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Sample records for endomembrane system low-molecular-weight

  1. Low-molecular-weight metabolite systems chemistry

    Directory of Open Access Journals (Sweden)

    Franz eHadacek

    2015-03-01

    Full Text Available Low-molecular-weight metabolites (LMWMs comprise primary or central and a plethora of intermediary or secondary metabolites, all of which are characterized by a molecular weight below 900 Dalton. The latter are especially prominent in sessile higher organisms, such as plants, corals, sponges and fungi, but are produced by all types of microbial organisms too. Common to all of these carbon molecules are oxygen, nitrogen and, to a lesser extent, sulfur, as heteroatoms. The latter can contribute as electron donators or acceptors to cellular redox chemistry and define the potential of the molecule to enter charge-transfer complexes. Furthermore, they allow LMWMs to serve as organic ligands in coordination complexes of various inorganic metals as central atoms. Especially the transition metals Fe, Cu and Mn can catalyze one electron reduction of molecular oxygen, which results in formation of free radical species and reactive follow-up reaction products. As antioxidants LMWMs can scavenge free radicals. Depending on the chemical environment, the same LMWMs can act as pro-oxidants by reducing molecular oxygen. The cellular regulation of redox homeostasis, a balance between oxidation and reduction, is still far from being understood. Charge-transfer and coordination complex formation with metals shapes LMWMs into gel-like matrices in the cytosol. The quasi-polymer structure is lost usually during the isolation procedure. In the gel state, LMWMs possess semiconductor properties. Also proteins and membranes are semiconductors. Together they can represent biotransistor components that can be part of a chemoelectrical signaling system that coordinates systems chemistry by initiating cell differentiation or tissue homeostasis, the activated and the resting cell state, when it is required. This concept is not new and dates back to Albert Szent-Györgyi.

  2. Preparation and evaluation of a novel oral delivery system for low molecular weight heparin

    OpenAIRE

    Lavanya, Nallaguntla; Muzib, Yallamalli Indira; Aukunuru, Jithan; Balekari, Umamahesh

    2016-01-01

    Objective: The objective of the present work was to prepare and evaluate a novel oral formulation for systemic delivery of low molecular weight heparin (LMWH). The formulation consisted of Eudragit S 100-coated positively charged liposomes encapsulating LMWH and a penetration enhancer. Materials and Methods: Positively charged liposomes were first prepared by the thin film hydration method using lipid (soy phosphotidylcholine and cholesterol) and stearyl amine (SA) in the optimum ratio of 16:...

  3. Research and Application on low molecular weight polymer fracturing fluid system

    Directory of Open Access Journals (Sweden)

    Wang Xiao Chao

    2016-01-01

    Full Text Available In order to reduce the secondary damage of melon gum fracturing fluid for the low permeability alkali sensitivity reservoir, Optimized a kind of low molecular weight polymer fracturing fluid, and solve the technical problem of crosslinking time is not easy to control, fracturing fluid gel breaking difficult in low temperature. Through the study of the optimization of main additives, The fracturing fluid use low molecular highly active three yuan low molecular polymer as a thickener, which use of special synthetic process of polymerization with multiple active node. Its molecular weight is 200000 ~ 300000, water soluble speed is fast, site preparation easy, and thickening ability is strong. When the concentration is 0.2% ~ 0.6% in the fracturing fluid ,it can satisfy the requirement of fracturing operation. With organic zirconium and aldehyde compounds as crosslinking agent, The fracturing fluid have been achieved in good results in erlian uli of north China oilfield, ordos basin yishan slope of oil well and gas well fracturing.

  4. Preparation of Low Molecular Weight Gelatin Using Microwave Discharge Electrodeless Lamp/TiO2 Photocatalyst Hybrid System.

    Science.gov (United States)

    Lee, Do-Jin; Kim, Hangun; Park, Young-Kwon; Kim, Byung Hoon; Lee, Heon; Jungf, Sana-Chul

    2016-02-01

    In this study, an MDEL/TiO2 photocatalyst hybrid system was applied to the production of low molecular weight gelatin. The molecular weight of produed gelatin decreased with increasing microwave intensity and increasing treatment time. The abscission of the chemical bonds between the con- stituents of gelatin by photocatalytic reaction did not alter the characteristics of gelatin. Formation of any by-products due to side reaction was not observed. It is suggested that gelatin was depolymerized by hydroxyl radicals produced during the MDEL/TiO2 photochemical reaction.

  5. Low molecular weight heparins.

    Science.gov (United States)

    Bergqvist, D

    1996-08-01

    Low molecular weight heparins (LMWHs) differ from unfractionated heparin (UFH) in a number of characteristics, which is probably due to differences in molecular weight distribution. From a clinical point of view the better subcutaneous bioavailability and longer biological half-life are important, making it sufficient to inject LMWHs once-daily only. For practical purposes it is also important that LMWHs be used without monitoring. They are effective as prophylaxis against postoperative venous thromboembolism after all types of surgery; in most studies, more effective than UFH. In most studies, this effect can be obtained safely and with less bleeding than with UFH. LMWHs compare favourably with UFH for starting treatment of deep vein thrombosis, as well as an anticoagulant during haemodialysis. Adverse effects such as thrombocytopenia and osteoporosis are more common with UFH than with LMWHs. Studies evaluating whether or not LMWHs can replace UFH in arterial diseases are still few with small sample sizes. Thus further systematic research is needed.

  6. Analytical system for stable carbon isotope measurements of low molecular weight (C2-C6) hydrocarbons

    NARCIS (Netherlands)

    Zuiderweg, A.T.; Holzinger, R.; Roeckmann, T.

    2011-01-01

    We present setup, testing and initial results from a new automated system for stable carbon isotope ratio measurements on C2 to C6 atmospheric hydrocarbons. The inlet system allows analysis of trace gases from air samples ranging from a few liters for urban samples and samples with high mixing

  7. Analytical system for stable carbon isotope measurements of low molecular weight (C2-C6 hydrocarbons

    Directory of Open Access Journals (Sweden)

    T. Röckmann

    2011-06-01

    Full Text Available We present setup, testing and initial results from a new automated system for stable carbon isotope ratio measurements on C2 to C6 atmospheric hydrocarbons. The inlet system allows analysis of trace gases from air samples ranging from a few liters for urban samples and samples with high mixing ratios, to many tens of liters for samples from remote unpolluted regions with very low mixing ratios. The centerpiece of the sample preparation is the separation trap, which is used to separate CO2 and methane from the compounds of interest. The main features of the system are (i the capability to sample up to 300 l of air, (ii long term (since May 2009 operational δ13C accuracy levels in the range 0.3–0.8 ‰ (1-σ, and (iii detection limits of order 1.5–2.5 ngC (collected amount of substance for all reported compounds. The first application of this system was the analysis of 21 ambient air samples taken during 48 h in August 2009 in Utrecht, the Netherlands. Results obtained are generally in good agreement with those from similar urban ambient air studies. Short sample intervals allowed by the design of the instrument help to illustrate the complex diurnal behavior of hydrocarbons in an urban environment, where diverse sources, dynamical processes, and chemical reactions are present.

  8. Systemic antibody responses of calves to low molecular weight Cooperia oncophora antigens.

    Science.gov (United States)

    Nieuwland, M G; Ploeger, H W; Kloosterman, A; Parmentier, H K

    1995-10-01

    The systemic antibody responses to adult Cooperia oncophora antigen were studied using sera obtained from calves during a 6-week period following a single oral infection with either 20,000 or 100,000 third-stage C. oncophora larvae. Dose dependent increasing titres of IgG binding complete adult Cooperia antigen were found in the sera of Cooperia-infected calves. SDS-gel electrophoresis under reducing conditions, followed by Western blotting, revealed that the increase of IgG binding Cooperia antigens could be attributed mainly to specific binding of IgG to a complex of 12-15 kDa protein fragments of Cooperia adult antigen. This protein may represent a Cooperia oncophora-specific component that can be used for serodiagnosis.

  9. Stabilization of Ostwald ripening in low molecular weight amino lipid nanoparticles for systemic delivery of siRNA therapeutics.

    Science.gov (United States)

    Gindy, Marian E; Feuston, Brad; Glass, Angela; Arrington, Leticia; Haas, R Matthew; Schariter, Joseph; Stirdivant, Steven M

    2014-11-03

    Lipid nanoparticles (LNPs) represent the most clinically advanced technology for the systemic delivery of therapeutic siRNA in vivo. Toward this end, a novel class of LNPs comprising low molecular weight (MW) ionizable amino lipids having asymmetric architecture was recently reported.1 LNPs of these amino lipids, termed asymmetric LNPs, were shown to be highly efficacious and well tolerated in vivo; advances were enabled by improved endosomal escape, coupled with enhanced amino lipid metabolism and clearance. In this work, we show that, in contrast to their desirable pharmacological performance, asymmetric LNPs present a significant pharmaceutical developability challenge, namely physical instability limiting extended shelf life. Using orthogonal characterization methods, we identify the mechanism of LNP instability as Ostwald ripening and establish it to be driven predominantly by the asymmetric amino lipid component. Through rational optimization of LNP physical and macromolecular properties, we are able to significantly attenuate or entirely eliminate the Ostwald ripening instability. Modulation of LNP size, for example, effectively halts particle growth. Similarly, optimization of LNP macromolecular packing through deliberate selection of structurally matched colipids significantly diminishes the rate of ripening. This later experimental observation is substantiated by molecular dynamics simulations of LNP self-assembly, which establish a quantitative dependence of LNP macromolecular order on colipid structure. In totality, the experimental and molecular dynamics outcomes of this work support the rational design of LNP physical and chemical properties leading to effective Ostwald ripening stabilization and enable the advance of asymmetric LNPs as a clinic-ready platform for siRNA therapeutics.

  10. The effect of low-molecular-weight organic acids on copper toxicity in E. fetida in an acute exposure system.

    Science.gov (United States)

    Zhou, Chuifan; Huang, Meiying; Yu, Jiaoda; Li, Ying; Liu, Aiqin

    2017-03-01

    In the present study, the effects of low-molecular-weight organic acids (OAs) on the toxicity of copper (Cu) to the earthworm Eisenia fetida (E. fetida) were investigated in a simulated soil solution. We exposed E. fetida to soil solution containing Cu and a variety of OAs (acetic acid, oxalic acid, citric acid, and EDTA). We found that the addition of OAs reduced the toxicity of Cu to E. fetida, where the reduction was strongest in EDTA and weakest in acetic acid. These compounds decreased the mortality rate of E. fetida that were exposed to Cu and reduced levels of antioxidant enzymes and malondialdehyde to unexposed control levels. E. fetida were exposed to Cu with OAs had reduced Cu(2+), which were likely caused by Cu forming complexes with the OAs, reducing the availability of Cu. The presence of OAs also reduced Cu-induced damage on earthworm cellular ultrastructures and changed the subcellular distribution of Cu. These results demonstrated that OAs could reduce the toxicity, as well as the bioavailability, of heavy metals in soil solutions where both OAs and heavy metals often coexist.

  11. POSSIBILITIES OF USING LOW-MOLECULAR-WEIGHT HEPARIN IN THE COMPLEX TREATMENT OF WOMEN WITH TUMORS OF THE REPRODUCTIVE SYSTEM

    Directory of Open Access Journals (Sweden)

    A. G. Kedrova

    2017-01-01

    Full Text Available Benign and malignant tumors of the organs of the female reproductive system are the most common diseases requiring medical and surgical treatment. They are rarely the cause of acute complications. However, the thromboembolic disease is a serious illness, sometimes causing death due to acute the pulmonary embolism. Venous thromboembolism secondary to Benign and malignant tumors of the organs of the female reproductive system should be considered in a female presenting with abdominal mass and pelvic pressure. Thromboembolic disease secondary to large tumors should be treated with anticoagulation then hysterectomy. The article presents an analysis of modern literature on optimal prevention of the pulmonary thromboembolism in patients with tumors of the female reproductive system. There are analysis data of 17 (0.7 % cases of the pulmonary thromboembolism that occurred of 2358 gynecological and oncogynecologic patients.

  12. Formation of Low-Molecular-Weight Dissolved Organic Nitrogen in Predenitrification Biological Nutrient Removal Systems and Its Impact on Eutrophication in Coastal Waters.

    Science.gov (United States)

    Eom, Heonseop; Borgatti, Douglas; Paerl, Hans W; Park, Chul

    2017-04-04

    To alleviate eutrophication in coastal waters, reducing nitrogen (N) discharge from wastewater treatment plants (WWTPs) by upgrading conventional activated sludge (CAS) to biological nutrient removal (BNR) processes is commonplace. However, despite numerous upgrades and successful reduction of N discharge from WWTPs, eutrophication problems persist. These unexpected observations raise the possibility that some aspects of BNR yield environmental responses as yet overlooked. Here, we report that one of the most common BNR processes, predenitrification, is prone to the production of low-molecular-weight dissolved organic N (LMW-DON), which is highly bioavailable and stimulates phytoplankton blooms. We found that in predenitrification BNR, LMW-DON is released during the post-aerobic step following the preanoxic step, which does not occur in CAS. Consequently, predenitrification systems produced larger amount of LMW-DON than CAS. In estuarine bioassays, predenitrification BNR effluents produced more phytoplankton biomass than CAS effluents despite lower N concentrations. This was also supported by stronger correlations found between phytoplankton biomass and LMW-DON than other N forms. These findings suggest that WWTPs upgraded to predenitrification BNR reduce inorganic N discharge but introduce larger quantities of potent LMW-DON into coastal systems. We suggest reassessing the N-removal strategy for WWTPs to minimize the eutrophication effects of effluents.

  13. Investigation of Galactosylated Low Molecular Weight Chitosan ...

    African Journals Online (AJOL)

    Purpose: To assess the hepatocyte targeting potential of galactosylated low molecular weight chitosan (Gal-LMWCs)-coated liposomes bearing doxorubicin hydrochloride (DOX). Methods: Chitosan (CS) was depolymerized and lactobionic acid (LA) containing a galactose group was coupled with low molecular weight ...

  14. Low-Molecular-Weight Heparin-Coated and Montelukast-Filled Inhalable Particles: A Dual-Drug Delivery System for Combination Therapy in Asthma.

    Science.gov (United States)

    Patel, Brijeshkumar; Rashid, Jahidur; Gupta, Nilesh; Ahsan, Fakhrul

    2017-04-01

    Montelukast, a cysteinyl leukotriene type 1 receptor antagonist, exhibits secondary anti-inflammatory properties when used at higher concentrations. Low-molecular-weight heparin (LMWH) evokes pronounced anti-inflammatory effects by interrupting leukocyte adhesion and migration. We hypothesized that inhalable particles containing montelukast plus LMWH release both drugs in a sustained fashion and protect the lungs against allergen-induced inflammation. Large porous particles of montelukast and LMWH were prepared using a double-emulsion-solvent-evaporation method. Montelukast was first encapsulated in copolymer-based particles using polyethylenimine as a porosigen; the resulting particles were then coated with LMWH. The particles were evaluated for physicochemical properties, respirability, and release profiles. The anti-inflammatory effect of the optimized formulation was studied in ovalbumin-sensitized asthmatic Sprague Dawley rats. The optimized large porous particles had a diameter of 10.3 ± 0.7 μm, exhibited numerous surface indentations and pores, showed acceptable drug entrapment efficiency (66.8% ± 0.4% for montelukast; 91.7% ± 0.8% adsorption efficiency for LMWH), demonstrated biphasic release patterns, and escaped the uptake by the rat alveolar macrophages. The number of infiltrating inflammatory cells in asthmatic rat lungs, treated with dual-drug particles, was >74% fewer than in untreated asthmatic rat lungs. Similarly, the airway walls of asthmatic animals treated with dual-drug particles were 3-fold thinner than those of untreated asthmatic animals (p montelukast and LMWH, into an inhalable particulate system and establishes that this novel combination therapy produces sustained drug release and elicits a robust anti-inflammatory response in the lungs. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  15. Low Molecular Weight Glucosamine/L-lactide Copolymers as Potential Carriers for the Development of a Sustained Rifampicin Release System: Mycobacterium Smegmatis as a Tuberculosis Model

    Science.gov (United States)

    Ragusa, Jorge Alejandro

    Tuberculosis, a highly contagious disease, ranks as the second leading cause of death from an infectious disease, and remains a major global health problem. In 2013, 9 million new cases were diagnosed and 1.5 million people died worldwide from tuberculosis. This dissertation aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (molecular core building unit) and L-lactide (GluN-LLA). Stable particles with a very high 50% drug loading capacity were made via electrohydrodynamic atomization. Prolonged release (>14 days) of RIF from these particles is demonstrated. Drug release data fits the Korsmeyer-Peppas equation, which suggests the occurrence of a modified diffusion-controlled RIF release mechanism, and is also supported by differential scanning calorimetry and drug leaching tests. Cytotoxicity tests on Mycobacterium smegmatis showed that antibiotic-free GluN-LLA and polylactides (PLA) (reference material) particles did not show any significant anti-bacterial activity. The minimum inhibitory concentration and minimum bactericidal concentration values obtained for RIF-loaded particles showed 2- to 4-fold improvements in the anti-bacterial activity relative to the free drug. Cytotoxicity tests on macrophages indicated an increment in cell death as particle dose increased, but was not significantly affected by material type or particle size. Confocal microscopy was used to track internalization and localization of particles in the macrophages. GluN-LLA particles led to higher uptakes than the PLA particles. In addition, after phagocytosis, the GluN-LLA particles stayed in the cytoplasm and the particles showed a favorable long term drug release effect in killing intracellular bacteria compared to free RIF. The studies presented and discussed in this dissertation

  16. Imaging the ER and Endomembrane System in Cereal Endosperm.

    Science.gov (United States)

    Ibl, Verena; Peters, Jenny; Stöger, Eva; Arcalís, Elsa

    2018-01-01

    The cereal endosperm is a complex structure comprising distinct cell types, characterized by specialized organelles for the accumulation of storage proteins. Protein trafficking in these cells is complicated by the presence of several different storage organelles including protein bodies (PBs) derived from the endoplasmic reticulum (ER) and dynamic protein storage vacuoles (PSVs). In addition, trafficking may follow a number of different routes depending on developmental stage, showing that the endomembrane system is capable of massive reorganization. Thus, developmental sequences involve progressive changes of the endomembrane system of endosperm tissue and are characterized by a high structural plasticity and endosomal activity.Given the technical dexterity required to access endosperm tissue and study subcellular structures and (seed storage protein) SSP trafficking in cereal seeds, static images are the state of the art providing a bulk of information concerning the cellular composition of seed tissue. In view of the highly dynamic endomembrane system in cereal endosperm cells, it is reasonable to expect that live cell imaging will help to characterize the spatial and temporal changes of the system. The high resolution achieved with electron microscopy perfectly complements the live cell imaging.We therefore established an imaging platform for TEM as well as for live cell imaging. Here, we describe the preparation of different cereal seed tissues for live cell imaging concomitant with immunolocalization studies and ultrastructure.

  17. Localization of small heat shock proteins to the higher plant endomembrane system.

    OpenAIRE

    Helm, K W; LaFayette, P R; Nagao, R T; Key, J L; Vierling, E

    1993-01-01

    Three related gene families of low-molecular-weight (LMW) heat shock proteins (HSPs) have been characterized in plants. We describe a fourth LMW HSP family, represented by PsHSP22.7 from Pisum sativum and GmHSP22.0 from Glycine max, and demonstrate that this family of proteins is endomembrane localized. PsHSP22.7 and GmHSP22.0 are 76.7% identical at the amino acid level. Both proteins have amino-terminal signal peptides and carboxyl-terminal sequences characteristic of endoplasmic reticulum (...

  18. Identification of a low molecular weight polypeptide of pregnant bovine uterine origin (LMW-UDF): influence on coagulation system in vitro. Part I.

    Science.gov (United States)

    Speidel, M T; Suzuki, M; Pantazis, C G

    1987-04-01

    Acidified extracts of pregnant bovine uterus were found to contain a heparin-affinity polypeptide(s). The eluted peak was assayed in the Chandler loop method for whole blood and fibrin thrombus generation. Significant differences in the mean weight and size of whole blood thrombi (243.5 +/- 50 mg and 3.5 cm +/- 0.6 cm) occurred with 1 microgram of purified polypeptide when compared to control samples containing albumin (47.87 +/- .30 g and 0.8 cm +/- 0.3 cm). This activity was detected by the Chandler loop method with 100 ng to 10 micrograms of protein when analyzed in a dose-response fashion. When tested for fibrin thrombus formation this activity persisted. Experiments with 125I fibrinogen revealed no net increase or decrease of uptake into whole blood thrombi when purified polypeptide was added. The heparin-affinity polypeptide(s) possessed a molecular weight of approximately 6-4 kDa when examined by SDS-PAGE. We have therefore designated this polypeptide as low molecular weight-uterine derived factor (LMW-UDF).

  19. Interactions between plant endomembrane systems and the actin cytoskeleton

    Directory of Open Access Journals (Sweden)

    Pengwei eWang

    2015-06-01

    Full Text Available Membrane trafficking, organelle movement and morphogenesis in plant cells are mainly controlled by the cytoskeleton. Not all proteins that regulate the actin cytoskeleton and membrane dynamics in animal systems have functional homologues in plants, especially for those proteins that form the bridge between the cytoskeleton and membrane; the membrane-actin adaptors. Their nature and function is only just beginning to be elucidated and this field has been greatly enhanced by the recent identification of the NETWORKED (NET proteins which act as membrane-actin adaptors. In this review, we will summarize the role of the actin cytoskeleton and its regulatory proteins in their interaction with endomembrane compartments and where they potentially act as platforms for cell signalling and the coordination of other subcellular events.

  20. Self-assembled drug delivery system based on low-molecular-weight bis-amide organogelator: synthesis, properties and in vivo evaluation.

    Science.gov (United States)

    Li, Zhen; Cao, Jinxu; Li, Heran; Liu, Hongzhuo; Han, Fei; Liu, Zhenyun; Tong, Chao; Li, Sanming

    2016-10-01

    Orgnaogels based on amino acid derivatives have been widely used in the area of drug delivery. An organogel system based on l-lysine derivatives was designed and prepared to induce a thermal sensitive implant with higher transition temperature, better mechanical strength, and shorter gelation time. The organogel was prepared by injectable soybean oil and methyl (S)-2,5-ditetradecanamidopentanoate (MDP), which was synthesized for the first time. Candesartan cilexetil (CC) was chosen as model drug. Different formulations were designed and optimized by response surface method. Thermal, rheology properties, and gelation kinetics of the optimized formulation had been characterized. The release behaviors in vitro, as well as in vivo were evaluated in comparison with the oily solution of drugs. Finally, the local inflammation response of in situ organogel was assessed by histological analysis. Results showed that the synthesized gelator, MDP, had a good gelation ability and the organogels obtained via the self-assembly of gelators in vegetable oils exhibited great thermal and rheology properties, which guaranteed their state in body. In vivo pharmacokinetic demonstrated that the organogel formulation could extend the drug release and maintain a therapeutically effective plasma concentration at least 10 d. In addition, this implant showed acceptable moderate inflammation. The in situ forming l-lysine-derivative-based organogel could be a promising matrix for sustained drug delivery of the drugs with low solubility.

  1. [Therapeutic indications of low molecular weight heparins].

    Science.gov (United States)

    Samama, M M; Michaut-Paterno, F

    1991-11-01

    The depolymerisation of the various chains of unfractionated heparin (UFH) by chemical or enzymatic reactions provides so-called low molecular weight heparin (LMWH), with an average molecular weight of approximately 5000 daltons. The specific biological and pharmacokinetic properties of LMWH with greater inhibition of factor Xa than of thrombin activity, less interaction with platelets, better bioavailability and a longer half life of anti-Xa activity, suggest possible new therapeutic applications. The hypothesis of reducing the risk of haemorrhage related to the antithrombin activity and the incidence of heparin-induced thrombocytopenia whilst preserving effective antithrombotic action has stimulated clinical and biological research. Clinical trials of prophylaxis of venous thrombo-embolism have been undertaken mainly in surgical patients. The results have shown identical if not better efficacy of LMWH compared to UFH in general surgical and above all orthopedic patients in whom subcutaneous heparin is only effective with a strict protocol which is difficult to adhere to in routine practice (adaptation of dosage to activated partial thromboplastin time). The risk of bleeding was not significantly lower using LMWH at the specified dosage, which in the latter indication, is twice that used in general surgery. There are many indications of prophylaxis of thromboembolism in the medical specialties but, paradoxically, LMWH has not been widely studied because of the difficulties in performing the therapeutic trials. Except in rare cases (extreme body weights, renal failure, haemorrhagic disease, thrombotic or haemorrhagic complications) the evaluation of amidolytic anti-Xa activity does not seem to be necessary. More recently, LMWH has been studied in a small number of trials for the treatment of deep venous thrombosis (DVT). The therapeutic efficacy is identical if not better than that of UFH without increasing the risk of bleeding. Biological monitoring seems to be

  2. Anticoagulant effect of low molecular weight heparin on central ...

    African Journals Online (AJOL)

    Purpose: To analyse the effect of low molecular weight heparin on venous catheters in haemodialysis patients. Methods: This study included 140 eligible patients who were randomly and evenly divided into two groups, viz, a study group that received low molecular weight heparin and a control group that received ...

  3. Anticoagulant effect of low molecular weight heparin on central ...

    African Journals Online (AJOL)

    Thus, low molecular weight heparin seems to be more suitable as an anticoagulant solution in patients with venous catheters. Keywords: Low molecular weight heparin, Haemodialysis, Central venous catheter, Vascular access. Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), ...

  4. Localization of small heat shock proteins to the higher plant endomembrane system.

    Science.gov (United States)

    Helm, K W; LaFayette, P R; Nagao, R T; Key, J L; Vierling, E

    1993-01-01

    Three related gene families of low-molecular-weight (LMW) heat shock proteins (HSPs) have been characterized in plants. We describe a fourth LMW HSP family, represented by PsHSP22.7 from Pisum sativum and GmHSP22.0 from Glycine max, and demonstrate that this family of proteins is endomembrane localized. PsHSP22.7 and GmHSP22.0 are 76.7% identical at the amino acid level. Both proteins have amino-terminal signal peptides and carboxyl-terminal sequences characteristic of endoplasmic reticulum (ER) retention signals. The two proteins closely resemble class I cytoplasmic LMW HSPs, suggesting that they evolved from the cytoplasmic proteins through the addition of the signal peptide and ER retention motif. The endomembrane localization of these proteins was confirmed by cell fractionation. The polypeptide product of PsHSP22.7 mRNA was processed to a smaller-M(r) form by canine pancreatic microsomes; in vivo, GmHSP22.0 polysomal mRNA was found to be predominantly membrane bound. In vitro-processed PsHSP22.7 corresponded in mass and pI to one of two proteins detected in ER fractions from heat-stressed plants by using anti-PsHSP22.7 antibodies. Like other LMW HSPs, PsHSP22.7 was observed in higher-molecular-weight structures with apparent masses of between 80 and 240 kDa. The results reported here indicate that members of this new class of LMW HSPs are most likely resident ER proteins and may be similar in function to related LMW HSPs in the cytoplasm. Along with the HSP90 and HSP70 classes of HSPs, this is the third category of HSPs localized to the ER.

  5. Ternary complexes of folate-PEG-appended dendrimer (G4)/α-cyclodextrin conjugate, siRNA and low-molecular-weight polysaccharide sacran as a novel tumor-selective siRNA delivery system.

    Science.gov (United States)

    Ohyama, Ayumu; Higashi, Taishi; Motoyama, Keiichi; Arima, Hidetoshi

    2017-06-01

    We previously developed a tumor-selective siRNA carrier by preparing polyamidoamine dendrimer (generation 4, G4) conjugates with α-cyclodextrin and folate-polyethylene glycol (Fol-PαC (G4)). In the present study, we developed ternary complexes of Fol-PαC (G4)/siRNA with low-molecular-weight-sacrans to achieve more effective siRNA transfer activity. Among the different molecular-weight sacrans, i.e. sacran 100, 1000 and 10,000 (MW 44,889Da, 943,692Da and 1,488,281Da, respectively), sacran 100 significantly increased the cellular uptake and the RNAi effects of Fol-PαC (G4)/siRNA binary complex with negligible cytotoxicity in KB cells (folate receptor-α positive cells). In addition, the ζ-potential and particle size of Fol-PαC (G4)/siRNA complex were decreased by the ternary complexation with sacran 100. Importantly, the in vivo RNAi effect of the ternary complex after the intravenous administration to tumor-bearing BALB/c mice was significantly higher than that of the binary complex. In conclusion, Fol-PαC (G4)/siRNA/sacran 100 ternary complex has a potential as a novel tumor-selective siRNA delivery system. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Preparation, characterization and potential application of new low-molecular-weight organogels

    OpenAIRE

    Schön, Eva-Maria

    2014-01-01

    In this thesis, four low molecular weight gelator based organogel systems were under investigation. Besides the exploration of two novel metallogels, a multicomponent liquid organogelator system and its organogels were discovered. Additionally, the gelation ability of a urea-based compound was analyzed.

  7. Drying affects the fiber network in low molecular weight hydrogels

    DEFF Research Database (Denmark)

    Mears, Laura L. E.; Draper, Emily R.; Castilla, Ana M.

    2017-01-01

    . Here, we use small angle neutron scattering (SANS) to probe low molecular weight hydrogels formed by the self-assembly of dipeptides. We compare scattering data for wet and dried gels, as well as following the drying process. We show that the assumption that drying does not affect the network...

  8. Clinical effects of low-molecular-weight heparin combined with ...

    African Journals Online (AJOL)

    Purpose: To explore the clinical effects of low-molecular-weight heparin (LMWH) combined with ulinastatin (UTI) in children with acute pancreatitis. Methods: In total, 560 patients with severe acute pancreatitis treated at Binzhou People's Hospital,. Shandong, China, from April 2012 to June 2014 were enrolled in this study.

  9. Preventive role of low-molecular-weight heparin in unexplained ...

    African Journals Online (AJOL)

    Preventive role of low-molecular-weight heparin in unexplained recurrent pregnancy loss. E S Khan,1 MBBS, FCPS ... with thromboprophylaxis as preventive therapy has been proposed. This open-access article is distributed under ... placental abruption or preeclampsia. A relationship with early pregnancy loss is less clear ...

  10. Permeability of low molecular weight organics through nanofiltration membranes.

    Science.gov (United States)

    Meylan, Sébastien; Hammes, Frederik; Traber, Jacqueline; Salhi, Elisabeth; von Gunten, Urs; Pronk, Wouter

    2007-09-01

    The removal of natural organic matter (NOM) using nanofiltration (NF) is increasingly becoming an option for drinking water treatment. Low molecular weight (LMW) organic compounds are nevertheless only partially retained by such membranes. Bacterial regrowth and biofilm formation in the drinking water distribution system is favoured by the presence of such compounds, which in this context are considered as the assimilable organic carbon (AOC). In this study, the question of whether NF produces microbiologically stable water was addressed. Two NF membranes (cut-off of about 300Da) were tested with different natural and synthetic water samples in a cross-flow filtration unit. NOM was characterised by liquid chromatography with organic carbon detection (LC-OCD) using a size-exclusion column in addition to specific organic acid measurements, while AOC was measured in a batch growth bioassay. Similarly to high molecular weight organic compounds like polysaccharides or humic substances that have a permeability lower than 1%, charged LMW organic compounds were efficiently retained by the NF membranes tested and showed a permeability lower than 3%. However, LMW neutrals and hydrophobic organic compounds permeate to a higher extent through the membranes and have a permeability of up to 6% and 12%, respectively. Furthermore, AOC was poorly retained by NF and the apparent AOC concentration measured in the permeated water was above the proposed limit for microbiologically stable water. This indicates that the drinking water produced by NF might be biologically unstable in the distribution system. Nevertheless, in comparison with the raw water, NF significantly reduced the AOC concentration.

  11. Low Molecular Weight Heparin Overdose: A 10 Year Case Series

    Directory of Open Access Journals (Sweden)

    Adeline Ngo

    2013-06-01

    Full Text Available Background: Low molecular weight heparin (LMWH is used for the treatment and prevention of coagulative disorders. Few patients receiving therapeutic doses of LMWH develop major hemorrhage. Currently there are few reports in the literature on acute overdose on adults.  In this study, clinical profile, treatment and outcome of 21 patients who acutely overdosed enoxaparin are described. Methods: A retrospective chart review of California Poison Control System (CPCS database: Visual Dot Lab during 1997 to 2007 was obtained. All patients with a definite reported overdose of subcutaneous injection of LMWH were included. Results: In total, 21 patients who were all exposed to enoxaparin were studied. The reasons for overdose included medical miscalculation (3 cases, all infants, intentional misuse (2 patients, accidental overdose (7 cases, suicidal attempt (7 cases and unknown in 2 patients. 7 cases were documented to have overdosed more than 2 times the therapeutic dose. The overdose ranged from 50 mg to 1300mg (0.1-80 times the therapeutic range. No patients were documented to experience bleeding or have thrombocytopenia although complete follow-up was only available for 11 patients. Reassurance was given to patients with less than 0.14 times the therapeutic dose. The 2 patients who received protamine were overdosed with more than 2.5 times the therapeutic dose of enoxaparin. Conclusion: Most patients had no complications and were not treated with protamine. This study suggests that a large dosage of LMWH is unlikely to result in any life threatening complications, though further studies are needed to certainly conclude about this. The use of protamine in LMWH overdose seems to remain controversial.

  12. Influence of low molecular weight heparin on cancer patients’ survival

    Directory of Open Access Journals (Sweden)

    V. V. Ptushkin

    2013-01-01

    Full Text Available There is an evidence of interaction between the hemostasis system and tumor progression factors. It is known that in addition to the fibrin formation and platelets activation, thrombin can influence many cells function interacting with protease-activating receptors including tumor cells. These receptors are involved in the malignant cell phenotype formation (adhesion, proliferation, proteolysis. Thrombin can also affect angiogenesis by stimulating endothelial cells penetration through basal membrane and its migration with new vessels formation. Furthermore, it can cause the release of main neoangiogenesis promoter – vascular endothelial growth factor. All of the above and many other linkages of coagulation and tumor create a theoretical background of possible affecting tumor by regulation of the coagulation activity. Thepromise of this approach is controversial, but there is some clinical and experimental evidence of their effectiveness. The most used group ofdrugs for this purpose was heparins. Several retrospective studies have shown a benefit of low molecular weight heparins (LMWH over unfractionated heparin in cancer patient survival. The appearance of a new heparins group – ultra LMWH are of interest from this point ofview and their possible use in cancer patients. To date bemiparin and semuloparin are used in clinic. Both (bemiparin about 3600 kDa,semuloparin 3000 kDa have substancially reduced molecular weight as compared with the smallest of LMWH – enoxaparin (4600 kDa.Use of bemiparin in patients with small cell lung cancer receiving chemotherapy resulted in increased of 2-year survival rate compared to the control group (68.6 % vs. 29.4 %, p = 0.0042.

  13. Influence of low molecular weight heparin on cancer patients’ survival

    Directory of Open Access Journals (Sweden)

    V. V. Ptushkin

    2014-07-01

    Full Text Available There is an evidence of interaction between the hemostasis system and tumor progression factors. It is known that in addition to the fibrin formation and platelets activation, thrombin can influence many cells function interacting with protease-activating receptors including tumor cells. These receptors are involved in the malignant cell phenotype formation (adhesion, proliferation, proteolysis. Thrombin can also affect angiogenesis by stimulating endothelial cells penetration through basal membrane and its migration with new vessels formation. Furthermore, it can cause the release of main neoangiogenesis promoter – vascular endothelial growth factor. All of the above and many other linkages of coagulation and tumor create a theoretical background of possible affecting tumor by regulation of the coagulation activity. Thepromise of this approach is controversial, but there is some clinical and experimental evidence of their effectiveness. The most used group ofdrugs for this purpose was heparins. Several retrospective studies have shown a benefit of low molecular weight heparins (LMWH over unfractionated heparin in cancer patient survival. The appearance of a new heparins group – ultra LMWH are of interest from this point ofview and their possible use in cancer patients. To date bemiparin and semuloparin are used in clinic. Both (bemiparin about 3600 kDa,semuloparin 3000 kDa have substancially reduced molecular weight as compared with the smallest of LMWH – enoxaparin (4600 kDa.Use of bemiparin in patients with small cell lung cancer receiving chemotherapy resulted in increased of 2-year survival rate compared to the control group (68.6 % vs. 29.4 %, p = 0.0042.

  14. Drying Affects the Fiber Network in Low Molecular Weight Hydrogels

    Science.gov (United States)

    2017-01-01

    Low molecular weight gels are formed by the self-assembly of a suitable small molecule gelator into a three-dimensional network of fibrous structures. The gel properties are determined by the fiber structures, the number and type of cross-links and the distribution of the fibers and cross-links in space. Probing these structures and cross-links is difficult. Many reports rely on microscopy of dried gels (xerogels), where the solvent is removed prior to imaging. The assumption is made that this has little effect on the structures, but it is not clear that this assumption is always (or ever) valid. Here, we use small angle neutron scattering (SANS) to probe low molecular weight hydrogels formed by the self-assembly of dipeptides. We compare scattering data for wet and dried gels, as well as following the drying process. We show that the assumption that drying does not affect the network is not always correct. PMID:28631478

  15. Low molecular weight salts combined with fluorinated solvents for electrolytes

    Science.gov (United States)

    Tikhonov, Konstantin; Yip, Ka Ki; Lin, Tzu-Yuan; Lei, Norman; Guerrero-Zavala, Guillermo; Kwong, Kristie W.

    2015-11-10

    Provided are electrochemical cells and electrolytes used to build such cells. An electrolyte includes at least one salt having a molecular weight less than about 250. Such salts allow forming electrolytes with higher salt concentrations and ensure high conductivity and ion transport in these electrolytes. The low molecular weight salt may have a concentration of at least about 0.5M and may be combined with one or more other salts, such as linear and cyclic imide salts and/or methide salts. The concentration of these additional salts may be less than that of the low molecular weight salt, in some embodiments, twice less. The additional salts may have a molecular weight greater than about 250. The electrolyte may also include one or more fluorinated solvents and may be capable of maintaining single phase solutions at between about -30.degree. C. to about 80.degree. C.

  16. Physical Properties of Low-Molecular Weight Polydimethylsiloxane Fluids

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, Christine Cardinal [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Graham, Alan [Univ. of Colorado, Denver, CO (United States); Nemer, Martin [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Phinney, Leslie M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Garcia, Robert M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Soehnel, Melissa Marie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Stirrup, Emily Kate [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-02-01

    Physical property measurements including viscosity, density, thermal conductivity, and heat capacity of low-molecular weight polydimethylsiloxane (PDMS) fluids were measured over a wide temperature range (-50°C to 150°C when possible). Properties of blends of 1 cSt and 20 cSt PDMS fluids were also investigated. Uncertainties in the measurements are cited. These measurements will provide greater fidelity predictions of environmental sensing device behavior in hot and cold environments.

  17. Low Molecular Weight Norbornadiene Derivatives for Molecular Solar?Thermal Energy Storage

    OpenAIRE

    Quant, Maria; Lennartson, Anders; Dreos, Ambra; Kuisma, Mikael; Erhart, Paul; B?rjesson, Karl; Moth?Poulsen, Kasper

    2016-01-01

    Abstract Molecular solar?thermal energy storage systems are based on molecular switches that reversibly convert solar energy into chemical energy. Herein, we report the synthesis, characterization, and computational evaluation of a series of low molecular weight (193?260?g?mol?1) norbornadiene?quadricyclane systems. The molecules feature cyano acceptor and ethynyl?substituted aromatic donor groups, leading to a good match with solar irradiation, quantitative photo?thermal conversion between t...

  18. Capillary electrophoresis for characterization of low molecular weight heparins.

    Science.gov (United States)

    Ramasamy, I; Kennedy, J; Tan, K

    2003-01-01

    In many instances, low molecular weight heparins (LMWH) have replaced unfractionated heparins for prevention and treatment of venous thromboembolism. Each LMWH is a specific compound with its own physicochemical and pharmacological properties. These properties are critical in determining the therapeutic efficacy of the product. In recent times, capillary electrophoresis (CE) has emerged as a means of analytical separation of biological molecules. There are few reports, however, detailing the separation of whole heparins by capillary electrophoresis. This paper reports the use of CE to characterize LMWH without prior oligosaccharide release, labeling, or derivatization. The paper also focuses on the advantages of CE separation for the monitoring of product consistency.

  19. Prophylaxis of postoperative thromboembolism with low molecular weight heparins

    DEFF Research Database (Denmark)

    Jørgensen, L N; Wille-Jørgensen, P; Hauch, O

    1993-01-01

    To evaluate the thromboprophylactic use of low molecular weight heparins (LMWHs), publications from 27 orthopaedic trials and 35 studies of patients undergoing general or gynaecological surgery were scrutinized and subjected to a partial meta-analysis. In orthopaedic surgery, LMWHs were superior...... in patients receiving LMWH and 1.22 per cent in controls. Seven orthopaedic patients (0.15 per cent) died from pulmonary embolism, none of whom received LMWH. In general surgery, the LMWHs were at least as efficient as unfractionated heparin, with a trend towards a lower risk of pulmonary embolism...

  20. Shifting paradigms: biopharmaceuticals versus low molecular weight drugs.

    Science.gov (United States)

    Crommelin, Daan J A; Storm, Gert; Verrijk, Ruud; de Leede, Leo; Jiskoot, Wim; Hennink, Wim E

    2003-11-06

    Biopharmaceuticals are pharmaceutical products consisting of (glyco)proteins. Nowadays a substantial part of the FDA-approved drugs belong to this class of drugs. Biopharmaceuticals deserve special attention as they have a number of characteristics that set them aside from low molecular weight drugs. Their activity depends on their complicated shape based on secondary, tertiary and (sometimes) quaternary structures. These structures cannot be fully defined with our present set of analytical techniques and approaches for potency testing. They often are the same as (or closely resemble) endogenous proteins. This means that in safety testing and clinical test programs questions have to be addressed regarding species specific responses, selection of dosing schedules and route of administration, and the possible occurrence of immunogenicity. As the conformational structure of a protein is easily disturbed, formulation and handling of biopharmaceuticals needs special attention in order to optimize the therapeutic effect and minimize adverse reaction, among which immune responses. The issue of biogenerics is gaining more and more interest and different critical elements in the development of biogenerics are touched upon. In conclusion, biopharmaceuticals cannot be characterized fully in terms of their structure like low molecular weight drugs. The performance of biopharmaceuticals relies on strict production protocols and close monitoring of their activity in the clinical situation.

  1. Low molecular weight heparins in acute ischaemic syndromes.

    Science.gov (United States)

    White, H D; Ellis, C J; French, J K

    1998-08-01

    Thrombus formation and ongoing generation play a major role in the pathogenesis of unstable angina and myocardial infarction (MI). Unfractionated heparin is widely used as an adjunctive therapy in the management of acute ischaemic syndromes, but it has a number of limitations including inter-patient variability, need for monitoring, and the fact that its use may be associated with thrombocytopenia. Low molecular weight heparins have pharmacological and pharmacokinetic properties that may result in better clinical outcomes and safety. They are easy to administer and do not require monitoring. Low molecular weight heparins have been shown to reduce mortality and the incidence of MI and recurrent ischaemia compared with placebo in patients with unstable angina and non-Q-wave MI, and have a more predictable anticoagulant effect than standard unfractionated heparin. They also can be used long term in the outpatient setting, in the form of self-administered subcutaneous injections. The clinical relevance of these new developments is still being defined in ongoing clinical trials and cost-effectiveness analyses.

  2. Alkyl cross-linked low molecular weight polypropyleneimine dendrimers as efficient gene delivery vectors

    Directory of Open Access Journals (Sweden)

    Faezeh Moghadam Ariaee

    2016-10-01

    Conclusion: Our results indicated that oligomerization of low molecular weight PPI (PPI G2-alkyl-PPI G2 conjugate could be an approach to increase the transfection efficiency and to lower the cytotoxicity of low molecular weight polycations.

  3. Obstetric outcome with low molecular weight heparin therapy during pregnancy.

    LENUS (Irish Health Repository)

    Donnelly, J

    2012-01-01

    This was a prospective study of women attending a combined haematology\\/obstetric antenatal clinic in the National Maternity Hospital (2002-2008). Obstetric outcome in mothers treated with low molecular weight heparin (LMWH) was compared to the general obstetric population of 2006. There were 133 pregnancies in 105 women. 85 (63.9%) received prophylactic LMWH and 38 (28.6%) received therapeutic LMWH in pregnancy. 10 (7.5%) received postpartum prophylaxis only. The perinatal mortality rate was 7.6\\/1000 births. 14 (11.3%) women delivered preterm which is significantly higher than the hospital population rate (5.7%, p<0.05). Despite significantly higher labour induction rates (50% vs 29.2% p<0.01), there was no difference in CS rates compared to the general hospital population (15.4% vs 18.9%, NS). If carefully managed, these high-risk women can achieve similar vaginal delivery rates as the general obstetric population.

  4. Peptides and peptidomimetics that behave as low molecular weight gelators.

    Science.gov (United States)

    Tomasini, Claudia; Castellucci, Nicola

    2013-01-07

    Gelators may be divided into chemical gels and physical gels: the internal structure of chemical gels is made of chemical bonds, while physical gels are characterized by dynamic cross-links that are constantly created and broken. The gelator present in physical gels may be an inorganic or an organic compound, the latter having a molecular weight of ≤500 amu. These compounds are generally called "low molecular weight gelators" (LMWGs). In this tutorial review we want to focus our attention on short peptides or peptidomimetics that behave as LMWGs. Peptidomimetics are small protein-like molecules designed to mimic natural peptides. To efficiently design a peptidomimetic, local constraints must be introduced into the skeleton, to induce the formation of preferred secondary structures.

  5. Adsorption of low-molecular-weight sodium polyacrylate on hydroxyapatite.

    Science.gov (United States)

    Misra, D N

    1993-10-01

    Adsorption of low-molecular-weight sodium polyacrylate from aqueous solution onto synthetic hydroxyapatite was studied at room temperature so that the mechanism of adhesion of polyacrylate cements to tooth mineral could be elucidated. The adsorption isotherm of sodium polyacrylate was Langmuirian in shape and was thus qualitatively different from that of polyacrylic acid (Misra, 1991), which exhibited an adsorption maximum. The self-association of the molecules that probably causes the maximum to occur with polyacrylic acid was effectively absent for the relatively well-ionized, electrostatically repelling polyacrylate ions of the salt. With the adsorption of acrylate ions, the concentration of phosphate ions increased monotonically, while the concentration of calcium ions showed a minimum. The adsorption of sodium polyacrylate was irreversible, as it was for polyacrylic acid.

  6. Low-molecular-weight carbohydrates from red seaweeds

    Energy Technology Data Exchange (ETDEWEB)

    Duarte, M.E.R.; Tischer, C.A.; Gorin, P.A.J.; Noseda, M.D. [Parana Univ., Curitiba, PR (Brazil). Dept. de Bioquimica

    1997-12-31

    Red algae (Rhodophyta) produce, as their principal photosynthetic metabolites, low-molecular-weight carbohydrates and polyols. The former are heterosides consisting of galactose and glycerol and are produced by all the orders of Phodophyta except the ceramiales. They are named: floridoside [{alpha}-D-galactopyranosyl (1->2)-glycerol], isofloridoside D-form [{alpha}-D-galactopyranosyl-(1->)D-glycerol] and L-form [{alpha}-D-galactopyranosyl-(1->1)-L-glycerol] (Meng et al., 1987, Karsten et al., 1993). The Ceramiales synthesize the chemically related digeneaside [{alpha}-D-mannopyranosyl-(1->2)-L-glycerate] (Kirst, 1980). Some of the red seaweeds also produce polyols such as dulcitol and D-sorbitol (Karsten et al., 1992). (author) 4 refs., 8 figs., 1 tabs.

  7. Practical Application of Aptamer-Based Biosensors in Detection of Low Molecular Weight Pollutants in Water Sources

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2018-02-01

    Full Text Available Water pollution has become one of the leading causes of human health problems. Low molecular weight pollutants, even at trace concentrations in water sources, have aroused global attention due to their toxicity after long-time exposure. There is an increased demand for appropriate methods to detect these pollutants in aquatic systems. Aptamers, single-stranded DNA or RNA, have high affinity and specificity to each of their target molecule, similar to antigen-antibody interaction. Aptamers can be selected using a method called Systematic Evolution of Ligands by EXponential enrichment (SELEX. Recent years we have witnessed great progress in developing aptamer selection and aptamer-based sensors for low molecular weight pollutants in water sources, such as tap water, seawater, lake water, river water, as well as wastewater and its effluents. This review provides an overview of aptamer-based methods as a novel approach for detecting low molecular weight pollutants in water sources.

  8. Structural Characteristics of Low Molecular Weight Laminarin Prepared by Ionizing Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jong-il [Chonnam National University, Gwangju (Korea, Republic of)

    2013-12-15

    Recently, it has been reported that low molecular weight laminarin had the enhanced biological activities. In this study, molecular structure of low molecular weight laminarin prepared by ionizing irradiation was studied. Low molecular weight laminarin samples of 13.5, 8.5, 7, and 6 kDa were obtained from 15 kDa laminarin by irradiation. From gel permeation chromatography data, low molecular weight laminarin was shown to have low polydispersity. To define the changes of functional groups in laminarin with different molecular weights, Fourier-transform infrared analysis was carried out. There was found no significant changes of functional groups in low molecular weight laminarin, except the increase of carbonyl group. The granular fissures from scanning electron microscopy showed the breakage of glycosidic bond in low molecular weight laminarin. These results could be utilized for the investigation of the enhanced biological activities of low molecular weight polysaccharides including laminarin.

  9. Low-molecular-weight heparins: pharmacologic profile and product differentiation.

    Science.gov (United States)

    Fareed, J; Jeske, W; Hoppensteadt, D; Clarizio, R; Walenga, J M

    1998-09-10

    The interchangeability of low-molecular-weight heparins (LMWHs) has been the subject of discussion since these products were first introduced for the prophylaxis of deep vein thrombosis. Experimental evidence now exists to show that LMWHs differ from each other in a number of characteristics. Products have been differentiated on the basis of molecular weight and biologic properties, but only limited information derived from the clinical setting is available. Potency has been described on the basis of anti-Factor Xa activity, but at equivalent anti-Xa activities, the anti-Factor IIa activity of different products shows marked variations. At the relatively small doses used for the management of postsurgical deep vein thrombosis, the effect of these interproduct differences may be relatively minor, but as LMWHs are developed for therapeutic use at much higher doses, such differences may become clinically important. Variations in safety and efficacy reported in clinical trials of LMWHs may reflect the known differences in their molecular composition and pharmacologic properties.

  10. Arterial indications for the low molecular weight heparins

    Directory of Open Access Journals (Sweden)

    Ageno Walter

    2001-09-01

    Full Text Available Abstract Antithrombotic treatment is of proven importance in patients with acute coronary syndromes. There is now accumulating evidence from several clinical trials in patients with unstable angina pectoris that the low molecular weight heparins (LMWHs are at least as effective as unfractionated heparin. The LMWHs are easier to use, with the potential to facilitate long-term outpatient treatment. The results of the trials have actually failed to show any clear advantage, however, of the LMWHs over the standard antiplatelet treatment, despite the evidence of a sustained hypercoagulability. Potentially, the use of higher doses of LMWHs could improve the outcomes, but this is as yet unproven and could be associated with unacceptably increased risk of bleeding. During the acute phase of a stroke, aspirin is the first choice of antithrombotic drug because it reduces the risk of recurrent stroke. LMWH cannot be recommended as an antithrombotic agent for the acute treatment of stroke. Prophylactic use of low dose LMWH for the prevention of venous thromboembolism should be considered in every patient with a stroke.

  11. Intravitreal low molecular weight heparin in PVR surgery.

    Directory of Open Access Journals (Sweden)

    Kumar Atul

    2003-01-01

    Full Text Available Purpose: To evaluate the efficacy of low molecular weight heparin (LMWH in prevention of postoperative fibrin formation following vitreoretinal surgery with proliferative vitreoretinopathy (PVR. Material and Methods: Thirty consecutive patients of retinal detachment with advanced PVR were enrolled in the study. They were randomised to study and control groups (n = 15 each. Study group patients received vitreoretinal surgery with 5 IU/cc of LMWH in vitrectomy infusion fluid. The control group patients received vitroretinal surgery without heparin in the infusion fluid. Patients were followed up at 1 week, 1 month and 3 months after surgery. Postoperative bleeding, media clarity, best-corrected visual acuity and success of the surgery at the end of 3 months were compared between the two groups. Results: At each follow-up visit, the study group showed a better media clarity, which was statistically significant ( P = 0.0042. The study group had a 50% better chance of retinal reattachment compared to the control group. Five patients had intraoperative bleeding in the study group (33% compared to 3 patients in the control group (20%. Conclusion: Use of intravitreal LMWH prevents postoperative fibrin formation and is beneficial in repair of retinal detachments with PVR.

  12. Alkyl cross-linked low molecular weight polypropyleneimine dendrimers as efficient gene delivery vectors.

    Science.gov (United States)

    Ariaee, Faezeh Moghadam; Hashemi, Maryam; Farzad, Sara Amel; Abnous, Khalil; Ramezani, Mohammad

    2016-10-01

    In recent years, polypropyleneimine (PPI) dendrimers have attracted great interest as non-viral gene delivery systems because of their attractive features including highly branched architecture with number of reactive end groups. However, without being structurally modified, they are not efficient gene carriers. In the present study, generation 2 and 3 (G2 and G3) of PPI dendrimers were conjugated with alkylcarboxylate groups as linker to enhance the transfection efficiency while maintaining their low cell toxicity. First, 10-bromodecanoic acid was covalently attached to all available surface primary amines of PPI G2 and G3 to increase their lipophilicity. In the subsequent step, PPIs were conjugated to the alkylcarboxylate groups of alkylcarboxylate-PPI derivatives to increase the number of surface primary amines. Physicochemical properties of modified PPIs were determined. Transfection experiments (using both luciferase and green fluorescent protein (GFP)- expressing plasmids) and cytotoxicity assay were performed to evaluate the efficiency of the final derivatives. Fabricated vectors condensed DNA effectively so that polyplexes with appropriate size (below 155 nm) and positive surface charge were constructed. Cross-linked low molecular weight PPIs (G2 or G3) with decanoate linkage increased transfection efficiency significantly while maintaining the low cytotoxicity. PPI G2 derivative exhibited increased buffering capacity which is believed to be responsible for better proton sponge mechanism leading to higher transfection efficiency. Our results indicated that oligomerization of low molecular weight PPI (PPI G2-alkyl-PPI G2 conjugate) could be an approach to increase the transfection efficiency and to lower the cytotoxicity of low molecular weight polycations.

  13. Biocompatibility of low molecular weight polymers for two-phase partitioning bioreactors.

    Science.gov (United States)

    Harris, Jesse; Daugulis, Andrew J

    2015-12-01

    Two phase partitioning bioreactors (TPPBs) improve the efficiency of fermentative processes by limiting the exposure of microorganisms to toxic solutes by sequestering them into a non-aqueous phase (NAP). A potential limitation of this technology, when using immiscible organic solvents as the NAP, is the cytoxicity that these materials may exert on the microbes. An improved TPPB configuration is one in which polymeric NAPs are used to replace organic solvents in order to take advantage of their low cost, improved handling qualities, and biocompatibility. A recent study has shown that low molecular weight polymers may confer improved solute uptake relative to high molecular weight polymers (i.e., have higher partition coefficients), but it is unknown whether sufficiently low molecular weight polymers may inhibit cell growth. This study has investigated the biocompatibility of a range of low molecular weight polymers, and compared trends in biocompatibility to the well-established "critical log P" concept. This was achieved by determining the biocompatibility of polypropylene glycol polymers over a molecular weight (MW) range of 425-4,000 to Saccharomyces cerevisiae and Pseudomonas putida, two organisms which have been previously used in TPPB systems. The lower MW polymers were shown to have lower average log P values, and showed more cytotoxicity than polymers of the same structure but with higher molecular weight. Since polymers are generally polydisperse (i.e., polymer samples contain a distribution of MWs), removal of the lower MW fractions via water washing was found to result in improved polymer biocompatibility. These results suggest that the critical log P concept remains useful for describing the toxicity of polymeric substances of different MWs, although it is complicated by the presence of the low MW fractions in the polymers arising from polydispersity. © 2015 Wiley Periodicals, Inc.

  14. Low molecular weight silicones particularly facilitate human serum albumin denaturation.

    Science.gov (United States)

    Nayef, Lamees M; Khan, Madiha F; Brook, Michael A

    2015-04-01

    There is a market trend towards the administration of therapeutic proteins using sterilized, pre-filled glass syringes lubricated with silicone oil. It has been widely reported that initially clear solutions of proteins can become turbid during transport and storage, with unclear outcomes with respect to bioefficacy. While the basic processes of interactions of proteins with hydrophobic entities, leading to denaturation and aggregation, are increasingly well understood, the apparently random occurrence of such processes in syringes is not. To better understand the parameters that may be responsible for this change, we report the systematic examination of a series of factors that can affect the behavior of the protein human serum albumin (HSA) when in contact with silicone oil in water. Fluorescence spectroscopy showed that greater mixing times and greater concentrations of silicones (polydimethylsiloxane (PDMS)), especially lower molecular weight hydrophobic silicones like octamethyltetracyclosiloxane (D4), were associated with increased protein denaturation. The turbidity of HSA solutions, due to the formation both of silicone oil-in-water (O/W) emulsions and protein aggregates, was also facilitated by the presence of D4. A series of mixtures of silicone oils, all of which exhibited a viscosity of 1000 cSt but which were comprised of different silicone constituents, clearly showed a correlation between the presence of lower molecular silicones and enhanced solution turbidity. While the addition of a non-ionic silicone-polyether surfactant led to greater turbidity by increasing the number of stabilized oil droplets, it was not accompanied by protein denaturation. These results are consistent with HSA denaturation and subsequent aggregation as a consequence of contact particularly with low molecular weight, hydrophobic silicones that are more mobile, leading to more efficient protein/silicone contact. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Anaphylactic reactions to low-molecular weight chemicals

    Directory of Open Access Journals (Sweden)

    Daria Nowak

    2015-02-01

    Full Text Available Low-molecular weight chemicals (haptens include a large group of chemical compounds occurring in work environment, items of everyday use (cleaning products, clothing, footwear, gloves, furniture, jewelry (earrings, bracelets, drugs, especially in cosmetics. They cause type IV hypersensitive reactions. During the induction phase of delayed-type hypersensitivity, haptens form complexes with skin proteins. After internalization through antigen presenting cells, they are bound to MHC class II molecules. Next, they are exposed against specific T-lymphocytes, what triggers activation of Th1 cells mainly. After repeating exposition to that hapten, during effector phase, Th1 induce production of cytokines affecting non-specific inflammatory cells. Usually, it causes contact dermatitis. However, occasionally incidence of immediate generalized reactions after contact with some kinds of haptens is noticed. A question arises, how the hapten does induce symptoms which are typical for anaphylaxis, and what contributes to amplification of this mechanism. It seems that this phenomenon arises from pathomechanism occurring in contact urticaria syndrome in which an anaphylactic reaction may be caused either by contact of sensitized skin with protein antigens, high-molecular weight allergens, or haptens. One of the hypotheses indicates the leading role of basophiles in this process. Their contact with haptens, may cause to release mediators of immediate allergic reaction (histamine, eicosanoids and to produce cytokines corresponding to Th2 cells profile. Furthermore, Th17 lymphocytes secreting pro-inflammatory interleukin-17 might be engaged into amplifying hypersensitivity into immediate reactions and regulatory T-cells may play role in the process, due to insufficient control of the activity of effector cells.

  16. Data set for the proteomics analysis of the endomembrane system from the unicellular Entamoeba histolytica

    Directory of Open Access Journals (Sweden)

    Doranda Perdomo

    2014-12-01

    Full Text Available Entamoeba histolytica is the protozoan parasite agent of amebiasis, an infectious disease of the human intestine and liver. This parasite contact and kills human cells by an active process involving pathogenic factors. Cellular traffic and secretion activities are poorly characterized in E. histolytica. In this work, we took advantage of a wide proteomic analysis to search for principal components of the endomembrane system in E. histolytica. A total of 5683 peptides matching with 1531 proteins (FDR of 1% were identified which corresponds to roughly 20% of the total amebic proteome. Bioinformatics investigations searching for domain homologies (Smart and InterProScan programs and functional descriptions (KEGG and GO terms allowed this data to be organized into distinct categories. This data represents the first in-depth proteomics analysis of subcellular compartments in E. histolytica and allows a detailed map of vesicle traffic components in an ancient single-cell organism that lacks a stereotypical ER and Golgi apparatus to be established. The data are related to [1].

  17. Low molecular weight heparin versus unfractionated heparin in the initial treatment of venous thromboembolism

    NARCIS (Netherlands)

    Hettiarachchi, R. J.; Prins, M. H.; Lensing, A. W.; Buller, H. R.

    1998-01-01

    In this review, we analyze data from randomized trials in which low molecular weight heparin was compared with unfractionated heparin, both to estimate the treatment effect of low molecular weight heparin in the initial treatment of venous thromboembolism and to evaluate the effect of the varied

  18. Low Molecular Weight Norbornadiene Derivatives for Molecular Solar-Thermal Energy Storage.

    Science.gov (United States)

    Quant, Maria; Lennartson, Anders; Dreos, Ambra; Kuisma, Mikael; Erhart, Paul; Börjesson, Karl; Moth-Poulsen, Kasper

    2016-09-05

    Molecular solar-thermal energy storage systems are based on molecular switches that reversibly convert solar energy into chemical energy. Herein, we report the synthesis, characterization, and computational evaluation of a series of low molecular weight (193-260 g mol(-1) ) norbornadiene-quadricyclane systems. The molecules feature cyano acceptor and ethynyl-substituted aromatic donor groups, leading to a good match with solar irradiation, quantitative photo-thermal conversion between the norbornadiene and quadricyclane, as well as high energy storage densities (396-629 kJ kg(-1) ). The spectroscopic properties and energy storage capability have been further evaluated through density functional theory calculations, which indicate that the ethynyl moiety plays a critical role in obtaining the high oscillator strengths seen for these molecules. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  19. Low Molecular Weight Norbornadiene Derivatives for Molecular Solar‐Thermal Energy Storage

    Science.gov (United States)

    Quant, Maria; Lennartson, Anders; Dreos, Ambra; Kuisma, Mikael; Erhart, Paul; Börjesson, Karl

    2016-01-01

    Abstract Molecular solar‐thermal energy storage systems are based on molecular switches that reversibly convert solar energy into chemical energy. Herein, we report the synthesis, characterization, and computational evaluation of a series of low molecular weight (193–260 g mol−1) norbornadiene–quadricyclane systems. The molecules feature cyano acceptor and ethynyl‐substituted aromatic donor groups, leading to a good match with solar irradiation, quantitative photo‐thermal conversion between the norbornadiene and quadricyclane, as well as high energy storage densities (396–629 kJ kg−1). The spectroscopic properties and energy storage capability have been further evaluated through density functional theory calculations, which indicate that the ethynyl moiety plays a critical role in obtaining the high oscillator strengths seen for these molecules. PMID:27492997

  20. Participation of Low Molecular Weight Electron Carriers in Oxidative Protein Folding

    Directory of Open Access Journals (Sweden)

    József Mandl

    2009-03-01

    Full Text Available Oxidative protein folding is mediated by a proteinaceous electron relay system, in which the concerted action of protein disulfide isomerase and Ero1 delivers the electrons from thiol groups to the final acceptor. Oxygen appears to be the final oxidant in aerobic living organisms, although the existence of alternative electron acceptors, e.g. fumarate or nitrate, cannot be excluded. Whilst the protein components of the system are well-known, less attention has been turned to the role of low molecular weight electron carriers in the process. The function of ascorbate, tocopherol and vitamin K has been raised recently. In vitro and in vivo evidence suggests that these redox-active compounds can contribute to the functioning of oxidative folding. This review focuses on the participation of small molecular weight redox compounds in oxidative protein folding.

  1. Low Molecular Weight Chitosan–Insulin Polyelectrolyte Complex: Characterization and Stability Studies

    Directory of Open Access Journals (Sweden)

    Zakieh I. Al-Kurdi

    2015-03-01

    Full Text Available The aim of the work reported herein was to investigate the effect of various low molecular weight chitosans (LMWCs on the stability of insulin using USP HPLC methods. Insulin was found to be stable in a polyelectrolyte complex (PEC consisting of insulin and LMWC in the presence of a Tris-buffer at pH 6.5. In the presence of LMWC, the stability of insulin increased with decreasing molecular weight of LMWC; 13 kDa LMWC was the most efficient molecular weight for enhancing the physical and chemical stability of insulin. Solubilization of insulin-LMWC polyelectrolyte complex (I-LMWC PEC in a reverse micelle (RM system, administered to diabetic rats, results in an oral delivery system for insulin with acceptable bioactivity.

  2. Antioxidation activities of low-molecular-weight gelatin hydrolysate isolated from the sea cucumber Stichopus japonicus

    Science.gov (United States)

    Wang, Jingfeng; Wang, Yuming; Tang, Qingjuan; Wang, Yi; Chang, Yaoguang; Zhao, Qin; Xue, Changhu

    2010-03-01

    Gelatin extracted from the body wall of the sea cucumber ( Stichopus japonicus) was hydrolyzed with flavourzyme. Low-molecular-weight gelatin hydrolysate (LMW-GH) of 700-1700 Da was produced using an ultrafiltration membrane bioreactor system. Chemiluminescence analysis revealed that LMW-GH scavenges high free radicals in a concentration-dependent manner; IC50 value for superoxide and hydroxyl radicals was 442 and 285 μg mL-1, respectively. LMW-GH exhibited excellent inhibitory characteristics against melanin synthesis and tyrosinase activity in B16 cells. Furthermore, LMW-GH notably increased intracellular glutathione (GSH), which in turn suppressed melanogenesis. LMW-GH performs antioxidation activity, holding the potential of being used as a valuable ingredient in function foods, cosmetics and pharmaceuticals or nutriceuticals.

  3. The emerging role of low-molecular-weight heparin in cardiovascular medicine.

    Science.gov (United States)

    Hirsh, J; Bates, S M

    2000-01-01

    Although unfractionated heparin is widely used in the treatment of acute coronary syndromes, it has several pharmacokinetic, biophysical, and biological limitations. The practical advantages and success of low-molecular-weight heparin administered subcutaneously without laboratory monitoring for the treatment of venous thromboembolism have prompted a number of randomized studies investigating the efficacy and safety of these agents in patients with acute coronary syndromes. This article will review the limitations of unfractionated heparin and the mechanisms by which low-molecular-weight heparin overcomes these limitations, as well as the results of recent trials involving low-molecular-weight heparin in the management of patients with acute coronary syndromes.

  4. Impact of Low Molecular Weight Poly(3-hexylthiophene)s as Additives in Organic Photovoltaic Devices.

    Science.gov (United States)

    Seibers, Zach D; Le, Thinh P; Lee, Youngmin; Gomez, Enrique D; Kilbey, S Michael

    2018-01-24

    Despite tremendous progress in using additives to enhance the power conversion efficiency of organic photovoltaic devices, significant challenges remain in controlling the microstructure of the active layer, such as at internal donor-acceptor interfaces. Here, we demonstrate that the addition of low molecular weight poly(3-hexylthiophene)s (low-MW P3HT) to the P3HT/fullerene active layer increases device performance up to 36% over an unmodified control device. Low MW P3HT chains ranging in size from 1.6 to 8.0 kg/mol are blended with 77.5 kg/mol P3HT chains and [6,6]-phenyl C 61 butyric acid methyl ester (PCBM) fullerenes while keeping P3HT/PCBM ratio constant. Optimal photovoltaic device performance increases are obtained for each additive when incorporated into the bulk heterojunction blend at loading levels that are dependent upon additive MW. Small-angle X-ray scattering and energy-filtered transmission electron microscopy imaging reveal that domain sizes are approximately invariant at low loading levels of the low-MW P3HT additive, and wide-angle X-ray scattering suggests that P3HT crystallinity is unaffected by these additives. These results suggest that oligomeric P3HTs compatibilize donor-acceptor interfaces at low loading levels but coarsen domain structures at higher loading levels and they are consistent with recent simulations results. Although results are specific to the P3HT/PCBM system, the notion that low molecular weight additives can enhance photovoltaic device performance generally provides a new opportunity for improving device performance and operating lifetimes.

  5. Low-Molecular-Weight Polyethyleneimine Grafted Polythiophene for Efficient siRNA Delivery

    Directory of Open Access Journals (Sweden)

    Pan He

    2015-01-01

    Full Text Available Owing to its hydrophilicity, negative charge, small size, and labile degradation by endogenous nucleases, small interfering RNA (siRNA delivery must be achieved by a carrier system. In this study, cationic copolymers composed of low-molecular-weight polyethylenimine and polythiophenes were synthesized and evaluated as novel self-tracking siRNA delivery vectors. The concept underlying the design of these copolymers is that hydrophobicity and rigidity of polythiophenes should enhance the transport of siRNA across the cell membrane and endosomal membrane. A gel retardation assay showed that the nanosized complexes formed between the copolymers and siRNA were stable even at a molar ratio of 1 : 2. The high cellular uptake (>80% and localization of the copolymer vectors inside the cells were easily analyzed by tracking the fluorescence of polythiophene using fluorescent microscopy and cytometry. An in vitro luciferase knockdown (KD assay in A549-luc cells demonstrated that the siRNA complexes with more hydrophobic copolymers achieved a higher KD efficiency of 52.8% without notable cytotoxicity, indicating protein-specific KD activity rather than solely the cytotoxicity of the materials. Our polythiophene copolymers should serve as novel, efficient, low cell toxicity, and label-free siRNA delivery systems.

  6. Low molecular weight thiol-dependent antioxidant and antinitrosative defenses in Salmonella pathogenesis

    Science.gov (United States)

    Song, Miryoung; Husain, Maroof; Jones-Carson, Jessica; Liu, Lin; Henard, Calvin A.; Vázquez-Torres, Andrés

    2012-01-01

    We found herein that the intracytoplasmic pool of the low-molecular weight (LMW) thiol glutathione (GSH) is readily oxidized in Salmonella exposed to nitric oxide (NO). The hypersusceptibility of gshA and gshB mutants lacking γ-glutamylcysteine and glutathione synthetases to NO and S-nitrosoglutathione indicates that GSH antagonizes the bacteriostatic activity of reactive nitrogen species. Metabolites of the GSH biosynthetic pathway do not affect the enzymatic activity of classical NO targets such as quinol oxidases. In contrast, LMW thiols diminish the nitrosative stress experienced by enzymes, such as glutamine oxoglutarate amidotransferase, that contain redox active cysteines. LMW thiols also preserve the transcription of Salmonella pathogenicity island 2 gene targets from the inhibitory activity of nitrogen oxides. These findings are consistent with the idea that GSH scavenges reactive nitrogen species (RNS) other than NO. Compared to the adaptive response afforded by inducible systems such as the hmp-encoded flavohemoprotein, gshA, encoding the first step of GSH biosynthesis, is constitutively expressed in Salmonella. An acute model of salmonellosis has revealed that the antioxidant and antinitrosative properties associated with the GSH biosynthetic pathway represent a first line of Salmonella resistance against reactive oxygen and nitrogen species engendered in the context of a functional NRAMP1R divalent metal transporter. PMID:23217033

  7. Three low molecular weight cysteine proteinase inhibitors of human seminal fluid: purification and enzyme kinetic properties.

    Science.gov (United States)

    Yadav, Vikash Kumar; Chhikara, Nirmal; Gill, Kamaldeep; Dey, Sharmistha; Singh, Sarman; Yadav, Savita

    2013-08-01

    The cystatins form a superfamily of structurally related proteins with highly conserved structural folds. They are all potent, reversible, competitive inhibitors of cysteine proteinases (CPs). Proteins from this group present differences in proteinase inhibition despite their high level of structural similarities. In this study, three cysteine proteinase inhibitors (CPIs) of low molecular weight were isolated from human seminal fluid (HSF) by affinity chromatography on carboxymethyl (CM)-papain-Sepharose column, purified using various chromatographic procedures and checked for purity on sodium-dodecyl PAGE (SDS-PAGE). Matrix-assisted laser desorption-ionization-time-of flight-mass spectrometry (MALDI-TOF-MS) identified these proteins as cystatin 9, cystatin SN, and SAP-1 (an N-terminal truncated form of cystatin S). All three CPIs suppressed the activity of papain potentially and showed remarkable heat stability. Interestingly SAP-1 also inhibits the activity of trypsin, chymotrypsin, pepsin, and PSA (prostate specific antigen) and acts as a cross-class protease inhibitor in in vitro studies. Using Surface Plasmon Resonance, we have also observed that SAP-1 shows a significant binding with all these proteases. These studies suggest that SAP-1 is a cross-class inhibitor that may regulate activity of various classes of proteases within the reproductive systems. To our knowledge, this is the first report about purification of CPIs from HSF; the identification of such proteins could provide better insights into the physiological processes and offer intimation for further research. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  8. Alginate hydrogels modified with low molecular weight hyaluronate for cartilage regeneration.

    Science.gov (United States)

    Park, Honghyun; Lee, Hyun Ji; An, Hyoseok; Lee, Kuen Yong

    2017-04-15

    Alginate is a typical biomaterial that forms hydrogels in the presence of calcium ions and has often been utilized in tissue engineering approaches. However, it lacks biofunctionality in the form of interactions with cells and proteins. Hyaluronate, a main component of glycosaminoglycans, provides CD44-specific interactions with chondrocytes but typically requires chemical cross-linking agents to fabricate hydrogels, which may cause unexpected side effects in the body. In this study, we propose the design and fabrication of a hybrid structure of alginate and hyaluronate useful for cartilage regeneration. Alginate was used as a backbone, and hyaluronate with a low molecular weight was introduced to the backbone to fabricate alginate-hyaluronate hybrid coupled by ethylenediamine. We hypothesized that alginate-hyaluronate hybrid (AH) could maintain its ability to form gels in the presence of calcium ions and could be useful for cartilage regeneration as an injectable system. Characteristics of AH hydrogels containing various composition ratios of hyaluronate to alginate were investigated, and the chondrogenic potential of ATDC5 cells encapsulated within AH hydrogels was evaluated in vitro. Consequently, AH hydrogels having a defined polymer composition and mechanical stiffness were useful to successfully regulate chondrogenic differentiation and to maintain the chondrocytic cell phenotype, which may lead to many useful applications in cartilage regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Efficient aquatic bacterial metabolism of dissolved low-molecular-weight compounds from terrestrial sources.

    Science.gov (United States)

    Berggren, Martin; Laudon, Hjalmar; Haei, Mahsa; Ström, Lena; Jansson, Mats

    2010-03-01

    Carboxylic acids (CAs), amino acids (AAs) and carbohydrates (CHs) in dissolved free forms can be readily assimilated by aquatic bacteria and metabolized at high growth efficiencies. Previous studies have shown that these low-molecular-weight (LMW) substrates are released by phytoplankton but also that unidentified LMW compounds of terrestrial origin is a subsidy for bacterial metabolism in unproductive freshwater systems. We tested the hypothesis that different terrestrially derived CA, AA and CH compounds can offer substantial support for aquatic bacterial metabolism in fresh waters that are dominated by allochthonous dissolved organic matter (DOM). Drainage water from three catchments of different characters in the Krycklan experimental area in Northern Sweden were studied at the rising and falling limb of the spring flood, using a 2-week bioassay approach. A variety of CA, AA and CH compounds were significantly assimilated by bacteria, meeting 15-100% of the bacterial carbon demand and explaining most of the observed variation in bacterial growth efficiency (BGE; R(2)=0.66). Of the 29 chemical species that was detected, acetate was the most important, representing 45% of the total bacterial consumption of all LMW compounds. We suggest that LMW organic compounds in boreal spring flood drainage could potentially support all in situ bacterial production in receiving lake waters during periods of weeks to months after the spring flood.

  10. Digging into the low molecular weight peptidome with the OligoNet web server.

    Science.gov (United States)

    Liu, Youzhong; Forcisi, Sara; Lucio, Marianna; Harir, Mourad; Bahut, Florian; Deleris-Bou, Magali; Krieger-Weber, Sibylle; Gougeon, Régis D; Alexandre, Hervé; Schmitt-Kopplin, Philippe

    2017-09-15

    Bioactive peptides play critical roles in regulating many biological processes. Recently, natural short peptides biomarkers are drawing significant attention and are considered as "hidden treasure" of drug candidates. High resolution and high mass accuracy provided by mass spectrometry (MS)-based untargeted metabolomics would enable the rapid detection and wide coverage of the low-molecular-weight peptidome. However, translating unknown masses (web server OligoNet responds to this challenge by attempting to decompose each individual mass into a combination of amino acids out of metabolomics datasets. It provides an additional network-based data interpretation named "Peptide degradation network" (PDN), which unravels interesting relations between annotated peptides and generates potential functional patterns. The ab initio PDN built from yeast metabolic profiling data shows a great similarity with well-known metabolic networks, and could aid biological interpretation. OligoNet allows also an easy evaluation and interpretation of annotated peptides in systems biology, and is freely accessible at https://daniellyz200608105.shinyapps.io/OligoNet/ .

  11. Improved method for synthesis of low molecular weight protamine–siRNA conjugate

    Directory of Open Access Journals (Sweden)

    Zhili Yu

    2018-01-01

    Full Text Available RNAi technology has aroused wide public interest due to its high efficiency and specificity to treat multiple types of diseases. However, the effective delivery of siRNA remains a challenge due to its large molecular weight and strong anionic charge. Considering their remarkable functions in vivo and features that are often desired in drug delivery carriers, biomimetic systems for siRNA delivery become an effective and promising strategy. Based on this, covalent attachment of synthetic cell penetrating peptides (CPP to siRNA has become of great interest. We developed a monomeric covalent conjugate of low molecular weight protamine (LMWP, a well-established CPP and siRNA via a cytosol-cleavable disulfide linkage using PEG as a crosslinker. Results showed that the conjugates didn't generate coagulation, and exhibited much better RNAi potency and intracellular delivery compared with the conventional charge-complexed CPP/siRNA aggregates. Three different synthetic and purification methods were compared in order to optimize synthesis efficiency and product yield. The methodology using hetero-bifunctional NHS–PEG–OPSS as a crosslinker to synthesize LMWP–siRNA simplified the synthesis and purification process and produced the highest yield. These results pave the way towards siRNA biomimetic delivery and future clinical translation.

  12. Preparation of Low Molecular Weight Heparin by Microwave Discharge Electrodeless Lamp/TiO2 Photo-Catalytic Reaction.

    Science.gov (United States)

    Lee, Do-Jin; Kim, Byung Hoon; Kim, Sun-Jae; Kim, Jung-Sik; Lee, Heon; Jung, Sang-Chul

    2015-01-01

    An MDEL/TiO2 photo-catalyst hybrid system was applied, for the first time, for the production of low molecular weight heparin. The molecular weight of produed heparin decreased with increasing microwave intensity and treatment time. The abscission of the chemical bonds between the constituents of heparin by photo-catalytic reaction did not alter the characteristics of heparin. Formation of by-products due to side reaction was not observed. It is suggested that heparin was depolymerized by active oxygen radicals produced during the MDEL/TiO2 photo-chemical reaction.

  13. Novel low-molecular-weight-gelator-based microcapsules with controllable morphology and temperature responsiveness.

    Science.gov (United States)

    Patel, Ashok R; Remijn, Caroline; Heussen, Patricia C M; den Adel, Ruud; Velikov, Krassimir P

    2013-02-04

    A new type of microcapsules with controllable morphology is presented. They are based on a low-molecular-weight gelator and can be switched from temperature-stable to temperature-responsive by simply modifying the preparation method. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. A novel low molecular weight chiral gelator for apolar organic solvents

    NARCIS (Netherlands)

    Snijder, Carina S.; Jong, Johannes C. de; Meetsma, Auke; Bolhuis, Fré van; Feringa, Bernard

    1995-01-01

    The synthesis, molecular structure, and properties of a new chiral gel-forming agent 1 are described. Key structural features in 1 are a gamma-alkoxybutyrolactone tetralin moiety and an angular phenylsulphone unit. The new low molecular weight gelator 1 can reversibly form stable gels in low

  15. Anion tuning and polymer templating in a simple low molecular weight organogelator.

    Science.gov (United States)

    Piepenbrock, Marc-Oliver M; Clarke, Nigel; Foster, Jonathan A; Steed, Jonathan W

    2011-02-21

    A simple triethoxysilane appended bis(urea) low molecular weight gelator (LMWG) affords strong gels in organic solvents that are susceptible to fine tuning by anion binding, while the gel structure can be rigidified into a porous hybrid polymer material by hydrolysis of the triethoxysilane end groups.

  16. Risk of postpartum hemorrhage in women receiving therapeutic doses of low-molecular-weight heparin

    NARCIS (Netherlands)

    Roshani, S.; Cohn, D.M.; Stehouwer, A.; Hamers, S.; Wolf, H.; Van Der Post, J.M.; Büller, H.R.; Kamphuisen, P.W.; Middeldorp, S.

    2009-01-01

    Introduction: Low-molecular-weight heparin (LMWH) is considered safe in pregnancy, but the optimal dose for prevention of venous thrombosis is unclear. Prophylactic doses may not prevent DVT adequately while higher doses may induce postpartum hemorrhage (PPH). We studied whether use of therapeutic

  17. Low molecular weight heparin as an anticoagulation strategy for left-sided ablation procedures.

    Science.gov (United States)

    Hinsley, Karen; Evans-Langhorst, Margaret; Porter, Courtney; Chandler, Stephanie; VanderPluym, Christina; Triedman, John; Bezzerides, Vassilios J

    2017-11-27

    This quality improvement study was implemented to demonstrate consistent and reliable post procedure anticoagulation for patients undergoing left-sided ablations. We evaluated the safety and efficacy of anticoagulation practice during a transition from anticoagulation with overnight infusion of unfractionated heparin to a single subcutaneous injection of low molecular weight heparin. Outcomes for patients who received unfractionated heparin from January 2014 to October 2014, were compared with outcomes of patients who received low molecular weight heparin from October 2014 to October 2015. Complications prepractice and postpractice change were documented and compared to establish confidence in the practice change and confirm the safety of the anticoagulation therapy management. There were no differences in the type or frequency of complications/adverse events demonstrated between the patients who had received unfractionated heparin for anticoagulation prophylaxis and those who received low molecular weight heparin. No thromboembolic events were reported or documented with either anticoagulation strategy. After confidence in the safety and efficacy of the practice change was established, a decision was made to discharge patients home the same day as there procedure, effectively reducing inpatient bed days and overall costs. Administration of low molecular weight heparin provides predictable anticoagulation and equally safe as unfractionated heparin when administered to patients post left-sided ablation. A secondary gain has been reduction of procedural costs by elimination of the previously required inpatient observation stay. © 2017 Wiley Periodicals, Inc.

  18. TOXICOLOGICAL HIGHLIGHT (REDOX REDUX: A CLOSER LOOK AT CONCEPTAL LOW MOLECULAR WEIGHT THIOLS)

    Science.gov (United States)

    Glutathione (GSH) is present as the most abundant low molecular weight thiol (LMWT) in virtually all mitochondria-bearing eucaryotic cells, often at millimolar concentrations (Meister, 1988). Functions of GSH include roles in DNA and protein synthesis, maintenance of cell membra...

  19. Impact modification of poly(caprolactam) by copolymerization with a low molecular weight polybutadiene

    NARCIS (Netherlands)

    Borggreve, R.J.M.; Gaymans, R.J.

    1988-01-01

    Caprolactam and a reactive, low molecular weight polybutadiene were polymerized in an autoclave, followed by post-condensation in the solid state. The rubber concentration was varied (0–30 wt%). The morphology of the reaction products was studied by transmission electron microscopy. In the materials

  20. Intercalation Study of Low-Molecular-Weight Hyperbranched Polyethyleneimine into Graphite Oxide

    NARCIS (Netherlands)

    Tsoufis, Theodoros; Katsaros, Fotios; Sideratou, Zili; Kooi, Bart J.; Karakassides, Michael. A.; Siozios, Anastasios

    2014-01-01

    We report for the first time the intercalation of low-molecular-weight hyperbranched polyethyleneimine (PEI) into graphite oxide (GO) for the facile, bulk synthesis of novel graphene-based hybrid (GO-PEI) materials exhibiting tailored interlayer galleries. The size of the intercalant as well as the

  1. Foam properties of proteins, low molecular weight surfactants and their complexes

    NARCIS (Netherlands)

    Lech, F.J.

    2016-01-01

    This thesis shows the effects that the addition of low molecular weight surfactants (LWMS) to proteins has on the foam stability of the mixture. For this, the bulk, interfacial, thin liquid films and foam properties are determined for different protein-LWMS mixtures at different molar ratios (MR).

  2. Low molecular weight Cooperia oncophora antigens. Potentials to discriminate between susceptible and resistant calves after infection.

    NARCIS (Netherlands)

    Diemen, van P.M.; Ploeger, H.W.; Nieuwland, M.G.B.; Rietveld, F.W.; Eijsker, M.; Kooijman, F.N.J.; Kloosterman, A.; Parmentier, H.K.

    1997-01-01

    The recognition of low molecular weight proteins by sera obtained during a single oral (primary) infection with 100 000 3rd-stage Cooperia oncophora larvae was studied in calves. Three groups of 6 or 7 calves were selected based on different egg excretion patterns. SDS-gel electrophoresis of adult

  3. Biomimetic studies of wood decay: Simulating the effect of low molecular weight compounds and fungal enzymes

    DEFF Research Database (Denmark)

    Hastrup, Anne Christine Steenkjær; Howell, Caitlin; Jellison, Jody

    The effect of FeCl3 (Fe3+), hydrogen peroxide (H2O2), a low molecular weight compound (2,3- Dihydroxybenzoic acid), and oxalic acid on wood were tested in a study designed to mimic wood degradation by brown rot fungi. Previous studies suggest that these components are involved in the early stages...

  4. Low molecular weight protein tyrosine phosphatases control antibiotic production in Streptomyces coelicolor A3(2)

    DEFF Research Database (Denmark)

    Sohoni, Sujata Vijay; Lieder, Sarah; Bapat, Prashant Madhusudhan

    2014-01-01

    Streptomyces coelicolor A3(2) possesses a low molecular weight protein tyrosine phosphatase (LMW-PTP),PtpA, that affects the production of undecylprodigionsin (RED) and actinorhodin (ACT). In this study we identifiedanother LMW-PTP called sco3700. Tyrosine phosphatase activity of the purified Sco...

  5. A global survey of low-molecular weight carbohydrates in lentils

    Science.gov (United States)

    Lentils contain a range of low-molecular weight carbohydrates (LMWC); however, those have not been well characterized. The objectives of this study were to (1) determine the concentrations of LMWC in lentils grown in six locations, and (2) identify any genetic and environmental effects on those LMWC...

  6. Entrapment and release of quinoline derivatives using a hydrogel of a low molecular weight gelator

    NARCIS (Netherlands)

    Friggeri, A; Feringa, BL; van Esch, J; Feringa, Bernard

    2004-01-01

    Gels of low molecular weight gelators (LMWGs) are self-assembled, thermoreversible, viscoelastic materials which can also be rendered sensitive to light, pH or chemical substances by simple chemical modifications. In addition, the ability of some of these LMWGs to gelate water (hydrogelators) makes

  7. Design and application of self-assembled low molecular weight hydrogels

    NARCIS (Netherlands)

    de Loos, M.; Feringa, B.L.; van Esch, J.

    2005-01-01

    Over the past years, the gelation of aqueous solutions by low molecular weight (LMW) compounds has become an area of increasing interest, owing to developments in the field of LMW organogelators. Until recently, LMW hydrogelators were found only by serendipity, nowadays rational design as well as

  8. Design and Application of Self-Assembled Low Molecular Weight Hydrogels

    NARCIS (Netherlands)

    Loos, Maaike de; Esch, Jan H. van; Feringa, Bernard

    2005-01-01

    Over the past years, the gelation of aqueous solutions by low molecular weight (LMW) compounds has become an area of increasing interest, owing to developments in the field of LMW organogelators. Until recently, LMW hydrogelators were found only by serendipity, nowadays rational design as well as

  9. LOW-MOLECULAR-WEIGHT PROTEINS AS CARRIERS FOR RENAL DRUG TARGETING - NAPROXEN LYSOZYME

    NARCIS (Netherlands)

    FRANSSEN, EJF; VANAMSTERDAM, RGM; VISSER, J; MOOLENAAR, F; DEZEEUW, D; MEIJER, DKF

    1991-01-01

    Low molecular weight proteins (LMWPs), such as lysozyme, may be suitable carriers to target drugs to the kidney. In this study the antiinflammatory drug naproxen was covalently bound to lysozyme (1:1). Pharmacokinetics of the conjugate, naproxen-lysozyme (nap-LYSO), were compared to that of an

  10. Modulation of Src Activity by Low Molecular Weight Protein Tyrosine Phosphatase During Osteoblast Differentiation

    NARCIS (Netherlands)

    Zambuzzi, Willian F.; Granjeiro, Jose M.; Parikh, Kaushal; Yuvaraj, Saravanan; Peppelenbosch, Maikel P.; Ferreira, Carmen V.

    2008-01-01

    Background: Src kinase plays a critical role in bone metabolism, particularly in osteoclasts. However, the ability of Src kinase to modulate the activity of other bone cells is less well understood. In this work, we examined the expression and activity of Src and low molecular weight protein

  11. The effect of self-sorting and co-assembly on the mechanical properties of low molecular weight hydrogels

    Science.gov (United States)

    Colquhoun, Catherine; Draper, Emily R.; Eden, Edward G. B.; Cattoz, Beatrice N.; Morris, Kyle L.; Chen, Lin; McDonald, Tom O.; Terry, Ann E.; Griffiths, Peter C.; Serpell, Louise C.; Adams, Dave J.

    2014-10-01

    Self-sorting in low molecular weight hydrogels can be achieved using a pH triggered approach. We show here that this method can be used to prepare gels with different types of mechanical properties. Cooperative, disruptive or orthogonal assembled systems can be produced. Gels with interesting behaviour can be also prepared, for example self-sorted gels where delayed switch-on of gelation occurs. By careful choice of gelator, co-assembled structures can also be generated, which leads to synergistic strengthening of the mechanical properties.Self-sorting in low molecular weight hydrogels can be achieved using a pH triggered approach. We show here that this method can be used to prepare gels with different types of mechanical properties. Cooperative, disruptive or orthogonal assembled systems can be produced. Gels with interesting behaviour can be also prepared, for example self-sorted gels where delayed switch-on of gelation occurs. By careful choice of gelator, co-assembled structures can also be generated, which leads to synergistic strengthening of the mechanical properties. Electronic supplementary information (ESI) available: Full experimental and synthetic details for the dipeptides, full experimental descriptions, further NMR, single crystal diffraction data, fXRD data and SANS data. See DOI: 10.1039/c4nr04039b

  12. Preparation, characterization and applications of low-molecular-weight alginate-oligochitosan nanocapsules

    Science.gov (United States)

    Wang, Ting; He, Nongyue

    2010-02-01

    The development of drug-delivering nanoparticles from natural materials for various biomedical applications is an area of great promise. However, the contradictory data on their uncontrollable diameter, unstable structure and toxic effects, highlight the need to study their preparation, characterization and cytotoxic effects in cells. In this work, nanocapsules are made from a type of W/O microemulsion system with low-molecular-weight alginate (LMWALG) and oligochitosan (OCS). The particles possess excellent biocompatibility and good biodegradability. The size of capsules is controlled and optimized by carefully adjusting the molecular weight and concentration of LMWALG and OCS. We found, from orthogonal experiments, the encapsulation time leading to a uniform size distribution with an average diameter of 136 nm. Furthermore, we found that molecular weights of LMWALG and OCS significantly influence the stability and size of capsules. The optimized nanocapsules are further used to study the drug release of BSA. Results show that the efficiency of encapsulation approximately reaches 88.4% and the concentration of BSA in phosphate-buffered solution (PBS, pH = 7.4) is well maintained at a level of 35 to 40% from 12 h to 48 h, due to the stable and slow degradation of the nanocapusules. The biocompatibility of LMWALG/OCS nanocapsules is cross-examined by cytotoxicity experiments and acute systemic toxicological tests, and they were found to enhance the survival rate of the cells from 80.30 to 95.39% in 7 days. The synthesized nanocapsules exhibit high biocompatibility, non-toxicity, biodegradation, and uniform size, providing a new potential candidate for drug releases in clinic experiments.

  13. Factors influencing the transfection efficiency of ultra low molecular weight chitosan/hyaluronic acid nanoparticles.

    Science.gov (United States)

    Duceppe, Nicolas; Tabrizian, Maryam

    2009-05-01

    The present work describes nanoparticles made of ultra low molecular weight chitosan (ULMWCh)/hyaluronic acid (HA) as novel potential carriers for gene delivery. Small and monodispersed nanoparticles with high in vitro transfection capabilities have been obtained by the complexation of these two polyelectrolytes. ULMWCh (over the higher molecular weight chitosan for clinical applications, namely increased solubility at physiological pH and improved DNA release. The ULMWCh:HA ratio and the HA molecular weights were varied with the aim of obtaining particles in the 100 nm range. Using chitosan (Ch) with a molecular weight of 5 kDa, HA with a molecular weight of 64 kDa, and a weight ratio of 4:1, nanoparticles with a Z-average size of 146+/-1 nm and narrow size distribution (polydispersity index: 0.073+/-0.030) were obtained. Nanoparticle images taken in dry conditions by SEM and AFM showed spherical particles. The optimal pH for transfection ranged from 6.4 to 6.8 for 0.25 microg of EGFP plasmid per well, with an incubation time of 4 h. Using these optimized parameters, DNA/ULMWCh:HA nanoparticles successfully transfected 25+/-1% of the 293T cells with pEGFP, compared to 0.7% obtained for DNA/ULMWCh under the same conditions. This high transfection efficiency of our non-viral gene delivery system could be attributed to the synergic effect of ULMWCh and low charge density of the HA chain for easy release of DNA which makes the system suitable for targeted gene delivery.

  14. Evolutionary Design of Low Molecular Weight Organic Anolyte Materials for Applications in Nonaqueous Redox Flow Batteries.

    Science.gov (United States)

    Sevov, Christo S; Brooner, Rachel E M; Chénard, Etienne; Assary, Rajeev S; Moore, Jeffrey S; Rodríguez-López, Joaquín; Sanford, Melanie S

    2015-11-18

    The integration of renewable energy sources into the electric grid requires low-cost energy storage systems that mediate the variable and intermittent flux of energy associated with most renewables. Nonaqueous redox-flow batteries have emerged as a promising technology for grid-scale energy storage applications. Because the cost of the system scales with mass, the electroactive materials must have a low equivalent weight (ideally 150 g/(mol·e(-)) or less), and must function with low molecular weight supporting electrolytes such as LiBF4. However, soluble anolyte materials that undergo reversible redox processes in the presence of Li-ion supports are rare. We report the evolutionary design of a series of pyridine-based anolyte materials that exhibit up to two reversible redox couples at low potentials in the presence of Li-ion supporting electrolytes. A combination of cyclic voltammetry of anolyte candidates and independent synthesis of their corresponding charged-states was performed to rapidly screen for the most promising candidates. Results of this workflow provided evidence for possible decomposition pathways of first-generation materials and guided synthetic modifications to improve the stability of anolyte materials under the targeted conditions. This iterative process led to the identification of a promising anolyte material, N-methyl 4-acetylpyridinium tetrafluoroborate. This compound is soluble in nonaqueous solvents, is prepared in a single synthetic step, has a low equivalent weight of 111 g/(mol·e(-)), and undergoes two reversible 1e(-) reductions in the presence of LiBF4 to form reduced products that are stable over days in solution.

  15. [Treatment of iron deficiency in predialysis state by low molecular weight iron dextran high doses intravenously].

    Science.gov (United States)

    Fievet, Patrick; Coppin, Mathilde; Brazier, François; Lefèvre, Magali; Stephan, Robin; Demontis, Renato

    2012-02-01

    Anemia is a common complication of chronic kidney disease (CKD) in predialysis stage. Iron deficiency is more common than in normal patients and plays a key role in the genesis of anemia. Its correction avoids the use of erythropoiesis stimulating agents (ESA) or reduces their dosage. Treatment with oral iron is often poorly tolerated and ineffective, necessitating the use of intravenous iron. New forms of injectable iron allow the use of high doses and correct iron deficiency in a single administration with consequent preservation of venous capital and lower costs. We studied the effectiveness of iron dextran of low molecular weight (LMWID) in high doses to correct iron deficiency and treat anemia in predialysis CKD patients. Twenty-nine doses of 500 to 1600 mg were administered to 25 patients followed for CKD (GFR between 60 and 10 ml/min per 1.73 m(2)), selected on biological criteria of iron deficiency defined by a ratio of transferrin saturation (TSAT) iron overload. Their serum ferritin was higher than the rest of the population before treatment, while the TSAT was no different, reflecting a functional deficiency. Their hemoglobin did not increase after treatment in contrast to the rest of the population suggesting the unavailability of iron for erythropoiesis with accumulation in the reticuloendothelial system. Renal function did not change significantly and there were no cases of acute renal failure. No immediate side effect was observed. Three patients presented delayed reactions to such self-limiting myalgia and arthralgia. No venous inflammatory reaction was noted. The administration of high doses of LMWID is effective in treating anemia of CKD in the predialysis stage with a satisfactory tolerance, without affecting kidney function and helps preserve the venous capital. It should be reserved for patients whose serum ferritin is less than or equal to 150 μg/L. Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights

  16. Auricularia auricular polysaccharide-low molecular weight chitosan polyelectrolyte complex nanoparticles: Preparation and characterization

    Directory of Open Access Journals (Sweden)

    Wei Xiong

    2016-06-01

    Full Text Available Novel polyelectrolyte complex nanoparticles (AAP/LCS NPs were prepared in this study and these were produced by mixing negatively charged auricularia auricular polysaccharide (AAP with positively charged low molecular weight chitosan (LCS in an aqueous medium. The AAP was extracted and purified from auricularia auricular, and then characterized by micrOTOF-Q mass spectrometry, UV/Vis spectrophotometry, moisture analyzer and SEM. The yield, moisture, and total sugar content of the AAP were 4.5%, 6.2% and 90.12% (w/w, respectively. The AAP sample was water-soluble and exhibited white flocculence. The characteristics of AAP/LCS NPs, such as the particle size, zeta potential, morphology, FT-IR spectra, DSC were investigated. The results obtained revealed that the AAP/LCS NPs had a spherical shape with a diameter of 223 nm and a smooth surface, and the results of the FT-IR spectra and DSC investigations indicated that there was an electrostatic interaction between the two polyelectrolyte polymers. Bovine serum albumin (BSA, pI = 4.8 and bovine hemoglobin (BHb, pI = 6.8 were used as model drugs to investigate the loading and release features of the AAP/LCS NPs. The results obtained showed that the AAP/LCS NPs had a higher entrapment efficiency (92.6% for BHb than for BSA (81.5%. The cumulative release of BSA and BHb from AAP/LCS NPs after 24 h in vitro was 95.4% and 91.9%, respectively. The in vitro release demonstrated that AAP/LCS NPs provided a sustained release matrix suitable for the delivery of protein drugs. These studies demonstrate that AAP/LCS NPs have a very promising potential as a delivery system for protein drugs.

  17. Synthesis and self-assembly of 1-deoxyglucose derivatives as low molecular weight organogelators

    Directory of Open Access Journals (Sweden)

    Sherwin Cheuk

    2011-02-01

    Full Text Available Low molecular weight gelators are an important class of molecules. The supramolecular gels formed by carbohydrate derived low molecular weight gelators are interesting soft materials that show great potential for many applications. Previously, we have synthesized a series of methyl 4,6-O-benzylidene-α-D-glucopyranoside derivatives and found that several of them are good gelators for water, aqueous mixtures of DMSO, or aqueous mixtures of ethanol. The gelation efficiency of these glycolipid derivatives is dependent upon the structures of their acyl chains. In order to understand the influence of the anomeric position of the sugar headgroup towards self-assembly, we synthesized a series of 1-deoxyglucose analogs, and examined their gelation properties in several solvents. Several long chain esters, including diacetylene containing esters, and aryl esters exhibited gelation in ethanol, aqueous ethanol, or aqueous DMSO. The synthesis and characterization of these novel analogs are reported.

  18. Synthesis and self-assembly of 1-deoxyglucose derivatives as low molecular weight organogelators.

    Science.gov (United States)

    Wang, Guijun; Yang, Hao; Cheuk, Sherwin; Coleman, Sherman

    2011-02-21

    Low molecular weight gelators are an important class of molecules. The supramolecular gels formed by carbohydrate derived low molecular weight gelators are interesting soft materials that show great potential for many applications. Previously, we have synthesized a series of methyl 4,6-O-benzylidene-α-D-glucopyranoside derivatives and found that several of them are good gelators for water, aqueous mixtures of DMSO, or aqueous mixtures of ethanol. The gelation efficiency of these glycolipid derivatives is dependent upon the structures of their acyl chains. In order to understand the influence of the anomeric position of the sugar headgroup towards self-assembly, we synthesized a series of 1-deoxyglucose analogs, and examined their gelation properties in several solvents. Several long chain esters, including diacetylene containing esters, and aryl esters exhibited gelation in ethanol, aqueous ethanol, or aqueous DMSO. The synthesis and characterization of these novel analogs are reported.

  19. Role of Laccase and Low Molecular Weight Metabolites from Trametes versicolor in Dye Decolorization

    Directory of Open Access Journals (Sweden)

    Diego Moldes

    2012-01-01

    Full Text Available The studies regarding decolorization of dyes by laccase may not only inform about the possible application of this enzyme for environmental purposes, but also may provide important information about its reaction mechanism and the influence of several factors that could be involved. In this paper, decolorization of crystal violet and phenol red was carried out with different fractions of extracellular liquids from Trametes versicolor cultures, in order to describe the role of laccase in this reaction. Moreover, the possible role of the low molecular weight metabolites (LMWMs also produced by the fungus was evaluated. The results confirm the existence of a nonenzymatic decolorization factor, since the nonprotein fraction of the extracellular liquids from cultures of T. versicolor has shown decolorization capability. Several experiments were performed in order to identify the main compounds related to this ability, which are probably low molecular weight peroxide compounds.

  20. Low-molecular-weight or unfractionated heparin in venous thromboembolism: the influence of renal function.

    Science.gov (United States)

    Trujillo-Santos, Javier; Schellong, Sebastian; Falga, Conxita; Zorrilla, Vanessa; Gallego, Pedro; Barrón, Manuel; Monreal, Manuel

    2013-05-01

    In patients with acute venous thromboembolism and renal insufficiency, initial therapy with unfractionated heparin may have some advantages over low-molecular-weight heparin. We used the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) Registry data to evaluate the 15-day outcome in 38,531 recruited patients. We used propensity score matching to compare patients treated with unfractionated heparin with those treated with low-molecular-weight heparin in 3 groups stratified by creatinine clearance levels at baseline: >60 mL/min, 30 to 60 mL/min, or 60 mL/min (n = 1598 matched pairs), 30 to 60 mL/min (n = 277 matched pairs), and 60 mL/min or <30 mL/min, but not in those with levels between 30 and 60 mL/min. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Influence of Blood Viscosity on Blood Flow and the Effect of Low Molecular Weight Dextran

    Science.gov (United States)

    Dormandy, John A.

    1971-01-01

    Changes in whole blood viscosity are related to changes in the leg blood flow during infusions of low-molecular-weight dextran and Hartmann's solution. A close inverse correlation exists between changes in viscosity and blood flow, the change in blood flow being about three times greater than the change in blood viscosity. The dextran and Hartmann's solution had a similar effect on blood viscosity and blood flow if corrections are made for the difference in haemodilution. PMID:5129616

  2. Antioxidative low molecular weight compounds in marinated herring (Clupea harengus) salt brine

    DEFF Research Database (Denmark)

    Gringer, Nina; Safafar, Hamed; du Mesnildot, Axelle

    2016-01-01

    This study aimed at unravelling the antioxidative capacity of low molecular weight compounds (LMWC) (peptides, amino acids and phenolic acids) present in salt brines from the marinated herring production. Brines were fractionated into ... using size exclusion chromatography. All samples were analysed for protein, total phenolic content (TPC) and antioxidant activities. Protein-enriched samples were pooled (P1, P2 and P3) and analysed for phenolic acids, total amino acids and peptide/protein sequence using advanced mass spectrometry. All...

  3. Low molecular-weight phenols in Tannat wines made by alternative winemaking procedures.

    Science.gov (United States)

    Favre, Guzmán; Peña-Neira, Álvaro; Baldi, Cecilia; Hernández, Natalia; Traverso, Sofía; Gil, Graciela; González-Neves, Gustavo

    2014-09-01

    Low molecular weight phenols of Tannat red wines produced by Traditional Maceration (TM), Prefermentative Cold Maceration (PCM), Maceration Enzyme (ENZ) and grape-Seed Tannins additions (ST), were performed and discussed. Alternatives to TM increased wine phenolic contents but unequally, ST increased mainly smaller flavans-3-ol, PCM anthocyanins and ENZ proanthocyanidins (up to 2250 mg/L). However low molecular weight flavan-3-ols remained below 9 mg/L in all wines, showing that there is not necessarily a correspondence between wine richness in total tannins and flavan-3-ols contents at low molecular weight. PCM wines had particularly high concentrations of tyrosol and tryptophol, yeast metabolism derived compounds. The use of grape-seed enological tannins did not increase grape seed derived phenolic compounds such as gallic acid. Caftaric acid was found in concentrations much higher than those reported in other grape varieties. Wine phenolic content and composition was considerably affected by the winemaking procedures tested. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Update on the clinical use of the low-molecular-weight heparin, parnaparin

    Directory of Open Access Journals (Sweden)

    Giuseppe Camporese

    2009-09-01

    Full Text Available Giuseppe Camporese1, Enrico Bernardi2, Franco Noventa31Unit of Angiology and 3Department of Clinical and Experimental Medicine, Clinical Epidemiology Group, University Hospital of Padua, Italy; 2Department of Emergency and Accident Medicine, Hospital of Conegliano Veneto, ItalyAbstract: Parnaparin is a low-molecular-weight heparin that has widely shown its efficacy and safety in prevention of venous thromboembolism, in the treatment of chronic venous disorders, and in the treatment of venous and arterial (stable and unstable angina, acute ST-segment elevation myocardial infarction thrombosis. Parnaparin at the respective dosages of 3200, 4250, 6400, or 12800 IUaXa for a period ranging from 3 to 5 days to 6 months, is usually administered subcutaneously by means of once-daily regimen and is better tolerated than unfractionated heparin at the injection site. In the variety of commercially available low-molecular-weight heparins, parnaparin represents a useful therapeutic option, even though little evidence is available comparing the superiority or the equivalent efficacy and safety of parnaparin to that of the unfractionated heparin or placebo. This review summarizes the available literature on the use of parnaparin in different settings of cardiovascular diseases, including papers published during the past year and ongoing studies.Keywords: low-molecular-weight heparin, heparin, parnaparin, acute coronary syndromes, venous thromboembolism

  5. Cellular Viscosity in Prokaryotes and Thermal Stability of Low Molecular Weight Biomolecules.

    Science.gov (United States)

    Cuecas, Alba; Cruces, Jorge; Galisteo-López, Juan F; Peng, Xiaojun; Gonzalez, Juan M

    2016-08-23

    Some low molecular weight biomolecules, i.e., NAD(P)H, are unstable at high temperatures. The use of these biomolecules by thermophilic microorganisms has been scarcely analyzed. Herein, NADH stability has been studied at different temperatures and viscosities. NADH decay increased at increasing temperatures. At increasing viscosities, NADH decay rates decreased. Thus, maintaining relatively high cellular viscosity in cells could result in increased stability of low molecular weight biomolecules (i.e., NADH) at high temperatures, unlike what was previously deduced from studies in diluted water solutions. Cellular viscosity was determined using a fluorescent molecular rotor in various prokaryotes covering the range from 10 to 100°C. Some mesophiles showed the capability of changing cellular viscosity depending on growth temperature. Thermophiles and extreme thermophiles presented a relatively high cellular viscosity, suggesting this strategy as a reasonable mechanism to thrive under these high temperatures. Results substantiate the capability of thermophiles and extreme thermophiles (growth range 50-80°C) to stabilize and use generally considered unstable, universal low molecular weight biomolecules. In addition, this study represents a first report, to our knowledge, on cellular viscosity measurements in prokaryotes and it shows the dependency of prokaryotic cellular viscosity on species and growth temperature. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  6. Investigating protein-protein interactions in the plant endomembrane system using multiphoton-induced FRET-FLIM.

    Science.gov (United States)

    Schoberer, Jennifer; Botchway, Stanley W

    2014-01-01

    Real-time noninvasive fluorescence-based protein assays enable a direct access to study interactions in their natural environment and hence overcome the limitations of other methods that rely on invasive cell disruption techniques. The determination of Förster resonance energy transfer (FRET) by means of fluorescence lifetime imaging microscopy (FLIM) is currently the most advanced method to observe protein-protein interactions at nanometer resolution inside single living cells and in real-time. In the FRET-FLIM approach, the information gained using steady-state FRET between interacting proteins is considerably improved by monitoring changes in the excited-state lifetime of the donor fluorophore where its quenching in the presence of the acceptor is evidence for a direct physical interaction. The combination of confocal laser scanning microscopy with the sensitive advanced technique of time-correlated single photon counting allows the mapping of the spatial distribution of fluorescence lifetimes inside living cells on a pixel-by-pixel basis that is the same as the fluorescence image. Moreover, the use of multiphoton excitation particularly for plant cells provides further advantages such as reduced phototoxicity and photobleaching. In this protocol, we briefly describe the instrumentation and experimental design to study protein interactions within the plant endomembrane system, with a focus on the imaging of plant cells expressing fluorescent proteins and acquisition and analysis of fluorescence lifetime resolved data.

  7. Caenorhabditis elegans SNAP-29 is required for organellar integrity of the endomembrane system and general exocytosis in intestinal epithelial cells

    Science.gov (United States)

    Sato, Miyuki; Saegusa, Keiko; Sato, Katsuya; Hara, Taichi; Harada, Akihiro; Sato, Ken

    2011-01-01

    It is generally accepted that soluble N-ethylmaleimide–sensitive factor attachment protein receptors mediate the docking and fusion of transport intermediates with target membranes. Our research identifies Caenorhabditis elegans homologue of synaptosomal-associated protein 29 (SNAP-29) as an essential regulator of membrane trafficking in polarized intestinal cells of living animals. We show that a depletion of SNAP-29 blocks yolk secretion and targeting of apical and basolateral plasma membrane proteins in the intestinal cells and results in a strong accumulation of small cargo-containing vesicles. The loss of SNAP-29 also blocks the transport of yolk receptor RME-2 to the plasma membrane in nonpolarized oocytes, indicating that its function is required in various cell types. SNAP-29 is essential for embryogenesis, animal growth, and viability. Functional fluorescent protein–tagged SNAP-29 mainly localizes to the plasma membrane and the late Golgi, although it also partially colocalizes with endosomal proteins. The loss of SNAP-29 leads to the vesiculation/fragmentation of the Golgi and endosomes, suggesting that SNAP-29 is involved in multiple transport pathways between the exocytic and endocytic organelles. These observations also suggest that organelles comprising the endomembrane system are highly dynamic structures based on the balance between membrane budding and fusion and that SNAP-29–mediated fusion is required to maintain proper organellar morphology and functions. PMID:21613542

  8. Citrate compared to low molecular weight heparin anticoagulation in chronic hemodialysis patients.

    Science.gov (United States)

    Janssen, M J; Deegens, J K; Kapinga, T H; Beukhof, J R; Huijgens, P C; van Loenen, A C; van der Meulen, J

    1996-03-01

    Citrate and nadroparin calcium, a low molecular weight heparin (LMWH), were compared in a randomized cross-over trial in 21 chronic hemodialysis patients regarding anticoagulation, calcium and magnesium kinetics, biocompatibility, dialysis efficiency, and aluminum contamination. Citrate was infused into the arterial line at a minimum rate of 0.68 mmol/min, combined with a calcium and magnesium-free dialysate and intravenous supplementation of calcium and magnesium at rates of 0.22 and 0.10 mmol/min, respectively. Seven patients with a dialysis session of six hours, received 2/3 of the nadroparin dose predialysis, and 1/3 after 2.5 hours (divided dose (DD) group). A single predialysis bolus injection of nadroparin was administered to eight patients not on coumarins [single dose (SD) group] and to six patients on coumarins [single dose + coumarins (SD + C) group], all with a dialysis session of four hours. Nineteen patients received a nadroparin dose of 200 ICU/kg. Two patients with a single dose, one of them on coumarins, received a dose of 150 ICU/kg because of a hematocrit containing 1.5 mmol/liter calcium and 0.75 mmol/liter magnesium used in combination with nadroparin. Ionized calcium increments during citrate were significant after the end of dialysis, while the dialysate containing 1.5 mmol/liter calcium induced significant increments during and postdialysis. No differences were observed between citrate and nadroparin regarding biocompatibility), (expressed as dialysis-induced leukopenia and thrombocytopenia), and dialysis efficiency [measured as dialyzer urea and creatinine clearance, normalized weekly whole body urea clearance (Kt/Vurea) and time averaged urea concentration (TACurea)]. The citrate solution, if sterilized in glass bottles, contained 2 to 3 micrograms aluminum per mmol citrate, the nadroparin solution 0.009 microgram per 1,000 ICU. Aluminum contamination of the citrate solution was prevented by sterilizing the solution in polypropylene

  9. Rheological Properties of Gels from Pyrene Based Low Molecular Weight Gelators

    Science.gov (United States)

    Leivo, Kimmo T.; Hahma, Arno P.

    2008-07-01

    Gels of pyrene derived low molecular weight organogelators (LMOGs) in primary alcohols have been characterized by rheometry and scanning electron microscopy. Total gelator concentration was 1-2.7 % w/w depending on the solvent and the gelator, including equimolar amounts of the gelator and 2,4,7-trinitrofluorenone (TNF), which is necessary for gelation. Thermoreversible and strongly shear thinning gels were achieved as the two components interact non-covalently to form a gel network. A qualitative correlation between the rheological properties and the nanoscale gel structure were found.

  10. Low-Molecular-Weight Heparin Use in a Case of Noncardiogenic Multifocal Perinatal Thromboembolic Stroke

    Directory of Open Access Journals (Sweden)

    Matthew A. Saxonhouse

    2009-01-01

    Full Text Available A full-term neonate suffered multifocal cerebral infarctions due to multiple large vessel thrombi. Thrombophilia and cardiovascular assessments were negative, but due to the severity of the lesions and the concern for expansion of the thrombi or future embolic events, treatment with low-molecular-weight heparin (LMWH was initiated. No complications from treatment were experienced. We present this severe case in order to highlight difficult management decisions for newborns with multifocal perinatal thromboembolic stroke and to stress the need for further practice guidelines and research in this area.

  11. Optimization of gradient reversed phase chromatographic peak capacity for low molecular weight solutes.

    Science.gov (United States)

    Soliven, Arianne; Haidar Ahmad, Imad A; Filgueira, Marcelo R; Carr, Peter W

    2013-01-18

    A general protocol for optimizing peak capacity for the separation of low molecular weight molecules under gradient elution conditions has not yet been developed. By studying the effects of gradient time, flow rate, temperature, final eluent composition, and column length on peak capacity, a protocol has been developed for the optimization of a separation of small molecules such as those seen in metabolomic studies. The strategy developed employs the Linear-Solvent-Strength Theory (LSS Theory) to predict retention, building on an approach for the optimization of the peak capacity of large molecules (peptides) in fixed column format separations. Published by Elsevier B.V.

  12. A Multidisciplinary Study of Ciguatoxin and Related Low Molecular Weight Toxins from Marine Source

    Science.gov (United States)

    1986-08-01

    Enzen, J. Clardy, Y. Gopichand and F.J. Schmitz. Okadaic acid, a cytotoxic polyether from two marine sponges of the species Helichondria. J. Am. Chem...ciguatera toxin. Nature 189:229-330, 196 1.. 12. Grenade, H.R., P.C. Cheng and N.J. Doorenbos. Ciguatera I. Brine shrimp (Artemia saline L.) larval assay...Ln ADa I iic Ek A MULTIDISCIPLINARY STUDY OF CIGUATOXIN AND SRELATED LOW MOLECULAR WEIGHT TOXINS FROM MARINE SOURCES ANNUAL REPORT LESLIE E. BAILEY

  13. Spatial distributions of and diurnal variations in low molecular weight carbonyl compounds in coastal seawater, and the controlling factors

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Kazuhiko, E-mail: takedaq@hiroshima-u.ac.jp [Graduate School of Biosphere Science, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8521 (Japan); Katoh, Shinya; Mitsui, Yumi; Nakano, Shinichi [Graduate School of Biosphere Science, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8521 (Japan); Nakatani, Nobutake [Graduate School of Biosphere Science, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8521 (Japan); Department of Environmental and Symbiotic Sciences, Rakuno Gakuen University, 582 Bunkyodai-Midorimachi, Ebetsu, Hokkaido 069-8501 (Japan); Sakugawa, Hiroshi [Graduate School of Biosphere Science, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8521 (Japan)

    2014-09-15

    We studied the spatial distributions of and the diurnal variations in four low molecular weight (LMW) carbonyl compounds, formaldehyde, acetaldehyde, propionaldehyde, and glyoxal, in coastal seawater. The samples were taken from the coastal areas of Hiroshima Bay, the Iyo Nada, and the Bungo Channel, western Japan. The formaldehyde, acetaldehyde, and glyoxal concentrations were higher in the northern part of Hiroshima Bay than at offshore sampling points in the Iyo Nada and the Bungo Channel. These three compounds were found at much higher concentrations in the surface water than in deeper water layers in Hiroshima Bay. It is noteworthy that propionaldehyde was not detected in any of the seawater samples, the concentrations present being lower than the detection limit (1 nanomole per liter (nM)) of the high performance liquid chromatography (HPLC) system we used. Photochemical and biological experiments were performed in the laboratory to help understand the characteristic distributions and fates of the LMW carbonyl compounds. The primary process controlling their fate in the coastal environment appears to be their biological consumption. The direct photo degradation of propionaldehyde, initiated by ultraviolet (UV) absorption, was observed, although formaldehyde and acetaldehyde were not degraded by UV irradiation. Our results suggest that the degradation of the LMW carbonyl compounds by photochemically formed hydroxyl radicals is relatively insignificant in the study area. Atmospheric deposition is a possible source of soluble carbonyl compounds in coastal surface seawater, but it may not influence the carbonyl concentrations in offshore waters. - Highlights: • Low molecular weight (LMW) carbonyl compounds in coastal seawater were determined. • Photochemical productions of LMW carbonyl compounds in seawater were observed. • LMW carbonyl compounds were largely consumed biologically. • Photochemical degradation was relatively insignificant in the study area.

  14. A low molecular weight polysaccharide isolated from Agaricus blazei suppresses tumor growth and angiogenesis in vivo.

    Science.gov (United States)

    Niu, Y C; Liu, J C; Zhao, X M; Wu, X X

    2009-01-01

    Previous studies indicated that the low molecular weight polysaccharide extracts from Agaricus blazei are potential antitumor agents or adjuvant in tumor treatment. In this study, we investigated the antitumor activity of LMPAB, a low molecular weight polysaccharide isolated from Agaricus blazei, and the molecular mechanisms of its antitumor activity. The antitumor effect of LMPAB was examined using mouse sarcoma 180 (S180) xenograft models. Antiangiogenic effect of LMPAB was determined by chicken embryo chorioallantoic membrane (CAM) angiogenesis and Matrigel-induced neovascularization in vivo models. The mRNA and protein levels of vascular endothelial growth factor (VEGF) were assessed using real-time reverse transcription-polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assays. Tumor inhibitory rates in the S180 xenograft models were 9.7, 23.9, and 33.0%, respectively, after administration of LMPAB at dose of 50, 100, and 200 mg/kg/day for 2 weeks. LMPAB also inhibited angiogenesis in the CAM model and Matrigel-induced neovascularization in C57BL/6 mice. The mRNA and protein levels of VEGF in tumor tissues were significantly down-regulated in the BALB/c mice received LMPAB treatment. Furthermore, significant down-regulation of serum VEGF levels was also observed in the mice. Our data suggest that LMPAB might be a promising agent for tumor therapy, and the antitumor and antiangiogenic effects of LMPAB may be related with down-regulation of VEGF.

  15. Production and characterization of a low-molecular-weight bacteriocin from Bacillus licheniformis MKU3.

    Science.gov (United States)

    Kayalvizhi, N; Gunasekaran, P

    2008-12-01

    Enhancing production and characterization of a low-molecular-weight bacteriocin from Bacillus licheniformis MKU3. The culture supernatant of B. licheniformis MKU3 exhibited bacteriocin-like activity against gram-positive and -negative bacteria and different fungi and yeast. SDS-PAGE analysis of the extracellular proteins of B. licheniformis MKU3 revealed a bacteriocin-like protein with a molecular mass of 1.5 kDa. This bacteriocin activity was found to be stable under a pH range of 3.0-10.0 and at temperatures up to 100 degrees C for 60 min, but inactivated by proteinase K, trypsin or pronase E. An experimental fractional factorial design for optimization of production medium resulted in a maximum activity of bacteriocin (11,000 AU ml(-1)) by B. licheniformis MKU3. A low-molecular-weight bacteriocin-like protein from B. licheniformis MKU3 exhibited a wide spectrum of antimicrobial activity against several gram-positive bacteria, several fungi and yeast. A 3.6-fold increase in the production of bacteriocin was achieved using the culture medium optimized through a fractional factorial design. A bacteriocin with wide spectrum of activity against gram-positive bacterial pathogens, filamentous fungi and yeast suggested its potential clinical use. Statistical method facilitated optimization of cultural medium for the improved production of bacteriocin.

  16. Insights into the Toxicological Properties of a Low Molecular Weight Fraction from Zoanthus sociatus (Cnidaria)

    Science.gov (United States)

    Domínguez-Pérez, Dany; Diaz-Garcia, Carlos Manlio; García-Delgado, Neivys; Sierra-Gómez, Yusvel; Castañeda, Olga; Antunes, Agostinho

    2013-01-01

    The phylum Cnidaria is an ancient group of venomous animals, specialized in the production and delivery of toxins. Many species belonging to the class Anthozoa have been studied and their venoms often contain a group of peptides, less than 10 kDa, that act upon ion channels. These peptides and their targets interact with high affinity producing neurotoxic and cardiotoxic effects, and even death, depending on the dose and the administration pathway. Zoanthiniaria is an order of the Subclass Hexacorallia, class Anthozoa, and unlike sea anemone (order Actiniaria), neither its diversity of toxins nor the in vivo effects of the venoms has been exhaustively explored. In this study we assessed some toxicological tests on mice with a low molecular weight fraction obtained by gel filtration in Sephadex G-50 from Zoanthus sociatus crude extract. The gel filtration chromatogram at 280 nm revealed two major peaks, the highest absorbance corresponding to the low molecular weight fraction. The toxicological effects seem to be mostly autonomic and cardiotoxic, causing death in a dose dependent manner with a LD50 of 792 μg/kg. Moreover, at a dose of 600 μg/kg the active fraction accelerated the KCl-induced lethality in mice. PMID:23945599

  17. Single-handed helical carbonaceous nanotubes prepared using a pair of cationic low molecular weight gelators

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Huayan; Wang, Qing; Guo, Yongmin; Li, Baozong; Li, Yi, E-mail: liyi@suda.edu.cn; Yang, Yonggang

    2016-08-15

    Highlights: • 3-aminophenol-formaldeyde resins were prepared through a templating method. • A pair of cationic gelators have been used as the templates. • Single-handed helical carbonaceous nanotubes were obtained after carbonization. • The carbonaceous nanotubes showed optical activity. - Abstract: We design a facile route to obtain enantiopure carbonaceous nanostructures, which have potential application as chiral sensors, electromagnetic wave absorbers, and asymmetric catalysts. A pair of cationic low molecular weight gelators was synthesized, which were able to self-assemble into twisted nanoribbons in ethanol at a concentration of 20 g L{sup −1} at 25 °C. Single-handed helical 3-aminophenol-formaldehyde resin nanotubes with optical activity were prepared using the self-assembly of the low molecular weight gelators as templates. After carbonization, single-handed helical carbonaceous nanotubes were obtained and characterized using circular dichroism, wide-angle X-ray diffraction, field-emission scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy. The results indicate that the walls of the nanotubes are amorphous carbon. Moreover, the left- and right-handed helical nanotubes exhibit opposite optical activity.

  18. Insights into the Toxicological Properties of a Low Molecular Weight Fraction from Zoanthus sociatus (Cnidaria

    Directory of Open Access Journals (Sweden)

    Agostinho Antunes

    2013-08-01

    Full Text Available The phylum Cnidaria is an ancient group of venomous animals, specialized in the production and delivery of toxins. Many species belonging to the class Anthozoa have been studied and their venoms often contain a group of peptides, less than 10 kDa, that act upon ion channels. These peptides and their targets interact with high affinity producing neurotoxic and cardiotoxic effects, and even death, depending on the dose and the administration pathway. Zoanthiniaria is an order of the Subclass Hexacorallia, class Anthozoa, and unlike sea anemone (order Actiniaria, neither its diversity of toxins nor the in vivo effects of the venoms has been exhaustively explored. In this study we assessed some toxicological tests on mice with a low molecular weight fraction obtained by gel filtration in Sephadex G-50 from Zoanthus sociatus crude extract. The gel filtration chromatogram at 280 nm revealed two major peaks, the highest absorbance corresponding to the low molecular weight fraction. The toxicological effects seem to be mostly autonomic and cardiotoxic, causing death in a dose dependent manner with a LD50 of 792 μg/kg. Moreover, at a dose of 600 μg/kg the active fraction accelerated the KCl-induced lethality in mice.

  19. Occupational Asthma: New Low-Molecular-Weight Causal Agents, 2000–2010

    Directory of Open Access Journals (Sweden)

    J. A. Pralong

    2012-01-01

    Full Text Available Background. More than 400 agents have been documented as causing occupational asthma (OA. The list of low-molecular-weight (LMW agents that have been identified as potential causes of OA is constantly expanding, emphasizing the need to continually update our knowledge by reviewing the literature. Objective. The objective of this paper was to identify all new LMW agents causing occupational asthma reported during the period 2000–2010. Methods. A Medline search was performed using the keywords occupational asthma, new allergens, new causes, and low-molecular-weight agents. Results. We found 39 publications describing 41 new LMW causal agents, which belonged to the following categories: drugs (n=12, wood dust (n=11, chemicals (n=8, metals (n=4, biocides (n=3, and miscellaneous (n=3. The diagnosis of OA was confirmed through SIC for 35 of 41 agents, peak expiratory flow monitoring for three (3 agents, and the clinical history alone for three (3 agents. Immunological tests provided evidence supporting an IgE-mediated mechanism for eight (8 (20% of the newly described agents. Conclusion. This paper highlights the importance of being alert to the occurrence of new LMW sensitizers, which can elicit OA. The immunological mechanism is explained by a type I hypersensitivity reaction in 20% of all newly described LMW agents.

  20. Effects of Cycloheximide and 5-Fluorouracil on Formation of Low-Molecular-Weight Ribonucleic Acid in Yeast

    Science.gov (United States)

    Hendricks, D. V.; Andrean, B. A. G.; De Kloet, S. R.

    1969-01-01

    The effects of cycloheximide and 5-fluorouracil on the formation of low-molecular-weight ribonucleic acid (RNA) in yeast were investigated. Both compounds were found to affect the synthesis of low-molecular-weight RNA of ribosomal origin more than transfer RNA but less than the high-molecular-weight ribosomal RNA. 5-Fluorouracil-containing transfer RNA was separated from normal transfer RNA by chromatography on diethylaminoethyl cellulose at 80 C in the presence of 7 m urea. PMID:5773027

  1. End-label free-solution electrophoresis of the low molecular weight heparins.

    Science.gov (United States)

    Sudor, J; Novotny, M V

    1997-08-15

    The intact heparins are highly charged oligosaccharides. Their charge polydispersity and the possible occurrence of numerous isomers complicate the analysis of these biomedically important glycoconjugates. After unsuccessful attempts to resolve the low molecular weight heparins in entangled matrixes, or through the use of counterions (Stefansson, M.; Novotny, M. V. Anal. Chem. 1994, 66, 3466-3471), we have designed a unique end-label reagent to incorporate both a fluorescent moiety and a desirable frictional increment to the analyte molecules. The resolution of small oligomers was improved dramatically following this approach. We also propose a scheme, based on the end-label free-solution electrophoresis model (Mayer, P.; Slater, G. W.; Drouin, G. Anal. Chem. 1994, 66, 1777-1780), that could potentially predict the migration times of some oligomers of complex heparin mixtures.

  2. Chloroalkane gel formations by tris-urea low molecular weight gelator under various conditions.

    Science.gov (United States)

    Yamanaka, Masamichi; Fujii, Hiromitsu

    2009-08-07

    C3-symmetrical tris-urea low molecular weight gelator 1 was synthesized in three steps from phloroglucin. The gelation ability of 1 in four chloroalkanes, i.e., CH2Cl2, CHCl3, 1,1,2-trichloroethane, and 1,1,2,2-tetrachloroethane, was investigated under various conditions. Thermal treatment was effective in gelating 1,1,2-trichloroethane. In the presence of equimolar 1 and CuBr2, 1,1,2-trichloroethane and 1,1,2,2-tetrachloroethane formed gels. Mixtures of 1 and CHCl3 or 1,1,2,2-tetrachloroethane gave gels after ultrasound irradiation. CH2Cl2 changed into a gel in the presence of equimolar 1 and BiCl3 after sonication. Spherical particles with rough surfaces were found by SEM observation of CHCl3 gel prepared from ultrasound irradiation of 1 and Y(NO3)3.

  3. Structural Characterization of the Low-Molecular-Weight Heparin Dalteparin by Combining Different Analytical Strategies

    Directory of Open Access Journals (Sweden)

    Antonella Bisio

    2017-06-01

    Full Text Available A number of low molecular weight heparin (LMWH products are available for clinical use and although all share a similar mechanism of action, they are classified as distinct drugs because of the different depolymerisation processes of the native heparin resulting in substantial pharmacokinetic and pharmacodynamics differences. While enoxaparin has been extensively investigated, little information is available regarding the LMWH dalteparin. The present study is focused on the detailed structural characterization of Fragmin® by LC-MS and NMR applied both to the whole drug and to its enzymatic products. For a more in-depth approach, size homogeneous octasaccharide and decasaccharide components together with their fractions endowed with high or no affinity toward antithrombin were also isolated and their structural profiles characterized. The combination of different analytical strategies here described represents a useful tool for the assessment of batch-to-batch structural variability and for comparative evaluation of structural features of biosimilar products.

  4. Venous thromboembolism in pregnancy: prophylaxis and treatment with low molecular weight heparin

    DEFF Research Database (Denmark)

    Andersen, Anita Sylvest; Berthelsen, Jørgen G.; Bergholt, Thomas

    2010-01-01

    side effects of treatment and no osteoporotic fractures or episodes of heparin-induced thrombocytopenia. The 166 pregnancies resulted in 159 live infants. There was a significantly higher risk of preterm delivery (13% vs. 6%) and intrauterine growth restriction (4.4% vs. 3.5%). Delivery by cesarean......-induced thrombocytopenia. The 166 pregnancies resulted in 159 live infants. There was a significantly higher risk of preterm delivery (13% vs. 6%) and intrauterine growth restriction (4.4% vs. 3.5%). Delivery by cesarean section was more common in these high-risk LMWH-treated pregnancies (33.1%) than in untreated......OBJECTIVE: To evaluate the safety of individually dosed low molecular weight heparin (LMWH) for prophylaxis and treatment of thromboembolic complications in pregnancy. DESIGN: Cohort study with a chronologic register-based control group. SETTING: Department of Obstetrics and Gynecology, Hiller...

  5. Venous thromboembolism in pregnancy: prophylaxis and treatment with low molecular weight heparin

    DEFF Research Database (Denmark)

    Andersen, Anita Sylvest; Berthelsen, Jørgen G; Bergholt, Thomas

    2010-01-01

    side effects of treatment and no osteoporotic fractures or episodes of heparin-induced thrombocytopenia. The 166 pregnancies resulted in 159 live infants. There was a significantly higher risk of preterm delivery (13% vs. 6%) and intrauterine growth restriction (4.4% vs. 3.5%). Delivery by cesarean......OBJECTIVE: To evaluate the safety of individually dosed low molecular weight heparin (LMWH) for prophylaxis and treatment of thromboembolic complications in pregnancy. DESIGN: Cohort study with a chronologic register-based control group. SETTING: Department of Obstetrics and Gynecology, Hillerød...... Hospital, Denmark. POPULATION: All 166 women treated with LMWH in pregnancy between 1 January 2001 and 31 December 2005. METHODS: Women treated with LMWH in pregnancy were identified and individual case records reviewed retrospectively. General data on the LMWH-treated women were compared to the 18...

  6. Toxicological Evaluation of Low Molecular Weight Fucoidan in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Pai-An Hwang

    2016-06-01

    Full Text Available For a long time, fucoidan has been well known for its pharmacological activities, and recently low molecular weight fucoidan (LMF has been used in food supplements and pharmaceutical products. In the present study, LMF was extracted from Laminaria japonica by enzyme hydrolysis. The toxicity of LMF in mouse and rat models was determined by many methods, such as total arsenic content, bacterial reverse mutation assay, chromosome aberration assay, and in vivo micronucleus assay. The present findings showed that LMF at 5000 μg/mL exhibited no mutagenicity. It also produced no formatting disruption of red blood cells in vivo. At 2000 mg/kg BW/day there were no toxicological indications. LMF is expected to be used as a safe food supplement.

  7. Spontaneous Hemocholecyst in an End-Stage Renal Failure Patient on Low Molecular Weight Heparin Hemodialysis

    Directory of Open Access Journals (Sweden)

    Konstantinos Blouhos

    2012-01-01

    Full Text Available The present paper describes a case of spontaneous hemocholecyst in a patient with end-stage renal failure on low molecular weight heparin hemodialysis. The patient presented with acute right upper quadrant pain. An initial ultrasound scan demonstrated a distended gallbladder containing echogenic bile without stones. During hospitalization the patient became febrile, and jaundiced, developed leukocytosis, and had an elevation in serum bilirubin, transaminases, and alkaline phosphatase. A new ultrasound demonstrated a thick-walled gallbladder containing echogenic bile and pericholecystic fluid. MRI depicted a distended gallbladder containing material of mixed signal intensity and a normal biliary tract. Open cholecystectomy revealed a gallbladder filled with blood and clots, and transcystic common bile duct exploration flushed blood clots out of the bile duct. To our knowledge this is the second case of spontaneous hemocholecyst reported in the literature as a consequence of uremic bleeding and LMWH hemodialysis in the absence of other pathology.

  8. Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery

    DEFF Research Database (Denmark)

    Rasmussen, Morten Schnack; Jørgensen, Lars Nannestad; Wille-Jørgensen, Peer

    2009-01-01

    BACKGROUND: Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low-molecular weight heparin (LMWH) administered during the in-hospital period is well documented, but the optimal duration of thromboprophylaxis after surgery...... remains controversial. Some studies suggest that patients undergoing major abdominal surgery benefit from prolongation of the thromboprophylaxis to 1 month after surgery. No systematic review on prolonged thromboprophylaxis after major abdominal or pelvic surgery has been published. OBJECTIVES......: To evaluate the efficacy and safety of prolonged thromboprophylaxis with LMWH for at least 1 month after abdominal or pelvic surgery with thromboprophylaxis administered during the in-hospital period only in preventing late VTE. SEARCH STRATEGY: Electronic searches were performed January 2008 in the Medline...

  9. Calcium binding to low molecular weight compounds and health promoting products

    DEFF Research Database (Denmark)

    Vavrusova, Martina

    absorption. Therefore, calcium as an essential nutrient should not be underestimated in our diet. Milk and dairy products are good sources of bioavailable calcium due to specific protein binding. Other sources of calcium, apart from a balanced and healthy diet, are calcium supplements and calcium fortified......Calcium precipitation in the almost neutral environment of the intestines is a process related to weight loss management and plays an important role in the prevention of colon cancer development. This process also affects calcium bioavailability which is decreased due to decreased calcium...... food. Therefore, an understanding of the basic chemistry of calcium binding to low molecular weight compounds can contribute to a general knowledge about calcium bioavailability and also to product improvement. Calcium precipitation with palmitate was described by a first-order reaction for conditions...

  10. Low molecular weight organic compounds of chestnut wood (Castanea sativa L.) and corresponding aged brandies.

    Science.gov (United States)

    Canas, S; Leandro, M C; Spranger, M I; Belchior, A P

    1999-12-01

    Oak and chestnut species have been largely used for the aging of brandies, but nowadays chestnut is rarely used. There have been no previous studies regarding the cooperage utilization of chestnut wood. This study provides, for the first time, specific information about the characterization of the northern Portuguese Castanea sativa wood and examines the influence of this wood and its heat treatment on the chemical composition of two-year-aged brandies, by the quantitative determination (HPLC) of low molecular weight phenolic compounds. The predominance of gallic acid among the analyzed extractable compounds both in chestnut wood and in the corresponding aged brandies was remarkable. The heat treatment has a very significant influence on the majority of extractable compounds analyzed. Thus, it could be responsible for the related sensorial properties of aged brandies and greatly affect their general balance.

  11. In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight

    Science.gov (United States)

    Dahlman, James E.; Barnes, Carmen; Khan, Omar F.; Thiriot, Aude; Jhunjunwala, Siddharth; Shaw, Taylor E.; Xing, Yiping; Sager, Hendrik B.; Sahay, Gaurav; Speciner, Lauren; Bader, Andrew; Bogorad, Roman L.; Yin, Hao; Racie, Tim; Dong, Yizhou; Jiang, Shan; Seedorf, Danielle; Dave, Apeksha; Singh Sandhu, Kamaljeet; Webber, Matthew J.; Novobrantseva, Tatiana; Ruda, Vera M.; Lytton-Jean, Abigail K. R.; Levins, Christopher G.; Kalish, Brian; Mudge, Dayna K.; Perez, Mario; Abezgauz, Ludmila; Dutta, Partha; Smith, Lynelle; Charisse, Klaus; Kieran, Mark W.; Fitzgerald, Kevin; Nahrendorf, Matthias; Danino, Dganit; Tuder, Rubin M.; von Andrian, Ulrich H.; Akinc, Akin; Panigrahy, Dipak; Schroeder, Avi; Koteliansky, Victor; Langer, Robert; Anderson, Daniel G.

    2014-08-01

    Dysfunctional endothelium contributes to more diseases than any other tissue in the body. Small interfering RNAs (siRNAs) can help in the study and treatment of endothelial cells in vivo by durably silencing multiple genes simultaneously, but efficient siRNA delivery has so far remained challenging. Here, we show that polymeric nanoparticles made of low-molecular-weight polyamines and lipids can deliver siRNA to endothelial cells with high efficiency, thereby facilitating the simultaneous silencing of multiple endothelial genes in vivo. Unlike lipid or lipid-like nanoparticles, this formulation does not significantly reduce gene expression in hepatocytes or immune cells even at the dosage necessary for endothelial gene silencing. These nanoparticles mediate the most durable non-liver silencing reported so far and facilitate the delivery of siRNAs that modify endothelial function in mouse models of vascular permeability, emphysema, primary tumour growth and metastasis.

  12. ADME-Tox profiling of some low molecular weight water soluble chitosan derivatives

    Directory of Open Access Journals (Sweden)

    Adriana Isvoran

    2017-09-01

    Full Text Available Within this study we use a few computational tools for predicting absorption, distribution, metabolism, excretion and toxicity (ADME-Tox, pharmacokinetics profiles, toxic/adverse effects, carcinogenicity, cardiotoxicity and endocrine disruption of some of low molecular weight water soluble derivatives of chitosan that are used in wound healing. Investigated compounds do not possess drug-like properties, their pharmacokinetics profiles reveal poor gastrointestinal absorption and low skin penetration. Chitosan derivatives cannot pass the blood-brain barrier and they are not able to inhibit the enzymes of the cytochrome P450 that are involved in the metabolism of xenobiotics. They do not reflect carcinogenicity and cardiotoxicity and reveal only a low probability to be endocrine disruptors. The main side effects in humans of the investigated compounds are: weight loss, acidosis, gastrointestinal toxicity, respiratory failure. This information is especially important for professional exposure and accidental contamination with these compounds.

  13. Low-molecular weight heparin increases circulating sFlt-1 levels and enhances urinary elimination.

    Directory of Open Access Journals (Sweden)

    Henning Hagmann

    Full Text Available RATIONALE: Preeclampsia is a devastating medical complication of pregnancy which leads to maternal and fetal morbidity and mortality. While the etiology of preeclampsia is unclear, human and animal studies suggest that excessive circulating levels of soluble fms-like tyrosine-kinase-1 (sFlt-1, an alternatively spliced variant of VEGF-receptor1, contribute to the signs and symptoms of preeclampsia. Since sFlt-1 binds to heparin and heparan sulfate proteoglycans, we hypothesized that the anticoagulant heparin, which is often used in pregnancy, may interfere with the levels, distribution and elimination of sFlt-1 in vivo. OBJECTIVE: We systematically determined serum and urine levels of angiogenic factors in preeclamptic women before and after administration of low molecular weight heparin and further characterized the interaction with heparin in biochemical studies. METHODS AND RESULTS: Serum and urine samples were used to measure sFlt-1 levels before and after heparin administration. Serum levels of sFlt-1 increased by 25% after heparin administration in pregnant women. The magnitude of the increase in circulating sFlt-1 correlated with initial sFlt-1 serum levels. Urinary sFlt-1 levels were also elevated following heparin administration and levels of elimination were dependent on the underlying integrity of the glomerular filtration barrier. Biochemical binding studies employing cation exchange chromatography revealed that heparin bound sFlt-1 had decreased affinity to negatively charged surfaces when compared to sFlt-1 alone. CONCLUSION: Low molecular weight heparin administration increased circulating sFlt1 levels and enhanced renal elimination. We provide evidence that both effects may be due to heparin binding to sFlt1 and masking the positive charges on sFlt1 protein.

  14. The association of low-molecular-weight hydrophobic compounds with native casein micelles in bovine milk.

    Science.gov (United States)

    Cheema, M; Mohan, M S; Campagna, S R; Jurat-Fuentes, J L; Harte, F M

    2015-08-01

    The agreed biological function of the casein micelles in milk is to carry minerals (calcium, magnesium, and phosphorus) from mother to young along with amino acids for growth and development. Recently, native and modified casein micelles were used as encapsulating and delivery agents for various hydrophobic low-molecular-weight probes. The ability of modified casein micelles to bind certain probes may derive from the binding affinity of native casein micelles. Hence, a study with milk from single cows was conducted to further elucidate the association of hydrophobic molecules into native casein micelles and further understand their biological function. Hydrophobic and hydrophilic extraction followed by ultraperformance liquid chromatography-high resolution mass spectrometry analysis were performed over protein fractions obtained from size exclusion fractionation of raw skim milk. Hydrophobic compounds, including phosphatidylcholine, lyso-phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin, showed strong association exclusively to casein micelles as compared with whey proteins, whereas hydrophilic compounds did not display any preference for their association among milk proteins. Further analysis using liquid chromatography-tandem mass spectrometry detected 42 compounds associated solely with the casein-micelles fraction. Mass fragments in tandem mass spectrometry identified 4 of these compounds as phosphatidylcholine with fatty acid composition of 16:0/18:1, 14:0/16:0, 16:0/16:0, and 18:1/18:0. These results support that transporting low-molecular-weight hydrophobic molecules is also a biological function of the casein micelles in milk. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  15. Effects of a supersulfated low molecular weight heparin (IK-SSH) on different hemostatic parameters.

    Science.gov (United States)

    Glusa, E; Barthel, W; Schenk, J; Radziwon, P; Butti, A; Markwardt, F; Breddin, K H

    1998-01-01

    In a phase I trial effects of a new supersulfated low molecular weight heparin (IK-SSH) on different hemostatic parameters were investigated in healthy volunteers. Parameters studied were activated partial thromboplastin time (aPTT), thrombin time, Heptest, anti-activated factor II (anti-FIIa) and anti-activated factor X (anti-FXa) activity, platelet adhesion, platelet count, platelet-induced thrombin generation time (PITT), bleeding time, antithrombin III, fibrinogen and several safety parameters. After single intravenous (i.v.) injections of IK-SSH (0.14, 0.33 and 0.66 mg/kg) aPTT, Heptest and PITT were strongly and dose-dependently prolonged. After ascending subcutaneous (s.c.) doses of IK-SSH (0.33, 0.66 and 1 mg/kg) aPTT, Heptest and PITT were prolonged in a dose-dependent manner. Repeat s.c. injections of 1 mg/kg IK-SSH for 5 days markedly prolonged aPTT, Heptest and PITT. No cumulative effects were observed. Anti-FIIa and anti-FXa activity were not or only slightly increased. Bleeding time, thrombin time and platelet adhesion were not significantly changed after i.v. and s.c. injections of IK-SSH. However, tissue factor pathway inhibitor (TFPI) concentration was markedly increased after each injection of IK-SSH and returned to the preinjection value 24 h later. IK-SSH prolongs aPTT, Heptest and PITT in a similar manner as other low molecular weight heparins but without significantly affecting thrombin time, FIIa and FXa activity. The release of TFPI may well be responsible for the prolongation of aPTT, Heptest and PITT. IK-SSH may be further developed as an antithrombotic agent.

  16. Aqueous geochemistry of low molecular weight hydrocarbons at elevated temperatures and pressures: constraints from mineral buffered laboratory experiments

    Science.gov (United States)

    Seewald, Jeffrey S.

    2001-05-01

    Organic matter, water, and minerals coexist at elevated temperatures and pressures in sedimentary basins and participate in a wide range of geochemical processes that includes the generation of oil and natural gas. A series of laboratory experiments were conducted at 300 to 350°C and 350 bars to examine chemical interactions involving low molecular weight aqueous hydrocarbons with water and Fe-bearing minerals under hydrothermal conditions. Mineral buffers composed of hematite-magnetite-pyrite, hematite-magnetite, and pyrite-pyrrhotite-magnetite were added to each experiment to fix the redox state of the fluid and the activity of reduced sulfur species. During each experiment the chemical system was externally modified by addition of ethene, ethane, propene, 1-butene, or n-heptane, and variations in the abundance of aqueous organic species were monitored as a function of time and temperature. Results of the experiments indicate that decomposition of aqueous n-alkanes proceeds through a series of oxidation and hydration reactions that sequentially produce alkenes, alcohols, ketones, and organic acids as reaction intermediaries. Organic acids subsequently undergo decarboxylation and/or oxidation reactions to form carbon dioxide and shorter chain saturated hydrocarbons. This alteration assemblage is compositionally distinct from that produced by thermal cracking under anhydrous conditions, indicating that the presence of water and minerals provide alternative reaction pathways for the decomposition of hydrocarbons. The rate of hydrocarbon oxidation decreases substantially under reducing conditions and in the absence of catalytically active aqueous sulfur species. These results represent compelling evidence that the stability of aqueous hydrocarbons at elevated temperatures in natural environments is not a simple function of time and temperature alone. Under the appropriate geochemical conditions, stepwise oxidation represents a mechanism for the decomposition of low

  17. In vivo intracellular pH measurements in tobacco and Arabidopsis reveal an unexpected pH gradient in the endomembrane system.

    Science.gov (United States)

    Martinière, Alexandre; Bassil, Elias; Jublanc, Elodie; Alcon, Carine; Reguera, Maria; Sentenac, Hervé; Blumwald, Eduardo; Paris, Nadine

    2013-10-01

    The pH homeostasis of endomembranes is essential for cellular functions. In order to provide direct pH measurements in the endomembrane system lumen, we targeted genetically encoded ratiometric pH sensors to the cytosol, the endoplasmic reticulum, and the trans-Golgi, or the compartments labeled by the vacuolar sorting receptor (VSR), which includes the trans-Golgi network and prevacuoles. Using noninvasive live-cell imaging to measure pH, we show that a gradual acidification from the endoplasmic reticulum to the lytic vacuole exists, in both tobacco (Nicotiana tabacum) epidermal (ΔpH -1.5) and Arabidopsis thaliana root cells (ΔpH -2.1). The average pH in VSR compartments was intermediate between that of the trans-Golgi and the vacuole. Combining pH measurements with in vivo colocalization experiments, we found that the trans-Golgi network had an acidic pH of 6.1, while the prevacuole and late prevacuole were both more alkaline, with pH of 6.6 and 7.1, respectively. We also showed that endosomal pH, and subsequently vacuolar trafficking of soluble proteins, requires both vacuolar-type H(+) ATPase-dependent acidification as well as proton efflux mediated at least by the activity of endosomal sodium/proton NHX-type antiporters.

  18. Low-molecular-weight heparins in the treatment of cancer-associated thrombosis: a new standard of care?

    Science.gov (United States)

    Burris, Howard A

    2006-04-01

    Cancer patients are twice as likely to develop postoperative venous thromboembolism (VTE) than non-cancer patients undergoing the same surgical procedure. Causes of cancer-associated thrombosis include: the capacity of tumor cells and their products to interact with platelets, clotting, and fibrinolytic proteins. Aggressive antitumor therapy with agents such as platinum compounds, high-dose fluorouracil, mitomycin-C, tamoxifen, and growth factors increase the risk of cancer-associated thrombosis. Despite the high risk of VTE in patients with cancer, thromboprophylaxis in surgical and medical oncology patients is low. Initial therapy of VTE in patients with cancer is low-molecular-weight heparin (LMWH) or unfractionated heparin. Long-term secondary prophylaxis of VTE is generally accomplished with oral anticoagulants, primarily warfarin. Evidence supports the use of LMWH for prevention and treatment of cancer-associated thrombosis because it is more easily administered, does not require laboratory monitoring, has a lower risk of adverse events, and is more cost effective than unfractionated heparin. In addition, the antineoplastic effects of LMWH have been demonstrated, including direct antitumor, antiangiogenic, and immune system modulatory action. Each LMWH is a unique biological entity having product-specific molecular and structural attributes; therefore, different LMWHs cannot be given interchangeably. Continued investigation of LMWH therapy in patients with cancer is warranted.

  19. Mechanism study of endothelial protection and inhibits platelet activation of low molecular weight fucoidan from Laminaria japonica

    Science.gov (United States)

    Chen, Anjin; Zhang, Fang; Shi, Jie; Zhao, Xue; Yan, Meixing

    2016-10-01

    Several studies have indicated that fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica could inhibit the activation of platelets directly by reducing the platelet aggregation. To explore the direct effect of LMW fucoidan on the platelet system furthermore and examine the possible mechanism, the endothelial protection and inhibits platelet activation effects of two LMW fucoidan were investigated. In the present study, Endothelial injury model of rats was made by injection of adrenaline (0.4 mg kg-1) and human umbilical vein endothelial cells were cultured. vWF level was be investigated in vivo and in vitro as an important index of endothelial injury. LMW fucoidan could significantly reduce vWF level in vascular endothelial injury rats and also significantly reduce vWF level in vitro. The number of EMPs was be detected as another important index of endothelial injury. The results showed that LMW fucoidan reduced EMPs stimulated by tumor necrosis factor. In this study, it was found that by inhibiting platelet adhesion, LMW fucoidan played a role in anti-thrombosis and the specific mechanism of action is to inhibit the flow of extracellular Ca2+. All in a word, LMW fucoidan could inhibit the activation of platelets indirectly by reducing the concentration of EMPs and vWF, at the same time; LMW fucoidan inhibited the activation of platelets directly by inhibiting the flow of extracellular Ca2+.

  20. Evalution of capillary electrophoresis-frontal analysis for the study of low molecular weight drug-human serum albumin interactions.

    Science.gov (United States)

    Østergaard, Jesper; Schou, Christian; Larsen, Claus; Heegaard, Niels H H

    2002-09-01

    Capillary electrophoresis frontal analysis was applied to 12 low molecular weight compounds including 8 drug substances displaying a range of different properties with respect to binding affinity, binding location, structure, lipophilicity, charge at physiological pH, and electrophoretic mobility. It was found that capillary electrophoresis frontal analysis can be used as a general method to study and quantify drug-human serum albumin interactions. The binding parameters obtained were consistent with literature values. Dextran was in some cases added to the run buffer to improve separation of the drug and human serum albumin plateau peaks. Results indicate that mobility differences between free and complexed human serum albumin give rise to only minor errors. Capillary electrophoresis frontal analysis was also found applicable to the study of human serum albumin drug displacement reactions. Low sensitivity of the UV-detection system was found to be the major limitation of capillary electrophoresis frontal analysis. The method is simple, and minimal effort has to be put into method development, which makes it well suited for screening in early drug development.

  1. In silico design of low molecular weight protein-protein interaction inhibitors: Overall concept and recent advances.

    Science.gov (United States)

    Kuenemann, Mélaine A; Sperandio, Olivier; Labbé, Céline M; Lagorce, David; Miteva, Maria A; Villoutreix, Bruno O

    2015-10-01

    Protein-protein interactions (PPIs) are carrying out diverse functions in living systems and are playing a major role in the health and disease states. Low molecular weight (LMW) "drug-like" inhibitors of PPIs would be very valuable not only to enhance our understanding over physiological processes but also for drug discovery endeavors. However, PPIs were deemed intractable by LMW chemicals during many years. But today, with the new experimental and in silico technologies that have been developed, about 50 PPIs have already been inhibited by LMW molecules. Here, we first focus on general concepts about protein-protein interactions, present a consensual view about ligandable pockets at the protein interfaces and the possibilities of using fast and cost effective structure-based virtual screening methods to identify PPI hits. We then discuss the design of compound collections dedicated to PPIs. Recent financial analyses of the field suggest that LMW PPI modulators could be gaining momentum over biologics in the coming years supporting further research in this area. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Potential antitumor activity of a low-molecular-weight protein fraction from Grifola frondosa through enhancement of cytokine production.

    Science.gov (United States)

    Kodama, Noriko; Mizuno, Shigeto; Nanba, Hiroaki; Saito, Naoaki

    2010-02-01

    Edible mushrooms contain an abundance of immune-enhancing nutritients. Some of these compounds, referred to as biological response modifiers (BRMs), have been used in biological therapies for cancer treatment. We obtained a low-molecular-weight protein fraction (MLP-Fraction) from the fruiting body of the maitake mushroom Grifola frondosa by multiple sequential steps, including ethanol precipitation, DEAE-exchange chromatography, and gel filtration. The effect of the MLP-Fraction on the immune system was determined using normal mice. This resulted in a simultaneous increase in splenocyte proliferation and production of cytokines such as interleukin (IL)-1alpha, tumor necrosis factor-alpha, IL-10, IL-12, and interferon (IFN)-gamma. The expression levels of IFN-gamma and IL-12 in antigen-presenting cells (APCs) and the activation of natural killer (NK) cells, macrophages, and dendritic cells were observed. These results suggest a mechanism in which NK cells are activated through cytokines produced by APCs. We also confirmed the possibility that the MLP-Fraction acts as a BRM using colon-26 carcinoma-bearing mice. This fraction enhanced the production of IL-12 and IFN-gamma by splenocytes in tumor-bearing mice and clearly showed an inhibitory effect on tumor cell growth.

  3. Ultrasound treatment increases transfection efficiency of low molecular weight chitosan in fibroblasts but not in KB cells.

    Directory of Open Access Journals (Sweden)

    Ureporn Kedjarune-Leggat

    Full Text Available The aim of this study was to optimize transfection efficiency (TE of the depolymerized low molecular weight (LW chitosan with molecular weight (Mw at 16 kDa and 54% degree of deacetylation (DDA on three primary cells of fibroblast (F, dental pulp (P, and periodontal ligament (PDL. The effect of low frequency ultrasound treatment on the chitosan-DNA complexes prior transfection on TE was also evaluated. This LW chitosan required high N/P ratio (>34 to bind DNA completely. An N/P ratio above 56 tended to improve TE in most primary cells nearly at the level of Lipofectamine. Ultrasonication can reduce the aggregation and sizes of the chitosan-DNA microparticles. It increased TE of F cells at an N/P ratio above 34, which was higher than Lipofectamine. However, this ultrasound treatment caused loss of TE in KB cells. MTT assay of these chitosan-DNA complexes revealed no significant cytotoxicity to both KB and F cells. This LW chitosan has potential for further development into a safer alternative to gene delivery systems in various cells of interest; however the optimal conditions have to be adjusted, depending on each cell source.

  4. Low molecular weight heparin biosimilars: how much similarity for how much clinical benefit?

    Science.gov (United States)

    Drouet, Ludovic

    2012-03-01

    The development of biosimilar versions of low molecular weight heparins (LMWHs) raises real medical concerns. To illustrate this, we have chosen as an example the specific clinical setting of antithrombotic management of acute coronary syndromes (ACS). In this indication, the LMWH enoxaparin has consistently shown its superiority in terms of efficacy when compared to unfractionated heparin (UFH) and in a number of direct or indirect comparisons to other LMWHs. For this reason, enoxaparin has become the gold standard for anticoagulation in cardiology, recommended by practice guidelines and extensively used in everyday practice. We are concerned by the fact that some patients might be treated with a biosimilar copy of enoxaparin, on the basis of simplified criteria that are not specific enough to differentiate between different available LMWHs and are thus unable to differentiate between enoxaparin and a biosimilar. In the absence of evidence from clinical trials, especially in ACS, we believe that it is difficult to ensure that the benefit/risk ratio of enoxaparin and its copy are equivalent. In addition to efficacy, safety issues also have to be taken into consideration, since biosimilars consist of glycan chain mixtures that exhibit specific immunoallergic features. Contamination of raw material with other glycans or xenobiotic material during extraction and fractionation may trigger potentially harmful immune reactions.

  5. Molecular imprinted polymer-coated optical fiber sensor for the identification of low molecular weight molecules.

    Science.gov (United States)

    Lépinay, Sandrine; Ianoul, Anatoli; Albert, Jacques

    2014-10-01

    A biomimetic optical probe for detecting low molecular weight molecules (maltol, 3-hydroxy-2-methyl-4H-pyran-4-one, molecular weight of 126.11 g/mol), was designed, fabricated, and characterized. The sensor couples a molecular imprinted polymer (MIP) and the Bragg grating refractometry technology into an optical fiber. The probe is fabricated first by inscribing tilted grating planes in the core of the fiber, and then by photopolymerization to immobilize a maltol imprinted MIP on the fiber cladding surface over the Bragg grating. The sensor response to the presence of maltol in different media is obtained by spectral interrogation of the fiber transmission signal. The results showed that the limit of detection of the sensor reached 1 ng/mL in pure water with a sensitivity of 6.3 × 10(8)pm/M. The selectivity of the sensor against other compounds and its reusability were also studied experimentally. Finally, the unambiguous detection of concentrations as little as 10nM of maltol in complex media (real food samples) by the MIP-coated tilted fiber Bragg grating sensor was demonstrated. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis

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    Oualid Haddad

    2015-10-01

    Full Text Available Induction of angiogenesis is a potential treatment for chronic ischemia. Low molecular weight fucoidan (LMWF, the sulfated polysaccharide from brown seaweeds, has been shown to promote revascularization in a rat limb ischemia, increasing angiogenesis in vivo. We investigated the potential role of two heparan sulfate (HS metabolism enzymes, exostosin-2 (EXT2 and heparanase (HPSE, and of two HS-membrane proteoglycans, syndecan-1 and -4 (SDC-1 and SDC-4, in LMWF induced angiogenesis. Our results showed that LMWF increases human vascular endothelial cell (HUVEC migration and angiogenesis in vitro. We report that the expression and activity of the HS-degrading HPSE was increased after LMWF treatment. The phenotypic tests of LMWF-treated and EXT2- or HPSE-siRNA-transfected cells indicated that EXT2 or HPSE expression significantly affect the proangiogenic potential of LMWF. In addition, LMWF increased SDC-1, but decreased SDC-4 expressions. The effect of LMWF depends on SDC-4 expression. Silencing EXT2 or HPSE leads to an increased expression of SDC-4, providing the evidence that EXT2 and HPSE regulate the SDC-4 expression. Altogether, these data indicate that EXT2, HPSE, and SDC-4 are involved in the proangiogenic effects of LMWF, suggesting that the HS metabolism changes linked to LMWF-induced angiogenesis offer the opportunity for new therapeutic strategies of ischemic diseases.

  7. Controllable production of low molecular weight heparins by combinations of heparinase I/II/III.

    Science.gov (United States)

    Wu, Jingjun; Zhang, Chong; Mei, Xiang; Li, Ye; Xing, Xin-Hui

    2014-01-30

    Enzymatic depolymerization of heparin by heparinases is promising for production of low molecular weight heparins (LMWHs) as anticoagulants, due to its mild reaction conditions and high selectivity. Here, different heparinase combinations were used to depolymerize heparin. Heparinase I and heparinase II can depolymerize heparin more efficiently than heparinase III, respectively, but heparinase III was the best able to protect the anticoagulant activities of LMWHs. Heparinase III and heparinase I/II combinations were able to efficiently depolymerize heparin to LMWHs with higher anticoagulant activity than the LMWHs produced by the respective heparinase I and heparinase II. HepIII and HepI is the best combination for maintaining high anti-IIa activity (75.7 ± 4.21 IU/mg) at the same Mw value. Furthermore, considering both the changes in molecular weight and anticoagulant activity, the action patterns of heparinase I and heparinase II were found not to follow the exolytic and processive depolymerizing mechanism from the reducing end of heparin. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Novel Ion-Exchange Coagulants Remove More Low Molecular Weight Organics than Traditional Coagulants.

    Science.gov (United States)

    Zhao, Huazhang; Wang, Lei; Hanigan, David; Westerhoff, Paul; Ni, Jinren

    2016-04-05

    Low molecular weight (MW) charged organic matter is poorly removed by conventional coagulants but contributes to disinfection byproduct formation during chlorination of drinking waters. We hypothesized that CIEX, a new Al-based hybrid coagulant with ion-exchange functional groups, would be new mechanistic approach to remove low MW organic matter during coagulation and would perform better than polyaluminum chloride (PACl) or metal-salt based coagulants. We measured coagulation performance using dissolved organic carbon (DOC) in a high hardness surface water. CIEX achieved excellent turbidity removal and removed 20% to 46% more DOC than FeCl3, Al2(SO4)3, or PACl, depending on dose. The improved DOC removal was attributable to better removal of low MW organic matter (organic acid (salicylic acid (SA)). CIEX achieved high removal of organic acids (>90% of SA) independent of pH, whereas removal by metal salts was lower (coagulants lack. Plus, unlike other cationic polymers that react with chloramines to form N-nitrosodimethylamine (NDMA), CIEX has a low molar yield (9.3 × 10(-7) mol NDMA per mol CIEX-N).

  9. Effect of low-molecular-weight organic acids on hematite dissolution promoted by desferrioxamine B.

    Science.gov (United States)

    Lin, Qingqi; Wang, Yingli; Yang, Xiuhong; Ruan, Dishen; Wang, Shizhong; Wei, Xiange; Qiu, Rongliang

    2018-01-01

    Siderophores, as strong chelators specific to iron, have been intensively studied in relation to the facilitation of biological iron acquisition from iron oxides. In this study, the dissolution of hematite in the presence of the siderophore desferrioxamine B (DFOB) and three low-molecular-weight organic acids (LMWOAs, i.e., oxalic, citric, or malic acid) was investigated at three pH conditions (3.0, 5.5, and 9.0). Hematite dissolution was pH-dependent and LMWOA-specific. The adsorption of DFOB on hematite was significantly higher at pH 9.0 than at the other pH values. The adsorption of oxalic acid on hematite, however, showed a descending trend as pH was increased, and adsorption of citric and malic acids was not significantly affected by pH. The Fourier transform infrared (FTIR) results also indicated the occurrence of these ligands' adsorption. After acidification, dissolved iron was detected only in suspensions of hematite pre-adsorbed with oxalic acid at pH 5.5 and 9.0 or pre-adsorbed with citric acid at pH 5.5, indicating that these LMWOAs promoted the formation of labile iron on the hematite surface. Based on previous research and the results of this study, a hypothetical model is proposed. These results provide insight into the effect of LMWOAs on the dissolution of hematite promoted by DFOB.

  10. Low molecular weight products from the aqueous alkaline degradation of cellulose

    Energy Technology Data Exchange (ETDEWEB)

    Molton, P. M.; Miller, R. K.; Donovan, J. M.; Demmitt, T. F.

    1977-11-01

    Low molecular weight products from the degradation of pure cellulose in 0.6 to 1.3 N alkali at 300/sup 0/C were identified by gas chromatography/mass spectrometry (GC/MS). Both the aqueous residual phase and the floating oil product phase were examined, and found to contain essentially the same compounds. Derivatization by trifluoroacetic anhydride was used as an ancillary method to aid identification of these compounds, which consisted primarily of unsaturated aliphatic and alicyclic hydrocarbons, aldehydes, ketones, alcohols, and furans. Many isomers were present. Specific compounds identified with a high level of confidence were cyclopentanone, cyclohexanone, phenol, cresols, 2-ethylcyclopentanone, 2- or 3-methylcyclopentanone, 2,5-dimethyl-2-cylopentenone, acrolein, 2,5-dimethyl-2,4-hexadiene, and octene. Compounds identified with a lower level of confidence include 2,4-dimethylfuran, 2,5-diethylfuran, ethylmethylfuran, 4-octyne, and decyne. The formation of these compounds from cellulose under alkaline conditions demonstrates not only the degradation of cellulose, but the resynthesis of molecules with carbon chain lengths greater than 6 atoms (the chain length of glucose). Such resynthesis must occur to a great extent in the formation of insoluble high molecular weight oils from cellulose by heating in aqueous alkali.

  11. Preparation of low molecular weight Sargassum fusiforme polysaccharide and its anticoagulant activity

    Science.gov (United States)

    Sun, Yuhao; Chen, Xiaolin; Liu, Song; Yu, Huahua; Li, Rongfeng; Wang, Xueqin; Qin, Yukun; Li, Pengcheng

    2017-10-01

    Heparin has been used as an anticoagulant drug for many years, but it has significant side effects. In the search for good substitutes, low molecular weight (MW) polysaccharides from Sargassum fusiforme have been examined and confirmed to possess biological activities. Here, S. fusiforme polysaccharides (SFP) were extracted and subjected to a hydrogen peroxide (H2O2) oxidation method for the preparation of low-MW SFP (LSFP). The effects of temperature, pH, and H2O2 concentration on the degradation process were also examined. Several LSFP of 36, 9, 5.7, and 2.7 kDa were obtained under different conditions, and their anticoagulant activities studied in vitro. The results showed that SFP and LSFP prolonged activated partial thromboplastin (APTT), prothrombin (PT) and thrombin times (TT) significantly, indicating that these low MW polysaccharides possessed anticoagulant activity in the intrinsic, extrinsic, and common coagulation pathways. As these effects were related to the MW of the polysaccharides in APTT and TT but not in PT, the contents of the monosaccharide fucose and sulfate and the polysaccharide MW could have exerted combined effects. The details of this mechanism require further verification.

  12. Study on antithrombotic and antiplatelet activities of low molecular weight fucoidan from Laminaria japonica

    Science.gov (United States)

    Chen, Anjin; Zhang, Fang; Shi, Jie; Zhao, Xue

    2012-06-01

    The antithrombotic and antiplatelet effects of two fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica were compared in order to examine the influence of chemical character on their antithrombotic activity and the possible mechanism. Both LMW fucoidan fractions exhibited favorable antithrombotic activity in an Fecl3-induced arterial thrombosis. The antithrombotic activity of LMW fucoidan was related with decrease of TXB2 and whole blood viscosity and hematocrit. LMW fucoidan showed a correlation between anticoagulant, antiaggregant and antithrombotic effects in vivo. For LMW fucoidan, antithrombotic activity required high dose of 5-10 nmol kg-1, concomitantly with increase in anticoagulant activity and inhibition of platelet aggregation. Administration of LMW fucoidan significantly promoted the 6-keto-PGF1α content and decreased the TXB2 content, indicating its inhibition of tissue factor pathway and regulation of metabolism of arachidonic acid. By comparison, highly sulfated fucoidan LF2 with Mw 3900 seemed to be a more suitable choice for antithrombotic drug for its antithrombotic activity accompanied with specific inhibitory activity on platelet aggregation, low anticoagulant activity and low hemorrhagic risk in vivo.

  13. Low molecular weight heparin and aspirin exacerbate human endometrial endothelial cell responses to antiphospholipid antibodies.

    Science.gov (United States)

    Quao, Zola Chihombori; Tong, Mancy; Bryce, Elena; Guller, Seth; Chamley, Lawrence W; Abrahams, Vikki M

    2018-01-01

    Women with antiphospholipid antibodies (aPL) are at risk for pregnancy complications despite treatment with low molecular weight heparin (LMWH) or aspirin (ASA). aPL recognizing beta2 glycoprotein I can target the uterine endothelium, however, little is known about its response to aPL. This study characterized the effect of aPL on human endometrial endothelial cells (HEECs), and the influence of LMWH and ASA. HEECs were exposed to aPL or control IgG, with or without low-dose LMWH and ASA, alone or in combination. Chemokine and angiogenic factor secretion were measured by ELISA. A tube formation assay was used to measure angiogenesis. aPL increased HEEC secretion of pro-angiogenic VEGF and PlGF; increased anti-angiogenic sFlt-1; inhibited basal secretion of the chemokines MCP-1, G-CSF, and GRO-α; and impaired angiogenesis. LMWH and ASA, alone and in combination, exacerbated the aPL-induced changes in the HEEC angiogenic factor and chemokine profile. There was no reversal of the aPL inhibition of HEEC angiogenesis by either single or combination therapy. By aPL inhibiting HEEC chemokine secretion and promoting sFlt-1 release, the uterine endothelium may contribute to impaired placentation and vascular transformation. LMWH and ASA may further contribute to endothelium dysfunction in women with obstetric APS. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Low Molecular Weight Fucoidan Inhibits Tumor Angiogenesis through Downregulation of HIF-1/VEGF Signaling under Hypoxia

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    Meng-Chuan Chen

    2015-07-01

    Full Text Available Activation of hypoxia-induced hypoxia-inducible factors-1 (HIF-1 plays a critical role in promoting tumor angiogenesis, growth and metastasis. Low molecular weight fucoidan (LMWF is prepared from brown algae, and exhibits anticancer activity. However, whether LMWF attenuates hypoxia-induced angiogenesis in bladder cancer cells and the molecular mechanisms involved remain unclear. This is the first study to demonstrate that LMWF can inhibit hypoxia-stimulated H2O2 formation, HIF-1 accumulation and transcriptional activity vascular endothelial growth factor (VEGF secretion, and the migration and invasion in hypoxic human bladder cancer cells (T24 cells. LMWF also downregulated hypoxia-activated phosphorylation of PI3K/AKT/mTOR/p70S6K/4EBP-1 signaling in T24 cells. Blocking PI3K/AKT or mTOR activity strongly diminished hypoxia-induced HIF-1α expression and VEGF secretion in T24 cells, supporting the involvement of PI3K/AKT/mTOR in the induction of HIF-1α and VEGF. Additionally, LMWF significantly attenuated angiogenesis in vitro and in vivo evidenced by reduction of tube formation of hypoxic human umbilical vascular endothelial cells and blood capillary generation in the tumor. Similarly, administration of LMWF also inhibited the HIF-1α and VEGF expression in vivo, accompanied by a reduction of tumor growth. In summary, under hypoxia conditions, the antiangiogenic activity of LMWF in bladder cancer may be associated with suppressing HIF-1/VEGF-regulated signaling pathway.

  15. Structure and activity of a new low-molecular-weight heparin produced by enzymatic ultrafiltration.

    Science.gov (United States)

    Fu, Li; Zhang, Fuming; Li, Guoyun; Onishi, Akihiro; Bhaskar, Ujjwal; Sun, Peilong; Linhardt, Robert J

    2014-05-01

    The standard process for preparing the low-molecular-weight heparin (LMWH) tinzaparin, through the partial enzymatic depolymerization of heparin, results in a reduced yield because of the formation of a high content of undesired disaccharides and tetrasaccharides. An enzymatic ultrafiltration reactor for LMWH preparation was developed to overcome this problem. The behavior, of the heparin oligosaccharides and polysaccharides using various membranes and conditions, was investigated to optimize this reactor. A novel product, LMWH-II, was produced from the controlled depolymerization of heparin using heparin lyase II in this optimized ultrafiltration reactor. Enzymatic ultrafiltration provides easy control and high yields (>80%) of LMWH-II. The molecular weight properties of LMWH-II were similar to other commercial LMWHs. The structure of LMWH-II closely matched heparin's core structural features. Most of the common process artifacts, present in many commercial LWMHs, were eliminated as demonstrated by 1D and 2D nuclear magnetic resonance spectroscopy. The antithrombin III and platelet factor-4 binding affinity of LMWH-II were comparable to commercial LMWHs, as was its in vitro anticoagulant activity. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Protection against cerebral malaria by the low-molecular-weight thiol pantethine.

    Science.gov (United States)

    Penet, Marie-France; Abou-Hamdan, Mhamad; Coltel, Nicolas; Cornille, Emilie; Grau, Georges E; de Reggi, Max; Gharib, Bouchra

    2008-01-29

    We report that administration of the low-molecular-weight thiol pantethine prevented the cerebral syndrome in Plasmodium berghei ANKA-infected mice. The protection was associated with an impairment of the host response to the infection, with in particular a decrease of circulating microparticles and preservation of the blood-brain barrier integrity. Parasite development was unaffected. Pantethine modulated one of the early steps of the inflammation-coagulation cascade, i.e., the transbilayer translocation of phosphatidylserine at the cell surface that we demonstrated on red blood cells and platelets. In this, pantethine mimicked the inactivation of the ATP-binding-cassette transporter A1 (ABCA1), which also prevents the cerebral syndrome in this malaria model. However, pantethine acts through a different pathway, because ABCA1 activity was unaffected by the treatment. The mechanisms of pantethine action were investigated, using the intact molecule and its constituents. The disulfide group (oxidized form) is necessary to lower the platelet response to activation by thrombin and collagen. Thio-sensitive mechanisms are also involved in the impairment of microparticle release by TNF-activated endothelial cells. In isolated cells, the effects were obtained by cystamine that lacks the pantothenic moiety of the molecule; however, the complete molecule is necessary to protect against cerebral malaria. Pantethine is well tolerated, and it has already been administered in other contexts to man with limited side effects. Therefore, trials of pantethine treatment in adjunctive therapy for severe malaria are warranted.

  17. Low molecular weight Cooperia oncophora antigens. Potential to discriminate between susceptible and resistant calves after infection.

    Science.gov (United States)

    van Diemen, P M; Ploeger, H W; Nieuwland, M G; Rietveld, F W; Eysker, M; Kooyman, F N; Kloosterman, A; Parmentier, H K

    1997-05-01

    The recognition of low molecular weight proteins by sera obtained during a single oral (primary) infection with 100,000 3rd-stage Cooperia oncophora larvae was studied in calves. Three groups of 6 or 7 calves were selected based on different egg excretion patterns. SDS-gel electrophoresis of adult Cooperia antigen under reducing conditions, followed by Western blotting, revealed that resistance of individual calves to C. oncophora might be related with antibody responses (42 days post infection) against at least 2 protein fragments (14-16 kDa and 27 kDa). The 14-16-kDa protein complex was bound, to some extent, by individual sera from all calves. The intensity of staining was negatively correlated with egg excretion on Day 42 p.i. Calves with high egg counts on Day 21 p.i. either did not or only weakly recognized the 27-kDa band. It has to be established whether the 14-16 kDa (or recombinant 14.2 kDa) provides a tool for immunodiagnostics and whether the 27-kDa fragment can help further unravel immune-mediated resistance to Cooperia.

  18. Electroejaculation increases low molecular weight proteins in seminal plasma modifying sperm quality in Corriedale rams.

    Science.gov (United States)

    Ledesma, A; Manes, J; Cesari, A; Alberio, R; Hozbor, F

    2014-04-01

    This study was conducted to evaluate the effect of seminal collection method (artificial vagina or electroejaculation) on the protein composition of seminal plasma and sperm quality parameters in Corriedale rams. To address this question, we assessed the effect of seminal collection method on motility, plasma membrane integrity and functionality, mitochondrial functionality and the decondensation state of nuclear chromatin in sperm cells. Volume, pH, osmolarity, protein concentration, total protein content and protein profile using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and 2-D polyacrylamide electrophoresis of seminal plasma collected with artificial vagina and electroejaculation were also analysed. The main findings from this study were that ejaculates obtained with electroejaculation had (i) a higher number of spermatozoa with intact plasma membrane and functional mitochondria and (ii) a higher proportion of seminal plasma, total protein content and relative abundance of low molecular weight proteins than ejaculates obtained with artificial vagina. Five of these proteins were identified by mass spectrometry: binder of sperm 5 precursor; RSVP14; RSVP22; epididymal secretory protein E1 and clusterin. One protein spot with molecular weight of approximately 31 kDa and isoelectric point of 4.8 was only found in the seminal plasma from electroejaculation. © 2014 Blackwell Verlag GmbH.

  19. Immune-enhancing activities of low molecular weight {beta}-glucan depolymerized by gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Nak-Yun [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Byun, Eui-Hong [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Laboratory of Food Chemistry, Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, 812-8581 (Japan); Kwon, Sun-Kyu; Song, Beom-Seok; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Yoo, Young-Choon [Department of Microbiology, College of Medicine, Konyang University, Daejeon 302-718 (Korea, Republic of); Kim, Mee-Ree [Department of Food and Nutrition, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Lee, Ju-Woon [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of)], E-mail: sjwlee@kaeri.re.kr

    2009-07-15

    {beta}-glucans are structural cell wall polymers of many microorganisms and cereals which possess immunomodulatory properties and have been used in the food, cosmetic and medical industry. In our previous study, {beta}-glucan was depolymerized by gamma irradiation and leads to improve the solubility and viscosity. This study was carried out to evaluate the functional properties, mainly immune-enhancing activities of low molecular weight {beta}-glucan fragmented by gamma irradiation. The results showed that RAW 264.7 macrophage cell stimulation activities of irradiated {beta}-glucan were higher than that of non-irradiated {beta}-glucan. In addition, the oral administration of gamma-irradiated {beta}-glucan significantly increased the proliferation and cytokine (IFN-{gamma} and IL-2) release of spleen and Peyer's patch cells compared with non-irradiated {beta}-glucan. In conclusion, gamma irradiation could be used as an effective method for the production of depolymerized {beta}-glucan improved functional property such as immunomodulatory activity.

  20. Isotope fractionation of mercury during its photochemical reduction by low-molecular-weight organic compounds.

    Science.gov (United States)

    Zheng, Wang; Hintelmann, Holger

    2010-04-01

    Photochemical reduction of Hg(II) by various low-molecular-weight organic compounds (LMWOC) was investigated to evaluate the effect of specific functional groups that are typically encountered in natural dissolved organic matters (DOM) on the photoreactivity and isotope fractionation of Hg. LMWOC with reduced sulfur functional groups (e.g., cysteine, glutathione) resulted in slower photochemical reduction of Hg(II) than those without reduced sulfur groups (e.g., serine, oxalic acid). Reduction rate constants were specifically determined for two contrasting LMWOC: dl-serine (0.640 h(-1)) and l-cysteine (0.047 h(-1)). Different mass independent isotope effects of Hg were induced by the two types of LMWOC. S-containing ligands specifically enriched magnetic isotopes ((199)Hg and (201)Hg) in the product (Hg(0)) while sulfurless ligands enriched (199)Hg and (201)Hg in the reactant (Hg(II)), suggesting that opposite magnetic isotope effects were produced by different types of ligands. The nuclear field shift effect was also observed in the photochemical reduction by serine. These isotope effects are related to specific functional groups and reduction mechanisms, and may be used to distinguish between primary and secondary photochemical reduction mechanisms of Hg(II) and to explain isotope fractionation during the photochemical reduction of Hg(II) by natural DOM, which provides mixed bonding conditions.

  1. Use of low molecular weight heparin in pregnant women with mechanical heart valves.

    Science.gov (United States)

    Yinon, Yoav; Siu, Samuel C; Warshafsky, Chelsie; Maxwell, Cynthia; McLeod, Anne; Colman, Jack M; Sermer, Mathew; Silversides, Candice K

    2009-11-01

    There are a number of different anticoagulation options for pregnant women with mechanical heart valves. The purpose of this study was to examine maternal thromboembolic complications in women with mechanical valves treated with low-molecular weight heparin (LMWH) throughout pregnancy. This was a substudy of a larger prospective cohort study of pregnant women with heart disease followed from 1998 to 2008. All pregnant women with mechanical left-sided valves who were treated with LMWH throughout pregnancy were included. Maternal thromboembolic events were defined as valve thrombosis, need for valve replacement, or stroke during pregnancy or postpartum (up to 6 months). Twenty-three pregnancies (17 women) occurred in women treated with LMWH and low-dose aspirin: 15 in women with mechanical mitral valves, 9 in women with mechanical aortic valves, and 1 in a woman with both. There was 1 maternal thromboembolic event (4%), which resulted in maternal and fetal death. Five women (22%) developed other adverse cardiac events during pregnancy. Nine pregnancies (43%) had fetal or neonatal adverse events, 5 of which had favorable outcomes. Three pregnancies were complicated by postpartum hemorrhage. In conclusion, carefully monitored LMWH may be a suitable anticoagulation strategy in pregnant women with mechanical heart valves who are unwilling to use warfarin. However, this group of women remains at risk for maternal cardiac and fetal complications. The occurrence of valve thrombosis resulting in maternal death despite therapeutic anti-Xa levels highlights current limitations with anticoagulation in this population.

  2. Epoxy resin synthesis using low molecular weight lignin separated from various lignocellulosic materials.

    Science.gov (United States)

    Asada, Chikako; Basnet, Sunita; Otsuka, Masaya; Sasaki, Chizuru; Nakamura, Yoshitoshi

    2015-03-01

    A low molecular weight lignin from various lignocellulosic materials was used for the synthesis of bio-based epoxy resins. The lignin extracted with methanol from steam-exploded samples (steaming time of 5 min at steam pressure of 3.5 MPa) from different biomasses (i.e., cedar, eucalyptus, and bamboo) were functionalized by the reaction with epichlorohydrin, catalyzed by a water-soluble phase transfer catalyst tetramethylammonium chloride, which was further reacted with 30 wt% aqueous NaOH for ring closure using methyl ethyl ketone as a solvent. The glycidylated products of the lignin with good yields were cured to epoxy polymer networks with bio-based curing agents i.e., lignin itself and a commercial curing agent TD2131. Relatively good thermal properties of the bio-based epoxy network was obtained and thermal decomposition temperature at 5% weight loss (Td5) of cedar-derived epoxy resin was higher than that derived from eucalyptus and bamboo. The bio-based resin satisfies the stability requirement of epoxy resin applicable for electric circuit boards. The methanol-insoluble residues were enzymatically hydrolyzed to produce glucose. This study indicated that the biomass-derived methanol-soluble lignin may be a promising candidate to be used as a substitute for petroleum-based epoxy resin derived from bisphenol A, while insoluble residues may be processed to give a bioethanol precursor i.e., glucose. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Activation of the low molecular weight protein tyrosine phosphatase in keratinocytes exposed to hyperosmotic stress.

    Directory of Open Access Journals (Sweden)

    Rodrigo A Silva

    Full Text Available Herein, we provide new contribution to the mechanisms involved in keratinocytes response to hyperosmotic shock showing, for the first time, the participation of Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP activity in this event. We reported that sorbitol-induced osmotic stress mediates alterations in the phosphorylation of pivotal cytoskeletal proteins, particularly Src and cofilin. Furthermore, an increase in the expression of the phosphorylated form of LMWPTP, which was followed by an augment in its catalytic activity, was observed. Of particular importance, these responses occurred in an intracellular milieu characterized by elevated levels of reduced glutathione (GSH and increased expression of the antioxidant enzymes glutathione peroxidase and glutathione reductase. Altogether, our results suggest that hyperosmostic stress provides a favorable cellular environment to the activation of LMWPTP, which is associated with increased expression of antioxidant enzymes, high levels of GSH and inhibition of Src kinase. Finally, the real contribution of LMWPTP in the hyperosmotic stress response of keratinocytes was demonstrated through analysis of the effects of ACP1 gene knockdown in stressed and non-stressed cells. LMWPTP knockdown attenuates the effects of sorbitol induced-stress in HaCaT cells, mainly in the status of Src kinase, Rac and STAT5 phosphorylation and activity. These results describe for the first time the participation of LMWPTP in the dynamics of cytoskeleton rearrangement during exposure of human keratinocytes to hyperosmotic shock, which may contribute to cell death.

  4. Nanowires Formed by the Co-Assembly of a Negatively Charged Low-Molecular Weight Gelator and a Zwitterionic Polythiophene

    NARCIS (Netherlands)

    Li, F.; Ganesan, P.; Jong, de M.R.; Aslund, A.; Konradsson, P.; Marcelis, A.T.M.; Sudhölter, E.J.R.; Cohen Stuart, M.A.; Leermakers, F.A.M.

    2010-01-01

    Conjugated organic nanowires have been prepared by co-assembling a carboxylate containing low-molecular weight gelator (LMWG) and an amino acid substituted polythiophene derivative (PTT). Upon introducing the zwitterionic polyelectrolyte PTT to a basic molecular solution of the organogelator, the

  5. Rapid Analysis of Apolar Low Molecular Weight Constituents in Wood Using High Pressure Liquid Chromatography with Evaporative Light Scattering Detection

    NARCIS (Netherlands)

    Claassen, F.W.; Haar, van de C.; Beek, van T.A.; Dorado, J.; Martinez-Inigo, M.; Sierra-Alvarez, R.

    2000-01-01

    A new high pressure liquid chromatographic method with evaporative light scattering detection was developed for the qualitative and quantitative analysis of apolar, low molecular weight constituents in wood. The wood extractives were obtained by means of a 6 h Soxhlet extraction with acetone. The

  6. Influence of low-molecular-weight glutenin subunit haplotypes on dough rheology and baking quality in elite common wheat varieties

    Science.gov (United States)

    The low molecular weight glutenin subunits (LMW-GSs) are a class of wheat seed storage proteins directly involved in the formation of gluten. Depending on the first amino acid residue of the mature proteins, the LMW-GSs are divided into methionine, serine or isoleucine type. These proteins are encod...

  7. Influence of low-molecular-weight glutenin subunit haplotypes on dough rheology in elite common wheat varieties

    Science.gov (United States)

    The low molecular weight glutenin subunits (LMW-GSs) are a class of wheat seed storage proteins. They are encoded by a multigene family located at the Glu-3 loci, and their allelic variation strongly influences wheat end-use quality. Due to ambiguities in the LMW-GS allele nomenclature and to the co...

  8. Airway morphology and function of rats following dermal sensitization and respiratory challenge with low molecular weight chemicals

    NARCIS (Netherlands)

    Arts, J.H.E.; Kuper, C.F.; Spoor, S.M.; Bloksma, N.

    1998-01-01

    Local lymph node activation and increased total serum IgE levels are suggested to be predictive parameters of airway hypersensitivity caused by low molecular weight (LMW) chemicals. Whether increases of total serum IgE are indicative of actual induction of specific airway reactions (morphological

  9. Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-limb immobilization.

    Science.gov (United States)

    Zee, Aniek Ag; van Lieshout, Kelly; van der Heide, Maaike; Janssen, Loes; Janzing, Heinrich Mj

    2017-08-06

    Immobilization of the lower limb is a risk factor for venous thromboembolism (VTE). Low molecular weight heparins (LMWHs) are anticoagulants, which might be used in adult patients with lower-limb immobilization to prevent deep venous thrombosis (DVT) and its complications. This is an update of the review first published in 2008. To assess the effectiveness of low molecular weight heparin for the prevention of venous thromboembolism in patients with lower-limb immobilization in an ambulatory setting. For this update, the Cochrane Vascular Information Specialist searched the Specialised Register, CENTRAL, and three trials registers (April 2017). Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that described thromboprophylaxis by means of LMWH compared with no prophylaxis or placebo in adult patients with lower-limb immobilization. Immobilization was by means of a plaster cast or brace. Two review authors independently selected trials, assessed risk of bias and extracted data. The review authors contacted the trial authors for additional information if required. Statistical analysis was carried out using Review Manager 5. We included eight RCTs that fulfilled our criteria, with a total of 3680 participants. The quality of evidence, according GRADE, varied by outcome and ranged from low to moderate. We found an incidence of DVT ranging from 4.3% to 40% in patients who had a leg injury that had been immobilized in a plaster cast or a brace for at least one week, and who received no prophylaxis, or placebo. This number was significantly lower in patients who received daily subcutaneous injections of LMWH during immobilization, with event rates ranging from 0% to 37% (odds ratio (OR) 0.45, 95% confidence interval (CI) 0.33 to 0.61; with minimal evidence of heterogeneity: I² = 26%, P = 0.23; seven studies; 1676 participants, moderate-quality evidence). Comparable results were seen in the following groups of participants: patients with below

  10. Development of subcutaneous sustained release nanoparticles encapsulating low molecular weight heparin

    Directory of Open Access Journals (Sweden)

    Satheesh Jogala

    2015-01-01

    Full Text Available The objective of the present research work was to prepare and evaluate sustained release subcutaneous (s.c. nanoparticles of low molecular weight heparin (LMWH. The nanoparticles were prepared by water-in-oil in-water (w/o/w emulsion and evaporation method using different grades of polylactide co-glycolide (50:50, 85:15, and different concentrations of polyvinyl alcohol (0.1%, 0.5%, 1% aqueous solution as surfactant. The fabricated nanoparticles were evaluated for size, shape, zeta potential, encapsulation efficiency, in vitro drug release, and in vivo biological activity (anti-factor Xa activity using the standard kit. The drug and excipient compatibility was analyzed by Fourier transform infrared spectroscopy (FTIR, differential scanning calorimetry (DSC and X-ray diffraction (XRD studies. The formation of nanoparticles was confirmed by scanning electron microscopy; nanoparticles were spherical in shape. The size of prepared nanoparticles was found between 195 nm and 251 nm. The encapsulation efficiency of the nanoparticles was found between 46% and 70%. In vitro drug, release was about 16-38% for 10 days. In vivo drug, release shows the sustained release of drug for 10 days in rats. FTIR studies indicated that there was no loss in chemical integrity of the drug upon fabrication into nanoparticles. DSC and XRD results demonstrated that the drug was changed from the crystalline form to the amorphous form in the formulation during the fabrication process. The results of this study revealed that the s.c. nanoparticles were suitable candidates for sustained delivery of LMWH.

  11. Profile of low molecular weight tinzaparin sodium for anticoagulation during hemodialysis

    Directory of Open Access Journals (Sweden)

    Al-Saran Khalid

    2010-01-01

    Full Text Available Low-molecular-weight heparin (LMWH has been suggested as providing safe, effi-cient, convenient, and possibly more cost-effective anticoagulation for hemodialysis (HD than un-fractionated heparin (UFH with a single bolus dose at the start of hemodialysis effectively pre-vents clot formation in the dialyzer and bubble trap with fewer side-effects and possible benefits on uremic dyslipidemia. In this study, we compared the safety, clinical efficacy, and cost effectiveness of Tinzaparin sodium (Innohep with unfractionated heparin (UFH in 23 chronic HD patients; their extracorporeal anticoagulant protocol-consisted of UFH was switched to Tinzaparin for a period of 6 months. Clinical clotting (grade 1-4 was evaluated by visual inspection after blood draining of the air trap every hour and the dialyzer after each session. Anticoagulation with Tinzaparin sodium re-sulted in less frequent dialyzer and air-trap clotting compared to UFH (P= 001 and 0.04 respec-tively. Over 24 weeks, we observed no alteration in the serum lipid profile of the patients. There was a statistically significant improvement in the dialysis single pool Kt/V after 6 months of Tinza-parin use (1.40 ± 0.28 for Tinzaparin versus 1.23 ± 0.28 for heparin without any modification in the hemodialysis prescription. The total cost for 24 weeks use of Tinzaparin sodium was 23% more expensive compared to that for UFH. We conclude that a single bolus of Tinzaparin sodium injec-tion at the start of the dialysis session was more effective and convenient in our patients than UFH, but at a higher total cost. Furthermore, at least on the short term, there was no observed benefit on the lipid profile.

  12. Aspirin and low-molecular weight heparin combination therapy effectively prevents recurrent miscarriage in hyperhomocysteinemic women.

    Directory of Open Access Journals (Sweden)

    Pratip Chakraborty

    Full Text Available The management of recurrent pregnancy loss (RPL still remains a great challenge, and women with polycystic ovarian syndrome (PCOS are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy, insulin resistance (IR and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 women with history of 2 or more consecutive first trimester abortions were screened and 336 were selected for the study. The selected patients were initially divided on the basis of presence or absence of PCOS, while subsequent stratification was based on HHcy, IR and/or obesity. The subjects had treatment with aspirin during one conception cycle and aspirin-LMWH combined anticoagulant therapy for the immediate next conception cycle, if the first treated cycle was unsuccessful. Pregnancy salvage was the sole outcome measure. The overall rate of pregnancy salvage following aspirin therapy was 43.15%, which was mostly represented by normohomocysteinemic women, while the salvage rate was lower in the HHcy populations irrespective of the presence or absence of PCOS, IR, or obesity. By contrast, aspirin-LMWH combined therapy could rescue 66.84% pregnancies in the aspirin-failed cases. Logistic regression analyses showed that HHcy remained a significant factor in predicting salvage rates in the PCOS, IR, and obese subpopulations controlled for other confounding factors. With regard to pregnancy salvage, combined anticoagulant therapy with aspirin and LMWH conferred added benefit to those with HHcy phenotype.

  13. Mechanistic investigation of Fe(III) oxide reduction by low molecular weight organic sulfur species

    Science.gov (United States)

    Eitel, Eryn M.; Taillefert, Martial

    2017-10-01

    Low molecular weight organic sulfur species, often referred to as thiols, are known to be ubiquitous in aquatic environments and represent important chemical reductants of Fe(III) oxides. Thiols are excellent electron shuttles used during dissimilatory iron reduction, and in this capacity could indirectly affect the redox state of sediments, release adsorbed contaminants via reductive dissolution, and influence the carbon cycle through alteration of bacterial respiration processes. Interestingly, the reduction of Fe(III) oxides by thiols has not been previously investigated in environmentally relevant conditions, likely due to analytical limitations associated with the detection of thiols and their oxidized products. In this study, a novel electrochemical method was developed to simultaneously determine thiol/disulfide pair concentrations in situ during the reduction of ferrihydrite in batch reactors. First order rate laws with respect to initial thiol concentration were confirmed for Fe(III) oxyhydroxide reduction by four common thiols: cysteine, homocysteine, cysteamine, and glutathione. Zero order was determined for both Fe(III) oxyhydroxide and proton concentration at circumneutral pH. A kinetic model detailing the molecular mechanism of the reaction was optimized with proposed intermediate surface structures. Although metal oxide overall reduction rate constants were inversely proportional to the complexity of the thiol structure, the extent of metal reduction increased with structure complexity, indicating that surface complexes play a significant role in the ability of these thiols to reduce iron. Taken together, these results demonstrate the importance of considering the molecular reaction mechanism at the iron oxide surface when investigating the potential for thiols to act as electron shuttles during dissimilatory iron reduction in natural environments.

  14. Use of viscoelastic coagulation testing to monitor low molecular weight heparin administration to healthy horses.

    Science.gov (United States)

    Tennent-Brown, Brett S; Epstein, Kira L; Whelchel, Dorothy D; Giguère, Steeve

    2013-01-01

    To evaluate the utility of thromboelastography (TEG) and Sonoclot analyses to monitor the effects of low molecular weight heparin (LMWH) administration to healthy horses. Randomized crossover study. Large animal veterinary teaching hospital. Six adult mixed breed healthy mares. LMWH (dalteparin) was administered (50 U/kg subcutaneously) either every 12 or 24 h for 3 consecutive days. Blood samples were collected before LMWH administration and then at selected time points for analysis. Thromboelastography derived R-time (R), K-time (K), angle (ANG), and maximum amplitude (MA), and Sonoclot activated clot time (ACT), clot rate (CR), and platelet function (PF) were measured in whole blood 30 min after sample collection. Change (Δ) and percentage change (%Δ) from baseline of each TEG and Sonoclot variable were subsequently calculated. Anti-factor Xa activity and activated partial thromboplastin time (aPTT) were assayed in harvested plasma. The association between anti-factor Xa activity and TEG and Sonoclot (measured and calculated) variables was assessed by calculating correlation coefficients and multiple regression analysis. The ability of measured and calculated TEG and Sonoclot variables to predict when anti-factor Xa activity fell below suggested thromboprophylactic levels was assessed using receiver operating characteristic curve analysis. The correlation between aPTT and anti-factor Xa activity was weak (r = 0.343). Changes in TEG and Sonoclot variables following LMWH administration were consistent with hypocoagulation. All measured and calculated TEG variables were significantly correlated with anti-factor Xa activity. Sonoclot ACT, ΔACT, CR, ΔCR, and %ΔCR were also significantly correlated with anti-factor Xa activity. TEG ΔR and %ΔR best predicted anti-factor Xa activity below the suggested thromboprophylactic level. Although correlations were modest, serial measurement of TEG variables may be used to monitor LMWH therapy in horses; however, further

  15. Efficacy and safety of once daily low molecular weight heparin (tinzaparin sodium) in high risk pregnancy.

    LENUS (Irish Health Repository)

    Ní Ainle, Fionnuala

    2008-10-01

    Low molecular weight heparin (LMWH) is widely regarded as the anticoagulant treatment of choice for the prevention and treatment of venous thromboembolism during pregnancy. However, previous studies have demonstrated that the pharmacokinetic profiles of LMWH vary significantly with increasing gestation. Consequently, it remains unclear whether LMWH regimens recommended for use in nonpregnant individuals can be safely extrapolated to pregnant women. The aims of this study were to assess the safety and the efficacy of tinzaparin sodium (Innohep) administered only once daily during pregnancy. A systematic retrospective review identified a cohort of 37 high-risk pregnancies which had been managed using tinzaparin 175 IU\\/kg once daily. In 26 cases, the index pregnancy had been complicated by development of an acute venous thromboembolism (17 deep vein thrombosis and nine pulmonary embolism). For each individual, case notes were examined and data extracted using a predetermined questionnaire. No episodes of recurrent venous thromboembolism were identified amongst this cohort of pregnancies managed using once daily LMWH administration. However, two unusual thrombotic complications were observed, including a parietal infarct in one patient, and a postpartum cerebral venous thrombosis in another. Once daily tinzaparin was well tolerated, with no cases of heparin-induced thrombocytopaenia, symptomatic osteoporosis, or foetal malformations. Tinzaparin dose modification based upon peak anti-Xa levels occurred in 45% of the cases examined. The present study is the largest study to have examined the clinical efficacy of once daily LMWH for use in pregnant women at high risk of venous thromboembolism. Our data support the safety and efficacy of antenatal tinzaparin at a dose of 175 IU\\/kg. In order to determine whether this once daily regimen provides equivalent (or indeed greater) thromboprophylaxis to twice daily LMWH regimens during pregnancy will require highly powered

  16. [Effect of wheat and faba bean intercropping on root exudation of low molecular weight organic acids].

    Science.gov (United States)

    Xiao, Jing-Xiu; Zheng, Yi; Tang, Li

    2014-06-01

    Pot experiment of wheat and faba bean intercropping was conducted and exudates from wheat and faba bean roots were collected at different growth stages. Low molecular weight organic acids (OA) in root exudates were examined by HPLC. The results showed that wheat and faba bean intercropping significantly increased the total amounts of OA exuded by roots. At tillering (57 d), booting (120 d) and filling stages (142 d), intercropping increased the total amounts of OA in wheat root exudates by 155%, 35.6% and 92.6% respectively, in comparison with that of monoculture wheat (MW). At branching (57 d) and filling stages (142 d), intercropping increased the total amounts of OA in faba bean root exudates by 87.4% and 38.7%, respectively, in comparison with that of monoculture faba bean (MF). Wheat and faba bean intercropping changed the types of OA exuded by roots. At tillering stage, lactic acid was identified in root exudates of intercropping wheat (IW), but not in that of MW. At jointing stage (98 d), citric acid was identified in root exudates of IW, but not in that of MW, and acetic acid was vice versa. At branching stage, acetic acid was identified in root exudates of intercropping faba bean (IF), but not in that of MF, and lactic acid was vice versa. At filling stage, lactic acid was identified in root exudates of IF, but not in that of MF. Wheat and faba bean intercropping increased the OA exudation rate of wheat. At booting stage, the exudation rates of citric and fumaric acid from IW were 179 and 184-times as that of from MW, respectively. At filling stage, the exudation rate of lactic acid from IW was 2.53-times as that from MW. In conclusion, wheat and faba bean intercropping increased the rate and total amount, and changed the types of OA exuded by roots.

  17. Interaction between perdeuterated dimyristoylphosphatidylcholine and low molecular weight pulmonary surfactant protein SP-C.

    Science.gov (United States)

    Simatos, G A; Forward, K B; Morrow, M R; Keough, K M

    1990-06-19

    A low molecular weight hydrophobic protein was isolated from porcine lung lavage fluid using silicic acid and Sephadex LH-20 chromatography. The protein migrated with an apparent molecular weight of 5000-6000 on SDS-PAGE under reducing and nonreducing conditions. Gels run under reducing conditions also showed a minor band migrating with a molecular weight of 12,000. Amino acid compositional analysis and sequencing data suggest that this protein preparation contains intact surfactant protein SP-C and about 30% of truncated SP-C (N-terminal leucine absent). The surfactant protein was combined with perdeuterated dimyristoylphosphatidylcholine (DMPC-d54) in multilamellar vesicles. The protein enhanced the rate of adsorption of the lipid at air-water interfaces. The ability of the protein to alter normal lipid organization was examined by using high-sensitivity differential scanning calorimetry (DSC) and 2H nuclear magnetic resonance spectroscopy (2H NMR). The calorimetric measurements indicated that the protein caused a decrease in the temperature maximum (Tm) and a broadening of the phase transition. At a protein concentration of 8% (w/w), the enthalpy change of transition was reduced to 4.4 kcal/mol compared to 6.3 kcal/mol determined for the pure lipid. NMR spectral moment studies indicated that protein had no effect on lipid chain order in the liquid-crystal phase but reduced orientational order in the gel phase. Two-phase coexistence in the presence of protein was observed over a small temperature range below the pure lipid transition temperature. Spin-lattice relaxation times (T1) were not substantially affected by the protein. Transverse relaxation time (T2e) studies suggest that the protein influences slow lipid motions.

  18. Low Molecular Weight Heparin Improves Endothelial Function in Pregnant Women at High Risk of Preeclampsia.

    Science.gov (United States)

    McLaughlin, Kelsey; Baczyk, Dora; Potts, Audrey; Hladunewich, Michelle; Parker, John D; Kingdom, John C P

    2017-01-01

    Low molecular weight heparin (LMWH) has been investigated for the prevention of severe preeclampsia, although the mechanisms of action are unknown. The objective of this study was to investigate the cardiovascular effects of LMWH in pregnant women at high risk of preeclampsia. Pregnant women at high risk of preeclampsia (n=25) and low-risk pregnant controls (n=20) at 22 to 26 weeks' gestation underwent baseline cardiovascular assessments. High-risk women were then randomized to LMWH or saline placebo (30 mg IV bolus and 1 mg/kg subcutaneous dose). Cardiovascular function was assessed 1 and 3 hours post randomization. The in vitro endothelial effects of patient serum and exogenous LMWH on human umbilical venous endothelial cells were determined. High-risk women demonstrated a reduced cardiac output, high resistance hemodynamic profile with impaired radial artery flow-mediated dilation compared with controls. LMWH increased flow-mediated dilation in high-risk women 3 hours after randomization compared with baseline and increased plasma levels of placental growth factor, soluble fms-like tyrosine kinase-1, and myeloperoxidase. Serum from high-risk women impaired endothelial cell angiogenesis and increased PlGF-1 and PlGF-2 transcription compared with serum from low-risk controls. Coexposure of high-risk serum with LMWH improved the in vitro angiogenic response such that it was equivalent to that of low-risk serum and promoted placental growth factor secretion. LMWH improves maternal endothelial function in pregnant women at high risk of developing preeclampsia, possibly mediated through increased placental growth factor bioavailability. © 2016 American Heart Association, Inc.

  19. Inhalable Lactose-Based Dry Powder Formulations of Low Molecular Weight Heparin

    Science.gov (United States)

    Bai, Shuhua; Gupta, Vivek

    2010-01-01

    Abstract Background Currently low molecular weight heparin (LMWH) is administered as subcutaneous injection. This study sought to investigate the feasibility of LMWH as an inhalable dry powder (DPI) formulation and evaluate the interaction of the drug with lactose when used as a carrier. The study also compares the extent of pulmonary absorption of LMWH administered as a dry powder with that administered as an aerosolized aqueous solution. Methods The formulations were prepared by mixing LMWH in an aqueous solution of lactose followed by lyophilization of the resulting solution. The lyophilized preparation was then ground and sieved. Physical characterization of the formulations was performed by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), particle size analysis, and determination of aerodynamic diameter. For in vivo studies, formulations were administered to anesthetized rats, and drug absorption was monitored by measuring plasma antifactor Xa activity. Results and Conclusions In the FTIR scan, all characteristic peaks of lactose and LMWH were observed, suggesting that there was no strong interaction between lactose and LMWH. Although the aerodynamic diameter of the formulation (DPI-2) that was sieved through 170- and 230-mesh screens was similar to that of the formulation (DPI-1) sieved through 120- and 170-mesh screens, the particle sizes of the two formulations were significantly different. Dry powder formulations of LMWH were better absorbed compared to an inhalable solution of LMWH. One of the dry powder formulations (DPI-2) produced an almost 1.5-fold increase in the relative bioavailability (41.6%) compared to the liquid formulation of LMWH (32.5%). Overall, the data presented here suggest that lactose does not adversely affect the physical-chemical characteristics of the drug, and that lactose can be used as a carrier for pulmonary delivery of LMWH. PMID:19778265

  20. Intravenous low molecular weight iron dextran in children with iron deficiency anemia unresponsive to oral iron.

    Science.gov (United States)

    Plummer, Ellen S; Crary, Shelley E; McCavit, Timothy L; Buchanan, George R

    2013-11-01

    Iron deficiency anemia (IDA) in children is usually treated with oral iron, yet many respond poorly. Intravenous low molecular weight iron dextran (LMWID) offers the opportunity of employing a single outpatient infusion to correct the anemia and reduce the overall burden of treatment, but its use in children has been limited due to concerns of serious adverse effects. In this study we report our initial experience using LMWID in children with iron deficiency in whom oral iron was ineffective. We performed a case series of LMWID treatment of children with IDA of diverse etiologies who were poorly responsive to oral iron therapy with the aim of measuring its efficacy and adverse effects. LMWID was administered as a total dose infusion over 60 minutes in the outpatient setting. Thirty-one patients age 11 months to 18 years received intravenous LMWID, and 24 were evaluable for hematologic response. Median hemoglobin increments were respectively 3.5, 1.9, and 1.8 g/dl in patients with IDA due to poor nutrition (n = 11), chronic blood loss (n = 13), and miscellaneous causes (n = 7). Two thirds of evaluable patients had a complete hematologic response. Nine of the patients (29%) had mild non-specific adverse effects upon initiation of the LMWID infusion. LMWID as a total dose infusion was well tolerated and effective in a heterogeneous group of children and adolescents with IDA who were refractory to oral iron therapy. Transient reactions were common but not serious. Copyright © 2013 Wiley Periodicals, Inc.

  1. Detoxification of Atrazine by Low Molecular Weight Thiols in Alfalfa (Medicago sativa).

    Science.gov (United States)

    Zhang, Jing Jing; Xu, Jiang Yan; Lu, Feng Fan; Jin, She Feng; Yang, Hong

    2017-10-16

    Low molecular weight (LMW) thiols in higher plants are a group of sulfur-rich nonprotein compounds and play primary and multiple roles in cellular redox homeostasis, enzyme activities, and xenobiotics detoxification. This study focused on identifying thiols-related protein genes from the legume alfalfa exposed to the herbicide atrazine (ATZ) residues in environment. Using high-throughput RNA-sequencing, a set of ATZ-responsive thiols-related protein genes highly up-regulated and differentially expressed in alfalfa was identified. Most of the differentially expressed genes (DEGs) were involved in regulation of biotic and abiotic stress responses. By analyzing the genes involved in thiols-mediated redox homeostasis, we found that many of them were thiols-synthetic enzymes such as γ-glutamylcysteine synthase (γECS), homoglutathione synthetase (hGSHS), and glutathione synthetase (GSHS). Using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS), we further characterized a group of ATZ-thiols conjugates, which are the detoxified forms of ATZ in plants. Cysteine S-conjugate ATZ-HCl+Cys was the most important metabolite detected by MS. Several other ATZ-conjugates were also examined as ATZ-detoxified metabolites. Such results were validated by characterizing their analogs in rice. Our data showed that some conjugates under ATZ stress were detected in both plants, indicating that some detoxified mechanisms and pathways can be shared by the two plant species. Overall, these results indicate that LMW thiols play critical roles in detoxification of ATZ in the plants.

  2. [Modified Mechanism of Cell Walls from Chinese Fir Treated with Low-Molecular-Weight Phenol Formaldehyde Resin].

    Science.gov (United States)

    Huang, Yan-hui; Fei, Ben-hua; Zhao, Rong-jun

    2015-12-01

    Study on the modified mechanism of wood cell walls, it is very important for improving treatment reagents, optimizing treatment technology, and enhancing wood density, mechanical properties, dimensional stability, and so on. Samples of plantation Chinese fir were treated gradually with synthesized water-soluble low-molecular-weight phenol formaldehyde (PF) resins under vacuum and pressure. The correlated physical and chemical properties of the treated and untreated reference samples were determined by X-ray diffractometer (XRD), Fourier transform infrared spectrometer (FTIR), and nuclear magnetic resonance spectrometer(NMR) (Using method of Cross Polarization/Magic Angle Spinning for continuous testing) with high precision and resolution. The results showed that, after treated with water-soluble low-molecular-weight PF resin, the average values of crystallinity from the treated samples were decreased obviously, and the average reduction rate was 12.67%, 11.91% and 6.26%, respectively. Comparing water-soluble, low-molecular-weight PF resin modified Chinese fir with untreated reference samples, no new chemical shifts and characteristic peaks of functional groups from esters, ethers, etc. were present by using FTIR and ¹³C NMR spectrum. It was considered that there was no distinct chemical reaction between the water-soluble low-molecular-weight PF resin and Chinese Fir cell walls. But water-soluble low-molecular-weight PF resin could enter into the structure relatively loose, large size spaces, relatively area large amorphous regions in cell walls of Chinese fir tracheids, and form physical filling, which resulting in the decreasing of relative crystallinity. This study has important reference value for the development of new wood modification reagents and the optimization of wood modification process. The findings also provide important theoretical foundation for further proving the modification mechanisms of wood cell walls and enriching the modified theories of

  3. The endomembrane sheath: a key structure for understanding the plant cell?

    Science.gov (United States)

    Reuzeau, C.; McNally, J. G.; Pickard, B. G.

    1997-01-01

    Recent evidence suggests that integrin is abundant in endomembranes of plant cells, and the endomembranes are clad by a sheath of cytoskeleton including F-actin. A role for endomembrane integrin and the endomembrane sheath is proposed: this system might orchestrate metabolic regulation by providing and modulating loci for channelling, and might accelerate channeling as needed by dragging the endoplasmic reticulum (ER) and organelles through the cytoplasm. To accomplish this "streaming", F-actin might lever against the rest of the endomembrane sheath and the ER might also lever against adhesion sites (i.e., plasmodesmata and plasmalemmal control centers). As an important agent in the control of cellular activities, according to this model, the endomembrane sheath would play a major part in responses to diverse signals and stresses, and under extreme stress cell survival would depend on the ability of the system to maintain enough integrity to direct critical syntheses and degradations.

  4. Low molecular weight heparin prevents CLP-induced acute lung injury in rats by anti-inflammatory coagulation.

    Science.gov (United States)

    Lu, Xiao; Zhao, Liang; Xu, Yong-Hua

    2013-02-01

    The aim of our study was to observe the influence of low molecular Weight heparin (LMWH) on systemic inflammation, including high mobility group box 1 protein (HMGB1) and protective effect on acute lung injury induced by cecal ligation and puncture(CLP). Discuss the mechanism of this effect. 144 male SD rats were randomly divided into sham operation group (A), normal treatment group (B), the LMWH treatment group (C), n=48.Group A received a sham operation and the other groups were underwent CLP operation. Groups A and B accepted intraperitoneal injection (i.p.) of normal saline (NS) at a dose of 2.0 ml/kg and ceftriaxone (30 mg/kg), Group C were intraperitoneal injection additional LMWH (150 U/kg) except saline and ceftriaxone. Observe points were made at 3, 6, 12, 18, 24, 48 h, the rats were anesthetized and killed, mortality, lungs wet/dry ratio and Pathology change were determined. HMGB-1 mRNA, protein of lung tissues was calculated by RT-PCR and Western blot. TNF-α and IL-6 of blood plasma calculated by ELSIA. There was significantly different in each index between A and B group (pCLP group, there was a significant decrease in the lung injury, the mortality, HMGB1 mRNA and protein expression on lung tissues (pCLP-induced inflammation. As a result, LMWH ameliorated lung pathology and reduces mortality in CLP-induced systemic inflammation in a rat model. This effect may be mediated through the inhibition of axis of inflammation and coagulation.

  5. Low molecular weight heparin prevents CLP-Induced acute lung injury in rats by anti-inflammatory coagulation

    Directory of Open Access Journals (Sweden)

    Xiao Lu

    2013-02-01

    Full Text Available The aim of our study was to observe the influence of low molecular Weight heparin (LMWH on systemic inflammation, including high mobility group box 1 protern (HMGB1 and protective effect on acute lung injury induced by cecal ligation and puncture(CLP. Discuss the mechanism of this effect. 144 male SD rats were randomly divided into sham operation group (A, normal treatment group (B, the LMWH treatment group (C, n=48. Group A received a sham operation and the other groups were underwent CLP operation. Groups A and B accepted intraperitoneal injection (i.p. of normal saline (NS at a dose of 2.oml/kg and ceftriaxone (30 mg/kg, Group C were intraperitoneal injection additional LMWH (isoU/kg except saline and ceftriaxone. Observe points were made at 3, 6, 12, 18, 24, 48 h, the rats were anesthetized and killed, mortality, lungs wet/dry ratio and Pathology change were determined. HMGB-1 mRNA, protein of lung tissues was calculated by RT-PCR and Western blot. TNF-α and IL-6 of blood plasma calculated by ELSIA. There was significantly different in each index between A and B group (p<0.05. Compared with CLP group, there was a significant decrease in the lung injury, the mortality, HMGB1 mRNA and protein expression on lung tissues (p<0.05. LMWH can decreases cytokine, HMGB1 levels of lung tissue during CLP-induced inflammation. As a result, LMWH ameliorated lung pathology and reduces mortality in CLP-induced systemic inflammation in a rat model. This effect may be mediated through the inhibition of axis of inflammation and coagulation.

  6. Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation

    Directory of Open Access Journals (Sweden)

    S.A. Andrade

    2012-10-01

    Full Text Available Lopap, found in the bristles of Lonomia obliqua caterpillar, is the first exogenous prothrombin activator that shows serine protease-like activity, independent of prothrombinase components and unique lipocalin reported to interfere with hemostasis mechanisms. To assess the action of an exogenous prothrombin activator reversing the anticoagulant and antihemostatic effect induced by low molecular weight heparin (LMWH, male New Zealand rabbits (N = 20, weighing 3.8-4.0 kg allocated to 4 groups were anticoagulated with 1800 IU/kg LMWH (iv over 2 min, followed by iv administration of saline (SG or recombinant Lopap (rLopap at 1 µg/kg (LG1 or 10 µg/kg (LG10, 10 min after the injection of LMWH, in a blind manner. Control animals (CG were treated only with saline. The action of rLopap was assessed in terms of activated partial thromboplastin time (aPTT, prothrombin fragment F1+2, fibrinogen, and ear puncture bleeding time (BT at 5, 10, 15, 17, 20, 30, 40, 60, and 90 min after initiation of LMWH infusion. LG10 animals showed a decrease of aPTT in more than 50% and BT near to normal baseline. The level of prothrombin fragment F1+2 measured by ELISA had a 6-fold increase with rLopap treatment (10 µg/kg and was inversely proportional to BT in LMWH-treated animals. Thus, Lopap, obtained in recombinant form using E. coli expression system, was useful in antagonizing the effect of LMWH through direct prothrombin activation, which can be a possible strategy for the reversal of bleeding and anticoagulant events.

  7. α, ω-Cholesterol-Functionalized Low Molecular Weight Polyethylene Glycol as a Novel Modifier of Cationic Liposomes for Gene Delivery

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    Cui-Cui Ma

    2014-11-01

    Full Text Available Here, three novel cholesterol (Ch/low molecular weight polyethylene glycol (PEG conjugates, termed α, ω-cholesterol-functionalized PEG (Ch2-PEGn, were successfully synthesized using three kinds of PEG with different average molecular weight (PEG600, PEG1000 and PEG2000. The purpose of the study was to investigate the potential application of novel cationic liposomes (Ch2-PEGn-CLs containing Ch2-PEGn in gene delivery. The introduction of Ch2-PEGn affected both the particle size and zeta potential of cationic liposomes. Ch2-PEG2000 effectively compressed liposomal particles and Ch2-PEG2000-CLs were of the smallest size. Ch2-PEG1000 and Ch2-PEG2000 significantly decreased zeta potentials of Ch2-PEGn-CLs, while Ch2-PEG600 did not alter the zeta potential due to the short PEG chain. Moreover, the in vitro gene transfection efficiencies mediated by different Ch2-PEGn-CLs also differed, in which Ch2-PEG600-CLs achieved the strongest GFP expression than Ch2-PEG1000-CLs and Ch2-PEG2000-CLs in SKOV-3 cells. The gene delivery efficacy of Ch2-PEGn-CLs was further examined by addition of a targeting moiety (folate ligand in both folate-receptor (FR overexpressing SKOV-3 cells and A549 cells with low expression of FR. For Ch2-PEG1000-CLs and Ch2-PEG2000-CLs, higher molar ratios of folate ligand resulted in enhanced transfection efficacies, but Ch2-PEG600-CLs had no similar in contrast. Additionally, MTT assay proved the reduced cytotoxicities of cationic liposomes after modification by Ch2-PEGn. These findings provide important insights into the effects of Ch2-PEGn on cationic liposomes for delivering genes, which would be beneficial for the development of Ch2-PEGn-CLs-based gene delivery system.

  8. Bilayered near-infrared fluorescent nanoparticles based on low molecular weight PEI for tumor-targeted in vivo imaging

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hao; Li, Ke [Xi’an Jiaotong University, Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology (China); Xu, Liang [The University of Kansas, Department of Molecular Biosciences (United States); Wu, Daocheng, E-mail: wudaocheng@mail.xjtu.edu.cn [Xi’an Jiaotong University, Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology (China)

    2014-12-15

    To improve the tumor fluorescent imaging results in vivo, bilayered nanoparticles encapsulating a lipophilic near-infrared (NIR) fluorescent dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotri-carbocyanine iodide (DiR) were prepared using low molecular weight stearic acid-grafted polyethyleneimine and hyaluronic acid (DiR-PgSHA nanoparticles), which were investigated as a novel NIR fluorescent nano-probe for in vivo tumor-targeted optical imaging. These nanoparticles were characterized by transmission electron microscopy (TEM), infrared (IR) spectra, UV-visual absorption, and fluorescent emission spectra. Their cytotoxicity in vitro and hepatotoxicity in vivo were tested by MTT assay and histological study, respectively. In vivo NIR fluorescence imaging of the DiR-PgSHA nanoparticles was performed using a Carestream imaging system. The DiR-PgSHA nanoparticles were sphere shaped with a diameter of approximately 50 nm according to the TEM images. The DiR-PgSHA nanoparticles had a low cytotoxicity in vitro according to the MTT assay and low hepatotoxicity in vivo as determined in histological studies. The fluorescent emission of DiR-PgSHA nanoparticles was stable in pH values of 5–9 in solution, with only slight blue-shifts of the emission maxima at the basic pH range. The DiR-PgSHA nanoparticles exhibited a substantial tumor-targeting ability in the optical imaging with the use of tumor-bearing mice. These results demonstrated that the DiR-PgSHA nanoparticle is an excellent biocompatible nano-probe for in vivo tumor-targeted NIR fluorescence imaging with a potential for clinical applications.

  9. Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-leg immobilization.

    Science.gov (United States)

    Testroote, Mark; Stigter, Willem; de Visser, Dianne C; Janzing, Heinrich

    2008-10-08

    Immobilization of the lower leg is associated with venous thromboembolism. Low molecular weight heparin (LMWH) is an anticoagulant treatment which might be used in adult patients with lower-leg immobilization to prevent deep venous thrombosis and its complications. To investigate the current literature on thromboprophylactic practice for patients with lower-limb injuries who are immobilized in plaster casts or braces, to assess the need for concrete guidelines, and to assess whether it is possible to come to an evidence-based conclusion. The Cochrane Peripheral Vascular Disease Group searched their Specialized Register (last searched 20 May 2008) and the Central Register of Controlled Trials (CENTRAL) (last searched The Cochrane Library 2008, Issue 2). We searched MEDLINE (until May 2008) and EMBASE (until May 2008) and reference lists of articles. We contacted pharmaceutical companies of LMWHs for relevant studies. Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that described thromboprophylaxis by means of LMWH compared with no prophylaxis or placebo in adult patients with lower-leg immobilization. Immobilization was by means of a plaster cast or brace. Two authors independently assessed trial quality and extracted data. The review authors contacted the trial authors for additional information if required. Statistical analysis was carried out using Review Manager (RevMan 5). We included six RCTs fulfilling the above criteria with a total of 1490 patients. We found an incidence of venous thromboembolism ranging from 4.3% to 40%, in patients who had a leg injury that had been immobilized in a plaster cast or a brace for at least one week and who received no prophylaxis, or placebo. This number was significantly lower in patients who received daily subcutaneous injections of LMWH during immobilization (event rates ranging from 0% to 37%; odds ratio (OR) 0.49; fixed 95% confidence interval (CI) 0.34 to 0.72; with minimal evidence of

  10. Hydrophobic modification of low molecular weight polyethylenimine for improved gene transfection.

    Science.gov (United States)

    Teo, Pei Yun; Yang, Chuan; Hedrick, James L; Engler, Amanda C; Coady, Daniel J; Ghaem-Maghami, Sadaf; George, Andrew J T; Yang, Yi Yan

    2013-10-01

    Hydrophobic modification of low molecular weight (LMW) polyethylenimine (PEI) is known to increase gene transfection efficiency of LMW PEI. However, few studies have explored how the conjugated hydrophobic groups influence the properties of the modified LMW PEI mainly due to difficulties in obtaining well defined final product compositions and limitations in current chemical synthesis routes. The aim of this study was to modify LMW PEI (Mn 1.8 kDa, PEI-1.8) judiciously with different hydrophobic functional groups and to investigate how hydrophobicity, molecular structure and inclusion of hydrogen bonding properties in the conjugated side groups as well as the conjugation degree (number of primary amine groups of PEI-1.8 modified with hydrophobic groups) influence PEI-1.8 gene transfection efficiency. The modified polymers were characterized for DNA binding ability, particle size, zeta potential, in vitro gene transfection efficiency and cytotoxicity in SKOV-3 human ovarian cancer and HepG2 human liver carcinoma cell lines. The study shows that modified PEI-1.8 polymers are able to condense plasmid DNA into cationic nanoparticles, of sizes ~100 nm, whereas unmodified polymer/DNA complexes display larger particle sizes of 2 μm. Hydrophobic modification also increases the zeta potential of polymer/DNA complexes. Importantly, modified PEI-1.8 shows enhanced transfection efficiency over the unmodified counterpart. Higher transfection efficiency is obtained when PEI-1.8 is modified with shorter hydrophobic groups (MTC-ethyl) as opposed to longer ones (MTC-octyl and MTC-deodecyl). An aromatic structured functional group (MTC-benzyl) also enhances transfection efficiency more than an alkyl functional group (MTC-octyl). An added hydrogen-bonding urea group in the conjugated functional group (MTC-urea) does not enhance transfection efficiency over one without urea (MTC-benzyl). The study also demonstrates that modification degree greatly influences gene transfection, and

  11. LOW-MOLECULAR WEIGHT HEPARIN (LMWH AS A PROPHYLAXISOF DEEP VEIN THROMBOSIS (DVT IN TRAUMATIC PATIENTS

    Directory of Open Access Journals (Sweden)

    Dian Megasafitri

    2013-07-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE Deep Vein Thrombosis (DVT is the formation of a blood clot (thrombus in a vein in which to channel blood back to the heart. Traumatic injury is one of the important risk factors for DVT formation. Thrombus formation involves three important factors include the blood flow, blood components, and blood vessels, known as Virchow's Triad. Classical findings of pain in the calf of foot at dorsiflexion position (Homans sign is a sign of a specific but not sensitive and occurs in half of patients with DVT. A thorough history and physical examination is very important in the approach to patients with suspicion of having DVT. Radiological examination is an important examination in diagnosing DVT. Although there are many choices modality, the level 1 clinical evidence now supports the use of pharmacologic therapy with anticoagulants Low-Molecular Weight Heparin (LMWH for primary DVT prophylaxis agent. Different types of LMWH have different indications approved by the Food and Drug Administration (FDA as DVT prophylaxis based on the varieties of clinical evidence. Enoxaparin is the most widely indicated as a prophylaxis and treatment for DVT. Tinzaparin is indicated as a therapy, but not as a DVT prophylaxis in some groups of patients. Dalteparin is indicated as a prophylaxis, but not as a DVT therapy. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0in; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso

  12. Total protein, albumin and low-molecular-weight protein excretion in HIV-positive patients

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    Campbell Lucy J

    2012-08-01

    Full Text Available Abstract Background Chronic kidney disease is common in HIV positive patients and renal tubular dysfunction has been reported in those receiving combination antiretroviral therapy (cART. Tenofovir (TFV in particular has been linked to severe renal tubular disease as well as proximal tubular dysfunction. Markedly elevated urinary concentrations of retinal-binding protein (RBP have been reported in patients with severe renal tubular disease, and low-molecular-weight proteins (LMWP such as RBP may be useful in clinical practice to assess renal tubular function in patients receiving TFV. We analysed 3 LMWP as well as protein and albumin in the urine of a sample of HIV positive patients. Methods In a cross-sectional fashion, total protein, albumin, RBP, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL were quantified in random urine samples of 317 HIV positive outpatients and expressed as the ratio-to-creatinine (RBPCR, CCR and NGALCR. Exposure to cART was categorised as none, cART without TFV, and cART containing TFV and a non-nucleoside reverse-transcriptase-inhibitor (TFV/NNRTI or TFV and a protease-inhibitor (TFV/PI. Results Proteinuria was present in 10.4 % and microalbuminuria in 16.7 % of patients. Albumin accounted for approximately 10 % of total urinary protein. RBPCR was within the reference range in 95 % of patients while NGALCR was elevated in 67 % of patients. No overall differences in urine protein, albumin, and LMWP levels were observed among patients stratified by cART exposure, although a greater proportion of patients exposed to TFV/PI had RBPCR >38.8 μg/mmol (343 μg/g (p = 0.003. In multivariate analyses, black ethnicity (OR 0.43, 95 % CI 0.24, 0.77 and eGFR 2 (OR 3.54, 95 % CI 1.61, 7.80 were independently associated with upper quartile (UQ RBPCR. RBPCR correlated well to CCR (r2 = 0.71, but not to NGALCR, PCR or ACR. Conclusions In HIV positive patients, proteinuria was predominantly of

  13. Vertical profiles of low molecular weight organic acids in sediment porewaters of six Chinese lakes

    Science.gov (United States)

    Xiao, M.; Wu, F. C.; Liao, H. Q.; Li, W.; Lee, X. Q.; Huang, R. S.

    2009-02-01

    SummaryThe composition and contents of low molecular weight organic acids (LMWOAs) were determined, their contributions to dissolved organic carbon (DOC) and vertical profiles were investigated in sediment porewaters of six lakes, China: Lake Sihai-Longwan (SHLW), Lake Bosten (BST), Lake Qinghai (QH), Lake Chenghai (CH), Lake Erhai (EH) and Lake Dianchi (DC). The sources and behaviors of LMWOAs during early diagenesis were also discussed. The results show that up to eight species of LMWOAs were detected in those sediment porewaters: lactic acid, acetic acid, formic acid, methanesulfonic acid (MSA), pyruvic acid, trifluoroacetic acid (TFA), sorbic acid and oxalic acid; acetic acid was the predominant species. The contents of organic acids in six lakes decrease in the rank order of QH > SHLW > BST > EH > DC > CH, with the total amount of organic acids in the northern lakes being about 27 times higher than those in the southern lakes. In total amounts of various organic acids, acetic acid were the highest and MSA was the lowest, they were 62.7 and 0.3 μM, respectively. The highest total amount of organic acids was in QH, with the average value of 92.0 μM and the contribution to DOC was 10.9% followed by SHLW, BST, EH and DC, which were 43.7 μM, 2.7%; 42.3 μM, 5.6%; 5.6 μM, 1.1%; 4.4 μM, 0.7%, respectively. Organic acid was the lowest in CH, with the average value of 0.5 μM and the contribution to DOC was just 0.04%. The main organic acids were acetic acid, pyruvic acid, sorbic acid and formic acid in SHLW, BST, DC and CH, lactic acid in both EH and QH. Vertical profiles of LMWOAs varied among different species and lakes due to the sources and complex microbial processes in early diagenesis. This study suggests LMWOAs played a significant role in the sources and transformation of DOM in the sediments in lakes.

  14. Unfractionated heparin versus low molecular weight heparins for avoiding heparin-induced thrombocytopenia in postoperative patients.

    Science.gov (United States)

    Junqueira, Daniela R; Zorzela, Liliane M; Perini, Edson

    2017-04-21

    Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody-mediated platelet activation. It is a paradoxical immune reaction resulting in thrombin generation in vivo, which leads to a hypercoagulable state and the potential to initiate venous or arterial thrombosis. A number of factors are thought to influence the incidence of HIT including the type and preparation of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin-exposed patient population, with the postoperative patient population at higher risk.Although LMWH has largely replaced UFH as a front-line therapy, there is evidence supporting a lack of superiority of LMWH compared with UFH regarding prevention of deep vein thrombosis and pulmonary embolism following surgery, and similar frequencies of bleeding have been described with LMWH and UFH. The decision as to which of these two preparations of heparin to use may thus be influenced by harmful effects such as HIT. We therefore sought to determine the relative impact of UFH and LMWH on HIT in postoperative patients receiving thromboembolism prophylaxis. This is an update of a review first published in 2012. The objective of this review was to compare the incidence of heparin-induced thrombocytopenia (HIT) and HIT complicated by venous thromboembolism in postoperative patients exposed to unfractionated heparin (UFH) versus low molecular weight heparin (LMWH). For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (May 2016), CENTRAL (2016, Issue 4) and trials registries. The authors searched Lilacs (June 2016) and additional trials were sought from reference lists of relevant publications. We included randomised controlled trials (RCTs) in which participants were postoperative patients allocated to receive prophylaxis with UFH or LMWH, in a blinded or unblinded fashion. Studies were excluded if they did not use

  15. Production of Laccase by Cochliobolus sp. Isolated from Plastic Dumped Soils and Their Ability to Degrade Low Molecular Weight PVC.

    Science.gov (United States)

    Sumathi, Tirupati; Viswanath, Buddolla; Sri Lakshmi, Akula; SaiGopal, D V R

    2016-01-01

    One of the utmost man-made problems faced today has been the ever-increasing plastic waste filling the world. It accounts for an estimated 20-30% (by volume) of municipal solid waste in landfill sites worldwide. Research on plastic biodegradation has been steadily growing over the past four decades. Several fungi have been identified that produce enzymes capable of plastic degradation in various laboratory conditions. This paper presents a study that determined the ability of fungi to degrade low molecular weight polyvinyl chloride (PVC) by the enzyme laccase. We have isolated a fungal species, Cochliobolus sp., from plastic dumped soils and they were cultured on Czapek Dox Agar slants at 30°C. The effectiveness of this fungal species on the degradation of commercial low molecular weight polyvinyl chloride (PVC) was studied under laboratory conditions. Significant differences were observed from the FTIR, GC-MS, and SEM results in between control and Cochliobolus sp. treated PVC.

  16. An innovative method for preparation of acid-free-water-soluble low-molecular-weight chitosan (AFWSLMWC).

    Science.gov (United States)

    Yue, Wu; Yao, Pingjia; Wei, Yuanan; Li, Shiqian; Lai, Fang; Liu, Xiongmin

    2008-06-01

    The ozone generated from compressed oxygen by a laboratory-scale corona discharge generator was used for the preparation of acid-free-water-soluble low-molecular-weight chitosan (AFWSLMWC). Factors affecting the percent yield of AFWSLMWC were studied in batch experiments. AFWSLMWC with a molecular weight of 4.3-13.1kDa was obtained. IR spectra demonstrated that the chemical structures of AFWSLMWC were not modified during the depolymerisation process. There was no significant change of the total degree of deacetylation (DD) of AFWSLMWC, compared with the initial chitosan. The method is promisingly suitable for scale-up manufacture of acid-free-water-soluble low-molecular-weight chitosan. Copyright © 2007 Elsevier Ltd. All rights reserved.

  17. Production of Laccase by Cochliobolus sp. Isolated from Plastic Dumped Soils and Their Ability to Degrade Low Molecular Weight PVC

    Directory of Open Access Journals (Sweden)

    Tirupati Sumathi

    2016-01-01

    Full Text Available One of the utmost man-made problems faced today has been the ever-increasing plastic waste filling the world. It accounts for an estimated 20–30% (by volume of municipal solid waste in landfill sites worldwide. Research on plastic biodegradation has been steadily growing over the past four decades. Several fungi have been identified that produce enzymes capable of plastic degradation in various laboratory conditions. This paper presents a study that determined the ability of fungi to degrade low molecular weight polyvinyl chloride (PVC by the enzyme laccase. We have isolated a fungal species, Cochliobolus sp., from plastic dumped soils and they were cultured on Czapek Dox Agar slants at 30°C. The effectiveness of this fungal species on the degradation of commercial low molecular weight polyvinyl chloride (PVC was studied under laboratory conditions. Significant differences were observed from the FTIR, GC-MS, and SEM results in between control and Cochliobolus sp. treated PVC.

  18. Randomized Phase III Trial of Low Molecular Weight Heparin Enoxaparin in Addition to Standard Treatment in Small Cell Lung Cancer

    DEFF Research Database (Denmark)

    Ek, L; Gezelius, E; Bergman, B

    2017-01-01

    Background: Coagulation activation and venous thromboembolism (VTE) are hallmarks of malignant disease and represent a major cause of morbidity and mortality in cancer. Coagulation inhibition with low molecular weight heparin (LMWH) may improve survival specifically in small cell lung cancer (SCLC...... in VTE incidence. Addition of LMWH cannot be generally recommended in the management of SCLC patients, and predictive biomarkers of VTE and LMWH-associated bleeding in cancer patients are warranted. ClinicalTrials.gov: NCT00717938....

  19. The impact of low molecular weight heparin on obstetric outcomes among unexplained recurrent miscarriages complicated with methylenetetrahydrofolate reductase gene polymorphism.

    Science.gov (United States)

    Cetin, Orkun; Karaman, Erbil; Cim, Numan; Dirik, Deniz; Sahin, Hanim Guler; Kara, Erdal; Esen, Ramazan

    2017-01-01

    The association between methylenetetrahydrofolate reductase gene polymorphisms and unexplained recurrent miscarriage is elusive. The recommendations for improving pregnancy outcomes in these patients keep changing based on the available evidence. The aim of this study is to analyze the impact of low molecular weight heparin on obstetric outcomes of recurrent miscarriage patients complicated with methylenetetrahydrofolate reductase gene polymorphism. We reviewed medical records of 121 patients with a history of recurrent miscarriage complicated by methylenetetrahydrofolate reductase gene polymorphisms, retrospectively. From among them, 68 patients were treated only with folic acid and iron. The remaining 53 patients were treated with folic acid, iron and prophylactic doses of low molecular weight heparin. The subsequent pregnancy outcomes of these patients were noted. The live birth rate was higher in patients with anticoagulant therapy than in patients without anticoagulant therapy (48.5% vs. 69.8%, respectively, p: 0.015) and the congenital anomaly rate was lower in anticoagulant therapy group (17.6% vs. 3.8%, respectively, p: 0.022). The other obstetric outcomes were found to be similar between the two groups. The current study demonstrated that low molecular weight heparin improved the live birth rates among unex-plained recurrent miscarriage patients complicated with methylenetetrahydrofolate reductase gene polymorphisms. How-ever, the routine use of low molecular weight heparin did not improve the late pregnancy complications in these selected patients in the eastern region of our country. Further studies are needed to discriminate the effect of anticoagulation on the live birth rate of each of methylenetetrahydrofolate reductase gene polymorphism type.

  20. Holographic investigations of azobenzene-containing low-molecular-weight compounds in pure materials and binary blends with polystyrene.

    Science.gov (United States)

    Audorff, Hubert; Walker, Roland; Kador, Lothar; Schmidt, Hans-Werner

    2011-11-04

    This paper reports on the synthesis and the thermal and optical properties of photochromic low-molecular-weight compounds, especially with respect to the formation of holographic volume gratings in the pure materials and in binary blends with polystyrene. Its aim is to provide a basic understanding of the holographic response with regard to the molecular structure, and thus to show a way to obtain suitable rewritable materials with high sensitivity for holographic data storage. The photoactive low-molecular-weight compounds consist of a central core with three or four azobenzene-based arms attached through esterification. Four different cores were investigated that influence the glass transition temperature and the glass-forming properties. Additional structural variations were introduced by the polar terminal substituent at the azobenzene chromophore to fine-tune the optical properties and the holographic response. Films of the neat compounds were investigated in holographic experiments, especially with regard to the material sensitivity. In binary blends of the low-molecular-weight compounds with polystyrene, the influence of a polymer matrix on the behavior in holographic experiments was studied. The most promising material combination was also investigated at elevated temperatures, at which the holographic recording sensitivity is even higher. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Deproteinization assessment using isotopically enriched compounds to trace the coprecipitation of low-molecular-weight selenium species with proteins.

    Science.gov (United States)

    Godin, Simon; Bouzas-Ramos, Diego; Fontagné-Dicharry, Stéphanie; Bouyssière, Brice; Bueno, Maïté

    2017-08-01

    Studies have shown that information related to the presence of low-molecular-weight metabolites is frequently lost after deproteinization of complex matrices, such as blood and plasma, during sample preparation. Therefore, the effect of several deproteinization reagents on low-molecular-weight selenium species has been compared by species-specific isotope labeling. Two isotopically enriched selenium tracers were used to mimic models of small inorganic anionic ((77)Se-selenite) and organic zwitterionic ((76)Se-selenomethionine) species. The results presented here show that the use of a methanol-acetonitrile-acetone (1:1:1 v/v/v) mixture provided approximately two times less tracer loss from plasma samples in comparison with the classic procedure using acetonitrile, which may not be optimal as it leads to important losses of low-molecular-weight selenium species. In addition, the possible interactions between selenium tracers and proteins were investigated, revealing that both coprecipitation phenomena and association with proteins were potentially responsible for selenite tracer losses during protein precipitation in blood samples. However, coprecipitation phenomena were found to be fully responsible for losses of both tracers observed in plasma samples and of the selenomethionine tracer in blood samples. This successfully applied strategy is anticipated to be useful for more extensive future studies in selenometabolomics. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Mass Spectrometry Imaging of low Molecular Weight Compounds in Garlic (Allium sativum L.) with Gold Nanoparticle Enhanced Target.

    Science.gov (United States)

    Misiorek, Maria; Sekuła, Justyna; Ruman, Tomasz

    2017-11-01

    Garlic (Allium sativum) is the subject of many studies due to its numerous beneficial properties. Although compounds of garlic have been studied by various analytical methods, their tissue distributions are still unclear. Mass spectrometry imaging (MSI) appears to be a very powerful tool for the identification of the localisation of compounds within a garlic clove. Visualisation of the spatial distribution of garlic low-molecular weight compounds with nanoparticle-based MSI. Compounds occurring on the cross-section of sprouted garlic has been transferred to gold-nanoparticle enhanced target (AuNPET) by imprinting. The imprint was then subjected to MSI analysis. The results suggest that low molecular weight compounds, such as amino acids, dipeptides, fatty acids, organosulphur and organoselenium compounds are distributed within the garlic clove in a characteristic manner. It can be connected with their biological functions and metabolic properties in the plant. New methodology for the visualisation of low molecular weight compounds allowed a correlation to be made between their spatial distribution within a sprouted garlic clove and their biological function. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Microbial utilization of low molecular weight organic substrates in soil depends on their carbon oxidation state

    Science.gov (United States)

    Gunina, Anna; Smith, Andrew; Jones, Davey; Kuzyakov, Yakov

    2017-04-01

    Removal of low molecular weight organic substances (LMWOS), originating from plants and microorganisms, from soil solution is regulated by microbial uptake. In addition to the concentration of LMWOS in soil solution, the chemical properties of each substance (e.g. C oxidation state, number of C atoms, number of -COOH groups) can affect their uptake and subsequent partitioning of C within the soil microbial community. The aim of this study was to trace the initial fate of three dominant classes of LMWOS in soil (sugars, carboxylic and amino acids), including their removal from solution and utilization by microorganisms, and to reveal the effect of substance chemical properties on these processes. Soil solution, spiked at natural abundance levels with 14C-labelled glucose, fructose, malate, succinate, formate, alanine or glycine, was added to the soil and 14C was traced in the dissolved organic carbon (DOC), CO2, cytosol and soil organic carbon (SOC) over 24 hours. The half-life time of all LMWOS in the DOC (T1 /2-solution) varied between 0.6-5.0 min showing extremely fast initial uptake of LMWOS. The T1 /2-solution of substances was dependent on C oxidation state, indicating that less oxidized organic substances (with C oxidation state "0") were retained longer in soil solution than oxidized substances. The LMWOS-C T1 /2-fast, characterizing the half-life time of 14C in the fast mineralization pool, ranged between 30 and 80 min, with the T1 /2-fast of carboxylic acids (malic acid) being the fastest and the T1 /2-fast of amino acids (glycine) being the slowest. An absence of correlation between T1 /2-fast and either C oxidation state, number of C atoms, or number of -COOH groups suggests that intercellular metabolic pathways are more important for LMWOS transformation in soil than their basic chemical properties. The CO2 release during LMWOS mineralization accounted for 20-90% of 14C applied. Mineralization of LMWOS was the least for sugars and the greatest for

  4. Low-molecular-weight heparin versus compression stockings for thromboprophylaxis after knee arthroscopy: a randomized trial.

    Science.gov (United States)

    Camporese, Giuseppe; Bernardi, Enrico; Prandoni, Paolo; Noventa, Franco; Verlato, Fabio; Simioni, Paolo; Ntita, Kadimashi; Salmistraro, Giovanna; Frangos, Christos; Rossi, Franco; Cordova, Rosamaria; Franz, Francesca; Zucchetta, Pietro; Kontothanassis, Dimitrios; Andreozzi, Giuseppe Maria

    2008-07-15

    Knee arthroscopy, the most common orthopedic operation worldwide, carries a definite risk for deep venous thrombosis; however, postsurgical thromboprophylaxis is not routinely recommended. To evaluate whether low-molecular-weight heparin (LMWH) better prevents deep venous thrombosis and does not cause more complications than graduated compression stockings in adults having knee arthroscopy. Assessor-blind, randomized, controlled trial. The Department of Knee Surgery, Abano Terme Clinic, Abano Terme (knee surgery, random assignment, and bleeding event survey), and the Unit of Angiology, University Hospital of Padua, Padua (efficacy outcomes evaluation, follow-up, data management, and analysis), Italy. 1761 consecutive patients undergoing knee arthroscopy between March 2002 and January 2006. Patients were randomly assigned to wear full-length graduated compression stocking for 7 days (660 patients) or to receive a once-daily subcutaneous injection of LMWH (nadroparin, 3800 anti-Xa IU) for 7 days (657 patients) or 14 days (444 patients). The data and safety monitoring board prematurely stopped the 14-day heparin group after the second interim analysis. Combined incidence of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality (primary efficacy end point) and combined incidence of major and clinically relevant bleeding events (primary safety end point). All patients had bilateral whole-leg ultrasonography at the end of the allocated prophylactic regimen or earlier if indicated. All patients with normal findings were followed for 3 months, and none was lost to follow-up. The 3-month cumulative incidence of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality was 3.2% (21 of 660 patients) in the stockings group, 0.9% (6 of 657 patients) in the 7-day LMWH group (absolute difference, 2.3 percentage points [95% CI, 0.7 to 4.0 percentage points]; P = 0.005), and 0.9% (4

  5. Unfractionated heparin versus low molecular weight heparin for avoiding heparin-induced thrombocytopenia in postoperative patients.

    Science.gov (United States)

    Junqueira, Daniela R G; Perini, Edson; Penholati, Raphael R M; Carvalho, Maria G

    2012-09-12

    Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody-mediated platelet activation. It is a poorly understood paradoxical immune reaction resulting in thrombin generation in vivo, which leads to a hypercoagulable state and the potential to initiate venous or arterial thrombosis. A number of factors are thought to influence the incidence of HIT including the type and preparation of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin-exposed patient population, with the postoperative patient population presenting a higher risk.Although LMWH has largely replaced UFH as a front-line therapy, there is evidence supporting a lack of superiority of LMWH compared with UFH regarding prevention of deep vein thrombosis and pulmonary embolism following surgery, and similar frequencies of bleeding have been described with LMWH and UFH. The decision as to which of these two preparations of heparin to use may thus be influenced by adverse reactions such as HIT. We therefore sought to determine the relative impact of UFH and LMWH specifically on HIT in postoperative patients receiving thromboembolism prophylaxis. The objective of this review was to compare the incidence of HIT and HIT complicated by thrombosis in patients exposed to UFH versus LMWH in randomised controlled trials (RCTs) of postoperative heparin therapy. The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (March 2012) and CENTRAL (2012, Issue 2). In addition, the authors searched LILACS (March 2012) and additional trials were sought from reference lists of relevant publications. We were interested in comparing the incidence of HIT occurring during exposure to UFH or LMWH after any surgical intervention. Therefore, we studied RCTs in which participants were postoperative patients allocated to receive UFH or LMWH, in a blinded or unblinded fashion. Eligible studies were

  6. High and Low Molecular Weight Fluorescein Isothiocyanate (FITC)-Dextrans to Assess Blood-Brain Barrier Disruption: Technical Considerations.

    Science.gov (United States)

    Hoffmann, Angelika; Bredno, Jörg; Wendland, Michael; Derugin, Nikita; Ohara, Peter; Wintermark, Max

    2011-03-01

    This note is to report how histological preparation techniques influence the extravasation pattern of the different molecular sizes of fluorescein isothiocyanate (FITC)-dextrans, typically used as markers for blood-brain barrier leakage. By using appropriate preparation methods, false negative results can be minimized. Wistar rats underwent a 2-h middle cerebral artery occlusion and magnetic resonance imaging. After the last imaging scan, Evans blue and FITC-dextrans of 4, 40, and 70 kDa molecular weight were injected. Different histological preparation methods were used. Sites of blood-brain barrier leakage were analyzed by fluorescence microscopy. Extravasation of Evans blue and high molecular FITC-dextrans (40 and 70 kDa) in the infarcted region could be detected with all preparation methods used. If exposed directly to saline, the signal intensity of these FITC-dextrans decreased. Extravasation of the 4-kDa low molecular weight FITC-dextran could only be detected using freshly frozen tissue sections. Preparations involving paraformaldehyde and sucrose resulted in the 4-kDa FITC-dextran dissolving in these reactants and being washed out, giving the false negative result of no extravasation. FITC-dextrans represent a valuable tool to characterize altered blood-brain barrier permeability in animal models. Diffusion and washout of low molecular weight FITC-dextran can be avoided by direct immobilization through immediate freezing of the tissue. This pitfall needs to be known to avoid the false impression that there was no extravasation of low molecular weight FITC-dextrans.

  7. Characterization of dacC, which encodes a new low-molecular-weight penicillin-binding protein in Bacillus subtilis

    DEFF Research Database (Denmark)

    Pedersen, Lotte Bang; Murray, T; Popham, D L

    1998-01-01

    The pbp gene (renamed dacC), identified by the Bacillus subtilis genome sequencing project, encodes a putative 491-residue protein with sequence homology to low-molecular-weight penicillin-binding proteins. Use of a transcriptional dacC-lacZ fusion revealed that dacC expression (i) is initiated...... at the end of stationary phase; (ii) depends strongly on transcription factor sigmaH; and (iii) appears to be initiated from a promoter located immediately upstream of yoxA, a gene of unknown function located upstream of dacC on the B. subtilis chromosome. A B. subtilis dacC insertional mutant grew...

  8. Use of Low Molecular Weight Heparin and Aminocaproic Acid in Chronic DIC Associated with Prostate Cancer- A Case Report

    Directory of Open Access Journals (Sweden)

    Keisuke Shirai

    2007-01-01

    Full Text Available Disseminated Intravascular Coagulopathy (DIC is the most common coagulopathy in patients with prostate cancer. Though rare, it could be fatal without treatment. Literature suggests that there is significant activation of fibrinolytic pathway. Pathophysiology of DIC in patients with prostate cancer is not completely understood. We present here a case of chronic DIC in a patient with metastatic androgen independent prostate cancer. His DIC was managed successfully with a combination of aminocaproic acid and low weight molecular heparin. The use of low molecular weight heparin may make management of chronic DIC in prostate cancer more feasible in an out patient setting.

  9. Low-molecular weight fractions of Japanese soy sauce act as a RAGE antagonist via inhibition of RAGE trafficking to lipid rafts.

    Science.gov (United States)

    Munesue, Seiichi; Yamamoto, Yasuhiko; Urushihara, Ryouta; Inomata, Kouhei; Saito, Hidehito; Motoyoshi, So; Watanabe, Takuo; Yonekura, Hideto; Yamamoto, Hiroshi

    2013-12-01

    Advanced glycation end-products (AGE) have been implicated in aging and the pathogenesis of diabetic complications, inflammation, Alzheimer's disease, and cancer. AGE engage the cell surface receptor for AGE (RAGE), which in turn elicits intracellular signaling, leading to activation of NF-κB to cause deterioration of tissue homeostasis. AGE are not only formed within our bodies but are also derived from foods, endowing them with flavor. In the present study, we assessed the agonistic/antagonistic effects of food-derived AGE on RAGE signaling in a reporter assay system and found that low-molecular weight AGE can antagonize the action of AGE-BSA. Foods tested were Japanese soy sauce, coffee, cola, and red wine, all of which showed fluorescence characteristics of AGE. Soy sauce and coffee contained N(ε)-carboxymethyl-lysine (CML). Soy sauce, coffee, and red wine inhibited the RAGE ligand-induced activation of NF-κB, whereas cola had no effect on the ligand induction of NF-κB. The liquids were then fractionated into high-molecular weight (HMW) fractions and low-molecular weight (LMW) fractions. Soy sauce-, coffee-, and red wine-derived LMW fractions consistently inhibited the RAGE ligand induction of NF-κB, whereas the HMW fractions of these foods activated RAGE signaling. Using the LMW fraction of soy sauce as a model food-derived RAGE antagonist, we performed a plate-binding assay and found that the soy sauce LMW fractions competitively inhibited AGE-RAGE association. Further, this fraction significantly reduced AGE-dependent monocyte chemoattractant protein-1 (MCP-1) secretion from murine peritoneal macrophages. The LMF from soy sauce suppressed the AGE-induced RAGE trafficking to lipid rafts. These results indicate that small components in some, if not all, foods antagonize RAGE signaling and could exhibit beneficial effects on RAGE-related diseases.

  10. Endomembrane Cation Transporters and Membrane Trafficking

    Energy Technology Data Exchange (ETDEWEB)

    Sze, Heven [Univ. of Maryland, College Park, MD (United States). Dept. of Cell Biology & Molecular Genetics

    2017-04-01

    Multicellular, as well as unicellular, organisms have evolved mechanisms to regulate ion and pH homeostasis in response to developmental cues and to a changing environment. The working hypothesis is that the balance of fluxes mediated by diverse transporters at the plasma membrane and in subcellular organelles determines ionic cellular distribution, which is critical for maintenance of membrane potential, pH control, osmolality, transport of nutrients, and protein activity. An emerging theme in plant cell biology is that cells respond and adapt to diverse cues through changes of the dynamic endomembrane system. Yet we know very little about the transporters that might influence the operation of the secretory system in plants. Here we focus on transporters that influence alkali cation and pH homeostasis, mainly in the endomembrane/ secretory system. The endomembrane system of eukaryote cells serves several major functions: i) sort cargo (e.g. enzymes, transporters or receptors) to specific destinations, ii) modulate the protein and lipid composition of membrane domains through remodeling, and iii) determine and alter the properties of the cell wall through synthesis and remodeling. We had uncovered a novel family of predicted cation/H+ exchangers (CHX) and K+ efflux antiporters (KEA) that are prevalent in higher plants, but rare in metazoans. We combined phylogenetic and transcriptomic analyses with molecular genetic, cell biological and biochemical studies, and have published the first reports on functions of plant CHXs and KEAs. CHX studied to date act at the endomembrane system where their actions are distinct from the better-studied NHX (Na/K-H+ exchangers). Arabidopsis thaliana CHX20 in guard cells modulate stomatal opening, and thus is significant for vegetative survival. Other CHXs ensure reproductive success on dry land, as they participate in organizing pollen walls, targeting of pollen tubes to the ovule or promoting

  11. Characterization of the modes of binding between human sweet taste receptor and low-molecular-weight sweet compounds.

    Directory of Open Access Journals (Sweden)

    Katsuyoshi Masuda

    Full Text Available One of the most distinctive features of human sweet taste perception is its broad tuning to chemically diverse compounds ranging from low-molecular-weight sweeteners to sweet-tasting proteins. Many reports suggest that the human sweet taste receptor (hT1R2-hT1R3, a heteromeric complex composed of T1R2 and T1R3 subunits belonging to the class C G protein-coupled receptor family, has multiple binding sites for these sweeteners. However, it remains unclear how the same receptor recognizes such diverse structures. Here we aim to characterize the modes of binding between hT1R2-hT1R3 and low-molecular-weight sweet compounds by functional analysis of a series of site-directed mutants and by molecular modeling-based docking simulation at the binding pocket formed on the large extracellular amino-terminal domain (ATD of hT1R2. We successfully determined the amino acid residues responsible for binding to sweeteners in the cleft of hT1R2 ATD. Our results suggest that individual ligands have sets of specific residues for binding in correspondence with the chemical structures and other residues responsible for interacting with multiple ligands.

  12. Determination of low molecular weight alcohols including fusel oil in various samples by diethyl ether extraction and capillary gas chromatography.

    Science.gov (United States)

    Woo, Kang-Lyung

    2005-01-01

    Low molecular weight alcohols including fusel oil were determined using diethyl ether extraction and capillary gas chromatography. Twelve kinds of alcohols were successfully resolved on the HP-FFAP (polyethylene glycol) capillary column. The diethyl ether extraction method was very useful for the analysis of alcohols in alcoholic beverages and biological samples with excellent cleanliness of the resulting chromatograms and high sensitivity compared to the direct injection method. Calibration graphs for all standard alcohols showed good linearity in the concentration range used, 0.001-2% (w/v) for all alcohols. Salting out effects were significant (p < 0.01) for the low molecular weight alcohols methanol, isopropanol, propanol, 2-butanol, n-butanol and ethanol, but not for the relatively high molecular weight alcohols amyl alcohol, isoamyl alcohol, and heptanol. The coefficients of variation of the relative molar responses were less than 5% for all of the alcohols. The limits of detection and quantitation were 1-5 and 10-60 microg/L for the diethyl ether extraction method, and 10-50 and 100-350 microg/L for the direct injection method, respectively. The retention times and relative retention times of standard alcohols were significantly shifted in the direct injection method when the injection volumes were changed, even with the same analysis conditions, but they were not influenced in the diethyl ether extraction method. The recoveries by the diethyl ether extraction method were greater than 95% for all samples and greater than 97% for biological samples.

  13. The polysaccharide and low molecular weight components of Opuntia ficus indica cladodes: Structure and skin repairing properties.

    Science.gov (United States)

    Di Lorenzo, Flaviana; Silipo, Alba; Molinaro, Antonio; Parrilli, Michelangelo; Schiraldi, Chiara; D'Agostino, Antonella; Izzo, Elisabetta; Rizza, Luisa; Bonina, Andrea; Bonina, Francesco; Lanzetta, Rosa

    2017-02-10

    The Opuntia ficus-indica multiple properties are reflected in the increasing interest of chemists in the identification of its natural components having pharmaceutical and/or cosmetical applications. Here we report the structural elucidation of Opuntia ficus-indica mucilage that highlighted the presence of components differing for their chemical nature and the molecular weight distribution. The high molecular weight components were identified as a linear galactan polymer and a highly branched xyloarabinan. The low molecular weight components were identified as lactic acid, D-mannitol, piscidic, eucomic and 2-hydroxy-4-(4'-hydroxyphenyl)-butanoic acids. A wound healing assay was performed in order to test the cicatrizing properties of the various components, highlighting the ability of these latter to fasten dermal regeneration using a simplified in vitro cellular model based on a scratched keratinocytes monolayer. The results showed that the whole Opuntia mucilage and the low molecular weight components are active in the wound repair. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Low Molecular Weight Chitosan (LMWC-based Polyplexes for pDNA Delivery: From Bench to Bedside

    Directory of Open Access Journals (Sweden)

    Mireia Agirre

    2014-06-01

    Full Text Available Non-viral gene delivery vectors are emerging as a safer alternative to viral vectors. Among natural polymers, chitosan (Ch is the most studied one, and low molecular weight Ch, specifically, presents a wide range of advantages for non-viral pDNA delivery. It is crucial to determine the best process for the formation of Low Molecular Weight Chitosan (LMWC-pDNA complexes and to characterize their physicochemical properties to better understand their behavior once the polyplexes are administered. The transfection efficiency of Ch based polyplexes is relatively low. Therefore, it is essential to understand all the transfection process, including the cellular uptake, endosomal escape and nuclear import, together with the parameters involved in the process to improve the design and development of the non-viral vectors. The aim of this review is to describe the formation and characterization of LMWC based polyplexes, the in vitro transfection process and finally, the in vivo applications of LMWC based polyplexes for gene therapy purposes.

  15. A low molecular weight ES-20 protein released in vivo and in vitro with diagnostic potential in lymph node tuberculosis

    Directory of Open Access Journals (Sweden)

    Shende N

    2008-01-01

    Full Text Available Purpose: To determine role of antigens released in vivo and in vitro in immunodiagnosis of tuberculosis (TB. Methods: In vivo released circulating tuberculosis antigen (CTA was obtained from TB sera by ammonium sulphate precipitation and in vitro released excretory-secretory (ES antigens from Mycobacterium tuberculosis culture filtrate. CTA and ES antigens were fractionated by SDS-PAGE and electro-eluted gel fractions were analysed for antigen by ELISA. Results: Low molecular weight proteins CTA-9 and ES-9 showed high titre of antigen activity. To explore the diagnostic potential of low molecular weight ES antigen, M. tuberculosis ES antigen was further fractionated by gel filtration chromatography followed by purification on anion exchange column using fast protein liquid chromatography and a highly seroreactive ESG-5D (ES-20 antigen was obtained. Competitive inhibition showed that CTA-9 and ES-9 antigens inhibit the binding of ES-20 antigen to its antibody. Seroanalysis showed sensitivity of 83 and 80% for ES-20 antigen and antibody detection, respectively, in pulmonary TB and 90% in lymph node TB. Conclusions: Seroreactivity studies using M. tuberculosis ES-20 antigen showed usefulness in detection of TB; in particular, lymph node TB.

  16. The low molecular weight protein PsaI stabilizes the light-harvesting complex II docking site of photosystem I

    DEFF Research Database (Denmark)

    Plöchinger, Magdalena; Torabi, Salar; Rantala, Marjaana

    2016-01-01

    PsaI represents one of three low molecular weight peptides of PSI. Targeted inactivation of the plastid PsaI gene in Nicotiana tabacum has no measurable effect on photosynthetic electron transport around PSI or on accumulation of proteins involved in photosynthesis. Instead, the lack of PsaI dest...... of mutant plants into state 2 in darkness represents a compensatory and/or protective metabolic mechanism. This involves an increased reduction and/or reduced oxidation of the PQ pool, presumably to sustain a balanced excitation of both photosystems upon the onset of light.......PsaI represents one of three low molecular weight peptides of PSI. Targeted inactivation of the plastid PsaI gene in Nicotiana tabacum has no measurable effect on photosynthetic electron transport around PSI or on accumulation of proteins involved in photosynthesis. Instead, the lack of Psa......I destabilizes the association of PsaL and PsaH to PSI, both forming the light-harvesting complex (LHC)II docking site of PSI. These alterations at the LHCII binding site surprisingly did not prevent state transition but led to an increased incidence of PSI-LHCII complexes, coinciding with an elevated...

  17. Meta-analysis of low-molecular-weight heparin to prevent recurrent placenta-mediated pregnancy complications.

    Science.gov (United States)

    Rodger, Marc A; Carrier, Marc; Le Gal, Grégoire; Martinelli, Ida; Perna, Annalisa; Rey, Evelyne; de Vries, J I P; Gris, Jean-Christophe

    2014-02-06

    A 35-year-old woman with recurrent severe placenta-mediated pregnancy complications in her 2 pregnancies asks: Will low-molecular-weight heparin help prevent recurrent placenta-mediated pregnancy complications in my next pregnancy? We performed a meta-analysis of randomized controlled trials (RCTs) comparing low-molecular-weight heparin (LMWH) vs no LMWH for the prevention of recurrent placenta-mediated pregnancy complications. We identified six RCTs that included a total of 848 pregnant women with prior placenta-mediated pregnancy complications. The primary outcome was a composite of pre-eclampsia (PE), birth of a small-for-gestational-age (SGA) newborn (pregnancy loss >20 weeks. Overall, 67 (18.7%) of 358 of women being given prophylactic LMWH had recurrent severe placenta-mediated pregnancy complications compared with 127 (42.9%) of 296 women with no LMWH (relative risk reduction, 0.52; 95% CI, 0.32 to 0.86; P = .01; I(2), 69%, indicating moderate heterogeneity). We identified similar relative risk reductions with LMWH for individual outcomes, including any PE, severe PE, SGA pregnancy complications, but further research is required.

  18. Composition and functional analysis of low-molecular-weight glutenin alleles with Aroona near-isogenic lines of bread wheat

    Directory of Open Access Journals (Sweden)

    Zhang Xiaofei

    2012-12-01

    Full Text Available Abstract Background Low-molecular-weight glutenin subunits (LMW-GS strongly influence the bread-making quality of bread wheat. These proteins are encoded by a multi-gene family located at the Glu-A3, Glu-B3 and Glu-D3 loci on the short arms of homoeologous group 1 chromosomes, and show high allelic variation. To characterize the genetic and protein compositions of LMW-GS alleles, we investigated 16 Aroona near-isogenic lines (NILs using SDS-PAGE, 2D-PAGE and the LMW-GS gene marker system. Moreover, the composition of glutenin macro-polymers, dough properties and pan bread quality parameters were determined for functional analysis of LMW-GS alleles in the NILs. Results Using the LMW-GS gene marker system, 14–20 LMW-GS genes were identified in individual NILs. At the Glu-A3 locus, two m-type and 2–4 i-type genes were identified and their allelic variants showed high polymorphisms in length and nucleotide sequences. The Glu-A3d allele possessed three active genes, the highest number among Glu-A3 alleles. At the Glu-B3 locus, 2–3 m-type and 1–3 s-type genes were identified from individual NILs. Based on the different compositions of s-type genes, Glu-B3 alleles were divided into two groups, one containing Glu-B3a, B3b, B3f and B3g, and the other comprising Glu-B3c, B3d, B3h and B3i. Eight conserved genes were identified among Glu-D3 alleles, except for Glu-D3f. The protein products of the unique active genes in each NIL were detected using protein electrophoresis. Among Glu-3 alleles, the Glu-A3e genotype without i-type LMW-GS performed worst in almost all quality properties. Glu-B3b, B3g and B3i showed better quality parameters than the other Glu-B3 alleles, whereas the Glu-B3c allele containing s-type genes with low expression levels had an inferior effect on bread-making quality. Due to the conserved genes at Glu-D3 locus, Glu-D3 alleles showed no significant differences in effects on all quality parameters. Conclusions This work

  19. In Vivo Anti-Cancer Mechanism of Low-Molecular-Weight Fucosylated Chondroitin Sulfate (LFCS from Sea Cucumber Cucumaria frondosa

    Directory of Open Access Journals (Sweden)

    Xiaoxiao Liu

    2016-05-01

    Full Text Available The low-molecular-weight fucosylated chondroitin sulfate (LFCS was prepared from native fucosylated chondroitin sulfate (FCS, which was extracted and isolated from sea cucumber Cucumaria frondosa, and the anti-cancer mechanism of LFCS on mouse Lewis lung carcinoma (LLC was investigated. The results showed that LFCS remarkably inhibited LLC growth and metastasis in a dose-dependent manner. LFCS induced cell cycle arrest by increasing p53/p21 expression and apoptosis through activation of caspase-3 activity in LLC cells. Meanwhile, LFCS suppressed the expression of vascular endothelial growth factor (VEGF, increased the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1 and downregulated the matrix metalloproteinases (MMPs level. Furthermore, LFCS significantly suppressed the activation of ERK1/2/p38 MAPK/NF-κB pathway, which played a prime role in expression of MMPs. All of these data indicate LFCS may be used as anti-cancer drug candidates and deserve further study.

  20. Colloidal Au replacement assay for highly sensitive quantification of low molecular weight analytes by surface plasmon resonance.

    Science.gov (United States)

    Takae, Seiji; Akiyama, Yoshitsugu; Yamasaki, Yuichi; Nagasaki, Yukio; Kataoka, Kazunori

    2007-01-01

    A novel sensing method based on surface plasmon resonance (SPR) was developed for the highly sensitive quantification of low molecular weight (LMW) analytes (colloidal Au replacement assay). Gold nanoparticles (diameter = 20 nm) functionalized with lactosyl-poly(ethylene glycol) (PEG) were prepared and were specifically adsorbed onto a Ricinus communis agglutinin (RCA120)-immobilized SPR sensor chip surface. Subsequent injection of free d-galactose elicited the elution of the preadsorbed lactosyl-PEGylated gold nanoparticles in a manner proportional to the galactose concentration, achieving a substantial and quantitative analysis over a wide range of galactose concentrations (0.1-50 ppm). This method of d-galactose sensing through the substituted elution of preadsorbed nanoparticles from the sensor chip surface would be applicable for the highly sensitive SPR quantification of various LMW analytes, which are known to be difficult to detect by the conventional SPR sensing regime.

  1. Fondaparinux (ARIXTRA) as an alternative anti-thrombotic prophylaxis when there is hypersensitivity to low molecular weight and unfractionated heparins.

    Science.gov (United States)

    Parody, Rocio; Oliver, Arturo; Souto, Juan Carlos; Fontcuberta, Jordi

    2003-11-01

    During the last decade, new anticoagulant drugs with anti-factor-Xa properties have been described (1, 2). Among them is fondaparinux that has been licensed recently. It is a pentasaccharide mimicking the site where heparin binds to antithrombin III (1). This new drug has produced very promising clinical results in the prophylaxis of venous thrombosis after orthopedic surgery (3). Here we report two different clinical situations in which fondaparinux has yielded a successful outcome: first, a patient with repeated cutaneus reaction to several different low molecular weight heparins (LMWH), and second, a patient with severe heparin-induced thrombocytopenia (HIT). We decided to use fondaparinux in both cases since it is commercially available in Spain and mostly because the absence of in vitro cross-reaction with heparins, as discussed later.

  2. Enrichment of serum low-molecular-weight proteins using C18 absorbent under urea/dithiothreitol denatured environment.

    Science.gov (United States)

    Wu, Jing; An, Yuan; Pu, Hai; Shan, Yue; Ren, Xiaoqing; An, Mingrui; Wang, Qingsong; Wei, Shicheng; Ji, Jianguo

    2010-03-01

    Serum low-molecular-weight proteins (LMWPs, molecular weightaffinity tag (ICAT) labeling quantification. Proteins existing in human serum at low nanograms/milliliter (ng/ml) levels, such as myeloid-related proteins (MRPs), could be identified directly from 2-DE coupled with matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS) and LTQ-Orbitrap MS. Sixteen proteins were confidentially identified and quantified using ICAT labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS). By virtue of its easy operation and high reproducibility to process large quantity complex serum samples, this method has potential uses in enriching LMWPs either in serum or in cell and tissue samples. Copyright 2009 Elsevier Inc. All rights reserved.

  3. Diffuse Alveolar Hemorrhage Associated With Low Molecular Weight Heparin and Dual Anti-platelet Therapy After Percutaneous Coronary Intervention.

    Science.gov (United States)

    Yildirim, Fatma; Kara, İskender; Okuyan, Hızır; Abaci, Adnan; Turkoglu, Melda; Aygencel, Gülbin

    2016-01-19

    A 54-year-old man had undergone to percutaneous coronary intervention (PCI) and two stents were placed to left anterior coronary artery and circumflex artery. Low molecular weight heparin (LMWH) together with ticagrelor 90 mg twice a day and acetylsalicylic acid (Aspirin) were started after PCI due to high risk of stent trombosis. On the fourth day of patient's follow-up in the intensive care unit (ICU), bloody secretion was started from endotracheal tube. Hemoglobin dropping, bilateral infiltration on the chest X-ray and bleeding from lung were diagnosed as diffuse alveolar hemorrhage (DAH). Apart from LMWH and antiplatelet therapies with aspirin and ticagrelor, there were no other identified risk factors for DAH. As far as we know, our report is the first case of DAH caused by LMWH and dual anti-platelet therapy including ticagrelor. This article is protected by copyright. All rights reserved. Copyright © 2016 John Wiley & Sons Ltd.

  4. Volatile organic compound and formaldehyde emissions from Populus davidiana wood treated with low molecular weight urea-formaldehyde resin.

    Science.gov (United States)

    Wang, Jing-Xian; Shen, Jun; Lei, Cheng-Shuai; Feng, Qi

    2014-09-01

    Populus davidiana wood was usually impregnated with low molecular weight thermosetting resins to improve its physical and mechanical properties. However, volatile organic compounds (VOCs) and formaldehyde emitted from treated wood have lead to poor indoor air quality (IAQ). The trends of VOC and formaldehyde emissions as a function of the weight percent gain (WPG) factor were mainly investigated in this work. Aldehydes and alkanes were the predominant compositions indentified in the VOC emissions, although low amount of ketones, terpenes and alcohols were also found. With the increase in WPG, VOC and formaldehyde concentrations improved. However, their concentration began to decrease when WPG was over 44.06% (VOC) and 36.35% (formaldehyde), respectively. The modulus of elasticity (MOE) of untreated and treated wood at different WPG levels was detected. It showed that treatment of wood with UF resin significantly improved the mechanical properties. Therefore, it is probably helpful to comprehensively analyze correlations among environmental performance, mechanical performance and processing costs.

  5. Cross-linked agarose for separation of low molecular weight natural products in hydrophilic interaction liquid chromatography.

    Science.gov (United States)

    Tan, Tianwei; Su, Zhi-Guo; Gu, Ming; Xu, Jun; Janson, Jan-Christer

    2010-05-01

    Following its market introduction in 1982, the cross-linked 12% agarose gel media Superose 12 has become widely known as a tool for size exclusion chromatography of proteins and other biological macromolecules. In this review it is shown that, when appropriate mobile phases are used, Superose possesses adsorption properties similar to that of traditional media for hydrophilic interaction liquid chromatography (HILIC). This is illustrated by the separation and purification of low molecular weight compounds such as polyphenols including active components of traditional Chinese medicinal herbs and green tea. Structural features of the cross-linked agarose that likely cause the observed adsorption effects are discussed as well. These are identified as being primarily ether bonds acting as strong hydrogen bond acceptors as well as hydrophobic residues originating from the cross-linking reagents.

  6. Effect of Intermolecular Hydrogen Bonding on the Dynamics of Poly (2-vinylpyridine) Mixtures Containing Low Molecular Weight Phenolic Compounds

    Science.gov (United States)

    Atorngitjawat, Pornpen; Klein, Robert; McDermott, Amanda; Painter, Paul; Runt, James

    2008-03-01

    The dynamics of poly(2-vinylpyridine) (P2VPy) mixed with a series of low molecular weight phenolic molecules (containing one to six hydroxyl groups) were investigated using broadband dielectric spectroscopy. For all mixtures, FTIR spectroscopy indicates significant intermolecular H-bonding. All mixtures were single phase except for that containing 10 mol% hexahydroxybenzophenone, which formed a H-bonded complex with P2VPy. Intermolecular hydrogen bonding resulted in significant suppression of the P2VPy local relaxation in the glassy state. The segmental relaxations for mixtures containing 30 and 50% polyhydroxy compounds where broadened, indicating dynamic heterogeneity, whereas all P2VPy - ethylphenol mixtures exhibited dynamic homogeneity. Changes in relaxation strength of the segmental process are considered in light of calculated dipole moments for all species under investigation.

  7. Low-Molecular-Weight Chitosan Supplementation Increases the Population of Prevotella in the Cecal Contents of Weanling Pigs

    Directory of Open Access Journals (Sweden)

    Ting Yu

    2017-11-01

    Full Text Available Low-molecular-weight chitosan (LC promoted growth in weaned piglets as an alternative to feed-grade antibiotics. To investigate the influence of LC supplementation on piglets' gut microbiome and compare the differences in community composition between LC and antibiotics with ZnO addition, we assessed the cecal microbial community by 16S rRNA gene sequencing with three treatments consisting of basal diet (CTR group, basal diet with low-molecular-weight chitosan (LC group, and basal diet with antibiotic and ZnO (AZ group. LC decreased pH more than AZ did in the cecum (both compared to CTR. Beta diversity analysis showed that community structure was distinctly different among the CTR, LC, and AZ treatments, indicating that either LC or AZ treatment modulated the piglet microbiota. Bacteroidetes, Firmicutes, and Proteobacteria dominated the community [>98% of operational taxonomic units (OTUs] in piglet cecal contents. Compared to CTR, both LC, and AZ increased the relative abundance of Bacteroidetes while they decreased the count of Firmicutes and AZ decreased the population of Proteobacteria. In CTR the top four abundant genera were Prevotella (~10.4%, Succinivibrio (~6.2%, Lactobacillus (~5.6%, and Anaerovibrio (5.4%. Both LC and AZ increased the relative abundance of Prevotella but decreased the ratio of Lactobacillus when they compared with CTR. Moreover, LC increased the relative abundance of Succinivibrio and Anaerovibrio while AZ decreased them. The microbial function prediction showed LC enriched more pathways in the metabolism of cofactors and vitamins than CTR or AZ did. LC may potentially function as an alternative to feed-grade antibiotics in weaned piglets due to its beneficial regulation of the intestinal microbiome.

  8. Multistimuli-responsive supramolecular organogels formed by low-molecular-weight peptides bearing side-chain azobenzene moieties.

    Science.gov (United States)

    Fatás, Paola; Bachl, Jürgen; Oehm, Stefan; Jiménez, Ana I; Cativiela, Carlos; Díaz Díaz, David

    2013-07-01

    This work demonstrates that the incorporation of azobenzene residues into the side chain of low-molecular-weight peptides can modulate their self-assembly process in organic solvents leading to the formation of stimuli responsive physical organogels. The major driving forces for the gelation process are hydrogen bonding and π-π interactions, which can be triggered either by thermal or ultrasound external stimuli, affording materials having virtually the same properties. In addition, a predictive model for gelation of polar protic solvent was developed by using Kamlet-Taft solvent parameters and experimental data. The obtained viscoelastic materials exhibited interconnected multistimuli responsive behaviors including thermal-, photo-, chemo- and mechanical responses. All of them displayed thermoreversability with gel-to-sol transition temperatures established between 33-80 °C and gelation times from minutes to several hours. Structure-property relationship studies of a designed peptide library have demonstrated that the presence and position of the azobenzene residue can be operated as a versatile regulator to reduce the critical gelation concentration and enhance both the thermal stability and mechanical strength of the gels, as demonstrated by comparative dynamic rheology. The presence of N-Boc protecting group in the peptides showed also a remarkable effect on the formation and properties of the gels. Despite numerous examples of peptide-based gelators known in the literature, this is the first time in which low-molecular-weight peptides bearing side chain azobenzene units are used for the synthesis of "intelligent" supramolecular organogels. Compared with other approaches, this strategy is advantageous in terms of structural flexibility since it is compatible with a free, unprotected amino terminus and allows placement of the chromophore at any position of the peptide sequence. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Affinity of low molecular weight fucoidan for P-selectin triggers its binding to activated human platelets.

    Science.gov (United States)

    Bachelet, Laure; Bertholon, Isabelle; Lavigne, Damien; Vassy, Roger; Jandrot-Perrus, Martine; Chaubet, Frédéric; Letourneur, Didier

    2009-02-01

    P-selectin is an adhesion receptor expressed on activated platelets and endothelial cells. Its natural ligand, P-selectin glycoprotein ligand-1, is expressed on leucocytes and the P-selectin/PSGL-1 interaction is involved in leukocyte rolling. We have compared the interaction of P-selectin with several low molecular weight polysaccharides: fucoidan, heparin and dextran sulfate. Binding assays were obtained from the interaction of the polysaccharides with Sialyl Lewis X and PSGL-1 based constructs onto microtiter plates coated with P-selectin. SELDI TOF mass spectrometry was performed with anionic chips arrays coated with P-selectin in the absence or in the presence of polysaccharides. Kd were obtained from surface plasmon resonance experiments with immobilized P-selectin constructs, polysaccharides being injected in the mobile phase. Human whole blood flow cytometry experiments were performed with fluorescein isothiocyanate labelled polysaccharides with or without platelets activators. The fucoidan prevented P-selectin binding to Sialyl Lewis X with an IC(50) of 20 nM as compared to 400 nM for heparin and affinity for immobilized P-selectin with a KD of 1.2 nM, two orders of magnitude greater than the K(D) of the other polysaccharides. Mass spectrometry evidenced the formation of a complex between P-selectin and fucoidan. The intensity of the fucoidan binding to platelets was dependent on the level of platelet activation. Competition between fucoidan and an anti P-selectin antibody demonstrated the specificity of the interaction. Low molecular weight fucoidan is a promising therapeutic agent of natural origin for biomedical applications.

  10. Pilot-scale recovery of low molecular weight organic acids from ...

    African Journals Online (AJOL)

    Clarification using rotary evaporator was found to be more suitable than distillation column. Due to the presence of more than 90% of water in POME, the final clarified product comprises only 7% of the total volume. The material balance for the overall process was estimated and integrated system for the bioconversion of ...

  11. Photophysical characterization of low-molecular weight organogels for energy transfer and light harvesting

    Science.gov (United States)

    Atsbeha, T.; Bussotti, L.; Cicchi, S.; Foggi, P.; Ghini, G.; Lascialfari, L.; Marcelli, A.

    2011-05-01

    The choice of a donor and an acceptor with suitable optical and self-assembly properties is essential in the design of organogel-based light harvesting systems. Organogels can provide supramolecular structures capable of enhancing energy transfer processes. In this work, we present the characterization of N-(naphthalene-1-carboxyamide)-(3 S,4 S)-pyrrolidin-(3,4)-bisdodecyl-carbamoyldiester ( 1) and N-(4-nitrobenzofurazan-7-amino)-(3 S,4 S)-pyrrolidin-(3,4)-bisdodecyl-carbamoyldiester ( 2) which are used as donor and acceptor moieties, respectively. The donor molecule is hardly capable to form a gelon its own but it can be assembled at reasonable concentrations with the acceptor gelator to form a two-component donor-acceptor organogels in cyclohexane. Stable organogels are formed from cyclohexane for gelator concentrations as low as ≈10 -3 M. UV-vis and steady-state fluorescence spectroscopies were used to provide a characterization of their molecular interactions. The optical changes observed during the cooling of two-component solutions of these systems are indicative of typical sol-gel transitions. The occurrence of excitation energy transfer processes in the gels is confirmed by comparison of their excitation and absorption spectra.

  12. Incorporation of Low Molecular Weight Molecules into α2- Macroglobulin by Nucleophilic Exchange*

    Science.gov (United States)

    Bond, Jennifer E.; Cianciolo, George J.; Pizzo, Salvatore V.

    2007-01-01

    α2-Macroglobulin (α2M) is a proteinase inhibitor that functions by a trapping mechanism which has been exploited such that the receptor-recognized, activated form (α2M*) can be employed to target antigens to antigen-presenting cells. Another potential use of α2M* is as a drug delivery system. In this study we demonstrate that guanosine triphosphate, labeled with Texas red (GTP-TR) formed complexes with α2M* following activation by proteolytic or non-proteolytic reactions. Optimal incorporation occurred with 20μM GTP-TR, pH 8.0 for 5h at 50°C. NaCl concentration (100mM or 200mM) had little effect on incorporation at this pH or temperature, but was significant at sub-optimum temperature and pH values. Maximum incorporation was 1.2 mol GTP-TR/mol α2M*. PAGE analysis showed that 70-90% of the GTP-TR is bound in a SDS/2-mercaptoethanol resistant manner. Guanosine, adenosine, and imidazole competed with GTP-TR to form complexes with α2M*. PMID:17428443

  13. Incorporation of low molecular weight molecules into alpha(2)-macroglobulin by nucleophilic exchange.

    Science.gov (United States)

    Bond, Jennifer E; Cianciolo, George J; Pizzo, Salvatore V

    2007-06-01

    alpha(2)-Macroglobulin (alpha(2)M) is a proteinase inhibitor that functions by a trapping mechanism which has been exploited such that the receptor-recognized, activated form (alpha(2)M( *)) can be employed to target antigens to antigen-presenting cells. Another potential use of alpha(2)M( *) is as a drug delivery system. In this study we demonstrate that guanosine triphosphate, labeled with Texas red (GTP-TR) formed complexes with alpha(2)M( *) following activation by proteolytic or non-proteolytic reactions. Optimal incorporation occurred with 20 microM GTP-TR, pH 8.0 for 5h at 50 degrees C. NaCl concentration (100 or 200 mM) had little effect on incorporation at this pH or temperature, but was significant at sub-optimum temperature and pH values. Maximum incorporation was 1.2 mol GTP-TR/mol alpha(2)M( *). PAGE showed that 70-90% of the GTP-TR is bound in a SDS/2-mercaptoethanol resistant manner. Guanosine, adenosine, and imidazole competed with GTP-TR to form complexes with alpha(2)M( *).

  14. Does low-molecular-weight heparin influence the antimyeloma effects of thalidomide?

    DEFF Research Database (Denmark)

    Beksac, Meral; Waage, Anders; Bringhen, Sara

    2015-01-01

    comparing melphalan and prednisolone with (MPT, n: 404) or without thalidomide (MP, n: 393) are analyzed for effects of LMWH. Forty percent (159/394) of the patients on MPT and 7.4% (29/390) in the MP arm received LMWH. RESULTS: Thalidomide improved response and progression-free survival (PFS). Regardless...... of thalidomide treatment, response rate was higher among those receiving LMWH vs. none vs. other anticoagulants (58.1 vs. 44.9 vs. 50.4%, p = 0.01). PFS was significantly longer (median 32 vs. 21 and 17 vs. 17 months, p = 0.004) only among international scoring system (ISS) I patients receiving MPT ± LMWH vs. MP...... ± LMWH. The group of MPT patients who also received LMWH had a better OS compared to those who did not [45 months, 95% confidence interval (CI) 27.7-62.3, vs. 32 months, 95% CI 26.1-37.9; p = 0.034]. When multivariate analysis was repeated in subgroups, thalidomide was no longer a significant factor...

  15. Assessment of the Potential Biological Activity of Low Molecular Weight Metabolites of Freshwater Macrophytes with QSAR

    Directory of Open Access Journals (Sweden)

    Evgeny A. Kurashov

    2016-01-01

    Full Text Available The paper focuses on the assessment of the spectrum of biological activities (antineoplastic, anti-inflammatory, antifungal, and antibacterial with PASS (Prediction of Activity Spectra for Substances for the major components of three macrophytes widespread in the Holarctic species of freshwater, emergent macrophyte with floating leaves, Nuphar lutea (L. Sm., and two species of submergent macrophyte groups, Ceratophyllum demersum L. and Potamogeton obtusifolius (Mert. et Koch, for the discovery of their ecological and pharmacological potential. The predicted probability of anti-inflammatory or antineoplastic activities above 0.8 was observed for twenty compounds. The same compounds were also characterized by high probability of antifungal and antibacterial activity. Six metabolites, namely, hexanal, pentadecanal, tetradecanoic acid, dibutyl phthalate, hexadecanoic acid, and manool, were a part of the major components of all three studied plants, indicating their high ecological significance and a certain universalism in their use by various species of water plants for the implementation of ecological and biochemical functions. This report underlines the role of identified compounds not only as important components in regulation of biochemical and metabolic pathways and processes in aquatic ecological systems, but also as potential pharmacological agents in the fight against different diseases.

  16. Highly Conductive Ionic-Liquid Gels Prepared with Orthogonal Double Networks of a Low-Molecular-Weight Gelator and Cross-Linked Polymer.

    Science.gov (United States)

    Kataoka, Toshikazu; Ishioka, Yumi; Mizuhata, Minoru; Minami, Hideto; Maruyama, Tatsuo

    2015-10-21

    We prepared a heterogeneous double-network (DN) ionogel containing a low-molecular-weight gelator network and a polymer network that can exhibit high ionic conductivity and high mechanical strength. An imidazolium-based ionic liquid was first gelated by the molecular self-assembly of a low-molecular-weight gelator (benzenetricarboxamide derivative), and methyl methacrylate was polymerized with a cross-linker to form a cross-linked poly(methyl methacrylate) (PMMA) network within the ionogel. Microscopic observation and calorimetric measurement revealed that the fibrous network of the low-molecular-weight gelator was maintained in the DN ionogel. The PMMA network strengthened the ionogel of the low-molecular-weight gelator and allowed us to handle the ionogel using tweezers. The orthogonal DNs produced ionogels with a broad range of storage elastic moduli. DN ionogels with low PMMA concentrations exhibited high ionic conductivity that was comparable to that of a neat ionic liquid. The present study demonstrates that the ionic conductivities of the DN and single-network, low-molecular-weight gelator or polymer ionogels strongly depended on their storage elastic moduli.

  17. Release Characteristics In Vitro and In Vivo of In Situ Gels for a Novel Peptide Compared with Low-Molecular-Weight Hydrophilic Drug.

    Science.gov (United States)

    Zhang, Guiying; Hu, Jie; Meng, Qingbin; Wang, Tao; Yang, Xi; Gao, Lijun; Quan, Dongqin

    2017-01-01

    The thermo-sensitive in situ gels based on copolymers are attractive as an injectable drug delivery carriers for sustained releasing of hydrophilic drugs. The purposes of this work are to investigate the release behavior in vitro and pharmacokinetic profiles in vivo of peptide and lowmolecular- weight hydrophilic drug loaded in the in situ gels. A triblock copolymer PLGA-PEG-PLGA (1402-1000-1402) 1115A (1115A) was synthesized and its rheological and gelatin properties were evaluated. The temperature-sensitive in situ gels based on 1115A of LXT-101, a polypeptide drug, were prepared and the release characteristics in vitro and pharmacokinetic behavior in vivo were investigated. Meanwhile, naltrexone hydrochloride (NTX), a water-soluble low-molecular-weight drug was chosen as the model drug and the in situ gels were also prepared and studied comparatively. Slow-release characteristics were observed in vitro with in situ gels of LXT-101 and NTX. The release profiles and the mechanisms were different manifested by that NTX was released from in situ gels faster and more completely than LXT-101. Otherwise, the release pattern of LXT-101 showed a biphasic mechanism, an initial Fickian diffusion followed by a combination of degradation and diffusion at a later stage. The results of pharmacokinetic study indicated that a sustained release behavior could be obtained with MRT0-t (30.34 ± 12.47) h for LXT-101 and MRT0-t (2.37 ± 0.876) h for NTX, about 10 and 4 times longer than those of aqueous solution respectively. The pharmacodynamics studies in vivo further showed that in situ gel formulations of LXT-101 could sustain efficacy 6 days compared with only 1 day for aqueous solutions. The results of release behavior in vitro and in vivo indicated that in situ gels with copolymer 1115A could be served as carriers for delay-released drug delivery systems and might be more suitable for polypeptide drugs compared to low-molecular-weight hydrophilic drugs. Copyright© Bentham

  18. Low molecular weight Cooperia oncophora antigens: characterization and humoral immune responses in calves mono-infected with 100,000 infective larvae.

    Science.gov (United States)

    Parmentier, H K; Ploeger, H W; Nieuwland, M G; Souren, P J; Van Pinxteren, L A; Rietveld, F W; De Vries Reilingh, G; Kloosterman, A

    1995-10-01

    Characteristics of the humoral immune response of Cooperia oncophora-infected calves to low molecular weight antigens of C. oncophora were studied. Immunoblotting with sera obtained from calves 6 weeks after a single oral infection with 100,000 third-stage (L3) C. oncophora larvae revealed several corresponding antigenic fragments between adult worms and the fourth-stage (L4) larvae. No reactivity in the immune sera was found against the L3 stage. A previously defined complex of low molecular weight proteins (12-15 kDa) was found on both L4 and adult Cooperia stages, but not on the L3 stage. C. oncophora adults differed from the L4 larvae at the 31/32 and 37 kDa level. Several adult and L4 proteins were bound by biotinylated Concanavalin A, as was also true for L3 proteins. A 31/32 kDa glycoprotein of adult worms was recognised by a monoclonal antibody with specificity for phosphorylcholine. Using monoclonal antibodies in ELISA and Western blotting, the serum antibody response of C. oncophora-infected calves to adult worm antigen was almost entirely IgG1. Binding of the IgG1 antibodies was restricted to a complex of reduced 12-15 kDa protein(s) and a 27 kDa fragment of adult worms. The data suggest that the systemic humoral immune response of calves during a primary infection with C. oncophora consists mainly of an IgG1 response, and is directed to a non-glycosylated Cooperia protein (molecular weight estimated at 12-15 kDa under reducing conditions and 18 kDa under nonreducing conditions). This protein is probably present in both L4 larvae and adults. Since it was not bound by immune sera from calves mono-infected with several other nematodes, the 12-15 kDa protein complex may represent a Cooperia-specific component that can be used for serodiagnosis.

  19. Unfractionated heparin and low-molecular-weight heparin in acute coronary syndrome without ST elevation: a meta-analysis.

    Science.gov (United States)

    Eikelboom, J W; Anand, S S; Malmberg, K; Weitz, J I; Ginsberg, J S; Yusuf, S

    2000-06-03

    In acute coronary syndrome without ST elevation, the role of unfractionated and low-molecular-weight heparin in aspirin-treated patients remains unclear, and there is conflicting evidence regarding the efficacy and safety of low-molecular-weight heparin (LMWH) relative to unfractionated heparin. We did a systematic overview of the randomised trials to assess the effect of unfractionated heparin and LMWH on death, myocardial infarction, and major bleeding. Randomised trials comparing unfractionated heparin or LMWH with placebo or untreated control, or comparing unfractionated heparin with LMWH, for the short-term and long-term management of patients with acute coronary syndrome without ST elevation, were identified by electronic and manual searches and through contact with experts and industry representatives. Odds ratios for death, myocardial infarction, and major bleeding were calculated for each trial, and results for the individual trials were combined by a modification of the Mantel-Haenszel method. 12 trials, involving a total of 17157 patients, were included. The summary odds ratio (OR) for myocardial infarction or death during short-term (up to 7 days) unfractionated heparin or LMWH compared with placebo or untreated control was 0.53 (95% CI 0.38-0.73; p=0.0001) or 29 events prevented per 1000 patients treated; during short-term LMWH compared with unfractionated heparin was 0.88 (0.69-1.12; p=0.34); and during long-term LMWH (up to 3 months) compared with placebo or untreated control was 0.98 (0.81-1.17; p=0.80). Long-term LMWH was associated with a significantly increased risk of major bleeding (OR 2.26, [95% CI 1.63-3.14], paspirin-treated patients with acute coronary syndrome without ST elevation, short-term unfractionated heparin or LMWH halves the risk of myocardial infarction or death. There is no convincing difference in efficacy or safety between LMWH and unfractionated heparin. Long-term LMWH has not been proven to confer benefit additional to

  20. Tween 85-Modified Low Molecular Weight PEI Enhances Exon-Skipping of Antisense Morpholino Oligomer In Vitro and in mdx Mice

    Directory of Open Access Journals (Sweden)

    Mingxing Wang

    2017-12-01

    Full Text Available We investigated a series of Tween 85 modified low molecular weight polyethylenimine (LPEI, 0.8k/1.2k/2.0k-copolymers (Zs through simple formulation and covalent conjugation with phosphorodiamidate morpholino oligomer (PMO for their potential to enhance delivery in vitro and in dystrophic mdx mice. Z polymers significantly enhanced PMO-induced exon-skipping in a GFP reporter-based cell culture system. Application of optimized formulations of Zs with PMO targeted to dystrophin exon 23 demonstrated a significant increase in exon-skipping efficiency in mdx mice. Consistent with our observations in vitro, optimization of molecular size and hydropholic-lipopholic balance (HLB of polymers are important factors to achieve enhanced PMO delivery in vivo. The best formulation of Zs enhanced PMO delivery with 20- and 6-fold over PMO alone in vitro and in vivo, respectively. Further, chemical conjugation of the polymer and PMO exhibits greater benefit than polymer/PMO simple formulation in PMO delivery efficiency. Observed cytotoxicity of the Zs was lower than Endo-porter and PEI 25k in vitro, and no tissue toxicity was clearly detected with the Zs at the dosage tested. These results indicate the potential of the Zs as effective and safe PMO delivery carriers for treating diseases such as muscular dystrophy.

  1. Low-molecular-weight fucoidan and high-stability fucoxanthin from brown seaweed exert prebiotics and anti-inflammatory activities in Caco-2 cells

    Directory of Open Access Journals (Sweden)

    Pai-An Hwang

    2016-08-01

    Full Text Available Background: The aim of this study is to investigate the anti-inflammatory effects of low-molecular-weight fucoidan (LMF and high-stability fucoxanthin (HS-Fucox in a lipopolysaccharide-induced inflammatory Caco-2 cell line co-culture with B. lactis. Methods: We used various methods such as transepithelial resistance (TER assay, cytokine secretion assay, and tight junction protein mRNA expression assay to examine LMF and HS-Fucox anti-inflammatory properties. Results: LMF and HS-Fucox activated probiotic growth and reduced the inflammation of the intestinal epithelial cells. Moreover, the combination of LMFHS-Fucox dramatically enhanced the intestinal epithelial barrier and immune function against the lipopolysaccharide effect by inhibiting IL-1β and TNF-α and promoting IL-10 and IFN-γ. Conclusion: These findings suggested that LMF and HS-Fucox, alone or in combination, could be the potential natural compounds to enhance the immune system and have an anti-inflammatory effect on the intestinal cells.

  2. Quantification of low molecular weight selenium metabolites in human plasma after treatment with selenite in pharmacological doses by LC-ICP-MS.

    Science.gov (United States)

    Flouda, Konstantina; Dersch, Julie Maria; Gabel-Jensen, Charlotte; Stürup, Stefan; Misra, Sougat; Björnstedt, Mikael; Gammelgaard, Bente

    2016-03-01

    The paper presents an analytical method for quantification of low molecular weight (LMW) selenium compounds in human plasma based on liquid chromatography inductively coupled plasma mass spectrometry (LC-ICP-MS) and post column isotope dilution-based quantification. Prior to analysis, samples were ultrafiltrated using a cut-off value of 3000 Da. The method was validated in aqueous solution as well as plasma using standards of selenomethionine (SeMet), Se-methylselenocysteine (MeSeCys), selenite, and the selenosugar Se-methylseleno-N-acetylgalactosamine (SeGal) for linearity, precision, recoveries, and limits of detection and quantitation with satisfactory results. The method was applied for analysis of a set of plasma samples from cancer patients receiving selenite treatment in a clinical trial. Three LMW selenium compounds were observed. The main compounds, SeGal and selenite were tentatively identified by retention time matching with standards in different chromatographic systems, while the third minor compound was not identified. The identity of the selenosugar was verified by ESI-MS-MS product ion scanning, while selenite was identified indirectly as the glutathione (GSH) reaction product, GS-Se-SG.

  3. Influence of Ca/Mg ratio on phytoextraction properties of Salix viminalis. II. Secretion of low molecular weight organic acids to the rhizosphere.

    Science.gov (United States)

    Magdziak, Z; Kozlowska, M; Kaczmarek, Z; Mleczek, M; Chadzinikolau, T; Drzewiecka, K; Golinski, P

    2011-01-01

    A hydroponic experiment in a phytotron was performed to investigate the effect of two different Ca/Mg ratios (4:1 and 1:10) and trace element ions (Cd, Cu, Pb and Zn) in solution on the efficiency of low molecular weight organic acid (LMWOA) formation in Salix viminalis rhizosphere. Depending on the Ca/Mg ratio and presence of selected trace elements at 0.5mM concentration, the amount and kind of LMWOAs in the rhizosphere were significantly affected. In physiological 4:1 Ca/Mg ratio the following complex of acids was observed: malonic (Pb, Zn), citric, lactic, maleic and succinic (Zn) acids. Under 1:10 Ca/Mg ratio, citric (Cd, Zn), maleic and succinic (Cd, Cu, Pb, Zn) acids were seen. Additionally, high accumulation of zinc and copper in all systems was observed, with the exception of those where one of the metals was at higher concentration. Summing up, the results indicate a significant role of LMWOAs in Salix phytoremediation abilities. Both effects can be modulated depending on the mutual Ca/Mg ratio. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. Characterization of low molecular weight fragments from gamma irradiated κ-carrageenan used as plant growth promoter

    Science.gov (United States)

    Abad, Lucille V.; Aurigue, Fernando B.; Relleve, Lorna S.; Montefalcon, Djowel Recto V.; Lopez, Girlie Eunice P.

    2016-01-01

    Radiation degraded κ-carrageenan (1% solution at absorbed doses of 20 kGy and 30 kGy) were tested for its plant growth promoter (PGP) effect on pechay plants under hydroponics condition. Results revealed that higher PGP effects were found in κ-carrageenan irradiated at an absorbed dose of 30 kGy. Mw of irradiated κ-carrageenan as measured by GPC were determined to be 7362 Da and 6762 Da for 20 kGy and 30 kGy, respectively. Fractionation of the irradiated κ-carrageenan (30 kGy) was done to separate different Mw fractions using Mw cut-off filters of 1 kDa, 3 kDa, and 5 kDa. The PGP effect of the different retentates showed that biological activity in plants followed the order of 5 kDa>3 kDa>1 kDa using hydroponics condition but the reverse was observed in the order of 1 kDa>3 kDa>5 kDa when absorbed in plants by foliar spraying. GPC chromatogram indicated at least three (3) low molecular weight (LMW) fragments from radiation modified κ-carrageenan solution with an Mw<2000 Da. A fragment has also been identified with an Mw of as low as 160 Da which was produced under acidic (un-neutralized) condition. This may be attributed to the formation of 5-hydroxymethylfurfural (5-HMF).

  5. Zwitterionic Polymer P(AM-DMC-AMPS as a Low-Molecular-Weight Encapsulator in Deepwater Drilling Fluid

    Directory of Open Access Journals (Sweden)

    Xin Zhao

    2017-06-01

    Full Text Available In deepwater oil and gas drilling, the high-molecular-weight encapsulator aggravates the thickening of the drilling fluid at low temperatures. Therefore, it is hard to manage the downhole pressure, and drilling fluid loss occurs. In this paper, a zwitterionic polymer P(AM-DMC-AMPS which was the terpolymer of acrylamide, methacrylatoethyl trimethyl ammonium chloride, and 2-acrylamido-2-methylpropane sulfonic acid, was developed as a low-molecular-weight encapsulator. It was characterized by Fourier transform infrared spectrum analysis, nuclear magnetic resonance, and gel permeation chromatography. Moreover, the low-temperature rheology, shale inhibition and filtration properties of water-based drilling fluids (WBDFs containing different encapsulators were experimentally investigated and compared. The results showed that the molecular weight of P(AM-DMC-AMPS was about 260,000, much lower than that of the conventional encapsulators. In the deepwater drilling temperature range 4–75 °C, WBDF containing P(AM-DMC-AMPS had lower and more stable rheological property because of its short molecular chains. The high shale recovery rate and low swelling rate indicated its strong shale inhibition performance, owing to its adsorption on the clay surface and the wrapping effect through both hydrogen bonding and electrostatic interaction. It also improved the filtration property of WBDF, and was compatible with other WBDF components. This product is expected to simultaneously realize the good encapsulation performance and low-temperature rheological property for deepwater drilling fluid.

  6. Development of Gel-Filter Method for High Enrichment of Low-Molecular Weight Proteins from Serum

    Science.gov (United States)

    Chen, Lingsheng; Zhai, Linhui; Li, Yanchang; Li, Ning; Zhang, Chengpu; Ping, Lingyan; Chang, Lei; Wu, Junzhu; Li, Xiangping; Shi, Deshun; Xu, Ping

    2015-01-01

    The human serum proteome has been extensively screened for biomarkers. However, the large dynamic range of protein concentrations in serum and the presence of highly abundant and large molecular weight proteins, make identification and detection changes in the amount of low-molecular weight proteins (LMW, molecular weight ≤ 30kDa) difficult. Here, we developed a gel-filter method including four layers of different concentration of tricine SDS-PAGE-based gels to block high-molecular weight proteins and enrich LMW proteins. By utilizing this method, we identified 1,576 proteins (n = 2) from 10 μL serum. Among them, 559 (n = 2) proteins belonged to LMW proteins. Furthermore, this gel-filter method could identify 67.4% and 39.8% more LMW proteins than that in representative methods of glycine SDS-PAGE and optimized-DS, respectively. By utilizing SILAC-AQUA approach with labeled recombinant protein as internal standard, the recovery rate for GST spiked in serum during the treatment of gel-filter, optimized-DS, and ProteoMiner was 33.1 ± 0.01%, 18.7 ± 0.01% and 9.6 ± 0.03%, respectively. These results demonstrate that the gel-filter method offers a rapid, highly reproducible and efficient approach for screening biomarkers from serum through proteomic analyses. PMID:25723528

  7. Novel Synthesis of Core-Shell Silica Nanoparticles for the Capture of Low Molecular Weight Proteins and Peptides

    Directory of Open Access Journals (Sweden)

    Sergio G. Hernandez-Leon

    2017-10-01

    Full Text Available Silica nanoparticles were functionalized with immobilized molecular bait, Cibacron Blue, and a porous polymeric bis-acrylamide shell. These nanoparticles represent a new alternative to capture low molecular weight (LMW proteins/peptides, that might be potential biomarkers. Functionalized core-shell silica nanoparticles (FCSNP presented a size distribution of 243.9 ± 11.6 nm and an estimated surface charge of −38.1 ± 0.9 mV. The successful attachment of compounds at every stage of synthesis was evidenced by ATR-FTIR. The capture of model peptides was determined by mass spectrometry, indicating that only the peptide with a long sequence of hydrophobic amino acids (alpha zein 34-mer interacted with the molecular bait. FCSNP excluded the high molecular weight protein (HMW, BSA, and captured LMW proteins (myoglobin and aprotinin, as evidenced by SDS-PAGE. Functionalization of nanoparticles with Cibacron Blue was crucial to capture these molecules. FCSNP were stable after twelve months of storage and maintained a capacity of 3.1–3.4 µg/mg.

  8. [Low molecular weight heparin inhibits cell apoptosis in the placenta of rats with preeclampsia-like symptoms].

    Science.gov (United States)

    Zhang, Yuan; Zhong, Mei; Liu, Fengyan

    2012-06-01

    To investigate the anti-apoptotic effect of low molecular weight heparin (LMWH) in the placenta of rats with preeclampsia-like symptoms. Thirty pregnant Wistar rats were randomized equally into 3 groups and received subcutaneous saline injection (control group), 200 mg/kg L-NAME injection to induce preeclampsia symptoms (PE group), or L-NAME with 40 µl/kg LMWH injections (LMWH group). The blood pressure, urine protein, the number of pups and the weight of the fetuses and placenta were measured, and the placental apoptotic index was measured by TUNEL assay. The expression of cleaved caspase-3, Bcl-2 and Bax in the placenta were examined by Western blotting. Compared with the control group, L-NAME injections caused significantly increased blood pressure and urine protein (P0.05). The LMWH group showed a significantly lower placental apoptosis index than the PE group (Papoptosis index and expressions of cleaved caspase-3, Bcl-2 and Bax protein were similar between LMWH group and normal pregnant group (P>0.05). LMWH can alleviate preeclampsia-like symptoms and decrease the apoptosis in the placenta of rats possibly by enhancing Bcl-2 and suppressing Bax expressions.

  9. Audit of the peri-delivery use of unfractionated heparin in women on therapeutic low-molecular weight heparin.

    Science.gov (United States)

    Lambert, J R; Austin, S K; Peebles, D; Cohen, H

    2008-07-01

    There is no evidence-based approach for the optimal management of peri-delivery anticoagulation in women receiving therapeutic dose of low-molecular weight heparin (LMWH) during pregnancy. Nevertheless, the maintenance of anticoagulation for the maximal period peri-delivery appears appropriate in women considered to be at high risk of venous or arterial thromboembolism. We developed a regimen based on fixed thromboprophylactic dose of unfractionated heparin (UFH) peri-delivery and undertook an audit to evaluate the use and feasibility of this approach and any adverse events. Fixed intravenous thromboprophylactic dose of UFH (15,000 units/24 h) was commenced on the evening prior to a planned delivery [induction of labour or elective caesarean section (CS)], stopped 4 h predelivery and restarted 2-6 h postdelivery. Compliance was good with 32/38 consecutive deliveries managed according to the regimen. There were no cases of postpartum haemorrhage and no thrombosis associated with these 32 deliveries. Twenty-one patients were delivered by CS (11 elective) and eight patients received epidural/spinal anaesthesia without complication. In conclusion, the fixed thromboprophylactic dose UFH regimen provided maintenance of anticoagulation except for a matter of hours without excessive bleeding risk (conducive to neuroaxial anaesthesia) and was simple, flexible and acceptable to staff and patients.

  10. Anti-angiogenic activity and antitumor efficacy of amphiphilic twin drug from ursolic acid and low molecular weight heparin

    Science.gov (United States)

    Cheng, Wenming; Zohra Dahmani, Fatima; Zhang, Juan; Xiong, Hui; Wu, Yuanyuan; Yin, Lifang; Zhou, Jianping; Yao, Jing

    2017-02-01

    Heparin, a potential blood anti-coagulant, is also known for its binding ability to several angiogenic factors through electrostatic interactions due to its polyanionic character. However, the clinical application of heparin for cancer treatment is limited by several drawbacks, such as unsatisfactory therapeutic effects and severe anticoagulant activity that could induce hemorrhaging. Herein, low molecular weight heparin (LMWH) was conjugated to ursolic acid (UA), which is also an angiogenesis inhibitor, by binding the amine group of aminoethyl-UA (UA-NH2) with the carboxylic groups of LMWH. The resulting LMWH-UA conjugate as an amphiphilic twin drug showed reduced anticoagulant activity and could also self-assemble into nanomicelles with a mean particle size ranging from 200-250 nm. An in vitro endothelial tubular formation assay and an in vivo Matrigel plug assay were performed to verify the anti-angiogenic potential of LMWH-UA. Meanwhile, the in vivo antitumor effect of LMWH-UA was also evaluated using a B16F10 mouse melanoma model. LMWH-UA nanomicelles were shown to inhibit angiogenesis both in vitro and in vivo. In addition, the i.v. administration of LMWH-UA to the B16F10 tumor-bearing mice resulted in a significant inhibition of tumor growth as compared to the free drug solutions. These findings demonstrate the therapeutic potential of LMWH-UA as a new therapeutic remedy for cancer therapy.

  11. Cryopreservation of spinach chloroplast membranes by low-molecular-weight carbohydrates. II. Discrimination between colligative and noncolligative protection.

    Science.gov (United States)

    Santarius, K A; Giersch, C

    1983-02-01

    Thylakoid membranes isolated from spinach leaves (Spinacia oleracea L. cv. Monatol) were subjected to a freeze-thaw cycle in the presence of various concentrations of sugars, polyhydric alcohols, and NaCl. Functional integrity of the membranes was assayed by means of cyclic photophosphorylation. From the nonideal activity-concentration profiles of the carbohydrates the effective NaCl concentrations in the surroundings of the membranes at the respective freezing temperatures were calculated. Comparison of the cryoprotective efficiency of the various polyols revealed that cryopreservation by low-molecular-weight compounds is predominantly due to colligative action of the solutes. In addition, specific effects of carbohydrates which cannot be explained by the colligative concept are involved in cryoprotection. At NaCl concentrations exceeding 15 mm, the relative contribution of noncolligative membrane protection of a given polyol to overall cryopreservation was independent of the salt concentration. However, during freezing in the presence of very low salt concentrations, for instance 1-4 mm NaCl, cryoprotection due to colligative phenomena is reduced in favor of other mechanisms.

  12. The role of microbial low-molecular-weight autoregulatory factors (alkylhydroxybenzenes) in resistance of microorganisms to radiation and heat shock

    Science.gov (United States)

    El-Registan, Galina I.; Mulyukin, Andrey L.; Nikolaev, Yuri A.; Stepanenko, Irina Yu.; Kozlova, Alla N.; Martirosova, Elena I.; Shanenko, Elena F.; Strakhovskaya, Marina G.; Revina, Aleksandra A.

    Low-molecular-weight cell-to-cell communication factors are produced by various pro- and eukaryotes and involved in autoregulation of the growth and development of microbial cultures. As for some bacterial and yeast species, these factors were identified as isomers and homologues of alkylhydroxybenzenes (AHB). Depending on the concentration, they participate in controlling the transition to stationary phase, entering the resting state, and stress resistance of vegetative cells to gamma-irradiation, photooxidation (singlet oxygen), and heat shock. Chemical analogues of microbial AHB protected microbial cultures from stressful situations and exerted (1) the stabilizing activity toward macromolecules and (2) the ability to scavenge active oxygen species. The stabilizing effect of AHBs resulted from their complex formation with protected macromolecules due to intermolecular hydrogen bonds, hydrophobic and electrostatic interactions and was demonstrated on models of individual enzymes (trypsin). Particularly, AHBs protected the yeast from the action of (a) active oxygen species formed during gamma-irradiation (500 Gy, 1.96 Gy/s) or (b) singlet oxygen generated in cells photosensitized by chlorin e 6 (10 μg/L). It is important that microbial AHBs were not species-specific and defended cultured microbial and animal cells from the action of organic toxicants. The use of AHBs as protectants and adaptogens is discussed as well as perspectives of further investigations.

  13. Nanowires formed by the co-assembly of a negatively charged low-molecular weight gelator and a zwitterionic polythiophene.

    Science.gov (United States)

    Li, Feng; Palaniswamy, Ganesan; de Jong, Menno R; Aslund, Andreas; Konradsson, Peter; Marcelis, Antonius T M; Sudhölter, Ernst J R; Stuart, Martien A Cohen; Leermakers, Frans A M

    2010-06-21

    Conjugated organic nanowires have been prepared by co-assembling a carboxylate containing low-molecular weight gelator (LMWG) and an amino acid substituted polythiophene derivative (PTT). Upon introducing the zwitterionic polyelectrolyte PTT to a basic molecular solution of the organogelator, the negative charges on the LMWG are compensated by the positive charges of the PTT. As a result, nanowires form through co-assembly. These nanowires are visualized by both transmission electron microscopy (TEM) and atomic force microscopy (AFM). Depending on the concentration and ratio of the components these nanowires can be micrometers long. These measurements further suggest that the aggregates adopt a helical conformation. The morphology of these nanowires are studied with fluorescent confocal laser scanning microscopy (CLSM). The interactions between LMWG and PTT are characterized by steady-state and time-resolved fluorescence spectroscopy studies. The steady-state spectra indicate that the backbone of the PTT adopts a more planar and more aggregated conformation when interacting with LMWG. The time- resolved fluorescence decay studies confirm this interpretation.

  14. Substitution of Percutaneous Ethanol Injection with a Low Molecular Weight Peptide Gel Mimicking Chemoembolization for Cancer Therapy

    Science.gov (United States)

    Xu, Long; Liang, Yan; Sun, Changzheng; Hao, Na; Yan, Jianqin; Gao, Wenxia; He, Bin

    2017-01-01

    In order to avoid the instability and quick separation between emulsifier and drug in the interventional chemoembolization, an injectable low molecular weight peptide gel (LMWG) was prepared to localize ethanol and chemotherapeutic for in situ synergistic therapy. The formation mechanism, rheological property and morphology of the LMWG were investigated by NMR, UV-vis, MS and SEM. The interaction between gelator and anticancer drug doxorubicin hydrochloride (DOX) was evaluated by fluorescence spectroscopy and its contribution on drug loading properties was demonstrated. The gel was non-toxic to both 3T3 fibroblasts and 4T1 breast cancer cells. DOX as well as ethanol were encapsulated in the gel and injected in breast cancer bearing mice with low drug dose (2.5 mg/kg body weight). The LMWG surrounded tumors act as a depot for ethanol release and release DOX to induce the apoptosis of cancer cells. With the combination of percutaneous ethanol injection (PEI) and chemotherapy, the DOX loaded LMWG exhibited great significance in necrosis of tumor tissue and exciting tumor inhibition efficiency. PMID:29071195

  15. Fullerene nanowires: self-assembled structures of a low-molecular-weight organogelator fabricated by the Langmuir-Blodgett method.

    Science.gov (United States)

    Tsunashima, Ryo; Noro, Shin-ichiro; Akutagawa, Tomoyuki; Nakamura, Takayoshi; Kawakami, Hiroko; Toma, Kazunori

    2008-01-01

    Fullerene derivative C60TT, which is substituted with the low-molecular-weight organogelator tris(dodecyloxy)benzamide, formed nanowire structures on application of the Langmuir-Blodgett (LB) method. The surface morphology of the C60TT LB film was dependent on the holding time before deposition at a surface pressure of 5 mN m(-1); it changed from a homogeneous monolayer to a bilayer fibrous structure via a fibrous monolayer structure, which was estimated to have dimensions of 1.2 nm in height, 8 nm in width, and 5-10 microm in length. From the structural and spectroscopic data, it is inferred that close packing of the fullerene moiety occurs along with intermolecular hydrogen bonding within the monolayer fibrous structure. The morphological changes in the LB film are explained kinetically by the Avrami theory, based on the decrease in the surface area of the monolayer at the air/water interface. The growth of the quasi-one-dimensional fibrous monolayer structures at holding times from 0 to 0.2 h is considered to be an interface-controlled process, whereas the growth of the quasi-one-dimensional bilayer fibrous structures from 0.2 to 18 h is thought to be a diffusion-controlled process.

  16. Normal values for 24-h urinary protein excretion: total and low molecular weight proteins with a sex-related difference.

    Science.gov (United States)

    Kawakami, H; Murakami, T; Kajii, T

    1990-05-01

    Urinary excretion of total and low molecular weight (LMW) (less than 40,000) proteins for a 24-h period was determined in 60 normal individuals, 30 men and 30 women, aged 21 to 44 years. 24-h urinary total protein excretion in men was 91.2 +/- 25.1 mg (mean +/- SD) (range: 40.2-146.8 mg), while that in women was 62.5 +/- 23.6 mg (range: 28.4-130.9 mg), as measured by a biuret method using bicinchoninic acid as a reagent. 24-h urinary LMW protein excretion in men was 37.3 +/- 13.6 mg (range: 12.7-62.7 mg), while that in women was 23.2 +/- 11.8 mg (range: 7.2-54.2 mg), as estimated by sodium dodecylsulfate-polyacrylamide gel electrophoresis of concentrated urine samples. Thus, a significantly higher (t-test, p less than 0.01) excretion of both the total and LMW proteins was found in men than in women. However, the percentage of the LMW proteins among the total proteins did not differ between the sexes: 40.3 +/- 7.5% (range: 21.7-54.9%) for men and 36.5 +/- 9.9% (range: 20.1-56.7%) for women.

  17. Low Molecular Weight Fucoidan Alleviates Cardiac Dysfunction in Diabetic Goto-Kakizaki Rats by Reducing Oxidative Stress and Cardiomyocyte Apoptosis

    Directory of Open Access Journals (Sweden)

    Xinfeng Yu

    2014-01-01

    Full Text Available Diabetic cardiomyopathy (DCM is characterized by cardiac dysfunction and cardiomyocyte apoptosis. Oxidative stress is suggested to be the major contributor to the development of DCM. This study was intended to evaluate the protective effect of low molecular weight fucoidan (LMWF against cardiac dysfunction in diabetic rats. Type 2 diabetic goto-kakizaki rats were untreated or treated with LMWF (50 and 100 mg/kg/day for three months. The establishment of DCM model and the effects of LMWF on cardiac function were evaluated by echocardiography and isolated heart perfusion. Ventricle staining with H-E or Sirius Red was performed to investigate the structural changes in myocardium. Functional evaluation demonstrated that LMWF has a beneficial effect on DCM by enhancing myocardial contractility and mitigating cardiac fibrosis. Additionally, LMWF exerted significant inhibitory effects on the reactive oxygen species production and myocyte apoptosis in diabetic hearts. The depressed activity of superoxide dismutase in diabetic heart was also improved by intervention with LMWF. Moreover, LMWF robustly inhibited the enhanced expression of protein kinase C β, an important contributor to oxidative stress, in diabetic heart and high glucose-treated cardiomyocytes. In conclusion, LMWF possesses a protective effect against DCM through ameliorations of PKCβ-mediated oxidative stress and subsequent cardiomyocyte apoptosis in diabetes.

  18. Expression of a Conserved Family of Cytoplasmic Low Molecular Weight Heat Shock Proteins during Heat Stress and Recovery.

    Science.gov (United States)

    Derocher, A E; Helm, K W; Lauzon, L M; Vierling, E

    1991-08-01

    Plants synthesize several families of low molecular weight (LMW) heat shock proteins (HSPs) in response to elevated temperatures. We have characterized two cDNAs, HSP18.1 and HSP17.9, that encode members of the class I family of LMW HSPs from pea (Pisum sativum). In addition, we investigated the expression of these HSPs at the mRNA and protein levels during heat stress and recovery. HSP18.1 and HSP17.9 are 82.1% identical at the amino acid level and are 80.8 to 92.9% identical to class I LMW HSPs of other angiosperms. Heat stress experiments were performed using intact seedlings subjected to a gradual temperature increase and held at a maximum temperature of 30 to 42 degrees Celsius for 4 hours. HSP18.1 and HSP17.9 mRNA levels peaked at the beginning of the maximum temperature period and declined rapidly after the stress period. Antiserum against a HSP18.1 fusion protein recognized both HSP18.1 and HSP17.9 but not members of other families of LMW HSPs. The accumulation of HSP18.1-immunodetected protein was proportional to the severity of the heat stress, and the protein had a half-life of 37.7 +/- 8 hours. The long half-life of these proteins supports the hypothesis that they are involved in establishing thermotolerance.

  19. The low molecular weight DNA diffusion assay as an indicator of cytotoxicity for the in vitro comet assay.

    Science.gov (United States)

    Speit, Günter; Vesely, Alexandra; Schütz, Petra; Linsenmeyer, Regina; Bausinger, Julia

    2014-07-01

    The low molecular weight DNA diffusion assay (LMW assay) has been recommended as a measure for cytotoxicity for the in vivo comet assay. To better understand the relationship between effects in the LMW assay, DNA migration in the comet assay and effects in established cytotoxicity tests, we performed in vitro experiments with cultured human cell lines (TK6, A549) and comparatively investigated five test substances (methyl methanesulfonate, (±)-benzo[a]pyrene diol epoxide, sodium dodecyl sulphate, menthol and sodium arsenite). We measured DNA migration (tail intensity) in the comet assay and the frequency of 'hedgehogs' (cells with almost all DNA in the tail), DNA diffusion in the LMW assay, cell viability (trypan blue and fluorescein diacetate/ethidium bromide staining) and inhibition of proliferation (relative cell counts). Our in vitro experiments indicate that effects in the LMW assay occur independently from DNA effects in the comet assay and are not related to the occurrence of hedgehogs. Results from the LMW assay are in good agreement with results from viability assays and seem to allow discriminating genotoxic from non-genotoxic substances when appropriate preparation times are considered. Measurements of cytotoxicity by these methods only at an early preparation time after exposure to genotoxic substances may lead to erroneous results. © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Changes in low molecular weight phenolic compounds in Spanish, French, and American oak woods during natural seasoning and toasting.

    Science.gov (United States)

    Cadahía, E; Muñoz, L; Fernández de Simón, B; García-Vallejo, M C

    2001-04-01

    The evolution of low molecular weight polyphenols in Spanish oak heartwood of Quercus robur,Quercus petraea, Quercus pyrenaica, and Quercus faginea was studied by HPLC, in relation to the processing of wood in barrel cooperage. The polyphenolic composition of Spanish woods subjected to natural seasoning for 3 years and to the toasting process was studied in relation to those of French oak of Q. robur (Limousin) and Q. petraea (Allier) and American oak of Q. alba (Missouri), which are habitually used in cooperage. The concentrations of benzoic and cinnamic acids and aldehydes of Spanish woods increased during seasoning depending on the duration of this process and in the same way as those of French and American woods. The process having the main influence on the phenolic composition of wood was the toasting. It led to high increases in the concentration of phenolic aldehydes and acids, especially cinnamic aldehydes (sinapic and coniferylic aldehydes), followed by benzoic aldehydes (syringaldehyde and vanillin) and benzoic acids (syringic and vanillic acids). This polyphenolic composition in Spanish oak species evolved during toasting as in French and American oak, but quantitative differences were found, which were especially important in American species with respect to the others.

  1. Steric stabilization of nanoparticles with grafted low molecular weight ligands in highly concentrated brines including divalent ions.

    Science.gov (United States)

    Worthen, Andrew J; Tran, Vu; Cornell, Kevin A; Truskett, Thomas M; Johnston, Keith P

    2016-02-21

    Whereas numerous studies of stabilization of nanoparticles (NPs) in electrolytes have examined biological fluids, the interest has grown recently in media with much higher ionic strengths including seawater and brines relevant to environmental science and subsurface oil and gas reservoirs. Given that electrostatic repulsion is limited at extremely high ionic strengths due to charge screening, we have identified ligands that are well solvated in concentrated brine containing divalent cations and thus provide steric stabilization of silica nanoparticles. Specifically, the hydrodynamic diameter of silica nanoparticles with grafted low molecular weight ligands, a diol ether, [3-(2,3-dihydroxypropoxy)propyl]-trimethoxysilane, and a zwitterionic sulfobetaine, 3-([dimethyl(3-trimethoxysilyl)propyl]ammonio)propane-1-sulfonate, is shown with dynamic light scattering to remain essentially constant, indicating lack of aggregation, at room temperature and up to 80 °C for over 30 days. An extended DLVO model signifies that steric stabilization is strongly dominant against van der Waals attraction for ∼10 nm particles given that these ligands are well solvated even in highly concentrated brine. In contrast, polyethylene glycol oligomers do not provide steric stabilization at elevated temperatures, even at conditions where the ligands are soluble, indicating complicating factors including bridging of the ether oxygens by divalent cations.

  2. Effect of toasting on non-volatile and volatile vine-shoots low molecular weight phenolic compounds.

    Science.gov (United States)

    Sánchez-Gómez, R; Zalacain, A; Alonso, G L; Salinas, M R

    2016-08-01

    Low molecular weight phenolic compounds (LMWPC), including non-volatile and volatile, of Airén and Moscatel vine-shoot cultivars waste submitted to different toasting conditions (light, 180°/15min; medium, 180°/30min; high 180°/45min) were studied in order to exploit them with oenological purposes. The LMWPC differences were mainly due to the toasting times rather than vine-shoot variety. In non-volatile LMWPC fraction, flavanols and almost all phenolic acids decreased by toasting. The presence of trans-resveratrol has a special relevance at light toasting: 14 times more concentrated in Airén and 6 times in Moscatel vine-shoots, than their respective non-toasted samples. The volatile LMWPC showed a significant increment with toasting, being vanillin the one with the highest difference respect to non-toasted samples at high conditions: more than 15 times in Airén and 11 in Moscatel. Although toasting reduced some LMWPC, particular characteristics of these vine-shoots must be taken into account when considering its future use. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. [Low molecular weight heparin (CY 222) levels during hemodialysis sessions. Comparison of various chromogenic and chronometric methods. Problem of standardization].

    Science.gov (United States)

    Roussel, B; Dieval, J; Bayrou, B; Delobel, J

    1987-01-01

    Current evaluation of biological activity of low molecular weight heparins (LMWH) is dependent solely on technics determining Xa inhibition. Comparison of these technics was carried out during 2 studies of the use of CY 222 during hemodialysis. In the first study, 66 plasma samples from 11 patients treated with 200 or 250 U A Xa IC kg/i.v. at start of session (sample collections at 2-4 h) were tested using a chronometric technic (Hepaclot Stago-plasma diluted to 1/3) and 2 chromogenic technics on microplates using C.B.S. 31-39 substrates (Stachrom-modified Stago: incubation time 90" for a wide range) and S 2222 (Coatest-modified Kabi: incubation time 180"). In the second, 28 plasma samples from 7 patients (sample collection 2-4 h, TO following session; anticoagulation CY 222 10,000-15,000-20,000 U A Xa IC) were studied by 2 chronometric methods: Hepaclot (Stago) and Heptest (Hemachem). Standardization was with CY 222 in each case (results expressed as U A Xa IC). Mean blood heparin in the first study was 2.39 +/- 0.7 with Hepaclot, 2.50 +/- 0.55 with Stachrom and 1.94 +/- 0.37 with Coatest. Student's test failed to show any difference between results with Strachrom and Hepaclot (t = 1.48 NS) whereas the difference was very significant between Hepaclot and Coatest and Stachrom and Coatest (p less than 10(-9).(ABSTRACT TRUNCATED AT 250 WORDS)

  4. [Screening, characterization and pharmaceutical and medical application of enzyme inhibitors from microbial origin with low-molecular-weight].

    Science.gov (United States)

    Aoyagi, T

    1996-07-01

    In living organisms a large number of enzymes are working in complicated networks to express various biological functions. In order to analyze such functions from various aspects, specific enzyme inhibitors are likely to become useful tools. They are also useful for the studies of reaction mechanisms and analysis of three-dimensional structures of enzymes. Moreover, they are of great value in elucidating disease processes and seem to have usefulness in treatment of various diseases. Searching for inhibitors in culture filtrate of microbes, we discovered many substances which specifically inhibit various enzymes such as endopeptidases, exopeptidases, glycosidases, lipases, an so forth. These inhibitors have low-molecular-weights and unique structures. We found significant activities of exopeptidases, alkaline phosphatases, esterases, and so forth, on surface membranes of various mammalian cells. Searching for specific inhibitors against these cell surface enzymes, we have discovered many interesting inhibitors. These inhibitors proved to bind to the cellular surface and to modify the functions of cells involved in immune responses. Thus the studies on these enzyme inhibitors may well afford important keys to understand various aspect of biological phenomena and diseases: inflammation, immune response, hypertension, hyperlipemia, diabetes, Alzheimer's disease, carcinogenesis, metastasis, viral infection, autoimmune diseases, and so forth. Because of their interesting pharmacological activities, some of the inhibitors are now under clinical evaluation for their uses as medical drugs. Enzyme inhibitors seems to propose a new promising field of science.

  5. A randomized controlled trial of combined 5-fluorouracil and low-molecular-weight heparin in management of established proliferative vitreoretinopathy.

    Science.gov (United States)

    Charteris, David G; Aylward, G William; Wong, David; Groenewald, Carl; Asaria, Riaz H Y; Bunce, Catey

    2004-12-01

    To determine the efficacy of a combination of 5-fluorouracil and low-molecular-weight heparin (LMWH) to improve the outcome of surgery for established proliferative vitreoretinopathy (PVR). Double-masked, prospective, randomized, placebo-controlled clinical trial. Three tertiary-referral teaching hospital vitreoretinal surgical units. One hundred fifty-seven patients with established PVR (grade C, anterior or posterior) undergoing vitrectomy surgery. All patients underwent vitreoretinal surgery and silicone oil exchange with or without membrane peeling and/or retinectomy. Patients were randomly allocated to perioperative infusion with or without 5-fluorouracil (200 microg/ml) and LMWH (5 IU/ml) in Hartmann's solution for 1 hour. The primary outcome measure was defined as posterior retinal reattachment after removal of silicone oil without any reoperations at 6 months. Secondary outcome measures recorded were posterior retinal reattachment, localized/tractional retinal detachment, visual acuity, macular pucker, hypotony, glaucoma, keratopathy, and cataract. Removal of silicone oil and reoperations were also recorded. Overall, at 6 months 84% of patients had full retinal reattachment and 94% had stable posterior retinal reattachment. There was no significant difference in success in the primary outcome measure (56%, treatment group; 51%, placebo group; P = 0.59) or in secondary outcome measures or rates of complications. Secondary macular pucker occurred less often in the treatment group (6% vs. 17% at 6 months, P = 0.068). A perioperative infusion of combined 5-fluorouracil and LMWH does not significantly increase the success rate of vitreoretinal surgery for established PVR.

  6. Development of gel-filter method for high enrichment of low-molecular weight proteins from serum.

    Directory of Open Access Journals (Sweden)

    Lingsheng Chen

    Full Text Available The human serum proteome has been extensively screened for biomarkers. However, the large dynamic range of protein concentrations in serum and the presence of highly abundant and large molecular weight proteins, make identification and detection changes in the amount of low-molecular weight proteins (LMW, molecular weight ≤ 30kDa difficult. Here, we developed a gel-filter method including four layers of different concentration of tricine SDS-PAGE-based gels to block high-molecular weight proteins and enrich LMW proteins. By utilizing this method, we identified 1,576 proteins (n = 2 from 10 μL serum. Among them, 559 (n = 2 proteins belonged to LMW proteins. Furthermore, this gel-filter method could identify 67.4% and 39.8% more LMW proteins than that in representative methods of glycine SDS-PAGE and optimized-DS, respectively. By utilizing SILAC-AQUA approach with labeled recombinant protein as internal standard, the recovery rate for GST spiked in serum during the treatment of gel-filter, optimized-DS, and ProteoMiner was 33.1 ± 0.01%, 18.7 ± 0.01% and 9.6 ± 0.03%, respectively. These results demonstrate that the gel-filter method offers a rapid, highly reproducible and efficient approach for screening biomarkers from serum through proteomic analyses.

  7. Differential Effects of Low-Molecular-Weight Organic Acids on the Mobilization of Soil-Borne Arsenic and Trace Metals.

    Science.gov (United States)

    Nworie, Obinna Elijah; Qin, Junhao; Lin, Chuxia

    2017-08-21

    A batch experiment was conducted to examine the effects of six low-molecular-weight organic acids on the mobilization of arsenic and trace metals from a range of contaminated soils. The results showed that the organic acids behaved differently when reacting with soil-borne As and trace metals. Oxalic acid and acetic acid had the strongest and weakest capacity to mobilize the investigated elements, respectively. The solubilisation of iron oxides by the organic acids appears to play a critical role in mobilizing other trace metals and As. Apart from acidification and complexation, reductive dissolution played a dominant role in the dissolution of iron oxides in the presence of oxalic acid, while acidification tended to be more important for dissolving iron oxides in the presence of other organic acids. The unique capacity of oxalic acid to solubilize iron oxides tended to affect the mobilization of other elements in different ways. For Cu, Mn, and Zn, acidification-driven mobilization was likely to be dominant while complexation might play a major role in Pb mobilization. The formation of soluble Fe and Pb oxalate complexes could effectively prevent arsenate or arsenite from combining with these metals to form solid phases of Fe or Pb arsenate or arsenite.

  8. Direct isolation of high-quality low molecular weight RNA of pear peel from the extraction mixture containing nucleic acid.

    Science.gov (United States)

    Wang, Xin-wei; Xiong, Ai-sheng; Yao, Quan-hong; Zhang, Zhen; Qiao, Yu-shan

    2010-01-01

    Low molecular weight RNA (LMW RNA) is generally obtained either from the total RNA or from total nucleic acids solution. Many steps and chemical reagents are involved in traditional methods for LMW RNA isolation where degradation of LMW RNA often occurs, especially for plant materials with high levels of secondary catabolites. In this study, an efficient method was developed to directly isolate pure LMW RNA from pear peel, a material rich in polyphenolics that is covered with a layer of wax. The method was based on polyethylene glycol (PEG) precipitation combining CTAB buffer which is often used to isolate RNA from polysaccharide-rich and polyphenolics-rich materials. The entire procedure could be completed within 6 h and many samples could be processed at the same time. Few and common chemicals are used with this method. Hence, it could be used as an ordinary method in the laboratory. The developed method was further tested by isolating LMW RNA from Arabidopsis. Using the isolated LMW RNA samples, microRNAs were successfully detected and characterized.

  9. Effect of high and low molecular weight glutenin subunits, and subunits of gliadin on physicochemical parameters of different wheat genotypes

    Directory of Open Access Journals (Sweden)

    Mariana Souza Costa

    2013-02-01

    Full Text Available Identification of functional properties of wheat flour by specific tests allows genotypes with appropriate characteristics to be selected for specific industrial uses. The objective of wheat breeding programs is to improve the quality of germplasm bank in order to be able to develop wheat with suitable gluten strength and extensibility for bread making. The aim of this study was to evaluate 16 wheat genotypes by correlating both glutenin subunits of high and low molecular weight and gliadin subunits with the physicochemical characteristics of the grain. Protein content, sedimentation volume, sedimentation index, and falling number values were analyzed after the grains were milled. Hectoliter weight and mass of 1000 seeds were also determined. The glutenin and gliadin subunits were separated using polyacrylamide gel in the presence of sodium dodecyl sulfate. The data were evaluated using variance analysis, Pearson's correlation, principal component analysis, and cluster analysis. The IPR 85, IPR Catuara TM, T 091015, and T 091069 genotypes stood out from the others, which indicate their possibly superior grain quality with higher sedimentation volume, higher sedimentation index, and higher mass of 1000 seeds; these genotypes possessed the subunits 1 (Glu-A1, 5 + 10 (Glu-D1, c (Glu-A3, and b (Glu-B3, with exception of T 091069 genotype that possessed the g allele instead of b in the Glu-B3.

  10. Low-Molecular-Weight Hydrophilic and Lipophilic Antioxidants in Nonmelanoma Skin Carcinomas and Adjacent Normal-Looking Skin.

    Science.gov (United States)

    Grammenandi, Konstantina; Kyriazi, Maria; Katsarou-Katsari, Alexandra; Papadopoulos, Othon; Anastassopoulou, Ioanna; Papaioannou, Georgios T; Sagriotis, Alexandros; Rallis, Michail; Maibach, Howard I

    2016-01-01

    Low-molecular-weight antioxidants are some of the most efficient agents of the skin defense mechanism against environmental factors, such as cosmic rays, smoke, and pollutants. The total skin concentrations of hydrophilic ascorbic and uric acids, as well as lipophilic α-tocopherol, β-carotene, and ubiquinol-10 antioxidants were determined by an HPLC-EC detector from 18 biopsies of human nonmelanoma skin carcinomas and 18 biopsies from skin areas adjacent to carcinomas. No significant differences in the concentrations of lipophilic antioxidants in both carcinomas and normal-looking skin areas adjacent to carcinomas were observed. On the contrary, ascorbic and uric acid concentrations were found to be 18 and 36% lower in carcinomas than in normal-looking skin areas, respectively. No statistical significance was observed between antioxidant concentrations and age, sex, phototype, profession, site of tumor, frequency, and time of UV light exposure either. Accordingly the antioxidant concentrations in both cancerous skin and adjacent normal-looking areas were found to be much higher than in normal skin, in contrast to literature data. © 2017 S. Karger AG, Basel.

  11. Antithrombotic therapy in patients with thrombocytopenic cancer: outcomes associated with reduced-dose, low-molecular-weight heparin during hospitalization.

    Science.gov (United States)

    Babilonia, Katrina M; Golightly, Larry K; Gutman, Jonathan A; Hassell, Kathryn L; Kaiser, Jeffrey N; Kiser, Tyree H; Klem, Patrick M; Trujillo, Toby C

    2014-11-01

    Guidelines are discordant concerning management of patients having thrombocytopenia with cancer-associated thrombosis (CAT). Hospitalized adults with CAT and platelets ≤50 × 10(9) cells/L were managed with dalteparin 100 units/kg subcutaneously once daily. Comparator patients with CAT and platelets >50 × 10(9) cells/L were managed with dalteparin 200 units/kg/d. Outcomes of 35 patients with thrombocytopenia (mean platelet count 26 ± 8.3 × 10(9) cells/L) and 58 comparator patients (mean platelet count 155 ± 75 × 10(9) cells/L) were evaluated. In all, 2 (5.7%) patients in the thrombocytopenia group and 1 patient (1.9%) in the comparator group experienced new-onset venous thromboembolism (odds ratio 3.31, 95% confidence interval [CI] 0.29-37.90, P = .556). The incidence of bleeding in patients with thrombocytopenia (8.6%) was similar to that in comparator patients (9.4%; risk ratio 0.94, 95% CI 0.37-2.39, P = .607). In hospitalized patients having thrombocytopenia with CAT, reduced-dose low-molecular-weight heparin was generally efficacious. © The Author(s) 2014.

  12. New Insights in Thrombin Inhibition Structure-Activity Relationships by Characterization of Octadecasaccharides from Low Molecular Weight Heparin.

    Science.gov (United States)

    Mourier, Pierre A J; Guichard, Olivier Y; Herman, Fréderic; Sizun, Philippe; Viskov, Christian

    2017-03-08

    Low Molecular Weight Heparins (LMWH) are complex anticoagulant drugs that mainly inhibit the blood coagulation cascade through indirect interaction with antithrombin. While inhibition of the factor Xa is well described, little is known about the polysaccharide structure inhibiting thrombin. In fact, a minimal chain length of 18 saccharides units, including an antithrombin (AT) binding pentasaccharide, is mandatory to form the active ternary complex for LMWH obtained by alkaline β-elimination (e.g., enoxaparin). However, the relationship between structure of octadecasaccharides and their thrombin inhibition has not been yet assessed on natural compounds due to technical hurdles to isolate sufficiently pure material. We report the preparation of five octadecasaccharides by using orthogonal separation methods including size exclusion, AT affinity, ion pairing and strong anion exchange chromatography. Each of these octadecasaccharides possesses two AT binding pentasaccharide sequences located at various positions. After structural elucidation using enzymatic sequencing and NMR, in vitro aFXa and aFIIa were determined. The biological activities reveal the critical role of each pentasaccharide sequence position within the octadecasaccharides and structural requirements to inhibit thrombin. Significant differences in potency, such as the twenty-fold magnitude difference observed between two regioisomers, further highlights the importance of depolymerisation process conditions on LMWH biological activity.

  13. Combined effects of low-molecular-weight organic acids on mobilization of arsenic and lead from multi-contaminated soils.

    Science.gov (United States)

    Onireti, Olaronke O; Lin, Chuxia; Qin, Junhao

    2017-03-01

    A batch experiment was conducted to examine the combined effects of three common low-molecular-weight organic acids (LMWOAs) on the mobilization of arsenic and lead in different types of multi-contaminated soils. The capacity of individual LMWOAs (at a same molar concentration) to mobilize soil-borne As and Pb varied significantly. The combination of the organic acids did not make a marked "additive" effect on the mobilization of the investigated three elements. An "antagonistic" effect on element mobilization was clear in the treatments involving oxalic acid for some soils. The acid strength of a LMWOA did not play an important role in controlling the mobilization of elements. While the mobilization of As and Pb was closely associated with the dissolution of soil-borne Fe, soil properties such as original soil pH, organic matter contents and the total amount of the element relative to the total Fe markedly complicated the mobility of that element. Aging led to continual consumption of proton introduced from addition of LMWOAs and consequently caused dramatic changes in solution-borne Fe, which in turn resulted in change in As and Pb in the soil solution though different elements behaved differently. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Removal of Low-Molecular Weight Aldehydes by Selected Houseplants under Different Light Intensities and CO2 Concentrations

    Directory of Open Access Journals (Sweden)

    Jian Li

    2016-11-01

    Full Text Available The removal of five low-molecular weight aldehydes by two houseplants (Schefflera octophylla (Lour. Harms and Chamaedorea elegans were investigated in a laboratory simulation environment with short-term exposure to different low light intensities and CO2 concentrations. Under normal circumstances, the C1–C5 aldehyde removal rates of Schefflera octophylla (Lour. Harms and Chamaedorea elegans (Lour. Harms ranged from 0.311 μmol/m2/h for valeraldehyde to 0.677 μmol/m2/h for formaldehyde, and 0.526 μmol/m2/h for propionaldehyde to 1.440 μmol/m2/h for formaldehyde, respectively. However, when the light intensities varied from 0 to 600 lx, a significant correlation between the aldehyde removal rate and the light intensity was found. Moreover, the CO2 experiments showed that the total aldehyde removal rates of Schefflera octophylla (Lour. Harms and Chamaedorea elegans (Lour. Harms decreased 32.0% and 43.2%, respectively, with increasing CO2 concentrations from 350 ppmv to 1400 ppmv. This might be explained by the fact that the excessive CO2 concentration decreased the stomatal conductance which limited the carbonyl uptake from the stomata.

  15. Low-molecular weight carbohydrates modulate dormancy and are required for post-germination growth in turions of Spirodela polyrhiza.

    Science.gov (United States)

    Appenroth, K-J; Palharini, L; Ziegler, P

    2013-03-01

    The aquatic duckweed Spirodela polyrhiza propagates itself vegetatively by forming turions - bud-like perennation organs - in the autumn, which spend the winter on the bottom of ponds and then germinate in the following spring and proliferate on the water surface. Newly formed turions usually require a period of cold after-ripening and light to germinate effectively, but an ample supply of exogenous sugar can lead to germination even in the dark and independent of after-ripening. The results of the present study indicate that the availability of readily metabolised carbohydrates is a determining factor for turion germination. Freshly harvested turions do not contain soluble, low-molecular weight carbohydrates at a level sufficient to allow germination to take place, but after-ripened turions do. Augmentation of the soluble carbohydrate content during after-ripening derives from gradual breakdown of reserve starch of the turions. The long time required for any germination to be observed in turions incubated in darkness and the limited frequency of germination in the dark (about 50% of turion population), even with an ample external sugar, supply emphasise that both after-ripening and light are essential for ensuring rapid germination and subsequent frond proliferation at an ecologically appropriate time. The carbohydrate supply required for rapid proliferation of the fronds produced at germination is provided by the rapid light-induced breakdown of turion reserve starch. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.

  16. Transdermal delivery of low molecular weight heparin loaded in flexible liposomes with bioavailability enhancement: comparison with ethosomes.

    Science.gov (United States)

    Song, Yun-Kyoung; Hyun, Seo Yeon; Kim, Hyung-Tae; Kim, Chong-Kook; Oh, Jung-Mi

    2011-01-01

    Low molecular weight heparin (LMWH)-loaded flexible liposomes (flexosomes) were formulated for transdermal delivery, and their physicochemical and pharmacokinetic parameters were compared with LMWH-loaded ethosomes. Flexosomes had similar particle size compared with ethosomes, but their deformability was higher than that of ethosomes (76.7% vs. 46.8%). In vitro, flexosomes demonstrated 2.6-fold higher permeability coefficient than ethosomes. In comparison to LMWH aqueous solution, skin deposition of flexosome increased 3.2-fold, while that of ethosome increased only 2.0-fold. In vivo, after the topical application of flexosome to hairless mouse, [anti-Xa](max) was 1.11 IU/mL, while ethosomes showed only 0.32 IU/mL. Moreover, AUC(0-24 h) of flexosomes was 2.5-fold higher than ethosomes. In conclusion, the enhanced skin permeation and bioavailability of LMWH can be achieved with flexosomes in comparison with ethosomes. The LMWH transdermal delivery via flexosomes has the potential to replace the parenteral dosage forms for the treatment of venous thromboembolism, pulmonary embolism and cardiovascular events.

  17. The role of microbial low-molecular-weight autoregulatory factors (alkylhydroxybenzenes) in resistance of microorganisms to radiation

    Science.gov (United States)

    El-Registan, G. I.; Mulyukin, A. L.; Nikolaev, Yu. A.; Stepanenko, I. Yu.; Shanenko, E. A.; Strakhovskaya, M. G.; Revina, A. A.

    Low-molecular-weight cell-to-cell communication factors are produced by various pro- and eukaryotes and involved in autoregulation of the growth and development of microbial cultures. As for some bacterial and yeast species, these factors were identified as isomers and homologs of alkylhydroxybenzenes (AHBs). Depending on the concentration, they participate in controlling the transition to stationary phase, entering the resting state, and stress resistance of vegetative cells to gamma-irradiation, photooxidation (singlet oxygen), heat shock. Chemical analogs of microbial AHBs protected microbial cultures from stressful situations and prolonged starvation and exerted (1) the stabilizing activity toward biomacromolecules and supermolecular structures (cell membranes) and (2) the ability to scavenge active oxygen species. The stabilizing effect of AHBs as chemical chaperones resulted from their complex formation with protected macromolecules due to intermolecular hydrogen bonds, hydrophobic and electrostatic interactions and was demonstrated on models of individual enzymes (trypsin, amylase, etc.). The action of AHBs as active oxygen species scavengers was related to their oxidative conversion to water-insoluble polymeric products. Particularly, AHBs protected the yeast from the action of (a) active oxygen species formed during gamma-irradiation (50 krad, 196 rad/sec) or (b) singlet oxygen generated in cells photosensitized by chlorin e6 (10 mkg/L). It is important that microbial AHBs were not species-specific and defended cultured animal cells (ras-transformed fibroblasts) from the action of organic toxicants. The use of AHBs as protectants and adaptogens will be discussed as well as perspectives of further investigations.

  18. Synthesis of gamma-glutamylcysteine as a major low-molecular-weight thiol in lactic acid bacteria Leuconostoc spp.

    Science.gov (United States)

    Kim, Eun-Kyoung; Cha, Chang-Jun; Cho, Yong-Joon; Cho, Yoo-Bok; Roe, Jung-Hye

    2008-05-16

    Some members of lactic acid bacteria are known to synthesize glutathione (GSH) or to import it from growth medium, whereas others are not. Analysis of the genome sequences of several Leuconostoc spp. indicate the presence of the gene gshA that encodes gamma-glutamylcysteine synthetase, but not the gene gshB encoding glutathione synthetase. We report here that, in cells of Leuconostoc kimchii and Leuconostoc mesenteroides, gamma-glutamylcysteine (gamma-GC) is present in large amount, whereas GSH is not detectable. The level of gamma-GC was higher at the stationary phase than at the exponential phase. Expression of the gshA gene in Leuconostoc spp. analyzed by S1 mapping showed the increased mRNA level upon hydrogen peroxide treatment. From high-resolution S1 mapping, the transcriptional start site was mapped and the putative promoter elements were suggested. This work suggests that gamma-GC has a significant role in Leuconostoc spp. as the major low-molecular-weight thiol.

  19. Studies of interaction of a low-molecular-weight heparinoid (Org 10172) with cloxacillin and ticarcillin in healthy male volunteers.

    Science.gov (United States)

    de Boer, A; Stiekema, J C; Danhof, M; van Dinther, T G; Boeijinga, J K; Cohen, A F; Breimer, D D

    1991-01-01

    Pharmacokinetic and pharmacodynamic interactions between Org 10172 (intravenous bolus injection of 3,250 anti-Xa units), which is a low-molecular-weight heparinoid, cloxacillin (500 mg orally four times daily for 3 days), and ticarcillin (4,000 mg intravenously four times daily for 2 days) were evaluated in two separate studies with healthy male volunteers (n = 18). Both cloxacillin and ticarcillin caused a significant increase in elimination half-life of anti-Xa activity, i.e., from 31 +/- 10 to 54 +/- 23 h and from 27 +/- 6 to 42 +/- 13 h, respectively (P less than 0.05). Ticarcillin decreased clearance (11%) and increased apparent volume of distribution (35%) (P less than 0.05), while for cloxacillin, these differences did not reach statistical significance. These changes in disposition of Org 10172 by the penicillins were not accompanied by important pharmacodynamic changes as evaluated by coagulation tests, platelet aggregation, and bleeding time. Cloxacillin appeared to influence blood coagulation (prolongation of the activated partial thromboplastin time and shortening of thrombin time; P less than 0.05) and facilitated thrombin-induced platelet aggregation, which coincided with a shorter bleeding time during the combined treatment in comparison with the time during treatment with Org 10172 alone (P less than 0.05). In conclusion, the disposition of Org 10172 was slightly changed by cloxacillin and ticarcillin, and, unexpectedly, cloxacillin appeared to have mild procoagulant effects. PMID:1759835

  20. Extraction/oxidation kinetics of low molecular weight compounds in wine brandy resulting from different ageing technologies.

    Science.gov (United States)

    Canas, Sara; Caldeira, Ilda; Belchior, A Pedro

    2013-06-15

    This study provides innovative information on the influence of new technologies of ageing (stainless steel tanks with wood staves or wood tablets of chestnut or Limousin oak), in comparison with traditional technology (oak wooden barrels), on the extraction/oxidation kinetics of low molecular weight compounds of wine brandy. The brandy was sampled and analysed by HPLC during the first year of ageing. The results show that most of the compounds tend to increase over the time, but their extraction/oxidation kinetics depend on the ageing technology. The wooden barrels promote greater enrichment in the majority of the compounds. However, gallic acid, ellagic acid and syringaldehyde, and vanillin and 5-methylfurfural, which are strong antioxidants and key-odourant compounds, respectively, present higher contents in the brandy aged with the alternative technologies. Chestnut proves to be a suitable alternative to Limousin oak for the ageing of brandy in all the studied technologies, inducing faster evolution and high quality. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Kinetic study of acid depolymerization of chitosan and effects of low molecular weight chitosan on erythrocyte rouleaux formation.

    Science.gov (United States)

    Tsao, Ching Ting; Chang, Chih Hao; Lin, Yu Yung; Wu, Ming Fung; Han, Jin Lin; Hsieh, Kuo Huang

    2011-01-03

    In this study, the depolymerization of chitosan was carried out in an acetic acid aqueous solution and was followed by viscometry for molecular weight determination. It was found that the depolymerization rate increased with elevated temperatures and with high acid concentrations. Based on FTIR analysis, the chitosan was depolymerized randomly along the backbone; no other structural change was observed during the acid depolymerization process. Revealed in the TGA study, the degradation temperature and char yield of LMWCs (low molecular weight chitosan) were molecular weight dependent. The blood compatibility of LMWCs was also investigated: rouleaux formation was observed when erythrocyte contacted with LMWCs, which showed that LMWCs are able to interfere with the negatively charged cell membrane through its polycationic properties. Furthermore, as regards a kinetics investigation, the values of M(n) (number-average molecular weight) were obtained from an experimentally determined relationship. The kinetics study showed that the complex salt, formed by amine on chitosan and acetic acid, acted as catalyst. Finally, the activation energy for the hydrolysis of the glycosidic linkage on chitosan was calculated to be 40kJ/mol; the mechanism of acid depolymerization is proposed. In summary, LMWCs could be easily and numerously generated with acid depolymerization for further biological applications. 2010 Elsevier Ltd. All rights reserved.

  2. Effect of low-molecular-weight organic acids on the adsorption of norfloxacin in typical variable charge soils of China.

    Science.gov (United States)

    Zhang, Jin-qiang; Dong, Yuan-hua

    2008-03-01

    Batch equilibrium experiments were used to study the adsorption of norfloxacin (NOR) onto three kinds of variable charge soils in China, namely Rho-Udic Ferralisols collected from Yunnan, Ali-Perudic Ferrisols collected from Jiangxi and Typ-Hap-Udic Ferralisols collected from Guangdong. Results show that NOR is strongly adsorbed by the soils, with lg Kd-values (linear model) of 4.41+/-0.01, 4.50+/-0.02, 4.44+/-0.01 and lg Kf-values (Freundlich model) of 4.32, 4.45, 3.08 for the three tested soils, respectively. Both curves of the Freundlich equation and Langmuir equation for the three soils were in excellent linear correlation. Low-molecular-weight (LMW) organic acids, including citric acid, malic acid and salicylic acid were added in the presence of acetate buffer (pH 4.5) to test their effects on NOR adsorption. It was observed that the addition of LMW organic acids inhibited the NOR adsorption process. It was assumed that several effects, including soil pH, solid surface charge and competitive adsorption of co-existing cations, dominated the NOR sorption processes onto variable charge soils. Further studies should be performed to reveal the mechanism of the adsorption.

  3. Low molecular weight fucoidan against renal ischemia-reperfusion injury via inhibition of the MAPK signaling pathway.

    Directory of Open Access Journals (Sweden)

    Jihui Chen

    Full Text Available BACKGROUND: Ischemia reperfusion injury (IRI is a leading cause of acute kidney injury (AKI in both native and transplanted kidneys. The objective of the present study was to evaluate whether low-molecular-weight fucoidan (LMWF could attenuate renal IRI in an animal model and in vitro cell models and study the mechanisms in which LMWF protected from IRI. METHODOLOGY/PRINCIPAL FINDINGS: Male mice were subjected to right renal ischemia for 30 min and reperfusion for 24 h, or to a sham operation with left kidney removed. Kidneys undergone IR showed characteristic morphological changes, such as tubular dilatation, and brush border loss. However, LMWF significantly corrected the renal dysfunction and the abnormal levels of MPO, MDA and SOD induced by IR. LMWF also inhibited the activation of MAPK pathways, which consequently resulted in a significant decrease in the release of cytochrome c from mitochondria, ratios of Bax/Bcl-2 and cleaved caspase-3/caspase-3, and phosphorylation of p53. LMWF alleviated hypoxia-reoxygenation or CoCl(2 induced cell viability loss and ΔΨm dissipation in HK2 renal tubular epithelial cells, which indicates LMWF may result in an inhibition of the apoptosis pathway through reducing activity of MAPK pathways in a dose-dependent manner. CONCLUSIONS/SIGNIFICANCE: Our in vivo and in vitro studies show that LMWF ameliorates acute renal IRI via inhibiting MAPK signaling pathways. The data provide evidence that LMWF may serve as a potential therapeutic agent for acute renal IRI.

  4. Occurrence of non-protein low molecular weight cardiotoxin in Indian King Cobra (Ophiophagus hannah) Cantor 1836, venom.

    Science.gov (United States)

    Saha, Archita; Gomes, Aparna; Giri, B; Chakravarty, A K; Biswas, A K; Dasgupta, S C; Gomes, A

    2006-04-01

    Pathophysiology due to snakebite is a combined effect of various actions of the complex venom constituents. Importance of protein toxins in snake envenomation is well known. The present investigation reports the existence of nonprotein/nonpetide low molecular weight toxin in Indian King Cobra venom, which plays an important role in envenomation consequences in experimental animal models. A group of non-peptidic toxins (OH-NPT1) was isolated from Indian King Cobra Ophiophagus hannah by thin layer chromatography and silica gel column chromatography. UV, IR, NMR and (ESI) TOF-MS studies characterized the OH-NPT1 as a mixture of aliphatic acids having molecular weights 256, 326 and 340Da. The minimum lethal dose of OH-NPT1 was found to be 2.5 microg/20g (iv) and 4microg/20g (ip) in male albino mice. The cardiotoxic property of OH-NPT1 was established through studies on isolated guinea pig heart and auricle preparations, ECG studies in albino rat and estimation of LDH1/LDH and CPK-MB/CPK ratio in Swiss albino mice. Commercial antiserum failed to neutralize the lethality and cardiotoxicity of the toxin. However, calcium and magnesium effectively neutralized the lethal action.

  5. Efficacy and safety of low molecular weight heparin in patients with mechanical heart valves: systematic review and meta-analysis.

    Science.gov (United States)

    Caldeira, D; David, C; Santos, A T; Costa, J; Pinto, F J; Ferreira, J J

    2014-05-01

    Low molecular weight heparins (LMWHs) are not approved for patients with mechanical heart valves (MHVs). However, in several guidelines, temporary LMWH off-label use in this clinical setting is considered to be a valid treatment option. Therefore, we reviewed the efficacy and safety of LMWHs in patients with MHVs. MEDLINE and CENTRAL databases were searched from inception to June 2013. Review articles and references were also searched. We included experimental and observational studies that compared LMWHs with unfractionated heparin (UFH) or vitamin K antagonists (VKAs). Data were analyzed and pooled to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for thromboembolic and major bleeding events. Statistical heterogeneity was evaluated with the I(2) -test. Nine studies were included: one randomized controlled trial (RCT) and eight observational studies, with a total of 1042 patients. No differences were found between LMWHs and UFH/VKAs in the risk of thromboembolic events (OR 0.67; 95% CI 0.27-1.68; I(2) = 9%) or major bleeding events (OR 0.66; 95% CI 0.36-1.19; I(2) = 0%). The best evidence available might support the temporary use of LMWHs as a prophylactic treatment option in patients with MHVs. However, conclusions are mostly based on observational data (with large CIs), and an adequately powered RCT is urgently needed in this clinical setting. © 2014 International Society on Thrombosis and Haemostasis.

  6. Renal drug delivery with low-molecular-weight proteins : The effect of charge modifications on the body distribution of drug-lysozyme conjugates

    NARCIS (Netherlands)

    Kok, R.J; Nederhoed, K.H; Moolenaar, Frits; de Zeeuw, D; Meijer, D.K F

    1999-01-01

    Low-molecular-weight proteins (LMWPs) can be used as drug carriers for renal drug delivery. The covalent attachment of drug molecules is commonly achieved via reaction to the primary amino groups of the protein. However, these positively charged groups are also important for the renal reabsorption

  7. Low molecular weight linear polyethylenimine-b-poly(ethylene glycol)-b-polyethylenimine triblock copolymers: synthesis, characterization, and in vitro gene transfer properties

    NARCIS (Netherlands)

    Zhong, Zhiyuan; Feijen, Jan; Christensen, L.

    2005-01-01

    Novel ABA triblock copolymers consisting of low molecular weight linear polyethylenimine (PEI) as the A block and poly(ethylene glycol) (PEG) as the B block were prepared and evaluated as polymeric transfectant. The cationic polymerization of 2-methyl-2-oxazoline (MeOZO) using PEG−bis(tosylate) as a

  8. Origin of low-molecular-weight alkylthiophenes in pyrolysates of sulfur-rich kerogens as revealed by micro-scale sealed vessel pyrolysis

    NARCIS (Netherlands)

    Sinninghe Damsté, J.S.; Kohnen, M.E.L.; Horsfield, B.

    1998-01-01

    Micro-scale sealed vessel (MSSV) pyrolysis experiments have been conducted at temperatures of 150, 200, 250, 300, 330 and 350¡ãC for various times on a thermally immature Type II-S kerogen from the Maastrichtian Jurf ed Darawish Oil Shale (Jordan) in order to study the origin of low-molecular-weight

  9. A systematic review on the accumulation of prophylactic dosages of low-molecular-weight heparins (LMWHs) in patients with renal insufficiency

    NARCIS (Netherlands)

    2015-01-01

    markdownabstractPurpose Although therapeutic dosages of most low-molecular-weight heparins (LMWHs) are known to accumulate in patients with renal insufficiency, for the lower prophylactic dosages this has not been clearly proven. Nevertheless, dose reduction is often recommended. We conducted a

  10. Children with atopic dermatitis and frequent emollient use have increased urinary levels of low-molecular-weight phthalate metabolites and parabens

    DEFF Research Database (Denmark)

    Overgaard, L E K; Main, K M; Frederiksen, H

    2017-01-01

    BACKGROUND: Parabens may be added to cosmetic and personal care products for preservation purposes. Low-molecular weight (LMW) phthalate diesters function as plasticizers, fixatives or solvents in such products, but may also be found in small quantities as contaminants from plastic containers. OB...

  11. Definition of the low molecular weight glutenin subunit gene family members in a set of standard bread wheat (Triticum aestivum L.) varieties

    Science.gov (United States)

    Low-molecular-weight glutenin subunits (LMW-GS) are a class of seed storage proteins that play a major role in the determination of the viscoelastic properties of wheat dough. Most of the LMW-GSs are encoded by a multi-gene family located on the short arms of the homoeologous group 1 chromosomes, at...

  12. Wheat IgE-mediated food allergy in European patients: alpha-amylase inhibitors, lipid transfer proteins and low-molecular-weight glutenins

    DEFF Research Database (Denmark)

    Pastorello, Elide A; Farioli, Laura; Conti, Amedeo

    2007-01-01

    /globulin fraction and several low-molecular-weight (LMW) glutenin subunits in the gluten fraction. All these allergens showed heat resistance and lack of cross-reactivity to grass pollen allergens. LTP was a major allergen only in Italian patients. CONCLUSIONS: The alpha-amylase inhibitor was confirmed...

  13. Anticoagulant treatment of cancer patients with pulmonary embolism in the real world Actual use of low-molecular-weight heparin in cancer

    NARCIS (Netherlands)

    Kleinjan, A.; Hutten, B. A.; Di Nisio, M.; Buller, H. R.; Kamphuisen, P. W.

    2014-01-01

    Background: Since 2004, guidelines recommend long-term treatment with low-molecular-weight heparin (LMWH) in patients with cancer and pulmonary embolism (PE). We assessed the proportion of cancer patients with PE actually treated with LMWH and the duration of anticoagulant treatment in the

  14. Anticoagulant treatment of cancer patients with pulmonary embolism in the real world. Actual use of low-molecular-weight heparin in cancer

    NARCIS (Netherlands)

    Kleinjan, A.; Hutten, B. A.; Di Nisio, M.; Büller, H. R.; Kamphuisen, P. W.

    2014-01-01

    Since 2004, guidelines recommend long-term treatment with low-molecular-weight heparin (LMWH) in patients with cancer and pulmonary embolism (PE). We assessed the proportion of cancer patients with PE actually treated with LMWH and the duration of anticoagulant treatment in the Netherlands. A

  15. The influence of the binding of low molecular weight surfactants on the thermal stability and secondary structure of IgG

    NARCIS (Netherlands)

    Vermeer, AWP; Norde, W

    2000-01-01

    The effect of low molecular weight surfactants on the thermal stability of immunoglobulin G is studied by differential scanning calorimetry. The corresponding change in the secondary structure is investigated using circular dichroism spectroscopy and the rate of aggregate formation, both in the

  16. Subcutaneous low-molecular weight heparin or oral anticoagulants for the prevention of deep-vein thrombosis in elective hip and knee replacement?

    NARCIS (Netherlands)

    Hamulyak, K; Lensing, AWA; vanderMeer, J; Smid, WM; vanOoy, A; Hoek, JA

    1995-01-01

    Objective. To compare efficacy, safety, and feasibility of adjusted-dose oral anticoagulants (OAC) versus fixed-dose subcutaneous low molecular weight heparin (LMWH) for the prevention of deep venous thrombosis (DVT) in patients who have undergone elective hip or knee replacement. Desin.

  17. Incidence of postpartum haemorrhage in women receiving therapeutic doses of low-molecular-weight heparin : results of a retrospective cohort study

    NARCIS (Netherlands)

    Roshani, Sara; Cohn, Danny M; Stehouwer, Alexander C; Wolf, Hans; van der Post, Joris A M; Büller, Harry R; Kamphuisen, Pieter W; Middeldorp, Saskia

    2011-01-01

    Background Low-molecular-weight heparin (LMWH) is the drug of choice to prevent venous thrombosis in pregnancy, but the optimal dose for prevention while avoiding bleeding is unclear. This study investigated whether therapeutic doses of LMWH increase the incidence of postpartum haemorrhage (PPH) in

  18. LOW-MOLECULAR-WEIGHT PROTEINS AS CARRIERS FOR RENAL DRUG TARGETING - NAPROXEN COUPLED TO LYSOZYME VIA THE SPACER L-LACTIC ACID

    NARCIS (Netherlands)

    FRANSSEN, EJF; MOOLENAAR, F; DEZEEUW, D; MEIJER, DKF

    Low molecular weight proteins (LMWPs) are potential carriers for targeting drugs to the kidney. To test whether ester bonds are suitable for the reversible drug conjugation, the antiinflammatory drug naproxen (Nap) was conjugated to the LMWP lysozyme (LYSO) via an ester bond using an L-lactic acid

  19. Highly active, recyclable catalyst for the manufacture of viscous, low molecular weight, CO–ethene–propene-based polyketone, base component for a new class of resins

    NARCIS (Netherlands)

    Broekhuis, Antonius A.; Dirkzwager, Hendrik; Mul, Wilhelmus P.; Heeres, Hero J.; Linden, Adrianus J. van der; Orpen, A. Guy

    2002-01-01

    A highly active, recyclable homogeneous palladium(II) catalyst is described for the manufacture of viscous, low molecular weight CO–ethene–propene-based polyketone (Carilite Oligomer), used for the manufacture of a new class of resins (Carilite Resins). The catalyst is composed of palladium acetate,

  20. Low-molecular-weight heparin and recurrent placenta-mediated pregnancy complications: a meta-analysis of individual patient data from randomised controlled trials.

    Science.gov (United States)

    Rodger, Marc A; Gris, Jean-Christophe; de Vries, Johanna I P; Martinelli, Ida; Rey, Évelyne; Schleussner, Ekkehard; Middeldorp, Saskia; Kaaja, Risto; Langlois, Nicole J; Ramsay, Timothy; Mallick, Ranjeeta; Bates, Shannon M; Abheiden, Carolien N H; Perna, Annalisa; Petroff, David; de Jong, Paulien; van Hoorn, Marion E; Bezemer, P Dick; Mayhew, Alain D

    2016-11-26

    Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and birth of a small-for-gestational-age (SGA) neonate. These complications are leading causes of maternal, fetal, and neonatal morbidity and mortality in high-income countries. Affected women are at high risk of recurrence in subsequent pregnancies; however, effective strategies to prevent recurrence are absent. Findings from our previous study-level meta-analysis suggested that low-molecular-weight heparin reduced the risk of recurrent placenta-mediated pregnancy complications. However, we identified significant heterogeneity in the results, possibly due to trial design or inclusion criteria. To identify which patients benefit from, and which outcomes are prevented by, low-molecular-weight heparin, we did an individual patient data meta-analysis. We did a systematic review in May, 2013, which identified eight eligible randomised trials done between 2000 and 2013 of low-molecular-weight heparin to prevent recurrent placenta-mediated pregnancy complications. We excluded studies on the basis of the wrong population, the study being ongoing, inability to confirm eligibility of participants, intervention stopped too early, and no response from the principal investigator. We requested individual patient data from the study authors for eligible women (women pregnant at the time of the study with a history of previous pregnancy that had been complicated by one or more of the following: pre-eclampsia, placental abruption, birth of an SGA neonate [pregnancy loss after 16 weeks' gestation, or two losses after 12 weeks' gestation) and recoded, combined, and analysed the data for our meta-analysis. The primary outcome was a composite of early-onset (pregnancy loss (≥20 weeks' gestation), or placental abruption leading to delivery, assessed on an intention-to-treat basis. We assessed risk of bias with the Cochrane Risk of Bias tool. This study is registered with

  1. Low molecular weight iron dextran increases fibroblast growth factor-23 concentration, together with parathyroid hormone decrease in hemodialyzed patients.

    Science.gov (United States)

    Hryszko, Tomasz; Rydzewska-Rosolowska, Alicja; Brzosko, Szymon; Koc-Zorawska, Ewa; Mysliwiec, Michal

    2012-04-01

    Fibroblast growth factor (FGF)-23 inhibits PTH production. Elevated FGF-23 and parathyroid hormone (PTH) levels are characteristic of hemodialyzed patients. Iron polymaltose was shown to increase FGF-23 concentration. The effect of intravenous low molecular weight iron dextran (LMID) on these hormones and bone metabolism has not been studied in hemodialysis (HD). Twelve HD patients were prospectively followed up for 3 weeks after a single infusion of LMID. Calcium, phosphate, FGF-23, PTH, degradation products of C-terminal telopeptides of type I collagen (CTX) and procollagen I N-terminal propeptide (PINP) were measured prior to, and at week 1 and week 3 after the LMID administration. FGF-23 increased significantly from 453.4 (68.6-3971.5) pg/mL at baseline to 971.8 (779.5-3361.4) pg/mL (P = 0.001) at week 1 and started to decrease toward the initial value at week 3. The changes were accompanied by a significant decline in PTH from 367.6 (21.4-1487.4) pg/mL at baseline to 315.7 (16.4-1339.8) pg/mL (P = 0.018) at week 1 and subsequently began to increase toward the initial values. Phosphate, calcium, CTX and PINP did not change over the study course. LMID causes an increase in FGF-23 concentration together with a decrease in PTH. Our study highlights a pathophysiological element, which may connect suppression of parathyroid glands with intravenous iron supplementation. © 2012 The Authors. Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis.

  2. Natural Compounds Interacting with Nicotinic Acetylcholine Receptors: From Low-Molecular Weight Ones to Peptides and Proteins

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    Denis Kudryavtsev

    2015-05-01

    Full Text Available Nicotinic acetylcholine receptors (nAChRs fulfill a variety of functions making identification and analysis of nAChR subtypes a challenging task. Traditional instruments for nAChR research are d-tubocurarine, snake venom protein α-bungarotoxin (α-Bgt, and α-conotoxins, neurotoxic peptides from Conus snails. Various new compounds of different structural classes also interacting with nAChRs have been recently identified. Among the low-molecular weight compounds are alkaloids pibocin, varacin and makaluvamines C and G. 6-Bromohypaphorine from the mollusk Hermissenda crassicornis does not bind to Torpedo nAChR but behaves as an agonist on human α7 nAChR. To get more selective α-conotoxins, computer modeling of their complexes with acetylcholine-binding proteins and distinct nAChRs was used. Several novel three-finger neurotoxins targeting nAChRs were described and α-Bgt inhibition of GABA-A receptors was discovered. Information on the mechanisms of nAChR interactions with the three-finger proteins of the Ly6 family was found. Snake venom phospholipases A2 were recently found to inhibit different nAChR subtypes. Blocking of nAChRs in Lymnaea stagnalis neurons was shown for venom C-type lectin-like proteins, appearing to be the largest molecules capable to interact with the receptor. A huge nAChR molecule sensible to conformational rearrangements accommodates diverse binding sites recognizable by structurally very different compounds.

  3. Phenylboronic Acid Appended Pyrene-Based Low-Molecular-Weight Injectable Hydrogel: Glucose-Stimulated Insulin Release.

    Science.gov (United States)

    Mandal, Deep; Mandal, Subhra Kanti; Ghosh, Moumita; Das, Prasanta Kumar

    2015-08-17

    A pyrene-containing phenylboronic acid (PBA) functionalized low-molecular-weight hydrogelator was synthesized with the aim to develop glucose-sensitive insulin release. The gelator showed the solvent imbibing ability in aqueous buffer solutions of pH values, ranging from 8-12, whereas the sodium salt of the gelator formed a hydrogel at physiological pH 7.4 with a minimum gelation concentration (MGC) of 5 mg mL(-1) . The aggregation behavior of this thermoreversible hydrogel was studied by using microscopic and spectroscopic techniques, including transmission electron microscopy, FTIR, UV/Vis, luminescence, and CD spectroscopy. These investigations revealed that hydrogen bonding, π-π stacking, and van der Waals interactions are the key factors for the self-assembled gelation. The diol-sensitive PBA part and the pyrene unit in the gelator were judiciously used in fluorimetric sensing of minute amounts of glucose at physiological pH. The morphological change of the gel due to addition of glucose was investigated by scanning electron microscopy, which denoted the glucose-responsive swelling of the hydrogel. A rheological study indicated the loss of the rigidity of the native gel in the presence of glucose. Hence, the glucose-induced swelling of the hydrogel was exploited in the controlled release of insulin from the hydrogel. The insulin-loaded hydrogel showed thixotropic self-recovery property, which hoisted it as an injectable soft composite. Encouragingly, the gelator was found to be compatible with HeLa cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. The HMGB1/RAGE Pro-Inflammatory Axis in the Human Placenta: Modulating Effect of Low Molecular Weight Heparin.

    Science.gov (United States)

    Zenerino, Cristian; Nuzzo, Anna Maria; Giuffrida, Domenica; Biolcati, Marilisa; Zicari, Alessandra; Todros, Tullia; Rolfo, Alessandro

    2017-11-17

    We evaluated whether physiological and pre-eclamptic (PE) placentae, characterized by exacerbated inflammation, presented alterations in pro-inflammatory High Mobility Group Box 1 (HMGB1) and its Receptor of Advanced Glycation End products (RAGE) expression. Moreover, we investigated, in physiological placental tissue, the ability of Low Molecular Weight Heparin (LMWH) to modify HMGB1 structural conformation thus inhibiting RAGE binding and HMGB1/RAGE axis inflammatory activity. HMGB1, RAGE, IL-6 and TNFα (HMGB1/RAGE targets) mRNA expression were assessed by Real Time PCR. HMGB1, RAGE protein levels were assessed by western blot assay. Physiological term placental explants were treated by 0.5 U LMWH for 24 or 48 h. HMGB1 and RAGE expression and association were evaluated in LMWH explants by RAGE immunoprecipitation followed by HMGB1 immunoblot. HMGB1 spatial localization was evaluated by immuofluorescent staining (IF). HMGB1 expression was increased in PE relative to physiological placentae while RAGE was unvaried. 24 h LMWH treatment significantly up-regulated HMGB1 expression but inhibited HMGB1/RAGE complex formation in physiological explants. RAGE expression decreased in treated relative to untreated explants at 48 h. IF showed HMGB1 localization in both cytoplasm and nucleus of mesenchymal and endothelial cells but not in the trophoblast. IL-6 and TNFα gene expression were significantly increased at 24 h relative to controls, while they were significantly down-regulated in 48 h vs. 24 h LMWH explants. Our data depicted a new molecular mechanism through which LMWH exerts its anti-inflammatory effect on PE placentae, underlying the importance of HMGB1/RAGE axis in PE inflammatory response.

  5. The HMGB1/RAGE Pro-Inflammatory Axis in the Human Placenta: Modulating Effect of Low Molecular Weight Heparin

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    Cristian Zenerino

    2017-11-01

    Full Text Available We evaluated whether physiological and pre-eclamptic (PE placentae, characterized by exacerbated inflammation, presented alterations in pro-inflammatory High Mobility Group Box 1 (HMGB1 and its Receptor of Advanced Glycation End products (RAGE expression. Moreover, we investigated, in physiological placental tissue, the ability of Low Molecular Weight Heparin (LMWH to modify HMGB1 structural conformation thus inhibiting RAGE binding and HMGB1/RAGE axis inflammatory activity. HMGB1, RAGE, IL-6 and TNFα (HMGB1/RAGE targets mRNA expression were assessed by Real Time PCR. HMGB1, RAGE protein levels were assessed by western blot assay. Physiological term placental explants were treated by 0.5 U LMWH for 24 or 48 h. HMGB1 and RAGE expression and association were evaluated in LMWH explants by RAGE immunoprecipitation followed by HMGB1 immunoblot. HMGB1 spatial localization was evaluated by immuofluorescent staining (IF. HMGB1 expression was increased in PE relative to physiological placentae while RAGE was unvaried. 24 h LMWH treatment significantly up-regulated HMGB1 expression but inhibited HMGB1/RAGE complex formation in physiological explants. RAGE expression decreased in treated relative to untreated explants at 48 h. IF showed HMGB1 localization in both cytoplasm and nucleus of mesenchymal and endothelial cells but not in the trophoblast. IL-6 and TNFα gene expression were significantly increased at 24 h relative to controls, while they were significantly down-regulated in 48 h vs. 24 h LMWH explants. Our data depicted a new molecular mechanism through which LMWH exerts its anti-inflammatory effect on PE placentae, underlying the importance of HMGB1/RAGE axis in PE inflammatory response.

  6. Histopathologic effects of a low molecular weight heparin on bone healing in rats: a promising adjuvant in dacryocystorhinostomy

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    Mehmet Numan Alp

    2016-06-01

    Full Text Available AIM: To investigate the effect of short-term prophylactic dose of a low molecular weight heparin (LMWH drug on the bone healing process in an animal model simulating the osteotomy obtained in dacryocystorhinostomy. METHODS: Forty male Wistar albino rats were divided into 2 groups. Subcutaneous injections of enoxaparin 1 mg/kg (enoxaparin-treated group and saline solution (control group were performed once daily for 4d, beginning on the first preoperative day. The osteotomy was created at the femoral diaphysis in all animals by using a Kirschner wire. Each group was further divided into 2 subgroups depending on the timing of the second operation, 14 or 21d following initial osteotomy. Patent osteotomy area on the second and the third weeks in each group were calculated by using a computer software on digital micrographs. RESULTS: The patent osteotomy areas at the second and the third weeks were significantly larger in the enoxaparin-treated group than those of the control group (P<0.001 for each time-period. In the control group, the patent osteotomy area at the third week of healing was significantly smaller than that of the second week (P=0.003, whereas there was no significant difference between these two measurements in the enoxaparin-treated group (P=0.185. CONCLUSION: Short-term administration of enoxaparin resultes in a significant alteration in bone healing at 14 and 21d after injury. LMWHs can be regarded as promising alternative adjuvants in dacryocystorhinostomy after being evaluated with further clinical and animal studies.

  7. Characterization of the Organic Component of Low-Molecular-Weight Chromium-Binding Substance and Its Binding of Chromium123

    Science.gov (United States)

    Chen, Yuan; Watson, Heather M.; Gao, Junjie; Sinha, Sarmistha Halder; Cassady, Carolyn J.; Vincent, John B.

    2011-01-01

    Chromium was proposed to be an essential element over 50 y ago and was shown to have therapeutic potential in treating the symptoms of type 2 diabetes; however, its mechanism of action at a molecular level is unknown. One chromium-binding biomolecule, low-molecular weight chromium-binding substance (LMWCr or chromodulin), has been found to be biologically active in in vitro assays and proposed as a potential candidate for the in vivo biologically active form of chromium. Characterization of the organic component of LMWCr has proven difficult. Treating bovine LMWCr with trifluoroacetic acid followed by purification on a graphite powder micro-column generates a heptapeptide fragment of LMWCr. The peptide sequence of the fragment was analyzed by MS and tandem MS (MS/MS and MS/MS/MS) using collision-induced dissociation and post-source decay. Two candidate sequences, pEEEEGDD and pEEEGEDD (where pE is pyroglutamate), were identified from the MS/MS experiments; additional tandem MS suggests the sequence is pEEEEGDD. The N-terminal glutamate residues explain the inability to sequence LMWCr by the Edman method. Langmuir isotherms and Hill plots were used to analyze the binding constants of chromic ions to synthetic peptides similar in composition to apoLMWCr. The sequence pEEEEGDD was found to bind 4 chromic ions per peptide with nearly identical cooperativity and binding constants to those of apoLMWCr. This work should lead to further studies elucidating or eliminating a potential role for LMWCr in treating the symptoms of type 2 diabetes and other conditions resulting from improper carbohydrate and lipid metabolism. PMID:21593351

  8. Intramolecular deactivation processes of electronically excited Lanthanide(III) complexes with organic acids of low molecular weight

    Science.gov (United States)

    Burek, Katja; Eidner, Sascha; Kuke, Stefanie; Kumke, Michael U.

    2018-02-01

    The luminescence of Lanthanide(III) complexes with different model ligands was studied under direct as well as sensitized excitation conditions. The research was performed in the context of studies dealing with deep-underground storages for high-level nuclear waste. Here, Lanthanide(III) ions served as natural analogues for Actinide(III) ions and the low-molecular weight organic ligands are present in clay minerals and furthermore, they were employed as proxies for building blocks of humic substances, which are important complexing molecules in the natural environment, e.g., in the far field of a repository site. Time-resolved luminescence spectroscopy was applied for a detailed characterization of Eu(III), Tb(III), Sm(III) and Dy(III) complexes in aqueous solutions. Based on the observed luminescence the ligands were tentatively divided into two groups (A, B). The luminescence of Lanthanide(III) complexes of group A was mainly influenced by an energy transfer to OH-vibrations. Lanthanide(III) complexes of group B showed ligand-related luminescence quenching, which was further investigated. To gain more information on the underlying quenching processes of group A and B ligands, measurements at different temperatures (77 K ≤ T ≤ 353 K) were performed and activation energies were determined based on an Arrhenius analysis. Moreover, the influence of the ionic strength between 0 M ≤ I ≤ 4 M on the Lanthanide(III) luminescence was monitored for different complexes, in order to evaluate the influence of specific conditions encountered in host rocks foreseen as potential repository sites.

  9. IgG antibodies from dourine infected horses identify a distinctive Trypanosoma equiperdum antigenic pattern of low molecular weight molecules.

    Science.gov (United States)

    Luciani, M; Di Pancrazio, C; Di Febo, T; Tittarelli, M; Podaliri Vulpiani, M; Puglielli, M O; Naessens, J; Sacchini, F

    2013-01-15

    Diagnosis and control of dourine is strongly based on serological evidence, but knowledge of the humoral response of horses during infection is limited. In this study we developed a chemiluminescent immunoblotting (cIB) assay to characterise the Trypanosoma equiperdum antigen pattern recognised by IgGs from naturally or experimentally dourine-infected horses and analyse the kinetics of IgG humoral response following the infection. One compounding factor is that sera from uninfected animals often cross-react with T. equiperdum antigens. Development of the cIB assay was based on the hypothesis that serum IgGs from healthy and infected animals recognise different T. equiperdum antigen patterns. We used sera from 8 naturally infected horses which had recovered from Italian outbreaks and 2 experimentally infected mares. In addition, sera from 10 healthy control animals, eight of which were CFT positive but IFA negative for dourine, were collected from disease free regions. Sera were compared by the complement fixation test (CFT), indirect immune fluorescence (IFA) and the cIB assay. cIB analysis revealed that IgGs from infected horses, in contrast to IgGs from healthy horses, specifically recognise a T. equiperdum antigenic profile with low molecular weight bands ranging between 16 and 35 kDa. A time course experiment indicated that IgGs specific for the 16-35 kDa parasite protein fraction appear 17 days post-infection. The cIB assay confirmed all ten infected animals as positive and all controls as negative. This study demonstrated that analysis of IgGs by cIB can provide clear confirmation of trypanosome infection in horses, suggesting that this technique can be applied as a confirmatory serological test for dourine infection. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. [Low molecular weight carboxylic acids in precipitation during the rainy season in the rural area of Anshun, West Guizhou Province].

    Science.gov (United States)

    Zhang, Yan-Lin; Lee, Xin-Qing; Huang, Dai-Kuan; Huang, Rong-Sheng; Jiang, Wei

    2009-03-15

    40 rainwater samples were collected at Anshun from June 2007 to October 2007 and analysed in terms of pH values, electrical conductivity, major inorganic anions and soluble low molecular weight carboxylic acids. The results showed that pH of individual precipitation events ranged from 3.57-7.09 and the volume weight mean pH value was 4.57. The most abundant carboxylic acids were acetic (volume weight mean concentration 6.75 micromol x L(-1)) and formic (4.61 micromol x L(-1)) followed by oxalic (2.05 micromol x L(-1)). The concentration levels for these three species during summer especially June and July were comparatively high; it implied that organic acids in Anshun may came primarily from emissions from growing vegetations or products of the photochemical reactions of unsaturated hydrocarbons. Carboxylic acids were estimated to account for 32.2% to the free acidity in precipitation. The contribution was higher than in Guiyang rainwater, which indicated contamination by industry in Guiyang was more than in Anshun. The remarkable correlation(p = 0.01) between formic acid and acetic acid suggest that they have similar sources or similar intensity but different sources. And the remarkable correlation (p = 0.01) between and formic acid and oxalic acid showed that the precursors of oxalic acid and formic acid had similar sources. During this period, the overall wet deposition of carboxylic acids were 2.10 mmol/m2. And it appeared mainly in the summer, during which both concentration and contribution to free acidity were also relatively high. Consequently, it was necessary to control emission of organic acids in the summer to reduce frequence of acid rain in Anshun.

  11. Spatiotemporal distribution and source apportionment of low molecular weight organic acids in wet precipitation at a coastal city, China.

    Science.gov (United States)

    Du, Wenjiao; Hong, Zhenyu; Chen, Yanting; Deng, Junjun; Chen, Jinsheng; Xu, Lingling; Hong, Youwei; Xiao, Hang

    2017-03-01

    To investigate the characteristics and sources of low molecular weight (LMW) organic acids in wet precipitation at a coastal city, Xiamen, a total of 313 rainwater samples were collected at seven different functional areas from September 2012 to August 2013. Spatiotemporal characteristics of LMW organic acids as well as pH and electrical conductivity were analyzed. Meanwhile, air mass clusters in different seasons and the positive matrix factorization (PMF) source apportion model were comprehensively used to identify the sources of organic acids. In conclusion, the volume-weighted mean (VWM) concentration of formic (3.20 μmol/L), acetic (1.84 μmol/L), lactic (0.44 μmol/L), and oxalic acid (0.53 μmol/L) were obtained, which jointly contributed to 4.33% of the total free acidity (TFA). At the same time, the highest wet deposition flux of LMW organic acids and contribution of that to TFA were achieved at the forest protection area during growing season in Xiamen. In addition, biogenic emissions (77.12%), sea salts (13.77%), regional agriculture activities (3.92%), soil emissions (2.56%), biomass burning (1.47%), and secondary aerosols (1.15%) were determined as the source of LMW organic acids. Besides, the dominancy of biomass burning via long-range transport in non-growing season (NGS) and the contribution of biogenic emission in growing season (GS) were recognized. Finally, the considerable influence of sea salts on the LMW organic acids (13.77%) in Xiamen was quantified, especially for oxalic acid.

  12. Strategies and outcomes of periprocedural bridging therapy with low-molecular-weight heparin in patients with mechanical heart valves.

    Science.gov (United States)

    Schulman, Jacqueline M; Majeed, Ammar; Mattsson, Eva; Schulman, Sam; Holmström, Margareta; Ågren, Anna

    2015-11-01

    Patients with mechanical heart valves (MHV) undergoing invasive procedures often receive periprocedural bridging with low-molecular-weight heparin (LMWH). The bridging strategies used in real-life and the predictors for bleeding and thrombosis are not well studied. We retrospectively assessed patients with MHV that underwent invasive procedures requiring vitamin K antagonist interruption and LMWH bridging. Thromboembolic and bleeding events occurring up to 30 days after the procedures were recorded. Predictors of major bleeding events (MBEs) were analyzed with logistic regression. We evaluated 547 patients with MHV who underwent 275 procedures during a 6.5-year period. Bridging with LMWH was used in 185 procedures in a total of 117 patients. Combined pre- and post-operative bridging was the most frequently employed (63 %). Doses of LMWH were prophylactic in 96 (52 %) of the procedures and therapeutic in 89 (48 %). The procedure-related bleeding risk was evaluated as high in 70 (38 %) and low in 115 (62 %) of the procedures. There was a trend to more frequent use of prophylactic doses (61 %) in high-risk surgery, and more therapeutic doses (53 %) in low-risk ones. There were 36 bleeding episodes, 21 (11 % of procedures) of which were classified as MBEs, but there were no thromboembolic events. Most MBEs (n = 14; 67 %) occurred in surgeries with high bleeding risk. In the multivariate analysis, the bleeding risk of the surgery itself was the only independent predictor for MBEs. For patients with MHV receiving perioperative bridging with LMWH, the major predictor for MBE is the bleeding risk of the surgery.

  13. Water-soluble low-molecular-weight -(1, 3–1, 6 D-Glucan inhibit cedar pollinosis

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    Tomoko Jippo

    2015-02-01

    Full Text Available Background: The incidence of allergic diseases such as allergic rhinitis, atopic dermatitis, asthma, and food allergies has increased in several countries. Mast cells have critical roles in various biologic processes related to allergic diseases. Mast cells express the high-affinity receptor for immunoglobulin (Ig E on their surface. The interaction of multivalent antigens with surface-bound IgE causes the secretion of granule-stored mediators, as well as the de novosynthesis of cytokines. Those mediators and cytokines proceed the allergic diseases. We investigated the effects of water-soluble, low-molecular-weight -(1, 3–1, 6 D-glucan isolated from Aureobasidium pullulans 1A1 strain black yeast (LMW--glucan on mast cell-mediated anaphylactic reactions. We reported that LMW--glucan dose-dependently inhibited the degranulation of mast cells. Furthermore, we found that orally administered LMW--glucan inhibited the IgE-mediated passive cutaneous anaphylaxis (PCA reaction in mice. Here, we examined if LMW--glucan had effects on Japanese cedar pollinosis. Findings: In a clinical study, a randomized, single-blind, placebo-controlled, parallel group study in 65 subjects (aged 2262 was performed. This study was undertaken 3 weeks before and until the end of the cedar pollen season. During the study, all subjects consumed one bottle of placebo or LMW--glucan daily and all subjects were required to record allergic symptoms in a diary. The LMW--glucan group had a significantly lower prevalence of sneezing, nose-blowing, tears, and hindrance to the activities of daily living than the placebo group. Conclusions: These results suggested that LMW--glucan could be an effective treatment for allergic diseases

  14. Low-molecular-weight heparin for prevention of placenta-mediated pregnancy complications: protocol for a systematic review and individual patient data meta-analysis (AFFIRM).

    Science.gov (United States)

    Rodger, Marc A; Langlois, Nicole J; de Vries, Johanna Ip; Rey, Evelyne; Gris, Jean-Christophe; Martinelli, Ida; Schleussner, Ekkehard; Ramsay, Timothy; Mallick, Ranjeeta; Skidmore, Becky; Middeldorp, Saskia; Bates, Shannon; Petroff, David; Bezemer, Dick; van Hoorn, Marion E; Abheiden, Carolien Nh; Perna, Annalisa; de Jong, Paulien; Kaaja, Risto

    2014-06-26

    Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and the small-for-gestational age newborn. They are leading causes of maternal, fetal, and neonatal morbidity and mortality in developed nations. Women who have experienced these complications are at an elevated risk of recurrence in subsequent pregnancies. However, despite decades of research no effective strategies to prevent recurrence have been identified, until recently. We completed a pooled summary-based meta-analysis that strongly suggests that low-molecular-weight heparin reduces the risk of recurrent placenta-mediated complications. The proposed individual patient data meta-analysis builds on this successful collaboration. The project is called AFFIRM, An individual patient data meta-analysis oF low-molecular-weight heparin For prevention of placenta-medIated pRegnancy coMplications. We conducted a systematic review to identify randomized controlled trials with a low-molecular-weight heparin intervention for the prevention of recurrent placenta-mediated pregnancy complications. Investigators and statisticians representing eight trials met to discuss the outcomes and analysis plan for an individual patient data meta-analysis. An additional trial has since been added for a total of nine eligible trials. The primary analyses from the original trials will be replicated for quality assurance prior to recoding the data from each trial and combining it into a common dataset for analysis. Using the anonymized combined data we will conduct logistic regression and subgroup analyses aimed at identifying which women with previous pregnancy complications benefit most from treatment with low-molecular-weight heparin during pregnancy. The goal of the proposed individual patient data meta-analysis is a thorough estimation of treatment effects in patients with prior individual placenta-mediated pregnancy complications and exploration of which complications are

  15. Combination chemotherapy of doxorubicin, all-trans retinoic acid and low molecular weight heparin based on self-assembled multi-functional polymeric nanoparticles

    Science.gov (United States)

    Zhang, Ting; Xiong, Hui; Zohra Dahmani, Fatima; Sun, Li; Li, Yuanke; Yao, Li; Zhou, Jianping; Yao, Jing

    2015-04-01

    Based on the complementary effects of doxorubicin (DOX), all-trans retinoic acid (ATRA) and low molecular weight heparin (LMWH), the combination therapy of DOX, ATRA and LMWH was expected to exert the enhanced anti-tumor effects and reduce the side effects. In this study, amphiphilic LMWH-ATRA conjugate was synthesized for encapsulating the DOX. In this way, DOX, ATRA and LMWH were assembled into a single nano-system by both chemical and physical modes to obtain a novel anti-tumor targeting drug delivery system that can realize the simultaneous delivery of multiple drugs with different properties to the tumor. LMWH-ATRA nanoparticles exhibited good loading capacities for DOX with excellent physico-chemical properties, good biocompatibility, and good differentiation-inducing activity and antiangiogenic activity. The drug-loading capacity was up to 18.7% with an entrapment efficiency of 78.8%. It was also found that DOX-loaded LMWH-ATRA nanoparticles (DHR nanoparticles) could be efficiently taken up by tumor cells via endocytic pathway, and mainly distributed in cytoplasm at first, then transferred into cell nucleus. Cell viability assays suggested that DHR nanoparticles maintained the cytotoxicity effect of DOX on MCF-7 cells. Moreover, the in vivo imaging analysis indicated that DiR-loaded LMWH-ATRA nanoparticles could target the tumor more effectively as compared to free DiR. Furthermore, DHR nanoparticles possessed much higher anticancer activity and reduced side effects compared to free drugs solution. These results suggested that DHR nanoparticles could be considered as a promising targeted delivery system for combination cancer chemotherapy with lower adverse effects.

  16. A Low-Molecular-Weight Gelator Composed of Pyrene and Fluorene Moieties for Effective Charge Transfer in Supramolecular Ambidextrous Gel.

    Science.gov (United States)

    Reddy, Samala Murali Mohan; Dorishetty, Pramod; Augustine, George; Deshpande, Abhijit P; Ayyadurai, Niraikulam; Shanmugam, Ganesh

    2017-11-28

    Charge-transfer (CT) gel materials obtained from low-molecular-weight (LMW) compounds through a supramolecular self-assembly approach have received fascinating attention by many researchers because of their interesting material property and potential applications. However, most of the CT gel materials constructed were of organogels while the construction of CT gels in the form of a hydrogel is a challenge because of the solubility issue in water, which considerably limits the use of CT hydrogels. Herein, for the first time, we report a new LMW gelator [Nα-(fluorenylmethoxycarbonyl)-Nε-(δ-butyric-1-pyrenyl)-l-lysine, (FmKPy)], composed of two functional moieties such as fluorenylmethoxycarbonyl and pyrene, which not only parade both hydro and organo (ambidextrous) supramolecular gel formation but also exhibit CT ambidextrous gels when mixed with an electron acceptor such as 2,4,7-trinitro-9-fluorenone (TNF). This finding is significant as the established CT organogelator in the literature did not form an organogel in the absence of an electron acceptor or lose their gelation property upon the addition of the acceptor. CT between pyrene and TNF was confirmed by the color change as well as the appearance of the CT band in the visible region of the absorption spectrum. CT between FmKPy and TNF was supported by the solvent dilution method using tetrahydrofuran as the gel breaker and pyrene fluorescence quenching in the case compound containing pyrene and TNF. The morphology of FmKPy ambidextrous gels indicates the fibrous nature while the self-assembled structure is primarily stabilized by π-π stacking among fluorenyl and pyrenyl moieties and hydrogen bonding between amide groups. The FmKPy-TNF CT ambidextrous gel retains the fibrous nature; however, the size of the fibers changed. In FmKPy-TNF CT gels, TNF is intercalated between pyrene moieties in the self-assembled structure as confirmed by fluorescence quenching and powder X-ray diffraction. The Fm

  17. Low molecular weight heparin may benefit nephrotic remission in steroid‑sensitive nephrotic syndrome via inhibiting elastase.

    Science.gov (United States)

    Zhai, Songhui; Hu, Lijuan; Zhong, Lin; Tao, Yuhong; Wang, Zheng

    2017-12-01

    Low molecular weight heparin (LMWH) has a structure similar to heparan sulfate, which exerts anti‑inflammatory effects via inhibiting elastase (Ela) activity. Release of Ela along the glomerular capillary wall may induce glomerular injury and proteinuria. The present study aimed to investigate the influence of LMWH on steroid‑sensitive nephrotic syndrome (SSNS) and the potential underlying mechanism. A total of 40 SSNS patients and 20 healthy controls were recruited. SSNS patients were treated with LMWH and prednisone simultaneously (LMWH+pred group) or with prednisone alone (pred group). Proteinuria, urinary glycosaminoglycans (GAGs), serum Ela and urinary creatinine levels were measured. The nephrotic period of SSNS was 15.93±5.78 days. The nephrotic period of SSNS in LMWH+pred group was significantly reduced compared with the pred group (14.13±4.56 vs. 18.63±6.49 days; PEla levels (77.64±10.99 ng/l) were significantly greater in the nephrotic period of SSNS compared with the remission period (0.107±0.026 g/24 h, 1.53±0.27 mg/mmol Cr and 41.92±7.81 ng/l, respectively) and the healthy control group (0.098±0.027 g/24 h, 1.40±0.26 mg/mmol creatinine and 38.43±9.83 ng/l, respectively; PEla levels in the LMWH+pred group were significantly reduced compared with the pred group (P0.05). Positive correlations were revealed between urinary GAG excretion and proteinuria (r=0.877; PEla levels (r=0.844; PEla levels and urinary GAG excretion (r=0.881; PEla levels may induce proteinuria by degrading GAGs in the glomerular basement membrane in children with SSNS. LMWH may benefit nephrotic remission of SSNS via inhibiting Ela.

  18. Renal Protective Effects of Low Molecular Weight of Inonotus obliquus Polysaccharide (LIOP on HFD/STZ-Induced Nephropathy in Mice

    Directory of Open Access Journals (Sweden)

    Yen-Jung Chou

    2016-09-01

    Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage renal disease in diabetes mellitus. Oxidative stress, insulin resistance and pro-inflammatory cytokines have been shown to play an important role in pathogeneses of renal damage on type 2 diabetes mellitus (DM. Inonotus obliquus (IO is a white rot fungus that belongs to the family Hymenochaetaceae; it has been used as an edible mushroom and exhibits many biological activities including anti-tumor, anti-oxidant, anti-inflammatory and anti-hyperglycemic properties. Especially the water-soluble Inonotus obliquus polysaccharides (IOPs have been previously reported to significantly inhibit LPS-induced inflammatory cytokines in mice and protect from streptozotocin (STZ-induced diabetic rats. In order to identify the nephroprotective effects of low molecular weight of IOP fraction (LIOP, from the fruiting bodies of Inonotus obliquus, high-fat diet (HFD plus STZ-induced type 2-like diabetic nephropathy C57BL/6 mice were investigated in this study. Our data showed that eight weeks of administration of 10–100 kDa, LIOP (300 mg/kg had progressively increased their sensitivity to glucose (less insulin tolerance, reduced triglyceride levels, elevated the HDL/LDL ratio and decreased urinary albumin/creatinine ratio(ACR compared to the control group. By pathological and immunohistochemical examinations, it was indicated that LIOP can restore the integrity of the glomerular capsules and increase the numbers of glomerular mesangial cells, associated with decreased expression of TGF-β on renal cortex in mice. Consistently, three days of LIOP (100 μg/mL incubation also provided protection against STZ + AGEs-induced glucotoxicity in renal tubular cells (LLC-PK1, while the levels of NF-κB and TGF-β expression significantly decreased in a dose-dependent manner. Our findings demonstrate that LIOP treatment could ameliorate glucolipotoxicity-induced renal fibrosis, possibly partly via the inhibition of NF

  19. Effect of Low Molecular Weight Heparins (LMWHs on antiphospholipid Antibodies (aPL-mediated inhibition of endometrial angiogenesis.

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    Silvia D'Ippolito

    Full Text Available Antiphospholipid syndrome (APS is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity in the presence of circulating antiphospholipid antibodies (aPL. Different pathogenic mechanisms for aPL-mediated pregnancy failure have been proposed. In particular a direct effect of aPL on both maternal and fetal side of the placental tissue has been reported, since their reactivity with β2-glycoprotein I (β2GPI makes them adhere to trophoblast and human endometrial endothelial cell (HEEC membranes. β2GPI can be recognized by aPL that, once bound, interfere with both trophoblast functions and with the HEEC differentiation.APS patients can be successfully treated with Low Molecular Weight Heparin (LMWH. Recent reports suggest that LMWH acts through mechanisms alternative to its well known anticoagulant effect, because of its ability to bind β2GPI. In our previous studies, we showed that LMWH is able to reduce the aPL binding to trophoblasts and restore cell invasiveness and differentiation. So far, however, no study has described its effects on endometrial angiogenesis.The aim of our research was to evaluate whether two LMWHs, tinzaparin and enoxaparin, have an effect on the aPL-inhibited endometrial angiogenesis. This prompted us to investigate: (i in vitro HEEC angiogenesis through a Matrigel assay; (ii VEGF secretion by ELISA; (iii matrix metalloproteinase-2 (MMP-2 activity by gelatin zymography; (iv Nuclear Factor-κB (NF-κB DNA binding activity by colorimetric assay; (v STAT-3 activation by a sandwich-ELISA kit. Furthermore, using an in vivo murine model we investigated the LMWHs effects on angiogenesis.We demonstrated that the addition of LMWHs prevents aPL-inhibited HEEC angiogenesis, both in vitro and in vivo, and is able to restore the aPL inhibited NF-κB and/or STAT-3 activity, the VEGF secretion and the MMPs activity.The demonstration of a beneficial role for LMWHs on the aPL-inhibited HEEC angiogenesis

  20. A multi-tolerant low molecular weight mannanase from Bacillus sp. CSB39 and its compatibility as an industrial biocatalyst.

    Science.gov (United States)

    Regmi, Sudip; G C, Pradeep; Choi, Yun Hee; Choi, Yoon Seok; Choi, Ji Eun; Cho, Seung Sik; Yoo, Jin Cheol

    2016-10-01

    Bacillus sp. CSB39, isolated from popular traditional Korean food (Kimchi), produced a low molecular weight, thermostable mannanase (MnCSB39); 571.14U/mL using locust bean gum galactomannan as a major substrate. It was purified to homogeneity using a simple and effective two-step purification strategy, Sepharose CL-6B and DEAE Sepharose Fast Flow, which resulted in 25.47% yield and 19.32-fold purity. The surfactant-, NaCl-, urea-, and protease-tolerant monomeric protein had a mass of ∼30kDa as analyzed by SDS-PAGE and galactomannan zymography. MnCSB39 was found to have optimal activity at pH 7.5 and temperature of 70°C. The enzyme showed ˃55% activity at 5.0-15% (w/v) NaCl, and ˃93% of the initial activity after incubation at 37°C for 60min. Trypsin and proteinase K had no effect on MnCBS39. The enzyme showed ˃80% activity in up to 3M urea. The N-terminal amino acid sequence, ALKGDGX, did not show identity with reported mannanases, which suggests the novelty of our enzyme. Activation energy for galactomannan hydrolysis was 26.85kJmol(-1) with a Kcat of 142.58×10(4)s(-1). MnCSB39 had Km and Vmax values of 0.082mg/mL and 1099±1.0Umg(-1), respectively. Thermodynamic parameters such as ΔH, ΔG, ΔS, Q10, ΔGE-S, and ΔGE-T supported the spontaneous formation of products and the high hydrolytic efficiency and feasibility of the enzymatic reaction, which strengthen its novelty. MnCSB39 activity was affected by metal ions, modulators, chelators, and detergents. Mannobiose was the principal end-product of hydrolysis. Bacillus subtilis CSB39 produced a maximum of 1524.44U mannanase from solid state fermentation of 1g wheat bran. MnCSB39 was simple to purify, was active at a wide pH and temperature range, multi-stress tolerant and catalyzes a thermodynamically possible reaction, characteristics that suggests its suitability for application as an industrial biocatalyst. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Bowel obstruction from intramural hematoma in two children treated with low molecular weight heparin: Case report and review of the literature

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    Richard M. Schroeder

    2014-10-01

    Full Text Available Low molecular weight heparin (LMWH is frequently employed in children to prevent extension of intravascular thrombosis. However, this therapy can result in pathologic bleeding, including spontaneous intramural hematoma of the intestinal wall. In this report, we describe two cases of intestinal obstruction resulting from intramural hematomas during therapeutic LMWH therapy in children. The diagnostic studies and management of spontaneous intramural hematoma in children are discussed.

  2. Low molecular weight poly (2-dimethylamino ethylmethacrylate) polymers with controlled.positioned fluorescent labeling: Synthesis, characterization and in vitro interaction with human endothelial cells

    DEFF Research Database (Denmark)

    Flebus, Luca; Lombart, Francois; Sevrin, Chantal

    2015-01-01

    ) fluorescent labeled PDMAEMA of low molecular weight (Mw) (below 15 kDa), controlling the position and density of fluorescein.The second goal was to analyze the possible difference in uptake and subcellular distribution of this labeled FF polycation between human umbilical vein endothelial cells (HUVEC) and h...... to a minor cytotoxicity compared to the higher ones.As main conclusion this study highlights the similitude in cell trafficking of FF PDMAEMA and data previously reported for PDMAEMA/DNA complexes....

  3. Investigation of colloidal graphite as a matrix for matrix-assisted laser desorption/ionisation mass spectrometry of low molecular weight analytes.

    Science.gov (United States)

    Warren, Alexander D; Conway, Ulric; Arthur, Christopher J; Gates, Paul J

    2016-07-01

    The analysis of low molecular weight compounds by matrix-assisted laser desorption/ionisation mass spectrometry is problematic due to the interference and suppression of analyte ionisation by the matrices typically employed - which are themselves low molecular weight compounds. The application of colloidal graphite is demonstrated here as an easy to use matrix that can promote the ionisation of a wide range of analytes including low molecular weight organic compounds, complex natural products and inorganic complexes. Analyte ionisation with colloidal graphite is compared with traditional organic matrices along with various other sources of graphite (e.g. graphite rods and charcoal pencils). Factors such as ease of application, spectra reproducibility, spot longevity, spot-to-spot reproducibility and spot homogeneity (through single spot imaging) are explored. For some analytes, considerable matrix suppression effects are observed resulting in spectra completely devoid of matrix ions. We also report the observation of radical molecular ions [M(-●) ] in the negative ion mode, particularly with some aromatic analytes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Production of plywood panels from Pinus taeda using veneers of differing densities and phenol-formaldehyde resin with high and low molecular weights

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    Graciela Ines Bolzon de Muniz

    2013-06-01

    Full Text Available This study aimed to evaluate the bonding quality of plywood panels from Pinus taeda using low and high molecular weight phenol-formaldehyde resin and veneers from three different density classes. The experiment consisted of six treatments, each of which produced three panels (replicates. Tests were conducted to evaluate glue line strength to shear stress after two boiling cycles and after 24 hours of cold water immersion. Also determined was the percentage of defects in wood samples. Results indicated that the density classes being assessed differed statistically. However, no significant difference was found between panels produced with high and panels produced with low molecular weight resin as to the mean values of glue line strength, whether subjecting them to two boiling cycles or after 24 hours of cold water immersion. Interactions between different density classes and adhesive formulations were found not significant either. Low molecular weight resin (BPM and panels produced with higher density veneers were found to have better behavior, regarding both bonding strength and percentage of defects. It was concluded that the bonding quality of plywood panels from Pinus taeda was satisfactory after using different densities of veneer and also high and low molecular weight phenolic resins. All treatments were found to comply with minimum requirements established in European standard EN 314-1/1993, which addresses bonding quality of plywood panels.

  5. Utilization of low molecular weight organics by soil microorganisms: combination of 13C-labelling with PLFA analysis

    Science.gov (United States)

    Gunina, Anna; Dippold, Michaela; Kuzyakov, Yakov

    2014-05-01

    Microbial metabolisation is the main transformation pathway of low molecular weight organic substances (LMWOS), but detailed knowledge concerning the fate of LMWOS in soils is strongly limited. Considering that various LMWOS classes enter biochemical cycles at different steps, we hypothesise that the percentage of their LMWOS-Carbon (C) used for microbial biomass (MB) production and consequently medium-term stabilisation in soil is different. We traced the three main groups of LMWOS: amino acids, sugars and carboxylic acids, by uniformly labelled 13C-alanine, -glutamate, -glucose, -ribose, -acetate and -palmitate. Incorporation of 13C from these LMWOS into MB (fumigation-extraction method) and into phospholipid fatty acids (PLFAs) (Bligh-Dyer extraction, purification and GC-C-IRMS measurement) was investigated under field conditions 3 d and 10 d after LMWOS application. The activity of microbial utilization of LMWOS for cell membrane construction was estimated by replacement of PLFA-C with 13C. Decomposition of LMWOS-C comprised 20-65% of the total label, whereas incorporation of 13C into MB amounted to 20-50% of initially applied 13C on day three and was reduced to 5-30% on day 10. Incorporation of 13C-labelled LMWOS into MB followed the trend sugars > carboxylic acids > amino acids. Differences in microbial utilisation between LMWOS were observed mainly at day 10. Thus, instead of initial rapid uptake, further metabolism within microbial cells accounts for the individual fate of C from different LMWOS in soils. Incorporation of 13C from each LMWOS into each PLFA occurred, which reflects the ubiquitous ability of all functional microbial groups for LMWOS utilization. The preferential incorporation of palmitate can be attributed to its role as a direct precursor for many fatty acids (FAs) and PLFA formation. Higher incorporation of alanine and glucose compared to glutamate, ribose and acetate reflect the preferential use of glycolysis-derived substances in the FAs

  6. [Effects of low molecular weight heparin on the inflammatory response and vascular injury in rat after electric burn].

    Science.gov (United States)

    Jiang, Nanhong; Xie, Weiguo; Wang, Hui; Jin, Dongmei; Tan, Hong; Zhao, Chaoli

    2014-04-01

    To observe the effects of low molecular weight heparin (LMWH) on the inflammatory response and vascular injury in rat after electric burn. A homemade regulator and transformer apparatus was used to reproduce the model of electric burn (0.5 cm×0.5 cm in size) with depth from full-thickness to full-thickness skin plus muscle and bone on the middle of the inside of right hind limb in 60 Wistar rats. The open wounds were covered with 20 g/L sulfadiazine silver paste immediately after injury. The wound condition was observed every day. The injured rats were divided into group LMWH and control group (C) according to the random number table, with 30 rats in each group. Rats in group LMWH were given subcutaneous injection of LMWH (1 U/g) in abdominal wall, 2 times a day. No other treatment was given in rats in group C. On post burn day (PBD) 3, 5, and 10, 10 rats respectively of two groups were sacrificed. The damaged tissue of wound and that around the wound (1.0 cm×0.5 cm in size) were excised, and heart blood was obtained. The pathological changes and thrombosis in damaged tissue were observed with HE, Masson, and aldehyde fuchsin staining, and the thrombosis rate was calculated. Serum contents of TNF-α and endothelin-1 were determined with ELISA. The mRNA expression of TNF-α in damaged tissue was detected with RT-PCR. Data were processed with Levene homogeneity test, analysis of variance of factorial design, LSD- t test, SNK- q test, and Friedman M nonparametric test. (1) The injured limb of rats was obviously swollen after electric burn, which reached deeply to the muscle and bone. Compared with those of group C, the swelling of rats subsided slightly faster and the inflammatory response was lighter in group LMWH at each time point. (2) The necrosis of damaged tissue and profuse infiltration of inflammatory cells were observed. Dilatation of blood vessels, congestion and thrombosis, and swelling, necrosis, and desquamation of vascular endothelial cells were

  7. A Novel Co-polymer Based on Hydroxypropyl α-Cyclodextrin Conjugated to Low Molecular Weight Polyethylenimine as an in Vitro Gene Delivery Vector

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    Hai Yu

    2008-11-01

    Full Text Available A novel co-polymer based on 2-hydroxypropyl-α-cyclodextrin cross-linked by low molecular weight polyethylenimine was synthesized as a gene delivery vector. The copolymer could bind and condense DNA tightly. It showed lower cytotoxicity than PEI 25kDa in SK-BR-3 cells. Transfection efficiency was increased over 5.5-fold higher than PEI 25 kDa in SK-BR-3 cells in complete serum medium. It is a potential candidate vector for gene therapy.

  8. A new chronometric assay to determine plasma antifactor Xa activity which is insensitive to the antithrombin activity of low molecular weight heparins.

    Science.gov (United States)

    Dignac, M; Gabaig, A M; Cambus, J P; Boneu, B

    1994-01-01

    Some commercially available chronometric assays are influenced by the residual antithrombin activity of low molecular weight heparins (LMWH) and they underestimate the ex vivo anti Xa activity. We have evaluated a new kit (Staclot-Heparin) highly specific for the anti Xa activity of LMWH. A comparison with the results given by a reference chromogenic method (Stachrom-Heparin) indicates a very good correlation between the 2 assays (r = 0.95, n = 59). This new assay is not influenced by vitamin K antagonist treatments. Clinical biologists now have the possibility of determining the anti Xa activity generated by LMWH easily and accurately, using a chronometric assay.

  9. Quantification of low molecular weight selenium metabolites in human plasma after treatment with selenite in pharmacological doses by LC-ICP-MS

    DEFF Research Database (Denmark)

    Flouda, Konstantina; Dersch, Julie Maria; Gabel-Jensen, Charlotte

    2016-01-01

    ultrafiltrated using a cut-off value of 3000 Da. The method was validated in aqueous solution as well as plasma using standards of selenomethionine (SeMet), Se-methylselenocysteine (MeSeCys), selenite, and the selenosugar Se-methylseleno-N-acetylgalactosamine (SeGal) for linearity, precision, recoveries......The paper presents an analytical method for quantification of low molecular weight (LMW) selenium compounds in human plasma based on liquid chromatography inductively coupled plasma mass spectrometry (LC-ICP-MS) and post column isotope dilution-based quantification. Prior to analysis, samples were...

  10. In vitro and in vivo siRNA delivery to hepatocyte utilizing ternary complexation of lactosylated dendrimer/cyclodextrin conjugates, siRNA and low-molecular-weight sacran.

    Science.gov (United States)

    Hayashi, Yuya; Higashi, Taishi; Motoyama, Keiichi; Jono, Hirofumi; Ando, Yukio; Arima, Hidetoshi

    2018-02-01

    In this study, we newly developed the ternary complexes consisting of lactosylated dendrimer (generation 3)/α-cyclodextrin conjugate (Lac-α-CDE), siRNA and the anionic polysaccharide sacrans, and evaluated their utility as siRNA transfer carriers. Three kinds of the low-molecular-weight sacrans, i.e. sacran (100) (Mw 44,889Da), sacran (1000) (Mw 943,692Da) and sacran (10,000) (Mw 1,488,281Da) were used. Lac-α-CDE/siRNA/sacran ternary complexes were prepared by adding the low-molecular-weight sacrans to the Lac-α-CDE/siRNA binary complex solution. Cellular uptake of the ternary complex with sacran (100) was higher than that of the binary complex or the other ternary complexes with sacran (1000) and sacran (10,000) in HepG2 cells. Additionally, the ternary complex possessed high serum resistance and endosomal escaping ability in HepG2 cells. High liver levels of siRNA and Lac-α-CDE were observed after the intravenous administration of the ternary complex rather than that of the binary complex. Moreover, intravenous administration of the ternary complex (siRNA 5mg/kg) induced the significant RNAi effect in the liver of mice with negligible change of blood chemistry values. Therefore, a ternary complexation of the Lac-α-CDE/siRNA binary complex with sacran is useful as a hepatocyte-specific siRNA delivery system. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Isolation, purification, and immunological activities of a low-molecular-weight polysaccharide from the Lingzhi or Reishi medicinal mushroom Ganoderma lucidum (higher Basidiomycetes).

    Science.gov (United States)

    Zhu, Lina; Luo, Xi; Tang, Qingjiu; Liu, Yanfang; Zhou, Shuai; Yang, Yan; Zhang, Jingsong

    2013-01-01

    To obtain a low-molecular-weight polysaccharide with immuno-enhancing activity, hot water extract of Ganoderma lucidum fruit bodies was separated by membrane ultrafiltration, anion exchange, and gel filtration chromatography, and the immunological activities of fractions were assessed on the basis of nitric oxide production by RAW 264.7 macrophages. A novel polysaccharide (TB3-2-2) was successfully isolated and purified. TB3-2-2 is a homogeneous polysaccharide, with a relative molecular weight of 5.11 × 103 Da, identified by high-performance liquid chromatography and was composed of galactose and glucose in a molar ratio of 2:3 determined by high-performance anion exchange chromatography. TB3-2-2 had a carbohydrate content of 99%, as measured using the phenol-sulfuric acid method. Proliferation of mouse spleen lymphocytes and the expression level of interleukin-6 was significantly increased by TB3-2-2. Results indicate that the low-molecular-weight polysaccharide with immunological activity in G. lucidum is worthy of further research and development.

  12. Heparina de baixo peso molecular no tratamento da tromboembolia pulmonar Low-molecular-weight heparin in the treatment of pulmonary embolism

    Directory of Open Access Journals (Sweden)

    RENATO MACIEL

    2002-06-01

    Full Text Available Este artigo de revisão analisa as propriedades farmacocinéticas das heparinas de baixo peso molecular, compara os resultados do seu uso com heparina não fracionada no tratamento da tromboembolia pulmonar, mostrando que são uma alternativa segura e efetiva. Sugere que as heparinas de baixo peso molecular administradas por via subcutânea uma ou duas vezes ao dia e sem necessidade de monitorização laboratorial freqüente permitem o manejo ambulatorial ou com internação hospitalar breve de alguns casos de tromboembolia pulmonar, resultando em redução de custos e maior satisfação do paciente.This article reviews the pharmacokinetic properties of low-molecular weight heparins, compares the results of their use to that of unfractioned heparin in a pulmonary embolism treatment, showing they are a safe an effective alternative. The authors suggest that low-molecular-weight heparins administered subcutaneously once or twice-daily and without frequent laboratory monitoring have permitted out-of-hospital or short hospitalization management in some cases of pulmonary embolism, resulting in cost savings and increased patient satisfaction.

  13. The methionine-rich low-molecular-weight chloroplast heat-shock protein: evolutionary conservation and accumulation in relation to thermotolerance.

    Science.gov (United States)

    Downs, C; Heckathorn, S; Bryan, J; Coleman, J

    1998-02-01

    The evolutionary conservation of the low-molecular-weight chloroplast-localized heat-shock protein (LMW chlpHsp) in vascular plants was examined using immunological methods. An antibody (Abmet) specific to the LMW chlpHsp was produced using a synthetic 28-residue peptide containing the most conserved elements of its unique "methionine-rich domain" as an antigen. This antibody detected a heat-inducible low-molecular-weight chloroplast protein in plants of six divergent Anthophyta species, including C3, C4, CAM, monocot, and dicot species. Abmet also detected a LMW chlpHsp in species from the Divisions Psilotophyta, Equisetophyta, Polypodiophyta, and Ginkgophyta. A preliminary examination of the relationship between accumulation of the LMW chlpHsp and habitat was also conducted. Seven Anthophyta species originating from both warm- and cool-temperature habitats were grown at 28C and then heat stressed at 40C. A positive qualitative relationship between the accumulation of the LMW chlpHsp and organismal thermotolerance in these species was observed; similar results were obtained separately with four nonAnthophyta species. The strong evolutionary conservation of this LMW Hsp and its localization to the chloroplast, and the correlation between production of this protein and plant thermotolerance, suggest that the LMW chlpHsp plays an important role in adaptation to heat stress.

  14. In maize, glutelin-2 and low molecular weight zeins are synthesized by membrane-bound polyribosomes and translocated into microsomal membranes.

    Science.gov (United States)

    Torrent, M; Poca, E; Campos, N; Ludevid, M D; Palau, J

    1986-09-01

    Experiments to establish the site of biosynthesis and the possible translocation into microsomes of glutelins-2 (28 kD G2) and low molecular weight zeins (10, 14, 15 kD Z2) have been carried out. Free and membrane-bound polyribosomes as well as microsomal membranes were isolated from immature endosperms of W64A Zea mays L. In vitro translation studies were carried out in the presence and in the absence of membranes using [(35)S]-methionine or [(35)S]-cysteine as precursors. Cell-free translation products were characterized by electrophoretic mobility, solubility and antigenic properties. The results obtained indicate that 28 kD G2 and low molecular weight zeins are primarily synthesized on membrane-bound polysomes. From experiments using proteinase K as a probe, we also conclude that these proteins are translocated into microsomes where they accumulate. The translocated and pre-28 kD G2 proteins do not present changes in the apparent molecular weight. However we show that there are differences in their isoelectric points, a fact that indicates the existence of 28 kD G2 processing.

  15. Analysis of iminosugars and other low molecular weight carbohydrates in Aglaonema sp. extracts by hydrophilic interaction liquid chromatography coupled to mass spectrometry.

    Science.gov (United States)

    Rodríguez-Sánchez, S; García-Sarrió, M J; Quintanilla-López, J E; Soria, A C; Sanz, M L

    2015-12-04

    A method by hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry (HILIC-MS(2)) has been successfully developed for the simultaneous analysis of bioactive iminosugars and other low molecular weight carbohydrates in Aglaonema leaf extracts. Among other experimental chromatographic conditions, mobile phase eluents, additives and column temperature were evaluated in terms of retention time, resolution, peak width and symmetry provided for target carbohydrates. In general, narrow peaks (wh: 0.2-0.6min) with good symmetry (As: 0.9-1.3) and excellent resolution (Rs>1.8) were obtained for iminosugars using an acetonitrile:water gradient with 5mM ammonium acetate in both eluents at 55°C. Tandem mass spectra were used to confirm the presence of previously detected iminosugars in Aglaonema extracts and to tentatively identify for the first time others such as miglitol isomer, glycosyl-miglitol isomers and glycosyl-DMDP isomers. Concentration of total iminosugars varied from 1.35 to 2.84mgg(-1) in the extracts of the different Aglaonema samples analyzed. To the best of our knowledge, this is the first time that a HILIC-MS(2) method has been proposed for the simultaneous analysis of iminosugars and other low molecular weight carbohydrates of Aglaonema sp. extracts. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Cryopreservation of spinach chloroplast membranes by low-molecular-weight carbohydrates. I. Evidence for cryoprotection by a noncolligative-type mechanism.

    Science.gov (United States)

    Santarius, K A; Bauer, J

    1983-02-01

    In freezing experiments with isolated spinach thylakoids (Spinacia oleracea L. cv. Monatol) the cryoprotective efficiency of various low-molecular-weight polyols was determined. The activity of cyclic photophosphorylation was used as an assay for the functional integrity of the membranes. The results were compared with the osmotic behavior of the cryoprotectants at high concentrations. Equimolal concentrations of polyols which exhibit nearly comparable freezing point depressions even at high concentrations differed considerably in their protective capacity during a freeze-thaw cycle. This was particularly distinct when glucose, galactose, and ethylene glycol monomethyl ether were compared, but was also evident when various pentoses and deoxy-hexoses were used as cryoprotectants. Even in the absence of freezing, carbohydrates exerted a stabilizing influence on biomembranes. From the data it is suggested that in addition to colligative action of the compounds, a specific noncolligative mechanism contributes to membrane protection during freezing.

  17. Effects of low-molecular-weight organic acids on the acute lethality, accumulation, and enzyme activity of cadmium in Eisenia fetida in a simulated soil solution.

    Science.gov (United States)

    Liu, Hai-Long; Wang, Yu-Jun; Xuan, Liang; Dang, Fei; Zhou, Dong-Mei

    2017-04-01

    In the present study, the effects of low-molecular-weight organic acids (LMWOAs) on the toxicity of cadmium (Cd) to Eisenia fetida were investigated in a simulated soil solution. The LMWOAs protected E. fetida from Cd toxicity, as indicated by the increased median lethal concentration (LC50) values and the increased activity of superoxide dismutase. In addition, Cd concentrations in E. fetida decreased dramatically in the presence of LMWOAs. These results were likely because of the complexation between Cd and LMWOAs, which decreased the bioavailability and consequential toxicity of Cd to E. fetida. Notably, LMWOAs reduced Cd toxicity in decreasing order (ethylenediamine tetraacetic acid [EDTA] > citric acid > oxalic acid > malic acid > acetic acid), which was consistent with the decreasing complexation constants between LMWOAs and Cd. These results advance our understanding of the interactions between Cd and LMWOAs in soil. Environ Toxicol Chem 2017;36:1005-1011. © 2016 SETAC. © 2016 SETAC.

  18. Cancer-specific gene silencing through therapeutic siRNA delivery with B vitamin-based nanoassembled low-molecular-weight hydrogelators.

    Science.gov (United States)

    Patil, Sachin Prakash; Kim, Seong-Hoon; Jadhav, Jyoti Ramesh; Lee, Ju-Hyun; Jeon, Eun Mi; Kim, Kyong-Tai; Kim, Byeang Hyean

    2014-08-20

    This paper describes the synthesis, characterization, and in vitro and in vivo siRNA transfection ability of B vitamin-based cationic clickable bolaamphiphiles (VBs). Our VBs derived from vitamins B₂, B₃, B₅, B₆, and B₇ formed nanoassembled low-molecular-weight hydrogelators (LMWGs, vitagels). The vitagels VB2, VB6, and VB7 (derived from vitamins B₂, B₆, and B₇, respectively) facilitated delivery of small interfering RNAs (siRNA), efficiently silencing gene expression specifically into cancer cell lines; in addition, the LMWGs derived from vitamins B₃, B₅, and B₆ were biocompatible. An ex vivo study in a mouse model revealed that the siRNA delivered by the vitagel VB7 was located primarily at the site of the tumor. The gene silencing efficiency of vascular endothelial growth factor siRNA delivered by vitagels was dependent on the nature of the vitamin headgroup, the N/P ratio, and, interestingly, the hydrogelation properties of the VBs.

  19. Authentication of animal origin of heparin and low molecular weight heparin including ovine, porcine and bovine species using 1D NMR spectroscopy and chemometric tools.

    Science.gov (United States)

    Monakhova, Yulia B; Diehl, Bernd W K; Fareed, Jawed

    2017-10-27

    High resolution (600MHz) nuclear magnetic resonance (NMR) spectroscopy is used to distinguish heparin and low-molecular weight heparins (LMWHs) produced from porcine, bovine and ovine mucosal tissues as well as their blends. For multivariate analysis several statistical methods such as principal component analysis (PCA), factor discriminant analysis (FDA), partial least squares - discriminant analysis (PLS-DA), linear discriminant analysis (LDA) were utilized for the modeling of NMR data of more than 100 authentic samples. Heparin and LMWH samples from the independent test set (n=15) were 100% correctly classified according to its animal origin. Moreover, by using 1H NMR coupled with chemometrics and several batches of bovine heparins from two producers were differentiated. Thus, NMR spectroscopy combined with chemometrics is an efficient tool for simultaneous identification of animal origin and process based manufacturing difference in heparin products. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Rates of clinically apparent heparin-induced thrombocytopenia for unfractionated heparin vs. low molecular weight heparin in non-surgical patients are low and similar

    Directory of Open Access Journals (Sweden)

    Gerber Jonathan

    2005-04-01

    Full Text Available Abstract With the growing use of low-molecular-weight heparins (LMWH for the treatment and prevention of venous thromboembolism (VTE, it is important to provide an evidence-based comparison with unfractionated heparin (UFH concerning rates of heparin-induced thrombocytopenia (HIT. Such comparisons are essential in clinical decision-making and cost-modeling. In this paper we review data regarding non-surgical (medical patients. We conclude that the lack of uniform evaluation and standardized testing for HIT in the current literature precludes making a reliable estimate of the relative risk of HIT in UFH vs. LMWH in either the treatment or prevention of VTE in non-surgical patients. However, current data suggest that the risk of thrombocytopenia and HIT is low and similar for non-surgical patients who receive either LMWH or UFH.

  1. Low-molecular-weight carbohydrate Pentaisomaltose may replace dimethyl sulfoxide as a safer cryoprotectant for cryopreservation of peripheral blood stem cells

    DEFF Research Database (Denmark)

    Svalgaard, Jesper Dyrendom; Haastrup, Eva Kannik; Reckzeh, Kristian

    2016-01-01

    BACKGROUND: Cryopreserved hematopoietic stem cell products are widely used for certain hematologic malignancies. Dimethyl sulfoxide (DMSO) is the most widely used cryoprotective agent (CPA) today, but due to indications of cellular toxicity, changes of the cellular epigenetic state, and patient......-related side effects, there is an increasing demand for DMSO-free alternatives. We therefore investigated whether Pentaisomaltose (PIM), a low-molecular-weight carbohydrate (1 kDa), can be used for cryopreservation of peripheral blood stem cells, more specifically hematopoietic progenitor cell apheresis (HPC......(A)) product. STUDY DESIGN AND METHODS: We cryopreserved patient or donor HPC(A) products using 10% DMSO or 16% PIM and quantified the recovery of CD34+ cells and CD34+ subpopulations by multicolor flow cytometry. In addition, we compared the frequency of HPCs after DMSO and PIM cryopreservation using...

  2. Analysis of low molecular weight acids by negative mode matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

    Science.gov (United States)

    Shroff, Rohit; Muck, Alexander; Svatos, Ales

    2007-01-01

    Free 9-aminoacridine base is demonstrated to be a suitable matrix for negative mode matrix-assisted laser desorption/ionization time-of-flight mass spectrometric (MALDI-TOFMS) analysis of a wide range of low molecular weight organic acids including aliphatic (from acetic to palmitic acid), aromatic acids, phytohormones (e.g. jasmonic and salicylic acids), and amino acids. Low limits of quantitation in the femtomolar range (jasmonic - 250 fmol; caffeic - 160 fmol and salicylic - 12.5 fmol) and linear detector response over two concentration orders in the pico- and femtomolar range are extremely encouraging for the direct study of such acids in complex biological matrices. Copyright (c) 2007 John Wiley & Sons, Ltd.

  3. Effects of low-molecular-weight organic ligands and phosphate on DNA adsorption by soil colloids and minerals.

    Science.gov (United States)

    Cai, Peng; Huang, Qiaoyun; Zhu, Jun; Jiang, Daihua; Zhou, Xueyong; Rong, Xingmin; Liang, Wei

    2007-01-15

    Adsorption of DNA on montmorillonite, kaolinite, goethite and soil clays from an Alfisol in the presence of citrate, tartrate and phosphate was studied. A marked decrease in DNA adsorption was observed on montmorillonite and kaolinite with increasing anion concentrations from 0 to 5 mM. However, the amount of DNA adsorbed by montmorillonite and kaolinite was enhanced when ligand concentration was higher than 5 mM. In the system of soil colloids and goethite, with the increase of anion concentrations, a steady decrease was found and the ability of ligands in depressing DNA adsorption followed the sequence: phosphate > citrate > tartrate. Compared to H2O2-treated clays (inorganic clays), a sharp decrease in DNA adsorption was observed on goethite and organo-mineral complexes (organic clays) with increasing ligand concentrations. The results suggest that the influence of anions on DNA adsorption varies with the type and concentration of anion as well as the surface properties of soil components. Introduction of DNA into the system before the addition of ligands had the greatest amount of DNA adsorption on soil colloids and goethite. Organic and inorganic ligands promoted DNA adsorption on montmorillonite and kaolinite when ligands were introduced into the system before the addition of DNA. The results obtained in this study have important implications for the understanding of the persistence and fate of DNA in soil environments especially rhizosphere soil where various organic and inorganic ligands are active.

  4. Toward personalized hemodialysis by low molecular weight amino-containing compounds: future perspective of patient metabolic fingerprint.

    Science.gov (United States)

    Sirolli, Vittorio; Rossi, Claudia; Di Castelnuovo, Augusto; Felaco, Paolo; Amoroso, Luigi; Zucchelli, Mirco; Ciavardelli, Domenico; Di Ilio, Carmine; Sacchetta, Paolo; Bernardini, Sergio; Arduini, Arduino; Bonomini, Mario; Urbani, Andrea

    2012-05-01

    L-carnitine deficiency is commonly observed in chronic hemodialysis patients, and this depletion may cause clinical symptoms like muscle weakness, anaemia, and hypotension. We pursued a targeted metabonomics investigation in 28 hemodialysis patients (13 non diabetics and 15 diabetics) and in 10 age-matched healthy controls, on plasma levels of all carnitine esters and of several amino acids. Samples were taken before and after the first hemodialysis treatment of the week. Multiplexed data were collected in LCMRM (Multiple Reaction Monitoring) and analysed by unsupervised multivariate analysis. In diabetic uremic patients, we observed lower values of propionylcarnitine than in other groups, while acylcarnitine concentration was higher in uremics compared to controls. The hemodialysis session induced a decline in free, short-chain, medium-chain and dicarboxylic acylcarnitines, whereas the long chain acylcarnitines remained unaffected. Plasma levels of amino acid proline, ornithine, citrulline and serine were significantly elevated in uremic patients before dialysis compared to controls. For most tested plasma amino acids, a significant reduction after hemodialysis session was found. Our study is the first that investigated on possible modifications of the system of carnitine in diabetic patients in hemodialysis not only in relation to the condition of deficiency but also compared to lipid and glucose homeostasis alteration typical of diabetics. We proposed the application of targeted metabolic fingerprint in the management of the hemodialysis patients.

  5. Low Molecular Weight pDMAEMA-block-pHEMA Block-Copolymers Synthesized via RAFT-Polymerization: Potential Non-Viral Gene Delivery Agents?

    Directory of Open Access Journals (Sweden)

    Thomas Kissel

    2011-03-01

    Full Text Available The aim of this study was to investigate non-viral pDNA carriers based on diblock-copolymers consisting of poly(2-(dimethyl aminoethyl methacrylate (pDMAEMA and poly(2-hydroxyethyl methacrylate (pHEMA. Specifically the block-lengths and molecular weights were varied to determine the minimal requirements for transfection. Such vectors should allow better transfection at acceptable toxicity levels and the entire diblock-copolymer should be suitable for renal clearance. For this purpose, a library of linear poly(2-(dimethyl aminoethyl methacrylate-block-poly(2-hydroxyl methacrylate (pDMAEMA-block-pHEMA copolymers was synthesized via RAFT (reversible addition-fragmentation chain transfer polymerization in a molecular weight (Mw range of 17–35.7 kDa and analyzed using 1H and 13C NMR (nuclear magnetic resonance, ATR (attenuated total reflectance, GPC (gel permeation chromatography and DSC (differential scanning calorimetry. Copolymers possessing short pDMAEMA-polycation chains were 1.4–9.7 times less toxic in vitro than polyethylenimine (PEI 25 kDa, and complexed DNA into polyplexes of 100–170 nm, favorable for cellular uptake. The DNA-binding affinity and polyplex stability against competing polyanions was comparable with PEI 25 kDa. The zeta-potential of polyplexes of pDMAEMA-grafted copolymers remained positive (+15–30 mV. In comparison with earlier reported low molecular weight homo pDMAEMA vectors, these diblock-copolymers showed enhanced transfection efficacy under in vitro conditions due to their lower cytotoxicity, efficient cellular uptake and DNA packaging. The homo pDMAEMA115 (18.3 kDa self-assembled with DNA into small positively charged polyplexes, but was not able to transfect cells. The grafting of 6 and 57 repeating units of pHEMA (0.8 and 7.4 kDa to pDMAEMA115 increased the transfection efficacy significantly, implying a crucial impact of pHEMA on vector-cell interactions. The intracellular trafficking, in vivo transfection

  6. Comparison of adverse-event profiles of intravenous low-molecular-weight iron dextran and iron sucrose in peritoneal dialysis patients.

    Science.gov (United States)

    Solak, Yalcin; Atalay, Huseyin; Guney, Ibrahim; Turkmen, Kultigin; Kaya, Emine; Turk, Suleyman

    2011-01-01

    Both erythropoiesis-stimulating agents and iron treatments are underutilized in peritoneal dialysis (PD) patients. Studies to evaluate safety profiles of various intravenous iron preparations are limited in PD patients compared to hemodialysis. No study in the literature compared safety of low-molecular-weight iron dextran (LMW-ID) with that of iron sucrose in PD patients. We aimed to compare adverse-effect profiles of LMW-ID and iron sucrose with varying dosing schedules in PD patients with a hope to foster use of parenteral iron solutions in PD patients. We retrospectively reviewed patient charts and included patients who were administered iron sucrose or LMW-ID parenterally. Sociodemographic characteristics, clinical features, and pertinent laboratory data were collected. Adverse events which were deemed to be related to infusion of parenteral iron were recorded. We double-checked both physician records and nursing documents for observed adverse events. A total of 167 chronic PD patients were included in the study, and 92 patients were administered LMW-ID, whereas 75 patients were administered iron sucrose. Only one adverse event occurred in a patient who was administered 500 mg iron sucrose in a single infusion. This study showed the comparable safety of LMW-ID in varying doses over that of iron sucrose in PD patients.

  7. Matrix-free and material-enhanced laser desorption/ionization mass spectrometry for the analysis of low molecular weight compounds.

    Science.gov (United States)

    Rainer, Matthias; Qureshi, Muhammad Nasimullah; Bonn, Günther Karl

    2011-06-01

    The application of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) for the analysis of low molecular weight (LMW) compounds, such as pharmacologically active constituents or metabolites, is usually hampered by employing conventional MALDI matrices owing to interferences caused by matrix molecules below 700 Da. As a consequence, interpretation of mass spectra remains challenging, although matrix suppression can be achieved under certain conditions. Unlike the conventional MALDI methods which usually suffer from background signals, matrix-free techniques have become more and more popular for the analysis of LMW compounds. In this review we describe recently introduced materials for laser desorption/ionization (LDI) as alternatives to conventionally applied MALDI matrices. In particular, we want to highlight a new method for LDI which is referred to as matrix-free material-enhanced LDI (MELDI). In matrix-free MELDI it could be clearly shown, that besides chemical functionalities, the material's morphology plays a crucial role regarding energy-transfer capabilities. Therefore, it is of great interest to also investigate parameters such as particle size and porosity to study their impact on the LDI process. Especially nanomaterials such as diamond-like carbon, C(60) fullerenes and nanoparticulate silica beads were found to be excellent energy-absorbing materials in matrix-free MELDI.

  8. Correlation between activated partial thromboplastin time and anti-Xa activity in patients who received low-molecular weight heparin as anticoagulation for haemodialysis.

    Science.gov (United States)

    Wong, Steve Siu-Man; Lau, Wai-Yan; Chan, Ping-Kwan; Wan, Ching-Kit; Cheng, Yuk-Lun

    2017-11-01

    Plasma anti-Xa activity, the recommended test to monitor low-molecular weight heparin (LMWH) therapy, is not readily available in many laboratories. In our clinical trials on the use of LMWH as anticoagulation for haemodialysis, a consistent prolongation of APTT in addition to the elevated anti-Xa activity was observed in the patients after LMWH administration. Hence, the paired anti-Xa activity and APTT data were re-analyzed. The APTT ratio, which was the proportional change in APTT from the baseline value after LMWH administration, was found to have a strong correlation with anti-Xa activity (coefficient of determination, R 2  = 0.72, P sensitivity was 88% and the specificity was 83.3% when an APTT ratio ≧1.4 was used as the cut point to predict the achievement of therapeutic anti-Xa activity. Our results illustrated that APTT is a potentially useful screening test to assess the degree of anticoagulation achieved by LMWH during haemodialysis, if the testing for plasma anti-Xa activity is not available. © 2017 Asian Pacific Society of Nephrology.

  9. FERMENTATION BY Lactobacillus paracasei OF GALACTOOLIGOSACCHARIDES AND LOW-MOLECULAR-WEIGHT CARBOHYDRATES EXTRACTED FROM SQUASH (Curcubita maxima AND LUPIN (Lupinus albus SEEDS

    Directory of Open Access Journals (Sweden)

    María I. Palacio

    2014-02-01

    Full Text Available The in vitro prebiotic activity of galactooligosaccharides (GOS and low-molecular-weight carbohydrates (LMWC extracted from lupin and squash seeds on the growth of Lactobacillus paracasei BGP1 was studied. To this end, the change in cell density after 24 h of L. paracasei growth on 1% (w/v glucose, 1% (w/v raffinose, 1% (w/v commercial inulin GR, 1% (w/v lupin extract, and 1% (w/v squash extract relative to the change in cell density of a mixture of enteric strains under the same culture conditions were evaluated. Additionally, the principal components of GOS and LMWC in the extracts were identified using Thin Layer Chromatography. The highest prebiotic activity score was for L. paracasei grown on squash extract (0.55±0.03, followed by lupin extract (0.49±0.02, inulin (0.38±0.05 and raffinose (0.37±0.05. These results will contribute to selecting plant species as potential sources of prebiotic ingredients for the development of functional foods.

  10. Thermal properties of the gel made by low molecular weight gelator 1,2-O-(1-ethylpropylidene)-alpha-D-glucofuranose with toluene and molecular dynamics of solvent.

    Science.gov (United States)

    Tritt-Goc, Jadwiga; Bielejewski, Michał; Luboradzki, Roman; Lapiński, Andrzej

    2008-01-15

    The studies of the gel-to-sol phase transition by the Raman, FT-IR, and 1H NMR methods of the gel made by low molecular weight organogelator 1,2-O-(1-ethylpropylidene)-alpha-D-glucofuranose with toluene as the solvent are reported. The FT-IR spectra revealed the existence of a hydrogen bond network formed by gelator molecules in the crystalline and gel phase. In both phases, the network formation is dominated by the gelator self-interaction. Upon gelation, only one stretching band of infrared absorption modes nualpha, assigned to the O(6)H hydroxyl protons of gelator, is shifted by Deltaupsilonalpha = 25 cm-1, which indicates the involvement of this proton in the interaction with the solvent molecules. The phase transition measurements performed as a function of gelator concentration allowed the calculation of the energy correlated with the transition from gel to solution phase. The obtained value of 72 kJ/mol is the largest one reported up until now for monosaccharide-based gels. The analysis of the temperature measurements of the toluene 1H NMR spectra provides evidence for a different chemical environment of toluene molecules in the gel. The toluene spin-lattice relaxation in bulk and gel indicate that the viscosity is most likely the main factor that influences the dynamics of toluene.

  11. Effects of low-molecular-weight-chitosan on the adenine-induced chronic renal failure rats in vitro and in vivo

    Science.gov (United States)

    Zhi, Xuan; Han, Baoqin; Sui, Xianxian; Hu, Rui; Liu, Wanshun

    2015-02-01

    The effects of low-molecular-weight-chitosan (LMWC) on chronic renal failure (CRF) rats induced by adenine were investigated in vivo and in vitro. Chitosan were hydrolyzed using chitosanase at pH 6-7 and 37° for 24 h to obtain LMWC. In vitro, the effect of LMWC on the proliferation of renal tubular epithelial cells (RTEC) showed that it had no cytotoxic effect and could promote cell growth. For the in vivo experiment, chronic renal failure rats induced by adenine were randomly divided into control group, Niaoduqing group, and high-, medium- and low-dose LMWC groups. For each group, we detected serum creatinine (SCR), blood urea nitrogen (BUN), and total superoxide dismutase (T-SOD), glutathione oxidase (GSH-Px) activities of renal tissue, and obtained the ratio of kidney weight/body weight, pathological changes of kidney. The levels of serum SCR, BUN were higher in the adenine-induced rats than those in the control group, indicating that the rat chronic renal failure model worked successfully. The results after treatment showed that LMWC could reduce the SCR and BUN levels and enhance the activities/levels of T-SOD and GSH-PX in kidney compared to control group. Histopathological examination revealed that adenine-induced renal alterations were restored by LMWC at three tested dosages, especially at the low dosage of 100 mg kg-1 d-1.

  12. Single-Handed Helical Polybissilsesquioxane Nanotubes and Mesoporous Nanofibers Prepared by an External Templating Approach Using Low-Molecular-Weight Gelators

    Directory of Open Access Journals (Sweden)

    Jing Hu

    2017-01-01

    Full Text Available Chiral low-molecular-weight gelators (LMWGs derived from amino acids can self-assemble into helical fibers and twisted/coiled nanoribbons by H-bonding and π–π interaction. Silica nanotubes with single-handed helices have been prepared using chiral LMWGs through sol–gel transcription. Molecular-scale chirality exists at the inner surfaces. Here, we discuss single-handed helical aromatic ring-bridged polybissilsesquioxane nanotubes and mesoporous nanofibers prepared using chiral LMWGs. This review aims at describing the formation mechanisms of the helical nanostructures, the origination of optical activity, and the applications for other helical nanomaterial preparation, mainly based on our group’s results. The morphology and handedness can be controlled by changing the chirality and kinds of LMWGs and tuning the reaction conditions. The aromatic rings arrange in a partially crystalline structure. The optical activity of the polybissilsesquioxane nanotubes and mesoporous nanofibers originates from chiral defects, including stacking and twisting of aromatic groups, on the inner surfaces. They can be used as the starting materials for preparation of silica, silicon, carbonaceous, silica/carbon, and silicon carbide nanotubes.

  13. Cyclodextrin-supported organic matrix for application of MALDI-MS for forensics. Soft-ionization to obtain protonated molecules of low molecular weight compounds

    Energy Technology Data Exchange (ETDEWEB)

    Yonezawa, Tetsu, E-mail: tetsu@eng.hokudai.ac.jp [Division of Materials Science and Engineering, Faculty of Engineering, Hokkaido University, Kita 13, Nishi 8, Kita-ku, Sapporo, Hokkaido 060-8628 (Japan); Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Asano, Takashi [Division of Materials Science and Engineering, Faculty of Engineering, Hokkaido University, Kita 13, Nishi 8, Kita-ku, Sapporo, Hokkaido 060-8628 (Japan); Criminal Investigation Laboratory, Metropolitan Police Department, 2-1-1 Kasumigaseki, Chiyoda-ku, Tokyo 100-8929 (Japan); Fujino, Tatsuya [Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo 192-0397 (Japan); Nishihara, Hiroshi [Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2013-06-20

    Highlights: ► MALDI-MS applications for drug identification in forensic science is investigated. ► Cyclodextrin-supported organic matrices strongly suppress the obstacle peaks of organic matrix compounds. ► Cyclodextrin-supported organic matrices also suppress the alkali adducted molecule peaks. ► Sugar units of cyclodextrins work for this specific features. - Abstract: A mass measurement technique for detecting low-molecular-weight drugs with a cyclodextrin-supported organic matrix was investigated. By using cyclodextrin-supported 2,4,6-trihydroxyacetophenone (THAP), the matrix-related peaks of drugs were suppressed. The peaks of protonated molecules of the sample and THAP were mainly observed, and small fragments were detected in a few cases. Despite the Na{sup +} and K{sup +} peaks were observed in the spectrum, Na{sup +} or K{sup +} adduct sample molecules were undetected, owing to the sugar units of cyclodextrin. The advantages of MALDI-MS with cyclodextrin-supported matrices as an analytical tool for forensic samples are discussed. The suppression of alkali adducted molecules and desorption process are also discussed.

  14. Three different chromogenic methods do not give equivalent anti-Xa levels for patients on therapeutic low molecular weight heparin (dalteparin) or unfractionated heparin.

    Science.gov (United States)

    Kovacs, M J; Keeney, M; MacKinnon, K; Boyle, E

    1999-02-01

    In this study we compare three chromogenic methods (IL-Heparin, Stachrom Heparin and Heparin Sigma) on two different instruments (ACL300+ and AMAX CS190) for patients on dalteparin (n = 41), a low molecular weight heparin or unfractionated heparin (n = 50). For dalteparin the mean anti-Xa levels for IL-Heparin, Stachrom Heparin and Heparin Sigma were 0.27, 0.30 and 0.21 U/ml, respectively, while for heparin they were 0.52, 0.55 and 0.41 U/ml, respectively. To test for instrument specific effects, IL-Heparin and Stachrom Heparin were repeated on both instruments on 42 patients receiving unfractionated heparin. For IL-Heparin the mean anti-Xa levels on the AMAX CS190 and ACL300+ were 0.51 and 0.59 U/ml, respectively, while for Stachrom Heparin they were 0.55 and 0.67 anti-Xa U/ml. We conclude that different chromogenic anti-Xa methods do not give equivalent anti-Xa levels for the same samples. Moreover, the differences are clinically significant. This is not explained entirely by instrumentation effects. Recommended therapeutic ranges may need to be method and instrument specific.

  15. Pharmacology of desmin (low molecular weight dermatan sulphate) in healthy volunteers following intravenous bolus administration of different dosages (200, 400, 800 mg).

    Science.gov (United States)

    Dettori, A G; Milani, M R; Manotti, C; Zamboni, V; Palazzini, E; Barbanti, M

    1995-08-01

    Eight healthy volunteers (6 males, 2 females, mean age 31.6 yrs), were administered--on three separate days--200, 400 and 800 mg of a new low molecular weight Dermatan sulphate (Desmin), given as a single i.v. bolus (2 min.) injection. Before each administration and 10, 20, 30 min., 1, 2, 4, 8, 12, 24 hours after, blood samples were drawn and the following coagulative assays performed: aPTT (activated Partial Thromboplastin Time), TT (Thrombin Time), anti Xa (Xa Factor inhibition), Heptest, Stachrom D.S.. Furthermore, a kinetic analysis was performed on the activity curves calculated on the Heptest and Stachrom data. Plasma peak values and half lives of the parameters checked showed a clear dose-effect relationship. aPTT and TT showed very short-lasting variations and the inhibition of Factor Xa was moderate, but significant. The most evident and specific effects of Desmin were those on Heptest and Stachrom D.S.: both tests were influenced in a clear-cut and dose-dependent way, mainly as a consequence of the action of Desmin on HCII, with partially different kinetic patterns. A series of in vitro experiments proved an anti Xa effect of Desmin, mediated by antithrombin III, well above the possible interference of the small (< 1%) heparin contaminants in Desmin. An even more marked anti Xa activity was seen in the in vivo study, an observation so far unrecognized for this type of drug: some possible interpretations of this fact are discussed.

  16. Salting-out assisted liquid-liquid extraction and partial least squares regression to assay low molecular weight polycyclic aromatic hydrocarbons leached from soils and sediments

    Science.gov (United States)

    Bressan, Lucas P.; do Nascimento, Paulo Cícero; Schmidt, Marcella E. P.; Faccin, Henrique; de Machado, Leandro Carvalho; Bohrer, Denise

    2017-02-01

    A novel method was developed to determine low molecular weight polycyclic aromatic hydrocarbons in aqueous leachates from soils and sediments using a salting-out assisted liquid-liquid extraction, synchronous fluorescence spectrometry and a multivariate calibration technique. Several experimental parameters were controlled and the optimum conditions were: sodium carbonate as the salting-out agent at concentration of 2 mol L- 1, 3 mL of acetonitrile as extraction solvent, 6 mL of aqueous leachate, vortexing for 5 min and centrifuging at 4000 rpm for 5 min. The partial least squares calibration was optimized to the lowest values of root mean squared error and five latent variables were chosen for each of the targeted compounds. The regression coefficients for the true versus predicted concentrations were higher than 0.99. Figures of merit for the multivariate method were calculated, namely sensitivity, multivariate detection limit and multivariate quantification limit. The selectivity was also evaluated and other polycyclic aromatic hydrocarbons did not interfere in the analysis. Likewise, high performance liquid chromatography was used as a comparative methodology, and the regression analysis between the methods showed no statistical difference (t-test). The proposed methodology was applied to soils and sediments of a Brazilian river and the recoveries ranged from 74.3% to 105.8%. Overall, the proposed methodology was suitable for the targeted compounds, showing that the extraction method can be applied to spectrofluorometric analysis and that the multivariate calibration is also suitable for these compounds in leachates from real samples.

  17. Influence of low-molecular-weight glutenin subunit genes at Glu-A3 locus on wheat sodium dodecyl sulfate sedimentation volume and solvent retention capacity value.

    Science.gov (United States)

    Li, Zhixia; Si, Hongqi; Xia, Yunxiang; Ma, Chuanxi

    2015-08-15

    To understand the effect of low-molecular-weight (LMW) glutenin alleles at the Glu-A3 locus on sodium dodecyl sulfate (SDS) sedimentation volume and solvent retention capacity (SRC) values, 244 accessions of Chinese wheat (Triticum aestivum L.) mini core collections were investigated. In this study the significant differences in wholemeal flour SDS sedimentation volume and SRC values associated with specific glutenin alleles at the Glu-A3 locus were explained. Seven glutenin alleles at the Glu-A3 locus were confirmed by locus-specific polymerase chain reaction (PCR). SDS sedimentation volume and lactic acid SRC value were significantly affected by alleles Glu-A3b and Glu-A3g. Based on total average values, 28 varieties carrying Glu-A3b had significantly higher means of SDS sedimentation volume and lactic acid SRC value, whereas 19 varieties carrying Glu-A3g had significantly lower means. Alleles Glu-A3d and Glu-A3f significantly increased only SDS sedimentation volume and sucrose SRC value respectively. Correlation analysis showed that SDS sedimentation volume was uncorrelated with lactic acid SRC and sucrose SRC values. The Glu-A3 LMW glutenin subunit could predict 12.8% of the variance in SDS sedimentation volume, 4.7% in lactic acid SRC and 6.4% in sucrose SRC. © 2014 Society of Chemical Industry.

  18. Effects of atorvastatin combined with low-molecular-weight heparin on plasma inflammatory cytokine level and pulmonary pathophysiology of rats with sepsis.

    Science.gov (United States)

    Jing, Fei; Li, Ming; Ren, Hongsheng; Zhang, Jitian; Yao, Qingchun; Chu, Yufeng; Wang, Chunting

    2016-08-01

    The aim of the present study was to investigate the effect of atorvastatin combined with low-molecular-weight heparin (LMWH) on plasma early inflammatory cytokine levels as well as pulmonary pathophysiology of rats with sepsis. A total of 122 rats were randomly divided into five groups including the sham operation group (n=10), CLP group (n=10), atorvastatin group (n=34, 20 mg/kg/day), LMWH group (n=34, 100 IU/kg/day), and atorvastatin combined with LMWH group (n=34). Blood samples from 6 rats in each group were collected to detect TNF-α, IL-1β and HMGB1 concentration in plasma by linked immunosorbent assay at baseline and postoperatively at 4, 8, 12 and 24 h. Pulmonary pathophysiology was observed postoperatively at 24 h. The remaining 10 rats in each group were used to calculate the 7-day cumulative mortality rate. Compared to the sham operation group, the scores in CLP were greater than those of the sham operation group (Ppathophysiology in CLP was more severe. Compared to the CLP group, the damage of pulmonary pathophysiology in other groups was slight. Compared to the CLP group, the 7-day cumulative mortality rate in other groups decreased significantly (Ppathophysiology, and the 7-day cumulative mortality rate. Atorvastatin, and LMWH may therefore be useful for the treatment of sepsis due to its ability to inhibit the release of TNF-α, IL-1β and HMGB1 in septic rats.

  19. Dissolution of mimetite Pb5(AsO4)3Cl in low-molecular-weight organic acids and EDTA.

    Science.gov (United States)

    Bajda, Tomasz

    2011-06-01

    Due to its relatively low solubility, mimetite Pb(5)(AsO(4))(3)Cl may control Pb and As(V) solution levels at a low value in contaminated soils. The time-dependent dissolution of mimetite by low-molecular-weight organic acids (LMWOAs) such as acetic, lactic, citric, and ethylene diamine tetra-acetic acid (EDTA) was determined. At pH 3.5, the presence of citric acid or EDTA significantly increases the solubility of mimetite while acetic or lactic acids show little effect. The effect of all organic anions on the dissolution of mimetite increased with the increase in solution pH. The rate of mimetite dissolution depended on the kind and concentration of organic solvents in the sequence r(EDTA)>r(lactate)>r(acetate)>r(citrate). Soluble Pb and As(V) released in LMWOAs and EDTA were higher than the WHO guideline value for these elements in drinking water (10 μg As(V)L(-1), 10 μg Pb L(-1)). This suggests that soil organic acids in rhizosphere can potentially liberate Pb and As(V) from mimetite in contaminated soils. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Effects of Low-Molecular-Weight Fucoidan and High Stability Fucoxanthin on Glucose Homeostasis, Lipid Metabolism, and Liver Function in a Mouse Model of Type II Diabetes

    Directory of Open Access Journals (Sweden)

    Hong-Ting Victor Lin

    2017-04-01

    Full Text Available The combined effects of low-molecular-weight fucoidan (LMF and fucoxanthin (Fx in terms of antihyperglycemic, antihyperlipidemic, and hepatoprotective activities were investigated in a mouse model of type II diabetes. The intake of LMF, Fx, and LMF + Fx lowered the blood sugar and fasting blood sugar levels, and increased serum adiponectin levels. The significant decrease in urinary sugar was only observed in LMF + Fx supplementation. LMF and Fx had ameliorating effects on the hepatic tissue of db/db mice by increasing hepatic glycogen and antioxidative enzymes, and LMF was more effective than Fx at improving hepatic glucose metabolism. As for glucose and lipid metabolism in the adipose tissue, the expression of insulin receptor substrate (IRS-1, glucose transporter (GLUT, peroxisome proliferator-activated receptor gamma (PPARγ, and uncoupling protein (UCP-1 mRNAs in the adipose tissue of diabetic mice was significantly upregulated by Fx and LMF + Fx, and levels of inflammatory adipocytokines, such as adiponectin, tumor necrosis factor-α (TNF-α, and interleukin-6 (IL-6, were significantly modulated only by LMF + Fx supplementation. The efficacy of LMF + Fx supplementation on the decrease in urinary sugar and on glucose and lipid metabolism in the white adipose tissue of db/db mice was better than that of Fx or LMF alone, indicating the occurrence of a synergistic effect of LMF and Fx.

  1. Hyaluronan viscosupplementation: state of the art and insight into the novel cooperative hybrid complexes based on high and low molecular weight HA of potential interest in osteoarthritis treatment.

    Science.gov (United States)

    Schiraldi, Chiara; Stellavato, Antonietta; de Novellis, Francesca; La Gatta, Annalisa; De Rosa, Mario

    2016-01-01

    Osteoarthritis (OA) represents a group of chronic, painful, disabling conditions affecting synovial joints. It is characterized by degeneration of articular cartilage, alterations of peri-articular and subchondral bone, low-grade synovial inflammation (synovitis). Despite OA is commonly described as a non-inflammatory disease, it is known that its progression and the subsequent increment of symptoms correlate to the production of inflammatory factors that induce the secretion of enzymes responsible for cartilage degradation. In clinical practice, to alleviate pain and stiffness, not only during acute phases but also as maintenance therapy, intra-articular injections of corticosteroids or similar drugs are used, besides it is well diffused the viscosupplementation procedure based on hyaluronan gel. There are many different products containing high molecular weight linear HA or cross-linked derivatives, however the novelty in the field consist in the hybrid cooperative complexes derived from high and low molecular weight HA through a patented processing. This technique permit to double the amount of HA delivered to the injured site without increasing the injected volume, beside in vitro assay on human chondrocytes suggested hybrid complexes as effective in the modulation of several inflammatory cytokines in joints.

  2. Tissue-Type-Specific Heat-Shock Response and Immunolocalization of Class I Low-Molecular-Weight Heat-Shock Proteins in Soybean.

    Science.gov (United States)

    Jinn, T. L.; Chang, PFL.; Chen, Y. M.; Key, J. L.; Lin, C. Y.

    1997-06-01

    A monospecific polyclonal antibody was used to study the tissue-type specificity and intracellular localization of class I low-molecular-weight (LMW) heat-shock proteins (HSPs) in soybean (Glycine max) under different heat-shock regimes. In etiolated soybean seedlings, the root meristematic regions contained the highest levels of LMW HSP. No tissue-type-specific expression of class I LMW HSP was detected using the tissue-printing method. In immunolocalization studies of seedlings treated with HS (40[deg]C for 2 h) the class I LMW HSPs were found in the aggregated granular structures, which were distributed randomly in the cytoplasm and in the nucleus. When the heat shock was released, the granular structures disappeared and the class I LMW HSPs became distributed homogeneously in the cytoplasm. When the seedlings were then given a more severe heat shock following the initial 40[deg]C -> 28[deg]C treatment, a large proportion of the class I LMW HSPs that originally localized in the cytoplasm were translocated into the nucleus and nucleolus. Class I LMW HSPs may assist in the resolubilization of proteins denatured or aggregated by heat and may also participate in the restoration of organellar function after heat shock.

  3. Efficacy and safety of low molecular weight heparin compared to unfractionated heparin for chronic outpatient hemodialysis in end stage renal disease: systematic review and meta-analysis

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    Ghanshyam Palamaner Subash Shantha

    2015-03-01

    Full Text Available Background. Low molecular weight heparin (LMWH is an effective anti-coagulant for thrombotic events. However, due to its predominant renal clearance, there are concerns that it might be associated with increased bleeding in patients with renal disease.Objectives. We systematically evaluated the efficacy and safety of LMWH compared to unfractionated heparin (UH in end stage renal disease (ESRD patients.Search Methods. Pubmed, Embase and cochrane central were searched for eligible citations.Selection Criteria. Randomized controlled trials, comparing LMWH and UH, involving adult (age > 18 years, ESRD patients receiving outpatient, chronic, intermittent hemodialysis were included.Data Collection and Analysis. Two independent reviewers performed independent data abstraction. I2 statistic was used to assess heterogeneity. Random effects model was used for meta-analysis.Results. Nineteen studies were included for systematic review and 4 were included for meta-analysis. There were no significant differences between LMWH and UFH for extracorporeal circuit thrombosis [risk ratio: 1 (95% CI [0.62–1.62

  4. Application of nonpolar matrices for the analysis of low molecular weight nonpolar synthetic polymers by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

    Science.gov (United States)

    Macha; Limbach; Savickas

    2000-08-01

    The application of nonpolar matrices for the analysis of low molecular weight nonpolar synthetic polymers using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is demonstrated. Anthracene, pyrene, and acenaphthene were utilized as nonpolar matrices for the analysis of polybutadiene, polyisoprene, and polystyrene samples of various average molecular weights ranging from about 700 to 5,000. The standard MALDI-MS approach for the analysis of these types of polymers involves the use of conventional acidic matrices, such as all-trans-retinoic acid, with an additional cationization reagent. The nonpolar matrices used in this study are shown to be as equally effective as the conventional matrices. The uniform mixing of the nonpolar matrices and the nonpolar analytes enhances the MALDI-MS spectral reproducibility. Silver salts were found to be the best cationization reagents for all of the cases studied. Copper salts worked well for polystyrene, poorly for polyisoprene, and not at all for polybutadiene samples. These matrices should be useful for the characterization of hydrocarbon polymers and other analytes, such as modified polymers, which may potentially be sensitive to acidic matrices.

  5. [Low molecular weight oxidation by-products produced during catalytic ozonation with ferric hydroxide of NOM fractions isolated from filtrated water].

    Science.gov (United States)

    Lu, Jin-Feng; Qiu, Jiao; Ma, Jun; Zhang, Tao; Chen, Zhong-Lin; Wang, Huan

    2009-03-15

    Natural organic matter (NOM) in a filtered river water from a water treatment plant was isolated and fractionated into six types of fractions. The aim of the work is to investigate the formation of the low molecular weight (LMW) oxidation by-products (i.e. aldehydes, ketones and ketoacids) after ferric hydroxide-catalyzed ozonation of individual NOM fractions. Results showed that catalytic ozonation could improve the reduction of the dissolved organic matter (DOC) and specific UV absorbance (SUVA) at 254 nm compared with ozonation alone. However, catalytic ozonation with ferric hydroxide could not produce less LMW oxidation by-products than ozonation. Hydrophobic neutral (HON) produced much higher yields of the LMW oxidation by-products than other fractions both during catalytic ozonation and ozonation alone, while the basic NOM fractions formed relatively lower productions of these by-products. Like the case of ozonation alone, the predominant contributors for the yields of aldehydes and ketoacids formed in catalytic ozonation were formaldehyde and pyruvic acid, respectively. Among these NOM fractions, HON produced the highest yields of the formaldehyde and pyruvic acid after catalytic ozonation. The yield of formaldehyde from HON was up to 71.6% of the total aldehydes and ketones, and the pyruvic acid concentration of HON was 78.6 microg/mg after catalytic ozonation. In addition, NOM fractions became more biodegradable after catalytic ozonation, because the percent of total LMW by-products carbon in the final DOC after catalytic ozonation was higher than ozonation alone.

  6. Comparison of Peritoneal Low-Molecular-Weight-Protein-Removal in CCPD and CAPD Patients Based on C-Terminal Agrin Fragment Clearance

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    Dominik Steubl

    2016-03-01

    Full Text Available Background/Aims: This study compares the peritoneal elimination of the low-molecular-weight-protein (LMWP C-terminal agrin fragment (tCAF, size 22 kDa, a promising biomarker for kidney function, in continuous cycling peritoneal dialysis (CCPD and continuous ambulatory peritoneal dialysis (CAPD. Methods: 103 sets of serum, 24h-urine and dialysate samples were obtained in 15 CCPD (63 sets and 11 CAPD (40 sets patients. Total, renal and peritoneal substrate removals/clearances were measured/calculated for tCAF, creatinine, blood-urea-nitrogen (BUN, cystatin C and albumin and correlated with the peritoneal transport type. Results: Serum und urine concentrations of all biomarkers did not differ between both groups, urinary substrate removal was higher in CAPD patients for all biomarkers due to better residual renal function. Peritoneal substrate removal of tCAF and albumin were significantly higher in CAPD (tCAF: 35.3 vs. 19.3 µg/d, p2 body-surface-area, pConclusions: CAPD was superior to CCPD concerning peritoneal tCAF removal. This finding was pronounced in high-transporters and CAPD patients using icodextrin twice daily.

  7. Antiproliferative effect of synthetic lignin against human breast cancer and normal fetal lung cell lines. Potency of low molecular weight fractions.

    Science.gov (United States)

    Andrijevic, Lj; Radotic, K; Bogdanovic, J; Mutavdzic, D; Bogdanovic, G

    2008-01-01

    Due to a lack of chemotherapeutics to efficiently control neoplastic processes, there is a need for discovering new, more efficient anticancer drugs that would distinguish malignant from normal cells. We studied the effect of short (4 h) and long (72 h) treatment with different concentrations of the enzymatically synthesized lignin model compound (DHP) on the proliferation of two human cell lines grown in tissue culture: breast adenocarcinoma (MCF7) and normal fetal lung fibroblast (MRC5) cell lines. The growth of both MRC5 and MCF7 cell lines was inhibited by DHP after 4 h-treatment, while the carcinoma cell line was also sensitive to the long-term treatment with lower dose of DHP in comparison with the fetal cells. The low molecular weight DHP fractions inhibited growth of the MRC5 cells at lower concentrations compared to the treatment with all DHP fractions. The higher sensitivity to DHP of the human malignant cells compared to the normal transformed ones gives the possibility to further study DHP as a therapeutic agent.

  8. Microbial use of low molecular weight DOM in filtered and unfiltered freshwater: Role of ultra-small microorganisms and implications for water quality monitoring.

    Science.gov (United States)

    Brailsford, F L; Glanville, H C; Marshall, M R; Golyshin, P N; Johnes, P J; Yates, C A; Owen, A T; Jones, D L

    2017-11-15

    Dissolved organic matter (DOM) plays a central role in regulating productivity and nutrient cycling in freshwaters. It is therefore vital that we can representatively sample and preserve DOM in freshwaters for subsequent analysis. Here we investigated the effect of filtration, temperature (5 and 25°C) and acidification (HCl) on the persistence of low molecular weight (MW) dissolved organic carbon (DOC), nitrogen (DON) and orthophosphate in oligotrophic and eutrophic freshwater environments. Our results showed the rapid loss of isotopically-labelled glucose and amino acids from both filtered (0.22 and 0.45μm) and unfiltered waters. We ascribe this substrate depletion in filtered samples to the activity of ultra-small (<0.45μm) microorganisms (bacteria and archaea) present in the water. As expected, the rate of C, N and P loss was much greater at higher temperatures and was repressed by the addition of HCl. Based on our results and an evaluation of the protocols used in recently published studies, we conclude that current techniques used to sample water for low MW DOM characterisation are frequently inadequate and lack proper validation. In contrast to the high degree of analytical precision and rigorous statistical analysis of most studies, we argue that insufficient consideration is still given to the presence of ultra-small microorganisms and potential changes that can occur in the low MW fraction of DOM prior to analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. [Long-term treatment with a low-molecular-weight heparin administered subcutaneously compared with a vitamin K antagonist: subanalysis of patients with cancer].

    Science.gov (United States)

    Romera-Villegas, Antonio; Martí Mestre, Xavier; Vila Coll, Ramón; Colomé Nafría, Esteve

    2015-01-01

    We performed a subanalysis of cancer patients enrolled in a clinical trial that compared long-term (6 months) treatment with a low-molecular-weight heparin (LMWH) administered subcutaneously or with acenocoumarol. The subanalysis assessed whether the characteristics of the tumor had an influence on the clinical response. A randomized open trial included 69 patients with cancer and symptomatic proximal deep vein thrombosis of the lower limbs. The tumor characteristics and treatment type were recorded. The main assessment criterion was the 12-month incidence of recurrent symptomatic venous thromboembolism (VTE). Sixty-one patients (88.4%) were analyzed. At the time of inclusion, the cancer characteristics and treatment were comparable between the 2 groups. Over the course of 12 months, the recurrent VTE was significantly greater in the elderly patients (71.5 ± 6.4 vs. 62.0 ± 15.1; p=.006). The logistic regression analysis showed no association between VTE recurrence and the location or extent of the tumor. However, the use of thrombogenic chemotherapy (p=.045) was independently associated with VTE recurrence, and longterm treatment with tinzaparin was almost a protective factor (p=.15). In this small sample, we observed an association between thrombogenic chemotherapy and recurrent VTE. The tendency towards a reduction in VTE recurrence at 12 months in patients with cancer in the LMWH group could be attributed to the effect of the full LMWH dosage. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  10. Efficacy of Low-Molecular-Weight Fucoidan as a Supplemental Therapy in Metastatic Colorectal Cancer Patients: A Double-Blind Randomized Controlled Trial

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    Hsiang-Lin Tsai

    2017-04-01

    Full Text Available Background: Low-molecular-weight fucoidan (LMF is widely used as a food supplement for cancer patients. However, all of the studies are in vitro or were conducted using mice. Therefore, powerful clinical evidence for LMF use is relatively weak. This study aimed to evaluate the efficacy of LMF as a supplemental therapy to chemo-target agents in metastatic colorectal cancer (mCRC patients. Methods: We conducted a prospective, randomized, double-blind, controlled trial to evaluate the efficacy of LMF as a supplemental therapy to chemotarget agents in patients with metastatic colorectal cancer (mCRC. Sixty eligible patients with mCRC were included. Finally, 54 patients were enrolled, of whom 28 were included in the study group and 26 in the control group. The primary endpoint was the disease control rate (DCR, and secondary endpoints included the overall response rate (ORR, progression-free survival (PFS, overall survival (OS, adverse effects (AEs, and quality of life (QOL. Results: The DCRs were 92.8% and 69.2% in the study and control groups, respectively (p = 0.026, in a median follow-up period of 11.5 months. The OS, PFS, ORR, AEs, and QOL did not significantly differ between the two groups. Conclusion: This is the first clinical trial evaluating the efficacy of LMF as a supplemental therapy in the management of patients with mCRC. The results indicate that LMF combined with chemotarget agents significantly improved the DCR.

  11. Low-Molecular-Weight Fucoidan Induces Endothelial Cell Migration via the PI3K/AKT Pathway and Modulates the Transcription of Genes Involved in Angiogenesis

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    Claire Bouvard

    2015-12-01

    Full Text Available Low-molecular-weight fucoidan (LMWF is a sulfated polysaccharide extracted from brown seaweed that presents antithrombotic and pro-angiogenic properties. However, its mechanism of action is not well-characterized. Here, we studied the effects of LMWF on cell signaling and whole genome expression in human umbilical vein endothelial cells and endothelial colony forming cells. We observed that LMWF and vascular endothelial growth factor had synergistic effects on cell signaling, and more interestingly that LMWF by itself, in the absence of other growth factors, was able to trigger the activation of the PI3K/AKT pathway, which plays a crucial role in angiogenesis and vasculogenesis. We also observed that the effects of LMWF on cell migration were PI3K/AKT-dependent and that LMWF modulated the expression of genes involved at different levels of the neovessel formation process, such as cell migration and cytoskeleton organization, cell mobilization and homing. This provides a better understanding of LMWF’s mechanism of action and confirms that it could be an interesting therapeutic approach for vascular repair.

  12. Impact of immobilizing of low molecular weight hyaluronic acid within gelatin-based hydrogel through enzymatic reaction on behavior of enclosed endothelial cells.

    Science.gov (United States)

    Khanmohammadi, Mehdi; Sakai, Shinji; Taya, Masahito

    2017-04-01

    The hydrogels having the ability to promote migration and morphogenesis of endothelial cells (ECs) are useful for fabricating vascularized dense tissues in vitro. The present study explores the immobilization of low molecular weight hyaluronic acid (LMWHA) derivative within gelatin-based hydrogel to stimulate migration of ECs. The LMWHA derivative possessing phenolic hydroxyl moieties (LMWHA-Ph) was bound to gelatin-based derivative hydrogel through the horseradish peroxidase-catalyzed reaction. The motility of ECs was analyzed by scratch migration assay and microparticle-based cell migration assay. The incorporated LMWHA-Ph molecules within hydrogel was found to be preserved stably through covalent bonds during incubation. The free and immobilized LMWHA-Ph did not lose an inherent stimulatory effect on human umbilical vein endothelial cells (HUVECs). The immobilized LMWHA-Ph within gelatin-based hydrogel induced the high motility of HUVECs, accompanied by robust cytoskeleton extension, and cell subpopulation expressing CD44 cell receptor. In the presence of immobilized LMWHA-Ph, the migration distance and the number of existing HUVECs were demonstrated to be encouraged in dose-dependent and time-dependent manners. Based on the results obtained in this work, it was concluded that the enzymatic immobilization of LMWHA-Ph within gelatin-based hydrogel represents a promising approach to promote ECs' motility and further exploitation for vascular tissue engineering applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. [Identification of low-molecular weight prostate-specific antigen(PSA) and lactoferrin in the prostatic secretion of benign prostatic hyperplasia].

    Science.gov (United States)

    Xu, Ke-xin; Wang, Xiao-feng

    2006-12-18

    To investigate the expression of low-molecular-weight PSA(lw-PSA) and lactoferrin in the expressed prostatic secretion (EPS) from both benign prostatic hyperplasia (BPH) and normal prostate. Forty human EPS samples obtained from 20 BPH patients and 20 normal males were subjected to two-dimensional gel electrophoresis (2-DE). Mass spectrometry was performed to confirm the nature of the secreted proteins in EPS. One uniquely expressed protein in BPH was detected and mass spectrometry determined its nature as lw-PSA (molecular weight 10x10(3), pI 8.5-9.3). More importantly, Western blotting analysis also revealed that lw-PSA detected in BPH-EPS, but was undetectable in BPH-free EPS. In addition, up-regulation of Lactoferrin (molecular weight 35x10(3), pI 7-7.5) in BPH-EPS, as compared with BPH-free EPS, was also observed. More interestingly, lactoferrin was absent in prostate cancer tissues. Our results indicate lw-PSA may be produced specifically by BPH epithelium and it has a potential to be used as a specific biological marker for the diagnosis of BPH. In addition, benign prostatic epithelium can produce more lactoferrin while prostate cancer tissues go without its lactoferrin secretion.

  14. Structural Characterization and Antioxidative Activity of Low-Molecular-Weights Beta-1,3-Glucan from the Residue of Extracted Ganoderma lucidum Fruiting Bodies

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    Pai-Feng Kao

    2012-01-01

    Full Text Available The major cell wall constituent of Ganoderma lucidum (G. lucidum is β-1,3-glucan. This study examined the polysaccharide from the residues of alkaline-extracted fruiting bodies using high-performance anion-exchange chromatography (HPAEC, and it employed nuclear magnetic resonance (NMR and mass spectrometry (MS to confirm the structures. We have successfully isolated low-molecular-weight β-1,3-glucan (LMG, in high yields, from the waste residue of extracted fruiting bodies of G. lucidum. The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT assay evaluated the capability of LMG to suppress H2O2-induced cell death in RAW264.7 cells, identifying that LMG protected cells from H2O2-induced damage. LMG treatment decreased H2O2-induced intracellular reactive oxygen species (ROS production. LMG also influenced sphingomyelinase (SMase activity, stimulated by cell death to induce ceramide formation, and then increase cell ROS production. Estimation of the activities of neutral and acid SMases in vitro showed that LMG suppressed the activities of both neutral and acid SMases in a concentration-dependent manner. These results suggest that LMG, a water-soluble β-1,3-glucan recycled from extracted residue of G. lucidum, possesses antioxidant capability against H2O2-induced cell death by attenuating intracellular ROS and inhibiting SMase activity.

  15. Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease - Fragmin in unstable coronary artery disease study (FRIC)

    NARCIS (Netherlands)

    Klein, W; Buchwald, A; Hillis, SE; Monrad, S; Sanz, G; Turpie, AGG; van der Meer, Jan; Olaisson, E; Undeland, S; Ludwig, K

    1997-01-01

    Background Low-molecular-weight heparin has a number of pharmacological and pharmacokinetic advantages over unfractionated heparin that make it potentially suitable, when used in combination with aspirin, for the treatment of unstable coronary artery disease. Method and Results Patients with

  16. The use of long-term low-molecular weight heparin for the treatment of venous thromboembolism in palliative care patients with advanced cancer : a case series of sixty two patients

    NARCIS (Netherlands)

    Noble, Sir; Hood, K.; Finlay, I. G.

    2007-01-01

    The advantages of low-molecular weight heparin (LMVVH) over warfarin, in the treatment of cancer associated venous thromboembolism (VTE) are well reported. However the studies supporting LMWH include few patients representative of the palliative care population. Although LMWH has advantages over

  17. Isolation and chemical characterization of some low molecular weight proteins of the bovine lens : Paper from the symposium “lens proteins and related subjects”, Ghent, Belgium, June 1967

    NARCIS (Netherlands)

    Dam, A.F. van

    1968-01-01

    Four low molecular weight proteins, designated as β2-, γ0-, γ1- and γ2-crystallin, have been isolated from the cortex of bovine lenses by gel filtration on Sephadex G-75, followed by chromatography on DEAE-Sephadex. The isolated proteins were found to be homogeneous in starch gel and/or agar

  18. Safety and efficacy of total-dose infusion of low molecular weight iron dextran for iron deficiency anemia in patients with inflammatory bowel disease.

    Science.gov (United States)

    Koutroubakis, Ioannis E; Oustamanolakis, Pantelis; Karakoidas, Christos; Mantzaris, Gerassimos J; Kouroumalis, Elias A

    2010-08-01

    Intravenous iron has been suggested as a safe and effective treatment of anemia complicating inflammatory bowel disease (IBD). Low molecular weight (LMW) iron dextran has the ability to administer the patient's total iron requirement in a single infusion. The aim of this study was to assess the safety and efficacy of the total dose of LMW iron dextran infusion for the treatment of iron deficiency in IBD. Fifty IBD patients (27 female, 35 Crohn's disease, 15 ulcerative colitis) were included in the study. Mean +/- standard deviation (SD) hemoglobin and ferritin levels before the infusion were 9.88 +/- 1.42 g/dl and 13.9 +/- 10.9 ng/ml, respectively. A 25-mg test dose was followed by infusion of the total dose of LMW iron dextran based on the iron deficit. Several clinical and laboratory parameters were measured before and on week 4 after infusion. Four patients (8%) developed adverse reactions during the test infusion and did not receive the total-dose infusion. Only one patient developed an allergic reaction during the total-dose infusion. In the remaining 45 patients, the mean +/- SD iron dose that was given was 1,075 +/- 269 mg. The mean +/- SD elevation of hematocrit and hemoglobin on week 4 was 4.9 +/- 1.9% and 1.7 +/- 0.8 g/dl, respectively. Hematopoietic response was observed in 23 of 45 patients (51.1%). Total parenteral iron replacement with LMW iron dextran is an easy, safe, and effective alternative method for treating iron deficiency anemia in IBD. Harmless adverse reactions may develop in a minority of patients.

  19. Lessons From the EThIGII Trial: Proper Putative Benefit Assessment of Low-Molecular-Weight Heparin Treatment in M2/ANXA5 Haplotype Carriers.

    Science.gov (United States)

    Rogenhofer, Nina; Markoff, Arseni; Wagner, Annett; Klein, Hanns-Georg; Petroff, David; Schleussner, Ekkehard; Thaler, Christian J

    2017-01-01

    This study presents sample size considerations derived from the Efficacy of Thromboprophylaxis as an Intervention during Gravidity (EThIGII) trial (ClinicalTrials.gov: NCT00400387) to address the question of low-molecular-weight heparin (LMWH) treatment in women with recurrent pregnancy loss (RPL) depending on the M2/ANXA5 haplotype. To evaluate the possible influence of such treatment on miscarriage rates of trial participants, a post hoc analysis of ANXA5 promoter genotypes in the light of M2/ANXA5 (RPRGL3) distribution was performed using logistic models. DNA for genotyping was available from 129 LMWH and 95 control patients, 44 (19.6%) of whom were M2/ANXA5 carriers. Miscarriages occurred in 1 (4.0%) of 25 M2/ANXA5 carriers from the LMWH group compared to 4 (21.1%) of 19 in the control group, resulting in an odds ratio (95% confidence interval) for miscarriage of 0.16 (0.016-1.5) for women treated with LMWH. In noncarriers, miscarriage rates were 6 (5.8%) of 104 versus 7 (9.2%) of 76 for the LMWH and the control groups, respectively, corresponding to an odds ratio for miscarriage of 0.60 (0.19-1.9). The apparent beneficial effects of miscarriage rate reduction in M2/ANXA5 carriers with RPL concur with biological considerations about improvement in reduced ANXA5 function through LMWH treatment in an adequate murine model. The data obtained were instrumental to design proper assessment of the existence and magnitude of this effect. © The Author(s) 2016.

  20. High Molecular Weight Glucan of the Culinary Medicinal Mushroom Agaricus bisporus is an α-Glucan that Forms Complexes with Low Molecular Weight Galactan

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    Harry J. Wichers

    2010-08-01

    Full Text Available An a-glucan was isolated from the culinary medicinal mushroom A. bisporus by hot water extraction, ethanol precipitation and DEAE-cellulose chromatography. The resulting material showed a single HMW peak excluded from a Sephadex G50 column that could completely be degraded by α-amylase treatment. After heating in 1% SDS a small additional peak of low MW eluted from the G50 column. The monosaccharide composition of the main peak was evaluated by HPLC, and was found to consist of a majority of glucose (97.6%, and a minor proportion of galactose (2.4%. Methylation analysis and degradation by a-amylase indicated the presence of an a-glucan with a main chain consisting of (1®4-linked units, substituted at O-6 by α-D-glucopyranose single-units in the relation 1:8. Mono- (13C-, 1H-NMR and bidimensional [1H (obs.,13C-HSQC] spectroscopy analysis confirmed the a-configuration of the Glcp residues by low frequency resonances of C-1 at d 100.6, 100.2, and 98.8 ppm and H-1 high field ones at d 5.06, 5.11, and 4.74 ppm. The DEPT-13C-NMR allowed assigning the non-substituted and O-substituted –CH2 signals at d 60.3/60.8 and 66.2 ppm, respectively. Other assignments were attributed to C-2, C-3, C-4, C-5 and C-6 of the non-reducing ends at d 71.8; 72.8; 70.0; 71.3 and 60.3/60.8 ppm, respectively. The minor proportion of galactose that was demonstrated was probably derived from a complex between the a-glucan and a low molecular weight galactan.

  1. Oligonol, a Low-Molecular Weight Polyphenol Derived from Lychee, Alleviates Muscle Loss in Diabetes by Suppressing Atrogin-1 and MuRF1

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    Hung-Wen Liu

    2017-09-01

    Full Text Available Stimulation of the ubiquitin-proteasome pathway—especially E3 ubiquitin ligases Atrogin-1 and MuRF1—is associated with muscle loss in diabetes. Elevated lipid metabolites impair myogenesis. Oligonol, a low molecular weight polyphenol derived from lychee, exhibited anti-diabetic and anti-obesity properties, suggesting it could be a proper supplement for attenuating muscle loss. Dietary (10 weeks oligonol supplementation (20 or 200 mg/kg diet on the skeletal muscle loss was investigated in diabetic db/db mice. Transcription factors NF-κB and FoxO3a involved in regulation of Atrogin-1 and MuRF1 were also investigated. Attenuation of muscle loss by oligonol (both doses was associated with down-regulation of Atrogin-1 and MuRF1 gene expression. Oligonol supplementation decreased NF-κB expression in the nuclear fraction compared with db/db mice without oligonol supplement. Upregulation of sirtuin1 (SIRT1 expression prevented FoxO3a nuclear localization in db/db mice supplemented with oligonol. Marked increases in AMPKα activity and Ppara mRNA expression leading to lower lipid accumulation by oligonol provided additional benefits for attenuating muscle loss. Oligonol limited palmitate-induced senescent phenotype and cell cycle arrest and suppressed Atrogin-1 and MuRF1 mRNA expression in palmitate-treated C2C12 muscle cells, thus contributing to improving the impaired myotube formation. In conclusion, oligonol-mediated downregulation of Atrogin-1 and MuRF1 gene expression alleviates muscle loss and improves the impaired myotube formation, indicating that oligonol supplementation may be useful for the attenuation of myotube loss.

  2. Use of Residual Biomass from the Textile Industry as Carbon Source for Production of a Low-Molecular-Weight Xylanase from Aspergillus oryzae

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    Gilvan Caetano Duarte

    2012-10-01

    Full Text Available Pretreated dirty cotton residue (PDCR from the textile industry was used as an alternative carbon source for the submerged cultivation of Aspergillus oryzae and the production of xylanases. The filtered culture supernatant was fractionated by ultrafiltration followed by three chromatographic steps, which resulted in the isolation of a homogeneous low-molecular-weight xylanase (Xyl-O1 with a mass of 21.5 kDa as determined by sodium dodecyl sulfate-polyacrilamide gel electrophoresis (SDS-PAGE co-polymerized with 0.1% oat spelt xylan. Enzyme catalysis was the most efficient at 50 °C and pH 6.0. The Km values (mg·mL−1 for the soluble fraction of oat spelt and birchwood xylans were 10.05 and 3.34, respectively. Xyl-O1 was more stable in the presence of 5,5-dithio-bis-(2-nitrobenzoic acid (DTNB, 1,4-dithiothreitol (DTT, l-cysteine or β-mercaptoethanol, which increased the rate of catalysis by 40%, 14%, 40% or 37%, respectively. The enzyme stability was improved at pH 7.0 in the presence of 20 mM l-cysteine, with the retention of nearly 100% of the activity after 6 h at 50 °C. Xyl-O1 catalyzed the cleavage of internal β-1,4 linkages of the soluble substrates containing d-xylose residues, with a maximum efficiency of 33% for the hydrolysis of birchwood xylan after 12 h of incubation. Identification of the hydrolysis products by high-performance anion exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD indicated the predominance of the hydrolysis products X2-X6 during the first 12 h of incubation and the accumulation of higher xylooligomers after the elution of the last xylooligomer standard, xylohexaose.

  3. Evaluation of benzofuroxan as a chromophoric oxidizing agent for thiol groups by using its reactions with papain, ficin, bromelain and low-molecular-weight thiols.

    Science.gov (United States)

    Shipton, M; Stuchbury, T; Brocklehurst, K

    1977-01-01

    1. Benzofuroxan (benzofurazan 1-oxide, benzo-2-oxa-1,3-diazole N-oxide) was evaluated as a specific chromophoric oxidizing agent for thiol groups. 2. Aliphatic thiol groups both in low-molecular-weight molecules and in the enzymes papain (EC 3.4.22.2), ficin (EC 3.4.22.3) and bromelain (EC 3.4.22.4) readily reduce benzofuroxan to o-benzoquinone dixime; potential competing reactions of amino groups are negligibly slow. 3. The fate of the thiol depends on its structure: a mechanism is proposed in which the thiol and benzofuroxan form an adduct which, if steric factors permit, reacts with another molecule of thiol to form a disulphide; when the thiol is located in the active site of a thiol proteinase and steric factors preclude enzyme dinner formation, the adduct reacts instead with water or HO- to form a sulphenic acid; attack on the sulphur atom of the adduct by either a sulphur or oxygen nucleophile releases o-benzoquinone dioxine. 4. Benzofuroxan contains n o proton-binding sites with pKa values in the range 3-10 and probably none in the range 0-14; o-benzoquinone dioxine undergoes a one-proton ionization with pKa=6.75.5. o-benzoquinone dioxime absorbs strongly at wavelengths greater than 410nm, where absorption by benzofuroxan, proteins and simple thiol compounds is negligible; 416 nm is an isosbestic point (epsilon 416 = 5110 litre. mol-1-cm-1); epsilon430=3740+[1460/(1+[H+]/Ka)] where pKa=6.75. 6. The possibility of acid-base catalysis of the oxidation by active-centre histidine residues of the thiol proteinases is discussed. PMID:851434

  4. Children with atopic dermatitis and frequent emollient use have increased urinary levels of low-molecular-weight phthalate metabolites and parabens.

    Science.gov (United States)

    Overgaard, L E K; Main, K M; Frederiksen, H; Stender, S; Szecsi, P B; Williams, H C; Thyssen, J P

    2017-11-01

    Parabens may be added to cosmetic and personal care products for preservation purposes. Low-molecular weight (LMW) phthalate diesters function as plasticizers, fixatives or solvents in such products, but may also be found in small quantities as contaminants from plastic containers. To evaluate the association between emollient use, atopic dermatitis and FLG mutations, respectively, with urinary concentrations of phthalate metabolites and parabens in Danish children. Eight hundred and forty-five Danish children 4-9 years of age were studied. Urinary concentrations of phthalate metabolites and parabens were determined, and children were genotyped for common FLG loss-of-function mutations. Information about atopic dermatitis and use of emollients was obtained from questionnaires completed by parents. The prevalence of atopic dermatitis was 16.1%. Phthalate metabolite and paraben levels were generally higher in children with frequent use of emollients compared to uncommon users, reaching statistical significance for some LMW phthalates and parabens. While there was no association with common FLG mutations, children with atopic dermatitis had significantly higher urinary levels of one LMW phthalate and two parabens, respectively, when compared to children without atopic dermatitis. Emollient use and atopic dermatitis were associated with modestly increased internal LMW phthalate and paraben exposure in 4-9 year old children. It is unknown whether the difference is explained by increased use of the specific emollients that are used to treat pruritic and inflamed skin, and/or whether the impaired skin barrier allows chemicals to penetrate more easily. Moreover, the putative toxicological burden is unknown. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  5. High molecular weight glucan of the culinary medicinal mushroom Agaricus bisporus is an alpha-glucan that forms complexes with low molecular weight galactan.

    Science.gov (United States)

    Smiderle, Fhernanda R; Sassaki, Guilherme L; van Arkel, Jeroen; Iacomini, Marcello; Wichers, Harry J; Van Griensven, Leo J L D

    2010-08-25

    An alpha-glucan was isolated from the culinary medicinal mushroom A. bisporus by hot water extraction, ethanol precipitation and DEAE-cellulose chromatography. The resulting material showed a single HMW peak excluded from a Sephadex G50 column that could completely be degraded by alpha-amylase treatment. After heating in 1% SDS a small additional peak of low MW eluted from the G50 column. The monosaccharide composition of the main peak was evaluated by HPLC, and was found to consist of a majority of glucose (97.6%), and a minor proportion of galactose (2.4%). Methylation analysis and degradation by alpha-amylase indicated the presence of an alpha-glucan with a main chain consisting of (1(R)4)-linked units, substituted at O-6 by alpha-D-glucopyranose single-units in the relation 1:8. Mono- (13C-, 1H-NMR) and bidimensional [1H (obs.),13C-HSQC] spectroscopy analysis confirmed the alpha-configuration of the Glcp residues by low frequency resonances of C-1 at delta 100.6, 100.2, and 98.8 ppm and H-1 high field ones at delta 5.06, 5.11, and 4.74 ppm. The DEPT-13C-NMR allowed assigning the non-substituted and O-substituted -CH(2) signals at delta 60.3/60.8 and 66.2 ppm, respectively. Other assignments were attributed to C-2, C-3, C-4, C-5 and C-6 of the non-reducing ends at delta 71.8; 72.8; 70.0; 71.3 and 60.3/60.8 ppm, respectively. The minor proportion of galactose that was demonstrated was probably derived from a complex between the alpha-glucan and a low molecular weight galactan.

  6. Low-Molecular-Weight Fucoidan Attenuates Mitochondrial Dysfunction and Improves Neurological Outcome After Traumatic Brain Injury in Aged Mice: Involvement of Sirt3.

    Science.gov (United States)

    Wang, Tao; Zhu, Mang; He, Zhong-Zheng

    2016-11-01

    Traumatic brain injury (TBI) is a leading cause of death and long-term disability. Fucoidan, a sulfated polysaccharide extracted from brown algae, possesses potent anti-oxidative and anti-inflammatory effects. Considering TBI happens frequently in adults, especially in aged individuals, we herein sought to define the protective effects of low-molecular-weight fucoidan (LMWF) in the aged mice. 16- to 18-month-old mice administered with LMWF (1-50 mg/kg) or vehicle were subjected to TBI using a controlled cortical impact (CCI) model. LMWF at the doses of 10 and 50 mg/kg significantly reduced both cortical and hippocampal lesion volume. This protection was associated with reduced neuronal apoptosis, as evidenced by TUNEL staining. Importantly, LMWF was effective even when administered up to 4 h after TBI. Treatment with LMWF improved long-term neurobehavioral outcomes, including sensorimotor function, and hippocampus-associated spatial learning and memory. In addition, LMWF significantly suppressed protein carbonyl, lipid peroxidation, reactive oxygen species (ROS) generation, as well as mitochondrial dysfunction, which was evidenced by mitochondrial cytochrome c release and collapse of mitochondrial membrane potential (MMP). To evaluate the underlying molecular mechanisms, the expression of sirtuin 3 (Sirt3) was detected by RT-PCR and Western blot. The results showed that TBI significantly increased the expression of Sirt3, which was further elevated by LMWF treatment. Knockdown of Sirt3 using intracerebroventricular injection of small interfering RNA (siRNA) partially prevented the therapeutic effects of LMWF. Collectively, these findings demonstrated that LMWF exerts neuroprotection against TBI in the aged brain, which may be associated with the attenuation of mitochondrial dysfunction through Sirt3 activation.

  7. Low-molecular-weight model study of peroxide cross-linking of ethylene-propylene-diene rubber using gas chromatography and mass spectrometry II. Addition and combination reactions.

    Science.gov (United States)

    Peters, R; van Duin, M; Tonoli, D; Kwakkenbos, G; Mengerink, Y; van Benthem, R A T M; de Koster, C G; Schoenmakers, P J; van der Wal, Sj

    2008-08-08

    The dicumyl-peroxide-initiated addition and combination reactions of mixtures of alkanes (n-octane, n-decane) and alkenes [5,6-dihydrodicyclopentadiene (DCPDH), 5-ethylidene-2-norbornane (ENBH) and 5-vinylidene-2-norbornane (VNBH)] were studied to mimic the peroxide cross-linking reactions of terpolymerised ethylene, propylene and a diene monomer (EPDM). The reaction products of the mixtures were separated by both gas chromatography (GC) and comprehensive two-dimensional gas chromatography (GCxGC). The separated compounds were identified from their mass spectra and their GC and GCxGC elution pattern. Quantification of the various alkyl/alkyl, alkyl/allyl and allyl/allyl combination products shows that allylic-radicals comprise approximately 60% of the substrate radicals formed. The total concentration of the products formed by combination is found to be independent of the concentration and the type of alkene. The total concentration of the products formed by addition to the alkene increases with increasing concentration of alkene. In addition, the total concentration of the formed addition products depends strongly on the type of the alkene used, viz. VNBH>ENBH approximately DCPDH, which is a consequence of differences in steric hindrance of the unsaturation. The peroxide curing efficiency, defined as the number of moles of cross-linked products formed per mol of peroxide, is 173% using 9% (w/w) 5-vinylidene-2-norbornane (VNBH). This indicates that the addition reaction is recurrent. All these findings are consistent with experimental studies on peroxide curing of EPDM rubber. In addition, the present results provide more-detailed structural information, increasing the understanding of the mechanism of peroxide curing of EPDM. The described approach to use low-molecular-weight model compounds followed by GC-mass spectrometry (MS) and GCxGC-MS analysis is proven to be a very powerful tool to study the cross-linking of EPDM.

  8. Biochemical and Thermodynamic Characterization of a Novel, Low Molecular Weight Xylanase from Bacillus Methylotrophicus CSB40 Isolated from Traditional Korean Food.

    Science.gov (United States)

    Panthi, Sandesh; Choi, Yoon Seok; Choi, Yun Hee; Kim, MiRi; Yoo, Jin Cheol

    2016-04-01

    A low molecular weight xylanase from Bacillus strain CSB40, isolated from traditional Korean food and produced in beechwood xylan, was biochemically and thermodynamically characterized. It was purified 8.12-fold with a 15.88 % yield using DEAE sepharose fast flow, and it was determined to have a mass of ∼27 kDa via sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and xylan zymography. The purified xylanase was optimally active at 50 °C and pH 6 and stable over a wide range of pH (4.5-12.5). The N-terminal amino acid sequence of xylanase was GIQQGDDGKL. The activation energy for beechwood xylan hydrolysis was 29.39 kJmol(-1) with k cat value of 927.582 × 10(2) s(-1). K m and V max were 0.080 mg/ml and 794.63 mmol min(-1) mg(-1). The analysis of other thermodynamic parameters like ∆H, ∆G, ∆S, Q10, ∆GE-S, and ∆GE-T also supported the spontaneous formation of products, greater hydrolytic efficiency, and feasibility of enzymatic reaction, which also ratifies the novelty of this xylanase. The enzyme was strongly activated by Zn(2+) and inhibited by Cu(2+). The principal hydrolyzed end-products of this xylanase are xylobiose, xylotriose, and xylotetrose, which can be used in the pharmaceutical industry and as prebiotic in food.

  9. Low molecular weight poly (2-dimethylamino ethylmethacrylate) polymers with controlled positioned fluorescent labeling: Synthesis, characterization and in vitro interaction with human endothelial cells.

    Science.gov (United States)

    Flebus, Luca; Lombart, François; Sevrin, Chantal; Defraigne, Jean-Olivier; Peters, Pierre; Parhamifar, Ladan; Molin, Daniel G M; Grandfils, Christian

    2015-01-15

    Poly (2-dimethylamino ethylmethacrylate) (PDMAEMA) is an attractive non-degradable polymer studied as nonviral vector for gene delivery but it can be also adopted for delivery of other biopharmaceutical drugs. As a parenteral carrier, the PDMAEMA free form (FF) might interact with tissues and cells. Few data are available on its selective internalization and efflux from cells, while the majority of studies published have followed the distribution of DNA complexed with PDMAEMA. In order to address polycation safety, the first aim was to synthesize by atom transfer radical polymerisation (ATRP) fluorescent labeled PDMAEMA of low molecular weight (Mw) (below 15 kDa), controlling the position and density of fluorescein. The second goal was to analyze the possible difference in uptake and subcellular distribution of this labeled FF polycation between human umbilical vein endothelial cells (HUVEC) and hCMEC/D3 cells. These two cell lines have been chosen in order to detect selectivity towards the blood-brain barrier (BBB). In both cases, polycation was detected along the plasma membrane followed by progressive migration to the peri-nuclear region, where it overlapped with lysosomal structures. The analysis by fluorescence-activated cell sorting (FACS) of the PDMAEMA uptake by hCMEC/D3 cells showed a significant (p<0.05) inhibition (40%) in presence of 2-dexoxy-D-glucose inhibitor, a result supporting an energy-dependence mechanism(s). Cytotoxicity study showed that low Mw PDMAEMA (10 kDa) lead to a minor cytotoxicity compared to the higher ones. As main conclusion this study highlights the similitude in cell trafficking of FF PDMAEMA and data previously reported for PDMAEMA/DNA complexes. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Contributions of low molecular weight carboxylic acids to aerosols and wet deposition in a natural subtropical broad-leaved forest environment

    Science.gov (United States)

    Tsai, Ying I.; Kuo, Su-Ching

    2013-12-01

    The carboxylic acid component of autumn aerosol and wet deposition (fog water and rainwater) in a broad-leaved forest in central Taiwan was investigated. High levels of low molecular weight carboxylic acids (LMWCAs) were noted in all deposition types. Acetic acid, oxalic acid and formic acid were the most prevalent carboxylic acids, together accounting for 72.2% (fog water), 86.7% (rain water), 77.2% (PM2.5) and 88.3% (PM2.5-10) of total carboxylic acid. The forest fog water contained 2453.9 ± 1030.5 ng mL-1 of carboxylic acid, 2.71 times more than was contained in forest rainwater. In PM, most carboxylic acid existed in the fine PM2.5 aerosol (576.6 ± 254.1 ng m-3 or 6.28 times more than was contained in PM2.5-10. Most carboxylic acids in PM had higher concentrations during the day. Pyruvic acid concentration was higher during the night (2.97 times), however, owing to its rapid photodegradation during the day. Citric acid accounted for 9.1% of the total carboxylic acid in fog water compared with just 1.8% in rainwater, confirming its origin from emissions from leaves. Raman spectroscopy was used to observe the photochemical conversion of citric acid into intermediate products and this observation confirmed that the carboxylic acids identified in the forest dry and wet depositions originated directly from biological emissions in the forest environment.

  11. Low Molecular Weight Fraction of Commercial Human Serum Albumin Induces Morphologic and Transcriptional Changes of Bone Marrow-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Bar-Or, David; Thomas, Gregory W; Rael, Leonard T; Gersch, Elizabeth D; Rubinstein, Pablo; Brody, Edward

    2015-08-01

    Osteoarthritis (OA) is the most common chronic disease of the joint; however, the therapeutic options for severe OA are limited. The low molecular weight fraction of commercial 5% human serum albumin (LMWF5A) has been shown to have anti-inflammatory properties that are mediated, in part, by a diketopiperazine that is present in the albumin preparation and that was demonstrated to be safe and effective in reducing pain and improving function when administered intra-articularly in a phase III clinical trial. In the present study, bone marrow-derived mesenchymal stem cells (BMMSCs) exposed to LMWF5A exhibited an elongated phenotype with diffuse intracellular F-actin, pronounced migratory leading edges, and filopodia-like projections. In addition, LMWF5A promoted chondrogenic condensation in "micromass" culture, concurrent with the upregulation of collagen 2α1 mRNA. Furthermore, the transcription of the CXCR4-CXCL12 axis was significantly regulated in a manner conducive to migration and homing. Several transcription factors involved in stem cell differentiation were also found to bind oligonucleotide response element probes following exposure to LMWF5A. Finally, a rapid increase in PRAS40 phosphorylation was observed following treatment, potentially resulting in the activation mTORC1. Proteomic analysis of synovial fluid taken from a preliminary set of patients indicated that at 12 weeks following administration of LMWF5A, a microenvironment exists in the knee conducive to stem cell infiltration, self-renewal, and differentiation, in addition to indications of remodeling with a reduction in inflammation. Taken together, these findings imply that LMWF5A treatment may prime stem cells for both mobilization and chondrogenic differentiation, potentially explaining some of the beneficial effects achieved in clinical trials. ©AlphaMed Press.

  12. Low molecular weight organic acids in aerosol particles from Rondônia, Brazil, during the biomass-burning, transition and wet periods

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    A. H. Falkovich

    2005-01-01

    Full Text Available Particles from biomass burning and regional haze were sampled in Rondônia, Brazil, during dry, transition and wet periods from September to November 2002, as part of the LBA-SMOCC (Large-Scale Biosphere-Atmosphere Experiment in Amazonia – Smoke, Aerosols, Clouds, Rainfall, and Climate field campaign. Water soluble organic and inorganic compounds in bulk (High Volume and Stacked Filter Unit sampler and size-resolved (Micro Orifice Uniform Deposit Impactor – MOUDI smoke samples were determined by ion chromatography. It was found that low molecular weight polar organic acids account for a significant fraction of the water soluble organic carbon (WSOC in biomass burning aerosols (C2-C6 dicarboxylic acids reached up to 3.7% and one-ring aromatic acids reached up to 2% of fine fraction WSOC during burning period. Short dicarboxylic (C2-C6 acids are dominated by oxalic acid followed by malonic and succinic acids. The largest ionic species is ammonium sulfate (60–70% of ionic mass. It was found that most of the ionic mass is concentrated in submicrometer-sized particles. Based on the size distribution and correlations with K+, a known biomass burning tracer, it is suggested that many of the organic acids are directly emitted by vegetation fires. Concentrations of dicarboxylic acids in the front and back filters of high volume sampler were determined. Based on these measurements, it was concluded that in the neutral or slightly basic smoke particles typical of this region, dicarboxylic acids are mostly confined to the particulate phase. Finally, it is shown that the distribution of water soluble species shifts to larger aerosols sizes as the aerosol population ages and mixes with other aerosol types in the atmosphere.

  13. Low Molecular Weight Heparin Inhibits Plasma Thrombin Generation via Direct Targeting of Factor IXa: Contribution of the Serpin-independent Mechanism

    Science.gov (United States)

    Buyue, Yang; Misenheimer, Tina M.; Sheehan, John P.

    2012-01-01

    Background While heparin possesses multiple mechanisms of action, enhanced factor Xa inhibition by antithrombin is accepted as the predominant therapeutic mechanism. The contribution of factor IXa inhibition to heparin activity in human plasma remains incompletely defined. Objectives To determine the relevance of factor IXa as a therapeutic target for heparins, particularly serpin-independent inhibition of intrinsic tenase (factor IXa-factor VIIIa) activity. Patient/Methods Thrombin generation was detected by fluorogenic substrate cleavage. Inhibitory potency (EC50) of low molecular weight heparin (LMWH), super-sulfated LMWH (ssLMWH), Fondaparinux, and unfractionated heparin (UFH) was determined by plotting concentration versus relative velocity index (ratio +/− heparin). Inhibition was compared under factor IX-dependent and independent conditions (0.2 or 4 pM TF, respectively) in normal plasma, and in mock- or antithrombin/factor IX-depleted plasma supplemented with recombinant factor IX. Results UFH and Fondaparinux demonstrated similar potency under factor IX-dependent and independent conditions, whereas LMWH (2.9-fold) and ssLMWH (5.1-fold) demonstrated increased potency with limiting TF. UFH (62-fold) and Fondaparinux (42-fold) demonstrated markedly increased EC50 values in antithrombin-depleted plasma, whereas LMWH (9.4-fold) and ssLMWH (2-fold) were less affected, with an EC50 within the therapeutic range for LMWH. The molecular target for LMWH/ssLMWH was confirmed by supplementing factor IX/antithrombin-depleted plasma with 90 nM recombinant factor IX possessing mutations in the heparin-binding exosite. Mutated factor IX demonstrated resistance to inhibition of thrombin generation by LMWH and ssLMWH that paralleled the effect of these mutations on intrinsic tenase inhibition. Conclusions Therapeutic LMWH concentrations inhibit plasma thrombin generation via antithrombin-independent interaction with the factor IXa heparin-binding exosite. PMID:22905983

  14. Evolution of Prophylaxis Protocols for Venous Thromboembolism in Neurosurgery: Results from a Prospective Comparative Study on Low-Molecular-Weight Heparin, Elastic Stockings, and Intermittent Pneumatic Compression Devices.

    Science.gov (United States)

    Chibbaro, Salvatore; Cebula, Helene; Todeschi, Julien; Fricia, Marco; Vigouroux, Doris; Abid, Houssem; Kourbanhoussen, Houssen; Pop, Raoul; Nannavecchia, Beniamino; Gubian, Arthur; Prisco, Lara; Ligarotti, Gianfranco K I; Proust, Francois; Ganau, Mario

    2018-01-01

    The incidence of venous thromboembolism (VT) in neurosurgical practice is astonishingly high, representing a major cause of morbidity and mortality. Prophylaxis strategies include elastic stockings, low-molecular-weight heparin (LMWH), and intermittent pneumatic compression (IPC) devices. To assess the safety and efficacy of 2 different VT prophylaxis protocols implemented in a European neurosurgical center. All patients admitted for neurosurgical intervention between 2012 and 2016 were stratified as low, moderate, and high risk of VT and received a combination of elastic stockings and LMWH. The protocol was modified in 2014 with the inclusion of perioperative IPC devices for all patients and only in the high-risk group also postoperatively. At time of post-hoc analysis, data obtained from patients included in this study before 2014 (Protocol A, 3169 patients) were compared with those obtained after the introduction of IPC (Protocol B, 3818 patients). Among patients assigned to protocol A, 73 (2.3%) developed deep-vein thrombosis (DVT) and 28 (0.9%) developed pulmonary embolism (PE), 9 of which were fatal (0.3%). Among patients assigned to protocol B, 32 developed DVT (0.8%) and 7 (0.18%) developed PE, with 2 eventually resulting in the death of the patient. A post-hoc analysis confirmed that the use of preoperative LMWH was not associated with a statistically significant greater risk of postoperative bleeding. This study, despite its limitations of the nonrandomized design, seems to suggest that perioperative IPC devices are a non-negligible support in the prophylaxis of clinically symptomatic DVT and PE. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Low-Molecular Weight Polyethylenimine Modified with Pluronic 123 and RGD- or Chimeric RGD-NLS Peptide: Characteristics and Transfection Efficacy of Their Complexes with Plasmid DNA

    Directory of Open Access Journals (Sweden)

    Jing Hu

    2016-05-01

    Full Text Available To solve the problem of transfection efficiency vs. cytotoxicity and tumor-targeting ability when polyethylenimine (PEI was used as a nonviral gene delivery vector, new degradable PEI polymers were synthesized via cross-linking low-molecular-weight PEI with Pluronic P123 and then further coupled with a targeting peptide R4 (RGD and a bifunctional R11 (RGD-NLS, which were termed as P123-PEI-R4 and P123-PEI-R11, respectively. Agarose gel electrophoresis showed that both P123-PEI-R4 and P123-PEI-R11 efficaciously condense plasmid DNA at a polymer-to-pDNA w/w ratio of 3.0 and 0.4, respectively. The polyplexes were stable in the presence of serum and could protect plasmid DNA against DNaseI. They had uniform spherical nanoparticles with appropriate sizes around 100–280 nm and zeta-potentials about +40 mV. Furthermore, in vitro experiments showed that these polyplexes had lower cytotoxicity at any concentration compared with PEI 25 kDa, thus giving promise to high transfection efficiency as compared with another P123-PEI derivate conjugated with trifunctional peptide RGD-TAT-NLS (P123-PEI-R18. More importantly, compared with the other polymers, P123-PEI-R11 showed the highest transfection efficiency with relatively lower cytotoxicity at any concentration, indicating that the new synthetic polymer P123-PEI-R11 could be used as a safe and efficient gene deliver vector.

  16. The Impact of Inherited Thrombophilia Types and Low Molecular Weight Heparin Treatment on Pregnancy Complications in Women with Previous Adverse Outcome.

    Science.gov (United States)

    Aracic, Nada; Roje, Damir; Jakus, Ivana Alujevic; Bakotin, Marinela; Stefanovic, Vedran

    2016-09-01

    To assess the distribution of births and spontaneous abortions, first-trimester abortion (FTA) and mid-trimester abortion (MTA), in untreated (n=128) and low molecular weight heparin (LMWH) treated pregnancies (n=50) of the same women with inherited thrombophilias and adverse pregnancy outcome (APO) in previous pregnancies. We particularly investigated the impact of LMWH on reducing the pregnancy complications in two thrombophilia types, "Conventional" and "Novel". 50 women with inherited thrombophilia (26 Conventional and 24 Novel) and APO in previous pregnancies were included in the study. Conventional group included factor V Leiden (FVL), prothrombin G20210A (PT) mutations and antithrombin (AT), protein S (PS), and protein C (PC) deficiency, while the Novel group included methylentetrahydrofolate-reductase (MTHFR), plasminogen activator inhibitor-1 (PAI-1), and angiotensin converting enzyme (ACE) polymorphism. APO was defined as one of the following: preterm birth (PTB), fetal growth restriction (FGR), preeclampsia (PE), intrauterine fetal death (IUFD), placental abruption (PA) and deep venous thrombosis (DVT). There was no difference in distribution of births and spontaneous abortions between Conventional and Novel thrombophilia in untreated pregnancies (χ²=2.7; p=0.100) and LMWH treated pregnancies (χ²=0.442; p=0.506). In untreaed pregnancies thrombophilia type did not have any impact on the frequency of FTA and MTA (χ²=0.14; p=0.711). In birth-ended pregnancies LMWH treatement reduced the incidence of IUFD (p=0.011) in Conventional and FGR, IUFD, and PTB in Novel thrombophilia group. The equal impact of two thrombophilia types on the pregnancy outcomes and a more favorable effect of LMWH therapy on pregnancy complications in Novel thrombophilia group point the need for Novel thrombophilias screening and the future studies on this issue should be recommended.

  17. Molecular Weight-Dependent Immunostimulative Activity of Low Molecular Weight Chitosan via Regulating NF-κB and AP-1 Signaling Pathways in RAW264.7 Macrophages

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    Bin Zheng

    2016-09-01

    Full Text Available Chitosan and its derivatives such as low molecular weight chitosans (LMWCs have been found to possess many important biological properties, such as antioxidant and antitumor effects. In our previous study, LMWCs were found to elicit a strong immunomodulatory response in macrophages dependent on molecular weight. Herein we further investigated the molecular weight-dependent immunostimulative activity of LMWCs and elucidated its mechanism of action on RAW264.7 macrophages. LMWCs (3 kDa and 50 kDa of molecular weight could significantly enhance the mRNA expression levels of COX-2, IL-10 and MCP-1 in a molecular weight and concentration-dependent manner. The results suggested that LMWCs elicited a significant immunomodulatory response, which was dependent on the dose and the molecular weight. Regarding the possible molecular mechanism of action, LMWCs promoted the expression of the genes of key molecules in NF-κB and AP-1 pathways, including IKKβ, TRAF6 and JNK1, and induced the phosphorylation of protein IKBα in RAW264.7 macrophage. Moreover, LMWCs increased nuclear translocation of p65 and activation of activator protein-1 (AP-1, C-Jun and C-Fos in a molecular weight-dependent manner. Taken together, our findings suggested that LMWCs exert immunostimulative activity via activation of NF-κB and AP-1 pathways in RAW264.7 macrophages in a molecular weight-dependent manner and that 3 kDa LMWC shows great potential as a novel agent for the treatment of immune suppression diseases and in future vaccines.

  18. Characterization of a Chitosanase from Jelly Fig (Ficus awkeotsang Makino Latex and Its Application in the Production of Water-Soluble Low Molecular Weight Chitosans.

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    Chen-Tien Chang

    Full Text Available A chitosanase was purified from jelly fig latex by ammonium sulfate fractionation (50-80% saturation and three successive column chromatography steps. The purified enzyme was almost homogeneous, as determined by SDS-polyacrylamide gel electrophoresis (SDS-PAGE and gel activity staining. The molecular mass of the enzyme was 20.5 kDa. The isoelectric point (pI was <3.5, as estimated by isoelectric focusing electrophoresis on PhastGel IEF 3-9. Using chitosan as the substrate, the optimal pH for the enzyme reaction was 4.5; the kinetic parameters Km and Vmax were 0.089 mg mL-1 and 0.69 μmol min-1 mg-1, respectively. The enzyme showed activity toward chitosan polymers which exhibited various degrees of deacetylation (21-94%. The enzyme hydrolyzed 70-84% deacetylated chitosan polymers most effectively. Substrate specificity analysis indicated that the enzyme catalyzed the hydrolysis of chitin and chitosan polymers and their derivatives. The products of the hydrolysis of chitosan polymer derivatives, ethylene glycol (EG chitosan, carboxymethyl (CM chitosan and aminoethyl (AE chitosan, were low molecular weight chitosans (LMWCs; these products were referred to as EG-LMWC, CM-LMWC and AE-LMWC, respectively. The average molecular weights of EG-LMWC, CM-LMWC and AE-LMWC were 11.2, 11.2 and 8.89 kDa, respectively. All of the LMWC products exhibited free radical scavenging activities toward ABTS•+, superoxide and peroxyl radicals.

  19. Molecular weight dependent glucose lowering effect of low molecular weight Chitosan Oligosaccharide (GO2KA1) on postprandial blood glucose level in SD rats model.

    Science.gov (United States)

    Jo, Sung-Hoon; Ha, Kyoung-Soo; Moon, Kyoung-Sik; Kim, Jong-Gwan; Oh, Chen-Gum; Kim, Young-Cheul; Apostolidis, Emmanouil; Kwon, Young-In

    2013-07-09

    This research investigated the effect of enzymatically digested low molecular weight (MW) chitosan oligosaccharide on type 2 diabetes prevention. Three different chitosan oligosaccharide samples with varying MW were evaluated in vitro for inhibition of rat small intestinal α-glucosidase and porcine pancreatic α-amylase (GO2KA1; 10,000 Da). The in vitro results showed that all tested samples had similar rat α-glucosidase inhibitory and porcine α-amylase inhibitory activity. Based on these observations, we decided to further investigate the effect of all three samples at a dose of 0.1 g/kg, on reducing postprandial blood glucose levels in Sprague-Dawley (SD) rat model after sucrose loading test. In the animal trial, all tested samples had postprandial blood glucose reduction effect, when compared to control, however GO2KA1 supplementation had the strongest effect. The glucose peak (Cmax) for GO2KA1 and control was 152 mg/dL and 193 mg/dL, respectively. The area under the blood glucose-time curve (AUC) for GO2KA1 and control was 262 h mg/dL and 305 h mg/dL, respectively. Furthermore, the time of peak plasma concentration of blood glucose (Tmax) for GO2KA1 was significantly delayed (0.9 h) compared to control (0.5 h). These results suggest that GO2KA1 could have a beneficial effect for blood glucose management relevant to diabetes prevention in normal and pre-diabetic individuals. The suggested mechanism of action is via inhibition of the carbohydrate hydrolysis enzyme α-glucosidase and since GO2KA1 (MW blood stream, relevant to blood glucose management.

  20. Molecular Weight Dependent Glucose Lowering Effect of Low Molecular Weight Chitosan Oligosaccharide (GO2KA1 on Postprandial Blood Glucose Level in SD Rats Model

    Directory of Open Access Journals (Sweden)

    Emmanouil Apostolidis

    2013-07-01

    Full Text Available This research investigated the effect of enzymatically digested low molecular weight (MW chitosan oligosaccharide on type 2 diabetes prevention. Three different chitosan oligosaccharide samples with varying MW were evaluated in vitro for inhibition of rat small intestinal α-glucosidase and porcine pancreatic α-amylase (GO2KA1; 10,000 Da. The in vitro results showed that all tested samples had similar rat α-glucosidase inhibitory and porcine α-amylase inhibitory activity. Based on these observations, we decided to further investigate the effect of all three samples at a dose of 0.1 g/kg, on reducing postprandial blood glucose levels in Sprague-Dawley (SD rat model after sucrose loading test. In the animal trial, all tested samples had postprandial blood glucose reduction effect, when compared to control, however GO2KA1 supplementation had the strongest effect. The glucose peak (Cmax for GO2KA1 and control was 152 mg/dL and 193 mg/dL, respectively. The area under the blood glucose-time curve (AUC for GO2KA1 and control was 262 h mg/dL and 305 h mg/dL, respectively. Furthermore, the time of peak plasma concentration of blood glucose (Tmax for GO2KA1 was significantly delayed (0.9 h compared to control (0.5 h. These results suggest that GO2KA1 could have a beneficial effect for blood glucose management relevant to diabetes prevention in normal and pre-diabetic individuals. The suggested mechanism of action is via inhibition of the carbohydrate hydrolysis enzyme α-glucosidase and since GO2KA1 (MW < 1000 Da had higher in vivo effect, we hypothesize that it is more readily absorbed and might exert further biological effect once it is absorbed in the blood stream, relevant to blood glucose management.

  1. The Impact of the Low Molecular Weight Heparin Tinzaparin on the Sensitization of Cisplatin-Resistant Ovarian Cancers-Preclinical In Vivo Evaluation in Xenograft Tumor Models.

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    Mueller, Thomas; Pfankuchen, Daniel Bastian; Wantoch von Rekowski, Kathleen; Schlesinger, Martin; Reipsch, Franziska; Bendas, Gerd

    2017-05-03

    Resistance formation of tumors against chemotherapeutics is the major obstacle in clinical cancer therapy. Although low molecular weight heparin (LMWH) is an important component in oncology referring to guideline-based antithrombotic prophylaxis of tumor patients, a potential interference of LMWH with chemoresistance is unknown. We have recently shown that LMWH reverses the cisplatin resistance of A2780cis human ovarian cancer cells in vitro. Here we address the question whether this LMWH effect is also valid under in vivo conditions. Therefore, we established tumor xenografts of A2780 and cisplatin resistant A2780cis cells in nude mice and investigated the impact of daily tinzaparin applications (10 mg/kg BW) on anti-tumor activity of cisplatin (6 mg/kg BW, weekly) considering the tumor growth kinetics. Intratumoral platinum accumulation was detected by GF-AAS. Xenografts of A2780 and A2780cis cells strongly differed in cisplatin sensitivity. As an overall consideration, tinzaparin co-treatment affected the response to cisplatin of A2780cis, but not A2780 tumors in the later experimental time range. A subgroup analysis confirmed that initially smaller A2780cis tumors benefit from tinzaparin, but also small A2780 xenografts. Tinzaparin did not affect cisplatin accumulation in A2780cis xenografts, but strongly increased the platinum content in A2780, obviously related to morphological differences in both xenografts. Although we cannot directly confirm a return of A2780cis cisplatin resistance by tinzaparin, as shown in vitro, the present findings give reason to discuss heparin effects on cytostatic drug efficiency for small tumors and warrants further investigation.

  2. Characterization of a Chitosanase from Jelly Fig (Ficus awkeotsang Makino) Latex and Its Application in the Production of Water-Soluble Low Molecular Weight Chitosans

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    Chang, Chen-Tien; Lin, Yen-Lu; Lu, Shu-Wei; Huang, Chun-Wei; Wang, Yu-Ting; Chung, Yun-Chin

    2016-01-01

    A chitosanase was purified from jelly fig latex by ammonium sulfate fractionation (50–80% saturation) and three successive column chromatography steps. The purified enzyme was almost homogeneous, as determined by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and gel activity staining. The molecular mass of the enzyme was 20.5 kDa. The isoelectric point (pI) was <3.5, as estimated by isoelectric focusing electrophoresis on PhastGel IEF 3-9. Using chitosan as the substrate, the optimal pH for the enzyme reaction was 4.5; the kinetic parameters Km and Vmax were 0.089 mg mL-1 and 0.69 μmol min-1 mg-1, respectively. The enzyme showed activity toward chitosan polymers which exhibited various degrees of deacetylation (21–94%). The enzyme hydrolyzed 70–84% deacetylated chitosan polymers most effectively. Substrate specificity analysis indicated that the enzyme catalyzed the hydrolysis of chitin and chitosan polymers and their derivatives. The products of the hydrolysis of chitosan polymer derivatives, ethylene glycol (EG) chitosan, carboxymethyl (CM) chitosan and aminoethyl (AE) chitosan, were low molecular weight chitosans (LMWCs); these products were referred to as EG-LMWC, CM-LMWC and AE-LMWC, respectively. The average molecular weights of EG-LMWC, CM-LMWC and AE-LMWC were 11.2, 11.2 and 8.89 kDa, respectively. All of the LMWC products exhibited free radical scavenging activities toward ABTS•+, superoxide and peroxyl radicals. PMID:26938062

  3. Low-molecular-weight color pI markers to monitor on-line the peptide focusing process in OFFGEL fractionation.

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    Michelland, Sylvie; Bourgoin-Voillard, Sandrine; Cunin, Valérie; Tollance, Axel; Bertolino, Pascal; Slais, Karel; Seve, Michel

    2017-08-01

    High-throughput mass spectrometry-based proteomic analysis requires peptide fractionation to simplify complex biological samples and increase proteome coverage. OFFGEL fractionation technology became a common method to separate peptides or proteins using isoelectric focusing in an immobilized pH gradient. However, the OFFGEL focusing process may be further optimized and controlled in terms of separation time and pI resolution. Here we evaluated OFFGEL technology to separate peptides from different samples in the presence of low-molecular-weight (LMW) color pI markers to visualize the focusing process. LMW color pI markers covering a large pH range were added to the peptide mixture before OFFGEL fractionation using a 24-wells device encompassing the pH range 3-10. We also explored the impact of LMW color pI markers on peptide fractionation labeled previously for iTRAQ. Then, fractionated peptides were separated by RP_HPLC prior to MS analysis using MALDI-TOF/TOF mass spectrometry in MS and MS/MS modes. Here we report the performance of the peptide focusing process in the presence of LMW color pI markers as on-line trackers during the OFFGEL process and the possibility to use them as pI controls for peptide focusing. This method improves the workflow for peptide fractionation in a bottom-up proteomic approach with or without iTRAQ labeling. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Application of basic and composite thrombelastography parameters in monitoring of the antithrombotic effect of the low molecular weight heparin dalteparin: an in vivo study

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    Frandsen Niels J

    2009-11-01

    Full Text Available Abstract Background Low molecular weight heparin (LMWH is in vast usage for treatment of thromboembolic diseases such as deep venous thrombosis and acute coronary syndromes. There are certain clinical situations where a quick point of care testing of the effect of LMWH would be useful. At this point there are no point of care devices available in the market for monitoring the effect of LMWH. Thrombelastography (TEG evaluates the viscoelastic properties of blood during coagulation. The clinical application of TEG in monitoring LMWH treatment is not yet well defined. The purpose of this in vivo study was to systematically evaluate the most suitable TEG parameters for evaluation of the antithrombotic effect of LMWH. We furthermore evaluated for the first time the usefulness of the composite TEG parameter the Thrombodynamic Ratio (TDR in monitoring LMWH treatment. Methods Healthy male volunteers (n = 7 were injected subcutaneously with the LMWH dalteparin 120 IU/kg. TEG parameters and antifactor Xa levels were measures at baseline, 2, 4, 5 and 24 hours after the injection. Correlation between TEG parameters and antiXa were calculated. The sensitivity and specificity of the TEG parameters for plasma levels of antiXa in the therapeutic range of 0.5 - 1.0 U/ml were calculated. Results All basic TEG parameters correlated significantly with antiXa levels. Among the basic parameters, the TEG reaction time R had the best correlation with antiXa levels with the most favorable combination of sensitivity and specificity for the therapeutic range of antiXa levels (r = 0.82, p Conclusion The TEG reaction time R and TDR are the most suitable TEG parameters for evaluation of the antithrombotic effect of dalteparin with a highly significant correlation with antiXa levels in healthy male volunteers. Measures for uniform clinical use of these parameters are proposed. Larger clinical trials are needed to correlate R and TDR with clinical outcomes.

  5. Enhanced levels of atmospheric low-molecular weight monocarboxylic acids in gas and particulates over Mt. Tai, North China, during field burning of agricultural wastes

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    Mochizuki, Tomoki; Kawamura, Kimitaka; Nakamura, Shinnosuke; Kanaya, Yugo; Wang, Zifa

    2017-12-01

    To understand the source and atmospheric behaviour of low molecular weight monocarboxylic acids (monoacids), gaseous (G) and particulate (P) organic acids were collected at the summit of Mt. Tai in the North China Plain (NCP) during field burning of agricultural waste (wheat straw). Particulate organic acids were collected with neutral quartz filter whereas gaseous organic acids were collected with KOH-impregnated quartz filter. Normal (C1-C10), branched (iC4-iC6), hydroxy (lactic and glycolic), and aromatic (benzoic) monoacids were determined with a capillary gas chromatography employing p-bromophenacyl esters. We found acetic acid as the most abundant gas-phase species whereas formic acid is the dominant particle-phase species. Concentrations of formic (G/P 1 570/1 410 ng m-3) and acetic (3 960/1 120 ng m-3) acids significantly increased during the enhanced field burning of agricultural wastes. Concentrations of formic and acetic acids in daytime were found to increase in both G and P phases with those of K+, a field-burning tracer (r = 0.32-0.64). Primary emission and secondary formation of acetic acid is linked with field burning of agricultural wastes. In addition, we found that particle-phase fractions (Fp = P/(G + P)) of formic (0.50) and acetic (0.31) acids are significantly high, indicating that semi-volatile organic acids largely exist as particles. Field burning of agricultural wastes may play an important role in the formation of particulate monoacids in the NCP. High levels (917 ng m-3) of particle-phase lactic acid, which is characteristic of microorganisms, suggest that microbial activity associated with terrestrial ecosystem significantly contributes to the formation of organic aerosols.

  6. Reduced graphene oxide nanosheets coated with an anti-angiogenic anticancer low-molecular-weight heparin derivative for delivery of anticancer drugs.

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    Shim, Gayong; Kim, Ji-Young; Han, Jeonghoon; Chung, Seung Woo; Lee, Soondong; Byun, Youngro; Oh, Yu-Kyoung

    2014-09-10

    Here, we report reduced graphene oxide (rGO) nanosheets coated with an anti-angiogenic anticancer taurocholate derivative of low-molecular-weight heparin (LHT7) as a tumor-targeting nanodelivery platform for anticancer drugs. Surface coating of LHT7 onto rGO was confirmed using fluorescein isothiocyanate-labeled LHT7, monitored as fluorescence quenching due to associated rGO. Unlike plain rGO, LHT7-coated rGO (LHT-rGO) nanosheets maintained a stable dispersion under physiological conditions for at least 24h. Moreover, LHT-rGO provided greater loading capacity for doxorubicin (Dox) compared with uncoated rGO nanosheets. Following intravenous administration into KB tumor-bearing mice, in vivo tumor accumulation of LHT-rGO/Dox was 7-fold higher than that of rGO/Dox 24h post dosing. In tumor tissues, LHT-rGO/Dox was shown to localize not to the tumor vasculature, but rather to tumor cells. Intravenously administered LHT-rGO/Dox showed the greatest anti-tumor effect in KB-bearing mice, reducing tumor volume by 92.5%±3.1% compared to the untreated group 25days after tumor inoculation. TUNEL assays revealed that the population of apoptotic cells was highest in the group treated with LHT-rGO/Dox. Taken together, our results demonstrate that LHT-rGO nanosheets confer improved dispersion stability, tumor distribution and in vivo antitumor effects, and may be further developed as a potential active nanoplatform of various anticancer drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Spatially segregated transcription and translation in cells of the endomembrane-containing bacterium Gemmata obscuriglobus.

    Science.gov (United States)

    Gottshall, Ekaterina Y; Seebart, Corrine; Gatlin, Jesse C; Ward, Naomi L

    2014-07-29

    The dogma of coupled transcription and translation in bacteria has been challenged by recent reports of spatial segregation of these processes within the relatively simple cellular organization of the model organisms Escherichia coli and Bacillus subtilis. The bacterial species Gemmata obscuriglobus possesses an extensive endomembrane system. The membranes generate a very convoluted intracellular architecture in which some of the cell's ribosomes appear to have less direct access to the cell's nucleoid(s) than others. This observation prompted us to test the hypothesis that a substantial proportion of G. obscuriglobus translation may be spatially segregated from transcription. Using immunofluorescence and immunoelectron microscopy, we showed that translating ribosomes are localized throughout the cell, with a quantitatively greater proportion found in regions distal to nucleoid(s). Our results extend information about the phylogenetic and morphological diversity of bacteria in which the spatial organization of transcription and translation has been studied. These findings also suggest that endomembranes may provide an obstacle to colocated transcription and translation, a role for endomembranes that has not been reported previously for a prokaryotic organism. Our studies of G. obscuriglobus may provide a useful background for consideration of the evolutionary development of eukaryotic cellular complexity and how it led to decoupled processes of gene expression in eukaryotes.

  8. Superbasic alkyl-substituted bisphosphazene proton sponges: a new class of deprotonating matrices for negative ion matrix-assisted ionization/laser desorption mass spectrometry of low molecular weight hardly ionizable analytes.

    Science.gov (United States)

    Calvano, C D; Cataldi, T R I; Kögel, J F; Monopoli, A; Palmisano, F; Sundermeyer, J

    2016-07-30

    Here hardly ionizable and low molecular weight compounds are detected in negative ion mode by using novel superbasic proton sponges based on 1,8-bisphosphazenylnaphthalene (PN) as MALDI matrices. Among the selected proton sponges, 1,8-bis(trispyrrolidinophosphazenyl)naphthalene (TPPN) has shown the best behaviour as matrix since it allows the direct detection of intact cholesterol without derivatization also in real challenging samples. Very weakly acidic compounds such as sterols, steroids, fatty alcohols and saccharides were detected in reflectron negative ion mode by a MALDI TOF/TOF system equipped with a neodymium-doped yttrium lithium fluoride (Nd:YLF) laser (345 nm) with typical mass accuracy of 10 ppm. MS/MS experiments were performed by using ambient air as the collision gas. Contrary to traditional MALDI matrices, superbasic proton sponges allowed the easy deprotonation of an alcohol functional group without a previous chemical derivatization step. Experimental evidence indicates that analyte deprotonation is achieved in the condensed phase, i.e. PN superbasic proton sponges operate according to a recently proposed model named matrix assisted ionization/laser desorption (MAILD). A detection limit of 3 pmol/spot of cholesterol (model compound) with a signal-to-noise ratio ≥ 10 was typically obtained. For the first time, the usefulness of novel superbasic proton sponges is demonstrated for MALDI detection of hardly ionizable compounds such as sterols, steroids, fatty alcohols and saccharides. The leading candidate TPPN has been successfully applied for negative ion MAILD-MS analysis of cholesterol, fatty acids and phospholipids in egg yolk and brain tissue extracts. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Monitoring low molecular weight heparins at therapeutic levels: dose-responses of, and correlations and differences between aPTT, anti-factor Xa and thrombin generation assays.

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    Owain Thomas

    Full Text Available Low molecular weight heparins (LMWH's are used to prevent and treat thrombosis. Tests for monitoring LMWH's include anti-factor Xa (anti-FXa, activated partial thromboplastin time (aPTT and thrombin generation. Anti-FXa is the current gold standard despite LMWH's varying affinities for FXa and thrombin.To examine the effects of two different LMWH's on the results of 4 different aPTT-tests, anti-FXa activity and thrombin generation and to assess the tests' concordance.Enoxaparin and tinzaparin were added ex-vivo in concentrations of 0.0, 0.5, 1.0 and 1.5 anti-FXa international units (IU/mL, to blood from 10 volunteers. aPTT was measured using two whole blood methods (Free oscillation rheometry (FOR and Hemochron Jr (HCJ and an optical plasma method using two different reagents (ActinFSL and PTT-Automat. Anti-FXa activity was quantified using a chromogenic assay. Thrombin generation (Endogenous Thrombin Potential, ETP was measured on a Ceveron Alpha instrument using the TGA RB and more tissue-factor rich TGA RC reagents.Methods' mean aPTT at 1.0 IU/mL LMWH varied between 54s (SD 11 and 69s (SD 14 for enoxaparin and between 101s (SD 21 and 140s (SD 28 for tinzaparin. ActinFSL gave significantly shorter aPTT results. aPTT and anti-FXa generally correlated well. ETP as measured with the TGA RC reagent but not the TGA RB reagent showed an inverse exponential relationship to the concentration of LMWH. The HCJ-aPTT results had the weakest correlation to anti-FXa and thrombin generation (Rs0.62-0.87, whereas the other aPTT methods had similar correlation coefficients (Rs0.80-0.92.aPTT displays a linear dose-response to LMWH. There is variation between aPTT assays. Tinzaparin increases aPTT and decreases thrombin generation more than enoxaparin at any given level of anti-FXa activity, casting doubt on anti-FXa's present gold standard status. Thrombin generation with tissue factor-rich activator is a promising method for monitoring LMWH's.

  10. Low-Molecular-Weight Iron Chelates May Be an Alternative to Gadolinium-based Contrast Agents for T1-weighted Contrast-enhanced MR Imaging.

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    Boehm-Sturm, Philipp; Haeckel, Akvile; Hauptmann, Ralf; Mueller, Susanne; Kuhl, Christiane K; Schellenberger, Eyk A

    2017-01-07

    Purpose To synthesize two low-molecular-weight iron chelates and compare their T1 contrast effects with those of a commercial gadolinium-based contrast agent for their applicability in dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging. Materials and Methods The animal experiments were approved by the local ethics committee. Two previously described iron (Fe) chelates of pentetic acid (Fe-DTPA) and of trans-cyclohexane diamine tetraacetic acid (Fe-tCDTA) were synthesized with stability constants several orders of magnitude higher than those of gadolinium-based contrast agents. The T1 contrast effects of the two chelates were compared with those of gadopentetate dimeglumine in blood serum phantoms at 1.5 T, 3 T, and 7 T. For in vivo studies, a human breast cancer cell line (MDA-231) was implanted in five mice per group. The dynamic contrast effects of the chelates were compared by performing DCE MR imaging with intravenous application of Fe-DTPA or Fe-tCDTA on day 1 and DCE MR imaging in the same tumors with gadopentetate dimeglumine on day 2. Quantitative DCE maps were generated with software and were compared by means of a one-tailed Pearson correlation test. Results Relaxivities in serum (0.94 T at room temperature) of Fe-tCDTA (r1 = 2.2 mmol(-1) · sec(-1), r2 = 2.5 mmol(-1) · sec(-1)) and Fe-DTPA (r1 = 0.9 mmol(-1) · sec(-1), r2 = 0.9 mmol(-1) · sec(-1)) were approximately twofold and fivefold lower, respectively, compared with those of gadopentetate dimeglumine (r1 = 4.1 mmol(-1) · sec(-1), r2 = 4.8 mmol(-1) · sec(-1)). Used at moderately higher concentrations, however, iron chelates generated similar contrast effects at T1-weighted MR imaging in vitro in serum, in vivo in blood, and for DCE MR imaging of breast cancer xenografts. The volume transfer constant values for Fe-DTPA and Fe-tCDTA in the same tumors correlated well with those observed for gadopentetate dimeglumine (Fe-tCDTA Pearson R, 0.99; P = .0003; Fe-DTPA Pearson R, 0

  11. Safety assessment and pharmacodynamics of a novel ultra low molecular weight heparin (RO-14) in healthy volunteers--a first-time-in-human single ascending dose study.

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    Rico, Salvador; Antonijoan, Rosa Maria; Gich, Ignasi; Borrell, Montserrat; Fontcuberta, Jordi; Monreal, Mayte; Martinez-Gonzalez, Javier; Barbanoj, Manel J

    2011-04-01

    RO-14 is a novel ultra low molecular heparin. The purpose of this study was to evaluate the safety and pharmacodynamic profile of RO-14 in healthy males. We conducted a two-stage, single-center, open-label, randomized study. Two cohorts of 6 volunteers were randomly assigned to 12 single, ascending subcutaneous doses (1750-19950IU of anti-FXa activity) in an alternating crossover fashion. Safety was assessed by spontaneous/elicited adverse events, medical examination and laboratory tests. Anti-FXa activity and anti-FIIa activity were assessed throughout the 24hours after dosing. Dose proportionality and linearity of the anti-FXa activity were evaluated. All doses were well tolerated and there were no bleeding events. At the lowest dose, anti-FXa activity A(max) was 0.16 (±0.02) IU/mL and AUC(0-24) was 1.11 (±0.24) IU*h/mL, At the highest dose anti-FXa activity A(max) was 1.67 (±0.15) IU/mL; AUC(0-24) was 21.48 (±4.46) IU*h/mL and t½ was 8.05h. Mean T(max) (all doses) was 2.86 (±0.39) h. RO-14 showed proportional and linear pharmacodynamics [normalized A(max) among doses (p=0.594) and normalized AUC(0-24) (p=0.092), correlations between A(max-)dose (R(2)=0.89, p<0.001) and AUC(0-24)-dose (R(2)=0.86, p<0.001)]. Anti-FIIa activity was below the detection limit (0.1IU/ml) at all dose levels. No clinically significant changes were observed in the platelet count, APTT, PT, TT, fibrinogen and antithrombin. In this phase I study, RO-14 exhibited a good safety profile, anti-FXa activity for either prophylaxis or treatment of venous thromboembolism, linear pharmacodynamics, a longer elimination half-life than currently marketed low molecular weight heparin and no anti-FIIa activity. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Low molecular weight (C1-C10) monocarboxylic acids, dissolved organic carbon and major inorganic ions in alpine snow pit sequence from a high mountain site, central Japan

    Science.gov (United States)

    Kawamura, Kimitaka; Matsumoto, Kohei; Tachibana, Eri; Aoki, Kazuma

    2012-12-01

    Snowpack samples were collected from a snow pit sequence (6 m in depth) at the Murodo-Daira site near the summit of Mt. Tateyama, central Japan, an outflow region of Asian dusts. The snow samples were analyzed for a homologous series of low molecular weight normal (C1-C10) and branched (iC4-iC6) monocarboxylic acids as well as aromatic (benzoic) and hydroxy (glycolic and lactic) acids, together with major inorganic ions and dissolved organic carbon (DOC). The molecular distributions of organic acids were characterized by a predominance of acetic (range 7.8-76.4 ng g-1-snow, av. 34.8 ng g-1) or formic acid (2.6-48.1 ng g-1, 27.7 ng g-1), followed by propionic acid (0.6-5.2 ng g-1, 2.8 ng g-1). Concentrations of normal organic acids generally decreased with an increase in carbon chain length, although nonanoic acid (C9) showed a maximum in the range of C5-C10. Higher concentrations were found in the snowpack samples containing dust layer. Benzoic acid (0.18-4.1 ng g-1, 1.4 ng g-1) showed positive correlation with nitrate (r = 0.70), sulfate (0.67), Na+ (0.78), Ca2+ (0.86) and Mg+ (0.75), suggesting that this aromatic acid is involved with anthropogenic sources and Asian dusts. Higher concentrations of Ca2+ and SO42- were found in the dusty snow samples. We found a weak positive correlation (r = 0.43) between formic acid and Ca2+, suggesting that gaseous formic acid may react with Asian dusts in the atmosphere during long-range transport. However, acetic acid did not show any positive correlations with major inorganic ions. Hydroxyacids (0.03-5.7 ng g-1, 1.5 ng g-1) were more abundant in the granular and dusty snow. Total monocarboxylic acids (16-130 ng g-1, 74 ng g-1) were found to account for 1-6% of DOC (270-1500 ng g-1, 630 ng g-1) in the snow samples.

  13. Post-Discharge Adherence With Venous Thromboembolism Prophylaxis After Orthopedic Trauma: Results From a Randomized Controlled Trial of Aspirin vs. Low Molecular Weight Heparin.

    Science.gov (United States)

    Haac, Bryce E; Van Besien, Richard; OʼHara, Nathan N; Slobogean, Gerard P; Manson, Theodore T; OʼToole, Robert V; Johal, Herman; Berger, Peter Z; Reahl, George B; Marinos, Dimitrius; Degani, Yasmin; Mascarenhas, Daniel; Connelly, Daniel; Scalea, Thomas M; Stein, Deborah M

    2017-12-14

    Orthopedic trauma patients are often treated with venous thromboembolism (VTE) chemoprophylaxis with aspirin or low molecular weight heparin (LMWH) after discharge from their index admission, but adherence patterns are not known. We hypothesized that overall adherence would be moderate and greater with aspirin compared to LMWH. We conducted a randomized controlled trial of adult trauma patients with an operative extremity fracture or any pelvic/acetabular fracture requiring VTE prophylaxis. Patients were randomized to receive either LMWH 30mg BID or aspirin 81mg BID. Patients prescribed outpatient prophylaxis were contacted between 10 to 21 days after discharge to assess adherence measured by the validated Morisky Medication Adherence Scale (MMAS-8). Adherence scores were compared between the two treatment arms with similar results for intention-to-treat and as-treated analyses. As-treated multivariable logistic regression was performed to determine factors associated with low-medium adherence scores. 150 patients (64 on LMWH, 86 on aspirin) on chemoprophylaxis at time of follow-up completed the questionnaire. As-treated analysis showed that adherence was high overall (mean MMAS 7.2 out of 8, SD 1.5) and similar for the two regimens (LMWH: 7.4 vs. aspirin: 7.0, p=0.13). However, patients on LMWH were more likely to feel hassled by their regimen (23% vs. 9%, p=0.02). In a multivariable model, low-medium adherence was associated with taking LMWH as the prophylaxis medication (aOR 2.34, CI 1.06 - 5.18, p=0.04), having to self-administer the prophylaxis (aOR 4.44, CI 1.45 - 13.61, p<0.01), being of male sex (aOR 2.46, CI 1.10 - 5.49, p=0.03) and of younger age (aOR 0.72 per additional 10 years of age, CI 0.57-0.91, p<0.01). Overall post-discharge adherence with VTE prophylaxis was high. Several factors, including prophylaxis by LMWH, were associated with decreased adherence. These factors should be considered when managing patients and designing efficacy trials. Level

  14. Unfractionated and low-molecular-weight heparin and the phosphodiesterase inhibitors, IBMX and cilostazol, block ex vivo Equid Herpesvirus type-1-induced platelet activation

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    Tracy Stokol

    2016-11-01

    Full Text Available Equid herpes virus type-1 (EHV-1 is a major pathogen of horses, causing abortion storms and outbreaks of herpes virus myeloencephalopathy. These clinical syndromes are partly attributed to ischemic injury from thrombosis in placental and spinal vessels. The mechanism of thrombosis in affected horses is unknown. We have previously shown that EHV-1 activates platelets through virus-associated tissue factor-initiated thrombin generation. Activated platelets participate in thrombus formation by providing a surface to localize coagulation factor complexes that amplify and propagate thrombin generation. We hypothesized that coagulation inhibitors that suppress thrombin generation (heparins or platelet inhibitors that impede post-receptor thrombin signaling (phosphodiesterase [PDE] antagonists would inhibit EHV-1-induced platelet activation ex vivo. We exposed platelet-rich plasma collected from healthy horses to the RacL11 abortigenic and Ab4 neuropathogenic strains of EHV-1 at 1 plaque forming unit/cell in the presence or absence of unfractionated heparin (UFH, low-molecular-weight (LMWH heparin or the PDE inhibitors, 3-isobutyl-1methylxanthine (IBMX and cilostazol. We assessed platelet activation status in flow cytometric assays by measuring P-selectin expression. We found that all of the inhibitors blocked EHV-1- and thrombin-induced platelet activation in a dose-dependent manner. Platelet activation in PRP was maximally inhibited at concentrations of 0.05 U/mL UFH and 2.5 μg/mL LMWH. These concentrations represented 0.1 to 0.2 U/mL anti-Factor Xa activity measured in chromogenic assays. Both IBMX and cilostazol showed maximal inhibition of platelet activation at the highest tested concentration of 50 μM but inhibition was lower than that seen with UFH and LMWH. Our results indicate that heparin anticoagulants and strong non-selective (IBMX or isoenzyme-3 selective (cilostazol PDE antagonists inhibit ex vivo EHV-1-induced platelet activation

  15. Comparison of intravenous low molecular weight iron dextran and intravenous iron sucrose for the correction of anaemia in pre-dialysis chronic kidney disease patients: a randomized single-centre study in Nigeria.

    Science.gov (United States)

    Waziri, Bala; Mabayoje, Monica; Bello, Babawale

    2016-12-01

    Intravenous low molecular weight iron dextran and iron sucrose have been used for correction of iron deficiency for many years and have been shown to improve anaemia in chronic kidney disease (CKD). However, there is a paucity of head to head comparisons of these parenteral iron preparations. Such comparative efficacy data would be of particular interest in resource-limited African countries, where the majority of CKD patients are unable to afford erythropoiesis-stimulating agents. Therefore, the aim of this study was to compare the effects of these two intravenous iron preparations in pre-dialysis CKD patients. Sixty-seven anaemic pre-dialysis CKD patients were randomized to one of two treatment groups. The low molecular weight iron dextran group (n = 33) received 1000 mg of low molecular weight iron dextran intravenously in four divided doses of 250 mg. The iron sucrose group (n = 34) received 1000 mg of iron sucrose intravenously in five divided doses of 200 mg. Complete blood count, serum creatinine, serum iron, unsaturated iron binding capacity, serum ferritin and transferrin saturation were assessed at baseline. The baseline parameters were repeated in all patients on Day 24. The primary outcome was the proportion of patients achieving a rise in haemoglobin (Hb) concentration of ≥1.0 g/dL after iron therapy. There was no significant difference in the proportion of patients achieving the primary end point between both arms of the study: [7 (21.9%) low molecular weight iron dextran versus 11 (32.4%) iron sucrose; relative risk 0.68, 95% confidence interval (CI): 0.19-1.70; P = 0.23]. At Day 24, the mean increase in Hb concentration from baseline was comparable between the two groups: low molecular weight iron dextran 0.4 ± 0.7 g/dL versus iron sucrose 0.6 ± 0.9 g/dL, mean difference 0.2 g/dL (95% CI: -0.26-0.61; P = 0.28). The proportion of patients that experienced at least one or more adverse events was 27.3% in the iron dextran group versus 14.7% in the

  16. Production of hydroxyl radicals from abiotic oxidation of pyrite by oxygen under circumneutral conditions in the presence of low-molecular-weight organic acids

    Science.gov (United States)

    Zhang, Peng; Yuan, Songhu

    2017-12-01

    Besides acidic environments, pyrite oxidation also occurs in circumneutral environments, such as well-buffered marine and estuarine sediments and salt marshes where low-molecular-weight organic acids (LMWOAs) (e.g., citrate and oxalate) prevail. However, the production of hydroxyl radicals (radOH) from pyrite oxidation by oxygen (O2) in these circumneutral environments is poorly understood. In this study, radOH production was measured during the abiotic oxidation of pyrite by O2 under circumneutral conditions. A pyrite suspension (50 g/L pyrite) that was buffered at pH 6-8 was exposed to air for oxygenation in the dark. Benzoate (20 mM) was added into the suspension to trap radOH. At pH 7, the cumulative radOH reached 7.5 μM within 420 min in the absence of LMWOAs, whereas it increased to 14.8, 12 and 11.2 μM in the presence of 1 mM ethylenediaminotetraacetate, citrate and oxalate, respectively. When the citrate concentration, which serves as a LMWOAs model, was increased from 0.5 to 5 mM, the cumulative radOH increased from 10.3 to 27.3 μM within 420 min at pH 7. With the decrease in pH from 8 to 6, the cumulative radOH increased from 2.1 to 23.3 μM in the absence of LMWOAs, but it increased from 8.8 to 134.9 μM in the presence of 3 mM citrate. The presence of LMWOAs enhanced the radOH production from pyrite oxidation under circumneutral conditions. In the absence of LMOWAs, radOH is produced mostly from the oxidation of adsorbed Fe(II) by O2. In the presence of citrate, radOH production is attributed mainly to the oxidation of Fe(II)-citrate- by O2 and secondarily to the oxidation of H2O on surface-sulfur defects. The acceleration of pyrite oxidation by Fe(III)-citrate increases radOH production. Fe(II)-citrate- is generated mainly from the complexation of adsorbed Fe(II) by citrate and the reduction of Fe(III)-citrate, and the generation is suppressed by the oxidation of adsorbed Fe(II). Fe(III)-citrate is generated predominantly from Fe

  17. Multi-stage inhibition in breast cancer metastasis by orally active triple conjugate, LHTD4 (low molecular weight heparin-taurocholate-tetrameric deoxycholate).

    Science.gov (United States)

    Alam, Farzana; Al-Hilal, Taslim A; Park, Jooho; Choi, Jeong Uk; Mahmud, Foyez; Jeong, Jee-Heon; Kim, In-San; Kim, Sang Yoon; Hwang, Seung Rim; Byun, Youngro

    2016-04-01

    Targeting multiple stages in metastatic breast cancer is one of the effective ways to inhibit metastatic progression. To target human metastatic breast cancer as well as improving patient compliance, we developed an orally active low molecular weight heparin (LMWH)-taurocholate conjugated with tetrameric deoxycholic acid, namely LHTD4, which followed by physical complexation with a synthetic bile acid enhancer, DCK. In breast cancer, both transforming growth factor-β1 (TGF-β1) and CXCL12 exhibit enhanced metastatic activity during the initiation and progression stages of breast cancer, thus we direct the focus on investigating the antimetastatic effect of LHTD4/DCK complex by targeting TGF-β1 and CXCL12. Computer simulation study and SPR analysis were performed for the binding confirmation of LHTD4 with TGF-β1 and CXCL12. We carried out in vitro phosphorylation assays of the consecutive receptors of TGF-β1 and CXCL12 (TGF-β1R1 and CXCR4, respectively). Effects of LHTD4 on in vitro cell migration (induced by TGF-β1) and chemotaxis (mediated by CXCL12) were investigated. The in vivo anti-metastatic effect of LHTD4 was evaluated in an accelerated metastasis model and an orthotopic MDA-MB-231 breast cancer model. The obtained KD values of TGF-β1 and CXCL12 with LHTD4 were 0.85 and 0.019 μM respectively. The simulation study showed that binding affinities of LHTD4 fragment with either TGF-β1 or CXCL12 through additional electrostatic interaction was more stable than that of LMWH fragment. In vitro phosphorylation assays of TGF-β1R1 and CXCR4 showed that the effective inhibition of receptor phosphorylation was observed with the treatment of LHTD4. The expressions of epithelial to mesenchymal transition (EMT) marker proteins such as vimentin and Snail were prevented by LTHD4 treatment in in vitro studies with TGF-β1 treated MDA-MB-231 cells. Moreover, we observed that LHTD4 negatively regulated the functions of TGF-β1 and CXCL12 on migration and

  18. Home treatment of deep vein thrombosis. An out-patient treatment model with once-daily injection of low-molecular-weight heparin (tinzaparin) in 555 patients.

    Science.gov (United States)

    Lapidus, Leif; Börretzen, Jens; Fahlén, Martin; Thomsen, Hans Grönlund; Hasselblom, Sverker; Larson, Lars; Nordström, Henrik; Stigendal, Lennart; Waller, Lotte

    2002-01-01

    During a 22-month period, 555 consecutive patients at seven hospitals in the western part of Sweden with an acute deep vein thrombosis (DVT) not involving the iliac vein and not having pulmonary embolism were included in a study testing the efficacy of implementing out-patient treatment. For all patients with a confirmed diagnosis of acute DVT, a folder was used that contained two checklists with detailed instructions for further treatment, one for the doctor and one for the nurse, an information pamphlet for the patient and prepared prescriptions for low-molecular-weight heparin (LMWH) tinzaparin (Innohep) of 175 anti-Xa IU/kg body weight subcutaneously once daily and warfarin. Patients not requiring hospitalisation, according to strict guidelines, were then eligible for treatment as out-patients. Prior to release from the emergency department for home treatment, a nurse provided detailed information to the patient and administered the first tinzaparin injection. In 194 (35.0%) out of 555 patients, the DVT was localised only in the lower leg not reaching the popliteal vein. Factors predisposing to venous thromboembolism were identified in 35.0% of the patients. 332 (59.8%) out of the 555 patients studied did not require hospitalisation and were therefore treated as out-patients. 140 of these patients (42.2%) injected themselves, the injection was given by a relative in 63 (19.0%) patients and by the community nurse in 129 (38.9%). Six (1.8%) patients reported a worsening of the DVT condition during the LMWH treatment period. No major bleedings were observed during the injection treatment period. Except for local minor skin bleedings at the injection site, only 3 (0.9%) patients reported minor bleedings during the injection treatment period. Recurrences of venous thromboembolism during the first 2 months were reported in 9 patients (2.7%) out of 332 patients who were sent home from the emergency department. Five (2.2%) patients out of the 223 who were admitted to

  19. Identification of Low Molecular Weight Glutenin Alleles by Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS) in Common Wheat (Triticum aestivum L.).

    Science.gov (United States)

    Wang, Aili; Liu, Li; Peng, Yanchun; Islam, Shahidul; Applebee, Marie; Appels, Rudi; Yan, Yueming; Ma, Wujun

    2015-01-01

    Low molecular weight glutenin subunits (LMW-GS) play an important role in determining dough properties and breadmaking quality. However, resolution of the currently used methodologies for analyzing LMW-GS is rather low which prevents an efficient use of genetic variations associated with these alleles in wheat breeding. The aim of the current study is to evaluate and develop a rapid, simple, and accurate method to differentiate LMW-GS alleles using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A set of standard single LMW-GS allele lines as well as a suite of well documented wheat cultivars were collected from France, CIMMYT, and Canada. Method development and optimization were focused on protein extraction procedures and MALDI-TOF instrument settings to generate reproducible diagnostic spectrum peak profiles for each of the known wheat LMW-GS allele. Results revealed a total of 48 unique allele combinations among the studied genotypes. Characteristic MALDI-TOF peak patterns were obtained for 17 common LMW-GS alleles, including 5 (b, a or c, d, e, f), 7 (a, b, c, d or i, f, g, h) and 5 (a, b, c, d, f) patterns or alleles for the Glu-A3, Glu-B3, and Glu-D3 loci, respectively. In addition, some reproducible MALDI-TOF peak patterns were also obtained that did not match with any known alleles. The results demonstrated a high resolution and throughput nature of MALDI-TOF technology in analyzing LMW-GS alleles, which is suitable for application in wheat breeding programs in processing a large number of wheat lines with high accuracy in limited time. It also suggested that the variation of LMW-GS alleles is more abundant than what has been defined by the current nomenclature system that is mainly based on SDS-PAGE system. The MALDI-TOF technology is useful to differentiate these variations. An international joint effort may be needed to assign allele symbols to these newly identified alleles and determine their effects on end

  20. ARF1 and SAR1 GTPases in Endomembrane Trafficking in Plants

    OpenAIRE

    Birsen Cevher-Keskin

    2013-01-01

    Small GTPases largely control membrane traffic, which is essential for the survival of all eukaryotes. Among the small GTP-binding proteins, ARF1 (ADP-ribosylation factor 1) and SAR1 (Secretion-Associated RAS super family 1) are commonly conserved among all eukaryotes with respect to both their functional and sequential characteristics. The ARF1 and SAR1 GTP-binding proteins are involved in the formation and budding of vesicles throughout plant endomembrane systems. ARF1 has been shown to pla...

  1. Determination of the Molecular Weight of Low-Molecular-Weight Heparins by Using High-Pressure Size Exclusion Chromatography on Line with a Triple Detector Array and Conventional Methods

    Directory of Open Access Journals (Sweden)

    Antonella Bisio

    2015-03-01

    Full Text Available The evaluation of weight average molecular weight (Mw and molecular weight distribution represents one of the most controversial aspects concerning the characterization of low molecular weight heparins (LMWHs. As the most commonly used method for the measurement of such parameters is high performance size exclusion chromatography (HP-SEC, the soundness of results mainly depends on the appropriate calibration of the chromatographic columns used. With the aim of meeting the requirement of proper Mw standards for LMWHs, in the present work the determination of molecular weight parameters (Mw and Mn by HP-SEC combined with a triple detector array (TDA was performed. The HP-SEC/TDA technique permits the evaluation of polymeric samples by exploiting the combined and simultaneous action of three on-line detectors: light scattering detectors (LALLS/RALLS; refractometer and viscometer. Three commercial LMWH samples, enoxaparin, tinzaparin and dalteparin, a γ-ray depolymerized heparin (γ-Hep and its chromatographic fractions, and a synthetic pentasaccharide were analysed by HP-SEC/TDA. The same samples were analysed also with a conventional HP-SEC method employing refractive index (RI and UV detectors and two different chromatographic column set, silica gel and polymeric gel columns. In both chromatographic systems, two different calibration curves were built up by using (i γ-Hep chromatographic fractions and the corresponding Mw parameters obtained via HP-SEC/TDA; (ii the whole γ-Hep preparation with broad Mw dispersion and the corresponding cumulative distribution function calculated via HP-SEC/TDA. In addition, also a chromatographic column calibration according to European Pharmacopoeia indication was built up. By comparing all the obtained results, some important differences among Mw and size distribution values of the three LMWHs were found with the five different calibration methods and with HP-SEC/TDA method. In particular, the detection of

  2. Covisualization in living onion cells of putative integrin, putative spectrin, actin, putative intermediate filaments, and other proteins at the cell membrane and in an endomembrane sheath

    Science.gov (United States)

    Reuzeau, C.; Doolittle, K. W.; McNally, J. G.; Pickard, B. G.; Evans, M. L. (Principal Investigator)

    1997-01-01

    Covisualizations with wide-field computational optical-sectioning microscopy of living epidermal cells of the onion bulb scale have evidenced two major new cellular features. First, a sheath of cytoskeletal elements clads the endomembrane system. Similar elements clad the inner faces of punctate plasmalemmal sites interpreted as plasmalemmal control centers. One component of the endomembrane sheath and plasmalemmal control center cladding is anti-genicity-recognized by two injected antibodies against animal spectrin. Immunoblots of separated epidermal protein also showed bands recognized by these antibodies. Injected phalloidin identified F-actin with the same cellular distribution pattern, as did antibodies against intermediate-filament protein and other cytoskeletal elements known from animal cells. Injection of general protein stains demonstrated the abundance of endomembrane sheath protein. Second, the endomembrane system, like the plasmalemmal puncta, contains antigen recognized by an anti-beta 1 integrin injected into the cytoplasm. Previously, immunoblots of separated epidermal protein were shown to have a major band recognized both by this antibody prepared against a peptide representing the cytosolic region of beta 1 integrin and an antibody against the matrix region of beta 1 integrin. The latter antiboby also identified puncta at the external face of protoplasts. It is proposed that integrin and associated transmembrane proteins secure the endomembrane sheath and transmit signals between it and the lumen or matrix of the endoplasmic reticulum and organellar matrices. This function is comparable to that proposed for such transmembrane linkers in the plasmalemmal control centers, which also appear to bind cytoskeleton and a host of related molecules and transmit signals between them and the wall matrix. It is at the plasmalemmal control centers that the endoplasmic reticulum, a major component of the endomembrane system, attaches to the plasma membrane.

  3. Spectral characterization and surface complexation modeling of low molecular weight organics on hematite nanoparticles: Role of electrolytes in the binding mechanism

    Science.gov (United States)

    Given the ubiquity of organic-metal oxide interfaces in environmental and medical systems, it is incumbent to obtain mechanistic details at the molecular level from experimental procedures that mimic real systems and conditions. We report herein the adsorption pH envelopes (range 9-5) and isotherms...

  4. Identification and Quantification of Oxidoselina-1,3,7(11)-Trien-8-One and Cyanidin-3-Glucoside as One of the Major Volatile and Non-Volatile Low-Molecular-Weight Constituents in Pitanga Pulp.

    Science.gov (United States)

    Josino Soares, Denise; Pignitter, Marc; Ehrnhöfer-Ressler, Miriam Margit; Walker, Jessica; Montenegro Brasil, Isabella; Somoza, Veronika

    2015-01-01

    The pulp of pitanga (Eugenia uniflora L.) is used to prepare pitanga juice. However, there are no reports on the identification and quantification of the main constituents in pitanga pulp. The aim of this study was to identify and quantify the major volatile and non-volatile low-molecular-weight constituents of the pulp. Isolation of volatile compounds was performed by solvent-assisted flavor evaporation technique. Characterization of the main volatile and non-volatile constituents was performed by GC-MS, LC-MS and NMR spectroscopy. For quantitative measurements, the main volatile compound needed to be isolated from pitanga pulp to obtain a commercially not available reference standard. Cyanidin-3-glucoside was determined as one of the most abundant non-volatile pulp compound yielding 53.8% of the sum of the intensities of all ions detected by LC-MS. Quantification of cyanidin-3-glucoside in pitanga pulp resulted in a concentration of 344 ± 66.4 μg/mL corresponding to 688 ± 133 μg/g dried pulp and 530 ± 102 μg/g fruit. For the volatile fraction, oxidoselina-1,3,7(11)-trien-8-one was identified as the main volatile pulp constituent (27.7% of the sum of the intensities of all ions detected by GC-MS), reaching a concentration of 89.0 ± 16.9 μg/mL corresponding to 1.34 ± 0.25 μg/g fresh pulp and 1.03 ± 0.19 μg/g fruit. The results provide quantitative evidence for the occurrence of an anthocyanin and an oxygenated sesquiterpene as one of the major volatile and non-volatile low-molecular-weight compounds in pitanga pulp.

  5. Identification and Quantification of Oxidoselina-1,3,7(11-Trien-8-One and Cyanidin-3-Glucoside as One of the Major Volatile and Non-Volatile Low-Molecular-Weight Constituents in Pitanga Pulp.

    Directory of Open Access Journals (Sweden)

    Denise Josino Soares

    Full Text Available The pulp of pitanga (Eugenia uniflora L. is used to prepare pitanga juice. However, there are no reports on the identification and quantification of the main constituents in pitanga pulp. The aim of this study was to identify and quantify the major volatile and non-volatile low-molecular-weight constituents of the pulp. Isolation of volatile compounds was performed by solvent-assisted flavor evaporation technique. Characterization of the main volatile and non-volatile constituents was performed by GC-MS, LC-MS and NMR spectroscopy. For quantitative measurements, the main volatile compound needed to be isolated from pitanga pulp to obtain a commercially not available reference standard. Cyanidin-3-glucoside was determined as one of the most abundant non-volatile pulp compound yielding 53.8% of the sum of the intensities of all ions detected by LC-MS. Quantification of cyanidin-3-glucoside in pitanga pulp resulted in a concentration of 344 ± 66.4 μg/mL corresponding to 688 ± 133 μg/g dried pulp and 530 ± 102 μg/g fruit. For the volatile fraction, oxidoselina-1,3,7(11-trien-8-one was identified as the main volatile pulp constituent (27.7% of the sum of the intensities of all ions detected by GC-MS, reaching a concentration of 89.0 ± 16.9 μg/mL corresponding to 1.34 ± 0.25 μg/g fresh pulp and 1.03 ± 0.19 μg/g fruit. The results provide quantitative evidence for the occurrence of an anthocyanin and an oxygenated sesquiterpene as one of the major volatile and non-volatile low-molecular-weight compounds in pitanga pulp.

  6. Low-molecular-weight heparinoid compared with warfarin for prophylaxis of deep-vein thrombosis in patients who are operated on for fracture of the hip. A prospective, randomized trial

    Energy Technology Data Exchange (ETDEWEB)

    Gerhart, T.N.; Yett, H.S.; Robertson, L.K.; Lee, M.A.; Smith, M.; Salzman, E.W. (Beth Israel Hospital, Boston, MA (USA))

    1991-04-01

    In a randomized, prospective trial, a low-molecular-weight heparinoid (Org 10172 (Lomoparan)) was compared with warfarin for efficacy and safety in preventing deep-vein thrombosis in 263 patients who had an operatively treated fracture of the hip. One group of patients received Org 10172 in a dose of 750 units subcutaneously every twelve hours until the ninth postoperative day; on the seventh postoperative day, warfarin was added to the regimen. The other group received only warfarin. Both drugs were begun preoperatively, immediately after the admission evaluation. In the patients who received warfarin, the desired prothrombin time was one and one-half times the control level. Deep-vein thrombosis was detected by {sup 125}I-fibrinogen scanning and impedance plethysmography and was confirmed by phlebography and compression ultrasonography. Deep-vein thrombosis was found in nine (7 per cent) of the 132 patients who received Org 10172 and in twenty-eight (21 per cent) of the 131 patients who received warfarin (p less than 0.001). Adverse reactions were not significantly different in the two groups. Major bleeding complications occurred in eight patients in the Org-10172 group, only four of whom were receiving the drug at the time of bleeding, and in five patients who were receiving warfarin (not significant). There was no difference in intraoperative loss of blood or in requirements for transfusion. We concluded that the low-molecular-weight heparinoid Org 10172 is a safe, convenient, effective antithrombotic agent for the prevention of venous thrombosis after an operation for fracture of the hip.

  7. ARF1 and SAR1 GTPases in Endomembrane Trafficking in Plants

    Directory of Open Access Journals (Sweden)

    Birsen Cevher-Keskin

    2013-09-01

    Full Text Available Small GTPases largely control membrane traffic, which is essential for the survival of all eukaryotes. Among the small GTP-binding proteins, ARF1 (ADP-ribosylation factor 1 and SAR1 (Secretion-Associated RAS super family 1 are commonly conserved among all eukaryotes with respect to both their functional and sequential characteristics. The ARF1 and SAR1 GTP-binding proteins are involved in the formation and budding of vesicles throughout plant endomembrane systems. ARF1 has been shown to play a critical role in COPI (Coat Protein Complex I-mediated retrograde trafficking in eukaryotic systems, whereas SAR1 GTPases are involved in intracellular COPII-mediated protein trafficking from the ER to the Golgi apparatus. This review offers a summary of vesicular trafficking with an emphasis on the ARF1 and SAR1 expression patterns at early growth stages and in the de-etiolation process.

  8. Low-molecular-weight gelators: elucidating the principles of gelation based on gelator solubility and a cooperative self-assembly model.

    Science.gov (United States)

    Hirst, Andrew R; Coates, Ian A; Boucheteau, Thomas R; Miravet, Juan F; Escuder, Beatriu; Castelletto, Valeria; Hamley, Ian W; Smith, David K

    2008-07-16

    This paper highlights the key role played by solubility in influencing gelation and demonstrates that many facets of the gelation process depend on this vital parameter. In particular, we relate thermal stability ( T gel) and minimum gelation concentration (MGC) values of small-molecule gelation in terms of the solubility and cooperative self-assembly of gelator building blocks. By employing a van't Hoff analysis of solubility data, determined from simple NMR measurements, we are able to generate T calc values that reflect the calculated temperature for complete solubilization of the networked gelator. The concentration dependence of T calc allows the previously difficult to rationalize "plateau-region" thermal stability values to be elucidated in terms of gelator molecular design. This is demonstrated for a family of four gelators with lysine units attached to each end of an aliphatic diamine, with different peripheral groups (Z or Boc) in different locations on the periphery of the molecule. By tuning the peripheral protecting groups of the gelators, the solubility of the system is modified, which in turn controls the saturation point of the system and hence controls the concentration at which network formation takes place. We report that the critical concentration ( C crit) of gelator incorporated into the solid-phase sample-spanning network within the gel is invariant of gelator structural design. However, because some systems have higher solubilities, they are less effective gelators and require the application of higher total concentrations to achieve gelation, hence shedding light on the role of the MGC parameter in gelation. Furthermore, gelator structural design also modulates the level of cooperative self-assembly through solubility effects, as determined by applying a cooperative binding model to NMR data. Finally, the effect of gelator chemical design on the spatial organization of the networked gelator was probed by small-angle neutron and X

  9. Synergic effects in the extraction of paracetamol from aqueous NaCl solution by the binary mixtures of diethyl ether and low molecular weight primary alcohols

    Science.gov (United States)

    Nikolić, G. M.; Živković, J. V.; Atanasković, D. S.; Nikolić, M. G.

    2013-12-01

    Liquid-liquid extraction of paracetamol from aqueous NaCl solutions was performed with diethyl ether, 1-propanol, 1-butanol, isobutanol, 1-pentanol, and binary mixtures diethyl ether/1-propanol, diethyl ether/1-butanol, and diethyl ether/isobutanol. Among the pure solvents investigated in this study best extraction efficacy was obtained with 1-butanol. Synergic effects in the extraction with binary mixtures was investigated and compared with some other systems used for the extraction of poorly extractable compounds. Results obtained in this study may be of both fundamental and practical importance.

  10. Venous thromboembolism prophylaxis in meningioma surgery - a population based comparative effectiveness study of routine mechanical prophylaxis with or without preoperative low molecular weight heparin

    DEFF Research Database (Denmark)

    Sjåvik, Kristin; Bartek, Jiri; Solheim, Ole

    2015-01-01

    OBJECT: Venous thromboembolism (VTE) is a serious complication after intracranial meningioma surgery. To what extent systemic prophylaxis with pharmacotherapy is beneficial with respect to VTE risk, or associated with increased risk of bleeding and postoperative hemorrhage, remains debated....... The current study aimed to clarify the risk-benefit of prophylactic pharmacotherapy initiated the evening before craniotomy for meningioma. METHODS: In a Scandinavian population-based cohort we conducted a retrospective review of 979 operations for intracranial meningioma between 2007 and 2013 at three...... intracranial meningioma surgery. Neither could we for primary outcomes detect a significant increase in clinically relevant postoperative hematomas secondary to this regimen. We suggest that "as-needed" perioperative administration of LMWH, reserved for patients with excess risk due to delayed mobilization...

  11. Immunostimulatory activities of a low molecular weight antitumoral polysaccharide isolated from Agaricus blazei Murill (LMPAB) in Sarcoma 180 ascitic tumor-bearing mice.

    Science.gov (United States)

    Niu, Ying-Cai; Liu, Ji-Cheng; Zhao, Xue-Mei; Su, Fu-Qin; Cui, Hong-Xia

    2009-07-01

    LMPAB is a linear beta-(1-3)-glucan we isolated from polysaccharide extract of Agaricus blazei Murill (AbM). Effects of LMPAB on splenic natural killer (NK) cell activity, splenocyte proliferation, index of spleen and thymus, IFN-gamma expression in spleen and the concentration of IL-12, IL-18 and TNF-alpha in serum of S180 ascitic tumor-bearing mice were detected. The results showed that intraperitoneal injection of LMPAB (100 mg x kg(-1) x d(-1)) significantly increased the thymus index. LMPAB augmented splenic NK cell activity in a dose-dependent manner (50-200 mg x kg(-1) x d(-1)). The concanavalin A (3 microg/ ml) stimulated splenocyte proliferation was significantly enhanced by LMPAB at dosages of 50, 100 or 200 mg x kg(-1) x d(-1). Further studies showed that LMPAB (50, 100 or 200 mg x kg(-1) x d(-1), 14d) significantly increased the production of IL-12, TNF-alpha, IL-18 and the expression IFN-gamma as determined by ELISA and immunohistochemistry, respectively. These results clearly indicate that the anti-tumor effects of LMPAB are closely associated with up-regulation of activity of NK cells, expression of IFN-gamma in spleen and the systemic level of IL-12, IL-18 and TNF-alpha in tumor-bearing mice.

  12. A SELDI-TOF approach to ecotoxicology: comparative profiling of low molecular weight proteins from a marine diatom exposed to CdSe/ZnS quantum dots.

    Science.gov (United States)

    Scebba, Francesca; Tognotti, Danika; Presciuttini, Gianluca; Gabellieri, Edi; Cioni, Patrizia; Angeloni, Debora; Basso, Barbara; Morelli, Elisabetta

    2016-01-01

    Quantum dots (QDs), namely semiconductor nanocrystals, due to their particular optical and electronic properties, have growing applications in device technology, biotechnology and biomedical fields. Nevertheless, the possible threat to human health and the environment have attracted increasing attention as the production and applications of QDs increases rapidly while standard evaluation of safety lags. In the present study we performed proteomic analyses, by means of 2D gel electrophoresis and Surface Enhanced Laser Desorption Ionization-Time of Flight-Mass Spectrometry (SELDI-TOF-MS). We aimed to identify potential biomarkers of exposure to CdSe/ZnS quantum dots. The marine diatom Phaeodactylum tricornutum exposed to 2.5nM QDs was used as a model system. Both 2DE and SELDI showed the presence of differentially expressed proteins. By Principal Component Analysis (PCA) we were able to show that the differentially expressed proteins can discriminate between exposed and not exposed cells. Furthermore, a protein profile specific for exposed cells was obtained by SELDI analysis. To our knowledge, this is the first example of the application of SELDI technology to the analysis of microorganisms used as biological sentinel model of marine environmental pollution. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Recognition of low molecular weight Cooperia oncophora antigens after primary and trickle infection of calves with third-stage infective larvae.

    Science.gov (United States)

    van Diemen, P M; Ploeger, H W; Nieuwland, M G; Rietveld, F W; Parmentier, H K

    1996-11-01

    Recognition of low molecular protein fragments of adult Cooperia oncophora of calves was studied using sera obtained after a single oral (primary) infection with 100,000 infective 3rd-stage C. oncophora larvae, and after a 10-week period of trickle infection with moderate doses of these larvae. SDS-gel electrophoresis under reducing conditions, followed by western blotting, revealed that a complex of 14-16 kDa protein fragments, a 27 kDa and a 31.6 kDa band of Cooperia oncophora adult antigen were recognized by sera from calves both after primary and trickle infection. A 19 kDa and 30 kDa protein fragment were additionally bound by sera from calves after trickle infection. The data suggest that the systemic humoral immune response of calves to Cooperia oncophora after trickle infection is more pronounced (14-16, 27, 31.6 kDa) and extended (19, 30 kDa) than after primary infection with Cooperia.

  14. Investigation of Galactosylated Low Molecular Weight Chitosan ...

    African Journals Online (AJOL)

    efficiency of drug. To optimize the molar ratio of the 3rd lipid, i.e., PG, the formulations were prepared with increasing molar ratio of PG and. 7:3 molar ratio of PC: CH. The size of the liposomes was further reduced using probe sonicator in order to make them suitable for hepatic delivery. The ratio of drug to total lipids.

  15. Utility of the clinical practice of administering thrombophilic screening and antithrombotic prophylaxis with low-molecular-weight heparin to healthy donors treated with G-CSF for mobilization of peripheral blood stem cells.

    Science.gov (United States)

    Martino, Massimo; Luise, Francesca; Oriana, Vincenzo; Console, Giuseppe; Moscato, Tiziana; Mammì, Corrado; Messina, Giuseppe; Massara, Elisabetta; Irrera, Giuseppe; Piromalli, Angela; Lombardo, Vincenzo Trapani; Laganà, Carmelo; Iacopino, Pasquale

    2007-01-01

    The aim of the study was to verify the utility of the clinical practice of administering thrombophilic screening and antithrombotic prophylaxis with low-molecular-weight heparin to healthy donors receiving granulocyte colony-stimulating factor to mobilize peripheral blood stem cells. Thrombophilia screening comprised of testing for factor V Leiden G1691A, prothrombin G20210A, the thermolabile variant (C677T) of the methylene tetrahydrofolate reductase gene, protein C, protein S, factor VIII and homocysteine plasmatic levels, antithrombin III activity, and acquired activated protein C resistance. We investigated prospectively 72 white Italian healthy donors, 39 men and 33 women, with a median age of 42 years (range, 18-65). Five donors (6.9%) were heterozygous carriers of Factor V Leiden G1691A; two healthy donors had the heterozygous prothrombin G20210A gene mutation; C677T mutation in the methylene tetrahydrofolate reductase gene was present in 34 (47.2%) donors in heterozygous and in 7 donors (9.7%) in homozygous. Acquired activated protein C resistance was revealed in 8 donors of the study (11.1%). The protein C plasmatic level was decreased in 3 donors (4.2%); the protein S level was decreased in 7 donors (9.7%). An elevated factor VIII dosage was shown in 10 donors (13.9%) and hyperhomocysteinemia in 9 donors (12.5%). Concentration of antithrombin III was in the normal range for all study group donors. The factor V Leiden mutation was combined with the heterozygous prothrombin G20210A in 2 cases and with protein S deficiency in one case; 2 healthy donors presented an associated deficiency of protein C and protein S. Although none of these healthy subjects had a previous history of thrombosis, low-molecular-weight heparin was administered to all donors during granulocyte colony-stimulating factor administration to prevent thrombotic events. No donor experienced short or long-term thrombotic diseases after a median follow-up of 29.2 months. Our data do not

  16. Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease. Fragmin in unstable coronary artery disease study (FRIC)

    Science.gov (United States)

    Klein, W; Buchwald, A; Hillis, S E; Monrad, S; Sanz, G; Turpie, A G; van der Meer, J; Olaisson, E; Undeland, S; Ludwig, K

    1997-07-01

    Low-molecular-weight heparin has a number of pharmacological and pharmacokinetic advantages over unfractionated heparin that make it potentially suitable, when used in combination with aspirin, for the treatment of unstable coronary artery disease. Patients with unstable angina or non-Q-wave myocardial infarction (1482) were included in the study, which had two phases. In an open, acute phase (days 1 to 6), patients were assigned either twice-daily weight-adjusted subcutaneous injections of dalteparin (120 i.u./kg) or dose-adjusted intravenous infusion of unfractionated heparin. In the double-blind, prolonged treatment phase (days 6 to 45), patients received subcutaneously either dalteparin (7500 i.u. once daily) or placebo. During the first 6 days, the rate of death, myocardial infarction, or recurrence of angina was 7.6% in the unfractionated heparin-treated patients and 9.3% in the dalteparin-treated patients (relative risk, 1.18; 95% confidence interval [CI], 0.84 to 1.66). The corresponding rates in the two treatment groups for the composite end point of death or myocardial infarction were 3.6% and 3.9%, respectively (relative risk, 1.07; 95% CI, 0.63 to 1.80). Revascularization procedures were undertaken in 5.3% and 4.8% of patients in unfractionated heparin and dalteparin groups, respectively (relative risk, 0.88; 95% CI, 0.57 to 1.35). Between days 6 and 45, the rate of death, myocardial infarction, or recurrence of angina was 12.3% in both the placebo and dalteparin groups (relative risk, 1.01; 95% CI, 0.74 to 1.38). The corresponding rates for death or myocardial infarction were 4.7% and 4.3% (relative risk, 0.92; 95% CI, 0.54 to 1.57). Revascularization procedures were undertaken in 14.2% and 14.3% of patients in the placebo and dalteparin groups, respectively. Our results add to previous evidence suggesting that the low-molecular-weight heparin dalteparin administered by twice-daily subcutaneous injection may be an alternative to unfractionated heparin

  17. Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, attenuates diabetes-induced renal damage through the advanced glycation end product-related pathway in db/db mice.

    Science.gov (United States)

    Park, Chan Hum; Yokozawa, Takako; Noh, Jeong Sook

    2014-08-01

    This study was conducted to examine whether oligonol, a low-molecular-weight polyphenol derived from lychee fruit, has an ameliorative effect on diabetes-induced alterations, such as advanced glycation end product (AGE) formation or apoptosis in the kidneys of db/db mice with type 2 diabetes. Oligonol [10 or 20 mg/(kg body weight · d), orally] was administered every day for 8 wk to prediabetic db/db mice, and its effect was compared with vehicle-treated db/db and normal control mice (m/m). The administration of oligonol decreased the elevated renal glucose concentrations and reactive oxygen species in db/db mice (P oxidase subunits (p22 phagocytic oxidase and NAD(P)H oxidase-4), AGEs (except for pentosidine), and c-Jun N-terminal kinase B-targeting proinflammatory tumor necrosis factor-α (P < 0.05). Oligonol improved the expressions of antiapoptotic [B-cell lymphoma protein 2 (Bcl-2) and survivin] and proapoptotic [Bcl-2-associated X protein, cytochrome c, and caspase-3] proteins in the kidneys of db/db mice (P < 0.05). In conclusion, these results provide important evidence that oligonol exhibits a pleiotropic effect on AGE formation and apoptosis-related variables, representing renoprotective effects against the development of diabetic complications in db/db mice with type 2 diabetes. © 2014 American Society for Nutrition.

  18. Geochemistry of low-molecular-weight hydrocarbons in core samples of lower foarcian age (posidonia shale) in the Hils syncline area. Hydrocarbon formation and maturity. Zur Geochemie niedrigmolekularer Kohlenwasserstoffe im Posidonienschiefer der Hilsmulde. Kohlenwasserstoffbildung und Reifeaspekte

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, R.G. (Forschungszentrum Juelich GmbH (Germany). Inst. fuer Erdoel und Organische Geochemie)

    1992-02-01

    Compositional changes in the light hydrocarbon fraction of sedimentary rocks and petroleum are known to reflect their maturation history. The present contribution comprises the analysis of low-molecular-weight hydrocarbons in core samples of Lower Toarcian age ('Posidonia Shale', Lias {epsilon}). The sample series, obtained by shallow-borehole drilling in the Hils syncline area, Lower Saxony Basin, northern Germany, represents an exceptionally organic matter rich petroleum source rock (type-II kerogen) of a wide maturity range (mean vitrinite reflectance, R{sub r} between 0.5 and 1.5%). About 30 compounds in the C{sub 2}-C{sub 7} molecular range, including benzene and toluene, were determined by means of a combined thermovapourization/capillary GC method. Both, quantity and composition are discussed in relation to maturity at seven locations. Correlations between R{sub r} and 'chemical' maturity parameters based on compositional changes of acyclic and alicyclic C{sub 7}-hydrocarbons as well as indications of migration processes are presented. (orig.).

  19. Cloning and characterization of a cDNA encoding an 18.0-kDa class-I low-molecular-weight heat-shock protein from rice.

    Science.gov (United States)

    Lee, Y L; Chang, P F; Yeh, K W; Jinn, T L; Kung, C C; Lin, W C; Chen, Y M; Lin, C Y

    1995-11-20

    A novel cDNA clone, Oshp18.0 cDNA, encoding a rice (Oryza sativa L. cv. Tainong 67) 18.0-kDa heat-shock protein (HSP), was isolated from a cDNA library of heat-shocked rice seedlings by use of the rice HSP cDNA, Oshsp17.3 cDNA, as a probe. The sequence showed that Oshsp18.0 cDNA contains a 749-bp insert encoding an ORF of 160 amino acids, with a predicted molecular mass of 18.0 kDa and a pI of 7.3. Sequence comparison reveals that Oshsp18.0 cDNA is highly homologous to other low-molecular-weight (LMW) HSP cDNAs. Also, the results of hybrid-selected in vitro translation clearly establish that Oshsp18.0 cDNA is the rice 18.0-kDa LMW HSP-encoding cDNA clone. The recombinant Oshsp18.0 fusion protein produced in Escherichia coli was of the size predicted, and was recognized by the class-I rice 16.9-kDa HSP antiserum. The results suggest that Oshsp18.0 cDNA is an 18.0-kDa class-I LMW HSP- encoding cDNA clone from rice.

  20. The potential of mycelium and culture broth of Lignosus rhinocerotis as substitutes for the naturally occurring sclerotium with regard to antioxidant capacity, cytotoxic effect, and low-molecular-weight chemical constituents.

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    Beng Fye Lau

    Full Text Available Previous studies on the nutritional and nutraceutical properties of Lignosus rhinocerotis focused mainly on the sclerotium; however, the supply of wild sclerotium is limited. In this investigation, the antioxidant capacity and cytotoxic effect of L. rhinocerotis cultured under different conditions of liquid fermentation (shaken and static were compared to the sclerotium produced by solid-substrate fermentation. Aqueous methanol extracts of the mycelium (LR-MH, LR-MT and culture broth (LR-BH, LR-BT demonstrated either higher or comparable antioxidant capacities to the sclerotium extract (LR-SC based on their radical scavenging abilities, reducing properties, metal chelating activities, and inhibitory effects on lipid peroxidation. All extracts exerted low cytotoxicity (IC50>200 µg/ml, 72 h against selected mammalian cell lines. Several low-molecular-weight compounds, including sugars, fatty acids, methyl esters, sterols, amides, amino acids, phenolics, and triterpenoids, were identified using GC-MS and UHPLC-ESI-MS/MS. The presence of proteins (<40 kDa in the extracts was confirmed by SDS-PAGE and SELDI-TOF-MS. Principal component analysis revealed that the chemical profiles of the mycelial extracts under shaken and static conditions were distinct from those of the sclerotium. Results from bioactivity evaluation and chemical profiling showed that L. rhinocerotis from liquid fermentation merits consideration as an alternative source of functional ingredients and potential substitute for the sclerotium.

  1. Atomic resolution crystal structure of VcLMWPTP-1 from Vibrio cholerae O395: Insights into a novel mode of dimerization in the low molecular weight protein tyrosine phosphatase family

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    Nath, Seema; Banerjee, Ramanuj; Sen, Udayaditya, E-mail: udayaditya.sen@saha.ac.in

    2014-07-18

    Highlights: • VcLMWPTP-1 forms dimer in solution. • The dimer is catalytically active unlike other reported dimeric LMWPTPs. • The formation of extended dimeric surface excludes the active site pocket. • The surface bears closer resemblance to eukaryotic LMWPTPs. - Abstract: Low molecular weight protein tyrosine phosphatase (LMWPTP) is a group of phosphotyrosine phosphatase ubiquitously found in a wide range of organisms ranging from bacteria to mammals. Dimerization in the LMWPTP family has been reported earlier which follows a common mechanism involving active site residues leading to an enzymatically inactive species. Here we report a novel form of dimerization in a LMWPTP from Vibrio cholera 0395 (VcLMWPTP-1). Studies in solution reveal the existence of the dimer in solution while kinetic study depicts the active form of the enzyme. This indicates that the mode of dimerization in VcLMWPTP-1 is different from others where active site residues are not involved in the process. A high resolution (1.45 Å) crystal structure of VcLMWPTP-1 confirms a different mode of dimerization where the active site is catalytically accessible as evident by a tightly bound substrate mimicking ligand, MOPS at the active site pocket. Although being a member of a prokaryotic protein family, VcLMWPTP-1 structure resembles very closely to LMWPTP from a eukaryote, Entamoeba histolytica. It also delineates the diverse surface properties around the active site of the enzyme.

  2. Prevention of Venous Thromboembolism in Major Orthopedic Surgery: Bayesian Network Meta-Analysis of 21 Randomized Trials Evaluating Unfractionated Heparins, Low-Molecular Weight Heparins, and New Oral Anticoagulants

    Directory of Open Access Journals (Sweden)

    Andrea Messori

    2014-09-01

    Full Text Available Background: In major orthopedic surgery, prevention of venous thromboembolism has been based on Unfractionated Heparins (UFHs over the past decades, then on Low-Molecular Weight Heparins (LMWHs, and on New Oral Anticoagulants (NOACs more recently. To summarize the comparative effectiveness of UFHs, LMWHs, and NOACs in this clinical indication, we applied Bayesian network meta-analysis to the clinical material (randomized studies published in two previous reviews focused on this issue.. Objectives: Our end-point was a composite of venous thromboembolism and pulmonary embolism.. Materials and Methods: Our analysis was based on standard Bayesian network meta-analysis (random-effect model.. Results: The analysis included 21 randomized trials for a total of 21,805 patients. Our results showed that the degree of effectiveness did not differ among UFHs, LMWHs, and NOACs. Although some trends emerged from an in-depth analysis of these data (e.g. according to the histogram of rankings, no significant differences were found (P > 0.05. Moreover, two agents among LMWHs proved to be adequately supported by randomized trials (enoxaparin and dalteparin, while limited evidence was available for other agents of this class.. Conclusions: Our synthesis of the effectiveness data can be useful as an overall reference in this area and can also contribute to defining the place of further innovative treatments for this clinical indication..

  3. Method for simultaneous imaging of endogenous low molecular weight metabolites in mouse brain using TiO2 nanoparticles in nanoparticle-assisted laser desorption/ionization-imaging mass spectrometry.

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    Shrivas, Kamlesh; Hayasaka, Takahiro; Sugiura, Yuki; Setou, Mitsutoshi

    2011-10-01

    We report the detection of a group of endogenous low molecular weight metabolites (LMWM) in mouse brain (80-500 Da) using TiO(2) nanoparticles (NPs) in nanoparticle-assisted laser desorption/ionization-imaging mass spectrometry (Nano-PALDI-IMS) without any washing and separation step prior to MS analysis. The identification of metabolites using TiO(2) NPs was compared with a conventional organic matrix 2,5-dihydroxybenzoic acid (DHB) where signals of 179 molecules were specific to TiO(2) NPs, 4 were specific to DHB, and 21 were common to both TiO(2) NPs and DHB. The use of TiO(2) NPs enabled the detection of a higher number of LMWM as compared to DHB and gold NPs as a matrix. This approach is a simple, inexpensive, washing, and separation free for imaging and identification of LMWM in mouse brain. We believe that the biochemical information from distinct regions of the brain using a Nano-PALDI-IMS will be helpful in elucidating the imbalances linked with diseases in biomedical samples.

  4. Feasibility of continuous, catheter-directed thrombolysis using low-dose urokinase in combination with low molecular-weight heparin for acute iliofemoral venous thrombosis in patients at risk of bleeding.

    Science.gov (United States)

    Chen, Guoping; Shi, Wangyin; He, Xu; Lou, Wensheng; Chen, Liang; Gu, Jianping

    2017-02-01

    The present study aimed to examine the feasibility of catheter-directed thrombolysis (CDT) using continuous infusion of low-dose urokinase in combination with low molecular weight heparin (LMWH) for acute iliofemoral venous thrombosis. This retrospective analysis included patients with symptomatic acute iliofemoral venous thrombosis who received CDT using continuous infusion of low-dose urokinase in combination with LMWH within the past four years. Urokinase was administered at 1×104 U/h and 2×104 U/h in patients at high-risk and low-risk of bleeding, respectively. Measurements included urokinase dosage, duration, clinical outcomes and CDT-related complications. A total of 46 patients were included (high-risk, n=17; low-risk, n=29). In the high-risk patients, 64.7% experienced dissolution of ≥50% thrombi after a median CDT duration of 8 days (range, 6-10 days) and median total urokinase dose of 1.92×106 units (range, 1.44-2.4×106 units). In the low-risk patients, 82.8% achieved dissolution of ≥50% thrombi after a median CDT duration of 7 days (range, 4-10 days) and a median total urokinase dose of 3.36×106 units (range, 1.92-4.80×106 units). Remission of clinical symptoms after CDT was achieved in 15 (88.2%) and 28 (96.6%) cases in high-risk and low-risk patients, respectively. No treatment-associated pulmonary embolism or major bleeding was observed. Three (6.5%) subjects (high-risk, n=1; low-risk, n=2) experienced minor bleeding. In conclusion, continuous infusion of low-dose urokinase via CDT in combination with LMWH is effective and safe for acute iliofemoral venous thrombosis in patients with one or more risk factor for bleeding.

  5. Development of C60-based labeling reagents for the determination of low-molecular-weight compounds by matrix assisted laser desorption ionization mass (I): Determination of amino acids in microliter biofluids.

    Science.gov (United States)

    Wu, Pin; Xiao, Hua-Ming; Ding, Jun; Deng, Qian-Yun; Zheng, Fang; Feng, Yu-Qi

    2017-04-01

    Quantification of low molecular weight compounds (C60 labeling-MALDI MS strategy was proposed for the fast, sensitive and reliable determination of amino acids (AAs) in biofluids. An N-hydroxysuccinimide functionalized C60 was synthesized as the labeling reagent and added as an 880 Da tag to AAs; a carboxyl acid containing C60 was employed as the internal standards to normalize MS variations. This solved the inherent problems of MALDI MS for small molecule analysis. The entire analytical procedure-which consisted of simple protein precipitation and 10 min of derivatization in a microwave prior to the MALDI MS analysis-could be accomplished within 20 min with high throughput and great sample matrix tolerance. AA quantification showed good linearity from 0.7 to 70.0 μM with correlation coefficients (R) larger than 0.9954. The limits of detection were 70.0-300.0 fmol. Good reproducibility and reliability of the method were demonstrated by intra-day and inter-day precision with relative standard deviations less than 13.8%, and the recovery in biofluid ranged from 80.4% to 106.8%. This approach could be used in 1 μL of urine, serum, plasma, whole blood, and cerebrospinal fluid. Most importantly, the C60 labeling strategy is a universal approach for MALDI MS analysis of various LMW compounds because functionalized C60 is now available on demand. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Antibacterial and Antioxidant Capacities and Attenuation of Lipid Accumulation in 3T3-L1 Adipocytes by Low-Molecular-Weight Fucoidans Prepared from Compressional-Puffing-Pretreated Sargassum Crassifolium

    Directory of Open Access Journals (Sweden)

    Chun-Yung Huang

    2018-01-01

    Full Text Available In this study, we extracted fucoidan from compressional-puffing-pretreated Sargassum crassifolium by hot water. The crude extract of fucoidan (SC was degraded by various degradation reagents and four low-molecular-weight (LMW fucoidans, namely SCO (degradation by hydrogen peroxide, SCA (degradation by ascorbic acid, SCOA (degradation by hydrogen peroxide + ascorbic acid, and SCH (degradation by hydrogen chloride were obtained. The degradation reagents studied could effectively degrade fucoidan into LMW fucoidans, as revealed by intrinsic viscosity, agarose gel electrophoresis, and molecular weight analyses. These LMW fucoidans had higher uronic acid content and sulfate content than those of SC. It was found that SCOA exhibited antibacterial activity. All LMW fucoidans showed antioxidant activities as revealed by DPPH (2,2-diphenyl-1-picrylhydrazyl, ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt, and FRAP (ferric reducing antioxidant power methods. Biological experiments showed that SC and SCOA had relatively high activity for the reversal of H2O2-induced cell death in 3T3-L1 adipocytes, and SCOA showed the highest effect on attenuation of lipid accumulation in 3T3-L1 adipocytes. Therefore, for the LMW fucoidans tested, SCOA showed antibacterial activity and had a high fucose content, high sulfate content, high activity for the reversal of H2O2-induced cell death, and a marked effect on attenuation of lipid accumulation. It can thus be recommended as a natural and safe antibacterial and anti-adipogenic agent for food, cosmetic, and nutraceutical applications.

  7. Efficacy and tolerance of an injectable medical device containing stable hybrid cooperative complexes of high- and low-molecular-weight hyaluronic acid: a monocentric 16 weeks open-label evaluation

    Directory of Open Access Journals (Sweden)

    Sparavigna A

    2016-09-01

    Full Text Available Adele Sparavigna, Beatrice Tenconi DermIng srl, Clinical Research and Bioengineering Institute, Monza, MB, Italy Background: An injectable medical device containing stable hybrid cooperative complexes of high- and low-molecular-weight hyaluronic acid (HA has been developed with characteristics suited for a global improvement of facial esthetics. Objective: To evaluate the HA product performance in improving some key facial esthetic features. The study employed clinical scales, subjective evaluations, and facial skin objective measurements. Methods: A single Italian site treated 64 female subjects aged 38–60 years, with injections at five predetermined points, on each side of the face, with a 4-week time lapse between the first and the second product administration. Subjects were evaluated after 4, 8, 12, and 16 weeks, using validated clinical scales, subjective evaluation, and objective quantitative outcome measures. Assessment of esthetic results included photographic documentation. Results: Both the clinical and subjective assessments, and the majority of objective instrumental parameters indicated an improvement throughout the study and were already significant at week 4 or 8 and were still significant at week 16 (3 months after the second treatment. Minor and temporary local skin reactions were observed in 23% of subjects at the site of the injections, and the global judgment on tolerability was good or excellent, both in the investigators’ opinion and volunteers’ self-evaluation. Conclusion: Both subjective and objective improvement of the facial parameters was consistent with the bio-remodeling purpose, and persistent and still statistically significant at the end of the study. The tolerability and safety profile of the product were judged good or excellent both by investigators and volunteers. This study supports the claim for bio-remodeling of these stable hybrid cooperative complexes of low- and high-molecular-weight HA. Keywords

  8. Effects of three low-molecular-weight organic acids (LMWOAs) and pH on the mobilization of arsenic and heavy metals (Cu, Pb, and Zn) from mine tailings.

    Science.gov (United States)

    Wang, Suiling; Mulligan, Catherine N

    2013-02-01

    Natural organic acids may play an important role in influencing the mobility of toxic contaminants in the environment. The mobilization of arsenic (As) and heavy metals from an oxidized Pb-Zn mine tailings sample in the presence of three low-molecular-weight organic acids, aspartic acid, cysteine, and succinic acid, was investigated at a mass ratio of 10 mg organic additive/g mine tailings in this study. The effect of pH was also evaluated. The mine tailings sample, containing elevated levels of As (2,180 mg/kg), copper (Cu, 1,100 mg/kg), lead (Pb, 12,860 mg/kg), and zinc (Zn, 5,075 mg/kg), was collected from Bathurst, New Brunswick, Canada. It was found that the organic additives inhibited As and heavy metal mobilization under acidic conditions (at pH 3 or 5), but enhanced it under neutral to alkaline conditions (at pH above 7) through forming aqueous organic complexes. At pH 11, As, Cu, Pb, and Zn were mobilized mostly by the organic additives, 45, 46, 1,660, and 128 mg/kg by aspartic acid, 31, 28, 1,040, and 112 mg/kg by succinic acid, and 53, 38, 2,020, and 150 mg/kg by cysteine, respectively, whereas those by distilled water were 6, 16, 260, and 52 mg/kg, respectively. It was also found that the mobilization of As and the heavy metals was closely correlated, and both were closely correlated to Fe mobilization. Arsenic mobilization by the three LMWOAs was found to be consistent with the order of the stability of Fe-, Cu-, Pb-, and Zn-organic ligand complexes. The organic acids might be used potentially in the natural attenuation and remediation of As and heavy metal-contaminated sites.

  9. Evolution of the endomembrane systems of trypanosomatids - conservation and specialisation.

    Science.gov (United States)

    Venkatesh, Divya; Boehm, Cordula; Barlow, Lael D; Nankissoor, Nerissa N; O'Reilly, Amanda; Kelly, Steven; Dacks, Joel B; Field, Mark C

    2017-04-15

    Parasite surfaces support multiple functions required for survival within their hosts, and maintenance and functionality of the surface depends on membrane trafficking. To understand the evolutionary history of trypanosomatid trafficking, where multiple lifestyles and mechanisms of host interactions are known, we examined protein families central to defining intracellular compartments and mediating transport, namely Rabs, SNAREs and RabGAPs, across all available Euglenozoa genomes. Bodonids possess a large trafficking repertoire, which is mainly retained by the Trypanosoma cruzi group, with extensive losses in other lineages, particularly African trypanosomes and phytomonads. There are no large-scale expansions or contractions from an inferred ancestor, excluding direct associations between parasitism or host range. However, we observe stepwise secondary losses within Rab and SNARE cohorts (but not RabGAPs). Major changes are associated with endosomal and late exocytic pathways, consistent with the diversity in surface proteomes between trypanosomatids and mechanisms of interaction with the host. Along with the conserved core family proteins, several lineage-specific members of the Rab (but not SNARE) family were found. Significantly, testing predictions of SNARE complex composition by proteomics confirms generalised retention of function across eukaryotes. © 2017. Published by The Company of Biologists Ltd.

  10. Anticoagulant mechanism and platelet deaggregation property of a non-cytotoxic, acidic phospholipase A2 purified from Indian cobra (Naja naja) venom: inhibition of anticoagulant activity by low molecular weight heparin.

    Science.gov (United States)

    Dutta, Sumita; Gogoi, Debananda; Mukherjee, Ashis K

    2015-03-01

    In the present study, anticoagulant and platelet modulating activities of an acidic phospholipase A2 (NnPLA2-I) purified from Indian cobra Naja naja venom was investigated. The NnPLA2-I displayed a mass of 15.2 kDa and 14,186.0 Da when analyzed by SDS-PAGE and MALDI-TOF-MS, respectively. Peptide mass fingerprinting analysis of the NnPLA2-I showed its significant similarity with phospholipase A2 enzymes purified from cobra venom. BLAST analysis of one tryptic peptide sequence of NnPLA2-I demonstrated putative conserved domains of the PLA2-like superfamily. The Km and Vmax values of NnPLA2-I toward hydrolysis of its most preferred substrate-phosphotidylcholine (PC)-were determined to be 0.72 mM and 29.3 μmol min(-1) mg(-1), respectively. The anticoagulant activity of NnPLA2-I was found to be higher than the anticoagulant activity of heparin/AT-III or warfarin. The histidine modifying reagent, monovalent and polyvalent antivenom differentially inhibited the catalytic and anticoagulant activities of NnPLA2-I. Low molecular weight heparin did not inhibit the catalytic and platelet deaggregation activity of NnPLA2-I, albeit its anticoagulant activity was significantly reduced. The NnPLA2-I showed a non-enzymatic, mixed inhibition of thrombin with a Ki value of 9.3 nM. Heparin significantly decreased, with an IC50 value of 15.23 mIU, the thrombin inhibitory activity of NnPLA2-I. The NnPLA2-I uniquely increased the amidolytic activity of FXa without influencing its prothrombin activating property. NnPLA2-I showed dose-dependent deaggregation of platelet rich plasma (PRP) and inhibited the collagen and thrombin-induced aggregation of PRP. However, deaggregation of washed platelets by NnPLA2-I demonstrated in presence of PC or platelet poor plasma. Alkylation of histidine residue of NnPLA2-I resulted in 95% and 21% reduction of its platelet deaggregation and platelet binding properties, respectively. NnPLA2-I did not show cytotoxicity against human glioblastoma U87MG cells

  11. (67/68)Ga-labeling agent that liberates (67/68)Ga-NOTA-methionine by lysosomal proteolysis of parental low molecular weight polypeptides to reduce renal radioactivity levels.

    Science.gov (United States)

    Uehara, Tomoya; Rokugawa, Takemi; Kinoshita, Mai; Nemoto, Souki; Fransisco Lazaro, Guerra Gomez; Hanaoka, Hirofumi; Arano, Yasushi

    2014-11-19

    The renal localization of gallium-67 or gallium-68 ((67/68)Ga)-labeled low molecular weight (LMW) probes such as peptides and antibody fragments constitutes a problem in targeted imaging. Wu et al. previously showed that (67)Ga-labeled S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-Bz-NOTA)-conjugated methionine ((67)Ga-NOTA-Met) was rapidly excreted from the kidney in urine following lysosomal proteolysis of the parental (67)Ga-NOTA-Bz-SCN-disulfide-stabilized Fv fragment (Bioconjugate Chem., (1997) 8, 365-369). In the present study, a new (67/68)Ga-labeling reagent for LMW probes that liberates (67/68)Ga-NOTA-Met was designed, synthesized, and evaluated using longer-lived (67)Ga in order to reduce renal radioactivity levels. We employed a methionine-isoleucine (MI) dipeptide bond as the cleavable linkage. The amine residue of MI was coupled with SCN-Bz-NOTA for (67)Ga-labeling, while the carboxylic acid residue of MI was derivatized to maleimide for antibody conjugation in order to synthesize NOTA-MI-Mal. A Fab fragment of the anti-Her2 antibody was thiolated with iminothiolane, and NOTA-MI-Mal was conjugated with the antibody fragment by maleimide-thiol chemistry. The Fab fragment was also conjugated with SCN-Bz-NOTA (NOTA-Fab) for comparison. (67)Ga-NOTA-MI-Fab was obtained at radiochemical yields of over 95% and was stable in murine serum for 24 h. In the biodistribution study using normal mice, (67)Ga-NOTA-MI-Fab registered significantly lower renal radioactivity levels from 1 to 6 h postinjection than those of (67)Ga-NOTA-Fab. An analysis of urine samples obtained 6 h after the injection of (67)Ga-NOTA-MI-Fab showed that the majority of radioactivity was excreted as (67)Ga-NOTA-Met. In the biodistribution study using tumor-bearing mice, the tumor to kidney ratios of (67)Ga-NOTA-MI-Fab were 4 times higher (6 h postinjection) than those of (67)Ga-NOTA-Fab. Although further studies including the structure of radiometabolites and

  12. Coordination nature of aluminum (oxy)hydroxides formed under the influence of low molecular weight organic acids and a soil humic acid studied by X-ray absorption spectroscopy

    Science.gov (United States)

    Xu, R. K.; Hu, Y. F.; Dynes, J. J.; Zhao, A. Z.; Blyth, R. I. R.; Kozak, L. M.; Huang, P. M.

    2010-11-01

    Organic ligands in the environment hinder the formation of crystalline Al precipitation products by perturbing the hydrolytic and polymeric reactions of Al resulting in the formation of short-range ordered (SRO) mineral colloids with varying degrees of crystallinity. However, the effect of these ligands on the mechanisms of their formation and nature of the transformation products of Al (oxy)hydroxides at the atomic and molecular levels is not well understood. In this study, the coordination structure of Al in Al (oxy)hydroxides formed under the influence of varying concentrations of low molecular weight (LMW) organic acids such as citric, malic, salicylic and acetic acids and a humic acid (HA) was investigated with X-ray absorption near edge structure (XANES) spectroscopy, Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction analysis. The Al K- and L-edge XANES spectra showed that with increasing LMW organic acid concentration the coordination number of Al changed from 6-fold to a mixture of 4- and 6-fold, except for acetate as acetate was unable to perturb the formation of Al (oxy)hydroxides at the acetate/Al molar ratio (MR) = 0.1. The proportion of 4-fold to 6-fold coordinated Al in the Al precipitation products depended on the structure and functionality of the LMW organic acids. The incorporation of the LMW organic acid into the network structure of Al (oxy)hydroxides prevented the formation of sheets/inter-layer H-bonding that was required for the formation of crystalline Al (oxy)hydroxides. The HA used in this study only slightly perturbed the crystallization of the Al (oxy)hydroxides at the concentrations used. The Al K-edge data showed that Al coordination number had not been altered in the presence of HA. The findings obtained in the present study are of fundamental significance in understanding the physicochemical behavior of soils and sediments, and their relation to the accumulation and transport of nutrients and pollutants in the

  13. Homologous series of low molecular weight (C1-C10) monocarboxylic acids, benzoic acid and hydroxyacids in fine-mode (PM2.5) aerosols over the Bay of Bengal: Influence of heterogeneity in air masses and formation pathways

    Science.gov (United States)

    Boreddy, Suresh K. R.; Mochizuki, Tomoki; Kawamura, Kimitaka; Bikkina, Srinivas; Sarin, M. M.

    2017-10-01

    Low molecular weight monocarboxylic acids (LMW monoacids) are most abundant volatile organic compounds (VOCs) in the atmosphere and often act as important contributors to the acidity of precipitation in addition to inorganic acids. However, there is a large uncertainty in the sources and secondary formations of these acids in the atmosphere. This study reports homologous series of LMW monoacids, including normal (C1-C10), branched chain (iC4-iC6), aromatic (benzoic acid) and hydroxyacids (lactic and glycolic acids) in the fine-mode (PM2.5) aerosols collected over the Bay of Bengal (BoB) during a winter cruise (December 2008 to January 2009). The samples were associated with two distinct continental air masses arriving from the Indo-Gangetic Plain (IGP-outflow) and Southeast Asia (SEA-outflow). The molecular distributions of organic acids are characterized by the dominance of formic acid (C1) followed by acetic acid (C2) and nonanoic acid (C9) in the IGP-outflow, whereas dominance of C1 or C9 was observed in the SEA-outflow followed by C2. Formic-to-acetic acid (C1/C2) ratios were higher than unity (mean: 1.3 ± 0.3) in the IGP-outflow, whereas they were less than unity (0.9 ± 0.5) in the SEA-outflow. These results suggest that secondary formation of organic acids is largely important in the IGP-outflow whereas primary emission is a major source of organic acids in the SEA-outflow. Based on the correlation coefficient matrix analysis and C1/C2 and C4/C3 ratios, we consider that the sources of C1 are probably associated with the secondary formation via the oxidation of biogenic VOCs, while C2 has both primary and secondary formations associated with anthropogenic sources in the IGP-outflow. On the other hand, C1 and C2 have similar sources (both primary and secondary) originated from biomass burning and bacterial activities via long-range atmospheric transport in the SEA-outflow, as inferred from the MODIS fire spot data, significant concentrations of isovaleric

  14. Influence of Low Molecular Weight Polymers on the Rheology of Bentonite Suspensions Influence de polymères de faible masse moléculaire sur la rhéologie de suspensions de bentonite

    Directory of Open Access Journals (Sweden)

    Rossi S.

    2006-12-01

    Full Text Available In this communication we demonstrate how relatively low molecular weight synthetic polymers significantly alter the rheological properties of Bentonite/water suspensions depending upon the polymer dosage and/or degree of surface coverage on the clay particle. The behaviour of two types of nonionic polymers are reported; a series of nonylphenol poly(propylene oxide poly(ethylene oxide polymers with varying EO chain length and a series consisting of an ABA block copolymer of poly(propylene oxide-poly(ethylene oxide with varying EO chain length. Adsorption isotherms of dilute clay suspensions showed a higher uptake of the lowest molecular weight polymer (in µmol/m² for each series. The adsorbed amount G increases in the order NPE > PEO > PE. The oscillatory shear and steady state shear stress-shear rate measurements of concentrated clay suspensions (3-6% w/v facilitate the interpretation of the particle-particle interactions. The yield stress, plastic viscosity and elastic modulus showed a maximum at about 50% surface coverage by the NPE polymers, and a subsequent decrease due to stabilisation of the suspension. For the PE polymers these parameters continously decreased as the surface of the clay particle was covered. Scaling of the elastic modulus with increasing clay content allows the determination of the exponent n from a power-law fit G = Kon which qualitatively describes the degree of dispersion for the different polymers. Preliminary results of the effect of temperature and pressure on Bentonite/polymer suspensions are also presented. Dans cette communication, nous démontrons comment les polymères synthétiques de masse moléculaire relativement faible modifient notablement les propriétés rhéologiques de suspensions de bentonite dans l'eau en fonction de polymère et/ou du degré de couverture superficielle de la particule d'argile. Les comportements de deux types de polymères non ioniques sont décrits: une série de polymères

  15. [Controls of the plant endomembrane-secretory pathway]. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1991-12-31

    These studies are focused on elucidating the molecular structure of plant cell membranes with special reference to cell surface glycoproteins. The studies reported herein include use of monoclonal antibodies to characterize cell surface epitopes, construction of cDNA libraries of cell surface proteins, isolation of plant cell mutants by flow cytometry, detection of beta-glucouronidase marker enzyme systems in plants, expression go VSVG (the major envelope glycoprotein of Vesicular Stomatis Virus) in plant cells, and control of gene expression of cell membrane glycoproteins.(DT)

  16. (Controls of the plant endomembrane-secretory pathway)

    Energy Technology Data Exchange (ETDEWEB)

    1991-01-01

    These studies are focused on elucidating the molecular structure of plant cell membranes with special reference to cell surface glycoproteins. The studies reported herein include use of monoclonal antibodies to characterize cell surface epitopes, construction of cDNA libraries of cell surface proteins, isolation of plant cell mutants by flow cytometry, detection of beta-glucouronidase marker enzyme systems in plants, expression go VSVG (the major envelope glycoprotein of Vesicular Stomatis Virus) in plant cells, and control of gene expression of cell membrane glycoproteins.(DT)

  17. Characterization of low-molecular-weight glutenin subunit genes of ...

    Indian Academy of Sciences (India)

    2015-09-16

    Sep 16, 2015 ... sub-clusters, respectively, excepting only one known gene ... branch (the black triangle) represents some genes obtained in this ... to another cluster. Besides the genes of B and D genomes, almost all other genes in this cluster are from Sitopsis species, except for one LMW-GS of Ae. cylindrica with D.

  18. Low molecular weight organic acids in root exudates and cadmium ...

    African Journals Online (AJOL)

    The S. nigrum accumulated and translocated more Cd than S. lycopersicum. The soil solution pH of S. nigrum was significantly lower than S. lycopersicum. The S. nigrum with higher concentrations of LMWOA in roots exudation accumulated more Cd in the plants. The results indicated tha LMWOA secretion by S. nigrum root ...

  19. Low molecular weight organic acids in root exudates and cadmium ...

    African Journals Online (AJOL)

    ajl yemi

    2011-11-28

    –234. Cieslinski G, Van Rees KCJ, Szmigielska AM, Krishnamurti GSR,. Huang PM (1998). Lowmolecular-weight organic acids in rhizosphere soils of durum wheat and their effect on cadmium bioaccumulation. Plant Soil, 203: ...

  20. Silk-inspired low-molecular-weight organogelator.

    Science.gov (United States)

    Escuder, Beatriu; Miravet, Juan F

    2006-08-29

    A minimal sequence from natural silks, the tetrapeptide GAGA, has been used as inspiration for the design of a new organogelator. Gels were obtained in several organic solvents, and their microscopic aspects were studied by transmission and cryo-scanning electron microscopies (TEM and cryo-SEM). FT-IR spectroscopy, circular dichroism, and wide-angle X-ray diffraction were used to study the self-assembly features of this molecule, and evidence of an antiparallel beta-sheet organization was obtained. Remarkably, the precise secondary structure uniqueness found in Nature was successfully transferred into a small synthetic analogue that self-assembles driven only by noncovalent interactions.

  1. Low-molecular-weight heparins allow selected outpatient treatment ...

    African Journals Online (AJOL)

    DVT) at present consists of an initial continuous intravenous infusion of unfractionated heparin, administered for a minimum of 5 - 7 days.' Oral anticoagulation is started at the same time, while the patient is still in hospital, and is continued for at ...

  2. Characterization of low-molecular-weight glutenin subunit genes of ...

    Indian Academy of Sciences (India)

    1. 0. 1. 5. 1. 1. 9. *Genes contain the 9th cysteine were found in the C-terminal domain of five clones of SL131-. 2, SL131-1, SL131-3, SL133-3, and SL133-1. Sig, signal peptide; N-, N-terminal domain; rep., repetitive domain. CI, CII and CIII indicate the CI, CII and CIII regions of C-terminal domain. Journal of Genetics ...

  3. Low-Molecular Weight Caldesmon in Glioma Neovascularization

    NARCIS (Netherlands)

    P.P. Zheng (Pingpin)

    2005-01-01

    textabstractOndanks grote vooruitgang in neuroradiologische beeldvorming, neurochirurgische technieken, radiotherapeutische methodieken en de recente successen met chemotherapeutische behandeling van gliale tumoren, blijft de prognose van patienten met dergelijke tumoren, in het bijzonder de maligne

  4. Clinical effects of low-molecular-weight heparin combined with ...

    African Journals Online (AJOL)

    The treatment lasted for 2 weeks. Clinical parameters, laboratory test indices, Acute Physiology and Chronic Health Evaluation (APACHE II) score, and computed tomography score of pancreatic necrosis (CTSPN) were assessed in both groups. Results: On admission, no significant differences were noted in clinical features, ...

  5. Low-molecular-weight oxidants involved in disulfide bond formation.

    Science.gov (United States)

    Ruddock, Lloyd W

    2012-05-15

    The biogenesis of most secreted and outer membrane proteins involves the formation of structure stabilizing disulfide bonds. Hence knowledge of the mechanisms for their formation is critical for understanding a myriad of cellular processes and associated disease states. Until recently it was thought that members of the Ero1 sulfhydryl oxidase family were responsible for catalyzing the majority of disulfide bond formation in the endoplasmic reticulum. However, multiple eukaryotic organisms are now known to show no or minor phenotypes when these enzymatic pathways are disrupted, suggesting that other pathways can catalyze disulfide bond formation to an extent sufficient to maintain normal physiology. This lack of a strong phenotype raises multiple questions regarding what pathways are acting and whether they themselves constitute the major route for disulfide bond formation. This review critically examines the potential low molecular oxidants that maybe involved in the catalyzed or noncatalyzed formation of disulfide bonds, with an emphasis on the mammalian endoplasmic reticulum, via an examination of their thermodynamics, kinetics, and availability and gives pointers to help guide future experimental work.

  6. Prophylaxis of postoperative thromboembolism with low molecular weight heparins

    DEFF Research Database (Denmark)

    Jørgensen, L N; Wille-Jørgensen, P; Hauch, O

    1993-01-01

    to placebo or dextran and at least as efficient as unfractionated heparin in the prevention of deep vein thrombosis (DVT). Compared with unfractionated heparin, one of the LMWH preparations significantly reduced the total incidence of DVT. The rate of non-fatal pulmonary embolism was 0.49 per cent...... in patients receiving LMWH and 1.22 per cent in controls. Seven orthopaedic patients (0.15 per cent) died from pulmonary embolism, none of whom received LMWH. In general surgery, the LMWHs were at least as efficient as unfractionated heparin, with a trend towards a lower risk of pulmonary embolism...

  7. Effects of low-molecular weight alcohols on bacterial viability

    Directory of Open Access Journals (Sweden)

    Man Adrian

    2017-10-01

    Full Text Available Alcohol based solutions are among the most convenient and wide spread aid in the prevention of nosocomial infections. The current study followed the efficacy of several types and isomers of alcohols on different bacterial species. Seven alcohols (ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl alcohol, and ethylene glycol were used to evaluate their minimal inhibitory and bactericidal effects by microdilution method on bacteria that express many phenotypical characteristics: different cell-wall structure (Gram positive/negative bacteria, capsule production (Klebsiella pneumoniae, antibiotic resistance (MRSA vs MSSA or high environmental adaptability (Pseudomonas aeruginosa. Results: The best inhibitory effect was noticed for n-propyl, followed by iso-propyl, n-butyl, and iso-butyl alcohols with equal values. Ethylene glycol was the most inefficient alcohol on all bacteria. In K. pneumoniae and P. aeruginosa, the bactericidal concentrations were higher than the inhibitory one, and to a level similar to that encountered for most of the Gram-positive bacteria. Among Gram-positive cocci, E. faecalis presented the lowest susceptibility to alcohols. Conclusions: All alcohols presented good effect on bacteria, even in low concentrations. Compared to ethanol as standard, there are better alternatives that can be used as antimicrobials, namely longer-chain alcohols such as propyl or butyric alcohols and their iso- isomers. Ethylene glycol should be avoided, due to its toxicity hazard and low antimicrobial efficacy. Bacterial phenotype (highly adaptable bacteria, biofilm formation and structure (cell wall structure, presence of capsule may drastically affect the responsiveness to the antimicrobial activity of alcohols, leading to higher bactericidal than inhibitory concentrations.

  8. Preventive role of low-molecular-weight heparin in unexplained ...

    African Journals Online (AJOL)

    All pregnant females between 18 and 44 years of age who reported at the unit of obstetrics and gynaecology, Shifa International Hospital, Islamabad, during April 2013 to January 2014, who had a history of ≥2 consecutive first trimester pregnancy losses were enrolled. All participants were randomly allocated to one of two ...

  9. Prophylaxis of postoperative thromboembolism with low molecular weight heparins

    DEFF Research Database (Denmark)

    Jørgensen, L N; Wille-Jørgensen, P; Hauch, O

    1993-01-01

    to placebo or dextran and at least as efficient as unfractionated heparin in the prevention of deep vein thrombosis (DVT). Compared with unfractionated heparin, one of the LMWH preparations significantly reduced the total incidence of DVT. The rate of non-fatal pulmonary embolism was 0.49 per cent...

  10. Extraction of low molecular weight RNA from Citrus trifolita tissues ...

    African Journals Online (AJOL)

    Jane

    2010-12-20

    Dec 20, 2010 ... total RNA extraction from citrus tissues, then generation of LMW RNA using 4M LiCl, which ... In addition, the entire procedure can be completed within 4 hours with many samples being processed ... many higher plants, especially in mature tissues, ... Use of trizol is convenient and gives high quality end.

  11. Low molecular weight block copolymers as plasticizers for polystyrene

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Karsten; Nielsen, Charlotte Juel; Hvilsted, Søren

    2005-01-01

    Polystyrene-b-alkyl, polystyrene-b-polybutadiene-b-polystyrene, and polystyrene-b-poly(propylene glycol)monotridecyl ether were synthesized using macro initiators and atom transfer radical polymerization or by esterifications of homopolymers. The aim was a maximum molecular weight of 4 kg....../mol and minimum polystyrene content of 50 w/w%, which by us is predicted as the limits for solubility of polystyrene-b-alkyl in polystyrene. DSC showed polystyrene was plasticized, as seen by a reduction in glass transition temperature, by block copolymers consisting of a polystyrene block with molecular weight...... of approximately 1 kg/mol and an alkyl block with a molecular weight of approximately of 0.3 kg/mol. The efficiency of the block copolymers as plasticizers increases with decreasing molecular weight and polystyrene content. In addition, polystyrene-b-alkyl is found to be an efficient plasticizer also...

  12. Extraction of low molecular weight RNA from Citrus trifolita tissues ...

    African Journals Online (AJOL)

    Jane

    2010-12-20

    Dec 20, 2010 ... air-dried for a few minutes and then exposed to BIOMAX X-ray film for 48 h using an intensifying screen (Sunkar and Zhu, 2004). RESULTS AND DISSCUSSION. Size of LMW RNA obtained. After isolation, the pure LMW RNA of different citrus tissues obtained using the protocol described above was.

  13. Extraction of low molecular weight RNA from Citrus trifolita tissues ...

    African Journals Online (AJOL)

    Most traditional methods for LMW RNA isolation involve many steps and chemical reagents which upon degradation may negatively affect results. We employed a simple and quick method involving trizol for total RNA extraction from citrus tissues, then generation of LMW RNA using 4M LiCl, which have been successfully ...

  14. Low molecular weight allergens of the pollen of Parietaria officinalis.

    Science.gov (United States)

    Ruffilli, A; Oreste, U; Santonastaso, V; Scotto D' Abusco, A; Sacerdoti, G

    1987-03-01

    The allergenic composition of a low mol. wt fraction of the pollen extract of Parietaria officinalis (PO) was investigated. Fraction C, that was eluted after oxytocin (mol. wt 1040) when the pollen extract was gel filtered on Sephadex or on Biogel, was cross-reactive in the RAST with the major allergen P015 and was capable of eliciting histamine release from leukocytes of sensitive donors. RAST inhibition (RAST I) analysis of the eluate of gel filtration on Sephadex G-10 revealed several peaks of IgE binding activity. Analysis of fine specificity of response of individual patients carried out by skin-prick tests and by RAST I, revealed individual patterns of reactivity, indicating that allergens contained in fraction C were minor allergens.

  15. Characterization of a Cryptic and Intriguing Low Molecular Weight Plasmid.

    Science.gov (United States)

    Carneiro, Lilian C; Mendes, Paulo Vinicius C; Silva, Silvana P; Souza, Guilherme R L; Bataus, Luiz Artur M

    2016-03-01

    The complete nucleotide sequence of cryptic plasmid pVCM04 isolated from Salmonella enterica serovar Enteritidis was determined and analyzed. pVCM04 contains 3853 bp with 53.6 % GC content and has twelve ORFs with more than 50 amino acids. Five of these sequences showed homology with replication and mobilization proteins. ORF1 and ORF2 showed homology with replication proteins, while ORFs 3-5 showed homology with mobilization proteins. The pVCM04 possesses a region associated with the theta-type replication mechanism. BLASTn search analysis revealed unexpectedly no similarity with sequences deposited in GenBank. The nucleotide sequence of pVCM04 can be divided into two arms: the region between nucleotides 552-1774 (encoding RepA and RepB) and the region between nucleotides 1775-3853 (encoding MobA, MobB and MobC). Codon bias pattern is distinct between mobA and repA, so the program Modeltest was used to select the best evolutionary model to study these genes. The result of ModelTest (model GTR+G for mobA and model HKY+G for repA) suggests that these genes would be subject to different selective pressures. Considering the differences in the codon usage, the selection of two different evolutionary models, and the absence of plasmids with homology to pVCM04 in GenBank, we believe that pVCM04 is a chimeric molecule and represents a new plasmid lineage.

  16. Cadmium stress disrupts the endomembrane organelles and endocytosis during Picea wilsonii pollen germination and tube growth.

    Directory of Open Access Journals (Sweden)

    Xiaoxia Wang

    Full Text Available As one of the most severe pollutants, cadmium has been reported to be harmful to plant cells, but the effects of cadmium on gymnosperm pollen germination and tube growth and the mechanism of this involvement are still unclear. Here, we report that cadmium not only strongly inhibited P. wilsonii pollen germination and tube growth, but also significantly altered tube morphology in a dose-dependent manner. Time-lapse images obtained with a laser scanning confocal microscope revealed that endocytosis was dramatically inhibited by cadmium stress. Further investigation with ER-Tracker dye indicated that cadmium stress reduced the number of the Golgi apparatus, and induced dilation of ER. Additionally, Lyso-Tracker staining showed that cadmium distinctly promoted the formation of acidic organelles in pollen tubes, likely derived from the dilated ER. Taken together, our studies indicated that P. wilsonii pollens were highly susceptible to cadmium stress, and that cadmium stress strongly inhibited pollen germination and tube growth by disrupting the endomembrane organelles, inhibiting endo/exocytosis, and forming acidic vacuoles, resulting in swollen tube tips and irregularly broadened tube diameters. These findings provide a new insight into the effects of cadmium toxicity on the tip growth of pollen tubes.

  17. Endomembrane-associated RSD-3 is important for RNAi induced by extracellular silencing RNA in both somatic and germ cells of Caenorhabditis elegans.

    Science.gov (United States)

    Imae, Rieko; Dejima, Katsufumi; Kage-Nakadai, Eriko; Arai, Hiroyuki; Mitani, Shohei

    2016-06-16

    RNA silencing signals in C. elegans spread among cells, leading to RNAi throughout the body. During systemic spread of RNAi, membrane trafficking is thought to play important roles. Here, we show that RNAi Spreading Defective-3 (rsd-3), which encodes a homolog of epsinR, a conserved ENTH (epsin N-terminal homology) domain protein, generally participates in cellular uptake of silencing RNA. RSD-3 is previously thought to be involved in systemic RNAi only in germ cells, but we isolated several deletion alleles of rsd-3, and found that these mutants are defective in the spread of silencing RNA not only into germ cells but also into somatic cells. RSD-3 is ubiquitously expressed, and intracellularly localized to the trans-Golgi network (TGN) and endosomes. Tissue-specific rescue experiments indicate that RSD-3 is required for importing silencing RNA into cells rather than exporting from cells. Structure/function analysis showed that the ENTH domain alone is sufficient, and membrane association of the ENTH domain is required, for RSD-3 function in systemic RNAi. Our results suggest that endomembrane trafficking through the TGN and endosomes generally plays an important role in cellular uptake of silencing RNA.

  18. The effect of prophylactic dose of a low molecular weight heparin on skin wound healing of rats Efeito da dose profilática de heparina de baixo peso molecular na cicatrização de feridas na pele de ratos

    Directory of Open Access Journals (Sweden)

    Ozdamar Fuad Oken

    2009-12-01

    Full Text Available PURPOSE: To investigate the effect of prophylactic dose of a low molecular weight heparin, enoxaparin, on skin wound healing of rats. METHODS: Forty rats were used for the study. Rats were randomly assigned to two equal groups. Experimental group received prophylactic dose of enoxaparin. Physiologic saline was administered to the control group. Parameters of wound healing of experimental and control groups were compared. For comparison of the groups in terms of fibrosis, vascularization, inflammation, epithelization, and tensile strength test (Newton. Mann-Whitney-U test was used because variables were categorical data (fibrosis, vascularization, inflammation and epithelization. Differences between groups were analyzed with independent samples t-test (tensile strength. Significance was set at pOBJETIVO: Investigar o efeito de dose profilática da heparina de baixo peso molecular, enoxaparina, na cicatrização de feridas na pele de ratos. MÉTODOS: Quarenta ratos foram utilizados para o estudo. Ratos foram distribuídos aleatoriamente a dois grupos iguais. O grupo experimental recebeu profilática de enoxaparina. Solução salina fisiologica foi administrada ao grupo controle. Foram comparados parâmetros de cicatrização dos grupos experimental e controle.Os grupos foram comparados em termos de fibrose, vascularização, inflamação, epitelização e força tensil (teste de Newton. Foi realizado o teste de Mann-Whitney-U para variáveis com dados categóricos (fibrose, cicatrização, inflamação e epitelização. Diferenças entre os grupos foram analisadas como amostras independentes pelo t-teste (força tensil. Significância foi fixada para p < 0,05. RESULTADOS: A ferida do grupo experimental apresentou força tensil diminuída significativamente (p < 0,001, o exame histopatológico revelou um significativo (p < 0,001 retardo na epitelização e diminuição na fibrose, cicatrização, inflamação (p < 0,001 no grupo experimental

  19. Estudo experimental dos efeitos da heparina de baixo peso molecular (Enoxaparina na formação de calo ósseo em fêmures de ratos The effects of low-molecular-weight heparin (Enoxaparin on bony callus formation in rats' femurs - an experimental study

    Directory of Open Access Journals (Sweden)

    Salim Mussi Filho

    2006-01-01

    Full Text Available O tromboembolismo venoso é uma complicação grave que pode ocorrer após fraturas. O tratamento anticoagulante mais utilizado é com a heparina de baixo peso molecular (HBPM. Existem estudos que mostram que essa droga pode interferir no metabolismo ósseo. Com o objetivo de avaliar a influência da HBPM no processo de formação de calo ósseo, realizamos um estudo experimental em ratos. A amostra constituiu-se de 22 ratos de linhagem Wistar, machos, que foram submetidos à fratura diafisária de seus fêmures direitos. Foram divididos em dois grupos de 11. No grupo controle, os animais recebiam soro fisiológico e no grupo de estudo, recebiam HBPM, enoxaparina, diariamente, por 28 dias. Após este período os ratos foram submetidos à eutanásia e os fêmures foram avaliados. No estudo macroscópico foi constatada consolidação em 11 animais (100% que não receberam enoxaparina, e, em dez animais (90,9% que receberam a droga em estudo. No estudo histológico foi constatada a formação de calo ósseo em todos os fêmures. Concluiu-se neste experimento que a enoxaparina não altera o processo de consolidação óssea em fêmures de ratos Wistar.Venous thromboembolism is a serious complication that may follow fractures. The most commonly used anticoagulant treatment is low-molecular-weight heparin (LMWH. There are some studies showing that this drug may interfere on bone metabolism. With the objective of evaluating the LMWH influence on the process of bony callus formation, we conducted an experimental study on rats. Sample was constituted of 22 Wistar male rats, which were submitted to diaphyseal fracture on their right femurs. They were divided into two groups of 11 subjects each. In the control group, the animals received saline solution and in the study group, they received LMWH - enoxaparin - in a daily basis, during 28 days. After that period, the rats were submitted to euthanasia for femur assessment purposes. At the macroscopic study

  20. Ácidos orgânicos de baixo peso molecular e ácidos húmicos e alterações em algumas propriedades físicas e químicas de Latossolos, Plintossolo e Neossolo Quartzarênico Low molecular weight organic and humic acids and effects on physical and chemical properties of Oxisols and related soils

    Directory of Open Access Journals (Sweden)

    Marcelo Metri Corrêa

    2008-02-01

    longa, podendo-se estabelecer a seguinte ordem, de acordo com seu efeito: ácido cítrico > ácido oxálico > ácidos húmicos. O conteúdo de argila dispersa em água mostrou ser o principal fator responsável pelo aumento da resistência à penetração.The organic acids from the organic matter decomposition, root exudation and microbial activity, play an important role on physical and chemical soil conditions. However their efficiency is conditioned to the quality and kind of organic acids and interactions with the soil mineral surface. The aim of this study was to evaluate the effect of humic and organic acids of high and low molecular weight on the physical and chemical properties of B horizons of four Oxisols and one Plinthustult, and a C horizon of Quartzipsamment. A completely randomized 6x3x5 factorial design (soils x organic acids x dose was used, with 3 replications. The following organic acid rates were applied: 0, 1, 3, 9 and 18 mM citric and oxalic acid and 0.0; 2.0; 4.0; 6.0 and 10.0 g kg-1 humic acids. The experimental units consisted of 25 cm³ of air-dried fine-earth fraction in PVC cylinders (2.0 cm height and 4.0 cm diameter, subjected to moistening and drying cycles in an isothermal chamber at 30 °C, for three days, in seven cycles. The water dispersible clay, penetration resistance and ammonium oxalate-extracted Fe and Al were determined. The contents of water dispersible clay were variable, related to the rate and type of organic acids, and also to soil texture and mineralogy. Thus, the dispersion resistance of the goethitic was higher than of the hematitic soils, which was in turn higher than of the gibbsitic soils. Moreover, organic acids of low molecular weight resulted in higher dispersion and penetration resistance than those of high molecular weight, in the following sequence: citric acid ³ oxalic acid > humic acid. The content of water dispersible clay proved to be an important factor in the increase of penetration resistance.

  1. Effect of high and low molecular weight glutenin subunits, and subunits of gliadin on physicochemical parameters of different wheat genotypes Efeito das subunidades de glutenina de alto e baixo peso molecular e das subunidades de gliadina sobre os parâmetros físico-químicos de diferentes genótipos de trigo

    Directory of Open Access Journals (Sweden)

    Mariana Souza Costa

    2013-02-01

    Full Text Available Identification of functional properties of wheat flour by specific tests allows genotypes with appropriate characteristics to be selected for specific industrial uses. The objective of wheat breeding programs is to improve the quality of germplasm bank in order to be able to develop wheat with suitable gluten strength and extensibility for bread making. The aim of this study was to evaluate 16 wheat genotypes by correlating both glutenin subunits of high and low molecular weight and gliadin subunits with the physicochemical characteristics of the grain. Protein content, sedimentation volume, sedimentation index, and falling number values were analyzed after the grains were milled. Hectoliter weight and mass of 1000 seeds were also determined. The glutenin and gliadin subunits were separated using polyacrylamide gel in the presence of sodium dodecyl sulfate. The data were evaluated using variance analysis, Pearson's correlation, principal component analysis, and cluster analysis. The IPR 85, IPR Catuara TM, T 091015, and T 091069 genotypes stood out from the others, which indicate their possibly superior grain quality with higher sedimentation volume, higher sedimentation index, and higher mass of 1000 seeds; these genotypes possessed the subunits 1 (Glu-A1, 5 + 10 (Glu-D1, c (Glu-A3, and b (Glu-B3, with exception of T 091069 genotype that possessed the g allele instead of b in the Glu-B3.A identificação das propriedades funcionais de farinhas de trigo através de testes específicos possibilita selecionar genótipos de trigo com características adequadas a cada uso industrial. O principal objetivo dos programas de melhoramento genético é melhorar a qualidade do banco de germoplasma para que seja possível desenvolver trigos com força de glúten e extensibilidade adequadas para produção de produtos panificáveis. O objetivo deste estudo foi avaliar 16 genótipos de trigo correlacionando as subunidades de gluteninas de alto e baixo peso

  2. Intracellular accommodation of rhizobia in legume host cell: the fine-tuning of the endomembrane system

    NARCIS (Netherlands)

    Gavrin, A.Y.

    2015-01-01

    The symbiosis of legumes with rhizobia leads to the formation of root nodules. Rhizobia which are hosted inside specialized infected cells are surrounded by hostderived membranes, forming symbiosomes. Although it is known that symbiosome formation involves proliferation of membranes and changing of

  3. The TGB1 movement protein of Potato virus X reorganizes actin and endomembranes into the X-body, a viral replication factory.

    Science.gov (United States)

    Tilsner, Jens; Linnik, Olga; Wright, Kathryn M; Bell, Karen; Roberts, Alison G; Lacomme, Christophe; Santa Cruz, Simon; Oparka, Karl J

    2012-03-01

    Potato virus X (PVX) requires three virally encoded proteins, the triple gene block (TGB), for movement between cells. TGB1 is a multifunctional protein that suppresses host gene silencing and moves from cell to cell through plasmodesmata, while TGB2 and TGB3 are membrane-spanning proteins associated with endoplasmic reticulum-derived granular vesicles. Here, we show that TGB1 organizes the PVX "X-body," a virally induced inclusion structure, by remodeling host actin and endomembranes (endoplasmic reticulum and Golgi). Within the X-body, TGB1 forms helically arranged aggregates surrounded by a reservoir of the recruited host endomembranes. The TGB2/3 proteins reside in granular vesicles within this reservoir, in the same region as nonencapsidated viral RNA, while encapsidated virions accumulate at the outer (cytoplasmic) face of the X-body, which comprises a highly organized virus "factory." TGB1 is both necessary and sufficient to remodel host actin and endomembranes and to recruit TGB2/3 to the X-body, thus emerging as the central orchestrator of the X-body. Our results indicate that the actin/endomembrane-reorganizing properties of TGB1 function to compartmentalize the viral gene products of PVX infection.

  4. Wide-range high-resolution transmission electron microscopy reveals morphological and distributional changes of endomembrane compartments during log to stationary transition of growth phase in tobacco BY-2 cells.

    Science.gov (United States)

    Toyooka, Kiminori; Sato, Mayuko; Kutsuna, Natsumaro; Higaki, Takumi; Sawaki, Fumie; Wakazaki, Mayumi; Goto, Yumi; Hasezawa, Seiichiro; Nagata, Noriko; Matsuoka, Ken

    2014-09-01

    Rapid growth of plant cells by cell division and expansion requires an endomembrane trafficking system. The endomembrane compartments, such as the Golgi stacks, endosome and vesicles, are important in the synthesis and trafficking of cell wall materials during cell elongation. However, changes in the morphology, distribution and number of these compartments during the different stages of cell proliferation and differentiation have not yet been clarified. In this study, we examined these changes at the ultrastructural level in tobacco Bright yellow 2 (BY-2) cells during the log and stationary phases of growth. We analyzed images of the BY-2 cells prepared by the high-pressure freezing/freeze substitution technique with the aid of an auto-acquisition transmission electron microscope system. We quantified the distribution of secretory and endosomal compartments in longitudinal sections of whole cells by using wide-range gigapixel-class images obtained by merging thousands of transmission electron micrographs. During the log phase, all Golgi stacks were composed of several thick cisternae. Approximately 20 vesicle clusters (VCs), including the trans-Golgi network and secretory vesicle cluster, were observed throughout the cell. In the stationary-phase cells, Golgi stacks were thin with small cisternae, and only a few VCs were observed. Nearly the same number of multivesicular body and small high-density vesicles were observed in both the stationary and log phases. Results from electron microscopy and live fluorescence imaging indicate that the morphology and distribution of secretory-related compartments dramatically change when cells transition from log to stationary phases of growth. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. Intracellular traffic of the lysine and glutamic acid rich protein KERP1 reveals features of endomembrane organization in Entamoeba histolytica.

    Science.gov (United States)

    Perdomo, Doranda; Manich, Maria; Syan, Sylvie; Olivo-Marin, Jean-Christophe; Dufour, Alexandre C; Guillén, Nancy

    2016-08-01

    The development of amoebiasis is influenced by the expression of the lysine and glutamic acid rich protei