Search results for: Drug gingival hyperplasia

Authors: Hui Wang, Harish Padmanabhan, David Thomson, Krassen Dimitrov

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Two optimized strategies were successfully established to develop biomolecule-based magnetic nanoassemblies. Streptavidin-coated and amine-coated magnetic nanoparticles were chosen as model scaffolds onto which double-stranded DNA and human immunoglobulin G were specifically conjugated in succession, using biotin-streptavidin interaction or covalent cross-linkers. The success of this study opens the prospect of developing selective and sensitive nanoparticle-based structures for diagnostics or drug delivery.

Keywords: Antibody, DNA, linker, magnetic nanoparticles, streptavidin

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Authors: Samy A. Selim, Nashwa I. Hagag

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Abstract–The objectives of the current study are to determine the prevalence, etiological agents, drug susceptibility pattern and plasmid profile of Acinetobacter baumannii isolates from Hospital-Acquired Infections (HAI) at Community Hospital, Al Jouf Province, Saudi Arabia. A total of 1890 patients had developed infection during hospital admission and were included in the study. Among those who developed nosocomial infections, 15(9.4), 10(2.7) and 118 (12.7) had respiratory tract infection (RTI), blood stream infections (BSI) and urinary tract (UTI) respectively. A total of 268 bacterial isolates were isolated from nosocomial infection. S. aureus was reported in 23.5% for of the total isolates followed by Klebsiella pneumoniae (17.5%), E. coli (17.2%), P. aeruginosa (11.9%), coagulase negative staphylococcus (9%), A. baumannii (7.1%), Enterobacter spp. (3.4%), Citrobacter freundii (3%), Proteus mirabilis (2.6%), and Proteus vulgaris and Enterococcous faecalis (0.7%). Isolated organisms are multi-drug resistant, predominantly Gram-positive pathogens with a high incidence of methicillin-resistant S. aureus, extended spectrum beta lactamase and vancomycin resistant enterococci organisms. The RFLP (Fragment Length Polymorphisms) patterns of plasmid preparations from isolated A. baumannii isolates had altered RFLP patterns, possibly due to the presence of plasmid(s). Five A. baumannii isolates harbored plasmids all of which were not less than 2.71kbp in molecular weight. Hence, it showed that the gene coding for the isolates were located on the plasmid DNA while the remaining isolates which have no plasmid might showed gene coding for antibiotic resistance being located on chromosomal DNA. Nosocomial infections represent a current problem in Community Hospital, Al Jouf Province, Saudi Arabia. Problems associated with SSI include infection with multidrug resistant pathogens which are difficult to treat and are associated with increased mortality.

Keywords: Hospital-Acquired Infections, Acinetobacter baumannii, antibiotic resistance, plasmid profile, RFLP patterns, Al Jouf Province, Saudi Arabia

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Authors: Rawia M. Khalil, Ahmed A. Abd El Rahman, Mahfouz A. Kassem, Mohamed S. El Ridi, Mona M. Abou Samra, Ghada E. A. Awad, Soheir S. Mansy

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Solid lipid nanoparticles (SLNs) have gained great attention for the topical treatment of skin associated fungal infection as they facilitate the skin penetration of loaded drugs. Our work deals with the preparation of nystatin loaded solid lipid nanoparticles (NystSLNs) using the hot homogenization and ultrasonication method. The prepared NystSLNs were characterized in terms of entrapment efficiency, particle size, zeta potential, transmission electron microscopy, differential scanning calorimetry, rheological behavior and in vitro drug release. A stability study for 6 months was performed. A microbiological study was conducted in male rats infected with Candida albicans, by counting the colonies and examining the histopathological changes induced on the skin of infected rats. The results showed that SLNs dispersions are spherical in shape with particle size ranging from 83.26±11.33 to 955.04±1.09 nm. The entrapment efficiencies are ranging from 19.73±1.21 to 72.46±0.66% with zeta potential ranging from -18.9 to -38.8 mV and shear-thinning rheological Behavior. The stability studies done for 6 months showed that nystatin (Nyst) is a good candidate for topical SLN formulations. A least number of colony forming unit/ ml (cfu/ml) was recorded for the selected NystSLN compared to the drug solution and the commercial Nystatin® cream present in the market. It can be fulfilled from this work that SLNs provide a good skin targeting effect and may represent promising carrier for topical delivery of Nyst offering the sustained release and maintaining the localized effect, resulting in an effective treatment of cutaneous fungal infection.

Keywords: Candida infections, Hot homogenization, Nystatin, Solid lipid nanoparticles, Stability, Topical delivery.

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Authors: Sérgio F. Sousa, Nuno M. F. S. A. Cerqueira, Marta A. S. Perez, Irina S. Moreira, António J. M.Ribeiro, Ana R. A. P. Neves, Maria J. Ramos, Pedro A. Fernandes

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In this work we report the recent progresses that have been achieved by our group in the last half decade on the field of computational proteomics. Specifically, we discuss the application of Molecular Dynamics Simulations and Electronic Structure Calculations in drug design, in the clarification of the structural and dynamic properties of proteins and enzymes and in the understanding of the catalytic and inhibition mechanism of cancer-related enzymes. A set of examples illustrate the concepts and help to introduce the reader into this important and fast moving field.

Keywords: Enzyme, Molecular Dynamics, Protein, Quantum Mechanics.

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Authors: Marzhan Baimurzayeva, Alibek Utyanov, Gulnar Shabdarbaeva, Damir Khussainov

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This article introduces the actual problem that is а study of proposed by the authors Hydrocele ointment in amino acids’ metabolism of cows’ blood in inflammation of traumatic origin. Hydrocele ointment has shown a positive effect on inflammatory process and amino acids’ metabolism of animals treated with the drug. Amino acid levels reached physiological parameters on the 10th day after treatment; in the control group this parameter was higher than normal.

Keywords: Amino acids, blood protein, Hydrocele ointment, inflammation, repair.

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Authors: Abdulkareem Hamid, Adam Daïch

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Camptothecin (CPT) is a cytotoxic quinoline alkaloid, which inhibits the DNA enzyme topoisomerase I (topo I). It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs. It was isolated from the bark and stem of Camptotheca acuminata (Camptotheca, Happy tree), a tree native in China. CPT showed remarkable anticancer activity in preliminary clinical trials but also low solubility and (high) adverse drug reaction. Because of these disadvantages synthetic and medicinal chemists have developed numerous syntheses of Camptothecine [1][2][3] and various derivatives to increase the benefits of the chemical, with good results. In our method CPT analogues has be six steps starting from available material DL Malic acid.

Keywords: Camptothecine, synthesis, analogue.

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Authors: I. Blazkova, A. Moulick, V. Milosavljevic, P. Kopel, M. Vaculovicova, V. Adam, R. Kizek

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Doxorubicin (DOX) is an anthracycline drug used to treat many cancer diseases. Similarly to other cytostatic drugs, DOX has serious side effects; the biggest obstacle is the cardiotoxicity. With the aim of lowering the negative side effects and to target the DOX into the tumor tissue, the different nanoparticles (NPs) are studied. The aim of this work was to synthetized different NPs and conjugated them with DOX and determine the binding capacity of the NPs. For this experiment, carbon nanotubes (CNTs), graphene oxide (GO), fullerene (FUL) and liposomes (LIP) were used. The highest binding capacity was observed in GO (85%). Subsequently the toxicity of NPs and NPs-DOX conjugates was analyzed in in vivo system (chicken embryos). Some NPs (GO) can increase the toxicity of DOX, whereas other NPs (LIP, CNTs) decrease DOX toxicity.

Keywords: Chicken embryos, Doxorubicin, Nanotransporters, Toxicity

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Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri

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In this study, ¹⁷⁷Lu-DOTATOC was prepared under optimized conditions (radiochemical purity: > 99%, radionuclidic purity: > 99%). The percentage of injected dose per gram (%ID/g) was calculated for organs up to 168 h post injection. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. The biodistribution data showed the significant excretion of the radioactivity from the kidneys. The adrenal and pancreas, as major expression sites for somatostatin receptor (SSTR), had significant uptake. A pharmacokinetic model of ¹⁷⁷Lu-DOTATOC was presented by compartmental analysis which demonstrates the behavior of the complex.

Keywords: Biodistribution, compartmental modeling, 177Lu, octreotide.

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Authors: Igbakura I. Luga, Alex A. Adikwu

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A comparison of resistance to quinolones was carried out on isolates of Shiga toxin-producing Escherichia coliO157:H7 from cattle and mecA and nuc genes harbouring Staphylococcus aureus from pigs. The isolates were separately tested in the first and current decades of the 21^st century. The objective was to demonstrate the dissemination of resistance to this frontline class of antibiotic by bacteria from food animals and bring to the limelight the spread of antibiotic resistance in Nigeria. A total of 10 isolates of the E. coli O157:H7 and 9 of mecA and nuc genes harbouring S. aureus were obtained following isolation, biochemical testing, and serological identification using the Remel Wellcolex E. coli O157:H7 test. Shiga toxin-production screening in the E. coli O157:H7 using the verotoxin E. coli reverse passive latex agglutination (VTEC-RPLA) test; and molecular identification of the mecA and nuc genes in S. aureus. Detection of the mecA and nuc genes were carried out using the protocol by the Danish Technical University (DTU) using the following primers mecA-1:5'-GGGATCATAGCGTCATTATTC-3', mecA-2: 5'-AACGATTGTGACACGATAGCC-3', nuc-1: 5'-TCAGCAAATGCATCACAAACAG-3', nuc-2: 5'-CGTAAATGCACTTGCTTCAGG-3' for the mecA and nuc genes, respectively. The nuc genes confirm the S. aureus isolates and the mecA genes as being methicillin-resistant and so pathogenic to man. The fluoroquinolones used in the antibiotic resistance testing were norfloxacin (10 µg) and ciprofloxacin (5 µg) in the E. coli O157:H7 isolates and ciprofloxacin (5 µg) in the S. aureus isolates. Susceptibility was tested using the disk diffusion method on Muller-Hinton agar. Fluoroquinolone resistance was not detected from isolates of E. coli O157:H7 from cattle. However, 44% (4/9) of the S. aureus were resistant to ciprofloxacin. Resistance of up to 44% in isolates of mecA and nuc genes harbouring S. aureus is a compelling evidence for the rapid spread of antibiotic resistance from bacteria in food animals from Nigeria. Ciprofloxacin is the drug of choice for the treatment of Typhoid fever, therefore widespread resistance to it in pathogenic bacteria is of great public health significance. The study concludes that antibiotic resistance in bacteria from food animals is on the increase in Nigeria. The National Food and Drug Administration and Control (NAFDAC) agency in Nigeria should implement the World Health Organization (WHO) global action plan on antimicrobial resistance. A good starting point can be coordinating the WHO, Office of International Epizootics (OIE), Food and Agricultural Organization (FAO) tripartite draft antimicrobial resistance monitoring and evaluation (M&E) framework in Nigeria.

Keywords: Fluoroquinolone, Nigeria, resistance, Staphylococcus aureus.

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Authors: G. Spada, E. Gavini, P. Giunchedi

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Aim of this work was to compare the efficacy of two loading methods of proteins onto polymeric nanocarriers: adsorption and encapsulation methods. Preliminary studies of protein loading were done using Bovine Serum Albumin (BSA) as model protein. Nanocarriers were prepared starting from polylactic co-glycolic acid (PLGA) polymer; production methods used are two different variants of emulsion evaporation method. Nanoparticles obtained were analyzed in terms of dimensions by Dynamic Light Scattering and Loading Efficiency of BSA by Bradford Assay. Loaded nanoparticles were then submitted to in-vitro protein dissolution test in order to study the effect of the delivery system on the release rate of the protein.

Keywords: Drug delivery, nanoparticles, PLGA, proteinadsorption, protein encapsulation.

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Authors: E. Krasnova, E. Bulgakova, V. Shchemelinin

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The paper deals with acoustic-spectrographic voice identification method in terms of its performance in non-native language speech. Performance evaluation is conducted by comparing the result of the analysis of recordings containing native language speech with recordings that contain foreign language speech. Our research is based on Tajik and Russian speech of Tajik native speakers due to the character of the criminal situation with drug trafficking. We propose a pilot experiment that represents a primary attempt enter the field.

Keywords: Speaker identification, acoustic-spectrographic method, non-native speech.

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Authors: M. Hoxha, V. Capra, C. Buccellati, A. Sala, C. Cena, R. Fruttero, M. Bertinaria, G. E. Rovati

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Today COXIBs are used in the treatment of arthritis and many other painful conditions in selected patients with high gastrointestinal risk and low cardiovascular (CV) risk. Previously, we have identified an unexpected mechanism of action of a traditional non-steroidal anti-inflammatory drug (NSAID) (diclofenac) and a specific inhibitor of cyclooxygenase-2 (COXIB) (lumiracoxib) demonstrating that they possess weak competitive antagonism at the thromboxane receptor (TP). We hypothesize that modifying the structure of a known COXIB so that it becomes also a more potent TP antagonist will preserve the anti-inflammatory and gastrointestinal safety typical of COXIBs and prevent the CV risk associated with long term therapy.

Keywords: Cyclooxygenase, inflammation, lumiracoxib, thromboxane A2.

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Authors: Manpreet Singh, Parminder Kaur Wadhwa, Surinder Kaur

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The drug discovery process starts with protein identification because proteins are responsible for many functions required for maintenance of life. Protein identification further needs determination of protein function. Proposed method develops a classifier for human protein function prediction. The model uses decision tree for classification process. The protein function is predicted on the basis of matched sequence derived features per each protein function. The research work includes the development of a tool which determines sequence derived features by analyzing different parameters. The other sequence derived features are determined using various web based tools.

Keywords: Sequence Derived Features, decision tree.

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Authors: R. C. Ferreira, H. H. C. De Lima, A. A. Cândido, O. M. Couto Junior, P. A. Arroyo, K. Q De Carvalho, G. F. Gauze, M. A. S. D. Barros

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Removal of the widespread used drug paracetamol from water was investigated using activated carbon originated from dende coconut mesocarp and babassu coconut mesocarp. Kinetic and equilibrium data were obtained at different values of pH. Both activated carbons showed high efficiency when pH ≤ pHPZC as the carbonil group of paracetamol molecule are adsorbed due to positively charged carbon surface. Microporosity also played an important role in such process. Pseudo-second order model was better adjusted to the kinetic results. Equilibrium data may be represented by Langmuir equation.

Keywords: Adsorption, activated carbon, babassu, dende.

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Authors: Sreenivasa Rao Parcha, Lakshmi P

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Artemisinin is a potential antimalarial drug effective against the multidrug resistant forms of Malarial Parasites. The current production of artemisinin is insufficient to meet the global demand. In the present study microbial biotransformation of arteannuin B, a biogenetic precursor of artemisinin to the later has been investigated. Screening studies carried out on several soil borne microorganisms have yielded one novel species with the bioconversion ability. Crude cell free extract of 72h old culture of the isolate had shown the bioconversion activity. On incubation with the substrate arteannuin B, crude cell free extract of the isolate had shown a bioconversion of 18.54% to artemisinin on molar basis with a specific activity of 0.18 units/mg.

Keywords: Arteannuin-B, Artemisia annua, Artemisinin, Bioconversion

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Authors: S. Buloyan, V. Mamikonyan, H. Hakobyan, H. Harutyunyan, H. Gasparyan

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The liver is the strongest regenerating organ of the organism, and even with 2/3 surgically removed, it can regenerate completely. Hence liver cirrhosis may only develop when the regenerating system is off. We present the results of a comparative study of structural and functional characteristics of rat liver tissue under the conditions of toxic liver cirrhosis development, induced by carbon tetrachloride, and its prevention/treatment by natural compounds with antioxidant and immune stimulating action. Studies were made on Wister rats, weighing 120~140 g. Grape seeds extracts, separately and in combination with well-known anticirrhotic drug ursodeoxycholic acid (Urdoxa), have demonstrated effectiveness in prevention of liver cirrhosis development and its treatment.

Keywords: Carbon tetrachloride, GSE, liver cirrhosis, prevention, treatment.

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Authors: H. Al-Khalaifa, A. Al-Nasser

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The viewpoint towards the use of drugs or vaccines against avian parasitic diseases is one of the most striking challenges in avian medical parasitology. This includes many difficulties associated with drug resistance and in developing prophylactic vaccines. In many instances, the potential success of a vaccination in controlling parasitic diseases in poultry is well-documented. However, some medical, technical and financial limitations are still paramount. On the other hand, chemotherapy is not very well-recommended due to a number of medical limitations. But in the absence of an effective vaccine, drugs are used against parasitic diseases. This paper sheds light on some the advantages and disadvantages of using vaccination and drugs in controlling parasitic diseases in poultry species. The usage of chemotherapeutic drugs is discussed with some examples. Then, more light will be shed on using vaccines as a potentially effective and promising control tool.

Keywords: Drugs, parasitology, poultry, vaccines.

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Authors: Leila Amjad, Zohreh Alizad

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Recent years have instance that there is a invigoration of interest in drug discovery from medicinal plants for the support of health in all parts of the world . This study was designed to examine the in vitro antimicrobial activities of the flowers and leaves methanolic and ethanolic extracts of Chenopodium album L. Chenopodium album Linn. flowers and leaves were collected from East Esfahan, Iran. The effects of methanolic and ethanolic extracts were tested against 4 bacterial strains by using disc,well-diffusion method. Results showed that flowers and leaves methanolic and ethanolic extracts of C.album don-t have any activity against the selected bacterial strains. Our study has indicated that ,there are effective different factors on antimicrobial properties of plant extracts

Keywords: Chennopodium album, antibacterial activity, extract

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Authors: Mustafa Erat

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Glutathione S-transferase was purified from human erythrocytes and effects of some polyphenols were investigated on the enzyme activity. The purification procedure was performed on Glutathione-Agarose affinity chromatography after preparation of erythrocytes hemolysate with a yield of 81%. The purified enzyme showed a single band on the SDS-PAGE. The effects of some poliphenolic compounds such as catechin, dopa, dopamine, progallol and catechol were examined on the in vitro GST activity. Catechin was determined to be inhibitor for the enzyme, but others were not effective on the enzyme as inhibitors or activators. IC50 value -the concentration of inhibitor which reduces enzyme activity by 50%- was estimated to be 10 mM. Ki constants were also calculated as 6.38 ± 0,70 mM with GSH substrate, and 3.86 ± 0,78 mM with CDNB substrate using the equations of graphs for the inhibitor, and its inhibition type was determined as non-competitive.

Keywords: Drug resistance, Glutathione S-transferase, Inhibition.

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Authors: Sandy Daley, Sandra Jones, Don Iverson

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The benefits of physical activity for children are promoted widely and well understood; however factors which impact on children-s beliefs and attitudes towards physical education need to be explored in more detail. The purpose of this study was to evaluate how primary school children value and perceive their involvement in physical education (PE) classes through the use of drawings. While this type of data collection has been used previously to determine a child-s response to specific health education classes, such as drug education, to the best of our knowledge it has not been used in the context of PE. Results from this study showed that kindergarten children found PE classes fun and engaging. Children in Year 4 and Year 6 were less satisfied with PE classes because of the activities offered, the lack of opportunity to play sport, and perception that teachers did not appear to value this area of the curriculum.

Keywords: attitudes, physical education, primary school children, write and draw

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Authors: A. Chirita, L. Alexandru, D. Marcoci, C. Ene-Draghici

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Minor law breaking seems more and more to be a part of adolescence behavior. An important risk factor which seems to influence delinquency appears to be the socio-economic one. According to Romanian statistics, during the first six months of 2012, 1,378 minors have committed various crimes, the most common being theft, sexual offenses and violent assaults. Drug-related offenses did not reach the gravity of those from high income countries of the European Union, but have a continuous upward during the last years. The aim of our research was to examine whether delinquency in adolescence is correlated to mental disorders or socio-economic and familial factors. Forensic psychiatric expertise was performed to 79 adolescents who committed offenses between 01 January 2012 and 31 December 2012. Teenagers, with ages between 12 and 17, were examined by day hospitalization in the University Clinic of Psychiatry Craiova.

Keywords: Adolescents, criminal behavior, mental illness.

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Authors: Irene Luque Ruiz, Manuel Urbano Cuadrado, Miguel Ángel Gómez-Nieto

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New graph similarity methods have been proposed in this work with the aim to refining the chemical information extracted from molecules matching. For this purpose, data fusion of the isomorphic and nonisomorphic subgraphs into a new similarity measure, the Approximate Similarity, was carried out by several approaches. The application of the proposed method to the development of quantitative structure-activity relationships (QSAR) has provided reliable tools for predicting several pharmacological parameters: binding of steroids to the globulin-corticosteroid receptor, the activity of benzodiazepine receptor compounds, and the blood brain barrier permeability. Acceptable results were obtained for the models presented here.

Keywords: Graph similarity, Nonisomorphic dissimilarity, Approximate similarity, Drug activity prediction.

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Authors: Sophio Kobauri, Vladimir P. Torchilin, David Tugushi, Ramaz Katsarava

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Nanotherapy is an actual newest mode of treatment numerous diseases using nanoparticles (NPs) loading with different pharmaceuticals. NPs of biodegradable polymeric micelles (PMs) are gaining increased attention for their numerous and attractive abilities to be used in a variety of applications in the various fields of medicine. The present paper deals with the synthesis of a class of biodegradable micelle-forming polymers, namely ABA triblock-copolymer in which A-blocks represent amino-poly(ethylene glycol) (H₂N-PEG) and B-block is biodegradable amino acid-based poly(ester amide) constituted of α-amino acid – L-phenylalanine. The obtained copolymer formed micelles of 70±4 nm size at 10 mg/mL concentration.

Keywords: Amino acids, biodegradable poly(ester amide), amphiphilic triblock-copolymer, micelles.

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Authors: Yi-Ping Fang, Yi-Ting Wong

Abstract:

Transcription factor p53 has a powerful tumor suppressing function that is associated with many cancers. However, p53 of the molecular weight was higher make the limitation across to skin or cell membrane. Thymidine dinucleotide (pTT), an oligonucleotide, can activate the p53 transcription factor. pTT is a hydrophilic and negative charge oligonucleotide, which delivery in to cell membrane need an appropriate carrier. The aim of this study was to improve the bioavailability of the nucleotide fragment, thymidine dinucleotide (pTT), using elasic liposome carriers to deliver the drug into the skin. The study demonstrate that dioleoylphosphocholine (DOPC) incorporated with sodium cholate at molar ratio 1:1 can archived the particle size about 220 nm. This elastic liposome could penetration through skin from stratum corneum to whole epidermis by confocal laser scanning microscopy (CLSM). Moreover, we observed the the slight increase in generation of p53 by western blot.

Keywords: Elastic liposome, Tymidine dinucleotide, p53, Topical delivery

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Authors: Khalida Boutemak, Nasssima Benali, Nadji Moulai-Mostefa

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Effect of enzyme on the yield and chemical composition of Artemisia campestris essential oil is reported in the present study. It was demonstrated that enzyme facilitated the extraction of essential oil with increase in oil yield and did not affect any noticeable change in flavour profile of the  volatile oil. Essential oil was tested for antibacterial activity using Escherichia coli; which was extremely sensitive against control with the largest inhibition (29mm), whereas Staphylococcus aureus was the most sensitive against essential oil obtained from enzymatic pre-treatment with the largest inhibition zone (25mm). The antioxidant activity of the essential oil with hemicellulase pre-treatment (EO2) and control sample (EO1) was determined through reducing power. It was significantly lower than the standard drug (vitamin C) in this order: vitamin C˃EO2˃EO1.

Keywords: Artemisia campestris, enzyme pre-treatment, hemicellulase, antibacterial activity, antioxidant activity.

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Authors: Sperisa Distantina, Fadilah Fadilah, Mujtahid Kaavessina

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Cross-linked konjac glucomannan and kappa carrageenan film were prepared by chemical crosslinking using glutaraldehyde (GA) as the crosslinking agent. The effect crosslinking on the swelling degree was investigated. Konjac glucomannan and its mixture with kappa carrageenan film was immersed in GA solution and then thermally cured. The obtained cross-linked film was washed and soaked in the ethanol to remove the unreacted GA. The obtained film was air dried at room temperature to a constant weight. The infrared spectra and the value of swelling degree of obtained crosslinked film showed that glucomannan and kappa carrageenan was able to be cross-linked using glutaraldehyde by film immersion and curing method without catalyst. The cross-linked films were found to be pH sensitive, indicating a potential to be used in drug delivery polymer system.

Keywords: Crosslinking, glucomannan, carrageenan, swelling.

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Authors: Patcharawalai Jaisamut, Kamonthip Wiwattanawongsa, Ruedeekorn Wiwattanapatapee

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Supersaturation of drugs in the gastrointestinal tract is one approach to increase the absorption of poorly water-soluble drugs. The stabilization of a supersaturated state was achieved by adding precipitation inhibitors that may act through a variety of mechanisms. In this study, the effect of the natural gums, acacia, gelatin, pectin and tragacanth on curcumin supersaturation in simulated gastric fluid (SGF) (pH 1.2), fasted state simulated gastric fluid (FaSSGF) (pH 1.6), and simulated intestinal fluid (SIF) (pH 6.8) was investigated. The results indicated that all natural gums significantly increased the curcumin solubility (about 1.2-6-fold) when compared to the absence of gum, and assisted in maintaining the supersaturated drug solution. Among the tested gums, pectin at 3% w/w was the best precipitation inhibitor with a significant increase in the degree of supersaturation about 3-fold in SGF, 2.4-fold in FaSSGF and 2-fold in SIF.

Keywords: Curcumin, Solubility, Supersaturation, Precipitation inhibitor.

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Authors: A. Nusrath Unissa, Sameer Hassan, Luke Elizabeth Hanna

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Altered drug binding may be an important factor in isoniazid (INH) resistance, rather than major changes in the enzyme’s activity as a catalase or peroxidase (KatG). The identification of structural or functional defects in the mutant KatGs responsible for INH resistance remains as an area to be explored. In this connection, the differences in the binding affinity between wild-type (WT) and mutants of KatG were investigated, through the generation of three mutants of KatG, Ser315Thr [S315T], Ser315Asn [S315N], Ser315Arg [S315R] and a WT [S315]) with the help of software-MODELLER. The mutants were docked with INH using the software-GOLD. The affinity is lower for WT than mutant, suggesting the tight binding of INH with the mutant protein compared to WT type. These models provide the in silico evidence for the binding interaction of KatG with INH and implicate the basis for rationalization of INH resistance in naturally occurring KatG mutant strains of Mycobacterium tuberculosis.

Keywords: Mycobacterium tuberculosis, KatG, INH resistance, Mutants, Modeling, Docking.

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Authors: S. S. Pati, L. Herojit Singh, A. C. Oliveira, V. K. Garg

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Chitosan functionalized Fe3O4-Au core shell nanoparticles have been prepared using a two-step wet chemical approach using NaBH4 as reducing agent for formation of Au in ethylene glycol. X-ray diffraction studies shows individual phases of Fe3O4 and Au in the as prepared samples with crystallite size of 5.9 and 11.4 nm respectively. The functionalization of the core-shell nanostructure with Chitosan has been confirmed using Fourier transform infrared spectroscopy along with signatures of octahedral and tetrahedral sites of Fe3O4 below 600cm-1. Mössbauer spectroscopy shows decrease in particle-particle interaction in presence of Au shell (72% sextet) than pure oleic coated Fe3O4 nanoparticles (88% sextet) at room temperature. At 80K, oleic acid coated Fe3O4 shows only sextets whereas the Chitosan functionalized Fe3O4 and Chitosan functionalized Fe3O4@Au core shell show presence of 5 and 11% doublet, respectively.

Keywords: Magnetic nanoparticles, Fe3O4@Au core shell, iron oxide, Au nanoparticles.

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Authors: Ren-Jy Ben, Jo-Chi Jao, Chiu-Ya Liao, Ya-Ru Tsai, Lain-Chyr Hwang, Po-Chou Chen

Abstract:

Cancer is still one of the serious diseases threatening the lives of human beings. How to have an early diagnosis and effective treatment for tumors is a very important issue. The animal carcinoma model can provide a simulation tool for the studies of pathogenesis, biological characteristics, and therapeutic effects. Recently, drug delivery systems have been rapidly developed to effectively improve the therapeutic effects. Liposome plays an increasingly important role in clinical diagnosis and therapy for delivering a pharmaceutic or contrast agent to the targeted sites. Liposome can be absorbed and excreted by the human body, and is well known that no harm to the human body. This study aimed to compare the therapeutic effects between encapsulated (doxorubicin liposomal, Lipodox) and un-encapsulated (doxorubicin, Dox) anti-tumor drugs using magnetic resonance imaging (MRI). Twenty-four New Zealand rabbits implanted with VX2 carcinoma at left thighs were classified into three groups: control group (untreated), Dox-treated group, and LipoDox-treated group, 8 rabbits for each group. MRI scans were performed three days after tumor implantation. A 1.5T GE Signa HDxt whole body MRI scanner with a high resolution knee coil was used in this study. After a 3-plane localizer scan was performed, three-dimensional (3D) fast spin echo (FSE) T2-weighted Images (T2WI) was used for tumor volumetric quantification. Afterwards, two-dimensional (2D) spoiled gradient recalled echo (SPGR) dynamic contrast-enhanced (DCE) MRI was used for tumor perfusion evaluation. DCE-MRI was designed to acquire four baseline images, followed by contrast agent Gd-DOTA injection through the ear vein of rabbit. A series of 32 images were acquired to observe the signals change over time in the tumor and muscle. The MRI scanning was scheduled on a weekly basis for a period of four weeks to observe the tumor progression longitudinally. The Dox and LipoDox treatments were prescribed 3 times in the first week immediately after the first MRI scan; i.e. 3 days after VX2 tumor implantation. ImageJ was used to quantitate tumor volume and time course signal enhancement on DCE images. The changes of tumor size showed that the growth of VX2 tumors was effectively inhibited for both LipoDox-treated and Dox-treated groups. Furthermore, the tumor volume of LipoDox-treated group was significantly lower than that of Dox-treated group, which implies that LipoDox has better therapeutic effect than Dox. The signal intensity of LipoDox-treated group is significantly lower than that of the other two groups, which implies that targeted therapeutic drug remained in the tumor tissue. This study provides a radiation-free and non-invasive MRI method for therapeutic monitoring of targeted liposome on an animal tumor model.

Keywords: Doxorubicin, dynamic contrast-enhanced MRI, lipodox, magnetic resonance imaging, VX2 tumor model.

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