Home About us Contact
|
Home About us Contact | ||
|
|
||
Res
Kinds of Res Selected AbstractsLong circulating nanoparticles of etoposide using PLGA-MPEG and PLGA-pluronic block copolymers: characterization, drug-release, blood-clearance, and biodistribution studiesDRUG DEVELOPMENT RESEARCH, Issue 4 2010Khushwant S. Yadav Abstract The anti-leukemic drug, etoposide (ETO), has variable oral bioavailability ranging from 24,74% with a short terminal half-life of 1.5,h i.v. necessitating continuous infusion for 24,34,h for the treatment of leukemia. In the present study, etoposide-loaded PLGA-based surface-modified nanoparticles (NPs) with long circulation were designed as an alternative to continuous i.v. administration. PLGA-mPEG and PLGA-PLURONIC copolymers were synthesised and used to prepared ETO-loaded NPs by high-pressure homogenization. The mean particle size of ETO-loaded PLGA-MPEG nanoparticles was 94.02±3.4,nm, with an Entrapment Efficiency (EE) of 71.2% and zeta potential value of ,6.9±1.3,mV. ETO-loaded PLGA-pluronic nanoparticles had a mean particle size of 148.0±2.1,nm, an EE of 73.12±2.7%, and zeta potential value of ,21.5±1.6,mV. In vitro release of the pure drug was complete within 4,h, but was sustained up to 7 days from PLGA-mPEG nanoparticles and for 5 days from PLGA-pluronic nanoparticles. Release was first order and followed non-Fickian diffusion kinetics in both instances. ETO and ETO-loaded PLGA nanoparticles labeled with 99mTc were used in blood clearance studies in rats where the two coated NPs, 99mTc- ETO-PLGA-PLU NP and 99mTc- ETO-PLGA-mPEG NP, were found to be available in higher concentrations in the circulation as compared to the pure drug. Biodistribution studies in mice showed that ETO-loaded PLGA-MPEG NP and PLGA-PLURONIC NP had reduced uptake by the RES due to their steric barrier properties and were present in the circulation for a longer time. Moreover, the NPs had greater uptake in bone and brain where concentration of the free drug, ETO, was negligible. Drug delivered from these NPs could result in a single i.v. injection that would release the drug for a number of days, which would be potentially beneficial and in better control of leukemia therapy. Drug Dev Res 71: 228,239, 2010. © 2010 Wiley-Liss, Inc. [source] Short-term scheduling of a wind generation and hydrogen storage in the electricity marketEUROPEAN TRANSACTIONS ON ELECTRICAL POWER, Issue 5 2010G. Tina Abstract Intermittent renewable energy sources (RES) are promising to be the future of electricity generation. In particular wind generation, owing to its stochastic behaviour, has to be carefully managed. Its lack of sufficient predictability decreases the energy value in the current framework of electrical markets, therefore, beyond a certain threshold; this kind of generation into the electrical system represents a problem for the transmission system operator (TSO) during its despatching service. The coupling of wind energy conversion system (WECS) with a storage medium (i.e. hydrogen) could improve the programmability of such generation plants in electrical markets. In this paper, an economical optimization tool has been developed in order to find the short-term scheduling so as to maximize the economic revenues in the day-ahead electricity market of a storage plant coupled with a wind farm. This tool needs as input the forecasts of both wind generation power and market prices, obtained with the adoption of pre-processing input data algorithm based on different methods that involve both statistical and probabilistic approaches. Copyright © 2009 John Wiley & Sons, Ltd. [source] Attenuation of half sulfur mustard gas-induced acute lung injury in ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2006Shannon D. McClintock Abstract Airway instillation into rats of 2-chloroethyl ethyl sulfide (CEES), the half molecule of sulfur mustard compound, results in acute lung injury, as measured by the leak of plasma albumin into the lung. Morphologically, early changes in the lung include alveolar hemorrhage and fibrin deposition and the influx of neutrophils. Following lung contact with CEES, progressive accumulation of collagen occurred in the lung, followed by parenchymal collapse. The co-instillation with CEES of liposomes containing pegylated (PEG)-catalase (CAT), PEG-superoxide dismutase (SOD), or the combination, greatly attenuated the development of lung injury. Likewise, the co-instillation of liposomes containing the reducing agents, N-acetylcysteine (NAC), glutathione (GSH), or resveratrol (RES), significantly reduced acute lung injury. The combination of complement depletion and airway instillation of liposomes containing anti-oxidant compounds maximally attenuated CEES-induced lung injury by nearly 80%. Delayed airway instillation of anti-oxidant-containing liposomes (containing NAC or GSH, or the combination) significantly diminished lung injury even when instillation was delayed as long as 1 h after lung exposure to CEES. These data indicate that CEES-induced injury of rat lungs can be substantially diminished by the presence of reducing agents or anti-oxidant enzymes delivered via liposomes. Copyright © 2005 John Wiley & Sons, Ltd. [source] Effect of 6-Month Whole Body Vibration Training on Hip Density, Muscle Strength, and Postural Control in Postmenopausal Women: A Randomized Controlled Pilot Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2004Sabine MP Verschueren Abstract High-frequency mechanical strain seems to stimulate bone strength in animals. In this randomized controlled trial, hip BMD was measured in postmenopausal women after a 24-week whole body vibration (WBV) training program. Vibration training significantly increased BMD of the hip. These findings suggest that WBV training might be useful in the prevention of osteoporosis. Introduction: High-frequency mechanical strain has been shown to stimulate bone strength in different animal models. However, the effects of vibration exercise on the human skeleton have rarely been studied. Particularly in postmenopausal women,who are most at risk of developing osteoporosis,randomized controlled data on the safety and efficacy of vibration loading are lacking. The aim of this randomized controlled trial was to assess the musculoskeletal effects of high-frequency loading by means of whole body vibration (WBV) in postmenopausal women. Materials and Methods: Seventy volunteers (age, 58,74 years) were randomly assigned to a whole body vibration training group (WBV, n = 25), a resistance training group (RES, n = 22), or a control group (CON, n = 23). The WBV group and the RES group trained three times weekly for 24 weeks. The WBV group performed static and dynamic knee-extensor exercises on a vibration platform (35,40 Hz, 2.28,5.09g), which mechanically loaded the bone and evoked reflexive muscle contractions. The RES group trained knee extensors by dynamic leg press and leg extension exercises, increasing from low (20 RM) to high (8 RM) resistance. The CON group did not participate in any training. Hip bone density was measured using DXA at baseline and after the 6-month intervention. Isometric and dynamic strength were measured by means of a motor-driven dynamometer. Data were analyzed by means of repeated measures ANOVA. Results: No vibration-related side effects were observed. Vibration training improved isometric and dynamic muscle strength (+15% and + 16%, respectively; p < 0.01) and also significantly increased BMD of the hip (+0.93%, p < 0.05). No changes in hip BMD were observed in women participating in resistance training or age-matched controls (,0.60% and ,0.62%, respectively; not significant). Serum markers of bone turnover did not change in any of the groups. Conclusion: These findings suggest that WBV training may be a feasible and effective way to modify well-recognized risk factors for falls and fractures in older women and support the need for further human studies. [source] Oxygen infusions (hemoglobin-vesicles and albumin-hemes) based on nano-molecular sciences,POLYMERS FOR ADVANCED TECHNOLOGIES, Issue 2-3 2005Professor Eishun Tsuchida Abstract Since the discovery of a red-colored saline solution of a heme derivative that reversibly binds and releases oxygen (1983), significant efforts have been made to realize an oxygen infusion as a red cell substitute based on the sciences of both molecular assembling phenomena and macromolecular metal complexes. The authors have specified that hemoglobin (Hb)-vesicles (HbV) and recombinant human serum albumin-hemes (rHSA-heme) would be the best systems that meet the clinical requirements. (A) Hb is rigorously purified from outdated, donated red cells via pasteurization and ultrafiltration, to completely remove blood type antigen and pathogen. The HbV encapsulates thus purified concentrated Hb solution with a phospholipid bimolecular membrane (diameter, 250,nm,), and its solution properties can be adjusted comparable with blood. Surface modification of HbV with a water-soluble polymer ensures stable dispersion state and storage over a year at 20°C. In vivo tests have clarified the efficacy for extreme hemodilution and resuscitation from hemorrhagic shock, and safety in terms of biodistribution, metabolism in reticuloendothelial system (RES), clinical chemistry, blood coagulation, etc. The HbV does not induce vasoconstriction thus maintains blood flow and tissue oxygenation. (B) rHSA is now manufactured in Japan as a plasma-expander. The rHSA can incorporate eight heme derivatives (axial base substituted hemes) as oxygen binding sites, and the resulting rHSA-heme is a totally synthetic O2 -carrier. Hb binds endothelium-derived relaxation factor, NO, and induces vasoconstriction. The rHSA-heme binds NO as Hb does, however, it does not induce vasoconstriction due to its low pI (4.8) and the resulting low permeability across the vascular wall (1/100 of Hb). A 5%-albumin solution possesses a physiologic oncotic pressure. Therefore, to increase the O2 -transporting capacity, albumin dimer is effective. Albumin dimer can incorporate totally 16 hemes with a regulated oncotic pressure. The rHSA-heme is effective not only as a red cell substitute but also for oxygen therapeutics (e.g. oxygenation for tumor). Significant efforts have been made to produce HbV and rHSA-heme with a facility of Good Manufacturing Practice (GMP) standard, and to start preclinical and finally clinical trials. Copyright © 2005 John Wiley & Sons, Ltd. [source] Regulation of cell survival by resveratrol involves inhibition of NF,B-regulated gene expression in prostate cancer cellsTHE PROSTATE, Issue 10 2009Dixan A. Benitez Abstract BACKGROUND Polyphenols have been proposed as antitumoral agents. We have shown that resveratrol (RES) induced cell cycle arrest and promoted apoptosis in prostate cancer cells by inhibition of the PI3K pathway. The RES effects on NF,B activity in LNCaP cells (inducible NF,B), and PC-3 cells (constitutive NF,B) are reported. METHODS Cells were treated with 1,150 µM of RES during 36 hr. NF,B subcellular localization was analyzed by western blot and immunofluorescence. I,B, was evaluated by immunoprecipitation followed by Western blot. Specific DNA binding of NF,B was determined by EMSA assays and NF,B-mediated transcriptional activity by transient transfection with a luciferase gene reporter system. RESULTS RES induced a dose-dependent cytoplasmic retention of NF,B mediated by I,B, in PC-3 cells but not in LNCaP. RES-induced inhibition of NF,B specific binding to DNA was more significant in PC-3 cells. NF,B-mediated transcriptional activity induced by EGF and TNF, were inhibited by RES in both cell lines. LY294002 mimicked RES effects on NF,B activity. CONCLUSION Antiproliferative and apoptotic effects of RES on human prostate cancer cells may be mediated by the inhibition of NF,B activity. This mechanism seems to be associated to RES-induced PI3K inhibition. RES could have therapeutic potential for prostate cancer treatment. Prostate 69:1045,1054, 2009. © 2009 Wiley-Liss, Inc. [source] High performance liquid chromatographic method for the determination and pharmacokinetic studies of oxyresveratrol and resveratrol in rat plasma after oral administration of Smilax china extractBIOMEDICAL CHROMATOGRAPHY, Issue 4 2008Huilian Huang Abstract A sensitive and simple HPLC method has been developed and validated for the determination of oxyresveratrol (trans -2,4,3,,5,-tetrahydroxystilbene, OXY) and resveratrol (trans -3,5,4,-trihydroxystilbene, RES) in rat plasma. The plasma samples were extracted with ethyl acetate and analyzed using HPLC on an Aglient Zorbax SB-C18 column (250 × 4.6 mm, 5 µm) at a wavelength 320 nm, with a linear gradient of (A) acetonitrile and (B) 0.5% aqueous acetic acid (v/v), at a flow rate of 1.0 mL/min. The method was linear over the range of 0.1265,25.3 µg/mL for OXY and 0.117,23.4 µg/mL for RES. The extraction recovery for OXY, RES and internal standard ranged from 71.1 to 88.3%. The intra- and inter-day precisions were better than 10%, and the accuracy ranged from 89 to 108%. The validated method was used to study the pharmacokinetic profiles of OXY and RES in rat plasma after oral administration of Smilax china root extract. Copyright © 2007 John Wiley & Sons, Ltd. [source] Epidemiology of exfoliation syndrome in the Reykjavik Eye StudyACTA OPHTHALMOLOGICA, Issue thesis3 2009Ársæll Már Arnarsson Abstract. Exfoliation syndrome (XFS) is a major risk factor for glaucoma. It is characterized by a pathological accumulation of polymorphic fibrillar material in the anterior segment of the eye. It is likely that the increase in intraocular pressure (IOP) seen in XFS patients is at least in part because of flakes of material clogging up the trabecular meshwork, and thereby increasing the resistance to outflow and increasing IOP. XFS glaucoma progresses more rapidly, is more resistant to medical treatment and has worse prognosis than other glaucomas. The prevalence of XFS has been found to vary greatly between different studies, raising the possibility of racial and/or environmental modulators. XFS has also been linked to other changes in ophthalmological structures such as; changes in central corneal thickness (CCT), steeper corneal curvature (CC) and nuclear lens opacifications. Some studies have found XFS to be associated with systemic diseases, mostly cardiovascular and cerebrovascular. Exposure to ultra-violet (UV) light has also been investigated as a possible culprit, along with several other plausible factors. The aim of the present study was to determine the prevalence and 5-year incidence of XFS, to establish possible risk factors and/or concomitant symptoms and finally to investigate the relationship between XFS and glaucomatous changes. The Reykjavík Eye Study (RES) is a prospective study based on a random sample from the Icelandic national population sample. The baseline examination was performed in the autumn of 1996, when 1045 persons older than 50 years participated. Of these, 846 (88.2% of survivors) participated in a follow-up 5 years later. All participants went through a standard examination protocol, and answered a comprehensive questionnaire on health and life style. In the prevalence study, XFS was found in 10.7% of subjects, more frequently in women and older persons. Five years later, a further 5.2% of those that participated in the follow-up study and had no signs of XFS at baseline were diagnosed having XFS. We found a strong correlation between IOP and XFS. No difference was found in the anterior segment parameters measured, but there was a significant loss of neural tissue in the XFS as demonstrated by measurements of cup/disk ratio. In conclusion, we find XFS to be frequent among Icelanders, increasing with age and more in women. Our diagnostic criteria are reliable over time. We have also identified possible risk factors that point to a role of antioxidants in the development of XFS. We find changes in corneal curvature and thickness more related to age than XFS. [source] From epidemiology to lysyl oxidase like one (LOXL1) polymorphisms discovery: phenotyping and genotyping exfoliation syndrome and exfoliation glaucoma in IcelandACTA OPHTHALMOLOGICA, Issue 5 2009Fridbert Jonasson Abstract. The first Icelandic articles on exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) appeared some 35 years ago in 1974. Articles since then have included epidemiology, pedigree-based and twin-studies as well as investigations into XFG response to medical therapy and XFS/XFG genetics. All studies found XFS/XFG to be common in Iceland and to be age-related. The Reykjavik Eye Study (RES), a population-based epidemiological study, was first conducted in 1996. The RES found that XFS and XFG prevalence in patients aged 50 years and older was 11% and that XFS/XFG was more common in women than in men. These results were confirmed in 5- and 12-year incidence studies that also suggested that detailed characterization of the phenotype is important, including pupil dilation. In the RES, eyes with XFS were found to be clinically unilateral in about half of cases and to have higher mean intraocular pressure (IOP) than non-XFS eyes. However, XFS was not found to be associated with central corneal thickness, corneal curvature, anterior chamber depth, lens thickness, lens opacification or optic disc morphology. About 15% of persons with XFS had XFG, and XFG eyes had higher risk of developing visual impairment and blindness than eyes with primary open-angle glaucoma. The first genetic studies on Icelanders, conducted about 12 years ago, were linkage studies and were unsuccessful in discovering the genetics behind XFS/XFG. However, in 2007 a genome-wide association study in Iceland using more than 300 000 markers [single nucleotide polymorphisms (SNPs)] on a relatively small number of patients did discover that lysyl oxidase like 1 (LOXL1) on chromosome 15q24 is a major gene for XFS/XFG. These results have now largely been replicated world-wide. [source] Deagglomeration of nanoparticle aggregates via rapid expansion of supercritical or high-pressure suspensionsAICHE JOURNAL, Issue 11 2009Daniel To Abstract Deagglomeration of suspensions of alumina and titania nanopowders (i.e., nanoparticle aggregates) via rapid expansion of supercritical suspensions (RESS) or high-pressure suspensions (REHPS) was studied. The size distribution of fragmented nanopowders was characterized by online Scanning Mobility Particle Spectrometer (SMPS) and Aerodynamic Particle Sizer (APS), and by offline Scanning Electron Microscopy (SEM). SMPS and SEM measurements indicate that the average agglomerate sizes were well below 1 ,m, consistent with the length scales observed in our complementary RESS/REHPS mixing experiments using alumina and silica nanopowders. The APS measurements, on the other hand, were affected by reagglomeration during sampling and yielded an agglomerate size range of 1 to 3 ,m. Analysis of the RESS/REHPS process through compressible flow models revealed that both the shear stress in the nozzle and the subsequent impact of the agglomerates with the Mach disc in the free expansion region can lead to micron or sub-micron level deagglomeration. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source] Rapid Expansion from Supercritical to Aqueous Solution to Produce Submicron Suspensions of Water-Insoluble DrugsBIOTECHNOLOGY PROGRESS, Issue 3 2000Timothy J. Young Stable suspensions of submicron particles of cyclosporine, a water-insoluble drug, have been produced by rapid expansion from supercritical to aqueous solution (RESAS). To minimize growth of the cyclosporine particles, which would otherwise occur in the free jet expansion, the solution was sprayed into an aqueous Tween-80 (Polysorbate-80) solution. Steric stabilization by the surfactant impedes particle growth and agglomeration. The particles were an order of magnitude smaller than those produced by RESS into air without the surfactant solution. Concentrations as high as 38 mg/mL for 400,700 nm particles were achieved in a 5.0% (w/w) Tween-80 solution. [source] AATYK1A phosphorylation by Cdk5 regulates the recycling endosome pathwayGENES TO CELLS, Issue 7 2010Tetsuya Takano Trafficking of recycling endosomes (REs) is regulated by the small GTPase, Rab11A; however, the regulatory mechanism remains elusive. Apoptosis-associated tyrosine kinase 1A (AATYK1A) is a Ser/Thr kinase expressed highly in brain. We have recently shown that AATYK1A localizes to Rab11A-positive RE and is phosphorylated at Ser34 by cyclin-dependent kinase 5 (Cdk5). Here, we have investigated a role of AATYK1A and its phosphorylation in recycling endosomal trafficking using Chinese hamster ovary-K1 (CHO-K1) cells. AATYK1A localizes predominantly to Rab11A-positive pericentrosomal endocytic recycling compartment (ERC). Phosphorylation at Ser34 of AATYK1A disrupts its accumulation in the pericentrosomal ERC. Consistently, phosphorylation-mimic mutant (AATYK1A-S34D) did not accumulate in the ERC and additionally attenuated ERC formation. ERC formation suppression can be reversed by constitutively active Rab11A-Q70L, suggesting a functional link between AATYK1A phosphorylation and Rab11A activity. Although no direct interaction between AATYK1A and Rab11A could be detected, the exchange of guanine nucleotides bound to Rab11A was significantly reduced in the presence of the phosphorylation-mimic AATYK1A-S34D. Together, our results reveal a regulatory role for AATYK1A in the formation of pericentrosomal ERC. They furthermore indicate that Cdk5 can disrupt ERC formation via Ser34 phosphorylation of AATYK1A. Finally, our data suggest a mechanism by which AATYK1A signaling couples Cdk5 to Rab11A activity. [source] Modelling the influence of reactive elements on the work of adhesion between a thermally grown oxide and a bond coat alloyMATERIALS AND CORROSION/WERKSTOFFE UND KORROSION, Issue 3 2006I. J. Bennett Abstract The durability of thermal barrier coating systems is primarily determined by the degree of adhesion between the thermally grown oxide (TGO) and the bond coat. Failure of the TBC is often the result of delamination at this interface. Adhesion can be improved by the addition of reactive elements (RE) to the bond coat alloy. REs include oxide forming elements such as Y, Zr and Hf. The so-called reactive element effect has been attributed to a direct improvement of the bonding between the TGO and the bond coat. A macroscopic atom model has been developed to allow the work of adhesion between two compounds (e.g. an oxide and a metal compound) to be estimated. By calculating the work of adhesion across a number of different interfaces, the influence of reactive elements and impurities present in the substrate can be assessed. It has been found that the REs have a limited direct influence on the work of adhesion and can even result in a weaker interface. A large reduction in the work of adhesion is calculated when S and C are present at the interface. REs have a high affinity for both S and C. This indicates that the RE effect is primarily that of impurity scavenging, preventing diffusion of impurities to the interface. A number of experiments are reported, which demonstrate the RE effect and support the modelling results. [source] Sacral nerve stimulation for voiding dysfunction: One institution's 11-year experience,NEUROUROLOGY AND URODYNAMICS, Issue 1 2007Suzette E. Sutherland Abstract Aim The purpose of this study was to review our institution's 11-year experience with SNS for the treatment of refractory voiding dysfunction. Dating back to 1993, it covers a span of time which describes the evolution of SNS as it includes PNE trials, non-tined (bone-anchored or fascial-anchored) leads, percutaneous tined leads with two-staged procedures, and even percutaneous pudendal trials. Methods A retrospective review was performed on SNS patients who received an implantable pulse generator (IPG) in our practice from 12/1993 to 12/2004. After Institutional Review Board approval, consents for chart review were obtained from 104 patients, representing 44% of this neuromodulatory patient population. Results Of our population, 87% were female and 13% were male. Average age at implant was 50 years,±,13.4 years. Duration of symptoms before implantation was 116 months (range 9,600 months). Eighty percent were implanted for a predominant complaint of urinary urgency and frequency (U/F). Overall, 22% had U/F only, 38% had concomitant urge incontinence (UI), and 20% had concomitant mixed incontinence (MI). Twenty percent were treated for non-obstructive urinary retention (UR), with half of these associated with a neurogenic etiology. Additionally, 46.2% had pelvic pain, 58.6% had bowel complaints, and 51% reported sexual dysfunction. In patients with U/F, mean voiding parameters as described by pre-implant voiding diaries revealed the following: 12.4 (±5.1) voids per 24 hr; 2.3 (±1.8) voids per night; 5.0 (±4.7) leaks per 24 hr; and 2.3 (±2.6) pads per 24 hr. Statistically significant improvements post-implantation were noted with mean decreases in the following: 4.3 voids per 24 hr; 1.0 void per night; 4.4 leaks per 24 hr; and 2.3 pads per 24 hr (all P,<,0.05). In the UR group a statistically significant improvement post-implantation was noted only in voids per night, with a mean decrease of 0.8 (P,<,0.05). With a mean follow up of 22 months (range 3,162 months), sustained subjective improvement was >50%, >80%, and >90% in 69%, 50%, and 35% of patients, respectively. By quality of life survey, 60.5% of patients were satisfied and 16.1% were dissatisfied with current urinary symptoms. Only 13% (14 patients) abandoned therapy, making up a significant portion of those dissatisfied with current urinary symptoms. Good overall lead durability was seen (mean 22 months, range 1,121 months), with the first successful lead proving to be the most durable (mean 28 months, range 1.4,120 months). Lead durability decreased progressively with subsequent trials. Overall, 53% of patients experienced at least one reportable event (RE) attributable to either lead or IPG. A total of 126 REs were noted, with 97% mild-to-moderate in severity. REs included lack of efficacy, loss of efficacy, infection, hematoma/seroma, migration, pain, undesirable change in sensation, and device malfunction. In this population, 47.1% of leads were tined while 52.9% were non-tined. Tined leads had an overall lower RE rate as compared to non-tined leads: 28% and 73%, respectively. Conclusions SNS is an effective method for treating certain types of voiding dysfunction. Although 53% of patients experienced at least one RE, 97% were mild-to-moderate and did not appear to affect the continued use of this therapy. With improved technology, such as percutaneous tined leads, the RE rate is decreasing. Further analyses of subsets of this population are currently underway. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc. [source] Prevalence of habitual refractive errors and anisometropia among Dutch schoolchildren and hospital employeesACTA OPHTHALMOLOGICA, Issue 5 2009Theo J.W. Hendricks Abstract. Purpose:, Refractive error (RE) is suggested to cause not only visual impairment, but also functional problems such as aspecific health complaints and lower levels of school achievement. During the last few decades the prevalence of myopia has increased worldwide, especially in Asia. We investigated the prevalence of habitual RE and anisometropia in a Dutch population of children and employees. Methods:, In a cross-sectional study, RE in both eyes of 520 children (aged 11,13 years) and 444 hospital employees (aged 17,60 years) were measured using an autorefractometer. The measurements were performed without using a cycloplegium. Pearson's correlation coefficient (r) was used to analyse correlations between the right and left eyes. Chi-square tests were used to test the differences between subgroups according to gender and age. Results:, In schoolchildren 28% of right eyes were myopic (> 0.50 D) and 8% hyperopic (> 0.50 D). Pearson's r between right and left eyes for spherical equivalent power (SEP) was 0.93. The mean cylinder deviation in right eyes was 0.26 D (range 0.00,4.50 D). Anisometropia > 1.00 D was present in 4.6% of children; 22% of children were not optimally (> 0.50 D) corrected. In hospital employees, 30% of right eyes were myopic (> 0.50 D) and 10% hyperopic (> 0.50 D). Pearson's r between right and left eyes for SEP was 0.53. The mean cylinder deviation in right eyes was 0.35 D (range 0.00,5.75 D). Anisometropia > 1.00 D was present in 25% of employees. Anisometropia was more frequently present in employees aged 40,60 years, than in those aged 17,39 years (30% versus 18%; p = 0.02, Cramer's V = 0.15). Conclusions:, Refractive errors are common in children aged 11,13 years and in working adults aged 17,60 years. Distributions of sphere and cylinder deviations are similar for Dutch schoolchildren and hospital employees. Surprisingly, anisometropia proved to be more prevalent with age. In children many eyes are not optimally corrected. Increased attention should be paid to uncorrected and miscorrected REs. [source] ChemInform Abstract: The Crystal Packing in Three Modifications of PPh4[ReO(S4)2] and PPh4[ReS(S4)2].CHEMINFORM, Issue 7 2001Ulrich Mueller Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Comments on papers reporting IR-spectra and other data of alleged L-alanine alaninium nitrate and L-alanine sodium nitrate crystalsCRYSTAL RESEARCH AND TECHNOLOGY, Issue 7 2009M. Fleck Abstract We argue that the IR- and Raman-spectra of "L-alanine alaninium nitrate" given in "Investigation on the growth, optical behaviour and factor group of an NLO crystal: L-Alanine Alaninium nitrate" by Aravindan et al., Cryst. Res. Technol. 42, 1097 (2007), actually concern L-Alanine. Correspondingly, the data presented in "A comparative study on the growth and characterization of nonlinear optical amino acid crystals: L-Alanine (LA) and L-alanine alaninium nitrate (LAAN)" by Aravindan et al., Spectrochim. Acta A 71, 297 (2008), seems to be erroneous, as is "Synthesis, Growth, and Characterization of a New Semiorganic Nonlinear Optical Crystal: L-Alanine Sodium Nitrate (LASN)", Sethuraman, et al., Cryst. Growth Des. 8, 1863 (2008). In these papers properties and data were reported for L-Alanine compounds that actually are L-Alanine crystals and, in addition, unit cell parameters were given that seem to have been copied from other papers. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] The ,II isotype of tubulin is present in the cell nuclei of a variety of cancersCYTOSKELETON, Issue 2 2004I-Tien Yeh Abstract Tubulin, the subunit protein of microtubules, has generally been thought to be exclusively a cytoplasmic protein in higher eukaryotes. We have previously shown that cultured rat kidney mesangial cells contain the ,II isotype of tubulin in their nuclei in the form of an ,,II dimer [Walss et al., 1999: Cell Motil. Cytoskeleton 42:274,284, 1999]. More recently, we examined a variety of cancerous and non-cancerous cell lines and found ,II in the nuclei of all of the former and only a few of the latter (Walss-Bass et al., 2002: Cell Tissue Res. 308:215,223]. In order to determine if ,II -tubulin occurs in the nuclei of actual cancers as well as in cancer cell lines, we used the immunoperoxidase method to look for nuclear ,II in a variety of tumors excised from 201 patients. We found that 75% of these tumors contain ,II in their nuclei. Distribution of nuclear ,II was highly dependent on the type of cancer, with 100% of the colon and prostate cancers, but only 19% of the skin tumors, having nuclear ,II. Nuclear ,II was particularly marked in tumors of epithelial origin, of which 83% showed nuclear ,II, in contrast to 54% in tumors of non-epithelial origin. In many cases, ,II staining occurred very strongly in the nuclei and not in the cytoplasm; in other cases, ,II was present in both. In many cases, particularly metastases, otherwise normal cells adjacent to the tumor also showed nuclear ,II, suggesting that cancer cells may influence nearby cells to synthesize ,II and localize it to their nuclei. Our results have implications for the diagnosis, biology, and chemotherapy of cancer. Cell Motil. Cytoskeleton 57:96,106, 2004. © 2004 Wiley-Liss, Inc. [source] Dystrophin upregulation in pressure-overloaded cardiac hypertrophy in ratsCYTOSKELETON, Issue 1 2003Masato Maeda Abstract Dystrophin is a cytoskeletal protein localized to the sarcolemma of skeletal and cardiac muscle, and neurons. We have recently demonstrated that a significant cardiac damage including myocytes injury, inflammation, and fibrosis, was found in dystrophin-deficient myocardium during pressure overload [Kamogawa et al., 2001: Cardiovasc Res 50:509,515]. However, little is known about how the cardiac sarcolemmal cytoskeleton produces qualitative and quantitative changes in response to pressure overload. Accordingly, we investigated dystrophin gene expression and protein accumulation during cardiac hypertrophy. Cardiac hypertrophy was produced by banding of the abdominal aorta of rats. Total RNA from the left ventricle of the heart was used for a quantitative reverse transcription-polymerase chain reaction (RT-PCR). Dystrophin mRNA expression significantly increased by 33 ± 18% at 1 day (P < 0.05) and 45 ± 19% at 2 days (P < 0.01) after banding, while G3PDH mRNA showed no significant change. RT-PCR for dystrophin tissue-specific exon 1 revealed that only muscle type promoter, but not non-muscle type promoter (brain and Purkinje-cell type), was activated immediately after banding. Immunohistochemistry for dystrophin showed intense cellular membrane staining with an increase in the perimeter of the myocytes by 14% at 3 days (46.3 ,m, P < 0.01) and 19% at 7 days (51.2 ,m, P < 0.01) after banding. Western blotting also showed dystrophin protein increased by 14 ± 6% at 2 days (P < 0.05) and by 32 ± 10% at 3 days (P < 0.01) after aortic banding. In conclusion, upregulation of dystrophin mRNA expression and protein accumulation occurs in response to cardiac hypertrophy. These data and the vulnerability of dystrophin-deficient myocardium to pressure overload suggest that dystrophin could play an important role in maintaining the integrity of the sarcolemma. Cell Motil. Cytoskeleton 55:26,35, 2003. © 2003 Wiley-Liss, Inc. [source] The expression of anger and its relationship to symptoms and cognitions in obsessive,compulsive disorderDEPRESSION AND ANXIETY, Issue 3 2005Stephen P. Whiteside Abstract We compared the association between obsessive,compulsive disorder (OCD) and the expression of anger in a sample of 71 patients and 71 college students. Some authors [Rubenstein et al., J Anxiety Disord 1995;9:1,9] have proposed that anger and hostility underlie the symptoms of OCD; however, there has been little empirical study of this relationship. One recent study [Whiteside and Abramowitz, Cog Therapy Res 2004;28:259,268] with college undergraduates found that the association between OCD symptoms and anger was attributable to depressive symptoms. In the present study, we compared the expression of anger in a sample of patients diagnosed with OCD and nonclinical volunteers. Consistent with the previous study, we found increased levels of anger in patients with OCD as compared to control participants; however, these differences could be attributed to between-group differences in general distress. These results were discussed within the framework of the cognitive theory of OCD. © 2005 Wiley-Liss, Inc. [source] Definition and spatial annotation of the dynamic secretome during early kidney developmentDEVELOPMENTAL DYNAMICS, Issue 6 2006Gemma Martinez Abstract The term "secretome" has been defined as a set of secreted proteins (Grimmond et al. [2003] Genome Res 13:1350,1359). The term "secreted protein" encompasses all proteins exported from the cell including growth factors, extracellular proteinases, morphogens, and extracellular matrix molecules. Defining the genes encoding secreted proteins that change in expression during organogenesis, the dynamic secretome, is likely to point to key drivers of morphogenesis. Such secreted proteins are involved in the reciprocal interactions between the ureteric bud (UB) and the metanephric mesenchyme (MM) that occur during organogenesis of the metanephros. Some key metanephric secreted proteins have been identified, but many remain to be determined. In this study, microarray expression profiling of E10.5, E11.5, and E13.5 kidney and consensus bioinformatic analysis were used to define a dynamic secretome of early metanephric development. In situ hybridisation was used to confirm microarray results and clarify spatial expression patterns for these genes. Forty-one secreted factors were dynamically expressed between the E10.5 and E13.5 timeframe profiled, and 25 of these factors had not previously been implicated in kidney development. A text-based anatomical ontology was used to spatially annotate the expression pattern of these genes in cultured metanephric explants. Developmental Dynamics 235:1709,1719, 2006. © 2006 Wiley-Liss, Inc. [source] ROCK inhibitor (Y27632) increases apoptosis and disrupts the actin cortical mat in embryonic avian corneal epitheliumDEVELOPMENTAL DYNAMICS, Issue 3 2004Kathy K.H. Svoboda Abstract The embryonic chicken corneal epithelium is a unique tissue that has been used as an in vitro epithelial sheet organ culture model for over 30 years (Hay and Revel [1969] Fine structure of the developing Avian cornea. Basel, Switzerland: S. Karger A.G.). This tissue was used to establish that epithelial cells could produce extracellular matrix (ECM) proteins such as collagen and proteoglycans (Dodson and Hay [1971] Exp Cell Res 65:215,220; Meier and Hay [1973] Dev Biol 35:318,331; Linsenmayer et al. [1977] Proc Natl Acad Sci U S A 74:39,43; Hendrix et al. [1982] Invest Ophthalmol Vis Sci 22:359,375). This historic model was also used to establish that ECM proteins could stimulate actin reorganization and increase collagen synthesis (Sugrue and Hay [1981] J Cell Biol 91:45,54; Sugrue and Hay [1982] Dev Biol 92:97,106; Sugrue and Hay [1986] J Cell Biol 102:1907,1916). Our laboratory has used the model to establish the signal transduction pathways involved in ECM-stimulated actin reorganization (Svoboda et al. [1999] Anat Rec 254:348,359; Chu et al. [2000] Invest Ophthalmol Vis Sci 41:3374,3382; Reenstra et al. [2002] Invest Ophthalmol Vis Sci 43:3181,3189). The goal of the current study was to investigate the role of ECM in epithelial cell survival and the role of Rho-associated kinase (p160 ROCK, ROCK-1, ROCK-2, referred to as ROCK), in ECM and lysophosphatidic acid (LPA) -mediated actin reorganization. Whole sheets of avian embryonic corneal epithelium were cultured in the presence of the ROCK inhibitor, Y27632 at 0, 0.03, 0.3, 3, or 10 ,M before stimulating the cells with either collagen (COL) or LPA. Apoptosis was assessed by Caspase-3 activity assays and visualized with annexin V binding. The ROCK inhibitor blocked actin cortical mat reformation and disrupted the basal cell lateral membranes in a dose-dependent manner and increased the apoptosis marker annexin V. In addition, an in vitro caspase-3 activity assay was used to determine that caspase-3 activity was higher in epithelia treated with 10 ,M Y-27632 than in those isolated without the basal lamina or epithelia stimulated with fibronectin, COL, or LPA. In conclusion, ECM molecules decreased apoptosis markers and inhibiting the ROCK pathway blocked ECM stimulated actin cortical mat reformation and increased apoptosis in embryonic corneal epithelial cells. Developmental Dynamics 229:579,590, 2004. © 2004 Wiley-Liss, Inc. [source] Targeting the development of resveratrol as a chemopreventive agent,DRUG DEVELOPMENT RESEARCH, Issue 6 2010Nian-Guang Li Abstract Tumor development consists of several separate, but closely linked, stages: tumor initiation, promotion, and progression. This long and complex process provides opportunities for intervention both in preventing cancer initiation and in treating the neoplasm during its premalignant stages. Resveratrol, a polyphenolic compound found in many plant species, including grapes, peanuts, and various herbs, has recently been investigated intensely for its cancer chemopreventive property. The present work is an overview of the chemopreventive mechanisms of resveratrol in anti-initiation, anti-promotion, and anti-progression. These, together with the low toxicity of resveratrol, suggest promise for novel chemopreventive agents. However, the low bioavailability and rapid clearance of resveratrol from the circulation require the design of new resveratrol-like chemopreventive agents, the structural modifications and the structure,activity relationship of which are also discussed in this review. Drug Dev Res 71:335,350, 2010. © 2010 Wiley-Liss, Inc. [source] Structure,activity relationships of isoeugenol-based chlorophenylpiperazine derivatives on serotonergic/adrenergic receptor, platelet aggregation, and lipid peroxidationDRUG DEVELOPMENT RESEARCH, Issue 5 2010Kuo-Ping Shen Abstract Three isoeugenol-based eugenosedin chlorphenylpiperazine derivatives, Eu-A, Eu-B, and Eu-C, were synthesized and tested for their serotonergic, adrenergic antagonist, antioxidant, and anti-aggregation activities. In radioligand binding assays, all three agents displayed significant binding affinities on ,1, ,2, ,1, 5-HT1B, and 5-HT2A receptors. In human platelet, they inhibited epinephrine and 5-HT-induced aggregation, and in human platelet with ,2 and 5-HT2A receptors they had a competitive binding effect. Eu-B and Eu-C were more potent than Eu-A. All compounds had antioxidant effects derived from aryloxypropanolamine. Eu- A, Eu-B, or Eu-C (1, 3, 5,mg/kg iv) given to normotensive Wistar rats produced a dose-dependent decrease in mean arterial blood pressure and heart rate and when injected into the cisternum, Eu-A, Eu-B, or Eu-C (0.3, 0.03,µmol) increased blood pressure within 15,min. Pretreatment with any of the three agents inhibited clonidine (38,pmol)-induced hypotension. In vitro experiments, Eu-A, Eu-B, or Eu-C (1, 10, and 100,µM) competitively antagonized norepinephrine-, clonidine-, and 5-HT (10,8,10,4,M)-induced vasocontraction in isolated rat aorta, and competitively antagonized isoproterenol (10,8,10,4,M)-induced positive inotropic effects in a concentration-dependent manner in the isolated rat left atrium. In isolated rabbit ear arteries sensitized with 16,mM K+, all three agents antagonized 5-nonyloxytryptamine- and 5-HT-induced vasocontractions. These findings show that Eu-A, Eu-B, and Eu-C possess functional ,1, ,2, ,1, 5-HT1B, and 5-HT2A receptor blocking activities. In conclusion, the changes in the position of chloride at phenylpiperazine influenced the serotonergic receptor, adrenoceptor antagonistic activities, but not anti-aggregation and antioxidant activities. Drug Dev Res 71:1,9, 2010. © 2010 Wiley-Liss, Inc. [source] Synthesis and in vitro cytotoxic activity on human anaplastic thyroid cancer cells of lipoamino acid conjugates of gemcitabineDRUG DEVELOPMENT RESEARCH, Issue 5 2010Rosario Pignatello Abstract Lipophilic derivatives of the antitumor drug gemcitabine (GEM) with the potential for improving drug loading in lipid-based colloidal carriers, like liposomes or lipid nanoparticles, are described. GEM free base was conjugated to lipoamino acids bearing an alkyl side chain of different length, by either a carbodiimide-assisted or an ethylchloroformiate-assisted coupling reaction, to obtain N4 -acyl GEM derivatives. These compounds retained the same in vitro cell growth inhibitory activity of the parent drug against two lines of human anaplastic thyroid cancer cells. Stability studies suggested that the observed activity was due mainly to intact derivatives and not to released GEM. Accordingly, these amphiphilic derivatives can be proposed in a further step for the encapsulation in liposomes or lipid nanocarriers, to achieve as a final goal an improvement of the pharmacokinetics and therapeutic activity of GEM. Drug Dev Res 2010. © 2010 Wiley-Liss, Inc. [source] Long circulating nanoparticles of etoposide using PLGA-MPEG and PLGA-pluronic block copolymers: characterization, drug-release, blood-clearance, and biodistribution studiesDRUG DEVELOPMENT RESEARCH, Issue 4 2010Khushwant S. Yadav Abstract The anti-leukemic drug, etoposide (ETO), has variable oral bioavailability ranging from 24,74% with a short terminal half-life of 1.5,h i.v. necessitating continuous infusion for 24,34,h for the treatment of leukemia. In the present study, etoposide-loaded PLGA-based surface-modified nanoparticles (NPs) with long circulation were designed as an alternative to continuous i.v. administration. PLGA-mPEG and PLGA-PLURONIC copolymers were synthesised and used to prepared ETO-loaded NPs by high-pressure homogenization. The mean particle size of ETO-loaded PLGA-MPEG nanoparticles was 94.02±3.4,nm, with an Entrapment Efficiency (EE) of 71.2% and zeta potential value of ,6.9±1.3,mV. ETO-loaded PLGA-pluronic nanoparticles had a mean particle size of 148.0±2.1,nm, an EE of 73.12±2.7%, and zeta potential value of ,21.5±1.6,mV. In vitro release of the pure drug was complete within 4,h, but was sustained up to 7 days from PLGA-mPEG nanoparticles and for 5 days from PLGA-pluronic nanoparticles. Release was first order and followed non-Fickian diffusion kinetics in both instances. ETO and ETO-loaded PLGA nanoparticles labeled with 99mTc were used in blood clearance studies in rats where the two coated NPs, 99mTc- ETO-PLGA-PLU NP and 99mTc- ETO-PLGA-mPEG NP, were found to be available in higher concentrations in the circulation as compared to the pure drug. Biodistribution studies in mice showed that ETO-loaded PLGA-MPEG NP and PLGA-PLURONIC NP had reduced uptake by the RES due to their steric barrier properties and were present in the circulation for a longer time. Moreover, the NPs had greater uptake in bone and brain where concentration of the free drug, ETO, was negligible. Drug delivered from these NPs could result in a single i.v. injection that would release the drug for a number of days, which would be potentially beneficial and in better control of leukemia therapy. Drug Dev Res 71: 228,239, 2010. © 2010 Wiley-Liss, Inc. [source] Econazole-induced Ca2+ fluxes and apoptosis in human oral cancer cellsDRUG DEVELOPMENT RESEARCH, Issue 4 2010Daih-Huang Kuo Abstract The effect of econazole on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability was explored in human oral cancer cells (OC2), using the fluorescent dyes fura-2 and WST-1, respectively. Econazole at concentrations of >1,µM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. The econazole-induced Ca2+ influx was sensitive to blockade of aristolochic acid (phospholipase A2 inhibitor) and GF109203X (PKC inhibitor). In Ca2+ -free medium, after treatment with 1,µM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 30,µM econazole failed to induce a [Ca2+]i rise. Inhibition of phospholipase C with 2,µM U73122 substantially suppressed econazole-induced [Ca2+]i rise. At concentrations of 5,70,µM econazole killed cells in a concentration-dependent manner. The cytotoxic effect of 50,µM econazole was enhanced by prechelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N,,N,-tetraacetic acid (BAPTA). The ERK MAPK inhibitor, PD98059 (10,µM), also enhanced 20,µM econazole-induced cell death. Propidium iodide staining data suggest that econazole induced apoptosis between concentrations of 10,70,µM. Collectively, in OC2 cells, econazole induced [Ca2+]i rises by causing Ca2+ release from the endoplasmic reticulum and Ca2+ influx from phospholipase A2/PKC-regulated Ca2+ channels. Furthermore, econazole caused cell death appeared to be regulated by ERK MAPK. Drug Dev Res 71: 240,248, 2010. © 2010 Wiley-Liss, Inc. [source] Comparison of xanthine oxidase-inhibiting and free radical-scavenging activities between plant adaptogens of Eleutherococcus senticosus and Rhodiola roseaDRUG DEVELOPMENT RESEARCH, Issue 4 2010Chi-Ting Horng Abstract The present study employed 2,2-diphenyl-l-picrylhydrazyl (DPPH) radical-scavenging and xanthine,xanthine oxidase (XO) assays to compare the antioxidant capacity between two plant adaptogens, Eleutherococcus senticosus (Araliaceae) and Rhodiola rosea (Crassulaceae). The IC50 value for XO activity for Rhodiola was 355.4,µg/ml, while that for Eleutherococcus was >1,000,µg/ml. Eleutherococcus inhibited DPPH generation by 58.3±2.8% at 1,000,µg/ml, whereas Rhodiola inhibited DPPH radical by 91.1±2.6% at the same concentration. The results suggested that Rhodiola inhibited not only XO but also served as a potent radical scavenger. Rhodiola has potential as a natural source of antioxidants. Drug Dev Res 71:249,252, 2010. © 2010 Wiley-Liss, Inc. [source] Bacterial protein kinase inhibitorsDRUG DEVELOPMENT RESEARCH, Issue 3 2010Michio Kurosu Abstract Protein kinases have become the second most important group of drug targets for the pharmaceutical industry next to G-protein-coupled receptors. Thus, over the past decade, a significant number of small molecules have been generated for protein kinase drug optimization programs. The vast majority of kinase inhibitors target the ATP binding site of the enzyme; however, the poor protein kinase selectivity of ATP-competitive protein kinase inhibitors (PKIs) limits their use for treating chronic diseases. In contrast, for inhibitors of bacterial signal transduction systems targeting bacterial kinase(s), there are no such selectivity requirements as long as the inhibitor does not act on any human kinases at the effective concentrations for killing bacteria in vivo. Protein phosphorylation in bacteria is performed by two-component signal transduction systems (2CSTSs) and eukaryotic-like serine/threonine kinases or bacterial tyrosine kinases. Recently, a large number of studies of protein kinases essential for sustaining bacterial growth and kinases required for virulence have been reported. Thus, bacterial protein kinases offer considerable potential as new drug targets. To identify bacterial PKIs, large chemical libraries of ATP-competitive inhibitors developed for eukaryotic protein kinases are an invaluable asset. This manuscript reviews progress on the development of prokaryotic protein kinase inhibitors. Drug Dev Res 2010. © 2010 Wiley-Liss, Inc. [source] Synthesis and screening of substituted 1,4-naphthoquinones (NPQs) as antifilarial agentsDRUG DEVELOPMENT RESEARCH, Issue 3 2010Nisha Mathew Abstract Eleven amino-substituted 1,4-naphthoquinones were synthesized via the reaction of 1,4-naphthoquinone with different primary and secondary mono- and diamines in the presence of dichloromethane ethanol (1:2) solvent at room temperature. All compounds were purified by flash column chromatography, characterized by TLC, HPLC, 13C-NMR, 1H-NMR, and FT-IR spectral analysis and were evaluated in vitro for antifilarial activity using adult bovine filarial worm Setaria digitata by assessing worm motility and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction. Seven of the 11 compounds had macrofilaricidal activity with compounds 9 (2-[(1,3-dimethylbutyl) amino] naphthalene-1,4-dione) and 11 (2-(4-methylpiperazin-1-yl) naphthalene-1,4-dione) having maximum activity (ED50 values of 0.91 and 1.2,µM, respectively, at 48,h). The effect of different substitutions on antifilarial activity is discussed. Drug Dev Res 2009. © 2009 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||