bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preventive effect of (−)epigallocatechin gallate on lipids, lipoproteins, and enzymes of lipid metabolism in isoproterenol‐induced myocardial infarction in rats
Authors: Devika P. T. , Stanely Mainzen Prince P. 
Published: December 2009

AbstractThis article reports data on the preventive effect of (−)epigallocatechin gallate (EGCG) on lipid metabolism and lipoproteins in isoproterenol (ISO)‐induced myocardial infarction (MI) in Wistar rats. The rats were induced MI by ISO (100 mg/kg) at an interval of 24 h for 2 days. EGCG (30 mg/kg) was given to rats as pretreatment for 21 days orally using an intragastric tube. EGCG significantly reduced the increased serum levels of cholesterol, triglycerides, and free fatty acids in the heart and serum phospholipids (PLs) in ISO‐treated rats. It also significantly increased the reduced levels of heart PLs in ISO‐induced rats. EGCG reduced the levels of serum low‐density lipoprotein cholesterol and very low‐density lipoprotein cholesterol and increased serum high‐density lipoprotein (HDL)‐cholesterol in ISO‐treated rats. It also reduced the increased cholesterol/PL ratio and atherogenic index and significantly increased the reduced ratio of HDL‐cholesterol/total cholesterol. Also EGCG significantly increased the reduced activity of lecithin cholesterol acyl transferase in ISO‐treated rats. Thus, EGCG prevented the accumulation of lipids and altered the levels of lipoproteins in myocardial‐infarcted rats. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:387–393, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20302
Metabolism of the mesoionic compound (MI‐D) by mouse liver microsome, detection of its metabolite In Vivo, and acute toxicity in mice
Authors: Romão Silvia , Cadena Silvia M. S. C. , Amorim Juliana C. , Méndez‐Sánchez Stelia C. , Echevarria Aurea , Silva Edson F. , Rocha Maria Eliane M. , Noleto Guilhermina R. , Carnieri Eva G. S. , Martinez Glaucia R. , Oliveira Maria Benigna M. 
Published: December 2009

AbstractThe mesoionic derivative 4‐phenyl‐5‐[4‐nitrocinnamoyl]‐1,3,4‐thiadiazolyl‐2‐phenylamine chloride (MI‐D) has antitumoral and anti‐inflammatory effects. In this study, we present aspects of its metabolism and toxicity in mice. MI‐D was metabolized in vitro by liver microsome, generating a main product with a much shorter retention time than MI‐D in high‐performance liquid chromatography (HPLC) analysis but with a spectrum similar to that of the original molecule. Mass spectrometry with electrospray ionization in positive mode analysis of the purified compound by HPLC indicated that the product of metabolism has four additional hydroxyl groups (m/z = 465) compared with MI‐D (m/z = 401). The HPLC analyses of plasma and urine samples from mice treated with MI‐D showed the presence of the metabolite product. The kinetic parameters Km (19.5 ± 4.5 μM) and Vmax [1.5 ± 0.4 units of fluorescence/(100 μg of microsomal protein/mL/s)] were estimated, confirming the metabolism of MI‐D and indicating that the reaction follows Michaelis‐Menten kinetics. Acute toxicity was established on the basis of an estimation of mean lethal dose (LD‐50; 181.2 mg/kg) and histopathological analysis of animals that survived the LD‐50 test. Abdominal adhesions, inflammatory foci, and formation of granulomas were observed. Altogether, the results contribute to the advancement of research in support of MI‐D as a future chemotherapeutic drug. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:394–405, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20303
The cathepsin K inhibitor AAE581 induces morphological changes in osteoclasts of treated patients
Authors: Chappard Daniel , Libouban Hélène , Mindeholm Linda , Baslé Michel F. , Legrand Erick , Audran Maurice 
Published: December 2009

AbstractInhibitors of Cathepsin K (Cat‐K) are recognized as an interesting way to inhibit osteoclast (OC) activity. OCs from patients treated with the anticathepsin‐K inhibitor AAE581 (balicatib) were found enlarged. They contained numerous vacuoles filled with tartrate resistant acid phosphatase (TRAcP), an intracellular enzyme that terminates the degradation of collagen internalized in OC transcytotic vesicles. In a phase 2 clinical study, 675 patients with postmenopausal osteoporosis received the Cat‐K inhibitor AAE581 at 0, 5, 10, 25, or 50 mg/D during 1 year. Eleven patients had a transiliac bone biopsy, studied undecalcified. Histoenzymatic detection of TRAcP was used to identify and count OC number. The histomorphometrist was not aware of the randomization of patients at the time of analysis. OC were unstained in one patient because of a failure in the fixation protocol, but easily observable in the 10 remaining patients. Whatever the received dose, treated patients exhibited a characteristic aspect of the OC cytoplasm which appeared filled of deeply‐stained brown vacuoles, making cells looking like bunches of grape. These round vacuoles, evidenced on TRAcP‐stained sections, were due to the accumulation of intracytoplasmic TRAcP. This led to a moderate enlargement of the OC size when compared to a series of control osteoporotic patients. AAE581 did not induce OC apoptosis at any dosage but it modified OC morphology. Cat‐K inhibition (inhibiting the extracellular collagen breakdown) is associated with a compensatory accumulation of intracellular TRAcP that could not be used to complete protein degradation. TRAcP is also known to be degraded by Cat‐K. Microsc. Res. Tech., 2010. © 2009 Wiley‐Liss, Inc.
Prothrombin kringle‐2 induces death of mesencephalic dopaminergic neurons in vivo and in vitro via microglial activation
Authors: Kim Sang Ryong , Chung Eun Sook , Bok Eugene , Baik Hyung Hwan , Chung Young Cheul , Won So Yoon , Joe Eunhye , Kim Tae Hyong , Kim Soung Soo , Jin Min Young , Choi Sang Ho , Jin Byung Kwan 
Published: December 2009

AbstractWe have shown that prothrombin kringle‐2 (pKr‐2), a domain of human prothrombin distinct from thrombin could activate cultured rat brain microglia in vitro. However, little is known whether pKr‐2‐induced microglial activation could cause neurotoxicity on dopaminergic (DA) neurons in vivo. To address this question, pKr‐2 was injected into the rat substantia nigra (SN). Tyrosine hydroxylase (TH) immunohistochemistry experiments demonstrate significant loss of DA neurons seven days after injection of pKr‐2. In parallel, pKr‐2‐activated microglia were detected in the SN with OX‐42 and OX‐6 immunohistochemistry. Reverse transcription PCR and double‐label immunohistochemistry revealed that activated microglia in vivo exhibit early and transient expression of inducible nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2) and several proinflammatory cytokines. The pKr‐2‐induced loss of SN DA neurons was partially inhibited by the NOS inhibitor NG‐nitro‐L‐arginine methyl ester hydrochloride, and the COX‐2 inhibitor DuP‐697. Extracellular signal‐regulated kinase 1/2, c‐Jun N‐terminal kinase and p38 mitogen‐activated protein kinase were activated in the SN as early as 1 hr after pKr‐2 injection, and localized within microglia. Inhibition of these kinases led to attenuation of mRNA expression of iNOS, COX‐2 and several proinflammatory cytokines, and rescue of DA neurons in the SN. Intriguingly, following treatment with pKr‐2 in vitro, neurotoxicity was detected exclusively in co‐cultures of mesencephalic neurons and microglia, but not microglia‐free neuron‐enriched mesencephalic cultures, indicating that microglia are required for pKr‐2 neurotoxicity. Our results strongly suggest that microglia activated by endogenous compound(s), such as pKr‐2, are implicated in the DA neuronal cell death in the SN. © 2009 Wiley‐Liss, Inc.
Interannual variability in rainfall and wet spell frequency during the New South Wales sugarcane harvest season
Authors: Everingham Yvette L. , Reason C. J. C. 
Published: December 2009

AbstractThe sugarcane harvest season in northern New South Wales (NSW), Australia operates from June to November. Rainfall during this period can delay harvest practices and push the harvest window into the wetter summer period which can have severe economic consequences for industry. Farmer groups acknowledge that, whilst information about seasonal rainfall totals can assist forward planning activities impacted by harvest rainfall, knowledge about the number of wet spells during the harvest season would also be helpful. This diagnostic study investigated the interaction between harvest rainfall totals and wet spell frequency for Harwood, a major sugarcane growing region in Northern NSW. The El Nino‐Southern Oscillation (ENSO) effect on harvest rainfall totals and wet spell frequency was also considered and climate diagnostics for extreme wet seasons were investigated. A moderate linear relationship between total rainfall and wet spell frequency exists for both winter (r = 0.68) and spring (r = 0.66). The ENSO had little influence in winter but La Niña events in spring favoured higher rainfall totals and wet spell frequency. Extreme wet seasons were largely influenced by positive pressure anomalies over southeastern Australia and the Tasman Sea. Copyright © 2009 Royal Meteorological Society
Effect of fat replacers on kefir quality
Authors: Ertekin Bilge , Guzel‐Seydim Zeynep B 
Published: December 2009

AbstractThe purpose of the study was to determine the effects of fat replacers on the quality of non‐fat kefir. Skim milk fortified with Dairy Lo® (DL) and inulin (INU) was fermented with kefir grains to manufacture kefir. The results of compositional, microbiological, rheological and sensorial analyses were compared with whole kefir (WK) and non‐fat kefir (NFK) controls. Results for dry matter, pH and lactic acid ranged between 82.4 and 109.1 g kg−1, 4.26 and 4.40, and 7.0 and 9.2 g L−1, respectively. Acetaldehyde and ethanol contents of samples were between 2.89 and 7.28 mg L−1, and 151.46 and 323.89 mg L−1, respectively. In all samples, Lactobacillus spp., Streptococcus spp. and yeast counts were between 9.1 and 9.9, 9.3 and 9.9, and 5.2 and 5.6 log cfu mL−1, respectively. Kefir samples had non‐Newtonian behaviour and pseudoplastic fluid with thixotropy. At the first day, DL had the highest apparent viscosity (3.119 Pa s) while NFK had the lowest value (1.830 Pa s). In the sensory evaluation, odour and taste scores of samples were not different. Dairy Lo® and inulin could be used without any adverse effect for the production of non‐fat kefir. Copyright © 2009 Society of Chemical Industry
Study of mass transfer in a dynamic hollow‐fibre liquid phase microextraction system
Authors: Hansson Helena , Colmsjö Anders , Nilsson Ulrika 
Published: December 2009

AbstractThe extraction characteristics of a dynamic hollow‐fibre liquid phase microextraction system were investigated by studying the mass transfer and diffusion rates of dinitrophenols from plasma samples over the liquid membrane (dihexylether). The measured diffusion coefficients were compared with theoretical values calculated from Stokes diameters. The diffusion mechanism was simulated by computer and the most polar compounds, 2,4‐dinitrophenol and 4,6‐o‐dinitrocresol, had associated diffusion coefficients that were close to the calculated theoretical values. 2‐sec‐Butyl‐4,6 dinitrophenol and 2‐tert‐butyl‐4,6‐dinitrophenol, the compounds with the highest log P values, were retained by the polypropylene membrane, which reduced the experimentally observed diffusion rates to about half of the theoretical values. The retention was most likely due to dispersive forces interacting with the pore inner walls. Extraction was linearly correlated with time for all compounds and the repeatability was high (RSDs 7–11%), even for the shortest extraction times. Method LOD as the amount injected ranged between 0.3 and 3.1 ng for an extraction cycle of 213 s.
2‐D hydrophilic interaction liquid chromatography‐RP separation in urinary proteomics – Minimizing variability through improved downstream workflow compatibility
Authors: Loftheim Håvard , Nguyen Thien Duc , Malerød Helle , Lundanes Elsa , Åsberg Anders , Reubsaet Léon 
Published: December 2009

AbstractOptimization of every step in a bottom‐up urinary proteomics approach was studied with respect to maximize the protein recovery and making the downstream steps in the workflow fully compatible without compromising on the amount of information obtained. Sample enrichment and desalting using centrifugal filtration (5 kDa cut‐off) yielded protein recoveries up to 97% when 8 M urea was used. Although yielding lower recoveries (88%), addition of Tris‐HCl/NaCl was considered a better choice due to good down‐stream compatibility. The consecutive depletion of HSA, using an immunoaffinity column was successfully adapted for use in urine. Separation of the trypsin generated peptides in an off‐line 2‐D chromatographic system consisting of a hydrophilic interaction liquid chromatography column, followed by a RP chromatography column showed a high peak capacity and good repeatability in addition to a high degree of orthogonality. All operations were modified in order to keep sample handling between every step to a minimum, reducing the variability of each process. In order to test the suitability of the full method in an extensive proteomic experiment, a urine sample from a kidney‐transplanted patient was analyzed (n=6). The total variability of the method was identified with RSD values ranging from 11 to 30%. Eventually, we identified a total of 1668 peptides and 438 proteins from a single urine sample despite the use of low‐resolution MS/MS equipment. The optimized and “streamlined” complex method has shown potential for use in future urinary proteomic studies.
Translational systems biology and voice pathophysiology
Authors: Li Nicole Y. K. , Verdolini Abbott Katherine , Rosen Clark , An Gary , Hebda Patricia A. , Vodovotz Yoram 
Published: December 2009

AbstractObjectives/Hypothesis:Personalized medicine has been called upon to tailor healthcare to an individual's needs. Evidence‐based medicine (EBM) has advocated using randomized clinical trials with large populations to evaluate treatment effects. However, due to large variations across patients, the results are likely not to apply to an individual patient. We suggest that a complementary, systems biology approach using computational modeling may help tackle biological complexity in order to improve ultimate patient care. The purpose of the article is: 1) to review the pros and cons of EBM, and 2) to discuss the alternative systems biology method and present its utility in clinical voice research.Study Design:Tutorial.Methods:Literature review and discussion.Results:We propose that translational systems biology can address many of the limitations of EBM pertinent to voice and other health care domains, and thus complement current health research models. In particular, recent work using mathematical modeling suggests that systems biology has the ability to quantify the highly complex biologic processes underlying voice pathophysiology. Recent data support the premise that this approach can be applied specifically in the case of phonotrauma and surgically induced vocal fold trauma, and may have particular power to address personalized medicine.Conclusions:We propose that evidence around vocal health and disease be expanded beyond a population‐based method to consider more fully issues of complexity and systems interactions, especially in implementing personalized medicine in voice care and beyond. Laryngoscope, 2010
Battles and beliefs: Rethinking the roles of today's leaders
Authors: Bolman Lee G. , Deal Terrence E. 
Published: December 2009

AbstractThe modern business environment is wild, messy, and unpredictable. That's why the two operating frameworks that leaders have typically relied on—the caregiver and the analyst—are no longer enough. Two additional frameworks—the wizard and the warrior—can help leaders make sense of the political and symbolic predicaments that organizations face daily.
Testing computational toxicology models with phytochemicals
Authors: Valerio Luis G. , Arvidson Kirk B. , Busta Emily , Minnier Barbara L. , Kruhlak Naomi L. , Benz R. Daniel 
Published: December 2009

AbstractComputational toxicology employing quantitative structure–activity relationship (QSAR) modeling is an evidence‐based predictive method being evaluated by regulatory agencies for risk assessment and scientific decision support for toxicological endpoints of interest such as rodent carcinogenicity. Computational toxicology is being tested for its usefulness to support the safety assessment of drug‐related substances (e.g. active pharmaceutical ingredients, metabolites, impurities), indirect food additives, and other applied uses of value for protecting public health including safety assessment of environmental chemicals. The specific use of QSAR as a chemoinformatic tool for estimating the rodent carcinogenic potential of phytochemicals present in botanicals, herbs, and natural dietary sources is investigated here by an external validation study, which is the most stringent scientific method of measuring predictive performance. The external validation statistics for predicting rodent carcinogenicity of 43 phytochemicals, using two computational software programs evaluated at the FDA, are discussed. One software program showed very good performance for predicting non‐carcinogens (high specificity), but both exhibited poor performance in predicting carcinogens (sensitivity), which is consistent with the design of the models. When predictions were considered in combination with each other rather than based on any one software, the performance for sensitivity was enhanced, However, Chi‐square values indicated that the overall predictive performance decreases when using the two computational programs with this particular data set. This study suggests that complementary multiple computational toxicology software need to be carefully selected to improve global QSAR predictions for this complex toxicological endpoint.
Pharmacological and genetic analysis of mechanisms underlying detrusor overactivity in rats
Authors: Yokoyama Osamu 
Published: December 2009

AbstractAimsSuprapontine lesions, such as those resulting from cerebrovascular disease, cause bladder storage dysfunction. Detrusor overactivity (DO) following cerebral infarction may be explained by impairment of the suprapontine regulatory system. However, precise mechanisms underlying DO is not clear. The following studies were undertaken to examine pharmacological and genetic mechanisms of DO in rats.Results and ConclusionsMechanisms of long‐lasting DO in rats with cerebral infarction require signal transfer, which begins with the opening of glutamate receptors at the dorsal pontine tegmentum. DO induced by cerebral infarction has been proven to be accompanied by an increase in c‐fos and zif268 expression in the dorsal pontine tegmentum and periaqueductal gray and mediated by the activation of N‐methyl‐D‐aspartate (NMDA) receptors, cyclooxygenase‐2 (COX‐2), and prostaglandin E synthase (PGES). Therefore, the arachidonic acid cascade is dynamically activated in the brain after brain ischemia. Bladder sensory pathways are potential targets for drugs used to treat various bladder dysfunctions because of their role in storage symptoms (i.e., urgency, frequency) and in triggering reflex bladder activity. Antimuscarinic drugs and α1‐blockers are the main treatments for overactive bladder, a condition caused by neurologic lesions, aging, bladder outlet obstruction, and other pathologies. These drugs affect sensory bladder storage symptoms, suggesting an action on bladder and urethral afferent pathways. Using animal models of DO, we demonstrated that these drugs improved bladder storage function via suppression of C‐fiber afferent nerves from the lower urinary tract. Neurourol. Urodynam. 29: 107–111, 2010. © 2009 Wiley‐Liss, Inc.
Beyond neurons: Involvement of urothelial and glial cells in bladder function
Authors: Birder Lori A. , Wolf‐Johnston Amanda S. , Chib Manjul K. , Buffington Charles A. , Roppolo James R. , Hanna‐Mitchell Ann T. 
Published: December 2009

AbstractAimThe urothelium, or epithelial lining of the lower urinary tract (LUT), is likely to play an important role in bladder function by actively communicating with bladder nerves, smooth muscle, and cells of the immune and inflammatory systems. Recent evidence supports the importance of non‐neuronal cells that may extend to both the peripheral and central processes of the neurons that transmit normal and nociceptive signals from the urinary bladder. Using cats diagnosed with a naturally occurring syndrome termed feline interstitial cystitis (FIC), we investigated whether changes in physiologic parameters occur within 3 cell types associated with sensory transduction in the urinary bladder: 1) the urothelium, 2) identified bladder dorsal root ganglion (DRG) neurons and 3) grey matter astrocytes in the lumbosacral (S1) spinal cord. As estrogen fluctuations may modulate the severity of many chronic pelvic pain syndromes, we also examined whether 17β‐estradiol (E2) alters cell signaling in rat urothelial cells.ResultsWe have identified an increase in nerve growth factor (NGF) and substance P (SP) in urothelium from FIC cats over that seen in urothelium from unaffected (control) bladders. The elevated NGF expression by FIC urothelium is a possible cause for the increased cell body size of DRG neurons from cats with FIC, reported in this study. At the level of the spinal cord, astrocytic GFAP immuno‐intensity was significantly elevated and there was evidence for co‐expression of the primitive intermediate filament, nestin (both indicative of a reactive state) in regions of the FIC S1 cord (superficial and deep dorsal horn, central canal and laminae V‐VIl) that receive input from pelvic afferents. Finally, we find that E2 triggers an estrus‐modifiable activation of p38 MAPK in rat urothelial cells. There were cyclic variations with E2‐mediated elevation of p38 MAPK at both diestrus and estrus, and inhibition of p38 MAPK in proestrous urothelial cells.ConclusionThough urothelial cells are often viewed as bystanders in the processing of visceral sensation, these and other findings support the view that these cells function as primary transducers of some physical and chemical stimuli. In addition, the pronounced activation of spinal cord astrocytes in an animal model for bladder pain syndrome (BPS) may play an important role in the pain syndrome and open up new potential approaches for drug intervention. Neurourol. Urodynam. 29: 88–96, 2010. © 2009 Wiley‐Liss, Inc.
Base‐stock policies in capacitated assembly systems: Convexity properties
Authors: Huh Woonghee Tim , Janakiraman Ganesh 
Published: December 2009

AbstractWe study an assembly system with a single finished product managed using an echelon base‐stock or order‐up‐to policy. Some or all operations have capacity constraints. Excess demand is either backordered in every period or lost in every period. We show that the shortage penalty cost over any horizon is jointly convex with respect to the base‐stock levels and capacity levels. When the holding costs are also included in the objective function, we show that the cost function can be written as a sum of a convex function and a concave function. Throughout the article, we discuss algorithmic implications of our results for making optimal inventory and capacity decisions in such systems.© 2009 Wiley Periodicals, Inc. Naval Research Logistics, 2010