Search results for: extremely drug- resistant

Authors: Shabnum Shaheen, Nida Haroon, Farah Khan, Sumera Javad, Mehreen Jalal, Samina Sarwar

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Coffee Senna is pharmaceutically very important and used for multiple health disorders such as gastric pains, indigestion, snakebites, asthma and fever, tuberculosis and menstrual problems. However, its immense medicinal value and great demand lead to adulteration issue which could be injurious for users. Some times its adulterant Seena weed (Senna occidentalis L.) is used as its substitute which definitely not as effective as Coffee Senna. Hence, the present study was undertaken to provide some tools for systematic and pharmaceutical authentication of a shrubby plant Coffee Senna (Cassia occidentalis Linn.). These parameters included macro and micro morphological characters, anatomical and palynomorph characterization, solubility, fluorescence and phytochemical analysis. By the application of these parameters acquired results revealed that, these two plants are distinct from each other. The Coffee Seena was found to be an annual shrub with trilobed pollen, diacytic, paracytic and anisocytic stomata whereas the Seena weed stands out as an annual or perennial herb with spheroidal and circular pollen and paracytic type of stomata. The powdered drug of Coffee seena is dark grayish green whereas the powdered drug of Seena weed is light green in color. These findings are constructive in authentic identification of these plants.

Keywords: coffee senna, Senna weed, taxonomic evaluation, pharmaceutical markers

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Authors: A. H. Taghdisi, M. Mirmohammadi, S. Kamali

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Evening primrose (Oenothera biennis L.) is a biennial and herbaceous and one of the most important species of medicinal plants in the world. due to the production of unsaturated fatty acids such as linoleic acid, alpha-linolenic acid, etc. in its seeds and roots, and compounds such as kaempferol in its leaves, Evening primrose has important medicinal efficiency such as reducing premenstrual problems, acceleration of wound healing, inhibiting platelet aggregation, sedation of cardiovascular diseases, and treatment of viral infections. The sap of the plant is used to treat warts, and the plant itself is used as a charm against mental and spiritual diseases and poisonous animals. Its leaves have significant antibacterial activity against yellow staphylococci. It is also used in the treatment of poisoning, especially the toxication caused by the consumption of alcoholic beverages, in the treatment of arteriosclerosis and diseases caused by liver cell insufficiency. Low germination and production speed are the problems of evening primrose growth and propagation. In the present study, extracts were obtained from four components (flowers, stems, seeds, leaves) of the evening primrose plant using the Soxhlet apparatus. To measure the antibacterial properties against MDR bacteria, microbial methods, including dilution, cultivation on a plate containing nutrient agar culture medium, and disc diffusion in agar, were performed using Staphylococcus aureus and Escherichia coli bacteria on all four extracts. The maximum antibacterial activity related to the dilution method was obtained in all extracts. In the plate culture method, antibacterial activity was obtained for all extracts in the nutrient agar medium. The maximum diameter of the non-growth halo was obtained in the disc diffusion method in agar in the leaf extract. The statistical analysis of the microbial part was done by one-way ANOVA test (SPSS). By comparing the amount of omega-3 in extracts of Iranian and foreign oils available in the market and the extracts extracted from evening primrose plant samples with gas chromatography, it is shown that the stem extract had the most omega-3 (oleic acid) and compared to the extract of the mentioned oils, it had the highest amount of omega-3 overall. Also, the amount of omega-3 in the extract of Iranian oils was much higher than in the extract of foreign oils. It should be noted that the extract of foreign oils had a more complete composition of omega-3 than the extract of Iranian oils.

Keywords: antibacterial activity, MDR bacteria, evening primrose, omega-3

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Authors: Shirin Jalili, Sadegh Hasannia, Hadi Shirzad, Afshin Khara

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Morphine is one of the most medicinally important analgesics and narcotics. Structurally, it is classified as an alkaloid because of the presence of nitrogen. Its structure is similar to that of codeine, thebaine, and heroin. An immunoassay to accurately discriminate between these analogous alkaloids would be highly beneficial. A key factor for such an assay is specificity with high sensitivity, which is totally dependent on the antibody employed. However, most antibodies against haptens are polyclonal serum antibodies that exhibit significant cross-reactivities with closely related compounds. The camel-derived single-chain antibody fragments (VHH) are the smallest molecules with antigen-binding capacity, possessing unique properties compared to other conventional antibodies. In this study, a library containing the VHH genes of a camel immunized with with morphine conjugated BSA following phage display technology was generated. By screening the camel-derived variable region of the heavy chain cDNA phage display library with the ability to bind the desired hapten, we obtained some nanobodies that recognize this hapten. Phage display expression of the Nbs from this library and pannings against this hapten resulted in a clear enrichment of four distinct Nb-displaying phages with specificity for morphine that could be a potential target site for the development of new strategies for the development of a biosensor for detecting illicit drug.

Keywords: phage display, nanobody, Morphine-3, glucuronide, ELISA, biosensor

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Authors: Zahid Manzoor, Shaukat Hussain Munawar, Zahid Iqbal, Imran Ahmad Khan, Abdul Aziz, Hafiz Muhammad Qasim

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The present study was aimed to investigate the pharmacokinetics behavior and optimal dosage regimen of danofloxacin in 8 adult healthy buffaloes of local breed (Nili Ravi) following single intravenous administration at the dose of 2.5 mg/kg body weight. Plasma drug concentrations at various time intervals were measured by HPLC method. In vitro plasma protein binding was determined employing the ultrafiltration technique. The distribution and elimination of danofloxacin was rapid, as indicated by the values (Mean±SD) of distribution half-life (t1/2α = 0.25±0.09 hours) and elimination half life (t1/2β = 3.26±0.43 hours), respectively. Volume of distribution at steady state (Vss) was 1.14±0.12 L/kg, displaying its extensive distribution into various body fluids and tissues. The high value of AUC (9.80±2.14 µg/ml.hr) reflected the vast area of the body covered by drug concentration. The mean residence time was noted to be 4.78±0.52 hours. On the basis of pharmacokinetic parameters, a suitable intravenous regimen for danofloxacin in adult buffaloes would be 6.5 mg/kg to be repeated after 12 hours intervals. The present study is the foremost pharmacokinetic study of danofloxacin in the local species which would provide the valueable contribution in the local manufacturing of danofloxacin in Pakistan in future.

Keywords: danofloxacin, pharmacokinetics, plasma protein binding, buffaloes, dosage regimen

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Authors: Yugander Arra, Florence Auguy, Melissa Stiebner, Sophie Chéron, Michael M. Wudick, Van Schepler-Luu, Sébastien Cunnac, Wolf B. Frommer, Laurence Albar

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Rice yellow mottle virus (RYMV) is one of the most important diseases affecting rice in Africa. The most promising strategy to reduce yield losses is the use of highly resistant varieties. The resistance gene RYMV2 is homolog of the Arabidopsis constitutive expression of pathogenesis related protein-5 (AtCPR5) nucleoporin gene. Resistance alleles are originating from African cultivated rice Oryza glaberrima, rarely cultivated, and are characterized by frameshifts or early stop codons, leading to a non-functional or truncated protein. Rice possesses two paralogs of CPR5 and function of these genes are unclear. Here, we evaluated the role of the two rice candidate nucleoporin paralogs OsCPR5.1 (pathogenesis-related gene 5; RYMV2) and OsCPR5.2 by CRISPR/Cas9 genome editing. Despite striking sequence and structural similarity, only loss-of-function of OsCPR5.1 led to full resistance, while loss-of-function oscpr5.2 mutants remained susceptible. Short N-terminal deletions in OsCPR5.1 also did not lead to resistance. In contrast to Atcpr5 mutants, neither OsCPR5.1 nor OsCPR5.2 knock out mutants showed substantial growth defects. Taken together, the candidate nucleoporin OsCPR5.1, but not its close homolog OsCPR5.2, plays a specific role for the susceptibility to RYMV, possibly by impairing the import of viral RNA or protein into the nucleus. Whereas gene introgression from O. glaberrima to high yielding O. sativa varieties is impaired by strong sterility barriers and the negative impact of linkage drag, genome editing of OsCPR5.1, while maintaining OsCPR5.2 activity, thus provides a promising strategy to generate O. sativa elite lines that are resistant to RYMV.

Keywords: CRISPR Cas9, genome editing, knock out mutant, recessive resistance, rice yellow mottle virus

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Authors: Samia A. El-Fiky, F. A. Abou-Zaid, Ibrahim M. Farag, Naira M. Efiky

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Clomipramine hydrochloride is one of the most used tricyclic antidepressant drug in Egypt. This drug contains in its chemical structure on two benzene rings. Benzene is considered to be toxic and clastogenic agent. So, the present study was designed to assess the genotoxic effect of Clomipramine hydrochloride on somatic and germ cells in mice. Three dose levels 0.195 (Low), 0.26 (Medium), and 0.65 (High) mg/kg.b.wt. were used. Seven groups of male mice were utilized in this work. The first group was employed as a control. In the remaining six groups, each of the above doses was orally administrated for two groups, one of them was treated for 5 days and the other group was given the same dose for 30 days. At the end of experiments, the animals were sacrificed for cytogenetic and sperm examination as well as histopathological investigations by using hematoxylin and eosin stains (H and E stains) and electron microscope. Concerning the sperm studies, these studies were confined to 5 days treatment with different dose levels. Moreover, the ultrastructural investigation by electron microscope was restricted to 30 days treatment with drug doses. The results of the dose dependent effect of Clomipramine showed that the treatment with three different doses induced increases of frequencies of chromosome aberrations in bone marrow and spermatocyte cells as compared to control. In addition, mitotic and meiotic activities of somatic and germ cells were declined. The treatments with medium or high doses were more effective for inducing significant increases of chromosome aberrations and significant decreases of cell divisions than treatment with low dose. The effect of high dose was more pronounced for causing such genetic deleterious in respect to effect of medium dose. Moreover, the results of the time dependent effect of Clomipramine observed that the treatment with different dose levels for 30 days led to significant increases of genetic aberrations than treatment for 5 days. Sperm examinations revealed that the treatment with Clomipramine at different dose levels caused significant increase of sperm shape abnormalities and significant decrease in sperm count as compared to control. The adverse effects on sperm shape and count were more obviousness by using the treatments with medium or high doses than those found in treatment with low dose. The group of mice treated with high dose had the highest rate of sperm shape abnormalities and the lowest proportion of sperm count as compared to mice received medium dose. In histopathological investigation, hematoxylin and eosin stains showed that, the using of low dose of Clomipramine for 5 or 30 days caused a little pathological changes in liver tissue. However, using medium and high doses for 5 or 30 days induced severe damages than that observed in mice treated with low dose. The treatment with high dose for 30 days gave the worst results of pathological changes in hepatic cells. Moreover, ultrastructure examination revealed, the mice treated with low dose of Clomipramine had little differences in liver histological architecture as compared to control group. These differences were confined to cytoplasmic inclusions. Whereas, prominent pathological changes in nuclei as well as dilated of rough Endoplasmic Reticulum (rER) were observed in mice treated with medium or high doses of Clomipramine drug. In conclusion, the present study adds evidence that treatments with medium or high doses of Clomipramine have genotoxic effects on somatic and germ cells of mice, as unwanted side effects. However, the using of low dose (especially for short time, 5 days) can be utilized as a therapeutic dose, where it caused relatively similar proportions of genetic, sperm, and histopathological changes as those found in normal control.

Keywords: clomipramine, mice, chromosome aberrations, sperm abnormalities, histopathology

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Authors: Fouzia Perveen, Rumana Qureshi

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The presently studied twelve anticancer drugs are the cytotoxic agents which inhibit the replication of DNA and activity of enzymes involved in DNA replication namely topoisomerase-II, polymerase and helicase and have shown remarkable anticancer activity in clinical trials. In this study, we performed molecular docking studies of twelve antitumor drugs against DNA and DNA enzymes in the presence and absence of ascorbic acid (AA) and developed the quantitative structure-activity relationship (QSAR) model for anticancer activity screening. A number of electronic and steric descriptors were calculated using MOE software package. QSAR was established showing a correlation of binding strength with various physicochemical descriptors. Out of these twelve, eight cytotoxic drugs were tested on Non-Small Cell Lung Cancer cell lines (H-157 and H-1299) in the absence and presence of ascorbic acid and experimental IC50 values were calculated. From the docking studies, binding constants were calculated indicating the strength of drug-DNA and drug-enzyme complex formation and it was correlated to the IC50 values (both experimental and theoretical). These results can offer useful references for directing the molecular design of DNA enzyme inhibitor with improved anticancer activity.

Keywords: ascorbic acid, binding constant, cytotoxic agents, cell culture, DNA, DNA enzymes, molecular docking

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Authors: Nonhlanhla Nkosi, Kulsum Kondiah

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The toxicological manifestation of heavy metals motivates interest towards the development of a reliable, eco-friendly biosorption process. With that being said, the aim of the current study was to characterise the EPS from heavy-metal resistant bacteria isolated from acid mine decant on the West Rand, Gauteng, South Africa. To achieve this, six exopolysaccharide (EPS) producing, metal resistant strains (Pb101, Pb102, Pb103, Pb204, Co101, and Ni101) were identified as Bacillus safensis strain NBRC 100820, Bacillus proteolyticus, Micrococcus luteus, Enterobacter sp. Pb204, Bacillus wiedmannii and Bacillus zhangzhouensis, respectively with 16S rRNA sequencing. Thereafter, EPS was extracted using chemical (formaldehyde/NaOH) and physical (ultrasonification) methods followed by physicochemical characterisation of carbohydrate, DNA, and protein contents using chemical assays and spectroscopy (FTIR- Fourier transformed infrared and 3DEEM- three-dimensional excitation-emission matrix fluorescence spectroscopy). EPS treated with formaldehyde/NaOH showed better recovery of macromolecules than ultrasonification. The results of the present study showed that carbohydrates were more abundant than proteins, with carbohydrate and protein concentrations of 8.00 mg/ml and 0.22 mg/ml using chemical method in contrast to 5.00 mg/ml and 0.77 mg/ml using physical method, respectively. The FTIR spectroscopy results revealed that the extracted EPS contained hydroxyl, amide, acyl, and carboxyl groups that corresponded to the aforementioned chemical analysis results, thus asserting the presence of carbohydrates, DNA, polysaccharides, and proteins in the EPS. These findings suggest that identified functional groups of EPS form surface charges, which serve as the binding sites for suspended particles, thus possibly mediating adsorption of divalent cations and heavy metals. Using the extracted EPS in the development of a cost-effective biosorption solution for industrial wastewater treatment is attainable.

Keywords: biosorbent, exopolysaccharides, heavy metals, wastewater treatment

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Authors: Maryam Ziaee, Himanshu Shee, Amrik Sohal

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Big Data Analytics (BDA) in supply chain management has recently drawn the attention of academics and practitioners. Big data refers to a massive amount of data from different sources, in different formats, generated at high speed through transactions in business environments and supply chain networks. Traditional statistical tools and techniques find it difficult to analyse this massive data. BDA can assist organisations to capture, store, and analyse data specifically in the field of supply chain. Currently, there is a paucity of research on BDA in the pharmaceutical supply chain context. In this research, the Australian pharmaceutical supply chain was selected as the case study. This industry is highly significant since the right medicine must reach the right patients, at the right time, in right quantity, in good condition, and at the right price to save lives. However, drug shortages remain a substantial problem for hospitals across Australia with implications on patient care, staff resourcing, and expenditure. Furthermore, a massive volume and variety of data is generated at fast speed from multiple sources in pharmaceutical supply chain, which needs to be captured and analysed to benefit operational decisions at every stage of supply chain processes. As the pharmaceutical industry lags behind other industries in using BDA, it raises the question of whether the use of BDA can improve transparency among pharmaceutical supply chain by enabling the partners to make informed-decisions across their operational activities. This presentation explores the impacts of BDA on supply chain management. An exploratory qualitative approach was adopted to analyse data collected through interviews. This study also explores the BDA potential in the whole pharmaceutical supply chain rather than focusing on a single entity. Twenty semi-structured interviews were undertaken with top managers in fifteen organisations (five pharmaceutical manufacturers, five wholesalers/distributors, and five public hospital pharmacies) to investigate their views on the use of BDA. The findings revealed that BDA can enable pharmaceutical entities to have improved visibility over the whole supply chain and also the market; it enables entities, especially manufacturers, to monitor consumption and the demand rate in real-time and make accurate demand forecasts which reduce drug shortages. Timely and precise decision-making can allow the entities to source and manage their stocks more effectively. This can likely address the drug demand at hospitals and respond to unanticipated issues such as drug shortages. Earlier studies explore BDA in the context of clinical healthcare; however, this presentation investigates the benefits of BDA in the Australian pharmaceutical supply chain. Furthermore, this research enhances managers’ insight into the potentials of BDA at every stage of supply chain processes and helps to improve decision-making in their supply chain operations. The findings will turn the rhetoric of data-driven decision into a reality where the managers may opt for analytics for improved decision-making in the supply chain processes.

Keywords: big data analytics, data-driven decision, pharmaceutical industry, supply chain management

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Authors: R. Sarjahani, M. Sheikhattar, S. Javadpour, B. Hashemi

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Glazes and their surface characterization is an important subject for ceramic industries. Fabrication of a super smooth surface resistant to stains is a big improvement for those industries. In this investigation, surface topography of popular glazes such as Zircon and Titania based opaque glazes, calcium based matte glaze and transparent glaze has been analyzed by Marsurf M300, SEM, EDS and XRD. Results shows that surface roughness of glazes seriously depends on surface crystallinity, crystal size and shapes.

Keywords: crystallinity, glaze, surface roughness, topography

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Authors: Klazina T. Havinga, Hilde R. H. de Geus

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Introduction: Pre-operative coagulation management of Apixaban prescribed patients, a new oral anticoagulant (a factor Xa inhibitor), is difficult, especially when chronic kidney disease (CKD) causes drug overdose. Apixaban is not dialyzable due to its high level of protein binding. An antidote, Andexanet α, is available but expensive and has an unfavorable short half-life. We report the successful extracorporeal removal of Apixaban prior to emergency surgery with the CytoSorb® Hemoadsorption device. Methods: A 89-year-old woman with CKD, with an Apixaban prescription for atrial fibrillation, was presented at the ER with traumatic rib fractures, a flail chest, and an unstable spinal fracture (T12) for which emergency surgery was indicated. However, due to very high Apixaban levels, this surgery had to be postponed. Based on the Apixaban-specific anti-factor Xa activity (AFXaA) measurements at admission and 10 hours later, complete clearance was expected after 48 hours. In order to enhance the Apixaban removal and reduce the time to operation, and therefore reduce pulmonary complications, CRRT with CytoSorb® cartridge was initiated. Apixaban-specific anti-factor Xa activity (AFXaA) was measured frequently as a substitute for Apixaban drug concentrations, pre- and post adsorber, in order to calculate the adsorber-related clearance. Results: The admission AFXaA concentration, as a substitute for Apixaban drug levels, was 218 ng/ml, which decreased to 157 ng/ml after ten hours. Due to sustained anticoagulation effects, surgery was again postponed. However, the AFXaA levels decreased quickly to sub-therapeutic levels after CRRT (Multifiltrate Pro, Fresenius Medical Care, Blood flow 200 ml/min, Dialysate Flow 4000 ml/h, Prescribed renal dose 51 ml-kg-h) with Cytosorb® connected in series into the circuit was initiated (within 5 hours). The adsorber-related (indirect) Apixaban clearance was calculated every half hour (Cl=Qe * (AFXaA pre- AFXaA post/ AFXaA pre) with Qe=plasma flow rate calculated with Ht=0.38 and system blood flow rate 200 ml-min): 100 ml/min, 72 ml/min and 57 ml/min. Although, as expected, the adsorber-related clearance decreased quickly due to saturation of the beads, still the reduction rate achieved resulted in a very rapid decrease in AFXaA levels. Surgery was ordered and possible within 5 hours after Cytosorb initiation. Conclusion: The CytoSorb® Hemoadsorption device enabled rapid correction of Apixaban associated anticoagulation.

Keywords: Apixaban, CytoSorb, emergency surgery, Hemoadsorption

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Authors: Lacramioara Ochiuz, Aurelia Vasile, Iulian Stoleriu, Cristina Ghiciuc, Maria Ignat

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Topical administration of chemotherapeutic agents (eg. carmustine, bexarotene, mechlorethamine etc.) in local treatment of cutaneous T-cell lymphoma (CTCL) is accompanied by multiple side effects, such as contact hypersensitivity, pruritus, skin atrophy or even secondary malignancies. A known method of reducing the side effects of anticancer agent is the development of modified drug release systems using drug incapsulation in biocompatible nanoporous inorganic matrices, such as mesoporous MCM-41 silica. Mesoporous MCM-41 silica is characterized by large specific surface, high pore volume, uniform porosity, and stable dispersion in aqueous medium, excellent biocompatibility, in vivo biodegradability and capacity to be functionalized with different organic groups. Therefore, MCM-41 is an attractive candidate for a wide range of biomedical applications, such as controlled drug release, bone regeneration, protein immobilization, enzymes, etc. The main advantage of this material lies in its ability to host a large amount of the active substance in uniform pore system with adjustable size in a mesoscopic range. Silanol groups allow surface controlled functionalization leading to control of drug loading and release. This study shows (I) the amino-grafting optimization of mesoporous MCM-41 silica matrix by means of co-condensation during synthesis and post-synthesis using APTES (3-aminopropyltriethoxysilane); (ii) loading the therapeutic agent (carmustine) obtaining a modified drug release systems; (iii) determining the profile of in vitro carmustine release from these systems; (iv) assessment of carmustine release kinetics by fitting on four mathematical models. Obtained powders have been described in terms of structure, texture, morphology thermogravimetric analysis. The concentration of the therapeutic agent in the dissolution medium has been determined by HPLC method. In vitro dissolution tests have been done using cell Enhancer in a 12 hours interval. Analysis of carmustine release kinetics from mesoporous systems was made by fitting to zero-order model, first-order model Higuchi model and Korsmeyer-Peppas model, respectively. Results showed that both types of highly ordered mesoporous silica (amino grafted by co-condensation process or post-synthesis) are thermally stable in aqueous medium. In what regards the degree of loading and efficiency of loading with the therapeutic agent, there has been noticed an increase of around 10% in case of co-condensation method application. This result shows that direct co-condensation leads to even distribution of amino groups on the pore walls while in case of post-synthesis grafting many amino groups are concentrated near the pore opening and/or on external surface. In vitro dissolution tests showed an extended carmustine release (more than 86% m/m) both from systems based on silica functionalized directly by co-condensation and after synthesis. Assessment of carmustine release kinetics revealed a release through diffusion from all studied systems as a result of fitting to Higuchi model. The results of this study proved that amino-functionalized mesoporous silica may be used as a matrix for optimizing the anti-cancer topical therapy by loading carmustine and developing prolonged-release systems.

Keywords: carmustine, silica, controlled, release

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Authors: Aussara Panya, Nunghathai Sawasdee, Mutita Junking, Chatchawan Srisawat, Kiattawee Choowongkomon, Pa-Thai Yenchitsomanus

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Dengue virus (DENV) infection is a global public health problem with approximately 100 million infected cases a year. Presently, there is no approved vaccine or effective drug available; therefore, the development of anti-DENV drug is urgently needed. The clinical reports revealing the positive association between the disease severity and viral titer has been reported previously suggesting that the anti-DENV drug therapy can possibly ameliorate the disease severity. Although several anti-DENV agents showed inhibitory activities against DENV infection, to date none of them accomplishes clinical use in the patients. The surface envelope (E) protein of DENV is critical for the viral entry step, which includes attachment and membrane fusion; thus, the blocking of envelope protein is an attractive strategy for anti-DENV drug development. To search the safe anti-DENV agent, this study aimed to search for novel peptide inhibitors to counter DENV infection through the targeting of E protein using a structure-based in silico design. Two selected strategies has been used including to identify the peptide inhibitor which interfere the membrane fusion process whereby the hydrophobic pocket on the E protein was the target, the destabilization of virion structure organization through the disruption of the interaction between the envelope and membrane proteins, respectively. The molecular docking technique has been used in the first strategy to search for the peptide inhibitors that specifically bind to the hydrophobic pocket. The second strategy, the peptide inhibitor has been designed to mimic the ectodomain portion of membrane protein to disrupt the protein-protein interaction. The designed peptides were tested for the effects on cell viability to measure the toxic to peptide to the cells and their inhibitory assay to inhibit the DENV infection in Vero cells. Furthermore, their antiviral effects on viral replication, intracellular protein level and viral production have been observed by using the qPCR, cell-based flavivirus immunodetection and immunofluorescence assay. None of tested peptides showed the significant effect on cell viability. The small peptide inhibitors achieved from molecular docking, Glu-Phe (EF), effectively inhibited DENV infection in cell culture system. Its most potential effect was observed for DENV2 with a half maximal inhibition concentration (IC50) of 96 μM, but it partially inhibited other serotypes. Treatment of EF at 200 µM on infected cells also significantly reduced the viral genome and protein to 83.47% and 84.15%, respectively, corresponding to the reduction of infected cell numbers. An additional approach was carried out by using peptide mimicking membrane (M) protein, namely MLH40. Treatment of MLH40 caused the reduction of foci formation in four individual DENV serotype (DENV1-4) with IC50 of 24-31 μM. Further characterization suggested that the MLH40 specifically blocked viral attachment to host membrane, and treatment with 100 μM could diminish 80% of viral attachment. In summary, targeting the hydrophobic pocket and M-binding site on the E protein by using the peptide inhibitors could inhibit DENV infection. The results provide proof of-concept for the development of antiviral therapeutic peptide inhibitors to counter DENV infection through the use of a structure-based design targeting conserved viral protein.

Keywords: dengue virus, dengue virus infection, drug design, peptide inhibitor

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Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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Authors: Bruno Baptista, Andreia S. R. Oliveira, Patricia V. Mendonca, Jorge F. J. Coelho, Fani Sousa

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Drug delivery systems are designed to allow adequate protection and controlled delivery of drugs to specific locations. These systems aim to reduce side effects and control the biodistribution profile of drugs, thus improving therapeutic efficacy. This study involved the synthesis of polymeric nanoparticles, based on amphiphilic diblock copolymers, comprising a biocompatible, poly (oligo (ethylene oxide) methyl ether methacrylate (POEOMA) as hydrophilic segment and a pH-sensitive block, the poly (2-diisopropylamino)ethyl methacrylate) (PDPA). The objective of this work was the development of polymeric pH-responsive nanoparticles to encapsulate and carry small RNAs as a model to further develop non-coding RNAs delivery systems with therapeutic value. The responsiveness of PDPA to pH allows the electrostatic interaction of these copolymers with nucleic acids at acidic pH, as a result of the protonation of the tertiary amine groups of this polymer at pH values below its pKa (around 6.2). Initially, the molecular weight parameters and chemical structure of the block copolymers were determined by size exclusion chromatography (SEC) and nuclear magnetic resonance (1H-NMR) spectroscopy, respectively. Then, the complexation with small RNAs was verified, generating polyplexes with sizes ranging from 300 to 600 nm and with encapsulation efficiencies around 80%, depending on the molecular weight of the polymers, their composition, and concentration used. The effect of pH on the morphology of nanoparticles was evaluated by scanning electron microscopy (SEM) being verified that at higher pH values, particles tend to lose their spherical shape. Since this work aims to develop systems for the delivery of non-coding RNAs, studies on RNA protection (contact with RNase, FBS, and Trypsin) and cell viability were also carried out. It was found that they induce some protection against constituents of the cellular environment and have no cellular toxicity. In summary, this research work contributes to the development of pH-sensitive polymers, capable of protecting and encapsulating RNA, in a relatively simple and efficient manner, to further be applied on drug delivery to specific sites where pH may have a critical role, as it can occur in several cancer environments.

Keywords: drug delivery systems, pH-responsive polymers, POEOMA-b-PDPA, small RNAs

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Authors: Ana Carolina Kogawa, Selma Gutierrez Antonio, Hérida Regina Nunes Salgado

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Rifaximin is an oral antimicrobial, gut - selective and not systemic with adverse effects compared to placebo. It is used for the treatment of hepatic encephalopathy, travelers diarrhea, irritable bowel syndrome, Clostridium difficile, ulcerative colitis and acute diarrhea. The crystalline form present in the rifaximin with minimal systemic absorption is α, being the amorphous form significantly different. Regulators are increasingly attention to polymorphisms. Polymorphs can change the form by altering the drug characteristics compromising the effectiveness and safety of the finished product. International Conference on Harmonization issued the ICH Guidance Q6A, which aim to improve the control of polymorphism in new and existing pharmaceuticals. The objective of this study was to obtain polymorphic forms of rifaximin employing recrystallization processes and characterize them by thermal analysis (thermogravimetry - TG and differential scanning calorimetry - DSC), X-ray diffraction, scanning electron microscopy and solubility test. Six polymorphic forms of rifaximin, designated I to VI were obtained by the crystallization process by evaporation of the solvent. The profiles of the TG curves obtained from polymorphic forms of rifaximin are similar to rifaximin and each other, however, the DTG are different, indicating different thermal behaviors. Melting temperature values of all the polymorphic forms were greater to that shown by the rifaximin, indicating the higher thermal stability of the obtained forms. The comparison of the diffractograms of the polymorphic forms of rifaximin with rifaximin α, β and γ constant in patent indicate that forms III, V and VI are formed by mixing polymorph β and α and form III is formed by polymorph β. The polymorphic form I is formed by polymorph β, but with a significant amount of amorphous material. Already, the polymorphic form II consists of polymorph γ, amorphous. In scanning electron microscope is possible to observe the heterogeneity of morphological characteristics of crystals of polymorphic forms among themselves and with rifaximin. The solubility of forms I and II was greater than the solubility of rifaximin, already, forms III, IV and V presented lower solubility than of rifaximin. Similarly, the bioavailability of the amorphous form of rifaximin is considered significantly higher than the form α, the polymorphic forms obtained in this work can not guarantee the excellent tolerability of the reference medicine. Therefore, studies like these are extremely important and they point to the need for greater requirements by the regulatory agencies competent about polymorphs analysis of the raw materials used in the manufacture of medicines marketed globally. These analyzes are not required in the majority of official compendia. Partnerships between industries, research centers and universities would be a viable way to consolidate researches in this area and contribute to improving the quality of solid drugs.

Keywords: electronic microscopy, polymorphism, rifaximin, solubility, X-ray diffraction

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Authors: Javed Sidiqi, Stephen Baezinger, Stephen Wegulo

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Wheat (Triticum aestivum L.) production continues to be challenged by foliar fungal diseases although significant improvement has been made to manage the diseases through developing resistant varieties and the fungicide use to ensure sufficient wheat is produced to meet the growing population’s need. Significant crop losses have been recorded in the history of grain production and yield losses due to fungal diseases, and the trend continues to threat food security in the world and particularly in the less developed countries. The impact of individual fungal diseases on grain yield has been studied extensively to determine crop losses. However, there is limited research available to find out the combined effects of fungal diseases on grain yield and the ways to effectively manage the diseases. Therefore, the objectives of this research were to study the effect of fungal pathogens on grain yield of pre-released winter wheat genotypes in fungicide treated and untreated plots, and to determine whether S7b gene was present in ‘Gage’ wheat as previously hypothesized. Sixty winter wheat genotypes in fungicide treated and untreated plots were studied across four environments. There was a significant effect of fungicide on grain yield consistently across four environments in three years. Fungicide treated wheat lines demonstrated (4,496 kg/ ha-1) grain yield compared to (3,147 kg/ ha-1) grain yield in untreated wheat lines indicating 43% increased grain yield due to severity of foliar fungal diseases. Furthermore, fungicide application also caused an increase in protein concentration from 153 (g kg-1) to 164 (g kg-1) in treated plots in along with test weight from 73 to 77 (kg hL-1) respectively. Gage wheat variety and ISr7b-Ra were crossed to determine presence of Sr7b in Gage. The F2 and F2:3 segregating families were screened and evaluated for stem rust resistance. The segregation of families fell within 15:1 ratio for two separate resistance genes suggesting that Sr7b segregates independently from an unknown resistance gene in Gage that needs to be characterized for its use in the future wheat breeding program to develop resistant wheat varieties.

Keywords: funicide, genetics, foliar diseases, grain

Procedia PDF Downloads 112

Authors: Nagwa Mourad Abdelazeem, Marwa El-hussieny

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Multicomponent reactions (MCRs), one-pot reactions form products from more than two different starting compounds. (MCRs) are ideal reaction systems leading to high structural diversity and molecular complexity through a single transformation. (MCRs) have a lot of advantage such as higher yield, less waste generation, use of readily available starting materials and high atom. (MCRs) provide a rapid process for efficient synthesis of key structures in discovery of drug on the other hand silica sulfuric acid (SSA) has been used as an efficient heterogeneous catalyst for many organic transformations. (SSA) is low cost, ease of preparation, catalyst recycling, and ease of handling, so in this article we used 2-(thiophen-2-yl)-1H-indole, N-substituted anilines and aldehyde in the presence of silica sulfuric acid (SSA) as a catalyst in water as solvent at room temperature to prepare 3,3'-(phenylmethylene)bis(2-(thiophen-2-yl)-1H-indole) and N-methyl-4-(phenyl(2-(thiophen-2-yl)-1H-indol-3-yl)methyl)aniline derivatives Via one-pot reaction. Compound 2-(thiophen-2-yl)-1H-indole belongs to the ubiquitous class of indoles which enjoy broad synthetic, biological and industrial applications ]. Cancer is considered the first or second most common reason of death all through the world. So the synthesized compounds will be tested as anticancer. We expected the synthesized compounds will give good results comparison to the reference drug.

Keywords: aldehydes, aza-friedel-crafts reaction, indole, multicomponent reaction

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Authors: Samia A. El-Fiky, Fouad A. Abou-Zaid, Ibrahim M. Farag, Naira M. El-Fiky

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Clomipramine hydrochloride is one of the most used tricyclic antidepressant drug in Egypt. This drug contains in its chemical structure on two benzene rings. Benzene is considered to be toxic and clastogenic agent. So, the present study was designed to assess the genotoxic effect of Clomipramine hydrochloride on somatic and germ cells in mice. Three dose levels 0.195 (Low), 0.26 (Medium), and 0.65 (High) mg/kg.b.wt. were used. Seven groups of male mice were utilized in this work. The first group was employed as a control. In the remaining six groups, each of the above doses was orally administrated for two groups, one of them was treated for 5 days and the other group was given the same dose for 30 days. At the end of experiments, the animals were sacrificed for cytogenetic and sperm examination as well as histopathological investigations by using hematoxylin and eosin stains (H and E stains) and electron microscope. Concerning the sperm studies, these studies were confined to 5 days treatment with different dose levels. Moreover, the ultrastructural investigation by electron microscope was restricted to 30 days treatment with drug doses. The results of the dose dependent effect of Clomipramine showed that the treatment with three different doses induced increases of frequencies of chromosome aberrations in bone marrow and spermatocyte cells as compared to control. In addition, mitotic and meiotic activities of somatic and germ cells were declined. The treatments with medium or high doses were more effective for inducing significant increases of chromosome aberrations and significant decreases of cell divisions than treatment with low dose. The effect of high dose was more pronounced for causing such genetic deleterious in respect to effect of medium dose. Moreover, the results of the time dependent effect of Clomipramine observed that the treatment with different dose levels for 30 days led to significant increases of genetic aberrations than treatment for 5 days. Sperm examinations revealed that the treatment with Clomipramine at different dose levels caused significant increase of sperm shape abnormalities and significant decrease in sperm count as compared to control. The adverse effects on sperm shape and count were more obviousness by using the treatments with medium or high doses than those found in treatment with low dose. The group of mice treated with high dose had the highest rate of sperm shape abnormalities and the lowest proportion of sperm count as compared to mice received medium dose. In histopathological investigation, hematoxylin and eosin stains showed that, the using of low dose of Clomipramine for 5 or 30 days caused a little pathological changes in liver tissue. However, using medium and high doses for 5 or 30 days induced severe damages than that observed in mice treated with low dose. The treatment with high dose for 30 days gave the worst results of pathological changes in hepatic cells. Moreover, ultrastructure examination revealed, the mice treated with low dose of Clomipramine had little differences in liver histological architecture as compared to control group. These differences were confined to cytoplasmic inclusions. Whereas, prominent pathological changes in nuclei as well as dilated of rough Endoplasmic Reticulum (rER) were observed in mice treated with medium or high doses of Clomipramine drug. In conclusion, the present study adds evidence that treatments with medium or high doses of Clomipramine have genotoxic effects on somatic and germ cells of mice, as unwanted side effects. However, the using of low dose (especially for short time, 5 days) can be utilized as a therapeutic dose, where it caused relatively similar proportions of genetic, sperm, and histopathological changes as those found in normal control.

Keywords: chromosome aberrations, clomipramine, mice, histopathology, sperm abnormalities

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Authors: Debraj Gangopadhyay, Moumita Das, Ranjan K. Singh, Poonam Tandon

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Creatinine is a toxic chemical waste generated from muscle metabolism. Abnormally high levels of creatinine in the body fluid indicate possible malfunction or failure of the kidneys. This leads to a condition termed as creatinine induced nephrotoxicity. N-acetylcysteine is an antioxidant drug which is capable of preventing creatinine induced nephrotoxicity and is helpful to treat renal failure in its early stages. Taurine is another antioxidant drug which serves similar purpose. The kidneys have a natural power that whenever reactive oxygen species radicals increase in the human body, the kidneys make an antioxidant shell so that these radicals cannot harm the kidney function. Taurine plays a vital role in increasing the power of that shell such that the glomerular filtration rate can remain in its normal level. Thus taurine protects the kidneys against several diseases. However, taurine also has some negative effects on the body as its chloramine derivative is a weak oxidant by nature. N-acetylcysteine is capable of inhibiting the residual oxidative property of taurine chloramine. Therefore, N-acetylcysteine is given to a patient along with taurine and this combination is capable of suppressing the negative effect of taurine. Both N-acetylcysteine and taurine being affordable, safe, and widely available medicines, knowledge of the mechanism of their combined effect on creatinine, the favored route of administration, and the proper dose may be highly useful in their use for treating renal patients. Raman spectroscopy is a precise technique to observe minor structural changes taking place when two or more molecules interact. The possibility of formation of a complex between a drug molecule and an analyte molecule in solution can be explored by analyzing the changes in the Raman spectra. The formation of a stable complex of creatinine with N-acetylcysteinein vitroin aqueous solution has been observed with the help of Raman spectroscopic technique. From the Raman spectra of the mixtures of aqueous solutions of creatinine and N-acetylcysteinein different molar ratios, it is observed that the most stable complex is formed at 1:1 ratio of creatinine andN-acetylcysteine. Upon drying, the complex obtained is gel-like in appearance and reddish yellow in color. The complex is hygroscopic and has much better water solubility compared to creatinine. This highlights that N-acetylcysteineplays an effective role in reducing the toxic effect of creatinine by forming this water soluble complex which can be removed through urine. Since the drug taurine is also known to be useful in reducing nephrotoxicity caused by creatinine, the aqueous solution of taurine with those of creatinine and N-acetylcysteinewere mixed in different molar ratios and were investigated by Raman spectroscopic technique. It is understood that taurine itself does not undergo complexation with creatinine as no additional changes are observed in the Raman spectra of creatinine when it is mixed with taurine. However, when creatinine, N-acetylcysteine and taurine are mixed in aqueous solution in molar ratio 1:1:3, several changes occurring in the Raman spectra of creatinine suggest the diminishing toxic effect of creatinine in the presence ofantioxidant drugs N-acetylcysteine and taurine.

Keywords: creatinine, creatinine induced nephrotoxicity, N-acetylcysteine, taurine

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Authors: Bing Lu, Shuang Li, Hongyuan Zhou

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The steel–concrete hybrid structure has been extensively employed in high–rise buildings and super high–rise buildings. The light gauge steel–concrete hybrid structure, including light gauge steel structure and concrete hybrid structure, is a new–type steel–concrete hybrid structure, which possesses some advantages of light gauge steel structure and concrete hybrid structure. The seismic behavior and loss assessment of three high–rise buildings with three different concrete hybrid structures were investigated through finite element software, respectively. The three concrete hybrid structures are reinforced concrete column–steel beam (RC‒S) hybrid structure, concrete–filled steel tube column–steel beam (CFST‒S) hybrid structure, and tubed concrete column–steel beam (TC‒S) hybrid structure. The nonlinear time-history analysis of three high–rise buildings under 80 earthquakes was carried out. After simulation, it indicated that the seismic performances of three high–rise buildings were superior. Under extremely rare earthquakes, the maximum inter–storey drifts of three high–rise buildings are significantly lower than 1/50. The inter–storey drift and floor acceleration of high–rise building with CFST‒S hybrid structure were bigger than those of high–rise buildings with RC‒S hybrid structure, and smaller than those of high–rise building with TC‒S hybrid structure. Then, based on the time–history analysis results, the post-earthquake repair cost ratio and repair time of three high–rise buildings were predicted through an economic performance analysis method proposed in FEMA‒P58 report. Under frequent earthquakes, basic earthquakes and rare earthquakes, the repair cost ratio and repair time of three high-rise buildings were less than 5% and 15 days, respectively. Under extremely rare earthquakes, the repair cost ratio and repair time of high-rise buildings with TC‒S hybrid structure were the most among three high rise buildings. Due to the advantages of CFST-S hybrid structure, it could be extensively employed in high-rise buildings subjected to earthquake excitations.

Keywords: seismic behavior, loss assessment, light gauge steel–concrete hybrid structure, high–rise building, time–history analysis

Procedia PDF Downloads 162

Authors: Maryam Shayani Rad, Seyed Ahmad Mohajeri, Mohsen Mouhebati, Seyed Danial Mousavi

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High blood pressure is one of the most important and serious health-threatening because of no symptoms in most people, which can lead to sudden heart attack, heart failure, and stroke. Nowadays, herbal medicine is one of the best and safest strategies for treatment that have no adverse effects. Apium graveolens (celery) can be used as an alternative treatment for many health conditions such as hypertension. Natural compounds reduce blood pressure via different mechanisms in which Apium graveolens extract provides potent calcium channel blocking properties. A randomized, double-blind, placebo-controlled, cross-over clinical trial was done to evaluate the efficacy of formulated Apium graveolens extract with a maximum yield of 3-n-butylphthalide to reduce systolic and diastolic blood pressure in patients with hypertension. 54 hypertensive patients in the range of 20-68 years old were randomly assigned to the treatment group (26 cases) and the placebo control group (26 cases) and were crossed over after washout duration. The treatment group received at least 2 grams of formulated powder in hard capsules orally, before each meal, 2 times daily. The control group received 2 grams of placebo in hard capsules orally, exactly as the same as shape, time, and doses of treatment group. Treatment was administrated in 12 weeks with 4 weeks washout period at the middle of the study, meaning 4 weeks drug consumption for the treatment group, 4 weeks washout and 4 weeks placebo consumption, and vice versa for the placebo control group. The clinical assessment was done 4 times, including at the beginning and ending of the drug and placebo consumption period by 24-hour ambulatory blood pressure monitoring (ABPM) holter, which measured blood pressure every 15 minutes continuously. There was a statistically significant decrease in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the end of drug duration compared to baseline. The changes after 4 weeks on average was about 12.34 mm Hg for the SBP (P < 0.005) and 7.83 mm Hg for the DBP (P < 0.005). The results from this clinical trial study showed this Apium graveolens extract formulation in the mentioned dosage had a significant effect on blood pressure-lowering for hypertensive patients.

Keywords: Apium graveolens extract, clinical trial, cross-over, hypertension

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Authors: Irene Yi

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Machine learning, natural language processing, and neural network models of language are becoming more and more prevalent in the fields of technology and linguistics today. Training data for machines are at best, large corpora of human literature and at worst, a reflection of the ugliness in society. Computational linguistics is a growing field dealing with such issues of data collection for technological development. Machines have been trained on millions of human books, only to find that in the course of human history, derogatory and sexist adjectives are used significantly more frequently when describing females in history and literature than when describing males. This is extremely problematic, both as training data, and as the outcome of natural language processing. As machines start to handle more responsibilities, it is crucial to ensure that they do not take with them historical sexist and misogynistic notions. This paper gathers data and algorithms from neural network models of language having to deal with syntax, semantics, sociolinguistics, and text classification. Computational analysis on such linguistic data is used to find patterns of misogyny. Results are significant in showing the existing intentional and unintentional misogynistic notions used to train machines, as well as in developing better technologies that take into account the semantics and syntax of text to be more mindful and reflect gender equality. Further, this paper deals with the idea of non-binary gender pronouns and how machines can process these pronouns correctly, given its semantic and syntactic context. This paper also delves into the implications of gendered grammar and its effect, cross-linguistically, on natural language processing. Languages such as French or Spanish not only have rigid gendered grammar rules, but also historically patriarchal societies. The progression of society comes hand in hand with not only its language, but how machines process those natural languages. These ideas are all extremely vital to the development of natural language models in technology, and they must be taken into account immediately.

Keywords: computational analysis, gendered grammar, misogynistic language, neural networks

Procedia PDF Downloads 101

Authors: Iva Blazkova, Amitava Moulick, Vedran Milosavljevic, Pavel Kopel, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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Doxorubicin is one of the most commonly used and the most effective chemotherapeutic drugs. This antracycline drug isolated from the bacteria Streptomyces peuceticus var. caesius is sold under the trade name Adriamycin (hydroxydaunomycin, hydroxydaunorubicin). Doxorubicin is used in single therapy to treat hematological malignancies (blood cancers, leukaemia, lymphoma), many types of carcinoma (solid tumors) and soft tissue sarcomas. It has many serious side effects like nausea and vomiting, hair lost, myelosupression, oral mucositis, skin reactions and redness, but the most serious one is the cardiotoxicity. Because of the risk of heart attack and congestive heart failure, the total dose administered to patients has to be accurately monitored. With the aim to lower the side effects and to targeted delivery of doxorubicin into the tumor tissue, the different nanoparticles are studied. The drug can be bound on a surface of nanoparticle, encapsulated in the inner cavity, or incorporated into the structure of nanoparticle. Among others, carbon nanoparticles (graphene, carbon nanotubes, fullerenes) are highly studied. Besides the number of inorganic nanoparticles, a great potential exhibit also organic ones mainly lipid-based and polymeric nanoparticle. The aim of this work was to perform a toxicity study of free doxorubicin compared to doxorubicin conjugated with various nanotransporters. The effect of liposomes, fullerenes, graphene, and carbon nanotubes on the toxicity was analyzed. As a first step, the binding efficacy of between doxorubicin and the nanotransporter was determined. The highest efficacy was detected in case of liposomes (85% of applied drug was encapsulated) followed by graphene, carbon nanotubes and fullerenes. For the toxicological studies, the chicken embryos incubated under controlled conditions (37.5 °C, 45% rH, rotation every 2 hours) were used. In 7th developmental day of chicken embryos doxorubicin or doxorubicin-nanotransporter complex was applied on the chorioallantoic membrane of the eggs and the viability was analyzed every day till the 17th developmental day. Then the embryos were extracted from the shell and the distribution of doxorubicin in the body was analyzed by measurement of organs extracts using laser induce fluorescence detection. The chicken embryo mortality caused by free doxorubicin (30%) was significantly lowered by using the conjugation with nanomaterials. The highest accumulation of doxorubicin and doxorubicin nanotransporter complexes was observed in the liver tissue

Keywords: doxorubicin, chicken embryos, nanotransporters, toxicity

Procedia PDF Downloads 438

Authors: Kitoholi V. Zhimo

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Unlike the cases of cases of homosexuals, haemophilic and or drug users in USA, France, Africa and other countries, in India the first case of HIV/AIDS was detected in heterosexual female sex workers (FSW) in Chennai in 1986. This image played an important role in understanding HIV/AIDS scenario in the country. Similar to popular and dominant metaphors on HIV/AIDS such as ‘gay plague’, ‘new cancer’, ‘lethal disease’, ‘slim disease’, ‘foreign disease’, ‘junkie disease’, etc. around the world, the social construction of the virus was largely attributed to women in India. It was established that women particularly sex workers are ‘carrier’ and ‘transmitter’ of virus and were categorised as High Risk Groups (HRG’s) alongside homosexuals, transgenders and injecting drug users. Recent literature reveals growing rate of HIV infection among housewives since 1997 which revolutionised public health scenario in India. This means shift from high risk group to general public through ‘bridge population’ encompassing long distance truckers and migrant labours who at the expense of their nature of work and mobility comes in contact with HRG’s and transmit the virus to the general public especially women who are confined to the domestic space. As HIV epidemic expands, married women in monogamous relationship/marriage stand highly susceptible to infection with limited control, right and access over their sexual and reproductive health and planning. In context of Nagaland, a small state in North-eastern part of India HIV/AIDS transmission through injecting drug use dominated the early scene of the epidemic. However, paradigm shift occurred with declining trend of HIV prevalence among injecting drug users (IDU’s) over the past years with the introduction of Opioid Substitution Therapy (OST) and easy access/availability of syringes and injecting needles. Reflection on statistical data reveals that out of 36 states and union territories in India, the position of Nagaland in HIV prevalence among IDU’s has significantly dropped down from 6th position in 2003 to 16th position in 2017. The present face of virus in Nagaland is defined by (hetero) sexual mode of transmission which accounts for about 91% of as reported by Nagaland state AIDS control society (NSACS) in 2016 wherein young and married woman were found to be most affected leading to feminization of HIV/AIDS epidemic in the state. Thus, not only is HIV epidemic feminised but emerged victim to domestic violence which is more often accepted as normal part of heterosexual relationship. In the backdrop of these understanding, the present paper based on ethnographic fieldwork explores the plight, lived experiences and images of HIV+ve women with regard to sexual and reproductive rights against the backdrop of patriarchal system in Nagaland.

Keywords: HIV/AIDS, monogamy, Nagaland, sex worker disease, women

Procedia PDF Downloads 145

Authors: Yiu K. C. Jacky, Tang S. K. Eric, W. Y. Tsang, C. Y. Li, C. K. Leung

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Objectives : (1) To enhance the competence of nurses on using IPMOE for drug administration; (2) To ensure the transition on implementation of IPMOE in safer and smooth way hospital-wide. Methodology: (1) Well-structured Governance: To make provision for IPMOE implementation, multidisciplinary governance structure at Corporate and Local levels are well established. (2) Staff Engagement: A series of staff engagement events were conducted including Staff Forum, IPMOE Hospital Visit, Kick-off Ceremony and establishment of IPMOE Webpage for familiarizing the forthcoming implementation with frontline staff. (3) Well-organized training program: from Workshop to Workplace Two different IPMOE training programs were tailor-made which aimed at introducing the core features of administration module. Fifty-five identical training classes and six train-the-trainer workshops were organized at 2-3Q 2015. Lending Scheme on IPMOE hardware for hands-on practicing was launched and further extended the training from workshop to workplace. (4) Standard Guidelines and Workflow: the related workflow and guidelines are developed which facilitates users to acquire the competence towards IPMOE and fully familiarize with the standardized contingency plan. (5) Facilities and Equipment: The installations of IPMOE hardware were promptly arranged for rollout. Besides, IPMOE training venue was well-established for staff training. (6) Risk Management Strategy: UCH Medication Safety Forum is organized in December 2015 for sharing “Tricks & Tips” on IPMOE which further disseminate at webpage for arousal of medication safety. Hospital-wide annual audit on drug administration was planned to figure out the compliance and deliberate the rooms for improvement. Results: Through the comprehensive training plan, over 1,000 UCH nurses attended the training program with positive feedback. They agreed that their competence on using IPMOE was enhanced. By the end of November 2015, 28 wards (over 1,000 Inpatient-bed) involving departments of M&G, SUR, O&T and O&G have been successfully rolled out IPMOE in 5-month. A smooth and safe transition of implementation of IPMOE was achieved. Eventually, we all get prepared for embedding IPMOE into daily nursing and work altogether for medication safety at UCH.

Keywords: drug administration, inpatient medication order entry system, medication safety, nursing informatics

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Authors: Bozena Tyliszczak, Anna Drabczyk, Sonia Kudlacik-Kramarczyk, Agnieszka Sobczak-Kupiec

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Introduction: Nanomaterials become one of the leading materials in the synthesis of various compounds. This is a reason for the fact that nano-size materials exhibit other properties compared to their macroscopic equivalents. Such a change in size is reflected in a change in optical, electric or mechanical properties. Among nanomaterials, particular attention is currently directed into gold nanoparticles. They find application in a wide range of areas including cosmetology or pharmacy. Additionally, nanogold may be a component of modern wound dressings, which antibacterial activity is beneficial in the viewpoint of the wound healing process. Specific properties of this type of nanomaterials result in the fact that they may also be applied in cancer treatment. Studies on the development of new techniques of the delivery of drugs are currently an important research subject of many scientists. This is due to the fact that along with the development of such fields of science as medicine or pharmacy, the need for better and more effective methods of administering drugs is constantly growing. The solution may be the use of drug carriers. These are materials that combine with the active substance and lead it directly to the desired place. A role of such a carrier may be played by gold nanoparticles that are able to covalently bond with many organic substances. This allows the combination of nanoparticles with active substances. Therefore gold nanoparticles are widely used in the preparation of nanocomposites that may be used for medical purposes with special emphasis on drug delivery. Methodology: As part of the presented research, synthesis of composites was carried out. The mentioned composites consisted of the polymer matrix and gold nanoparticles that were introduced into the polymer network. The synthesis was conducted with the use of a crosslinking agent, and photoinitiator and the materials were obtained by means of the photopolymerization process. Next, incubation studies were conducted using selected liquids that simulated fluids are occurring in the human body. The study allows determining the biocompatibility of the tested composites in relation to selected environments. Next, the chemical structure of the composites was characterized as well as their sorption properties. Conclusions: Conducted research allowed for the preliminary characterization of prepared polymer composites containing gold nanoparticles in the viewpoint of their application for biomedical use. Tested materials were characterized by biocompatibility in tested environments. What is more, synthesized composites exhibited relatively high swelling capacity that is essential in the viewpoint of their potential application as drug carriers. During such an application, composite swells and at the same time releases from its interior introduced active substance; therefore, it is important to check the swelling ability of such material. Acknowledgements: The authors would like to thank The National Science Centre (Grant no: UMO - 2016/21/D/ST8/01697) for providing financial support to this project. This paper is based upon work from COST Action (CA18113), supported by COST (European Cooperation in Science and Technology).

Keywords: nanocomposites, gold nanoparticles, drug carriers, swelling properties

Procedia PDF Downloads 97

Authors: Atul Khurana, Rajul Rastogi, Hans-Joachim Gamperl

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The pharmaceutical companies are getting more inclined towards patient support programs (PSPs) which assist patients and/or healthcare professionals (HCPs) in more desirable disease management and cost-effective treatment. The utmost objective of these programs is patient care. The PSPs may include financial assistance to patients, medicine compliance programs, access to HCPs via phone or online chat centers, etc. The PSP has a crucial role in terms of customer acquisition and retention strategies. During the conduct of these programs, Marketing Authorisation Holder (MAH) may receive information related to concerned medicinal products, which is usually reported by patients or involved HCPs. This information may include suspected adverse reaction(s) during/after administration of medicinal products. Hence, the MAH should design PSP to comply with regulatory reporting requirements and avoid non-compliance during PV inspection. The emergence of wireless health devices is lowering the burden on patients to manually incorporate safety data, and building a significant option for patients to observe major swings in reference to drug safety. Therefore, to enhance the adoption of these programs, MAH not only needs to aware patients about advantages of the program, but also recognizes the importance of time of patients and commitments made in a constructive manner. It is indispensable that strengthening the public health is considered as the topmost priority in such programs, and the MAH is compliant to Pharmacovigilance (PV) requirements along with regulatory obligations.

Keywords: drug safety, good pharmacovigilance practice, patient support program, pharmacovigilance

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Authors: Hossein Navid, Maryam Adeli Khadem, Shahin Oustan, Mahmoud Zareie

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Among the nutrients needed by the plants, three elements containing nitrate, phosphorus and potassium are more important. The objective of this research was measuring these nutrient amounts in soil using Fourier transform infrared spectroscopy in range of 400- 4000 cm-1. Soil samples for different soil types (sandy, clay and loam) were collected from different areas of East Azerbaijan. Three types of fertilizers in conventional farming (urea, triple superphosphate, potassium sulphate) were used for soil treatment. Each specimen was divided into two categories: The first group was used in the laboratory (direct measurement) to extract nitrate, phosphorus and potassium uptake by colorimetric method of Olsen and ammonium acetate. The second group was used to measure drug absorption spectrometry. In spectrometry, the small amount of soil samples mixed with KBr and was taken in a small pill form. For the tests, the pills were put in the center of infrared spectrometer and graphs were obtained. Analysis of data was done using MINITAB and PLSR software. The data obtained from spectrometry method were compared with amount of soil nutrients obtained from direct drug absorption using EXCEL software. There were good fitting between these two data series. For nitrate, phosphorus and potassium R2 was 79.5%, 92.0% and 81.9%, respectively. Also, results showed that the range of MIR (mid-infrared) is appropriate for determine the amount of soil nitrate and potassium and can be used in future research to obtain detailed maps of land in agricultural use.

Keywords: nitrate, phosphorus, potassium, soil nutrients, spectroscopy

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Authors: Sheimah El Bejjaji, Lara Gorsek, Chandler Quilchez, Joaquim Suñer, Mireia Mallandrich

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Flurbiprofen is an anti-inflammatory drug used in several treatments. The purpose of this study was to compare the permeation of two different formulations of flurbiprofen through the human skin. The first formulation was a solution of flurbiprofen dissolved with polyethylene glycol 3350 (PEG 3350). The second formulation was flurbiprofen encapsulated in poly-ɛ-caprolactone (PɛCL) nanoparticles (NPs), stabilized with poloxamer 188, submitted individually for freeze-drying with PEG 3350 as a cryoprotectant and sterilized by gamma-irradiation. Human skin was obtained from the abdominal region of a healthy patient. The experimental protocol was approved by the Bioethics Committee of Barcelona SCIAS Hospital (Spain), and they obtained the written informed consent forms. After being frozen to -20ºC, the skin samples were cut with a dermatome at 400 µm. The ex vivo permeation study was performed in Franz diffusion cells with a diffusion area of 2.54 cm². Skin samples were placed between two compartment sites, the dermal side in contact with the receptor medium and the epidermis side in contact with the donor chamber to which the formulation was applied. The permeation study was conducted for 24 hours at 32 ± 0.5 °C in accordance with sink conditions. The results were analyzed with an unpaired t-test, and the p-values indicate the formulation with nanoparticles had a higher permeability coefficient, flux, partition parameter, diffusion parameter, and lag time. The applicability of this formulation topically can benefit articulations and ligament inflammation as an alternative to oral drugs.

Keywords: anti-inflammatory drug, flurbiprofen, human skin, nanoparticles, skin permeation

Procedia PDF Downloads 73