bluuebunny/crossref_metadata_2025 huggingface dataset:
The palaeogeography of Mesolithic settlement-subsistence and shell midden formation in the Muge valley, Lower Tagus Basin, Portugal
Authors: van der Schriek Tim , Passmore David G. , Stevenson Anthony C. , Rolao Jose
Published: July 2007

This paper reports the first detailed palaeogeographical analysis of the environmental context of late Mesolithic shell midden sites in the lower Tagus area and focuses on the lower Muge valley, which contains an internationally significant Mesolithic record. The lower Muge valley fill comprises buried estuarine and fluvial environments contemporary with Mesolithic settlement. Holocene environmental and palaeogeographic changes influenced Mesolithic settlement-subsistence and midden accumulation. The sudden appearance of large late Mesolithic shell middens throughout Portugal represents a process of increased visibility and preferential preservation of the archaeological record. Prior to ~6100 cal. BC, aggrading valley floor environments did not occupy the entire width of the present lower Tagus floodplain and any sites located in the early Holocene valley are currently deeply buried. Shell midden occupation on terrace levels followed the establishment of aggrading estuarine environments, containing productive shell beds, near the mouth of the lower Muge valley at ~6100 cal. BC. The critical factors in site choice appear to have been the nearby presence of (i) rich shell resources and (ii) freshwater environments. Long-term site occupation and (semi-)sedentary behaviour was favoured by the local presence, for over 2000 years, of rich resources from estuarine, freshwater and open woodland environments. Site abandonment (~5300—4800 cal. BC) coincided with the regional establishment of an open landscape (~5000 cal. BC) and the contraction of local estuarine environments (~5555—3800 cal. BC). The associated gradual decrease in resources and cultural interaction with the expanding early Neolithic communities may have influenced Mesolithic site abandonment.
Hydrography and climate of the last 4400 years in a SW Greenland fjord: implications for Labrador Sea palaeoceanography
Authors: Seidenkrantz M.-S. , Aagaard-Sørensen S. , Sulsbrück H. , Kuijpers A. , Jensen K.G. , Kunzendorf H.
Published: July 2007

A multiproxy record including benthic foraminifera, diatoms and XRF data of a marine sediment core from a SW Greenland fjord provides a detailed reconstruction of the oceanographic and climatic variations of the region during the last 4400 cal. years. The lower part of our record represents the final termination of the Holocene Thermal Maximum. After the onset of the `Neoglaciation' at approximately 3.2 ka cal. BP, the fjord system was subject to a number of marked hydrographical changes that were closely linked to the general climatic and oceanographic development of the Labrador Sea and the North Atlantic region. Our data show that increased advection of Atlantic water (Irminger Sea Water) from the West Greenland Current into the Labrador Sea was a typical feature of Northeast Atlantic cooling episodes such as the `Little Ice Age' and the `European Dark Ages', while the advection of Irminger Sea Water decreased significantly during warm episodes such as the `Mediaeval Warm Period' and the `Roman Warm Period'. Whereas the `Mediaeval Warm Period' was characterized by relatively cool climate as suggested by low meltwater production, the preceding `Dark Ages' display higher meltwater runoff and consequently warmer climate. When compared with European climate, these regional climate anomalies indicate persisting patterns of advection of colder, respectively warmer air masses in the study region during these periods and thus a long-term seesaw climate pattern between West Greenland and Europe.
Methane gas release from the Storegga submarine landslide linked to earlyHolocene climate change: a speculative hypothesis
Authors: Beget James E. , Addison Jason A.
Published: July 2007

The 3000 km3 Storegga submarine landslide occurred c. 8150 years ago from an area rich in gas hydrates off the western coast of Norway. A synchronous increase of 80—100 ppb in atmospheric methane concentrations is recorded in the Greenland GRIP ice core. This increase is hypothesized to reflect methane releases from the Storegga slide debris at an estimated rate of 20—25 Tg/yr for several hundred years following the slide. Methane is a powerful greenhouse gas, and methane release from the Storegga submarine landslide may have contributed to the rapid termination of the brief but intense 8200 yr cold event and the subsequent evolution of Holocene climate.
Chironomid responses (Insect: Diptera) to Younger Dryas and Holocene environmental changes in a river floodplain from northern France (St-Momelin, St-Omer basin)
Authors: Gandouin Emmanuel , Ponel Philippe , Franquet Evelyne , Van Vliet-Lanoë Brigitte , Andrieu-Ponel Valérie , Keen David H. , Brulhet Jacques , Brocandel Marcel
Published: July 2007

Lateglacial to Holocene subfossil chironomids from the St-Omer basin at St-Momelin (northern France) were analysed. At the end of the Lateglacial, stratigraphic and chironomid sequences indicate a shallow, oligotrophic and slow-flowing freshwater stream, with abundant aquatic macrophytic vegetation. Cold-water adapted taxa indicate a cold climate. During the early Holocene, from about 9500 to 7700 conventional radiocarbon yr BP, climate improvement is marked by an increase in warm-water adapted taxa and a decrease in cold-water fauna. However, the cold-water fauna persist, probably because of both the instability and continentality of the climate. During the mid Holocene, from about 7700 to 6000 BP, the marine transgression strongly influenced the river's hydrological regime and consequently the chironomid assemblages. At that time, eutrophic, warm and shallow stagnant-water conditions occured throughout the basin. From 6000 to 3200 BP, the St-Momelin basin was subjected to a marine regression. Chironomids indicate a hydrological regime marked by an alternance of phases with either a dominance of rheophilous or limnophilous fauna. During this period, equivalent percentages of warm- and cold-adapted taxa may be explained by cold-water input in context of a temperate climate.
Effects of Deliberative Democracy on School Self-Evaluation
Authors: Davidsdottir Sigurlina , Lisi Penelope
Published: July 2007

In 1996, Icelandic schools were mandated to evaluate their work.This article focuses on four schools that were selected for this case study, two primary schools and two secondary schools.They all received support from two researchers: one from Central Connecticut State University and another from the University of Iceland.These researchers coached school-evaluation teams in their self-evaluation efforts and assessed change in the schools. The schools received empowerment-based support, where the researchers taught staff to evaluate school work and take responsibility for development based on outcomes from longitudinal data collection and dissemination of evaluation information. Researcher findings include changes in teacher perceptions of administration facilitating their professional growth; systematic data collection; teacher ownership and collaboration; and shared decision-making for improvement efforts in the schools. Findings were triangulated, using different data collection methods. Results indicate that evaluation worked best when schools took a democratic stance. Program fidelity was an indication of improvement within the schools.
Toward a Group Facilitation Technique for Project Teams
Authors: Witte Erich H.
Published: July 2007

This article presents the development of a group facilitation technique (PROMOD — Procedural Moderation). The author points toward the importance of integrating theoretical assumptions, theory testing and basic empirical research with practical application. The results are based on the observation of various three-member task groups faced with a complex non-heureka problem. These comprise naturally interacting groups, simple arithmetic assembled groups of individuals without any interaction (synthetic groups), and groups in which a group technique of reduced interaction which focuses on individual contribution through facilitated knowledge elicitation is applied.The task involves decisions on what to do after a plane crash and ranking objects with regard to their importance for survival in an alarming situation (Lafferty & Pond, 1974). The group decision quality is determined by relating to conclusions reached by an independent expert. Results indicate that the observed teams performed best when the PROMOD procedure was applied.
Enhanced tribological properties of lotus leaf-like surfaces fabricated by capillary force lithography
Authors: Singh R. A. , Yoon E.-S. , Kim H. J. , Kong H. , Park S. , Jeong H. E. , Suh K. Y.
Published: July 2007

The surface topography of a real lotus leaf was successfully replicated using a capillarity directed soft lithographic technique. The replication was carried out on poly(methyl methacrylate) (PMMA) film coated on a silicon wafer. The friction property of the patterned surfaces was investigated on a microscale. Its friction coefficient was almost six times lower than that of the PMMA thin film. The reduced real area of contact projected by the patterned surface appears to be the main reason for its superior friction property.
Hydrogenated amorphous carbon based solar cells by pulsed laser deposition with mixture of graphite and camphor as precursor materials
Authors: Rusop M. , Tian X. M. , Soga T. , Jimbo T. , Umeno M. , Sharon M.
Published: July 2007

The authors have deposited hydrogenated amorphous carbon films (a-C:H) on quartz and p type silicon substrates (100) by pulsed laser deposition (PLD) using a mixture of graphite and camphor powders at room temperature. The presence of hydrogen in the a-C:H films has been revealed by fourier transform infrared spectroscopy (FTIR) measurement. The solar cell structure of a-C:H/p-Si was also fabricated. The formation of a heterojunction between the a-C:H films and silicon substrate was confirmed by the current–voltage ( I–V) measurement in the dark and under illumination conditions. The structure of a-C:H/p-Si showed photovoltaic characteristics with an open circuit voltage Voc of 400 mV and short circuit current density Jsc of ∼15 mA cm−2 under illumination [air mass (AM) 1·5, 100 mW cm−2, 25°C]. From the calculation, the energy conversion efficiency and fill factor were found to be approximately 2·1% and 0·38 respectively. The carbon layer is contributed to the energy conversion efficiency, which was proved by the measurement of quantum efficiency.
Influence of processing parameters on deposition rate and crystal structure of reactively sputtered HfC
Authors: Mohammad F. Z. , Lawson K. J. , Nicholls J. R.
Published: July 2007

Hafnium carbide is one of the materials with the most potential that can be used for high temperature oxidation resistant coatings. So far, HfC coatings are mainly being produced by chemical vapour deposition technique. In this work, HfC coatings were produced using a reactive magnetron sputtering method. The reactive gas used in these experiments was mixture of CH4 and H2. The study is focused mainly on the effect of process parameters, applied radio frequency (RF) power, process pressure and reactive gas flow, on the deposition rate and crystal structure of the deposited HfC coatings.
Tribological properties of electrodeposited Ni–Co–PTFE composite coatings
Authors: Tang H.-K. , Zhao W.-Z.
Published: July 2007

Nickel and cobalt matrix coatings and their composite coatings with polytetrafluoroethylene (PTFE) particle have been prepared on mild steel substrates by electrocodeposition technique. Microstructural studies, microhardness, friction and wear tests under various loads and sliding speeds have been carried out on these coatings. Scanning electron microscopy (SEM) studies on the worn surfaces were conducted. All the composite coatings exhibited a lower coefficient of friction and better wear resistance when compared with nickel and nickel–cobalt coatings at all loads and sliding velocities studied. However, nickel–cobalt–PTFE composite coatings possessed the lowest coefficient of friction and wear rates. Significant effect of load and sliding velocities on both the coefficient of friction and wear rates of these coatings has been observed. Scanning electron microscopy studies of the worn surfaces reveal delamination process at higher loads.
Porous films on surface of titanium prepared by low voltage micro arc oxidation
Authors: Hou T. , Zhang J. Z.
Published: July 2007

Porous TiO2 films were prepared by using micro arc oxidation (MAO) in an electrolytic solution of Na3PO4 with a voltage of 200 V. Three different concentrations of Na3PO4 electrolyte were used, i.e. 10, 15 and 20 g L−1. The oxidation time ranged from 5 to 15 min. The oxide films were characterised by scanning electron microscopy, energy dispersive X-ray spectrometer and X-ray diffraction. Scanning electron microscopy analysis shows that the oxide films had numerous pores with dimensions between 0·5 and 2·5 μm. The phosphorous concentrations on the surfaces of the oxide films were found to be between 4·73 and 5·73%. The anatase TiO2 phase was determined in all the films, and no rutile phase was detected. The titanium phosphate phase was only found in the oxide films prepared with 20 g L−1 of concentration of Na3PO4 electrolyte. The experimental results suggest that the low voltage MAO method is an effective way to prepare porous TiO2 film containing a high concentration of phosphorous.
Fretting wear studies on PVD TiN coated, ion implanted and thermally oxidised biomedical titanium alloys
Authors: Vadiraj A. , Kamaraj M. , Gnanamoorthy R.
Published: July 2007

Fretting damage is normally expected in biomedical implants due to body movements. Titanium alloys are most commonly used for biomedical devices and surface modified alloys have superior tribological properties to virgin materials. In the present study, the fretting wear resistance of physical vapour deposition (PVD) TiN coated, ion implanted and thermally oxidised biomedical alloys have been investigated and compared. PVD TiN coating has shown the best fretting wear resistance with minimum friction coefficient, less wear scar depth and diameter, and minimum wear rate compared to other coatings. The ion implanted specimen has undergone fretting assisted electrochemical dissolution to give higher wear loss after the modified layer has eroded away. Thermal oxidation has shown intermediate response to fretting. Fretting resistance can be improved with layers of high hardness and thickness.
Ion nitrided AISI H13 tool steel Part 2 – High temperature performance under sliding wear conditions
Authors: Cruz M. R. , Staia M. H.
Published: July 2007

In this work, a systematic variation of the processing parameters, such as gas mixture, time of nitriding and current density, has been carried out to determine how these will influence the sliding wear behaviour of plasma nitrided layers on AISI H13. Optical profilometry and scanning electron microscopy were used to characterise the worn sample and to determine the wear mechanism. The results revealed the strong influence of the current density on the formation of different diffusion and nitrided layers, which explained the wear behaviour of the studied samples, especially for those which were tested at room temperature. It was found that the wear volume of the nitrided samples without the existence of a compound layer was around 200 times smaller than that of the untreated samples and nearly 7 times smaller than that of nitrided samples when the compound layer was present. During the tests carried out at 300°C, the wear behaviour for the nitrided samples was worse than that for the untreated ones, due to the formation of higher amount of debris as a consequence of the breakdown of the compound layer and the subsequent removal of the enriched CrN from the ferritic matrix, generating a severe abrasion wear mechanism. All the samples tested at 600°C presented a similar tribological behaviour irrespective to the processing parameters values chosen for nitriding, as a consequence of the formation of a uniform and ‘lubricious’ iron oxide layer which, however, was insufficient to protect the steel against wear at this temperature to the levels which were obtained for the samples tested at room temperature.
Comparison of mechanical properties of various PVD hard coatings for forming tools
Authors: Goršćak Đ. , Panjan P. , Čekada M. , Ćurković L.
Published: July 2007

In the present paper the basic mechanical properties of PVD hard coatings, which are currently used in Končar Alati company for wear protection of forming tools manufactured on request of the Electrolux Group, with emphasis on the Electrolux Home Products company, Denmark A/S, have been compared. This company has high demands on tool performance for machining and forming of several different workpiece materials, such as sheet steel, stainless steel, aluminium and Teflon coated sheet. Two different deposition methods were used for preparation of hard coatings: sputtering using unballanced magnetron sources – CC800 (CemeCon) and cathode arc evaporation [BAI 1200 (Balzers)]. The coatings for test were deposited on four different tool steels. It was found that the hard coatings investigated in the present work showed a wide range of mechanical properties: microhardness in the range of 900–3200 HV, critical load for total delamination in the range of 75–135 N, indentation modulus in the range of 120–390 GPa and the scratching coefficient in the range of 0·02–0·09.
4-(2-pyridylazo-)-resorcinol as effective corrosion inhibitor for mild steel in 0·5M sulphuric acid
Authors: Dheer N. , Kanojia R. , Chandra C. , Kim H. , Singh G.
Published: July 2007

The efficiency of 4-(2-pyridylazo-)-resorcinol (PAR) as corrosion inhibitor for mild steel in H2SO4 was investigated by electrochemical methods such as steady state galvanostatic and potentiostatic polarisation measurements. The dissolution parameters such as corrosion currents, passive current, flade potential, open circuit potential, cathodic and anodic Tafel slopes and efficiencies were determined. Potentiodynamic polarisation was used to assess the ability of heterocyclic organic inhibitor/PAR to provide an effective barrier to corrosion in acidic environments. Electrochemical measurements showed that the heterocyclic compound investigated has a fairly good inhibiting properties. The absorption and corrosion rates based on heat of adsorption and activation energies are calculated from Langmuir's adsorption isotherm. The inhibition efficiency range of 84–93% is obtained for a concentration range of 10−7–10−1 mol L−1. Passivating parameters revealed that this inhibitor is strongly passivating. Scanning electronic microscopy observations and quantum chemical calculations along with the electrochemical data suggested that the ability of PAR to act as a physical barrier was more important in providing corrosion protection of mild steel surface against acidic environments.
Oral maintenance clinical trial with miglustat for type I Gaucher disease: switch from or combination with intravenous enzyme replacement
Authors: Elstein Deborah , Dweck Altoon , Attias Drorit , Hadas-Halpern Irith , Zevin Shoshana , Altarescu Gheona , Aerts Johannes F. M. G. , van Weely Sonja , Zimran Ari
Published: July 2007

Enzyme replacement therapy (ERT) with imiglucerase reduces hepatosplenomegaly and improves hematologic parameters in Gaucher disease type 1 within 6-24 months. Miglustat reduces organomegaly, improves hematologic parameters, and reverses bone marrow infiltration. This trial evaluates miglustat in patients clinically stable on ERT. Tolerability of miglustat and imiglucerase, alone and in combination, pharmacokinetic profile, organ reduction, and chitotriosidase activity were assessed. Thirty-six patients stable on imiglucerase were randomized into this phase II, open-label trial. Statistically significant changes from baseline were assessed (paired t test) on primary objectives with secondary analyses on biochemical and safety parameters. Liver and spleen volume were unchanged in switched patients. No significant differences were seen between groups regarding mean change in hemoglobin. Mean change in platelet counts was only significant between miglustat and imiglucerase groups (P = .035). Chitotriosidase activity remained stable. In trial extension, clinical endpoints were generally maintained. Miglustat was well tolerated alone or in combination. Miglustat's safety profile was consistent with previous trials; moreover, no new cases of peripheral neuropathy were observed. Gaucher disease type 1 (GD1) parameters were stable in most switched patients. Combination therapy did not show benefit. Findings suggest miglustat could be an effective maintenance therapy in stabilized patients with GD1.
Salinosporamide A (NPI-0052) potentiates apoptosis, suppresses osteoclastogenesis, and inhibits invasion through down-modulation of NF-κB–regulated gene products
Authors: Ahn Kwang Seok , Sethi Gautam , Chao Ta-Hsiang , Neuteboom Saskia T. C. , Chaturvedi Madan M. , Palladino Michael A. , Younes Anas , Aggarwal Bharat B.
Published: July 2007

Salinosporamide A (also called NPI-0052), recently identified from the marine bacterium Salinispora tropica, is a potent inhibitor of 20S proteasome and exhibits therapeutic potential against a wide variety of tumors through a poorly understood mechanism. Here we demonstrate that salinosporamide A potentiated the apoptosis induced by tumor necrosis factor α (TNF), bortezomib, and thalidomide, and this correlated with down-regulation of gene products that mediate cell proliferation (cyclin D1, cyclooxygenase-2 [COX-2], and c-Myc), cell survival (Bcl-2, Bcl-xL, cFLIP, TRAF1, IAP1, IAP2, and survivin), invasion (matrix metallopro-teinase-9 [MMP-9] and ICAM-1), and angiogenesis (vascular endothelial growth factor [VEGF]). Salinosporamide A also suppressed TNF-induced tumor cell invasion and receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis. We also found that it suppressed both constitutive and inducible NF-κB activation. Compared with bortezomib, MG-132, N-acetyl-leucyl-leucyl-norleucinal (ALLN), and lactacystin, salinosporamide A was found to be the most potent suppressor of NF-κB activation. Further studies showed that salinosporamide A inhibited TNF-induced inhibitory subunit of NF-κB α (IκBα) degradation, nuclear translocation of p65, and NF-κB-dependent reporter gene expression but had no effect on IκBα kinase activation, IκBα phosphorylation, or IκBα ubiquitination. Thus, overall, our results indicate that salinosporamide A enhances apoptosis, suppresses osteoclastogenesis, and inhibits invasion through suppression of the NF-κB pathway.
Complete responses of relapsed lymphoma following genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer
Authors: Bollard Catherine M. , Gottschalk Stephen , Leen Ann M. , Weiss Heidi , Straathof Karin C. , Carrum George , Khalil Mariam , Wu Meng-fen , Huls M. Helen , Chang Chung-Che , Gresik M. Victoria , Gee Adrian P. , Brenner Malcolm K. , Rooney Cliona M. , Heslop Helen E.
Published: July 2007

Epstein-Barr virus (EBV)–associated tumors developing in immunocompetent individuals present a challenge to immunotherapy, since they lack expression of immunodominant viral antigens. However, the tumors consistently express viral proteins including LMP2, which are immunologically “weak” but may nonetheless be targets for immune T cells. We previously showed that a majority of cytotoxic T lymphocytes (CTLs) reactivated using EBV-transformed B-lymphoblastoid cells lines (LCLs) contained minor populations of LMP2-specific T cells and homed to tumor sites. However, they did not produce remissions in patients with bulky disease. We have now used gene transfer into antigen-presenting cells (APCs) to augment the expression and immunogenicity of LMP2. These modified APCs increased the frequency of LMP2-specific CTLs by up to 100-fold compared with unmodified LCL-APCs. The LMP2-specific population expanded and persisted in vivo without adverse effects. Nine of 10 patients treated in remission of high-risk disease remain in remission, and 5 of 6 patients with active relapsed disease had a tumor response, which was complete in 4 and sustained for more than 9 months. It is therefore possible to generate immune responses to weak tumor antigens by ex vivo genetic modification of APCs and the CTLs so produced can have substantial antitumor activity. This study is registered at http://www.cancer.gov/clinicaltrials (protocol IDs: BCM-H-9936, NCT00062868, NCT00070226).
Toward accurate high-throughput SNP genotyping in the presence of inherited copy number variation
Authors: MacConaill Laura E , Aldred Micheala A , Lu Xincheng , LaFramboise Thomas
Published: July 2007

Background

The recent discovery of widespread copy number variation in humans has forced a shift away from the assumption of two copies per locus per cell throughout the autosomal genome. In particular, a SNP site can no longer always be accurately assigned one of three genotypes in an individual. In the presence of copy number variability, the individual may theoretically harbor any number of copies of each of the two SNP alleles.

Results

To address this issue, we have developed a method to infer a "generalized genotype" from raw SNP microarray data. Here we apply our approach to data from 48 individuals and uncover thousands of aberrant SNPs, most in regions that were previously unreported as copy number variants. We show that our allele-specific copy numbers follow Mendelian inheritance patterns that would be obscured in the absence of SNP allele information. The interplay between duplication and point mutation in our data shed light on the relative frequencies of these events in human history, showing that at least some of the duplication events were recurrent.

Conclusion

This new multi-allelic view of SNPs has a complicated role in disease association studies, and further work will be necessary in order to accurately assess its importance. Software to perform generalized genotyping from SNP array data is freely available online [1].
Population kinetics during simultaneous infection of insect cells with two different recombinant baculoviruses for the production of rotavirus-like particles
Authors: Mena Jimmy A , Ramírez Octavio T , Palomares Laura A
Published: July 2007

Background

The simultaneous production of various recombinant proteins in every cell of a culture is often needed for the production of virus-like particles (VLP) or vectors for gene therapy. A common approach for such a purpose is the coinfection of insect cell cultures with different recombinant baculoviruses, each containing one or more recombinant genes. However, scarce information exists regarding kinetics during multiple infections, and to our knowledge, no studies are available on the behavior of the different populations that arise during coinfections. Such information is useful for designing infection strategies that maximize VLP or vector yield. In this work, kinetics of cell populations expressing rotavirus GFPVP2 (infected with bacGFPVP2), VP6 (infected with bacVP6), or both proteins simultaneously (coinfected with both baculoviruses) were followed by flow cytometry.

Results

In single infections, the population infected with any of the recombinant baculoviruses followed the Poisson distribution, as the population expressing a recombinant protein exhibited a hyperbolic-type function with respect to the multiplicity of infection (MOI) up to 5 pfu/cell. In coinfections, the population fraction expressing each recombinant protein could not be anticipated from results of single infections, as in some cases interference and synergistic effects were found. Only cultures with a total MOI below 5 pfu/cell followed the Poisson distribution. For cultures with a MOI of bacGFPVP2 above that of bacVP6 (overall MOI above 5 pfu/cell), the total population expressing one or both recombinant proteins was as low as 50% below that predicted by Poisson. In contrast, the population fraction expressing VP6 increased in coinfections, compared to that in single infections. The largest population fraction simultaneously expressing both recombinant proteins was 58%, and corresponded to cultures infected at a MOI of 5 and 1 pfu/cell of bacGFPVP2 and bacVP6, respectively.

Conclusion

The infection conditions that maximize the cell population simultaneously expressing two recombinant proteins were determined. Such conditions could not have been anticipated from population kinetics in individual infections. This information should be taken into account for improved simultaneous production of various recombinant proteins in any work dealing with coinfections.
Deep venous thrombosis in the antenatal period in a large cohort of pregnancies from western India
Authors: Vora Sonal , Ghosh Kanjaksha , Shetty Shrimati , Salvi Vinita , Satoskar Purnima
Published: July 2007

Background

Deep venous thrombosis (DVT) is an important complication in the peripartal and postpartal period.

Methods

We followed up prospectively the prevalence of DVT in 34720 prenatal mothers between June 2002 and July 2006 attending the antenatal clinics of two major hospitals in Mumbai, India. Thirty two women (0.1%) presented for the first time with symptomatic DVT i.e. 17 in the first trimester, 6 in the second and 9 in the third trimester of pregnancy. Nine had history of fetal loss while in the remaining twenty three there was no history of fetal loss.

Results

The evaluation of both acquired and heritable thrombophilia showed a conglomeration of thrombophilia in this group when compared to 100 normal pregnant women who have given birth to at least one healthy baby with no history of fetal death, DVT or other obstetrical complications. The relative risks for all the antiphospholipid antibodies (APA) studied i.e lupus anticoagulant (LA), IgG/IgM antibodies for cardiolipin (ACA), β2 glycoprotein 1 (β2 GP 1) and annexin V were significantly higher in women with pregnancy associated DVT (RR 7.4 95% CI 4.3–11.3 P < 0.05). Among the genetic thrombophilia markers studied, Protein S (PS) deficiency was the strongest risk factor (RR 5.00 95% CI 3.02–5.00 P < 0.05) followed by factor V Leiden (FVL) mutation (RR 4.57 95% CI 2.23–4.57 P < 0.05) and PAI 4G/4G homozygosity (RR 3.24 95% CI 1.85–5.12 P < 0.05). Protein C (PC) and endothelial protein C receptor (EPCR) 23 bp insertion polymorphism was also increased in the patient group as compared to controls but the difference was not statistically significant. The MTHFR C677T, fibrinogen gene β448 Arg/Lys polymorphisms were not significantly different from the normal controls, while antithrombin III (AT III) deficiency and PT G20210A polymorphism were absent in both controls and patients. Two or more risk factors were present in 22 out of 32 cases (68.75%).

Conclusion

We conclude that the prevalence of DVT in India is more or less similar to other reports published and both acquired and heritable thrombophilia show strong association with DVT associated with pregnancy.
Kinetics of antibody-induced modulation of respiratory syncytial virus antigens in a human epithelial cell line
Authors: Sarmiento Rosa E , Tirado Rocio G , Valverde Laura E , Gómez-Garcia Beatriz
Published: July 2007

Background

The binding of viral-specific antibodies to cell-surface antigens usually results in down modulation of the antigen through redistribution of antigens into patches that subsequently may be internalized by endocytosis or may form caps that can be expelled to the extracellular space. Here, by use of confocal-laser-scanning microscopy we investigated the kinetics of the modulation of respiratory syncytial virus (RSV) antigen by RSV-specific IgG. RSV-infected human epithelial cells (HEp-2) were incubated with anti-RSV polyclonal IgG and, at various incubation times, the RSV-cell-surface-antigen-antibody complexes (RSV Ag-Abs) and intracellular viral proteins were detected by indirect immunoflourescence.

Results

Interaction of anti-RSV polyclonal IgG with RSV HEp-2 infected cells induced relocalization and aggregation of viral glycoproteins in the plasma membrane formed patches that subsequently produced caps or were internalized through clathrin-mediated endocytosis participation. Moreover, the concentration of cell surface RSV Ag-Abs and intracellular viral proteins showed a time dependent cyclic variation and that anti-RSV IgG protected HEp-2 cells from viral-induced death.

Conclusion

The results from this study indicate that interaction between RSV cell surface proteins and specific viral antibodies alter the expression of viral antigens expressed on the cells surface and intracellular viral proteins; furthermore, interfere with viral induced destruction of the cell.
Molecular biology of cantharidin in cancer cells
Authors: Rauh Rolf , Kahl Stefan , Boechzelt Herbert , Bauer Rudolf , Kaina Bernd , Efferth Thomas
Published: July 2007

Herbal medicine is one of the forms of traditional medical practice. Traditional Chinese medicine (TCM) and traditional Vietnamese medicine (TVM) are well-known for their long-standing tradition of herbal medicine.

Secreted by many species of blister beetle, most notably by the 'Spanish fly' (Lytta vesicatoria), cantharidin inhibits protein phosphatases 1 and 2A (PP1, PP2A). Blister beetle has been used in Asian traditional medicine to treatMolluscum contagiosumvirus (MCV) infections and associated warts, and is now also used for cancer treatment. A combination of both genomic and postgenomic techniques was used in our studies to identify candidate genes affecting sensitivity or resistance to cantharidin. Cantharidin was not found to be related to multidrug resistance phenotype, suggesting its potential usefulness for the treatment of refractory tumors. Oxidative stress response genes diminish the activity of cantharidin by inducing DNA strand breaks which may be subject to base excision repair and induce apoptosis in a p53- and Bcl2-dependent manner.

Cantharidin is one of many natural products used in traditional Chinese medicine and traditional Vietnamese medicine for cancer treatment. Combined methods of pharmaceutical biology and molecular biology can help elucidate modes of action of these natural products.
Rapid Maturation of Glycoprotein Hormone Free α-Subunit (GPHα) and GPHαα Homodimers
Authors: Krause Jean-Michel , Berger Peter , Roig Jordi , Singh Vinod , Merz Wolfgang E.
Published: July 2007

The dynamics of glycoprotein hormone α-subunit (GPHα) maturation and GPHαα homodimer formation were studied in presence (JEG-3 choriocarcinoma cells) and absence (HeLa cells) of hCGβ. In both cases, the major initially occurring GPHα variant in [35S]Met/Cys-labeled cells carried two N-glycans (Mr app = 22 kDa). Moreover, a mono-N-glycosylated in vivo association-incompetent GPHα variant (Mr app = 18 kDa) was observed. In JEG-3 cells the early 22-kDa GPHα either associated with hCGβ, or showed self-association to yield GPHαα homodimers, or was later converted into heavily glycosylated large free GPHα (Mr app = 24 kDa). Micro-preparative isolation of intracellular GPHαα homodimers of JEG-3 cells and their conversion by reduction revealed that they consisted of 22-kDa GPHα monomers and not of large free GPHα. In HeLa cells, the large free GPHα variant was not observed, whereas GPHαα homodimers were present. Intracellularly, early GPHαα homodimers (35 kDa) and late variants (JEG-3: 44 kDa, HeLa: 39 kDa) were found. Both cell types secreted 45 kDa GPHαα homodimers. Large free GPHα and GPHαα homodimers were more rapidly sialylated than hCG αβ-heterodimers indicating a sequestration mechanism in the secretory pathway. In GPHαα homo- as well as hCG αβ-heterodimers the subunit interaction site, located on loop 2 of GPHα (amino acids 33–42), became immunologically inaccessible indicating similar spatial orientation of GPHα in both types of dimers. The studies demonstrate the formation, in vivo dynamics of GPHαα homodimers, and the pathways of the cellular metabolism of variants of GPHα, monoglycosylated GPHα and large free GPHα.
Transcriptional Cross Talk between the Forkhead Transcription Factor Forkhead Box O1A and the Progesterone Receptor Coordinates Cell Cycle Regulation and Differentiation in Human Endometrial Stromal Cells
Authors: Takano Masashi , Lu Zhenxiao , Goto Tomoko , Fusi Luca , Higham Jenny , Francis Julia , Withey Anna , Hardt Jennifer , Cloke Brianna , Stavropoulou Alexandra V. , Ishihara Osamu , Lam Eric W.-F. , Unterman Terry G. , Brosens Jan J. , Kim J. Julie
Published: July 2007

Differentiation of human endometrial stromal cells (HESCs) into decidual cells is associated with induction of the forkhead transcription factor forkhead box O1A (FOXO1). We performed a genomic screen to identify decidua-specific genes under FOXO1 control. Primary HESCs were transfected with small interfering RNA targeting FOXO1 or with nontargeting control small interfering RNA before treatment with a cAMP analogue and the progestin, medroxyprogesterone acetate for 72 h. Total RNA was processed for whole genome analysis using high-density oligonucleotide arrays. We identified 3405 significantly regulated genes upon decidualization of HESCs, 507 (15.3%) of which were aberrantly expressed upon FOXO1 knockdown. Among the most up-regulated FOXO1-dependent transcriptional targets were WNT signaling-related genes (WNT4, WNT16 ), the insulin receptor (INSR), differentiation markers (PRL, IGFBP1, and LEFTY2), and the cyclin-dependent kinase inhibitor p57Kip2 (CDKN1C). Analysis of FOXO1-dependent down-regulated genes uncovered several factors involved in cell cycle regulation, including CCNB1, CCNB2, MCM5, CDC2 and NEK2. Cell viability assay and cell cycle analysis demonstrated that FOXO1 silencing promotes proliferation of differentiating HESCs. Using a glutathione-S-transferase pull-down assay, we confirmed that FOXO1 interacts with progesterone receptor, irrespectively of the presence of ligand. In agreement, knockdown of PR disrupted the regulation of FOXO1 target genes involved in differentiation (IGFBP1, PRL, and WNT4) and cell cycle regulation (CDKN1, CCNB2 and CDC2) in HESCs treated with either cAMP plus medroxyprogesterone acetate or with cAMP alone. Together, the data demonstrate that FOXO1 engages in transcriptional cross talk with progesterone receptor to coordinate cell cycle regulation and differentiation of HESCs.
Pharmacists’ Knowledge and Attitudes Toward Herbal Medicine
Authors: Chang Ziba Gorji , Kennedy Daniel T , Holdford David A , Small Ralph E
Published: July 2007

Objective:

The use and sales of herbal medications have increased dramatically over the past several years. Pharmacists are in an ideal position to educate patients about herbal medicines. This study was intended to determine the knowledge and attitudes of pharmacists regarding herbal medications.

Methods:

A survey was distributed to pharmacists at several state and regional meetings in Virginia and North Carolina between August and October 1998. The survey evaluated demographic data, attitudinal scales, and a 15-item herbal medicine knowledge test. Pharmacists immediately returned the surveys to the distributor on completion.

Results:

Of the 217 surveys distributed. 164 met the Inclusion criteria for further evaluation. Of the pharmacists surveyed, 68.0% practiced in a community pharmacy, 45.1% had previous continuing education on herbal medications, and 73.6% sold herbal medications in their practice settings. The average score on the herbal knowledge test was 6.3 (maximum score of 15). Pharmacists with previous continuing education scored significantly higher than those without prior continuing education (p < 0.001). Of the 15 questions, the five that pharmacists were most likely to answer correctly assessed the uses of herbal medications. Additionally, pharmacists with prior continuing education or with access to herbal medication information at their practice site were more likely to agree that providing information about herbal medication is a pharmacist's professional responsibility (p = 0.02 and p = 0.01, respectively).

Conclusions:

The findings from this study demonstrate that pharmacists were more likely to answer correctly about the uses of herbal medications than about drug interactions, adverse drug effects, and precautions of herbal medications. Additionally, pharmacists with previous continuing education on herbal medications were more knowledgeable about these products. With the increasing use of herbal medications, there is a greater need for pharmacy training programs in this area.
Nonselective Nonsteroidal Antiinflammatory Drugs and Cardiovascular Risk: Are They Safe?
Authors: Waksman Javier C , Brody Aaron , Phillips Scott D
Published: July 2007

Objective:

To assess possible cardiovascular risks associated with use of nonselective nonsteroidal antiinflammatory drugs (NSAIDs).

Data Sources:

Medline and Embase were searched from January 1985 through April 2007 and relevant studies were retrieved.

Study Selection and Data Extraction:

Peer-reviewed, prospective, double-blind, case–control, and cohort-design studies published in the English language literature were considered eligible for review. Previous meta-analyses and systematic reviews were also analyzed. In total, 17 case–control studies; 9 cohort studies; 1 prospective, double-blind study; 3 meta-analyses; and 1 systematic review of observational studies were identified.

Data Synthesis:

Three studies were prospective and the remainder consisted of observational, retrospective studies, with most reporting acute fatal or nonfatal myocardial infarction as the cardiovascular endpoint. Among the nonselective NSAIDs, diclofenac appears to pose the highest risk for cardiovascular toxicity; other agents trend toward a neutral effect with respect to cardiovascular risk. Although the data are suggestive, it remains unclear whether naproxen provides protective cardiovascular effects among patients on chronic therapy.

Conclusions:

Currently available data are insufficient for defining evidence-based clinical guidelines for the use of NSAIDs, and the need for additional research, specifically randomized controlled trials, is evident. Diclofenac demonstrates a significant risk while naproxen appears to pose the lowest, albeit nonsignificant, risk for cardiovascular morbidity. Although the current clinical evidence may not warrant recommending naproxen as the preferred NSAID treatment, it may be prudent to avoid diclofenac for patients with cardiovascular risk factors requiring NSAID treatment.
Management Options for Patients with Aspirin and Nonsteroidal Antiinflammatory Drug Sensitivity
Authors: Knowles Sandra R , Drucker Aaron M , Weber Elizabeth A , Shear Neil H
Published: July 2007

Objective:

To evaluate and provide management strategies for patients with aspirin or nonselective nonsteroidal antiinflammatory drug (NSAID) sensitivity.

Data Sources:

Literature retrieval was accessed through MEDLINE (1966–March 2007) using the terms acetaminophen, aspirin, antiinflammatory agents nonsteroidal, urticaria, angioedema, asthma, leukotriene antagonists, desensitization, and tacrolimus. Article references retrieved were hand-searched for other relevant articles.

Study Selection and Data Extraction:

All studies published in English were evaluated. Studies, review articles, and commentaries on aspirin-induced asthma and aspirin- or NSAID-induced urticaria/angioedema were included in the review.

Data Synthesis:

Aspirin sensitivity is most often manifested as respiratory reactions (eg, bronchospasm, profuse rhinorrhea, conjunctival injection) or urticaria/angioedema. The primary mechanism is believed to be inhibition of the cyclooxygenase 1 (COX-1) enzyme; as such, patients with aspirin sensitivity often display cross-reactions to nonselective NSAIDs that inhibit the COX-1 enzyme. Management strategies include avoidance of aspirin and cross-reacting nonselective NSAIDs. However, desensitization to aspirin is a viable option for patients with aspirin-induced respiratory reactions, especially for those who require aspirin for thromboembolic prophylaxis. Aspirin desensitization is maintained indefinitely with a daily aspirin dose. There is limited evidence of the use of leukotriene modifiers in preventing aspirin-induced asthma. COX-2 selective NSAIDs, especially in patients with aspirin-induced asthma, have not been found to cross-react. However, approximately 4% of patients with a history of aspirin-induced skin reactions may experience a cutaneous reaction following a challenge to a COX-2 selective NSAID. Since acetaminophen is a weak inhibitor of the COX-1 enzyme, patients with aspirin-induced asthma should not take more than 1000 mg of acetaminophen in a single dose.

Conclusions:

Management of patients with aspirin/NSAID sensitivity includes avoidance of aspirin/nonselective NSAIDs, use of COX-2 selective NSAIDs, acetaminophen in doses less than 1000 mg, and desensitization. The role of leukotriene modifiers requires further study before they can be recommended for patients.
Hypersensitivity Reaction to Amiodarone in a Patient with a Previous Reaction to an lodinated Radiocontrast Agent
Authors: Stafford Leanne
Published: July 2007

Objective:

To describe a case of a hypersensitivity reaction to oral amiodarone in a patient with a previous reaction to an iodinated radiocontrast agent.

Case Summary:

A 55-year-old man experienced facial urticaria after intraarterial injection of iohexol, an iodinated radiocontrast agent, during coronary angiography, which was successfully treated with intravenous hydrocortisone and promethazine. The procedure revealed significant triple vessel disease, and the patient subsequently underwent coronary artery bypass grafting in October 2006. Postoperatively, the patient experienced 2 episodes of fast atrial fibrillation, the first of which was treated successfully with intravenous amiodarone. The second episode resulted in the commencement of therapy with oral amiodarone 400 mg 3 times daily. Within one hour after the first dose, the patient experienced tip swelling and tingling, which was again treated with intravenous promethazine. Amiodarone was stopped; the patient remained in sinus rhythm and was discharged without further incident.

Discussion:

Amiodarone is a class III antiarrhythmic agent frequently used in the management of atrial fibrillation after cardiac surgery. The approved product information lists known hypersensitivity to iodine as a contraindication to its administration, but no other cases of amiodarone hypersensitivity in a patient with a previous reaction to an iodinated radiocontrast agent have been published, Conversely, it has been suggested that the drug may be safely used in such patients. The Naranjo probability scale supported a probable adverse reaction of hypersensitivity associated with amiodarone therapy in this patient.

Conclusions:

Prescribers should exercise caution in the administration of amiodarone to patients with a true, documented history of hypersensitivity to an iodinated compound.