bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early drug discovery and the rise of pharmaceutical chemistry
Authors: Jones Alan Wayne 
Published: June 2011

AbstractStudies in the field of forensic pharmacology and toxicology would not be complete without some knowledge of the history of drug discovery, the various personalities involved, and the events leading to the development and introduction of new therapeutic agents. The first medicinal drugs came from natural sources and existed in the form of herbs, plants, roots, vines and fungi. Until the mid‐nineteenth century nature's pharmaceuticals were all that were available to relieve man's pain and suffering. The first synthetic drug, chloral hydrate, was discovered in 1869 and introduced as a sedative‐hypnotic; it is still available today in some countries. The first pharmaceutical companies were spin‐offs from the textiles and synthetic dye industry and owe much to the rich source of organic chemicals derived from the distillation of coal (coal‐tar). The first analgesics and antipyretics, exemplified by phenacetin and acetanilide, were simple chemical derivatives of aniline and p‐nitrophenol, both of which were byproducts from coal‐tar. An extract from the bark of the white willow tree had been used for centuries to treat various fevers and inflammation. The active principle in white willow, salicin or salicylic acid, had a bitter taste and irritated the gastric mucosa, but a simple chemical modification was much more palatable. This was acetylsalicylic acid, better known as Aspirin®, the first blockbuster drug. At the start of the twentieth century, the first of the barbiturate family of drugs entered the pharmacopoeia and the rest, as they say, is history. Copyright © 2011 John Wiley & Sons, Ltd.
Redefining the extent of the aquatic subterranean biotope—shallow subterranean habitats
Authors: Culver David C. , Pipan Tanja 
Published: June 2011

AbstractCaves are the best known subterranean habitats, harbouring animals with a convergent morphology of reduced eyes and pigment and elongated appendages (troglomorphy). We have identified a group of aphotic aquatic habitats close to the surface [shallow subterranean habitats (SSHs)] that also harbour troglomorphic species, but with intimate surface connections, typically small in size but very abundant, with high levels of organic matter compared to caves. SSHs are hypotelminorheic, hyporheic, and epikarstic habitats. All SSHs show a pattern of environmental variation intermediate between that of surface and deep subterranean habitats, and all show seasonal and sometimes daily fluctuations in temperature but with truncated extremes. Initial colonization of these habitats was likely the result of environmental changes, especially increasing aridity, perhaps during the Pleistocene and the Messinian salinity crisis. The evolution of the troglomorphic morphology of reduced eyes and pigment and elaborated extra‐sensory structures likely occurred in situ rather than by dispersal from other habitats. SSHs may be a stepping stone to colonization of deeper subterranean habitats. Copyright © 2011 John Wiley & Sons, Ltd.
Does Self‐Esteem Mediate the Relationship between Interpersonal Problems and Symptoms of Disordered Eating?
Authors: Lampard Amy M. , Byrne Susan M. , McLean Neil 
Published: June 2011

AbstractIt has been proposed that interpersonal problems play a role in the maintenance of disordered eating because of an adverse effect on self‐esteem, which in turn encourages the pursuit of achievement in the valued domain of weight and shape. This study aimed to identify the types of interpersonal problems that are associated with disordered eating and to determine whether self‐esteem mediates the relationship between interpersonal problems and eating disorder symptoms. Female university students (n = 227) completed the Inventory of Interpersonal Problems‐32, Eating Disorder Examination Questionnaire and Rosenberg Self‐Esteem Scale. Regression analysis identified two forms of interpersonal problems that were associated with disordered eating: difficulties being sociable and being too dependent on the opinion of others. Self‐esteem mediated the relationship between interpersonal problems and overevaluation of weight and shape but did not mediate the relationship between interpersonal problems and dietary restraint. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association.
Study on microstructure and electrical properties of oil‐impregnated paper insulation after exposure to partial discharge
Authors: Yan Jiaming , Liao Ruijin , Yang Lijun , Li Jian 
Published: June 2011

SUMMARYThis paper studied microstructure and its relationship with electrical properties for oil‐impregnated paper insulation during partial discharge damage process. Material analysis apparatuses such as for atomic force microscopy and X‐ray diffraction instrument, combined with electrical analysis apparatuses such as high‐resistance meter, dielectric spectra meter, and cylinder–cylinder electrodes, were employed to investigate molecule chain structure, aggregation state structure, permittivity, dielectric loss factor, volume conductivity, and electrical strength of oil‐impregnated paper insulation during the damage process. Results reveal that crystal regions of insulation paper suffer more severe damage during partial discharge damage process compared with the amorphous regions. Crystallinity exhibits an increasing trend and crystal grain orientation is enhanced, whereas crystal grain size, crystal type, and two‐phase‐coexistent structure are retained. Increased crystallinity and enhanced crystal grain orientation result in permittivity, volume conductivity, and dielectric loss factor decreasing, but electrical strength increasing. Changes in the activity of molecules, ions, and electrons are the results of variations of crystallinity and orientation; these are the main reasons for the change in electrical properties. Copyright © 2011 John Wiley & Sons, Ltd.
Analysis of the interaction of food components with model lingual epithelial cells: the case of sweet proteins
Authors: Asakura Tomiko , Miyano Motohiro , Yamashita Haruyuki , Sakurai Takanobu , Nakajima Ken‐ichiro , Ito Keisuke , Misaka Takumi , Ishimaru Yoshiro , Abe Keiko 
Published: June 2011

ABSTRACTWe have developed a device that analyses the interaction of food components with model epithelial cells using surface plasmon resonance (SPR). A model of epithelial lingual cells was devised using a liposome composed of a mixture of four phospholipids. The liposome was immobilised to the L1 sensor tip attached to the sensor port of the SPR system. The interaction of food components with the model lingual epithelial cells was determined by the patterns of sensorgrams. According to this method, food components were classified into three groups: group A, strong interaction with the lipid bilayer; group B, weak interaction; and group C, neither A‐ nor B‐type interaction. The sensorgrams of group A showed gradual binding and slow dissociation from the surface of the lipid bilayer. In group B, the food components showed rapid binding and rapid dissociation from the lipid bilayer. The compounds in group C exhibited weak binding to the lipid bilayer, but parts of these samples formed rigid complexes with the lipid bilayer. Sweet proteins producing prolonged sweetness perception as well as miraculin with its taste‐modifying activity were classified into group A. The sensory activities of these substances are probably induced by their strong interactions with the epithelial cell surface; they have distinct binding constants with the lipid bilayer. Thaumatin exhibited the strongest interaction, followed by monellin and miraculin. Copyright © 2011 John Wiley & Sons, Ltd.
Time since first sexual intercourse and the risk of cervical cancer
Authors: Plummer Martyn , Peto Julian , Franceschi Silvia ,   ; on behalf of the International Collaboration of Epidemiological Studies of Cervical Cancer
Published: June 2011

AbstractYoung age at first sexual intercourse (AFI) is an important risk factor for cervical cancer, but no simple statistical model of its influence has been established. We investigated the relationship between risk of cervical carcinoma and time since first intercourse using data on monogamous women (5,074 cases and 16,137 controls) from the International Collaboration of Epidemiological Studies of Cervical Cancer. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from pooled data on 20 studies using conditional logistic regression. The OR for invasive cervical carcinoma is approximately proportional to the square of time since first intercourse (exponent 1.95, 95% CI: 1.76–2.15) up to age 45. First cervical infection with human papillomavirus (HPV) often occurs soon after first sexual intercourse, so early AFI is a reasonable proxy for early age at first exposure to HPV. In addition, age‐specific incidence rates of cervical cancer in unscreened populations remain fairly constant above age 45. Cervical cancer thus resembles other cancers caused by strong early‐stage carcinogens, with incidence rates proportional to a power of time since first exposure and also resembles cancers of the breast and other hormone‐dependent epithelia, where a similar flattening of age‐specific incidence rates is seen at the time menopausal changes start. Taken together, these observations suggest that HPV vaccination may prevent the majority of cervical cancers by delaying HPV infection without necessarily providing lifetime protection against HPV.
ROS implication in a new antitumor strategy based on non‐thermal plasma
Authors: Vandamme Marc , Robert Eric , Lerondel Stéphanie , Sarron Vanessa , Ries Delphine , Dozias Sébastien , Sobilo Julien , Gosset David , Kieda Claudine , Legrain Brigitte , Pouvesle Jean‐Michel , Pape Alain Le 
Published: June 2011

AbstractNon‐thermal plasma (NTP) is generated by ionizing neutral gas molecules/atoms leading to a highly reactive gas at ambient temperature containing excited molecules, reactive species and generating transient electric fields. Given its potential to interact with tissue or cells without a significant temperature increase, NTP appears as a promising approach for the treatment of various diseases including cancer. The aim of our study was to evaluate the interest of NTP both in vitro and in vivo. To this end, we evaluated the antitumor activity of NTP in vitro on two human cancer cell lines (glioblastoma U87MG and colorectal carcinoma HCT‐116). Our data showed that NTP generated a large amount of reactive oxygen species (ROS), leading to the formation of DNA damages. This resulted in a multiphase cell cycle arrest and a subsequent apoptosis induction. In addition, in vivo experiments on U87MG bearing mice showed that NTP induced a reduction of bioluminescence and tumor volume as compared to nontreated mice. An induction of apoptosis was also observed together with an accumulation of cells in S phase of the cell cycle suggesting an arrest of tumor proliferation. In conclusion, we demonstrated here that the potential of NTP to generate ROS renders this strategy particularly promising in the context of tumor treatment.
The protective role of polymorphism MKK4‐1304 T>G in nasopharyngeal carcinoma is modulated by Epstein–Barr virus' infection status
Authors: Zheng Jian , Liu Bin , Zhang Liyuan , Jiang Lan , Huang Binfang , You Yonghe , Jiang Qingping , Zhang Shuxu , Lu Jiachun , Zhou Yifeng 
Published: June 2011

AbstractMKK4 is a candidate tumor suppressor, which acts as a critical mediator of Epstein–Barr Virus (EBV)‐induced c‐Jun N‐terminal kinase (JNK) activation. Functional polymorphism MKK4 −1304T>G has been showed to be protective in colorectal cancer or lung cancer. We hypothesized that genetic variants in the MKK4 promoter were associated with the risk of nasopharyngeal carcinoma (NPC). Two common polymorphisms in MKK4, −1304T>G and −1044A>T were genotyped in two independent case‐control panels of Eastern and Southern Chinese populations, totally containing 1237 NPC and 1328 controls. We found that compared to the most common −1304TT genotype, carriers of variant genotypes (−1304TG+GG) were associated with a significantly reduced risk for NPC in total subjects (adjusted OR = 0.78; 95%CI = 0.67–0.94). Further stratification analysis showed that the protective effect was more pronounced in EBV negative status (adjusted OR = 0.51; 95%CI = 0.41–0.68) but restrained in those with EBV infection (adjusted OR = 1.05; 95%CI = 0.88–1.26), and that the −1304GG variant genotypes interacted with EBV negative status on reducing cancer risk (p = 0.011). However, no significant association was observed between the −1044A>T polymorphism and risk of NPC. Our data suggest that the protective role of genetic variant MKK4 −1304T>G is restrained in NPC with EBV infection. These findings implicate the role of EBV and MKK4 −1304 T>G interaction as a causative factor for the NPC.
Genome structure‐based screening identified epigenetically silenced microRNA associated with invasiveness in non‐small‐cell lung cancer
Authors: Watanabe Kousuke , Emoto Noriko , Hamano Emi , Sunohara Mitsuhiro , Kawakami Masanori , Kage Hidenori , Kitano Kentaro , Nakajima Jun , Goto Akiteru , Fukayama Masashi , Nagase Takahide , Yatomi Yutaka , Ohishi Nobuya , Takai Daiya 
Published: June 2011

AbstractMicroRNA (miRNA) expression is frequently altered in human cancers. To search for epigenetically silenced miRNAs in non‐small‐cell lung cancer (NSCLC), we mapped human miRNAs on autosomal chromosomes and selected 55 miRNAs in silico. We treated six NSCLC cell lines with the DNA methylation inhibitor 5‐aza‐2′‐deoxycytidine (5‐aza‐CdR) and determined the expressions of the 55 miRNAs. Fourteen miRNAs were decreased in the cancer cell lines and were induced after 5‐aza‐CdR treatment. After a detailed DNA methylation analysis, we found that mir‐34b and mir‐126 were silenced by DNA methylation. Mir‐34b was silenced by the DNA methylation of its own promoter, whereas mir‐126 was silenced by the DNA methylation of its host gene, EGFL7. A chromatin immunoprecipitation assay revealed H3K9me2 and H3K9me3 in mir‐34b and EGFL7, and H3K27me3 in EGFL7. The overexpression of mir‐34b and mir‐126 decreased the expression of c‐Met and Crk, respectively. The 5‐aza‐CdR treatment of lung cancer cell line resulted in increased mir‐34b expression and decreased c‐Met protein. We next analyzed the DNA methylation status of these miRNAs using 99 primary NSCLCs. Mir‐34b and mir‐126 were methylated in 41 and 7% of all the cases, respectively. The DNA methylation of mir‐34b was not associated with c‐Met expression determined by immunohistochemistry, but both mir‐34b methylation (p = 0.007) and c‐Met expression (p = 0.005) were significantly associated with lymphatic invasion in a multivariate analysis. The DNA methylation of mir‐34b can be used as a biomarker for an invasive phenotype of lung cancer.
Alcohol drinking and primary liver cancer: A pooled analysis of four Japanese cohort studies
Authors: Shimazu Taichi , Sasazuki Shizuka , Wakai Kenji , Tamakoshi Akiko , Tsuji Ichiro , Sugawara Yumi , Matsuo Keitaro , Nagata Chisato , Mizoue Tetsuya , Tanaka Keitaro , Inoue Manami , Tsugane Shoichiro ,   for the Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan
Published: June 2011

AbstractBecause studies of the association between alcohol intake and the risk of primary liver cancer use varying cut‐off points to classify alcohol intake, it is difficult to precisely quantify this association by meta‐analysis of published data. Furthermore, there are limited data for women in prospective studies of the dose‐specific relation of alcohol intake and the risk of primary liver cancer. We analyzed original data from 4 population‐based prospective cohort studies encompassing 174,719 participants (89,863 men and 84,856 women). After adjustment for a common set of variables, we used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of primary liver cancer incidence according to alcohol intake. We conducted a meta‐analysis of the HRs derived from each study. During 1,964,136 person‐years of follow‐up, 804 primary liver cancer cases (605 men and 199 women) were identified. In male drinkers, the multivariate‐adjusted HRs (95% CI) for alcohol intakes of 0.1–22.9, 23.0–45.9, 46.0–68.9, 69.0–91.9 and ≥92.0 g/day, as compared to occasional drinkers, were 0.88 (0.57–1.36), 1.06 (0.70–1.62), 1.07 (0.69–1.66), 1.76 (1.08–2.87) and 1.66 (0.98–2.82), respectively (p for trend = 0.015). In women, we observed a significantly increased risk among those who drank ≥23.0 g/day, as compared to occasional drinkers (HR: 3.60; 95% CI: 1.22–10.66). This pooled analysis of data from large prospective studies in Japan indicates that avoidance of (1) heavy alcohol drinking (≥69.0 g alcohol/day) in men and (2) moderate drinking (≥23.0 g alcohol/day) in women may reduce the risk of primary liver cancer.
MiR‐34a chemosensitizes bladder cancer cells to cisplatin treatment regardless of p53‐Rb pathway status
Authors: Vinall Ruth L. , Ripoll Alexandra Z. , Wang Sisi , Pan Chong‐Xian , deVere White Ralph W. 
Published: June 2011

AbstractMiR‐34a is a downstream effector of p53 that has been shown to target several molecules associated with cell cycle and cell survival pathways. As alterations in these pathways are frequent in muscle invasive transitional cell carcinoma of the bladder (MI‐TCC), for example mutation or loss of p53 and Rb, the goal of this study was to determine whether manipulation of miR‐34a expression levels could abrogate the effect of these alterations and sensitize bladder cancer cells to chemotherapy. We demonstrate that transfection of T24, TCCSUP and 5637 with pre‐miR‐34a followed by cisplatin treatment results in a dramatic reduction in clonogenic potential and induction of senescence compared to treatment with cisplatin alone. Molecular analyses identified Cdk6 and sirtuin (SIRT)‐1 as being targeted by miR‐34a in MI‐TCC cells, however, inhibition of Cdk6 and SIRT‐1 was not as effective as pre‐miR‐34a in mediating chemosensitization. Analysis of 27 preneoadjuvant chemotherapy patient samples revealed many of the patients who subsequently did not respond to treatment (based on surgical resection postchemotherapy and 5‐year survival data) express lower levels of miR‐34a, however, a statistically significant difference between the responder and nonresponder groups was not observed (p = 0.1174). Analysis of eight sets of pre‐ and postneoadjuvant chemotherapy patient samples determined miR‐34a expression increased postchemotherapy in only two of the eight patients. The combined data indicate that elevation of miR‐34a expression levels before chemotherapy would be of benefit to MI‐TCC patients, particularly in a setting of low miR‐34a expression.
Uptake of faecal immunochemical test screening among nonparticipants in a flexible sigmoidoscopy screening programme
Authors: Hol Lieke , Kuipers Ernst J. , van Ballegooijen Marjolein , van Vuuren Anneke J. , Reijerink Jaqueline C.I.Y. , Habbema Dik J.F. , van Leerdam Monique E. 
Published: June 2011

AbstractScreening programmes based on single modality testing may prevent individuals with a preference for a different test from participating. We conducted a population‐based trial to determine whether nonparticipants in flexible sigmoidoscopy (FS) screening were willing to attend faecal immunochemical test (FIT) screening. In total, 8,407 subjects were invited in a primary FS screening programme. Invitees did not know at the time of FS invitation that nonparticipants would be offered FIT screening. A total of 4,407 nonparticipants of FS screening were invited for FIT screening (cut‐off 50 ng haemoglobin/ml). The participation rate to FS screening was 31% [95% confidence interval (CI): 30–32%]. Among the FS nonparticipants 25% (CI: 24–26%) did attended FIT screening. The participation rate of the two‐stage recruitment for FS and FIT screening was 45% (CI: 44–46%). FIT screenees were older (p = 0.02), more often women (p < 0.001) and had a lower social economic status (p = 0.01) than FS screenees. The detection rate (DR) for advanced adenoma was 3.5% (CI: 2.5–4.8%), and for colorectal cancer (CRC) it was 0.3% (CI: 0.1–0.8%) among participants to FIT screening. The DR of the two‐stage recruitment was 6.1% (n = 202) for an advanced adenoma and 0.5% (n = 16) for a CRC. In conclusion, offering FIT screening to nonparticipants in a FS screening programme increases the overall participation rate considerably, as a quarter of nonparticipants of FS screening was willing to attend FIT screening. The participation rate remains lower for primary FIT screening in the same population (62%). Women in the target population were more likely to refuse FS than FIT screening. Countries introducing FS screening should be aware of these preferences.
Comparison of the skeletal effects induced by daily administration of PTHrP (1–36) and PTHrP (107–139) to ovariectomized mice
Authors: de Castro Luis Fernández , Lozano Daniel , Portal‐Núñez Sergio , Maycas Marta , De la Fuente Mónica , Caeiro José R. , Esbrit Pedro 
Published: June 2011

AbstractWe here compared the changes induced by subcutaneous injection of PTHrP (1–36) or PTHrP (107–139) (80 µg/kg/day, 5 days/week for 4 or 8 weeks) in bone histology and bone remodeling factors, and in bone marrow cells (BMCs) ex vivo, in ovariectomized (OVX) mice. We also examined the osteogenic effects of these peptides in mouse mesenchymal C3H10T1/2 cells under oxidative stress condition in vitro, which recapitulates the effects of OVX. We confirmed that PTHrP (1–36) exerts bone anabolic actions, as assessed by bone histology and osteoblast differentiation markers in the long bones and plasma from OVX mice. PTHrP (107–139) was also efficient in stimulating several bone formation parameters, and it dramatically decreased bone resorption markers. Moreover, both PTHrP peptides modulate DKK‐1 and Sost/sclerostin in osteoblast‐like UMR‐106 cells highly expressing these Wnt pathway inhibitors, related to their osteogenic action in this in vivo scenario. Administration of either PTHrP peptide improved osteogenic differentiation in BMCs from OVX mice ex vivo and in mouse mesenchymal C3H10T1/2 cells under oxidative stress condition in vitro. These data demonstrate that PTHrP (1–36) and PTHrP (107–139) can exert similar osteogenic effects in the appendicular skeleton of OVX mice. Our results suggest that these effects might occur in part by modulating the Wnt pathway. These findings lend credence to the notion that the osteogenic action of PTHrP (107–139) is likely a consequence of its anti‐resorptive and anabolic features, and further support the usefulness of PTHrP (1–36) as a bone anabolic peptide in the setting of estrogen‐depletion. J. Cell. Physiol. 227: 1752–1760, 2012. © 2011 Wiley Periodicals, Inc.
Simultaneous extraction and purification of myricetin from Chamaecyparis obtusa by multi‐phase extraction with ionic liquid‐modified mesoporous MCM‐41
Authors: Tian Minglei , Bi Wentao , Row Kyung Ho 
Published: June 2011

AbstractBACKGROUND: Multi‐phase extraction is a novel method for the simultaneous extraction and separation of myricetin from Chamaecyparis obtusa. In this research, an amino ionic liquid‐modified MCM‐41 was used as the sorbent and the sample was packed with it into a cartridge. A fixed volume of solvent was then use to extract the target compound with several repetitions and to remove the myricetin to the sorbent. The washing and elution of solvent were investigated.RESULTS: FT‐IR and element contents tests confirmed that the ionic liquid groups were successfully immobilized on MCM‐41. 0.184 mg myricetin was extracted with five repetitions of 1.0 mL methanol. Then 2.0 mL n‐hexane and water were removed all the interference and 1.0 mL methanol was purified 0.1 mg myricetin from 0.2 g ionic liquid‐modified MCM‐41.CONCLUSION: Base on a comparison with traditional extraction methods, the low deviation error (3.16%), small amount of solvent required, highly selective separation and stability of the proposed method justify continuing its development. Copyright © 2011 Society of Chemical Industry