bluuebunny/crossref_metadata_2025 huggingface dataset:
Actin Cytoskeleton Manipulation by Effector Proteins Secreted by DiarrheagenicEscherichia coliPathotypes
Authors: Navarro-Garcia Fernando , Serapio-Palacios Antonio , Ugalde-Silva Paul , Tapia-Pastrana Gabriela , Chavez-Dueñas Lucia
Published: December 2012

The actin cytoskeleton is a dynamic structure necessary for cell and tissue organization, including the maintenance of epithelial barriers. Disruption of the epithelial barrier coincides with alterations of the actin cytoskeleton in several disease states. These disruptions primarily affect the paracellular space, which is normally regulated by tight junctions. Thereby, the actin cytoskeleton is a common and recurring target of bacterial virulence factors. In order to manipulate the actin cytoskeleton, bacteria secrete and inject toxins and effectors to hijack the host cell machinery, which interferes with host-cell pathways and with a number of actin binding proteins. An interesting model to study actin manipulation by bacterial effectors isEscherichia colisince due to its genome plasticity it has acquired diverse genetic mobile elements, which allow having differentE. colivarieties in one bacterial species. TheseE. colipathotypes, including intracellular and extracellular bacteria, interact with epithelial cells, and their interactions depend on a specific combination of virulence factors. In this paper we focus onE. colieffectors that mimic host cell proteins to manipulate the actin cytoskeleton. The study of bacterial effector-cytoskeleton interaction will contribute not only to the comprehension of the molecular causes of infectious diseases but also to increase our knowledge of cell biology.
Quantification of Lumefantrine in Human Plasma Using LC-MS/MS and Its Application to a Bioequivalence Study
Authors: Pingale Satish G. , Mangaonkar Kiran V.
Published: December 2012

An analytical method based on protein precipitation has been developed and validated for analysis of lumefantrine in human plasma. Artesunate was used as an internal standard for lumefantrine. Inertsil ODS column provided chromatographic separation of analytes followed by detection with mass spectrometry. The method involves simple isocratic chromatographic condition and mass spectrometric detection in the positive ionization mode using an API-3000 system. The total run time was 2.5 minutes. The proposed method has been validated with linear range of 200–20000 ng/mL for lumefantrine. The intrarun and interrun precision values are within 6.66% and 5.56%, respectively, for lumefantrine at the lower limit of quantification level. The overall recovery for lumefantrine and artesunate was 93.16% and 91.05%, respectively. This validated method was used successfully for analysis of plasma samples from a bioequivalence study.
Chronic Alcohol Ingestion Changes the Landscape of the Alveolar Epithelium
Authors: Downs Charles A. , Trac David , Brewer Elizabeth M. , Brown Lou Ann , Helms My N.
Published: December 2012

Similar to effects of alcohol on the heart, liver, and brain, the effects of ethanol (EtOH) on lung injury are preventable. Unlike other vital organ systems, however, the lethal effects of alcohol on the lung are underappreciated, perhaps because there are no signs of overt pulmonary disorder until a secondary insult, such as a bacterial infection or injury, occurs in the lung. This paper provides overview of the complex changes in the alveolar environment known to occur following both chronic and acute alcohol exposures. Contemporary animal and cell culture models for alcohol-induced lung dysfunction are discussed, with emphasis on the effect of alcohol on transepithelial transport processes, namely, epithelial sodium channel activity (ENaC). The cascading effect of tissue and phagocytic Nadph oxidase (Nox) may be triggered by ethanol exposure, and as such, alcohol ingestion and exposure lead to a prooxidative environment; thus impacting alveolar macrophage (AM) function and oxidative stress. A better understanding of how alcohol changes the landscape of the alveolar epithelium can lead to improvements in treating acute respiratory distress syndrome (ARDS) for which hospitalized alcoholics are at an increased risk.
Immunogenic Cell Death: Can It Be Exploited in PhotoDynamic Therapy for Cancer?
Authors: Panzarini Elisa , Inguscio Valentina , Dini Luciana
Published: December 2012

Immunogenic Cell Death (ICD) could represent the keystone in cancer management since tumor cell death induction is crucial as well as the control of cancer cells revival after neoplastic treatment. In this context, the immune system plays a fundamental role. The concept of Damage-Associated Molecular Patterns (DAMPs) has been proposed to explain the immunogenic potential of stressed or dying/dead cells. ICD relies on DAMPs released by or exposed on dying cells. Once released, DAMPs are sensed by immune cells, in particular Dendritic Cells (DCs), acting as activators of Antigen-Presenting Cells (APCs), that in turn stimulate both innate and adaptive immunity. On the other hand, by exposing DAMPs, dying cancer cells change their surface composition, recently indicated as vital for the stimulation of the host immune system and the control of residual ill cells. It is well established that PhotoDynamic Therapy (PDT) for cancer treatment ignites the immune system to elicit a specific antitumor immunity, probably linked to its ability in inducing exposure/release of certain DAMPs, as recently suggested. In the present paper, we discuss the DAMPs associated with PDT and their role in the crossroad between cancer cell death and immunogenicity in PDT.
Hydrogen Bond Acceptors and Additional Cationic Charges in Methylene Blue Derivatives: Photophysics and Antimicrobial Efficiency
Authors: Felgenträger Ariane , Maisch Tim , Dobler Daniel , Späth Andreas
Published: December 2012

Photodynamic inactivation of bacteria (PIB) by efficient singlet oxygen photosensitizers might be a beneficial alternative to antibiotics in the struggle against multiresistant bacteria. Phenothiazinium dyes belong to the most prominent classes of such sensitizers due to their intense absorption in the red-light region ( ca. 600–680 nm,  L mol−1 cm−1), their low toxicity, and their attachment/penetration abilities. Except simple substituents like alkyl or hydroxyalkyl residues, nearly no modifications of the phenothiaziniums have been pursued at the auxochromic sites. By this, the properties of methylene blue derivatives and their fields of application are limited; it remains unclear if their potential antimicrobial efficacy may be enhanced, also to compete with porphyrins. We prepared a set of six mainly novel methylene blue derivatives with the ability of additional hydrogen bonding and/or additional cationic charges to study the substituents’ effect on their activity/toxicity profiles and photophysical properties. Direct detection of singlet oxygen was performed at 1270 nm and the singlet oxygen quantum yields were determined. In suspensions with both, Gram-positive and Gram-negative bacteria, some derivatives were highly active upon illumination to inactivateS. aureusandE. coliup to 7 log10steps (99.99999%) without inherent toxicities in the nonirradiated state.
Sabiporide Reduces Ischemia-Induced Arrhythmias and Myocardial Infarction and Attenuates ERK Phosphorylation and iNOS Induction in Rats
Authors: Doods Henri , Wu Dongmei
Published: December 2012

The aim of the present study was to investigate the effects of sabiporide, a potent and selective NHE1 inhibitor, on myocardial ischemia-induced arrhythmias and myocardial infarction and the possible pathways related to the cardioprotection afforded by sabiporide treatment. Anesthetized rats were subjected to myocardial ischemia via left main coronary artery occlusion for 30 minutes, followed by 2 hours of reperfusion. Administration of sabiporide (0.01–3.0 mg/kg) prior to coronary artery occlusion dose-dependently reduced ischemia-induced arrhythmias and infarct size with an ED50 value of 0.14 mg/kg. Administration of sabiporide (1.0 mg/kg) prior to reperfusion also reduced infarct size by 38.6%. The reduction in infarct size was accompanied by a decrease in circulating levels of creatine phosphokinase and troponin I. In addition, sabiporide (1.0 mg/kg) given prior to coronary artery occlusion or immediately before reperfusion significantly reduced phosphorylation of the extracellular signal-regulated kinase (ERK1/2) and the expression of the inducible nitric oxide synthase (iNOS) following myocardial ischemia-reperfusion. This study demonstrates that sabiporide is a potent and effective cardioprotective agent during myocardial ischemia and reperfusion, by reducing serious ventricular arrhythmias and myocardial infarct size. The cardioprotection afforded by sabiporide is attributed in part to inhibition of ERK1/2 phosphorylation and suppression of iNOS expression.
Prediction of the Styrene Butadiene Rubber Performance by Emulsion Polymerization Using Backpropagation Neural Network
Authors: Jin Yan-jiang , Shen Ben-xian , Ren Ruo-fan , Yang Lei , Sui Jun , Zhao Ji-gang
Published: December 2012

The effect of the amounts of initiator, emulsifier, and molecular weight regulator on the styrene butadiene rubber performance was investigated, based on the industrial original formula. It was found that the polymerization rate was increased with the increased dosage of initiator and emulsifier, and together with replenishing molecular weight regulator will make the Mooney viscosity of rubber meet the national standard when the conversion rate reaches 70%. The backpropagation neural network was trained by the original formula and ameliorated formula on the basis of Levenberg-Marquardt algorithm, and the relative error between the simulation results and experimental data is less than 1%. The good consistency shows that the BP neural network could predict the product performances in different formula conditions. It would pave the way for adjustment of the SBR formulation and prediction of the product performances.
In VitroAnalysis of Photosensitizer Accumulation for Assessment of Applicability of Fluorescence Diagnosis of Squamous Cell Carcinoma of Epidermolysis Bullosa Patients
Authors: Larisch Patrick , Verwanger Thomas , Onder Kamil , Krammer Barbara
Published: December 2012

Epidermolysis bullosa (EB) is a group of inherited skin disorders characterized by blistering following mechanical trauma. Chronic wounds of EB patients often lead to tumors such as squamous cell carcinoma (SCC). Early diagnosis may prevent its invasive growth—frequently the reason of premature mortality of EB-patients. Early detection of tumors is achieved by fluorescence diagnosis (FD), where photosensitizers localize selectively in tumors and fluoresce upon illumination. Excessive accumulation of photosensitizers in inflamed areas, as occasionally found at chronic wounds and tumors due to inflammatory processes, leads to false-positive results in FD. This study analyzed accumulation kinetics of the photosensitizers hypericin and endogenous protoporphyrin IX (PpIX) in different skin cell lines including the three EB subtypes under normal and proinflammatory conditions (stimulated with TNF-alpha). The aim was to assess the applicability of FD of SCC in EB. All cell lines accumulate hypericin or PpIX mostly increasing with incubation time, but with different kinetics. SCC cells of recessive dystrophic EB (RDEB) accumulate less hypericin or PpIX than nonmalignant RDEB cells. Nevertheless, tumor selectivityin vivomight be existent. Non-EB cell lines are more active concerning photosensitizer enrichment. Proinflammatory conditions of skin cell lines seem to have no major influence on photosensitizer accumulation.
Neurodegenerative Diseases: Multifactorial Conformational Diseases and Their Therapeutic Interventions
Authors: Sheikh Saba , Safia  , Haque Ejazul , Mir Snober S.
Published: December 2012

Neurodegenerative diseases are multifactorial debilitating disorders of the nervous system that affect approximately 30 millionindividuals worldwide. Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis diseases are the consequence of misfolding and dysfunctional trafficking of proteins. Beside that, mitochondrial dysfunction, oxidative stress, and/or environmental factors strongly associated with age have also been implicated in causing neurodegeneration. After years of intensive research, considerable evidence has accumulated that demonstrates an important role of these factors in the etiology of common neurodegenerative diseases. Despite the extensive efforts that have attempted to define the molecular mechanisms underlying neurodegeneration, many aspects of these pathologies remain elusive. However, in order to explore the therapeutic interventions directed towards treatment of neurodegenerative diseases, neuroscientists are now fully exploiting the data obtained from studies of these basic mechanisms that have gone awry. The novelty of these mechanisms represents a challenge to the identification of viable drug targets and biomarkers for early diagnosis of the diseases. In this paper, we are reviewing various aspects associated with the disease and the recent trends that may have an application for the treatment of the neurodegenerative disorders.
Biochemical Characterization and Pharmacological Properties of New Basic PLA2BrTX-I Isolated fromBothrops roedingeri(Roedinger's Lancehead) Mertens, 1942, Snake Venom
Authors: Gomes Heleno Mauricio Aurelio , Baldasso Paulo Aparecido , Ponce-Soto Luis Alberto , Marangoni Sérgio
Published: December 2012

BrTX-I, a PLA2, was purified fromBothrops roedingerivenom after only one chromatographic step using reverse-phase HPLC onμ-Bondapak C-18 column. A molecular mass of 14358.69 Da was determined by MALDI-TOF mass spectrometry. Amino acid analysis showed a high content of hydrophobic and basic amino acids as well as 14 half-cysteine residues. The total amino acid sequence was obtained using SwissProt database and showed high amino acid sequence identity with other PLA2from snake venom. The amino acid composition showed that BrTX-I has a high content of Lys, Tyr, Gly, Pro, and 14 half-Cys residues, typical of a basic PLA2. BrTX-I presented PLA2activity and showed a minimum sigmoidal behavior, reaching its maximal activity at pH 8.0, 35–45°C, and required Ca2+.In vitro, the whole venom and BrTX-I caused a neuromuscular blockade in biventer cervicis preparations in a similar way to otherBothropsspecies. BrTX-I induced myonecrosis and oedema-forming activity analyzed through injection of the purified BrTX-I in mice. Since BrTX-I exerts a strong proinflammatory effect, the enzymatic phospholipid hydrolysis might be relevant for these phenomena; incrementing levels of IL-1, IL-6, and TNFαwere observed at 15 min, 30 min, one, two, and six hours postinjection, respectively.
A Price-Dependent Demand Model in the Single Period Inventory System with Price Adjustment
Authors: Forghani Kamran , Mirzazadeh Abolfazl , Rafiee Mehdi
Published: December 2012

The previous efforts toward single period inventory problem with price-dependent demand only investigate the optimal order quantity to minimize the total inventory costs; however, there is no method in the literature to avoid unwanted costs due to the deviation between the actual demand and the previously estimated demand. To fill this gap, the present paper supposes that stochastic demand rate with normal distribution is sensitive to the selling price; this means that increasing the selling price would decrease the demand rate and vice versa. After monitoring the consumption trend within a section of the period, a new selling price is implemented to change the demand rate and reduce the shortage or salvage costs at the end of the period. Three functions were suggested to represent the demand rate as a function of selling price, and the numerical analysis was implemented to solve the proposed problem. Finally, an illustrative numerical example was solved for different configurations in order to show the advantages of the proposed model. The results revealed that there is a significant improvement in the system costs when price revision is considered.
DNA Interaction Studies of a Cobalt(II) Mixed-Ligand Complex Containing Two Intercalating Ligands: 4,7-Dimethyl-1, 10-Phenanthroline and Dipyrido[3,2-a:2′,3′-c]phenazine
Authors: Shahabadi Nahid , Mahdavi Maryam
Published: December 2012

A new cobalt(II) complex [Co(dppz)2(4,7-dmp)]2+ (4,7-dmp = 4,7-dimethyl-1,10-phenanthrolline) and dppz = dipyrido[3,2-a:2′-3′-c]phenazine has been synthesized and characterized by elemental analysis (CHN), FT-IR, and UV-visible (UV-Vis) spectroscopic techniques. The DNA-binding property of the complex has been investigated employing absorption spectroscopy, fluorescence spectroscopy, circular dichroism, and viscosity measurements. The experimental results show that the complex can bind to DNA in an intercalation mode. In comparison with previous study, the DNA-binding affinity of [Co(dppz)2(4,7-dmp)]2+ (Kb=1.1·106 M−1) is smaller than that of complex [Co(dppz)2(2,9-dmp)]2+ (Kb=2.5·106 M−1).
Differentiation of Induced Pluripotent Stem Cells into Male Germ CellsIn Vitrothrough Embryoid Body Formation and Retinoic Acid or Testosterone Induction
Authors: Li Peng , Hu Hongliang , Yang Shi , Tian Ruhui , Zhang Zhenzhen , Zhang Wei , Ma Meng , Zhu Yong , Guo Xizhi , Huang Yiran , He Zuping , Li Zheng
Published: December 2012

Generation of germ cells from pluripotent stem cellsin vitrocould have great application for treating infertility and provides an excellent model for uncovering molecular mechanisms controlling gametogenesis. In this study, we explored the differentiation potential of mouse induced pluripotent stem (iPS) cells towards male germ cells. Embryoid body formation and retinoic acid/testosterone induction were applied to promote differentiation of mouse iPS cells into male germ cellsin vitro. Quantitative RT-PCR and immunoflourescence were performed to characterize the iPS cell differentiation process, and notably there were different temporal expression profiles of male germ cell-associated genes. The expression of proteins, including MVH, CDH1, and SCP3, was remarkably increased. mRNA expression ofStra8,Odf2,Act, andPrm1was upregulated in iPS cells by retinoic acid or testosterone induction, whereasOct-4transcription was reduced in these cells compared to the controls. Hormones were also measured in the EB medium. DNA content analysis by flow cytometry revealed that iPS cells could differentiate into haploid cells through retinoic acid or testosterone treatment. Collectively, our results suggest that mouse iPS cells possess the potency to differentiate into male germ cellsin vitrothrough embryoid body formation and retinoic acid or testosterone induction.
Biochemical, Pharmacological, and Structural Characterization of New Basic Bbil-TX fromBothriopsis bilineataSnake Venom
Authors: Corasolla Carregari Victor , Stuani Floriano Rafael , Rodrigues-Simioni Lea , Winck Flavia V. , Baldasso Paulo Aparecido , Ponce-Soto Luis Alberto , Marangoni Sergio
Published: December 2012

Bbil-TX, a PLA2, was purified fromBothriopsis bilineatasnake venom after only one chromatographic step using RP-HPLC onμ-Bondapak C-18 column. A molecular mass of 14243.8 Da was confirmed by Q-Tof Ultima API ESI/MS (TOF MS mode) mass spectrometry. The partial protein sequence obtained was then submitted to BLASTp, with the search restricted to PLA2from snakes and shows high identity values when compared to other PLA2s. PLA2activity was presented in the presence of a synthetic substrate and showed a minimum sigmoidal behavior, reaching its maximal activity at pH 8.0 and 25–37∘C. Maximum PLA2activity required Ca2+and in the presence of Cd2+, Zn2+, Mn2+, and Mg2+it was reduced in the presence or absence of Ca2+. Crotapotin fromCrotalus durissus cascavellarattlesnake venom and antihemorrhagic factor DA2-II fromDidelphis albiventrisopossum sera under optimal conditions significantly inhibit the enzymatic activity. Bbil-TX induces myonecrosis in mice. The fraction does not show a significant cytotoxic activity in myotubes and myoblasts (C2C12). The inflammatory events induced in the serum of mice by Bbil-TX isolated fromBothriopsis bilineatasnake venom were investigated. An increase in vascular permeability and in the levels of TNF-a, IL-6, and IL-1 was was induced. Since Bbil-TX exerts a stronger proinflammatory effect, the phospholipid hydrolysis may be relevant for these phenomena.
Lipoprotein(a) in Cardiovascular Diseases
Authors: Malaguarnera Michele , Vacante Marco , Russo Cristina , Malaguarnera Giulia , Antic Tijana , Malaguarnera Lucia , Bella Rita , Pennisi Giovanni , Galvano Fabio , Frigiola Alessandro
Published: December 2012

Lipoprotein(a) (Lp(a)) is an LDL-like molecule consisting of an apolipoprotein B-100 (apo(B-100)) particle attached by a disulphide bridge to apo(a). Many observations have pointed out that Lp(a) levels may be a risk factor for cardiovascular diseases. Lp(a) inhibits the activation of transforming growth factor (TGF) and contributes to the growth of arterial atherosclerotic lesions by promoting the proliferation of vascular smooth muscle cells and the migration of smooth muscle cells to endothelial cells. Moreover Lp(a) inhibits plasminogen binding to the surfaces of endothelial cells and decreases the activity of fibrin-dependent tissue-type plasminogen activator. Lp(a) may act as a proinflammatory mediator that augments the lesion formation in atherosclerotic plaques. Elevated serum Lp(a) is an independent predictor of coronary artery disease and myocardial infarction. Furthermore, Lp(a) levels should be a marker of restenosis after percutaneous transluminal coronary angioplasty, saphenous vein bypass graft atherosclerosis, and accelerated coronary atherosclerosis of cardiac transplantation. Finally, the possibility that Lp(a) may be a risk factor for ischemic stroke has been assessed in several studies. Recent findings suggest that Lp(a)-lowering therapy might be beneficial in patients with high Lp(a) levels. A future therapeutic approach could include apheresis in high-risk patients in order to reduce major coronary events.
Biotechnological Approaches to Study Plant Responses to Stress
Authors: Pérez-Clemente Rosa M. , Vives Vicente , Zandalinas Sara I. , López-Climent María F. , Muñoz Valeria , Gómez-Cadenas Aurelio
Published: December 2012

Multiple biotic and abiotic environmental stress factors affect negatively various aspects of plant growth, development, and crop productivity. Plants, as sessile organisms, have developed, in the course of their evolution, efficient strategies of response to avoid, tolerate, or adapt to different types of stress situations. The diverse stress factors that plants have to face often activate similar cell signaling pathways and cellular responses, such as the production of stress proteins, upregulation of the antioxidant machinery, and accumulation of compatible solutes. Over the last few decades advances in plant physiology, genetics, and molecular biology have greatly improved our understanding of plant responses to abiotic stress conditions. In this paper, recent progresses on systematic analyses of plant responses to stress including genomics, proteomics, metabolomics, and transgenic-based approaches are summarized.
Prediction of Mechanism and Thermochemical Properties of O3 + H2S Atmospheric Reaction
Authors: Vahedpour Morteza , Baghary Reza , Khalili Freshte
Published: December 2012

Ozone and hydrogen sulfide reaction mechanism including a complex was studied at the B3LYP/6‐311++G(3df,3pd) and CCSD/6‐311++G(3df,3pd)//B3LYP/6‐311++G(3df,3pd) levels of computation. The interaction between sulfur atom of hydrogen sulfide and terminal oxygen atom of ozone produces a stable H2S‐O3 complex with no barrier. With the decomposition of this complex, four possible product channels have been found. Intrinsic reaction coordinate, topological analyses of atom in molecule, and vibrational frequency calculation have been used to confirm the suggested mechanism. Thermodynamic data at T = 298.15 K and the atmospheric pressure have been calculated. The results show that the production of H2O + SO2 is the main reaction channel with ΔG° = −645.84 kJ/mol. Rate constants of H2S + O3 reaction show two product channels, SO2 + H2O and HSO + HOO, which compete with each other based on the temperature.
Size-Dependent Photodynamic Activity of Gold Nanoparticles Conjugate of Water Soluble Purpurin-18-N-Methyl-D-Glucamine
Authors: Lkhagvadulam Byambajav , Kim Jung Hwa , Yoon Il , Shim Young Key
Published: December 2012

Gold nanoparticles (GNPs) conjugates of water soluble ionic photosensitizer (PS), purpurin-18-N-methyl-D-glucamine (Pu-18-NMGA), were synthesized using various molar ratios between HAuCl4and Pu-18-NMGA without adding any particular reducing agents and surfactants. The PS-GNPs conjugates showed long wavelength absorption of range 702–762 nm, and their different shapes and diameters depend on the molar ratios used in the synthesis.In vitroanticancer efficacy of the PS-GNPs conjugates was investigated by MTT assay against A549 cells, resulting in higher photodynamic activity than that of the free Pu-18-NMGA. Among the PS-GNPs conjugates, the GNPs conjugate from the molar ratio of 1 : 2 (Au(III): Pu-18-NMGA) exhibits the highest photodynamic activity corresponding to bigger size (~60 nm) of the GNPs conjugate which could efficiently transport the PS into the cells than that of smaller size of the GNPs conjugate.
Preparation and Characterization of Self-Microemulsifying Drug Delivery System of Olmesartan Medoxomil for Bioavailability Improvement
Authors: Prajapati Shailesh T. , Joshi Harsh A. , Patel Chhaganbhai N.
Published: December 2012

Olmesartan medoxomil (OLM) is an angiotensin II receptor blocker (ARB) antihypertensive agent administered orally that has absolute bioavailability of only 26% due to the poor aqueous solubility (7.75 μg/ml). The aim of the present investigation was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral absorption of OLM. The solubility of OLM in various oils, surfactants, and cosurfactants was determined. Pseudoternary phase diagrams were constructed using Acrysol EL 135, Tween 80, Transcutol P, and distilled water to identify the efficient self-microemulsification region. Prepared SMEDDS was further evaluated for its emulsification time, drug content, optical clarity, droplet size, zeta potential, in vitro dissolution, and in vitro and ex vivo drug diffusion study. The optimized formulation S2 contained OLM (20 mg), Tween 80 (33%v/v), Transcutol P (33%v/v), and Acrysol EL 135 (34%v/v) had shown the smallest particle size, maximum solubility, less emulsification time, good optical clarity, and in vitro release. The in vitro and ex vivo diffusion rate of the drug from the SMEDDS was significantly higher than that of the plain drug suspension. It was concluded that SMEDDS would be a promising drug delivery system for poorly water-soluble drugs by the oral route.
The Sonodynamic Effect of Curcumin on THP-1 Cell-Derived Macrophages
Authors: Wang Fengping , Gao Qianping , Guo Shuyuan , Cheng Jiali , Sun Xin , Li Qiannan , Wang Tengyu , Zhang Zhiguo , Cao Wenwu , Tian Ye
Published: December 2012

Curcumin is extracted from the rhizomes of the traditional Chinese herbCurcuma longaand has been proposed to function as a photosensitizer. The potential use of curcumin as a sonosensitizer for sonodynamic therapy (SDT) requires further exploration. This study investigated the sonodynamic effect of curcumin on macrophages, the pivotal inflammatory cells in atherosclerotic plaque. THP-1-derived macrophages were incubated with curcumin at a concentration of 40.7 μmol/L for 2 h and then exposed to pulse ultrasound irradiation (2 W/cm2with 0.86 MHz) for 5–15 min. Six hours later, cell viability was decreased in cells that had been treated with ultrasound for 10 and 15 min. After ultrasound irradiation for 15 min, the ratio of apoptotic and necrotic cells in SDT group was higher than that in ultrasound group, and the ratio of apoptotic cells was higher than that of necrotic cells. Both loss of mitochondrial membrane potential and morphological changes of cytoskeleton were apparent 2 h after treatment with curcumin SDT. These findings support that curcumin had sonodynamic effect on THP-1-derived macrophages and that curcumin SDT could be a promising treatment for atherosclerosis.
Pathophysiological Significance of Hepatic Apoptosis
Authors: Wang Kewei , Lin Bingliang
Published: December 2012

Apoptosis is a classical pathological feature in liver diseases caused by various etiological factors such as drugs, viruses, alcohol, and cholestasis. Hepatic apoptosis and its deleterious effects exacerbate liver function as well as involvement in fibrosis/cirrhosis and carcinogenesis. An imbalance between apoptotic and antiapoptotic capabilities is a prominent characteristic of liver injury. The regulation of apoptosis and antiapoptosis can be a pivotal step in the treatment of liver diseases.
The Protective Effect of Silybin against Lasalocid Cytotoxic Exposure on Chicken and Rat Cell Lines
Authors: Radko Lidia , Cybulski Wojciech , Rzeski Wojciech
Published: December 2012

Lasalocid, an ionophore coccidiostat, extensive use implies a risk of toxicological impacts. Protective effects of silybin, a herbal compound ofSilybum marianum, are reported elsewhere. The aim of this study was to compare effects of the combined use of lasalocid and silybin in chicken hepatoma cells (LMH) and rat myoblasts (L6) cell lines cultures. The cytoprotective effect resulting from an interaction of both pharmaceuticals was measured with the help of MTT reduction and, coomassie brilliant blue binding (CBB) and LDH release assays. Isobolography and the combination index (CI) estimated the nature and scale of interaction. In all performed tests, the lowest lasalocid EC50-values were obtained for chicken hepatocytes. In the rat myoblasts cultures, the lowest lasalocid EC50-values were found with LDH test. Simultaneously, a lack of silybin cytotoxic effect was proven for the studied cell lines. An interaction between both substances led to a considerable decrease of lasalocid cytotoxicity. The isobolograms and combination index showed a significant antagonistic nature of silybin effect in the course of lasalocid cytotoxicity. It is concluded that the mechanism of cytoprotection results from complex reaction at biochemical and biophysical endpoints during chicken hepatocytes and rat myoblasts cell lines exposure to silybin and lasalocid co-action.
Cytotoxic Effect of Ethanol Extract of Microalga,Chaetoceros calcitrans, and Its Mechanisms in Inducing Apoptosis in Human Breast Cancer Cell Line
Authors: Ebrahimi Nigjeh Siyamak , Yusoff Fatimah Md , Mohamed Alitheen Noorjahan Banu , Rasoli Mehdi , Keong Yeap Swee , Omar Abdul Rahman bin
Published: December 2012

Marine microalgae have been prominently featured in cancer research. Here, we examined cytotoxic effect and apoptosis mechanism of crude ethanol extracts of an indigenous microalga,Chaetoceros calcitrans(UPMAAHU10) on human breast cell lines. MCF-7 was more sensitive than MCF-10A with IC50 value of3.00±0.65, whilst the IC50 value of Tamoxifen against MCF-7 was12.00±0.52 μg/mL after 24 hour incubation. Based on Annexin V/Propidium iodide and cell cycle flow cytometry analysis, it was found that inhibition of cell growth by EEC on MCF-7 cells was through the induction of apoptosis without cell cycle arrest. The apoptotic cells at subG0/G1 phase in treated MCF-7 cells at 48 and 72 hours showed 34 and 16 folds increased compared to extract treated MCF-10A cells which showed only 6 and 7 folds increased at the same time points, respectively. Based on GeXP study, EEC induced apoptosis on MCF-7 cells via modulation of CDK2, MDM2, p21Cip1, Cyclin A2, Bax and Bcl-2. The EEC treated MCF-7 cells also showed an increase in Bax/Bcl-2 ratio that in turn activated the caspase-dependent pathways by activating caspase 7. Thus, marine microalga,Chaetoceros calcitransmay be considered a good candidate to be developed as a new anti-breast cancer drug.
Endothelial Progenitor Cell Dysfunction in Cardiovascular Diseases: Role of Reactive Oxygen Species and Inflammation
Authors: Lin Chih-Pei , Lin Feng-Yen , Huang Po-Hsun , Chen Yuh-Lien , Chen Wen-Chi , Chen Huey-Yi , Huang Yu-Chuen , Liao Wen-Ling , Huang Huey-Chun , Liu Po-Len , Chen Yung-Hsiang
Published: December 2012

Endothelial progenitor cells (EPCs) move towards injured endothelium or inflamed tissues and incorporate into foci of neovascularisation, thereby improving blood flow and tissue repair. Patients with cardiovascular diseases have been shown to exhibit reduced EPC number and function. It has become increasingly apparent that these changes may be effected in response to enhanced oxidative stress, possibly as a result of systemic and localised inflammatory responses. The interplay between inflammation and oxidative stress affects the initiation, progression, and complications of cardiovascular diseases. Recent studies suggest that inflammation and oxidative stress modulate EPC bioactivity. Clinical medications with anti-inflammatory and antioxidant properties, such as statins, thiazolidinediones, angiotensin II receptor 1 blockers, and angiotensin-converting enzyme inhibitors, are currently administered to patients with cardiovascular diseases. These medications appear to exert beneficial effects on EPC biology. This review focuses on EPC biology and explores the links between oxidative stress, inflammation, and development of cardiovascular diseases.
Synthesis and Antimicrobial Activity of Silver-Doped Hydroxyapatite Nanoparticles
Authors: Ciobanu Carmen Steluta , Iconaru Simona Liliana , Chifiriuc Mariana Carmen , Costescu Adrian , Le Coustumer Philippe , Predoi Daniela
Published: December 2012

The synthesis of nanosized particles of Ag-doped hydroxyapatite with antibacterial properties is of great interest for the development of new biomedical applications. The aim of this study was the evaluation ofCa10−xAgx(PO4)6(OH)2nanoparticles (Ag:HAp-NPs) for their antibacterial and antifungal activity. Resistance to antimicrobial agents by pathogenic bacteria has emerged in the recent years and became a major health problem. Here, we report a method for synthesizing Ag doped nanocrystalline hydroxyapatite. A silver-doped nanocrystalline hydroxyapatite was synthesized at 100°C in deionised water. Also, in this paper Ag:HAp-NPs are evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria and fungal strains. The specific antimicrobial activity revealed by the qualitative assay is demonstrating that our compounds are interacting differently with the microbial targets, probably due to the differences in the microbial wall structures.
Scientific Investigations of a 16th Century Stall Belonging to the Evangelic Church in Bistriţa, Bistriţa-Năsăud County, Romania
Authors: Marutoiu C. , Grapini S. P. , Baciu A. , Miclaus M. , Marutoiu V. C. , Dreve S. , Kacso I. , Bratu I.
Published: December 2012

The Evangelic Church in Bistriţa city is one of the important gothic monuments in Romania. Inside the church there have been preserved a series of furniture pieces from different centuries, and the stall that has been analysed in this study is one of them. The study presents the investigations that were made on the occasion of restoring the stall. The nature and the status of the wooden supports and also the composition of the painting layer which covers the front side of the stall were investigated by several methods: Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and differential scanning calorimetry (DSC) analyses. The back side of the stall was made of spruce fir wood and its status was also investigated. The nature of the component elements and the heritage value of the ensemble were also established.
In Vivo Imaging of Leukocyte Recruitment to the Atheroprone Femoral Artery Reveals Anti-Inflammatory Effects of Rosuvastatin
Authors: Osaka Mizuko , Hagita Sumihiko , Yoshida Masayuki
Published: December 2012

Objective. To monitor the anti-inflammatory effect of rosuvastatin in leukocyte endothelial interactions in the atheroprone femoral artery in vivo.Methods and Results. Male Apolipoprotein E null mice (ApoE−/− mice, 6 weeks old) were fed a high-fat diet (20% fat, 1.25% cholesterol) with or without the HMG CoA reductase inhibitor rosuvastatin (10 mg/kg/day) for 6 weeks. Significant leukocyte adhesion was observed in the femoral artery of ApoE−/− mice, but not of wild type mice, in the absence of rosuvastatin. Interestingly, no obvious plaque formation was observed in the artery at this time point. The number of adherent leukocytes was dramatically diminished in ApoE−/− mice treated with rosuvastatin. DHE-associated oxidative stress and the expression of gp91-phox, a component of NADPH oxidase, were induced in ApoE−/− mice and were abolished by rosuvastatin treatment.Conclusion. Our data documented leukocyte recruitment prior to lipid accumulation and subsequent inhibition by rosuvastatin. The underlying mechanism seemed to involve oxidative stress and an anti-inflammatory effect on the endothelium of atheroprone vessels.
A Modified Deterministic Model for Reverse Supply Chain in Manufacturing
Authors: Mahapatra R. N. , Biswal B. B. , Parida P. K.
Published: December 2012

Technology is becoming pervasive across all facets of our lives today. Technology innovation leading to development of new products and enhancement of features in existing products is happening at a faster pace than ever. It is becoming difficult for the customers to keep up with the deluge of new technology. This trend has resulted in gross increase in use of new materials and decreased customers' interest in relatively older products. This paper deals with a novel model in which the stationary demand is fulfilled by remanufactured products along with newly manufactured products. The current model is based on the assumption that the returned items from the customers can be remanufactured at a fixed rate. The remanufactured products are assumed to be as good as the new ones in terms of features, quality, and worth. A methodology is used for the calculation of optimum level for the newly manufactured items and the optimum level of the remanufactured products simultaneously. The model is formulated depending on the relationship between different parameters. An interpretive-modelling-based approach has been employed to model the reverse logistics variables typically found in supply chains (SCs). For simplicity of calculation a deterministic approach is implemented for the proposed model.
Comparative Study of Visual Pathways in Owls (Aves: Strigiformes)
Authors: Gutiérrez-Ibáñez Cristián , Iwaniuk Andrew N. , Lisney Thomas J. , Wylie Douglas R.
Published: December 2012

Although they are usually regarded as nocturnal, owls exhibit a wide range of activity patterns, from strictly nocturnal, to crepuscular or cathemeral, to diurnal. Several studies have shown that these differences in the activity pattern are reflected in differences in eye morphology and retinal organization. Despite the evidence that differences in activity pattern among owl species are reflected in the peripheral visual system, there has been no attempt to correlate these differences with changes in the visual regions in the brain. In this study, we compare the relative size of nuclei in the main visual pathways in nine species of owl that exhibit a wide range of activity patterns. We found marked differences in the relative size of all visual structures among the species studied, both in the tectofugal and the thalamofugal pathway, as well in other retinorecipient nuclei, including the nucleus lentiformis mesencephali, the nucleus of the basal optic root and the nucleus geniculatus lateralis, pars ventralis. We show that the barn owl (Tyto alba), a species widely used in the study of the integration of visual and auditory processing, has reduced visual pathways compared to strigid owls. Our results also suggest there could be a trade-off between the relative size of visual pathways and auditory pathways, similar to that reported in mammals. Finally, our results show that although there is no relationship between activity pattern and the relative size of either the tectofugal or the thalamofugal pathway, there is a positive correlation between the relative size of both visual pathways and the relative number of cells in the retinal ganglion layer.
Similarities in Serum Acylcarnitine Patterns in Type 1 and Type 2 Diabetes Mellitus and in Metabolic Syndrome
Authors: Bene Judit , Márton Magdolna , Mohás Márton , Bagosi Zoltán , Bujtor Zoltán , Oroszlán Tamás , Gasztonyi Beáta , Wittmann Istvan , Melegh Bela
Published: December 2012

Background/Aims: In type 1 diabetes (T1D), type 2 diabetes (T2D) and metabolic syndrome (MetS), the associated complex metabolomic changes in the involvement of carnitine metabolism in total carnitine ester level has already been documented; here we extended the investigations to the individual acylcarnitines. Methods: The fasting serum acylcarnitine concentrations were determined in 49 T1D, 38 T2D and 38 MetS patients and 40 controls by isotope dilution electrospray ionization tandem mass spectrometry. Results: The acylcarnitine profiles of the 3patient groups shared elements with the controls. Considerably higher levels of almost all short-chain acylcarnitines (p < 0.05) and lower levels of some long-chain acylcarnitines were detected in T2D and MetS patients. The amounts of C3 and C4 carnitine were higher and most of the medium-chain and long-chain acylcarnitine levels were lower (p < 0.05) in T1D and MetS patients than in the controls. In T1D and T2D, the levels of C3 and C4 acylcarnitines were markedly elevated and some long-chain acylcarnitines were lower than the controls (p < 0.05). Moreover, significantly lower concentrations of free- and total carnitine were observed in T1D patients (p < 0.05). Conclusions: Profound alterations were detected in acylcarnitine profiles in the 3 patient groups. Similarities in the patterns suggest different degrees of involvement of the same metabolic systems in a systems biology approach.
Determinants of Immediate Extubation in the Operating Room after Total Thoracoscopic Closure of Congenital Heart Defects
Authors: Yu Ai-Lan , Cai Xing-Zhi , Gao Xiu-Juan , Zhang Zong-Wang , Ma Zeng-Shan , Ma Long-Le , Wang Le-Xin
Published: December 2012

Objective: This study was designed to assess the factors that influence immediate extubation following totally thoracoscopic closure of congenital heart defects. Subjects and Methods: Clinical and operational data of 216 patients (87 males, average age 13.6 ± 10.9 years) were retrospectively analyzed. Atrial (ASD, n = 90) or ventricular septal defects (VSD, n = 126) were closed via a totally thoracoscopic approach. Ultra-fast-track anesthesia (UFTA) was used in all patients. Results: Immediate extubation in the operating room was successfully performed in 156 (72.2%) patients. A delayed extubation was completed in the intensive care unit in the remaining 60 (27.8%) patients. There was no significant difference in the age, sex, body weight, or type of congenital heart defect between the immediate and delayed extubation groups (p > 0.05). However, more patients in the delayed extubation group had severe preoperational pulmonary hypertension [8 (13.3%) vs. 4 (2.3%), p < 0.05]. The cardiopulmonary bypass time, aortic clamp time, and total duration of the surgery in the immediate extubation group were shorter than in the delayed extubation group (p < 0.05). Multivariate logistic regression analysis showed that preoperational pulmonary hypertension, duration of the surgery or cardiopulmonary bypass, and dosage of fentanyl used during the surgery were independent predictors for immediate extubation. Conclusions: UFTA and immediate extubation in the operating room was feasible and safe in the majority of patients undergoing totally thoracoscopic closure of ASD or VSD. Preoperational pulmonary hypertension, duration of the surgery, and the dosage of fentanyl used for UFTA were the determining factors for immediate extubation.
The ICD for Primary Prevention in Patients With Inherited Cardiac Diseases
Authors: Olde Nordkamp Louise R.A. , Wilde Arthur A.M. , Tijssen Jan G.P. , Knops Reinoud E. , van Dessel Pascal F.H.M. , de Groot Joris R.
Published: December 2012

Background—

Indications for prophylactic implantable cardioverter-defibrillator (ICD) therapy in patients with inherited cardiac diseases stem from observational studies and are uncertain. This study evaluates the efficacy and harm rate of ICD implantations for primary prevention compared with secondary prevention in inherited cardiac diseases.

Methods and Results—

Between January 1, 1993, and April 1, 2011, 354 patients with inherited cardiac diseases were treated with ICDs. Incidence rates of appropriate shocks in primary prevention patients with arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy were 4.2 to 6.7/100 patient-years, whereas the risk for appropriate shocks in primary prevention patients with Brugada syndrome, long QT syndrome, or carrying the
DPP6
haplotype approached zero. Conversely, in secondary prevention patients there was a considerably higher incidence rate of appropriate shocks. None of the indications for primary prevention were associated with appropriate shock therapy. One hundred twenty-three patients (35%) experienced ICD-related adverse events.

Conclusions—

For Brugada syndrome, long QT syndrome, and DPP6 the efficacy of an ICD for primary prevention contrasts with the amount of harm, and factors that formed the indication for ICD implantation do not relate to the occurrence of appropriate shocks. The higher appropriate discharge rates in arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy compared with primary electric diseases might result from a more advanced risk stratification scheme in these inherited cardiomyopathies.
High Prevalence of Catecholamine-facilitated Focal Ventricular Tachycardia in Patients With Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Authors: Philips Binu , Madhavan Srinivasa , James Cynthia , Tichnell Crystal , Murray Brittney , Needleman Matthew , Bhonsale Aditya , Nazarian Saman , Laurita Kenneth R. , Calkins Hugh , Tandri Harikrishna
Published: December 2012

Background—

Exercise-related ventricular tachycardia (VT) and high burden of premature ventricular contractions (PVCs) are common in arrhythmogenic right ventricular dysplasia/cardiomyopathy. We hypothesized that VT in arrhythmogenic right ventricular dysplasia/cardiomyopathy shows a high degree of association with the PVC at baseline.

Methods and Results—

The study population included 16 consecutive arrhythmogenic right ventricular dysplasia/cardiomyopathy patients with recurrent VT who underwent catheter ablation. Median age of the patients was 27 years (range, 18–66) and 50% were men. All patients had frequent ectopy at baseline with a median PVC count of 7275 (range, 1353–19 084). During EP study, a total of 27 VTs were induced, of which 16 (59%) occurred during high-dose isoproterenol infusion. VT morphology was identical to the baseline PVCs in all the VTs induced during high-dose isoproterenol infusion. Focal ablation at the site of earliest activation and 12/12 pace map of the PVC eliminated the VT in all cases. Target site for focal ablation localized to scar border. Cumulative freedom from VT after ablation was 85.2% and 74.5% at 1 and 2 years, respectively, which was associated with a reduction in PVC count.

Conclusions—

We report a high degree of association between PVCs at baseline and the VTs induced during catecholamine infusion. These VTs originated from the border region of scar most commonly in the right ventricular outflow tract and right ventricle basal regions. These findings highlight the importance of catecholamine challenge and PVC mapping, which can in turn facilitate ablation of the VT in arrhythmogenic right ventricular dysplasia/cardiomyopathy.