bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-ischaemic activity of an antioxidant aldose reductase inhibitor on diabetic and non-diabetic rat hearts
Authors: Calderone Vincenzo , Testai Lara , Martelli Alma , Motta Concettina La , Sartini Stefania , Da Settimo Federico , Breschi Maria C 
Published: October 2010

AbstractObjectivesMany observations report the cardioprotective effects of inhibitors of aldose reductase in different models of ischaemia–reperfusion injury in diabetic myocardium. In this paper, the inhibitory effects of the new pyrido[1,2-a]-pyrimidin-4-one derivative PPO, whose aldose reductase-inhibitory and antioxidant effects were shown in a previous study, were evaluated.MethodsThe effect of PPO was evaluated on aldose reductase from hearts of diabetic and non-diabetic rats, and compared with that of the reference drug epalrestat. Moreover, the two drugs were tested on isolated and Langendorff-perfused diabetic and non-diabetic hearts submitted to ischaemia–reperfusion cycle.Key findingsEpalrestat showed equivalent levels of potency in inhibiting the activity of the enzyme in the diabetic and in the non-diabetic hearts. On the contrary, the inhibitory potency of PPO was decreased in the diabetic organs. In the diabetic hearts submitted to ischaemia–reperfusion, an increased level of heart aldose reductase activity was recorded, and both PPO and epalrestat produced cardioprotective effects, suggesting that aldose reductase is deeply involved in the process of ischaemia–reperfusion injury in diabetic myocardium. In non-diabetic hearts, where aldose reductase has a lower activity, epalrestat failed to produce significant protection, while PPO still maintained cardioprotective effects, which may be reasonably attributed to useful ‘ancillary’ effects – such as antioxidant activity – independent from the aldose reductase inhibition.ConclusionsTherefore PPO, a new molecule endowed with both aldose reductase-inhibitory effects and antioxidant activity, may represent the prototype of a new class of multitarget drugs, focused on two different steps deeply involved in the pathogenesis of ischaemic injury of diabetic hearts.
JS-K has potent anti-angiogenic activityin vitroand inhibits tumour angiogenesis in a multiple myeloma modelin vivo
Authors: Kiziltepe Tanyel , Anderson Kenneth C , Kutok Jeffery L , Jia Lee , Boucher Kenneth M , Saavedra Joseph E , Keefer Larry K , Shami Paul J 
Published: October 2010

AbstractObjectivesGlutathione S-transferases (GSTs) play an important role in multidrug resistance and are upregulated in multiple cancers. We have designed a prodrug class that releases nitric oxide on metabolism by GST. O2-(2,4-Dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, a member of this class) has potent antineoplastic activity.MethodsWe studied the effect of JS-K on angiogenesis in human umbilical vein endothelial cells (HUVECs), OPM1 multiple myeloma cells, chick aortic rings and in mice.Key findingsJS-K inhibited the proliferation of HUVECs with a 50% inhibitory concentration (IC50) of 0.432, 0.466 and 0.505 μm at 24, 48 and 72 h, respectively. In the cord formation assay, JS-K led to a decrease in the number of cord junctions and cord length with an IC50 of 0.637 and 0.696 μm, respectively. JS-K inhibited cell migration at 5 h using VEGF as a chemoattractant. Migration inhibition occurred with an IC50 of 0.493 μm. In the chick aortic ring assay using VEGF or FGF-2 for vessel growth stimulation, 0.5 μm JS-K completely inhibited vessel growth. JS-K inhibited tumour angiogenesis in vivo in NIH III mice implanted subcutaneously with OPM1 multiple myeloma cells.ConclusionsJS-K is a potent inhibitor of angiogenesis in vitro and tumour vessel growth in vivo. As such, it establishes a new class of antineoplastic agent that targets the malignant cells directly as well as their microenvironment.
Methodological and statistical issues in pharmacogenomics
Authors: Peters Bas J M , Rodin Andrei S , De Boer Anthonius , Maitland-van der Zee Anke-Hilse 
Published: October 2010

Abstract
Pharmacogenomics strives to explain the interindividual variability in response to drugs due to genetic variation. Although technological advances have provided us with relatively easy and cheap methods for genotyping, promises about personalised medicine have not yet met our high expectations. Successful results that have been achieved within the field of pharmacogenomics so far are, to name a few, HLA-B*5701 screening to avoid hypersensitivity to the antiretroviral abacavir, thiopurine S-methyltransferase (TPMT) genotyping to avoid thiopurine toxicity, and CYP2C9 and VKORC1 genotyping for better dosing of the anticoagulant warfarin. However, few pharmacogenetic examples have made it into clinical practice in the treatment of complex diseases. Unfortunately, lack of reproducibility of results from observational studies involving many genes and diseases seems to be a common pattern in pharmacogenomic studies.
In this article we address some of the methodological and statistical issues within study design, gene and single nucleotide polymorphism (SNP) selection and data analysis that should be considered in future pharmacogenomic research. First, we discuss some of the issues related to the design of epidemiological studies, specific to pharmacogenomic research. Second, we describe some of the pros and cons of a candidate gene approach (including gene and SNP selection) and a genome-wide scan approach. Finally, conventional as well as several innovative approaches to the analysis of large pharmacogenomic datasets are proposed that deal with the issues of multiple testing and systems biology in different ways.
Anti-inflammatory effects of synthetic compound KT-14480 in lipopolysaccharide-stimulated microglia cells
Authors: Ock Jiyeon , Suk Kyoungho 
Published: October 2010

Abstract

Objectives
Neurodegenerative diseases have a prominent inflammatory component. Several synthetic fluorovinyloxyacetamide derivatives were screened by microglia cell-based assay in order to identify novel compounds that inhibit the inflammatory activation of microglia.

Methods
Microglia cell-based nitric oxide assay was employed to screen the compounds. RT-PCR and ELISA were conducted to evaluate the expression of inflammatory gene expression. Molecular mechanisms were determined by western blot analysis, immunocytochemistry, EMSA, and microglia/neuroblastoma cocultures.

Key findings
A fluorovinyloxyacetamide compound KT-14480 significantly suppressed nitric oxide production in lipopolysaccharide-stimulated microglia cells. KT-14480 also suppressed the secretion and expression of several inflammatory mediators such as tumour necrosis factor-α, interleukin-1β and inducible nitric oxide synthase. Additional studies showed that these inhibitory effects were accompanied by the suppression of nuclear factor-κB and neuroprotection in the microglia/neuroblastoma coculture.

Conclusions
Our results indicate that the anti-inflammatory compound KT-14480 may be a novel therapeutic drug candidate against neuroinflammatory diseases.
Intratumoural chemotherapy of lung cancer for diagnosis and treatment of draining lymph node metastasis
Authors: Celikoglu Firuz , Celikoglu Seyhan I , Goldberg Eugene P 
Published: October 2010

Abstract

Objectives
Reviewed here is the potential effectiveness of cytotoxic drugs delivered by intratumoural injection into endobronchial tumours through a bronchoscope for the treatment of non-small cell lung cancer and the diagnosis of occult or obvious cancer cell metastasis to mediastinal lymph nodes.

Key findings
Intratumoural lymphatic treatment may be achieved by injection of cisplatin or other cytotoxic drugs into the malignant tissue located in the lumen of the airways or in the peribronchial structures using a needle catheter through a flexible bronchoscope. This procedure is termed endobronchial intratumoural chemotherapy and its use before systemic chemotherapy and/or radiotherapy or surgery may provide a prophylactic or therapeutic treatment for eradication of micrometastases or occult metastases that migrate to the regional lymph nodes draining the tumour area.

Conclusions
To better elucidate the mode of action of direct injection of cytotoxic drugs into tumours, we review the physiology of lymphatic drainage and sentinel lymph node function. In this light, the potential efficacy of intratumoural chemotherapy for prophylaxis and locoregional therapy of cancer metastasis via the sentinel and regional lymph nodes is indicated. Randomized multicenter clinical studies are needed to evaluate this new and safe procedure designed to improve the condition of non-small cell lung cancer patients and prolong their survival.
Hydroxypropylmethylcellulose films for prolonged delivery of the antipsychotic drug chlorpromazine
Authors: Luppi Barbara , Bigucci Federica , Baldini Mattia , Abruzzo Angela , Cerchiara Teresa , Corace Giuseppe , Zecchi Vittorio 
Published: October 2010

Abstract

Objectives
The aim of this study was to develop transdermal films based on hydroxypropylmethylcellulose with the purpose of improving transdermal permeation of chlorpromazine hydrochloride, an antipsychotic drug used to alleviate the symptoms and signs of psychosis.

Methods
Hydroxypropylmethylcellulose films were prepared and evaluated for their drug content, film thickness, residual water content and bioadhesive properties. In-vitro permeation experiments were performed in the absence and in the presence of permeation enhancers (oleic acid, polysorbate 80, or both) with the purpose of improving drug availability. Other formulative parameters, such as drug and plasticizer concentration and hydroxypropylmethylcellulose type, were investigated.

Key findings
Both oleic acid and polysorbate 80 had significant effect on drug permeation with respect to the control formulation. In particular films containing a mixture of oleic acid and polysorbate 80 provided the best enhancement activity for chlorpromazine. Moreover, a decrease in propylene glycol or chlorpromazine content or an increase of hydroxypropylmethylcellulose viscosity provided lower cumulative amounts of drug permeated.

Conclusions
The results obtained confirm that chlorpromazine permeation can be easily modulated by varying the composition of hydroxypropylmethylcellulose-based films. These formulations could serve as candidates for transdermal delivery of antipsychotic drugs.
The pharmacokinetics of morphine and its glucuronide conjugate in a rat model of streptozotocin-induced diabetes and the expression of MRP2, MRP3 and UGT2B1 in the liver
Authors: Hasegawa Yoshitaka , Kishimoto Shuichi , Shibatani Naoki , Nomura Hiromichi , Ishii Yuko , Onishi Mika , Inotsume Nobuo , Takeuchi Yoshikazu , Fukushima Shoji 
Published: October 2010

Abstract

Objectives
The aim was to investigate the pharmacokinetics of morphine and its metabolite, morphine-3-glucuronide (M3G), in a rat model of streptozotocin (STZ)-induced diabetes.

Methods
Morphine (15 mg/kg) was administered intravenously, and the concentrations of morphine and M3G in the plasma, urine and bile were measured by HPLC. Changes in the expression of multidrug resistance-associated proteins (MRP2 and MRP3) and UDP-glucuronosyltransferase 2B1 (UGT2B1) mRNA in the liver were also estimated by reverse-transcriptase PCR.

Key findings
Plasma morphine concentrations were lower in the STZ-diabetic rats than controls although the elimination half-life of morphine was similar in the two groups (47.9 ± 10.7 min and 47.2 ± 8.6 min, respectively). The concentration of M3G in plasma was higher in STZ-diabetic than control rats, and the biliary excretion of M3G was lower in the STZ-diabetic rats (7.4 ± 2.3% vs 13.3 ± 2.0%). The urinary excretion of M3G was similar in the two groups (10.1 ± 6.8% vs 10.9 ± 4.9%). The expression of MRP3 and UGT2B1 mRNA was increased in STZ-diabetic rats, whereas expression of MRP2 mRNA was decreased.

Conclusions
In STZ-diabetic rats, the distribution volume of morphine increased, the glucuronidation rate and M3G transportation into the blood were enhanced, and the excretion of M3G was decreased, leading to an increase in the plasma M3G concentration.
Evaluation of the effects ofOlea europaeaL. subsp. africana (Mill.) P.S. Green (Oleaceae) leaf methanol extract against castor oil-induced diarrhoea in mice
Authors: Amabeoku George J , Bamuamba Kapinga 
Published: October 2010

AbstractObjectivesOlea europaea L. subsp. africana (Mill.) P.S. Green is widely used in South Africa by traditional medicine practitioners to treat diarrhoea. However, little is known scientifically about this South African species in the treatment of diarrhoea. The main aim of the study therefore was to investigate the antidiarrhoeal effect of the leaf methanol extract of the plant species in mice.MethodsThe antidiarrhoeal activity of the leaf methanol extract of O. europaea subsp. africana was studied using a castor oil-induced diarrhoeal test. The antipropulsive activity of the plant extract was also investigated using the charcoal meal transit test. Standard methods were used to investigate the acute toxicity and effect of O. europaea subsp. africana on castor oil-induced intraluminal fluid accumulation.ResultsLeaf methanol extract of O. europaea subsp. africana and loperamide, a standard antidiarrhoeal drug, significantly reduced the number of diarrhoeal episodes induced by castor oil, significantly decreased the stool mass, significantly delayed the onset of the diarrhoea and protected the animals against castor oil-induced diarrhoea. Both O. europaea subsp. africana and loperamide significantly decreased the gastrointestinal transit of charcoal meal and castor oil-induced intraluminal fluid accumulation in mice. The LD50 value was found to be 3475 mg/kg (p.o.).ConclusionsThe results obtained suggest that the leaf methanol extract of O. europaea subsp. africana has an antidiarrhoeal property and that, given orally, it may be non-toxic and/or safe in mice.
Centralizing Inventory in Supply Chains by Using Shapley Value to Allocate the Profits
Authors: Kemahlıoğlu-Ziya Eda , Bartholdi John J. 
Published: October 2010

How should the excess profit because of inventory pooling be shared amongst firms at different levels along the supply chain? Suppose each of several retailers observes local demand for a common item and places an order at the supplier, which is immediately filled if the supplier has the item in stock. The supplier can fill retailer orders either from their reserved inventories or from a shareable pool of inventory. Using terminology from cooperative game theory, we say that the supplier and the retailers whose orders are filled from the common pool have formed an inventory-pooling coalition and study the use of Shapley value to allocate the expected excess profit because of pooling. We find that under Shapley value allocations the retailers have incentive to join the inventory-pooling coalition, and the supplier carries the level of inventory that is optimal for the coalition. Shapley value allocations might not lie within the core of the game, but the grand coalition of all players is stable in the farsighted sense. And, although the supplier's share of the expected excess profit is largest when all the retailers participate in the inventory-pooling coalition, the allocations to the retailers may diminish as the coalition grows. Colluding against the supplier (by merging and forming larger retailers) may seem like an appealing strategy for the retailers to increase their share of the total supply chain profit, but we find that the total expected after-pooling profits of retailers may instead go down because of collusion.
Obesity, Food Selectivity, and Physical Activity in Individuals With Fragile X Syndrome
Authors: Raspa Melissa , Bailey Donald B. , Bishop Ellen , Holiday David , Olmsted Murrey 
Published: October 2010

Abstract
National survey data from 884 families were used to examine the overall health of children and adults with fragile X syndrome. Results indicate the rate of obesity in adults with fragile X syndrome is similar to the general population (∼30%). Male children with fragile X syndrome, however, had higher rates of obesity (31%) when compared with typically developing same-aged peers (18%). Both males and females displayed food selectivity, especially with regard to texture. Physical activity levels for children were higher than for adults, but neither group met recommended levels. Several cognitive and behavioral characteristics, food selectivity, and physical activity were related to overall health and body mass index. Continued monitoring of the health status of individuals with fragile X syndrome is recommended.
Effectiveness of a Novel Community-Based Early Intervention Model for Children With Autistic Spectrum Disorder
Authors: Smith Isabel M. , Koegel Robert L. , Koegel Lynn K. , Openden Daniel A. , Fossum Kristin L. , Bryson Susan E. 
Published: October 2010

Abstract
The Nova Scotia early intensive behavior intervention model—NS EIBI (Bryson et al., 2007) for children with autistic spectrum disorders was designed to be feasible and sustainable in community settings. It combines parent training and naturalistic one-to-one behavior intervention employing Pivotal Response Treatment—PRT (R. Koegel & Koegel, 2006). We followed 45 children (33 males, mean baseline age  =  50 months) for 12 months. Mean gains of 14.9 and 19.5 months were observed on expressive and receptive language measures, respectively, for children with an IQ of 50 or more at baseline versus 6.1 and 8.4 months for children with IQs less than 50. Behavior problems decreased significantly over the 1-year treatment for both groups, but autism symptoms decreased only for those with an IQ of 50 or more.
Expression Profile of MicroRNAs in Serum: A Fingerprint for Esophageal Squamous Cell Carcinoma
Authors: Zhang Chunni , Wang Cheng , Chen Xi , Yang Cuihua , Li Ke , Wang Junjun , Dai Juncheng , Hu Zhibin , Zhou Xiaojun , Chen Longbang , Zhang Yanni , Li Yanfang , Qiu Hong , Xing Jicheng , Liang Zhichao , Ren Binhui , Yang Chen , Zen Ke , Zhang Chen-Yu 
Published: October 2010

BACKGROUND
Sensitive and specific biomarkers for the early detection of esophageal squamous cell carcinoma (ESCC) are urgently needed to reduce the high morbidity and mortality of the disease. The discovery of serum microRNAs (miRNAs) and their unique concentration profiles in patients with various diseases makes them attractive, novel noninvasive biomarkers for tumor diagnosis. In this study, we investigated the serum miRNA profile in ESCC patients to develop a novel diagnostic ESCC biomarker.

METHODS
Serum samples were taken from 290 ESCC patients and 140 age- and sex-matched controls. Solexa sequencing technology was used for an initial screen of miRNAs in serum samples from 141 patients and 40 controls. A hydrolysis probe–based stem–loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted in the training and verification phases to confirm the concentrations of selected miRNAs in serum samples from 149 patients and 100 controls.

RESULTS
The Solexa sequencing results demonstrated marked upregulation of 25 serum miRNAs in ESCC patients compared with controls. RT-qPCR analysis identified a profile of 7 serum miRNAs (miR-10a, miR-22, miR-100, miR-148b, miR-223, miR-133a, and miR-127-3p) as ESCC biomarkers. The area under the ROC curve for the selected miRNAs ranged from 0.817 to 0.949, significantly higher than for carcinoembryonic antigen (0.549; P &lt; 0.0005). More importantly, this panel of 7 miRNAs clearly distinguished stage I/II ESCC patients from controls.

CONCLUSIONS
This panel of 7 serum miRNAs holds promise as a novel blood-based biomarker for the diagnosis of ESCC.
CA125 Immune Complexes in Ovarian Cancer Patients with Low CA125 Concentrations
Authors: Cramer Daniel W , O'Rourke Dennis J , Vitonis Allison F , Matulonis Ursula A , DiJohnson Daniel A , Sluss Patrick M , Crum Christopher P , Liu Brian C-S 
Published: October 2010

BACKGROUND
About 20% of women with ovarian cancer have low concentrations of serum cancer antigen 125 (CA125), and this important tumor marker cannot be used to monitor their disease. The measured concentration for mucin 1 (MUC1), or CA15-3, another tumor marker, can be lowered in breast and ovarian cancer patients when circulating immune complexes (CICs) containing antibodies bound to the free antigen are present. Because CA125 and MUC1 are related members of the mucin family, we sought to determine whether CICs might also exist for CA125 and interfere with its clinical assay.

METHODS
We developed an antigen capture–based assay to determine the presence of CICs for CA125. We spotted mouse antibodies to CA125 onto nanoparticle slides, incubated them with patient serum, and added Cy5-tagged goat antihuman IgG antibodies. Fluorescence intensities were read and normalized to the intensities for glutathione S-transferase A1 as a control.

RESULTS
Assay results for 23 ovarian cancer cases with high CA125 concentrations, 43 cases with low CA125 concentrations, and 19 controls (mean CA125 concentrations, 2706, 23, and 11 kilounits/L, respectively) revealed mean fluorescence intensities for CA125 CIC of 2.30, 2.72, and 1.99 intensity units (iu), respectively. A generalized linear model adjusted for batch and age showed higher CA125 CIC fluorescence intensities in low-CA125 cases than in high-CA125 cases (P = 0.03) and controls (P = 0.0005). Four ovarian cancer patients who had recurrent disease and always had low CA125 values had a mean CA125 CIC value of 3.06 iu (95% CI, 2.34–4.01 iu).

CONCLUSIONS
These preliminary results suggest the existence of CICs involving CA125, which may help explain some ovarian cancer cases with low CA125 concentrations.
Analytical Ancestry: Evolution of the Array in Analysis
Authors: Kricka Larry J , Imai Kenta , Fortina Paolo 
Published: October 2010

BACKGROUNDMacro-, micro-, and nanosized arrays of test sites at various densities have emerged as important types of analytical devices in response to the need for high volume parallel analysis in both the research and the clinical laboratory.CONTENTThis review explores the diversity of arrays of reaction vessels and arrays of reagents and of samples, with an emphasis on the earliest descriptions of the different variations. The scope of such arrays includes linear and 2-dimensional arrays of reaction vessels (e.g., microwell strips, microplates); linear and 2-dimensional arrays of reagents arrayed on pillars and posts; beads in wells; and reagents randomly arrayed (or dis-ordered) for use in next-generation sequencing. Micro- and nanofabrication technologies have been applied to the miniaturization of arrays to increase array density (e.g., DNA probe arrays) and produce arrays of analytical structures (e.g., cantilevers, nanoelectrospray nozzles).SUMMARYArrays are now firmly established in many types of analytical devices, and this analytical format has gained widespread acceptance owing to the advantages of high-throughput automation and multiplex analysis. Ongoing “big biology” genomic and proteomic studies will ensure the continued dominance of array-based methods into the foreseeable future.