Search results for: drug synergy

Authors: Mohammad Javad Behzadnia, Hamidreza Javadzadeh

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Background: Pain management is essential to surmounting multi-injured people in an overcrowded emergency setting. Its role would be more apparent when the physician encounters a mass casualty in a war zone or even a military prehospital. Having sedative and analgesic properties, rapid onset and offset effects, and maintaining the cardiovascular and respiratory contain are the main reason for selecting Ketamine as a good choice in the war zone. Methods: In a prospective interventional study in a war zone, we have selected and followed two groups of casualties for pain management. All were men with an average age of 26.6±8 y/o and 27.5 ±7 y/o in A and B groups, respectively. Group A received only Ketamine and Group B received Ketamine and diazepam. Results: This study showed that all of the injured patients who received Ketamine had experienced some agitation, and they may finally need benzodiazepines for sedation, but in group B that received benzodiazepine before or simultaneous with Ketamine, the agitation was significantly reduced. (P Value ≤0.05) Conclusion: Various factors may affect pain score and perception; patients' culture, mental health, previous drug usage, and addiction could alter the pain score in similar situations. It seems that the significant agitation is due to catecholamine release in stressful Moments of the battlefield. Accordingly, this situation could be exacerbated due to ketamine properties. Nonetheless, as a good choice in the war zone, Ketamine is now recommended to combine with benzodiazepines for procedural sedation and analgesia (PSA).

Keywords: battlefield, ketamine, benzodiazepine, pain control

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Authors: Debasish Pradhan, Shaktiprasad Pradhan, Rakesh Kumar Pradhan, Gitanjali Tripathy

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Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. The current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was a positive correlation between them. At that point, we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi, the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise, the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: breast cancer, multidrug resistance, SOCS1 gene, MDR1 gene, RNA interference

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Authors: Kalaumari Mayoral-Peña, Ana I. Montejano-Montelongo, Josué Reyes-Muñoz, Gonzalo A. Ortiz-Mancilla, Mayrin Rodríguez-Cruz, Víctor Hernández-Villalobos, Jesús A. Guzmán-López, Santiago García-Jacobo, Iván Licona-Vázquez, Grisel Fierros-Romero, Rosario Flores-Vallejo

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The group B-lactamic antibiotics include some of the most frequently used small drug molecules against bacterial infections. Nevertheless, an alarming decrease in their efficacy has been reported due to the emergence of antibiotic-resistant bacteria. Infections caused by bacteria expressing extended Spectrum B-lactamases (ESBLs) are difficult to treat and account for higher morbidity and mortality rates, delayed recovery, and high economic burden. According to the Global Report on Antimicrobial Resistance Surveillance, it is estimated that mortality due to resistant bacteria will ascend to 10 million cases per year worldwide. These facts highlight the importance of developing low-cost and readily accessible detection methods of drug-resistant ESBLs bacteria to prevent their spread and promote accurate and fast diagnosis. Bacterial detection is commonly done using molecular diagnostic techniques, where PCR stands out for its high performance. However, this technique requires specialized equipment not available everywhere, is time-consuming, and has a high cost. Loop-Mediated Isothermal Amplification (LAMP) is an alternative technique that works at a constant temperature, significantly decreasing the equipment cost. It yields double-stranded DNA of several lengths with repetitions of the target DNA sequence as a product. Although positive and negative results from LAMP can be discriminated by colorimetry, fluorescence, and turbidity, there is still a large room for improvement in the point-of-care implementation. DNA origami is a technique that allows the formation of 3D nanometric structures by folding a large single-stranded DNA (scaffold) into a determined shape with the help of short DNA sequences (staples), which hybridize with the scaffold. This research aimed to generate DNA origami structures using LAMP products as scaffolds to improve the sensitivity to detect ESBLs in point-of-care diagnosis. For this study, the coding sequence of the CTM-X-15 ESBL of E. coli was used to generate the LAMP products. The set of LAMP primers were designed using PrimerExplorerV5. As a result, a target sequence of 200 nucleotides from CTM-X-15 ESBL was obtained. Afterward, eight different DNA origami structures were designed using the target sequence in the SDCadnano and analyzed with CanDo to evaluate the stability of the 3D structures. The designs were constructed minimizing the total number of staples to reduce costs and complexity for point-of-care applications. After analyzing the DNA origami designs, two structures were selected. The first one was a zig-zag flat structure, while the second one was a wall-like shape. Given the sequence repetitions in the scaffold sequence, both were able to be assembled with only 6 different staples each one, ranging between 18 to 80 nucleotides. Simulations of both structures were performed using scaffolds of different sizes yielding stable structures in all the cases. The generation of the LAMP products were tested by colorimetry and electrophoresis. The formation of the DNA structures was analyzed using electrophoresis and colorimetry. The modeling of novel detection methods through bioinformatics tools allows reliable control and prediction of results. To our knowledge, this is the first study that uses LAMP products and DNA-origami in combination to delect ESBL-producing bacterial strains, which represent a promising methodology for diagnosis in the point-of-care.

Keywords: beta-lactamases, antibiotic resistance, DNA origami, isothermal amplification, LAMP technique, molecular diagnosis

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Authors: Bashar Al-Sabti, Jehad Harbali

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Background: Pyridine is a reactive base that might be used in preparing sitagliptin. International Agency for Research on Cancer classifies pyridine in group 2B; this classification means that pyridine is possibly carcinogenic to humans. Therefore, pyridine should be monitored at the allowed limit in sitagliptin pharmaceutical ingredients. Objective: The aim of this study was to develop a novel ultra high performance liquid chromatography mass spectrometry (UHPLC-MS) method to estimate the quantity of pyridine impurity in sitagliptin pharmaceutical ingredients. Methods: The separation was performed on C8 shim-pack (150 mm X 4.6 mm, 5 µm) in reversed phase mode using a mobile phase of water-methanol-acetonitrile containing 4 mM ammonium acetate in gradient mode. Pyridine was detected by mass spectrometer using selected ionization monitoring mode at m/z = 80. The flow rate of the method was 0.75 mL/min. Results: The method showed excellent sensitivity with a quantitation limit of 1.5 ppm of pyridine relative to sitagliptin. The linearity of the method was excellent at the range of 1.5-22.5 ppm with a correlation coefficient of 0.9996. Recoveries values were between 93.59-103.55%. Conclusions: The results showed good linearity, precision, accuracy, sensitivity, selectivity, and robustness. The studied method was applied to test three batches of sitagliptin raw materials. Highlights: This method is useful for monitoring pyridine in sitagliptin during its synthesis and testing sitagliptin raw materials before using them in the production of pharmaceutical products.

Keywords: genotoxic impurity, pyridine, sitagliptin, UHPLC -MS

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Authors: Yu Zhang, Il Kim

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Polypeptides with defined peptide sequences illustrate the power of remarkable applications in drug delivery, tissue engineering, sensing and catalysis. Especially the cyclic polypeptides, the distinctive topological architecture imparts many characteristic properties comparing to linear polypeptides. Here, a facile and highly efficient strategy for the synthesis of linear and cyclic polypeptides is reported using N-heterocyclic carbenes (NHCs)-mediated ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCA) in the presence or absence of primary amine initiator. The polymerization proceeds rapidly in a quasi-living manner, allowing access to linear and cyclic polypeptides of well-defined chain length and narrow polydispersity, as evidenced by nuclear magnetic resonance spectrum (1H NMR and 13C NMR spectra) and size exclusion chromatography (SEC) analysis. The cyclic architecture of the polypeptides was further verified by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectra (MALDI-TOF MS) and electrospray ionization (ESI) mass spectra, as well as viscosity studies. This approach can also simplify workup procedures and make bulk scale synthesis possible, which thereby opens avenues for practical uses in diverse areas, opening up the new generation of polypeptide synthesis.

Keywords: α-amino acid N-carboxyanhydrides, living polymerization, polypeptides, N-heterocyclic carbenes, ring-opening polymerization

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Authors: Ahmed Jibrin Uttu, Maimuna Waziri

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The root bark of Glossonema boveanum (Decne), a member of Apocynaceae family, is used by traditional medicine practitioner to treat urinary and respiratory tract infections, bacteremia, typhoid fever, bacillary dysentery, diarrhea and stomach pain. This present study aims to validate the medicinal claims ascribed to the root bark of the plant. Preliminary phytochemical study of the root bark extracts (n-hexane, ethyl acetate, chloroform and methanol extracts) showed the presence of alkaloids, carbohydrates, steroids, triterpenes, cardiac glycosides, saponins, tannins and flavonoids. Antimicrobial study of the extracts showed activities against Staphylococus aureus, Bacillus subtilis, Salmonella typhii, Shigella dysenteriae, Escherichia coli, Enterobacter cloacae, Streptococcus agalactiae and Candida albicans while Micrococcus luteus, Pseudomonas aeruginosa and Klebsiella Pneumoniae showed resistance to all the extracts. The inhibitory effect was compared with the standard drug ciprofloxacin and fluconazole. MIC and MBC for both extracts were also determined using the tube dilution method. This study concluded that the root bark of G. boveanum, used traditionally as a medicinal plant, has antimicrobial activities against some causative organisms.

Keywords: Glossonema boveanum (Decne.), phytochemical, antimicrobial, minimum inhibitory concentration, minimum bactericidal concentration

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Authors: Salem Abdalla

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Objective: Dipyrone is a widely used, well tolerated analgesic drug which, however, is compromised by agranulocytosis as an adverse effect. Subsequent to no enzymatic hydrolysis, the primary metabolic step is N-demethylation of 4-methylaminoantipyrine (4-MAA) to 4-aminoantipyrine (4-AA). The aim of the present study was to identify the cytochrome P-450 enzyme (CYP) mediating this reaction. Methods: We identified the relevant CYP using virus expressed isolated rat liver microsomes with chemical inhibition studies. The substrate of 4-methylaminantipyrine was employed at six different concentrations (25, 50, 100, 400, 800, and 1200 µmol/l) with varying concentrations of selective inhibitors of CYP1A2 (furafylline, fluvoxamine), CYP3A4 (ketoconazole), CYP2A6 (coumarin), CYP2D6 (quinidine), CYP2C19 (omeprazole, fluvoxamine, tranylcypromine), CYP2C9 (sulfaphenazole), and CYP1A1 (alpha-naphthoflavone). 4-MAA and 4-AA were analyzed by HPLC, and enzyme kinetic parameters (Km and Vmax) were determined by regression (Sigma plot 9.0). Results: The N-demethylation of 4-MAA by microsomes prepared from baculovirus-expressing human CYP was pronounced with CYP2C19. Intrinsic clearances of the most active enzymes were 0.092, 0.027, and 0.026 for the CYP enzymes 2C19, 2D6, and 1A2, respectively. Metabolism by rat liver microsomes was strongly inhibited by omeprazole (IC50 of 0.05). Conclusion: The enzyme CYP2C19 apparently has an important role in N-demethylation of 4-methylaminoantipyrine which should be further analyzed in clinical studies and which may also be interesting concerning the agranulocytosis.

Keywords: dipyrone, 4-methylaminoantipyrine (4-MAA), 4- aminoantipyrine (4-AA), metabolism, human CYP2C19

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Authors: Joe Modise, Bamidel Joseph Okoli, Nas Molefe, Imelda Ledwaba

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The present study describes the chemical profile and antioxidant potential of the stem bark of Acacia decurrens. The methanol fraction of A. decurrens stem bark gave the highest yield (20 %), while the hexane fraction had the lowest yield (0.2 %). The GC-MS spectra of the hexane, chloroform and ethyl acetate fractions confirm the presence of fifty two major compounds and the ICP-OES analysis of the stem bark was found to contain Co(0.41), Zn(1.75), Mn(3.69), Ca(8.67), Ni(10.54), Mg(12.98), Cr(24.38), K(47.88), Fe(154.62) ppm; which is an indication of hyper-accumulation capacity. The UV-Visible spectra of showed four absorption maxima for hexane fraction at 665 (0.028), 410 (0.116), 335 (0.278) and 250 (0.007) nm, three for chloroform fraction at 665 (0.028), 335 (0.278) and 250 (0.007) nm , three for ethyl acetate fraction at 665 (0.070), 390 (0.648) and 345 (0.663) nm and three for methanol fraction at 385 (0.508), 310 (0.886) and 295 (0.899) nm respectively. Quantitative phytochemical screening indicated that the alkaloid (0.6-3.3) % and saponins (5.1-8.6) % contents of the various fractions were significantly lower than the tannin (30.9-55.8) mg TAE/g, steroid(13.92-41.2) %, phenol (40.6-65.5) mgGAE/g and flavonoids (210.2 -284.9) mg RUE/g contents. The antioxidant activity of the fractions was analysed by different methods and revealed good to moderate antioxidant potential with different IC50 values viz. (42.2-49.6) mg/mL for ABTS and (37.8-75.0) μg/ml for DPPH respectively, compared to standard antioxidants. Based on obtained results, the A.decurrens stem bark fractions can be a source of safe, sustainable natural antioxidant drug and can be exploited as a source of controlled green-heavy metal cleaner.

Keywords: Acacia decurrens, antioxidant, DPPH, ABTS, hyperaccumulation, Menstruum, ICP-OES, GC-MS, UV/visible

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Authors: Uzma Saqib, Mirza S. Baig

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Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

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Authors: Elham Zarenezhad, Ali Zarenezhad, Mehdi Mardkhoshnood

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We described the synthesis and biological study of O-oxime ethers having a-amino acid residues as new analogs of IPS-339. In this synthesis, the reaction of fluorene O-oxime with epichlorohydrin or epibromohydrin afforded the corresponding O-oxime ether adducts. The N-alkylation of valine amino acid with O-oxime ether adducts led to the synthesis of new analogs of IPS-339. The cardiovascular properties of the compound have been studied. In this regard, six clinically healthy same sex mongrel dogs were examined. The dogs were randomly divided into 3 groups of two members. 1 groups received 2 mg kg-1 body weight of compound (2-(3-(9H-fluoren-9-ylideneaminooxy)-2- hydroxypropylamino)-3-methylbutanoic acid) intravenously, whereas group 2 and 3 received only DMSO–water (distil.) and propranolol (Inderal) (2 mg kg-1), respectively. The electrocardiograph (ECG) was recorded with lead II. The recording was run successively by 5 min time interval on each dog before, simultaneously, and after compound infusion. Data after administration were taken from normal sinus beats that were closely related to the arrhythmias whenever they occurred. In general, no detectable arrhythmia was observed in all ECG records regardless of increasing the heart rate that likely caused by stress origin from invasive procedure just after infusion. Compound diminished the heart rate during study especially at 20th minute compared to propranolol as a reference drug. Compound (2-(3-(9H-fluoren-9-ylideneaminooxy)-2- hydroxypropylamino)-3-methylbutanoic acid) was the most effective compound with remarkable ability in declining of the heart rate.

Keywords: electrocardiograph (ECG), cardiovascular, IPS-339, dogs

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Authors: Abdullah Mohammad, Abdullah Alshemali, Esmaeil Alsaleh

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The chemical composition of desalinated water is modified to make it more acceptable to the end-user. Sometimes, this modification is approached by mixing with brackish water that is known to contain a variety of minerals. Expectedly, besides minerals, brackish water indigenous bacterial communities access the final mixture hence reaching the end consumer. The current project examined the safety of using brackish water as an ingredient in potable water. Pseudomonas aeruginosa strains were detected in potable and brackish water samples collected from storage facilities in residential areas as well as from main water distribution and storage tanks. The application of molecular and biochemical fingerprinting methods, including phylogeny, RFLP (restriction fragment length polymorphism), MLST (multilocus sequence typing) and substrate specificity testing, suggested that the potable water P. aeruginosa strains were most probably originated from brackish water. Additionally, all the sixty-four isolates showed multi-drug resistance (MDR) phenotype and harboured the three genes responsible for biofilm formation. These virulence factors represent serious health hazards compelling the scientific community to revise the WHO (World Health Organization) and USEP (US Environmental Protection Agency) A potable water quality guidelines, particularly those related to the types of bacterial genera that evade the current water quality guidelines.

Keywords: potable water, brackish water, pseudomonas aeroginosa, multidrug resistance

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Authors: Saji George, Eng Khuan Seng, Christof Luda

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Nanotechnology has been recognized as an important tool for modern agriculture and has the potential to overcome some of the pressing challenges faced by aquaculture industry. A strategy for optimizing nanotechnology-based therapeutic delivery platform for immunizing farmed fish was developed. Accordingly, a compositional library of nanomaterials of natural chemistry (Halloysite (clay), Chitosan, Hydroxyapatite, Mesoporous Silica and a composite material of clay-chitosan) was screened for their toxicity and efficiency in delivering models antigens in cellular and zebrafish embryo models using high throughput screening platforms. Through multi-parametric optimization, chitosan modified halloysite (clay) nanomaterial was identified as an optimal vaccine delivery platform. Further, studies conducted in juvenile seabass showed the potential of clay-chitosan in delivering outer membrane protein of Tenacibaculum maritimum- TIMA (pathogenic bacteria) to and its efficiency in eliciting immune responses in fish. In short, as exemplified by this work, the strategy of using compositional nanomaterial libraries and their biological profiling using high-throughput screening platform could fasten the discovery process of nanomaterials with potential applications in food and agriculture.

Keywords: nanotechnology, fish-vaccine, drug-delivery, halloysite-chitosan

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Authors: Jhonas Geraldo Peixoto Flauzino, Pedro Pompeo Boechat Araujo, Alexia Allis Rocha Lima, Giovanna Biângulo Lacerda Chaves, Victor Ryan Ferrão Chaves

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Schizophrenia is characterized as a set of psychiatric signs and symptoms (syndrome) that commonly erupt in the stages of adolescence or early adulthood, being recognized as one of the most serious diseases, as it causes important problems during the life of the patient. carrier - both in mental health and in physical health and in social life. Objectives: This is an integrative literature review that aimed to verify what has been produced of scientific knowledge in the field of child and adolescent psychiatry regarding schizophrenia in these stages of life, correlated to the most discussed themes and methodologies of choice for the preparation of studies. Methods: Articles were selected from the following databases: Virtual Health Library and CAPES Journal Portal, published in the last five years; and on Google Scholar, published in 2021, totaling 62 works, searched in September 2021. Results: The studies focus mainly on diagnosis through the DSM-V (25.8%), on drug treatment (25.8%) and in psychotherapy (24.2%), most of them in the literature review format: integrative (27.4%) and systematic (24.2%). Conclusion: The themes and study methods are redundant, and do not cover in depth the immense aspects that encompass Schizophrenia in Childhood and Adolescence, giving attention to the disease in a general way or focusing on the adult patient.

Keywords: schizophrenia, mental health, childhood, adolescence

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Authors: Shuafeng Yuan, Bojian Zheng

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The RNA-dependent RNA polymerase of influenza a virus comprises conserved and independently folded subdomains with defined functionalities. The N-terminal domain of the PA subunit (PAN) harbors the endonuclease function so that it can serve as a desired target for drug discovery. To identify a class of anti-influenza inhibitors that impedes PAN endonuclease activity, a screening approach that integrated the fluorescence resonance energy transfer based endonuclease inhibitor assay with the DNA gel-based endonuclease inhibitor assay was conducted, followed by the evaluation of antiviral efficacies and potential cytotoxicity of the primary hits in vitro and in vivo. A small-molecule compound ANA-0 was identified as a potent inhibitor against the replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2, in cell cultures. Combinational treatment of zanamivir and ANA-0 exerted synergistic anti-influenza effect in vitro. Intranasal administration of ANA-0 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. Docking analyses predicted ANA-0 bound the endonuclease cavity of PAN by interacting with the metal-binding and catalytic residues. In summary, ANA-0 shows potential to be developed to novel anti-influenza agents.

Keywords: anti-influenza, novel compound, inhibition of endonuclease, PA

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Authors: Alessandra Swiny, Yiorgos Hadjichristou

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There exists an on-going geographical scar creating a division through the Island of Cyprus and its capital, Nicosia. The currently amputated city center is accessed legally by the United Nations convoys, infiltrated only by Turkish and Greek Cypriot army scouts and illegal traders and scavengers. On Christmas day 1963 in Nicosia, Captain M. Hobden of the British Army took a green chinagraph pencil and on a large scale Joint Army-RAF map ‘marked’ the division. From then on this ‘buffer zone’ was called the ‘green line.' This once dividing form, separating the main communities of Greek and Turkish Cypriots from one another, has now been fully reclaimed by an autonomous intruder. It's currently most captivating inhabitant is nature. She keeps taking over, for the past fifty years indigenous and introduced fauna and flora thrive; trees emerge from rooftops and plants, bushes and flowers grow randomly through the once bustling market streets, allowing this ‘no man’s land’ to teem with wildlife. And where are its limits? The idea of fluidity is ever present; it encroaches into the urban and built environment that surrounds it, and notions of ownership and permanence are questioned. Its qualities have contributed significantly in the search for new ‘identities,' expressed in the emergence of new living conditions, be they real or surreal. Without being physically reachable, it can be glimpsed at through punctured peepholes, military bunker windows that act as enticing portals into an emotional and conceptual level of inhabitation. The zone is mystical and simultaneously suspended in time, it triggers people’s imagination, not just that of the two prevailing communities but also of immigrants, refugees, and visitors; it mesmerizes all who come within its proximity. The paper opens a discussion on the issues and the binary questions raised. What is natural and artificial; what is private and public; what is ephemeral and permanent? The ‘green line’ exists in a central fringe condition and can serve in mixing generations and groups of people; mingling functions of living with work and social interaction; merging nature and the human being in a new-found synergy of human hope and survival, allowing thus for new notions of place to be introduced. Questions seek to be answered, such as, “Is the impossibility of dwelling made possible, by interweaving these ‘in-between conditions’ into eloquently traced spaces?” The methodologies pursued are developed through academic research, professional practice projects, and students’ research/design work. Realized projects, case studies and other examples cited both nationally and internationally hold global and local applications. Both paths of the research deal with the explorative understanding of the impossibility of dwelling, testing the limits of its autonomy. The expected outcome of the experience evokes in the user a sense of a new urban landscape, created from human topographies that echo the voice of an emerging identity.

Keywords: urban wildlife, human topographies, buffer zone, no man’s land

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Authors: Mehmet Akoz, Mustafa Kul

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Ewes and goats are seasonally polyestrus animals. Their reproductive activities are associated with the reduction or extending of daylight. Melatonin releasing from pineal gland regulates the sexual activities depending on daylight. In recent years, number of ewes decreased in our country. This situation dispatched to developing of some methods to increase productivity. Small ruminants can be synchronized with the natural and medical methods. known methods from natural light set with ram and goat participation. The most important natural methods of male influence, daylight is regulated and feed. On the other hand, progestagens, PGF2α, melatonin, and gonadotropins are commonly used for the purpose of estrus synchranization. But it is not effective PGF2α anestrous season The short-term and long-term progesterone treatment was effective to synchronize estrus in small ruminats during both breeding and anestrus seasons. Alternative choices of progesterone/progestagen have been controlled internal drug release (CIDR) devices, supplying natural progesterone, norgestomet implants, and orally active melengestrol acetate Melatonin anestrous season and should be applied during the transition period, but the season can be synchronized. Estrus synchronisation shortens anestrus season, decreases labor for mating/insemination and estrus pursuit, and induces multiple pregnancies.

Keywords: ewes, goat, synchronization, progestagen, PGF2α

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Authors: Katharigatta N. Venugopala, Melendhran Pillay, Bander E. Al-Dhubiab

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Tuberculosis (TB) infection is caused mainly by Mycobacterium tuberculosis (MTB) and it is one of the most threatening and wide spread infectious diseases in the world. Benzothiazole derivatives are found to have diverse chemical reactivity and broad spectrum of pharmacological activity. Some of the important pharmacological activities shown by the benzothiazole analogues are antitumor, anti-inflammatory, antimicrobial, anti-tubercular, anti-leishmanial, anticonvulsant and anti-HIV properties. Keeping all these facts in mind in the present investigation it was envisaged to synthesize a series of novel {2-(benzo[d]-thiazol-2-yl-methoxy)-substitutedaryl}-(substitutedaryl)-methanones (4a-f) and characterize by IR, NMR (1H and 13C), HRMS and single crystal x-ray studies. The title compounds are investigated for in vitro anti-tubercular activity against two TB strains such as H37Rv (ATCC 25177) and MDR-MTB (multi drug resistant MTB resistant to Isoniazid, Rifampicin and Ethambutol) by agar diffusion method. Among the synthesized compounds in the series, test compound {2-(benzo[d]thiazol-2-yl-methoxy)-5-fluorophenyl}-(4-chlorophenyl)-methanone (2c) was found to exhibit significant activity with MICs of 1 µg/mL and 2 µg/mL against H37Rv and MDR-MTB, respectively when compared to standard drugs. Single crystal x-ray studies was used to study intra and intermolecular interactions, including polymorphism behavior of the test compounds, but none of the compounds exhibited polymorphism behavior.

Keywords: benzothiazole analogues, characterization, crystallography, anti-TB activity

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Authors: Md. Danish Eqbal, Venkat Gundabala

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Microparticles and microcapsules are basically used as a carrier for cells, tissues, drugs, and chemicals. Due to its biocompatibility, non-toxicity and biodegradability, alginate based microparticles have numerous applications in drug delivery, tissue engineering, organ repair and transplantation, etc. The production of uniform monodispersed microparticles was a challenge for the past few decades. However, emergence of microfluidics has provided controlled methods for the generation of the uniform monodispersed microparticles. In this work, we present a successful method for the generation of both microparticles and microcapsules (single and double core) using merging approach of two droplets, completely inside the microfluidic device. We have fabricated hybrid glass- PDMS (polydimethylsiloxane) based microfluidic device which has coflow geometry as well as the T junction channel. Coflow is used to generate the single as well as double oil-alginate emulsion in oil and T junction helps to form the calcium chloride droplets in oil. The basic idea is to match the frequency of the alginate droplets and calcium chloride droplets perfectly for controlled generation. Using the merging of droplets technique, we have successfully generated the microparticles and the microcapsules having single core as well as double and multiple cores. The cores in the microcapsules are very stable, well separated from each other and very intact as seen through cross-sectional confocal images. The size and the number of the cores along with the thickness of the shell can be easily controlled by controlling the flowrate of the liquids.

Keywords: double-core, droplets, microcapsules, microparticles

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Authors: Argaw Amare, Abbuna Fuffa, Stringer Andy

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Improving public knowledge and changing their attitudes towards antibiotic use will be a crucial early strategy to contain Antibiotic resistance. The current study was undertaken from November 2015 to June 2016. A cross-sectional survey using a pretested questionnaire was conducted on 392 residents (330 male and 62 female) aged 18 and above. Participants were selected randomly. Data was analyzed using simple descriptive statistics; the Chi-square test was used to determine any significant difference. The majority of participants (81%) were farmers in their occupation. Most of the respondents (76%) were not able to define the difference between antimicrobials and antibiotics. Furthermore, (61%) of participants were not able to define what antibiotics and for what purpose they are used. Thirty-four percent of participants do not know the names of antibiotics they have used for their animals and for themselves. Nearly 68% have no knowledge about the disease they have been treated for. The majority of participants (73.5%) agree to complete their course of treatment even if they feel better. About 72.5% of participants disagree that antibiotics are safe and can be used to treat different diseases, without prescription. Most of the participants (95%) treat their animals after diagnosis; more than 80% of them agree to not purchase veterinary drugs from local traders. This study showed that the participants have poor knowledge and good attitude, with an average score of 41.3±16.1% and 79.6±16, respectively. Knowledge and attitude are significantly correlated (p<0.01). The participants in this study had a good attitude toward the rational use of antibiotics. Whereas they lack knowledge with regard to the kinds of antibiotics and the diseases they are prescribed for. Therefore, further educational interventions are necessary to improve their understanding of the antibiotics currently available and the major bacterial diseases they are prescribed.

Keywords: AMR, knoweledge, attitude, perception

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Authors: F. Kashanian, M. M. Masoudi, A. Akbari, A. Shamloo, M. R. Zand, S. S. Salehi

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Nano-sized materials present new opportunities in biology and medicine and they are used as biomedical tools for investigation, separation of molecules and cells. To achieve more effective cancer therapy, it is essential to select cancer cells exactly. This research suggests that using the antibody-functionalized nontoxic Arginine-doped magnetic nanoparticles (A-MNPs), has been prosperous in detection, capture, and magnetic separation of circulating tumor cells (CTCs) in tumor tissue. In this study, A-MNPs were synthesized via a simple precipitation reaction and directly immobilized Ep-CAM EBA-1 antibodies over superparamagnetic A-MNPs for Mucin BCA-225 in breast cancer cell. The samples were characterized by vibrating sample magnetometer (VSM), FT-IR spectroscopy, Tunneling Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). These antibody-functionalized nontoxic A-MNPs were used to capture breast cancer cell. Through employing a strong permanent magnet, the magnetic separation was achieved within a few seconds. Antibody-Conjugated nontoxic Arginine-doped Fe₃O₄ nanoparticles have the potential for the future study to capture CTCs which are released from tumor tissue and for drug delivery, and these results demonstrate that the antibody-conjugated A-MNPs can be used in magnetic hyperthermia techniques for cancer treatment.

Keywords: tumor tissue, antibody, magnetic nanoparticle, CTCs capturing

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Authors: Hosein Alimadadi, Fatemeh Farahmand, Ali Jafarian, Nasir Fakhar, Mohammad Hassan Sohouli, Neda Raeesi

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Backgroundsː Regarding the important role of liver transplantation as the only treatment in many cases of end-stage liver disease in children, the aim of this study is to investigate the complications of liver transplantation and their management in children referred to the Children's Medical Center. Methods: This study is a cross-sectional study on pediatric patients who have undergone liver transplants in the years 2016 to 2021. The indication for liver transplantation in this population was confirmed by a pediatric gastroenterologist, and a liver transplant was performed by a transplant surgeon. Finally, information about the patient before and after the transplantation was collected and recorded. Results: A total of 53 patients participated in this study, including 25 (47.2%) boys and 28 (52.8%) girls. The most common causes of liver transplantation were cholestatic and metabolic diseases. The most common early complication of liver transplantation in children was acute cellular rejection (ACR) and anastomotic biliary stricture. The most common late complication in these patients was an infection which was observed in 56.6% of patients. Among the drug side effects, neurotoxicity (convulsions) was seen more in patients, and 15.1% of the transplanted patients died. Conclusion: In this study, the most common early complication of liver transplantation in children was ACR and biliary stricture, and the most common late complication was infection. Neurotoxicity (convulsions) was the most common side effect of drugs.

Keywords: liver transplantation, complication, infection, survival rate

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Authors: Jawad Alzeer

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Natural products are well recognized as sources of drugs in several human ailments. To investigate the impact of variable extraction techniques on the cytotoxic effects of medicinal plant extracts, 5 well-known medicinal plants from Palestine were extracted with 90% ethanol, 80% methanol, acetone, coconut water, apple vinegar, grape vinegar or 5% acetic acid. The resulting extracts were screened for cytotoxic activities against three different cancer cell lines (B16F10, MCF-7, and HeLa) using a standard resazurin-based cytotoxicity assay and Nile Blue A as the positive control. Highly variable toxicities and tissue sensitivity were observed, depending upon the solvent used for extraction. Acetone consistently gave lower extraction yields but higher cytotoxicity, whereas other solvent systems gave much higher extraction yields with lower cytotoxicity. Interestingly, coconut water was found to offer a potential alternative to classical organic solvents; it gave consistently highest extraction yields, and in the case of S. officinalis L., highly toxic extracts towards MCF-7 cells derived from human breast cancer. These results demonstrate how the cytotoxicity of plant extracts can be inversely proportional to the yield, and that solvent selection plays an important role in both factors.

Keywords: plant extract, natural products, anti cancer drug, cytotoxicity

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Authors: Lynn Lehmann, Dinorah Leyva, Ana Lazic, Stefan Duhr, Philipp Baaske

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Characterization of biomolecular interactions, such as protein-protein, protein-nucleic acid or protein-small molecule, provides critical insights into cellular processes and is essential for the development of drug diagnostics and therapeutics. Here we present a novel, label-free, and tether-free technology to analyze picomolar to millimolar affinities of biomolecular interactions by Microscale Thermophoresis (MST). The entropy of the hydration shell surrounding molecules determines thermophoretic movement. MST exploits this principle by measuring interactions using optically generated temperature gradients. MST detects changes in the size, charge and hydration shell of molecules and measures biomolecule interactions under close-to-native conditions: immobilization-free and in bioliquids of choice, including cell lysates and blood serum. Thus, MST measures interactions under close-to-native conditions, and without laborious sample purification. We demonstrate how MST determines the picomolar affinities of antibody::antigen interactions, and protein::protein interactions measured from directly from cell lysates. MST assays are highly adaptable to fit to the diverse requirements of different and complex biomolecules. NanoTemper´s unique technology is ideal for studies requiring flexibility and sensitivity at the experimental scale, making MST suitable for basic research investigations and pharmaceutical applications.

Keywords: biochemistry, biophysics, molecular interactions, quantitative techniques

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Authors: Luc Conti, Dimitry Dumont-Fillon, Harald van Lintel, Eric Chappel

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Flow control valves comprise a silicon flexible membrane that deflects against a substrate, usually made of glass, containing pillars, an outlet hole, and anti-stiction features. However, there is a strong interest in using silicon instead of glass as substrate material, as it would simplify the process flow by allowing the use of well controlled anisotropic etching. Moreover, specific devices demanding a bending of the substrate would also benefit from the inherent outstanding mechanical strength of monocrystalline silicon. Unfortunately, direct Si-Si bonding is not easily achieved with highly structured wafers since residual stress may prevent the good adhesion between wafers. Using a thermoplastic polymer, such as parylene, as intermediate layer is not well adapted to this design as the wafer-to-wafer alignment is critical. An alternative anodic bonding method using an intermediate borosilicate layer has been successfully tested. This layer has been deposited onto the silicon substrate. The bonding recipe has been adapted to account for the presence of the SOI buried oxide and intermediate glass layer in order not to exceed the breakdown voltage. Flow control valves dedicated to infusion of viscous fluids at very high pressure have been made and characterized. The results are compared to previous data obtained using the standard anodic bonding method.

Keywords: anodic bonding, evaporated glass, flow control valve, drug delivery

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Authors: Joseph K. A. Johnson

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Hypertension affects 20 percent of the people within the ages 55 upward in Ghana. Of these, almost one-third are unaware of their condition. Also at the age of 55, more men turned to have hypertension than women. After that age, the condition becomes more prevalent with women. Hypertension is significantly more common in African Americans of both sexes than the racial or ethnic groups. This study was conducted to determine the causes of high blood pressure in Ashanti Region, Ghana. The study employed One Hundred and Seventy (170) respondents. The sample population for the study was all the available respondents at the time of the data collection. The research was conducted using primary data where convenience sampling was used to locate the respondents. A set of questionnaire were used to gather the data for the study. The gathered data was analysed using principal component analysis. The study revealed that, personal description, lifestyle behavior and risk awareness as some of the causes of high blood pressure in Ashanti Region. The study therefore recommend that people must be advice to see to their personal characteristics that may contribute to high blood pressure such as controlling of their temper and how to react perfectly to stressful situations. They must be educated on the factors that may increase the level of their blood pressure such as the essence of seeing a medical doctor before taking in any drug. People must also be made known by the public health officers to those lifestyles behaviour such as smoking and drinking of alcohol which are major contributors of high blood pressure.

Keywords: high blood pressure, principal component analysis, hypertension, public health

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Authors: Lina M. Vidal

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This paper discusses yoga practices involvement in both self-transformation and social transformations by means of an embodied ethnographic approach to different initiatives for social change in Medellín. In the context of gradual popularization of embodied spiritualities, yoga practices have opened their way in calls for social change in a performative perspective which involves collective experiences, reflections and production of embodied knowledge. Through the reflection on bodily dimension and corporal experience, this ethnographic approach acknowledges inter-corporality and somatic modes of attention during observations and personal experiences. In social change initiatives that include yoga practices were identified transformations of common understanding on social issues such as it is produced by institutionalized education, health system and other fields of knowledge. This is clearly visible in yoga projects for children in vulnerable conditions, homeless people, prisoners, and young people recovering from drug addiction. These projects are often promoted by organizations and networks, which incorporate individual life stories into collective experiences. Dissemination of yoga is heading to a broad institutional and cultural legitimation of yoga and of spirituality that impact different fields of social work and everyday life in general. This way, yoga is becoming an embodied activist way of life and a legitimate field for social work.

Keywords: embodied ethnography, Medellin, social transformation, embodied spiritualities, yoga practices

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Authors: Mahmoud Hassanin, Amita Gupta

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Background: During current practice, Thiopentone is not cost-effectively added to resources wastage, risk of drug error with antibiotics, short shelf life, infection risk, and risk of delay while preparing during category one cesarean section. There is no significant difference or preference to the other alternative as per current use. Aims and Objectives: Patient safety, Cost-effective use of trust resources, problem awareness, Consider improvising on the current practice. Methods: In conjunction with the local department survey results, many studies support the change. Results: More than 50%(15 from 29) are already using Propofol, more than 75% of the participant are willing to shift to Propofol if it becomes standard, and the cost analysis also revealed that Thiopentone 10 X500=£60 Propofol 10X200= £5.20, Cost of Thiopentone/year =£2190. Approximately GA in a year =35-40 could cost approximately £20 Propofol, given it is a well-established practice. We could save not only money, but it will be environmentally friendly also to avoid adding any carbon footprints. Recommendation: Thiopentone is rarely used as an induction agent for the category one Caesarean section in our obstetric emergency theatres. Most obstetric anesthetists are using Propofol. Keep both Propofol and thiopentone(powder not withdrawn) in the cat one cesarean section emergency drugs tray ready until the department completely changes the practice protocol. A further retrospective study is required to compare the outcomes for these induction agents through the local database.

Keywords: thiopentone, propofol, category 1 caesarean, induction agents

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Authors: Bouaziz Amira, Zaatout Nawel

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Background: Antimicrobial resistance is an urgent global health challenge in human and veterinary medicine, where migratory birds play a major role in the dissemination of multi-drug-resistant bacteria. The aim of this study was to screen for the presence of carbapenemase-producing Gram-negative bacteria (GNB) in the little egret (Egrettagarzetta) migratory bird stools in Algeria. Materials/Methods: In January 2014, 12 feacal samples were collected in Garaet El-Tarf, Oum El-Bouaghi city, Algeria. Samples were subjected to selective isolation of carbapenem-resistant GNB. Representative colonies were identified using the VITEK system. The obtained isolates were subjected to antibiotic susceptibility testing using the disc-diffusion method as well as carbapenemase production was verified by the modified Carba NP test. Results: In total, ten E. coli were obtained and were resistant to amoxicillin/clavulanic acid (100%), ertapenem (70%), cefoxitin (60%) cefotaxime (20%), cefepime (20%), ciprofloxacin (20%) and aztreonam (10%). The phenotypic detection results revealed that six out of the obtained strains were positive for the modified Carba NP test. Conclusion: The present study suggests that the little egret (Egretta garzetta) could be considered a reservoir of carbapenem-resistant Gram-negative bacteria.

Keywords: antimicrobial resistance, E. coli, Egretta garzetta, carbapenem resistance, dissemination

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Authors: Madhu Gupta, Vikas Sharma, Suresh P. Vyas

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CD13 receptors are abundantly overexpressed in tumor cells as well as in neovasculature. The CD13 receptors were selected as a targeted site and polymeric nanoparticles (NPs) as a targeted delivery system. By combining these, a cyclic NGR (cNGR) peptide ligand was coupled on the terminal end of polyethylene glycol-b-poly(lactic-co-glycolic acid) (PEG-b-PLGA) and prepared the dual targeted-NPs (cNGR-PEG-PTX-NPs) to enhance the intracellular delivery of anticancer drug to tumor cells and tumor endothelial cells via ligand-receptor interaction. In-vitro cytotoxicity studies confirmed that the presence of cNGR enhanced the cytotoxic efficiency by 2.8 folds in Human Umbilical Vein Endothelial (HUVEC) cells, while cytotoxicity was improved by 2.6 folds in human fibrosarcoma (HT-1080) cells as compared to non-specific stealth NPs. Compared with other tested NPs, cNGR-PEG-PTX-NPs revealed more cytotoxicity by inducing more apoptosis and higher intracellular uptake. The tumor volume inhibition rate was 59.7% in case of cNGR-PEG-PTX-NPs that was comparatively more with other formulations, indicating that cNGR-PEG-PTX-NPs could more effectively inhibit tumor growth. As a consequence, the cNGR-PEG-PTX-NPs play a key role in enhancing tumor therapeutic efficiency for treatment of CD13 receptor specific solid tumor.

Keywords: cyclic NGR, CD13 receptor, targeted polymeric NPs, solid tumor, intracellular delivery

Procedia PDF Downloads 437

Authors: Young-Ji Kim, Jin-Hyeong Park, Hong-Seok Kim, Jung-Whan Chon, Kwang-Yeop Kim, Dong-Hyeon Kim, Il-Byeong Kang, Da-Na Jeong, Jin-Hyeok Yim, Ho-Seok Jang, Kwang-Young Song, Kun-Ho Seo

Abstract:

Stenotrophomonas maltophilia is one of the emerging opportunistic pathogens, and also known to have extensive drug resistance intrinsically including carbepenems which is last resort for most serious infections. One possible way for S. maltophilia to infect human is via wastewater treatment plant (WWTP). In the period between October 2016 and February 2017, effluent samples of WWTP from 3 different pig farms were collected once a month and screened for isolation of S. maltophilia. Total 16 strains of S. maltophilia were isolated and, the antibiotic susceptibility phenotypes were determined by Vitek 2 system for 16 antibiotics, ampicillin (AMP), amoxicillin/clavulanic acid (AMC), piperacillin/tazobactam (TZP), cefazolin (CZ), cefoxitin (FOX), cefotaxime (CTX), ceftazidime (CAZ), cefepime (FEP), aztreonam (AZT), ertapenem (ETP), imipenem (IMP), amikacin (AK), gentamicin (GN), ciprofloxacin (CIP), tigecycline (TGC) and trimethoprim/sulfamethoxazole (SXT). All isolates showed high resistance to AMP (100%), CZ (100%), FOX (100%), CTX (100%), CAZ (100%), FEP (94%), AZT (100%), ETP (100%), IMP (100%), AK (100%), GN (100%) whereas were susceptible to CIP (0%), TGC (0%), SXT (6%). All strains harbored at least one of the antibiotic resistance determinant such as spgM, rmlA, and rpfF. Some isolates had similar MLST (multilocus sequence typing) types with clinical isolates, suggesting WWTP could have potential role in the transmission of S. maltophilia to aquatic environment and, possibly, to humans.

Keywords: Stenotrophomonas maltophilia, Carbapenem resistance, waste water treatment plant, pig farm

Procedia PDF Downloads 463