bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in the incidence of oral cavity and oropharyngeal cancers in Spain
Authors: de Souza Dyego Leandro Bezerra , de Camargo Cancela Marianna , Pérez María Milagros Bernal , Curado Maria‐Paula
Published: June 2011

Background

The purpose of this study was to analyze and compare incidence trends of oral cavity and oropharyngeal cancers, using data from population‐based Spanish cancer registries.

Methods

Adjusted rates were calculated using the standard world population, and incidence trends were analyzed for individual and pooled registries using joinpoint regression.

Results

Analysis of 7 pooled registries revealed a statistically significant reduction in the incidence of oral cavity cancer in men (annual percent change [APC] = −3.1) and a nonsignificant decrease in women (APC = −4.5) over the period from 1991 to 2001. For oropharyngeal cancer, the trend was for a statistically significant increase in men in 4 registries.

Conclusion

There is growing evidence that the incidence of oral cavity cancer is in decline, while the incidence of oropharyngeal cancer has been increasing over the past 3 decades, especially in developed countries, and this study reinforces such evidence. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Prognostic significance of RB1‐inducible coiled‐coil 1 in salivary gland cancers
Authors: Tameno Hitosuke , Chano Tokuhiro , Ikebuchi Kaichiro , Ochi Yasuko , Arai Akihito , Kishimoto Mitsuo , Shimada Taketoshi , Hisa Yasuo , Okabe Hidetoshi
Published: June 2011

Background

No generally agreed‐upon method is available for predicting the prognosis of salivary gland cancers. RB1‐inducible coiled‐coil 1 (RB1CC1) is a positive regulator for the retinoblastoma tumor suppressor (RB1) pathway, and is a suitable marker for evaluating the clinical course of breast cancer. We investigated whether RB1CC1 predicts the prognosis of salivary gland cancers.

Methods

Molecules involved in the RB1CC1 pathway, including RB1CC1, RB1, p53, and Ki‐67, were evaluated immunohistochemically in 36 cases of salivary gland cancers. The relationships between clinicopathologic features and disease‐free‐survival intervals were analyzed by a Kaplan–Meier log‐rank test and a multivariate Cox proportional hazard regression.

Results

Nuclear RB1CC1 loss in the tumors was significantly associated with a worse disease‐free survival (log‐rank test, chi‐square value = 11.644, p = .0006), and was the maximum critical risk (multivariate Cox proportional hazard ratio = 11.112, 95% confidence interval [CI] = 1.776–69.510, p = .0100).

Conclusions

Nuclear expression of RB1CC1 predicts a better clinical outcome and is useful in the follow‐up of salivary gland cancers. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Land use changes, torrent control works and sediment mining: effects on channel morphology and sediment flux, case study of the Reno River (Northern Italy)
Authors: Preciso Emanuele , Salemi Enzo , Billi Paolo
Published: June 2011

As with most Italian rivers, the Reno River has a long history of human modification, related also to morphological changes of the lower Po River since Roman times, but in the last decades, significant land use changes in the headwaters, dam construction, torrent control works and extensive bed material mining have caused important channel morphology and sediment budget changes. In this paper, two main types of channel adjustment, riverbed incision and channel narrowing, are analysed. Riverbed degradation is discussed by comparing four different longitudinal profiles surveyed in 1928, 1951, 1970 and 1998 in the 120 km long reach upstream of the outlet. The analysis of channel narrowing is carried out by comparing a number of cross‐sections surveyed in different years across the same downstream reach. Field sediment transport measurements of seven major floods that occurred between 2003 and 2006 are compared with the bedload transport rates predicted by the most renowned equations. The current low bedload yield is discussed in terms of sediment supply limited conditions due to land use changes, erosion‐control works and extensive and out of control bed material mining that have affected the Reno during the last decades. Copyright © 2011 John Wiley & Sons, Ltd.
Spatial variation in sap flow velocity in semiarid region trees: its impact on stand‐scale transpiration estimates
Authors: Kume Tomonori , Otsuki Kyoichi , Du Sheng , Yamanaka Norikazu , Wang Yi‐Long , Liu Guo‐Bin
Published: June 2011

In this study, we aimed to clarify spatial variations in xylem sap flow, and to determine the impacts of these variations on stand‐scale transpiration (E) estimates. We examined circumferential and radial variations in sap flow velocity (Fd) measured at several directions and depths in tree trunks of black locust (Robinia pseudoacacia) and native oak (Quercus liaotungensis), both of which have ring‐porous wood anatomy, in forest stands on the Loess Plateau, China. We evaluated the impacts of circumferential variations in Fd on stand‐scale transpiration estimates using a simple scaling exercise. We found significant circumferential variations in Fd in the outermost xylem in both species (coefficients of variation = 20–45%). For both species, Fd measured at the inner xylem was smaller than that of the outermost xylem and the Fd at the depth of > 10 mm was almost zero. The simple exercises showed that omitting circumferential variations in Fd affected the E estimate by 16–21%, which was less than the effects of omitting within‐tree radial and tree‐to‐tree variations in Fd in both species. These results suggest that circumferential variations in Fd can be a minor source of error for E estimates compared with within‐tree radial and tree‐to‐tree variations in Fd, regardless of the significant circumferential variations. Copyright © 2011 John Wiley & Sons, Ltd.
An inexpensive and portable drill rig for bedrock groundwater studies in headwater catchments
Authors: Gabrielli C. P. , McDonnell J. J.
Published: June 2011

Bedrock groundwater dynamics in headwater catchments are poorly understood and poorly characterized. Here, we present an inexpensive and portable bedrock drilling system designed for use in remote locations. Our system is capable of drilling bedrock wells up to 11 m deep and 38 mm in diameter in a wide range of bedrock types. The drill consists of a lawn mower engine adapted to rotate a diamond tipped coring bit, a small water pump to cool and flush the drill bit and a scaffolding platform for stable footing on steep slopes. The complete drilling assembly costs under $ 2000 USD. Here, we show proof‐of‐concept of our approach with 40 successful wells drilled in different geological substrates, including a conglomerate at the Maimai experimental catchment in New Zealand, volcanic breccias at the HJ Andrews experimental watershed in Oregon, USA, sandstone and siltstone at the Alsea watershed in Oregon, USA, and basalt at the Los Gavilanes experimental watershed in Veracruz, Mexico. We also present a transparent comparison between our design and other portable bedrock drilling systems and outline the strengths and weaknesses of each system. Copyright © 2011 John Wiley & Sons, Ltd.
Impacts of climate change on soil moisture and evapotranspiration in reconstructed watersheds in northern Alberta, Canada
Authors: Keshta Nader , Elshorbagy Amin , Carey Sean
Published: June 2011

This study aims at developing a generalized understanding of the sensitivity of soil moisture patterns in reconstructed watersheds, in northern Alberta, to changes in the projected precipitation in the twenty‐first century. The GSDW model is applied to three watersheds using climate scenarios generated using daily precipitation and air temperature output from a global climate model (CGCM3), under A2 and B1 emission scenarios, to simulate the corresponding soil moisture. CGCM3 results indicate an increase in the mean annual temperature for Fort McMurray, Alberta of 3·3 (A2) and 2·4 °C (B1), and an increase in the predicted annual precipitation of 34% (A2) and 8·6% with A2 and B1 emission scenarios, respectively. The GSDW model is used, along with onsite historical data, to downscale A2 and B1 emission scenarios and to evaluate the future hydrological performance of the designated watersheds with respect to soil moisture deficit and actual evapotranspiration using a probabilistic framework. The forecasted maximum soil moisture deficit values based on A2 and B1 emission scenarios are expected to decrease compared to those based on the current, largely because of the expected increase in precipitation rates, associated with an expected increase in evapotranspiration. Copyright © 2011 John Wiley & Sons, Ltd.
Cholecystectomy and risk of laryngeal and pharyngeal cancer
Authors: Lagergren Jesper , Mattsson Fredrik
Published: June 2011

Duodeno‐gastro‐esophageal reflux of bile might cause laryngeal and pharyngeal cancer, but more research is required. Since cholecystectomy is followed by an increased risk such reflux, the risk of developing laryngeal or pharyngeal cancer after cholecystectomy was addressed. A population‐based cohort study was conducted in Sweden during the period 1965–2008. The number of laryngeal or pharyngeal cancer cases observed in a large cohort of cholecystectomized patients was compared with the expected number, calculated from the entire Swedish population of corresponding age, gender and calendar year. Risk of laryngeal or pharyngeal cancer was calculated as standardized incidence ratio (SIR) with 95% confidence interval (CI). The cholecystectomy cohort included 345,251 patients who were followed up for 1–43 years and contributed 4,854,969 person‐years at risk. The 192 new cases of laryngeal cancer and the 175 cases of pharyngeal cancer were not greater than the expected, providing SIR 0.99 (95% CI 0.85–1.14) and SIR 1.06 (95% CI 0.91–1.23), respectively. A longer latency period after cholecystectomy was not associated with any increased risk of any of these tumors. No differences between age groups or sexes were detected. Analyses restricted to verified squamous‐cell carcinomas revealed similar results. In conclusion, cholecystectomy does not appear to be followed by any increased risk of laryngeal or pharyngeal cancer.
Dietary intake of heme iron and risk of gastric cancer in the European prospective investigation into cancer and nutrition study
Authors: Jakszyn Paula , Agudo Antonio , Lujan‐Barroso Leila , Bueno‐de‐Mesquita H Bas , Jenab Mazda , Navarro Carmen , Palli Domenico , Boeing Heiner , Manjer Jonas , Numans Mattijs E , Igali Laszlo , Boutron‐Ruault Marie‐Christine , Clavel‐Chapelon Françoise , Morois Sophie , Grioni Sara , Panico cSalvatore , Tumino Rosario , Sacerdote Carlotta , Quirós J. Ramon , Molina‐Montes Esther , Ma Huerta Castaño Jose , Barricarte Aurelio , Amiano Pilar , Khaw Kay‐Tee , Wareham Nicholas , Allen Naomi E. , Key Timothy J , Jeurnink Suzanne M. , Peeters Petra HM , Bamia Christina , Valanou Elisabeth , Trichopoulou Antonia , Kaaks Rudolf , Lukanova Annekatrin , Bergmann Manuela M. , Lindkvist Björn , Stenling Roger , Johansson Ingegerd , Dahm Christina C. , Overvad Kim , Olsen Anja , Tjonneland Anne , Skeie Guri , Ragnhild Broderstad Ann , Lund Eiliv , Michaud Dominique S. , Mouw Traci , Riboli Elio , González Carlos A
Published: June 2011

Even though recent studies suggest that a high intake of heme iron is associated with several types of cancer, epidemiological studies in relation to gastric cancer (GC) are lacking. Our previous results show a positive association between red and processed meat and non cardia gastric cancer, especially in Helicobacter pylori infected subjects. The aim of the study is to investigate the association between heme iron intake and GC risk in the European prospective investigation into cancer and nutrition (EURGAST‐EPIC). Dietary intake was assessed by validated center‐specific questionnaires. Heme iron was calculated as a type‐specific percentage of the total iron content in meat intake, derived from the literature. Antibodies of H. pylori infection and vitamin C levels were measured in a sub‐sample of cases and matched controls included in a nested case‐control study within the cohort. The study included 481,419 individuals and 444 incident cases of GC that occurred during an average of 8.7 years of followup. We observed a statistically significant association between heme iron intake and GC risk (HR 1.13 95% CI: 1.01–1.26 for a doubling of intake) adjusted by sex, age, BMI, education level, tobacco smoking and energy intake. The positive association between heme iron and the risk of GC was statistically significant in subjects with plasma vitamin C <39 mmol/l only (log2 HR 1.54 95% CI (1.01–2.35). We found a positive association between heme iron intake and gastric cancer risk.
Effects of small molecule inhibitors of PI3K/Akt/mTOR signaling on neuroblastoma growth in vitro and in vivo
Authors: Segerström Lova , Baryawno Ninib , Sveinbjörnsson Baldur , Wickström Malin , Elfman Lotta , Kogner Per , Johnsen John Inge
Published: June 2011

Activation of the PI3K/Akt signaling pathway is correlated with poor prognosis in neuroblastoma, the most common and deadly extracranial tumor of childhood. In this study, we show that the small‐molecule inhibitors of phosphoinositide‐dependent protein kinase‐1 (PDK1) OSU03012 and the dual class I PI3K/mTOR inhibitor PI103 have profound effects on neuroblastoma survival in vitro and in vivo. Both OSU03012 and PI103 inhibited neuroblastoma growth in vitro. In treated cells, OSU03012 induced apoptosis and an S phase cell cycle arrest, whereas only minor apoptosis was detected in PI103 treated cells together with a G1 arrest. Both OSU03012 and PI103 downregulated phosphorylation of Akt and inhibited the downstream targets glycogen synthase kinase‐3β (GSK3β) and p70 S6 kinase‐1 (S6K1), as well as downregulated the expression of cyclin D1 and Mycn protein. Neuroblastoma cells expressing high levels of Mycn were more sensitive to OSU03012 or PI103 compared with cells expressing low Mycn levels. Both compounds significantly inhibited the growth of established, subcutaneous MYCN‐amplified neuroblastoma xenografts in nude NMRI nu/nu mice. These results suggest that inhibition of the PI3K/Akt signaling pathway represent a clinical relevant target for the treatment of patients with high‐risk MYCN‐amplified neuroblastoma.
Health and economic impact of HPV 16/18 vaccination and cervical cancer screening in Eastern Africa
Authors: Campos Nicole G. , Kim Jane J. , Castle Philip E. , Ortendahl Jesse D. , O'Shea Meredith , Diaz Mireia , Goldie Sue J.
Published: June 2011

Eastern Africa has the world's highest cervical cancer incidence and mortality rates. We used epidemiologic data from Kenya, Mozambique, Tanzania, Uganda, and Zimbabwe to develop models of HPV‐related infection and disease. For each country, we assessed HPV vaccination of girls before age 12 followed by screening with HPV DNA testing once, twice, or three times per lifetime (at ages 35, 40, 45). For women over age 30, we assessed only screening (with HPV DNA testing up to three times per lifetime or VIA at age 35). Assuming no waning immunity, mean reduction in lifetime cancer risk associated with vaccination ranged from 36 to 45%, and vaccination followed by screening once per lifetime at age 35 with HPV DNA testing ranged from 43 to 51%. For both younger and older women, the most effective screening strategy was HPV DNA testing three times per lifetime. Provided the cost per vaccinated girl was less than I$10 (I$2 per dose), vaccination had an incremental cost‐effectiveness ratio [I$ (international dollars)/year of life saved (YLS)] less than the country‐specific per capita GDP, a commonly cited heuristic for “very cost‐effective” interventions. If the cost per vaccinated girl was between I$10 (I$2 per dose) and I$25 (I$5 per dose), vaccination followed by HPV DNA testing would save the most lives and would be considered good value for public health dollars. These results should be used to catalyze design and evaluation of HPV vaccine delivery and screening programs, and contribute to a dialogue on financing HPV vaccination in poor countries.
PARTIAL ROOTZONE DRYING TO SAVE WATER WHILE GROWING APPLES IN A SEMI‐ARID REGION
Authors: Zegbe Jorge A. , Serna‐Pérez Alfonso
Published: June 2011

Water availability represents the main environmental limitation in arid and semi‐arid agro‐ecosystems. In these regions, irrigation water is a scarce and expensive resource for apple and other horticultural production systems. The north‐central part of Mexico, where 70% (≈ 44 thousand hectares) of apples are grown, is such a semi‐arid system. The objective of this research was to determine the impact of partial rootzone drying (PRD) on tree physiology, yield, water use efficiency (WUE), and irrigation water use efficiency of ‘Golden Delicious’ apple trees growing in a semi‐arid region. Treatments were commercial irrigation (CI, as control) and PRD (50% of the irrigation water supplied to CI). The PRD trees had slightly reduced leaf xylem water potential, stomatal conductance, and transpiration rate. Yield, fruit size and quality, vegetative growth, and pruning weight were not modified by the irrigation treatments. Over three years, average WUE increased by 51% under PRD irrigation and water savings were ≈ 3, 240 m3 water per hectare. Therefore, PRD is a potential irrigation technique to make apple production sustainable not only in the semi‐arid regions of Mexico, but also in other regions where water resources are becoming insufficient. Copyright © 2011 John Wiley & Sons, Ltd.
Dynamic factors controlling carrier anchoring on vascular cells
Authors: Swaminathan Tirumani N. , Liu Jin , Balakrishnan Uma , Ayyaswamy Portonovo S. , Radhakrishnan Ravi , Eckmann David M.
Published: June 2011

This article reviews experimental and modeling methods for determining the critical roles played by the various factors that control nanocarrier drug delivery to vascular endothelial cells. © 2011 IUBMB IUBMB Life, 2011
Magnetic nanoparticles for targeted vascular delivery
Authors: Chorny Michael , Fishbein Ilia , Forbes Scott , Alferiev Ivan
Published: June 2011

Magnetic targeting has shown promise to improve the efficacy and safety of different classes of therapeutic agents by enabling their active guidance to the site of disease and minimizing dissemination to nontarget tissues. However, its translation into clinic has proven difficult because of inherent limitations of traditional approaches inapplicable for deep tissue targeting in human subjects and a need for developing well‐characterized and fully biocompatible magnetic carrier formulations. A novel magnetic targeting scheme based on the magnetizing effect of deep‐penetrating uniform fields is presented as an example of a strategy providing a potentially clinically viable solution for preventing injury‐triggered reobstruction of stented blood vessels (in‐stent restenosis). The design of optimized magnetic carrier formulations and experimental results showing the feasibility of uniform field‐controlled targeting for site‐specific vascular delivery of small‐molecule pharmaceuticals, biotherapeutics, and cells are discussed in the context of antirestenotic therapy. The versatility of this approach applicable to different classes of therapeutic agents exerting their antirestenotic effects through distinct mechanisms prompts exploring the utility of uniform field‐mediated magnetic stent targeting for combination therapies with enhanced efficiencies and improved safety profiles. Additional improvements in terms of site specificity and protracted carrier retention at the site of injury may be expected from the development and use of magnetic carriers exhibiting affinity for arterial wall‐specific antigens. © 2011 IUBMB IUBMB Life, 2011
Effects of melamine on pregnant dams and embryo‐fetal development in rats
Authors: Kim Sung‐Hwan , Lee In‐Chul , Lim Jeong‐Hyeon , Shin In‐Sik , Moon Changjong , Kim Sung‐Ho , Park Seung‐Chun , Kim Hyoung‐Chin , Kim Jong‐Choon
Published: June 2011

There are worldwide concerns regarding the potential adverse effect of melamine. This study investigated the potential effects of melamine on pregnant dams and embryo‐fetal development in Sprague–Dawley rats following maternal exposure on gestational days (GD) 6–20. Melamine was administered to pregnant rats by gavage at doses of 0, 200, 400 and 800 mg kg−1 per day (n = 8–10 for each group). All dams were subjected to a Caesarean section on GD 21 and their fetuses were examined for morphological abnormalities. With administration of melamine at 800 mg kg−1 per day, maternal toxicity manifested as increased incidences of clinical signs and death, lower body weight gain and food intake, and increases in heart, adrenal gland and kidney weights. Histopathological examinations revealed an increase in incidences of congestion, tubular necrosis/degeneration, crystals, casts, inflammatory cells in tubules, tubular dilation and tubular hyaline droplets in the maternal kidneys, while fetal kidneys (one fetus/litter) did not show any histopathological changes. Developmental toxic effects included a decrease in fetal weight, an increase in the incidence of skeletal variations and a delay in fetal ossification. No treatment‐related maternal or developmental effects were observed at doses ≤400 mg kg−1 per day. These results show that 15‐day repeated oral dosing of melamine is embryo‐/fetotoxic at a maternotoxic dose, but not teratogenic in rats. The no‐observed‐adverse‐effect level of melamine for pregnant dams and embryo‐fetal development is considered to be 400 mg kg−1 per day. Copyright © 2011 John Wiley & Sons, Ltd.
Amelioration of experimental autoimmune myasthenia gravis rats by blood purification treatment using 4‐mercaptoethylpyridine‐based adsorbent
Authors: Ren Jun , Bai Ying , Hao Lan , Dong Yan , Pi Zhiqian , Jia Lingyun
Published: June 2011

The role of immunoadsorption therapy is well established in the management of myasthenia gravis (MG), an autoimmune disorder characterized by muscle weakness and caused by circulating IgG antibodies with specificity against the acetylcholine receptor. Conventional immunoadsorbents that employ recombinant protein A as immobilized ligand suffer from the drawbacks of high cost and low stability. The objective of this work is to assess the safety and efficacy of a synthetic adsorbent for treating MG. Adsorption columns were prepared from a Sepharose‐based adsorbent coupled to 4‐mercaptoethylpyridine (MEP), which acted as immobilized ligands. Animal model of experimental autoimmune MG (EAMG) using Lewis rats was developed and treated by whole blood perfusion. The results showed that the treatments provided a significant amelioration of clinical weakness for EAMG rats, with clinic score decreasing from 2.08 ± 0.38 to 1.25 ± 0.27. After a treatment session of about 1.5 h, blood cell counts were not significantly changed. Serum levels of total IgG and acetylcholine receptor antibody were reduced by 37.1 ± 6.5% and 35.6 ± 8.6%, respectively. In addition, reduction in complement components C3 (47.1 ± 6.7%), C4 (34.3 ± 3.4%), inflammatory cytokines interleukin‐17 (10.4 ± 2.7%), and tumor necrosis factor‐α (8.2 ± 3.1%) were also observed. This study demonstrated that MEP‐based adsorbent not only removed pathogenic autoantibodies directly from the blood as with protein A adsorbents but also modulated cellular immunity through removal of complement components and related proinflammatory cytokines, thereby providing a potentially superior strategy for the treatment of MG. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
In vivo comparative biokinetics and biocompatibility of titanium and zirconium microparticles
Authors: Olmedo Daniel G. , Tasat Deborah R. , Evelson Pablo , Rebagliatti Raúl , Guglielmotti María B. , Cabrini Rómulo L.
Published: June 2011

Titanium and zirconium are biomaterials that present a layer of titanium dioxide (TiO2) or zirconium dioxide (ZrO2). As a result of corrosion, microparticles can be released into the bioenvironment, and their effect on tissues is seemingly associated with differences in the physicochemical properties of these metals. The aim of this study was to perform a long‐term evaluation of the distribution, destination, and potential risk of TiO2 and ZrO2 microparticles that might result from the corrosion process. Wistar rats were i.p. injected with an equal dose of either TiO2 or ZrO2 suspension. The following end‐points were evaluated at 3, 6, and 18 months: (a) the presence of particles in blood cells and liver and lung tissue, (b) Ti and Zr deposit quantitation, (c) oxidant–antioxidant balance in tissues, and (d) O2− generation in alveolar macrophages. Ti and Zr particles were detected in blood mononuclear cells and in organ parenchyma. At equal doses and times postadministration, Ti content in organs was consistently higher than Zr content. Ti elicited a significant increase in O2− generation in the lung compared to Zr. The consumption of antioxidant enzymes was greater in the Ti than in the Zr group. The present study shows that the biokinetics of TiO2 and ZrO2 depends on particle size, shape, and/or crystal structure. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Preparation, structure, and in vitro chemical durability of yttrium phosphate microspheres for intra‐arterial radiotherapy
Authors: Kawashita Masakazu , Matsui Naoko , Li Zhixia , Miyazaki Toshiki , Kanetaka Hiroyasu
Published: June 2011

Chemically durable microspheres containing yttrium and/or phosphorus are useful for intra‐arterial radiotherapy. In this study, we attempted to prepare yttrium phosphate (YPO4) microspheres with high chemical durability. YPO4 microspheres with smooth surfaces and diameters of around 25 μm were successfully obtained when gelatin droplets containing yttrium and phosphate ions were cooled and solidified in a water‐in‐oil emulsion and then heat‐treated at 1100°C. The chemical durability of the heat‐treated microspheres in a simulated body fluid at pH = 6 and 7 was high enough for clinical application of intra‐arterial radiotherapy. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
Characterization and preliminary in vivo evaluation of a novel modified hydroxyapatite produced by extrusion and spheronization techniques
Authors: Cortez P. P. , Atayde L. M. , Silva M. A. , Armada‐da‐Silva P. , Fernandes M. H. , Afonso A. , Lopes M. A. , Maurício A. C. , Santos J. D.
Published: June 2011

A glass‐reinforced hydroxyapatite (HA) composite, recently registered as Bonelike®, was developed for bone grafting. This biomaterial is composed of a modified HA matrix with α‐ and β‐tricalcium phosphate secondary phases and ionic species that mimic the chemical composition of human bone. Several in vitro and in vivo studies have confirmed the benefits of these properties. However, these studies were all executed with Bonelike® polygonal granules obtained by crushing. In this study, Bonelike® pellets were produced through a patented process, which required the use of techniques such as extrusion and spheronization. The final product presented a homogeneous size, a 55.1% global porosity and a spherical shape. This spherical shape permitted a better adaptation to the implantation site and improved injectability. Additionally, it also may contribute to formation of macropores as pellets packaging leaves open spaces. After implantation of Bonelike® polygonal granules and Bonelike® pellets in monocortical defects in sheep for 8 and 12 weeks, light microscopy and scanning electron microscopy showed extensive osteointegration simultaneously with bone regeneration for both presentations. Histomorphometric analysis did not reveal statistically significant differences between defects treated with Bonelike® polygonal granules and Bonelike® pellets, which suggests similar in vivo performances. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
Formulated siRNAs targeting Rankl prevent osteolysis and enhance chemotherapeutic response in osteosarcoma models
Authors: Rousseau Julie , Escriou Virginie , Lamoureux François , Brion Régis , Chesneau Julie , Battaglia Séverine , Amiaud Jérome , Scherman Daniel , Heymann Dominique , Rédini Françoise , Trichet Valérie
Published: June 2011

The development of osteosarcoma, the most common malignant primary bone tumor is characterized by a vicious cycle established between tumor proliferation and paratumor osteolysis. This osteolysis is mainly regulated by the receptor activator of nuclear factor κB ligand (RANKL). Preclinical studies have demonstrated that Rankl blockade by soluble receptors is an effective strategy to prevent osteolytic lesions leading to osteosarcoma inhibition. A new therapeutic option could be to directly inhibit Rankl expression by small interfering RNAs (Rkl-siRNAs) and combine these molecules with chemotherapy to counteract the osteosarcoma development more efficiently. An efficient siRNA sequence directed against both mouse and rat mRNAs coding Rankl was first validated in vitro and tested in two models of osteosarcoma: a syngenic osteolytic POS-1 model induced in immunocompetent mice and a xenograft osteocondensant model of rat OSRGA in athymic mice. Intratumor injections of Rankl-directed siRNAs in combination with the cationic liposome RPR209120/DOPE reduced the local and systemic Rankl production and protected bone from paratumor osteolysis. Although Rkl-siRNAs alone had no effect on tumor development in both osteosarcoma models, it significantly blocked tumor progression when combined with ifosfamide compared with chemotherapy alone. Our results indicate that siRNAs could be delivered using cationic liposomes and thereby could inhibit Rankl production in a specific manner in osteosarcoma models. Moreover, the Rankl inhibition mediated by RNA interference strategy improves the therapeutic response of primary osteosarcoma to chemotherapy. © 2011 American Society for Bone and Mineral Research
Bone marrow processing with the AMICUS™ separator system
Authors: Witt V. , Beiglböck E. , Fritsch G.
Published: June 2011

ABO incompatible bone marrow transplantation (BMT) requires processing of the donated bone marrow (BM), either erythrocyte depletion, or also a volume reduction. The AMICUS™ system was introduced in the field of peripheral blood mononuclear cell collection, showing a good performance regarding efficiency and safety. To evaluate the performance of the MNC collection program of the Amicus device for BM, we analysed our data obtained from the Amicus and the Fenwal CS3000omnix™ plus device. Methods: From 2005 to 2008, we performed 22 automated erythrocyte depletions of BM for ABO mismatched BMT in 21 patients, 11 with the Amicus (A; 10 patients) and 11 with the CS3000 (F; 11) device. Results: There were no statistical differences in donor age, recipient age, type of ABO mismatch, and CD34+ cell yield [group A pre 7.03 post 4.93 vs. group F pre 8.55 and post 6.2 × 10E06 cells per kilogram of bodyweight] for both devices. The efficiency for the CD34+ cell collection was lower, but not statistically significant, in the Amicus device (70% ± 12 vs. 84% ± 12; U‐test P = 0.123). The erythrocyte volume in the final product was higher but not statistically significant different in the Amicus device (9.46 ± 2.3 vs. 6.98 ± 3.3 ml; U‐test P = 0.17). During the evaluation period, no technical problems were observed. Allpatients but one, who died at d + 11, showed a sustained engraftment. Conclusions: We conclude that, in principle, the Amicus device can be used for MNC collection from BM to deplete erythrocytes from BM grafts in allogeneic stem cell transplantations. J. Clin. Apheresis 2011. © 2011 Wiley‐Liss, Inc.
Ab Initio prediction of protein–ligand binding structures by replica‐exchange umbrella sampling simulations
Authors: Kokubo Hironori , Tanaka Toshimasa , Okamoto Yuko
Published: June 2011

We have developed a prediction method for the binding structures of ligands with proteins. Our method consists of three steps. First, replica‐exchange umbrella sampling simulations are performed along the distance between a putative binding site of a protein and a ligand as the reaction coordinate. Second, we obtain the potential of mean force (PMF) of the unbiased system using the weighted histogram analysis method and determine the distance that corresponds to the global minimum of PMF. Third, structures that have this global‐minimum distance and energy values around the average potential energy are collected and analyzed using the principal component analysis. We predict the binding structure as the global‐minimum free energy state on the free energy landscapes along the two major principal component axes. As test cases, we applied our method to five protein–ligand complex systems. Starting from the configuration in which the protein and the ligand are far away from each other in each system, our method predicted the ligand binding structures in excellent agreement with the experimental data from Protein Data Bank. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
A continuous ultrasound‐assisted packed‐bed bioreactor for the lipase‐catalyzed synthesis of caffeic acid phenethyl ester
Authors: Chen Hsiao‐Ching , Kuo Chia‐Hung , Twu Yawo‐Kuo , Chen Jiann‐Hwa , Chang Chieh‐Ming J. , Liu Yung‐Chuan , Shieh Chwen‐Jen
Published: June 2011

BACKGROUND: The focus of this paper is the ultrasound‐assisted synthesis of caffeic acid phenethyl ester (CAPE) from caffeic acid and phenyl ethanol in a continuous packed‐bed bioreactor. Immobilized Novozym® 435 (from Candida antarctica) is used as the catalyst. A three‐level–three‐factor Box–Behnken design and a response surface methodology (RSM) are employed to evaluate the effects of temperature, flow rate, and ultrasonic power on the percentage molar conversion of CAPE.

RESULTS: Based on ridge max analysis, it is concluded that the optimum condition for synthesis is reaction temperature 72.66 °C, flow rate 0.046 mL min−1, and ultrasonic power 1.64 W cm−2. The expected molar conversion value is 97.84%. An experiment performed under these optimal conditions resulted in a molar conversion of 92.11 ± 0.75%. The enzyme in the bioreactor was found to be stable for at least 6 days.

CONCLUSIONS: The lipase‐catalyzed synthesis of CAPE by an ultrasound‐assisted packed‐bed bioreactor uses mild reaction conditions. Enzymatic synthesis of CAPE is suitable for use in the nutraceutical and food production industries. Copyright © 2011 Society of Chemical Industry
Application of magnetite modified with aluminum/silica to adsorb phosphate in aqueous solution
Authors: Lin Ya‐Fen , Chen Hua‐Wei , Chang Chia‐Chi , Hung Wen‐Chiang , Chiou Chyow‐San
Published: June 2011

BACKGROUND: Phosphate is one of the main contaminants responsible for the eutrophication of surface waters, and adsorption is a potential treatment method for this pollutant. A magnetic adsorbent manufactured from magnetite (Fe3O4) can be recovered easily from treated water by magnetic force, without requiring further downstream treatment. In this research, the surface of magnetite modified with aluminum and silica (Al/SiO2/Fe3O4) was used to adsorb phosphate in an aqueous solution in a batch system.

RESULTS: The optimum solution pH for phosphate adsorption by Al/SiO2/Fe3O4 was found to be 4.5. The phosphate adsorption behavior of Al/SiO2/Fe3O4 was in good agreement with both the Langmuir and Freundlich adsorption isotherm, and the maximum adsorption capacity (qm) and Gibbs free energy of phosphate was 25.64 mg g−1 and − 21.47 kJ mol−1, respectively. A pseudo‐second‐order model could best describe the adsorption kinetics, and the derived activation energy was 3.52 kJ mol−1. The optimum condition to desorb phosphate from Al/SiO2/Fe3O4 is provided by a solution with 0.05 mol L−1 NaOH.

CONCLUSIONS: Magnetic adsorbent is a potential material for a water treatment method. The results of this study will be helpful in the development of aluminum modified silica magnetic adsorbents that can be used to remove phosphate in aqueous solution. Copyright © 2011 Society of Chemical Industry
Vinylferrocene copolymers based biosensors for phenol derivatives
Authors: Dursun Fuat , Ozoner Seyda Korkut , Demirci Ali , Gorur Mesut , Yilmaz Faruk , Erhan Elif
Published: June 2011

BACKGROUND: Newly synthesized composite films of P(glycidyl methacrylate85‐co‐vinylferrocene15)/Poly(glutaraldehyde)/ Polypyrrole [P(GMA85‐co‐VFc15)/PGA/PPy] and Poly(3‐methylthienyl methacrylate85‐co‐vinylferrocene15)/Polypyrrole [P (MTM85‐co‐VFc15)/PPy] were used as matrices for tyrosinase based working electrodes. Direct covalent attachment of enzyme was carried out via the pendant epoxy groups of P(GMA85‐co‐VFc15) film, and the entrapment of enzyme was achieved for electrode containing P(MTM85‐co‐VFc15) film via electropolymerization of pyrrole in the presence of enzyme. The aim of the study is amperometric determination of various phenolics and investigation of the effect of interfacial interactions between enzyme and matrices on biosensor response.

RESULTS: The lowest detection limit and the highest sensitivity for a P(GMA85‐co‐VFc15) based working electrode was found to be 0.113 µmol L−1 for 4‐methoxyphenol, 40 nA (µmol L−1)−1 for pyrocatechol, respectively. Results showed that sensitivities were at least 8500–55000 times higher than the results in previous P(GMA‐co‐VFc) related studies.

CONCLUSION: Facilitated electron transfer was achieved by means of mediator incorporated in conductive composites of VFc based redox copolymers. The effect was greater when enzyme was covalently bonded via epoxy groups due to the proximity of enzyme, mediator and electrode surface. Results showed that a multifunctional surface was provided on electrodes since the suggested copolymers could mediate an electrochemical reaction, and the multifunctional surface was capable of coating with conductive PPy. Copyright © 2011 Society of Chemical Industry
Biodegradation of phenol at high concentration by a novel bacterium: Gulosibacter sp. YZ4
Authors: Zhai Zhijun , Wang Hailei , Yan Shoubao , Yao Jianming
Published: June 2011

BACKGROUND: A novel bacterial strain, Gulosibacter sp. YZ4, has been isolated from activated sludge. Its application potential for phenol biodegradation has not yet been reported, therefore, in this study, biodegradation tests using strain YZ4 were executed under different conditions.

RESULTS: The strain was identified as a new member of the genus Gulosibacter and nominated as Gulosibacter sp. YZ4. Phenol biodegradation tests showed that strain YZ4 could thoroughly biodegrade 1000 mg L−1 phenol across a wide temperature range from 10 to 42 °C and pH range 5 to 11. Degradation of 1000 mg L−1 phenol was not inhibited by the coexistence of p‐cresol or quinoline. During phenol degradation, strain YZ4 excreted both phenol hydroxylase and catechol 1,2‐dioxygenase to efficiently metabolize phenol. At 36 °C, pH 7.5, strain YZ4 could effectively degrade phenol at concentrations as high as 2000 mg L−1 within 76 h. Haldane's model with the parameters obtained from the experiments could successfully describe the behavior of the phenol biodegradation by the strain YZ4.

CONCLUSIONS: The strain YZ4 has a high potential for applications in phenol wastewater treatment in view of its adaptability to temperature and pH fluctuations and great tolerance to other coexistent toxics. Copyright © 2011 Society of Chemical Industry
Sustained, high transgene expression in liver with plasmid vectors using optimized promoter‐enhancer combinations
Authors: Magnusson Terese , Haase Rudolf , Schleef Martin , Wagner Ernst , Ogris Manfred
Published: June 2011

Background

Plasmid‐based gene therapy approaches often lack long‐term transgene expression in vivo as a result of silencing or loss of the vector. One way to overcome these limitations is to combine nonsilenced promoters with strong enhancers.

Methods

In the present study, we combine murine or human cytomegalovirus (CMV)‐derived enhancer elements with the human elongation factor 1α (EF1α) promoter in a plasmid backbone devoid of potentially immunostimulating cytosine‐guanine repeat sequences. Luciferase transgene activity was monitored in mouse liver after hydrodynamic plasmid delivery.

Results

Luciferase activity of a CMV‐promoter driven plasmid rapidly declined within days, whereas the activity of the EF1α driven plasmid remained high for 2 weeks (murine enhancer) and detectable for > 80 days (human enhancer). Expression levels clearly correlated with higher plasmid copy number found in the liver at 2 months after gene delivery. Furthermore, we developed a novel synthetic CMV‐EF1α hybrid promoter (SCEP) combining the high activity of CMV and sustained activity of EF1α promoter. The SCEP led to a constitutive three‐fold increase in expression levels compared to the EF1α promoter in vivo.

Conclusions

This novel combination of enhancer and promoter element with optimized plasmid backbones will pave the way for more efficient nonviral approaches in gene therapy. Copyright © 2011 John Wiley & Sons, Ltd.
Assignment of the 15N resonances of the antifungal agent posaconazole
Authors: Hilton Bruce D. , Feng Wenqing , Martin Gary E.
Published: June 2011

The structurally complex antifungal agent posaconazole has been well characterized by conventional 1H‐ and 13C‐NMR studies. In contrast, 15N resonance assignments have never been reported. We now wish to report the assignment of the eight 15N resonances of posaconazole using two‐dimensional long‐range 1H‐15N GHMBCAD NMR data. The 15N resonance assignments were undertaken to facilitate the evaluation of the impact of 1H‐15N heteronuclear shift correlation data in the Computer‐Assisted Structure Elucidation (CASE) of complex molecular structures. J. Heterocyclic Chem., (2011).
Piperidine‐mediated synthesis of thiazolyl chalcones and their derivatives as potent antimicrobial agents
Authors: Venkatesan P. , Maruthavanan T.
Published: June 2011

A series of new thiazolyl chalcones, 1‐[2‐amino‐4‐methyl‐1, 3‐thiazol‐5‐yl]‐3‐aryl‐prop‐2‐en‐1‐one were prepared by piperidine mediated Claisen‐Schmidt condensation of thiazolyl ketone with substituted aromatic aldehyde. These chalcones on cyclization gave 2‐amino‐6‐(2‐amino‐4‐methyl‐1,3‐thiazol‐5‐yl)‐4‐aryl‐4H‐pyridine‐3‐carbonitrile and 2‐amino‐6‐(2‐amino‐4‐methyl‐1,3‐thiazol‐5‐yl)‐4‐aryl‐4H‐pyran‐3‐carbonitrile. The results showed that this skeletal framework exhibited marked potency as antimicrobial agents. The most active antibacterial agent was 2‐amino‐6‐(2‐amino‐4‐methyl‐1,3‐thiazol‐5‐yl)‐4‐(4‐chlorophenyl)‐4H‐pyran‐3‐carbonitrile while 2‐amino‐6‐(2‐amino‐4‐methyl‐1,3‐thiazol‐5‐yl)‐4‐(4‐methoyphenyl)‐4H‐pyran‐3‐carbonitrile appeared to be the most active antifungal agent. J. Heterocyclic Chem., (2011).
Oximes as products in the reactions of 5‐substituted 2‐nitrothiophenes with arylacetonitriles
Authors: Rad Nazar I. , Teslenko Yuriy O. , Obushak Mykola D. , Matiychuk Vasyl S. , Lytvyn Roman Z.
Published: June 2011

It has been shown that reactions 5‐substituted 2‐nitrothiophenes with arylacetonitriles in the presence of potassium hydroxide in methanol lead to the formation of the new [2‐(hydroxyimino)‐5‐R‐3(2H)‐thienylidene](aryl)acetonitriles. Under proposed reaction conditions, the formation of thieno[2,3‐c]isoxazole was not the case. J. Heterocyclic Chem., (2011).
Synthesis, characterization, and evaluation of antimicrobial activities of a new class of macrocyclic phosphonates
Authors: Chandra Sekhar Reddy G. , Uma Ravi Sankar A. , Veera Narayana Reddy M. , Radha Rani C. , Suresh Reddy C.
Published: June 2011

A series of a new class of phosphorus analogue macrocycles was accomplished by condensation of N‐substituted‐[bis(3,5‐dimethyl‐2‐hydroxybenzyl)]‐amines with various phosphorus dichlorides in dry toluene in the presence of triethylamine at 0–50°C. All the title compounds were evaluated for antimicrobial activity to determine their efficacy and were effective in suppressing the growth of bacteria and fungi. The chemical structures of the title products were characterized by IR, 1H, 13C, 31P‐NMR, mass spectral studies, and elemental analysis. J. Heterocyclic Chem., (2011).
NMR and X‐ray structural studies on 3‐benzyl‐8‐bromoadenine
Authors: Siah Huey‐San Melanie , Görbitz Carl Henrik , Gundersen Lise‐Lotte
Published: June 2011

8‐Bromoadenine was benzylated in the presence of base to give a mixture of two regioisomers. One was easily recognized as 9‐benzyl‐8‐bromoadenine, but the other structure could not be determined with absolute certainty by NMR. Therefore, X‐ray crystallography was used to prove that the benzyl group was attached to N‐3. Furthermore, it is shown that the 3‐benzyl adenine derivative exists as the amine tautomer both in the crystalline state as well as in solution (DMSO‐d6), with restricted rotation around the N6C6 bond. J. Heterocyclic Chem., (2011).
Vascular endothelial growth factor polymorphisms in patients with steroid‐induced femoral head osteonecrosis
Authors: Lee Yun Jong , Lee Jong Seok , Kang Eun Ha , Lee Young‐Kyun , Kim Shin‐Yoon , Song Yeong Wook , Koo Kyung‐Hoi
Published: June 2011

To investigate an association between steroid‐induced femoral head osteonecrosis (FHON) and functional vascular endothelial growth factor (VEGF) gene (−2578A/C, −1154A/G, −634C/G, and +405C/G) polymorphisms polymerase chain reaction‐restriction fragment length polymorphism genotyping was performed in 160 patients (86 idiopathic FHON and 74 steroid‐induced FHON) and 160 gender‐ and age‐matched controls. The steroid‐induced subgroup had a significantly lower prevalence of −1154A allele (7.4% vs. 18.1%, odds ratio (OR) = 0.363) and genotype carrying −1154A (14.9% vs. 32.5%, OR = 0.333 in a recessive model) than controls. In a dominant model, the frequency of genotype carrying +405G (74.3% vs. 84.4%, OR = 0.492) was significantly lower in steroid‐induced FHON than in controls. The distribution of haplotypes was significantly different between controls and FHON patients (p = 0.00011). Especially, when haplotypes were classified into high (CGCG and AAGG) or low (CGGC and AGGC) VEGF inducing haplotypes, patients with steroid‐induced FHON had a significantly lower prevalence of high inducing haplotypes (7.4% vs. 15.9%, OR = 0.424) and a significantly higher prevalence of low inducing haplotypes (4.7% vs. 0.6%, OR = 7.894) than controls. Low inducing VEGF haplotypes may confer an increased risk and high inducing haplotypes have a protective effect for the development of steroid‐induced FHON in Korea. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:21–27, 2012
Pressure‐induced phase transitions in palmitic acid: C form
Authors: de Sousa F. F. , Saraiva G. D. , Freire P. T. C. , Lima J. A. , Alcantara P. , Melo F. E. A. , Mendes Filho J.
Published: June 2011

In this article, we report a high‐pressure Raman spectroscopy study of palmitic acid (PA, C form) from ambient pressure up to 21 GPa. The effects of hydrostatic pressure on the vibrational spectrum of PA are reported, and the data show that PA experiences a rich sequence of phase transformations. These changes in the crystal structure occur gradually as the pressure increases and they are related to the highly flexible crystalline structure. Copyright © 2011 John Wiley & Sons, Ltd.