-MeSATP stimulated Ca2+influx and evoked catecholamine release, whereas UTP elicited Ca2+release from intracellular stores but did not evoke secretion. 2-MeSATP-induced secretion was strongly inhibited by Cd2+and suppressed by extracellular Ca2+or Na+removal. TTX inhibited 2-MeSATP-evoked secretion by ~20%.Conclusion2-MeSATP is a specific P2X purinoceptor agonist and a potent secretagogue in bovine chromaffin cells. Activation of 2-MeSATP-sensitive receptors stimulates Ca2+influx mainlyviavoltage-sensitive Ca2+channels. For the most part, these are activated by the depolarization brought about by Na+influx across P2X receptor pores.
The interactive role of type 2 diabetes mellitus and E-selectin S128R mutation on susceptibility to coronary heart disease
Authors: Abu-Amero Khaled K , Al-Mohanna Futwan , Al-Boudari Olayan M , Mohamed Gamal H , Dzimiri Nduna 
Published: June 2007

Abstract

Background
The role of gene-environment interactions as risk factors for coronary heart disease (CAD) remains largely undefined. Such interactions may involve gene mutations and disease conditions such as type 2 diabetes mellitus (DM2) predisposing individuals to acquiring the disease.

Methods
In the present study, we assessed the possible interactive effect of DM2 and E-selectin S128R polymorphism with respect to its predisposing individuals to CAD, using as a study model a population of 1,112 patients and 427 angiographed controls of Saudi origin. E-selectin genotyping was accomplished by polymerase chain reaction (PCR) amplification followed by PstI restriction enzyme digestion.

Results
The results show that DM2 is an independent risk factor for CAD. In the absence of DM2, the presence of the R mutant allele alone is not significantly associated with CAD (p = 0.431, OR 1.28). In contrast, in the presence of DM2 and the S allele, the likelihood of an individual acquiring CAD is significant (odds ratio = 5.44; p = < 0.001). This effect of DM2 becomes remarkably greater in the presence of the mutant 128R allele, as can be observed from the odds ratio of their interaction term (odds ratio = 6.11; p = < 0.001).

Conclusion
Our findings indicate therefore that the risk of acquiring CAD in patients with DM2 increases significantly in the presence of the 128R mutant allele of the E-selectin gene.
Small primary adenocarcinoma in adenomyosis with nodal metastasis: a case report
Authors: Puppa Giacomo , Shozu Makio , Perin Tiziana , Nomura Kazuhito , Gloghini Annunziata , Campagnutta Elio , Canzonieri Vincenzo 
Published: June 2007

Abstract

Background
Malignant transformation of adenomyosis is a very rare event. Only about 30 cases of this occurrence have been documented till now.

Case presentation
The patient was a 57-year-old woman with a slightly enlarged uterus, who underwent total hysterectomy and unilateral adnexectomy. On gross inspection, the uterine wall displayed a single nodule measuring 5 cm and several small gelatinous lesions. Microscopic examination revealed a common leiomyoma and multiple adenomyotic foci. A few of these glands were transformed into a moderately differentiated adenocarcinoma. The endometrium was completely examined and tumor free. The carcinoma was, therefore, considered to be an endometrioid adenocarcinoma arising from adenomyosis. Four months later, an ultrasound scan revealed enlarged pelvic lymph nodes: a cytological diagnosis of metastatic adenocarcinoma was made.
Immunohistochemical studies showed an enhanced positivity of the tumor site together with the neighbouring adenomyotic foci for estrogen receptors, aromatase, p53 and COX-2 expression when compared to the distant adenomyotic glands and the endometrium. We therefore postulate that the neoplastic transformation of adenomyosis implies an early carcinogenic event involving p53 and COX-2; further tumor growth is sustained by an autocrine-paracrine loop, based on a modulation of hormone receptors as well as aromatase and COX-2 local expression.

Conclusion
Adenocarcinoma in adenomyosis may be affected by local hormonal influence and, despite its small size, may metastasize.