Search results for: antibiotic drugs

Authors: Wissem Abdaoui, Ilhem Mokhtari, Adel Gouri, Benouareth Djamel Eddine

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Contracted in a health facility, hospital-acquired infections are a major public health problem in recent years. The increase of nosocomial infections is partly related to diagnostic and therapeutic advances in medicine. The aim of our study was to isolate and diagnose some types of bacteria that are circulating in the hospital by performing different samples at two medical services: Pulmonary and Infectious Diseases. The antibiotic susceptibility tests were performed for bacterial isolates. The results have shown that there is a predominance of enterobacteria followed by the staphylococcus with its two species epidermidis ans saprophyticus. The study of the antibiogramme identified that some of these bacteria have a resistant profile against all the tested antibiotics. The fight against nosocomial infections is difficult because it must act on several factors: quality of care, safety of the hospital environment, hygiene, wearing gloves etc. are all areas that should be of heightened vigilance and preventive measures.

Keywords: nosocomial infection, isolation, identification, sensitivity and resistance to antibiotics

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Authors: Monika Ksiezopolska-Gocalska, Pawel Albrycht, Robert Holyst

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Surface Enhanced Raman Spectroscopy (SERS) is a technique used to analyze very low concentrations of substances in solutions, even in aqueous solutions - which is its advantage over IR. This technique can be used in the pharmacy (to check the purity of products); forensics (whether at a crime scene there were any illegal substances); or medicine (serving as a medical test) and lots more. Due to the high potential of this technique, its increasing popularity in analytical laboratories, and simultaneously - the absence of appropriate platforms enhancing the SERS signal (crucial to observe the Raman effect at low analyte concentration in solutions (1 ppm)), we decided to invent our own SERS platforms. As an enhancing layer, we have chosen gold and silver nanoparticles, because these two have the best SERS properties, and each has an affinity for the other kind of particles, which increases the range of research capabilities. The next step was to commercialize them, which resulted in the creation of the company ‘SERSitive.eu’ focusing on production of highly sensitive (Ef = 10⁵ – 10⁶), homogeneous and reproducible (70 - 80%) substrates. SERStive SERS substrates are made using the electrodeposition of silver or silver-gold nanoparticles technique. Thanks to a very detailed analysis of data based on studies optimizing such parameters as deposition time, temperature of the reaction solution, applied potential, used reducer, or reagent concentrations using a standardized compound - p-mercaptobenzoic acid (PMBA) at a concentration of 10⁻⁶ M, we have developed a high-performance process for depositing precious metal nanoparticles on the surface of ITO glass. In order to check a quality of the SERSitive platforms, we examined the wide range of the chemical compounds and the biological substances. Apart from analytes that have great affinity to the metal surfaces (e.g. PMBA) we obtained very good results for those fitting less the SERS measurements. Successfully we received intensive, and what’s more important - very repetitive spectra for; amino acids (phenyloalanine, 10⁻³ M), drugs (amphetamine, 10⁻⁴ M), designer drugs (cathinone derivatives, 10⁻³ M), medicines and ending with bacteria (Listeria, Salmonella, Escherichia coli) and fungi.

Keywords: nanoparticles, Raman spectroscopy, SERS, SERS applications, SERS substrates, SERSitive

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Authors: Ponchang Apollos Wuyep, Alice Njolke Mafe, Longchi Satkat Zacheaus, Dogun Ojochogu, Dabot Ayuba Yakubu

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Fungi causes huge losses when infections occur both in plants and animals. Synthetic Antifungal drugs are mostly very expensive and highly cytotoxic when taken. This study was aimed at determining the in vitro and in vivo antifungal activities of the leaves and stem extracts of Terminalia mantaly (Umbrella tree)H. Perrier on Aspergillus species in a bid to identify potential sources of cheap starting materials for the synthesis of new drugs to address the growing antimicrobial resistance. T. mantaly leave and stem powdered plant was extracted by fractionation using the method of solvent partition co-efficient in their graded form in the order n-hexane, Ethyl acetate, methanol and distilled water and phytochemical screening of each fraction revealed the presence of alkaloids, saponins, Tannins, flavonoids, carbohydrates, steroids, anthraquinones, cardiac glycosides and terpenoids in varying degrees. The Agar well diffusion technique was used to screen for antifungal activity of the fractions on clinical isolates of Aspergillus species (Aspergillus flavus and Aspergillus fumigatus). Minimum inhibitory concentration (MIC50) of the most active extracts was determined by the broth dilution method. The fractions test indicated a high antifungal activity with zones of inhibition ranging from 6 to 26 mm and 8 to 30mm (leave fractions) and 10mm to 34mm and 14mm to36mm (stem fractions) on A. flavus and A. fumigatus respectively. All the fractions indicated antifungal activity in a dose response relationship at concentrations of 62.5mg/ml, 125mg/ml, 250mg/ml and 500mg/ml. Better antifungal efficacy was shown by the Ethyl acetate, Hexane and Methanol fractions in the in vitro as the most potent fraction with MIC ranging from 62.5 to 125mg/ml. There was no statistically significant difference (P>0.05) in the potency of the Eight fractions from leave and stem (Hexane, Ethyl acetate, methanol and distilled water, antifungal (fluconazole), which served as positive control and 10% DMSO(Dimethyl Sulfoxide)which served as negative control. In the in vivo investigations, the ingestion technique was used for the infectious studies Female Drosophilla melanogaster(UAS-Diptericin)normal flies(positive control),infected and not treated flies (negative control) and infected flies with A. fumigatus and placed on normal diet, diet containing fractions(MSM and HSM each at concentrations of 10mg/ml 20mg/ml, 30mg/ml, 40mg/ml, 50mg/ml, 60mg/ml, 70mg/ml, 80mg/ml, 90mg/ml and 100mg/ml), diet containing control drugs(fluconazole as positive control)and infected flies on normal diet(negative control), the flies were observed for fifteen(15) days. Then the total mortality of flies was recorded each day. The results of the study reveals that the flies were susceptible to infection with A. fumigatus and responded to treatment with more effectiveness at 50mg/ml, 60mg/ml and 70mg/ml for both the Methanol and Hexane stem fractions. Therefore, the Methanol and Hexane stem fractions of T. mantaly contain therapeutically useful compounds, justifying the traditional use of this plant for the treatment of fungal infections.

Keywords: Terminalia mantaly, Aspergillus fumigatus, cytotoxic, Drosophila melanogaster, antifungal

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Authors: Adil Mustafa, Ahmet Erten, Alper Kiraz, Melikhan Tanyeri

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Work presented here is based on a novel experimental technique used to hydrodynamically trap oil microdroplets inside a microfluidic chip at the junction of microchannels known as stagnation point. Hydrodynamic trapping has been recently used to trap and manipulate a number of particles starting from microbeads to DNA and single cells. Benzyl Benzoate (BB) is used as droplet material. The microdroplets are trapped individually at stagnation point and their dissolution was observed. Experiments are performed for two concentrations (10mM or 10µM) of AOT surfactant (Docusate Sodium Salt) and two flow rates for each case. Moreover, experimental data is compared with Zhang-Yang-Mao (ZYM) model which studies dissolution of liquid microdroplets in the presence of a host fluid experiencing extensional creeping flow. Industrial processes like polymer blending systems in which heat or mass transport occurs experience extensional flow and an insight into these phenomena is of significant importance to many industrial processes. The experimental technique exploited here gives an insight into the dissolution of liquid microdroplets under extensional flow regime. The comparison of our experimental results with ZYM model reveals that dissolution of microdroplets at lower surfactant concentration (10µM) fits the ZYM model at saturation concentration (Cs) value reported in literature (Cs = 15×10⁻³Kg\m³) while for higher surfactant concentration (10mM) which is also above the critical micelle concentration (CMC) of surfactant (5mM) the data fits ZYM model at (Cs = 45×10⁻³Kg\m³) which is 3X times the value reported in literature. The difference in Cs value from the literature shows enhancement in dissolution rate of sparingly soluble BB microdroplets at surfactant concentrations higher than CMC. Enhancement in the dissolution of sparingly soluble materials is of great importance in pharmaceutical industry. Enhancement in the dissolution of sparingly soluble drugs is a key research area for drug design industry. The experimental method is also advantageous because it is robust and has no mechanical contact with droplets under study are freely suspended in the fluid as compared existing methods used for testing dissolution of drugs. The experiments also give an insight into CMC measurement for surfactants.

Keywords: extensional flow, hydrodynamic trapping, Zhang-Yang-Mao, CMC

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Authors: Amlan Kumar Das, Avinash Marwal, Vikram Pareek

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Liposome plays an important role in medical and pharmaceutical science as e.g. nano scale drug carriers. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment. Magnet-driven liposome used for the targeted delivery of drugs to organs and tissues1. These liposome preparations contain encapsulated drug components and finely dispersed magnetic particles. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment that are generated in vitro. These are useful in terms of biocompatibility, biodegradability, and low toxicity, and can control biodistribution by changing the size, lipid composition, and physical characteristics2. Furthermore, liposomes can entrap both hydrophobic and hydrophilic drugs and are able to continuously release the entrapped substrate, thus being useful drug carriers. Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magneticor paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI)3. The biological synthesis of nanoparticles using plant extracts plays an important role in the field of nanotechnology4. Green-synthesized magnetite nanoparticles-protein hybrid has been produced by treating Iron (III)/Iron(II) chloride with the leaf extract of Dhatura Inoxia. The phytochemicals present in the leaf extracts act as a reducing as well stabilizing agents preventing agglomeration, which include flavonoids, phenolic compounds, cardiac glycosides, proteins and sugars. The magnetite nanoparticles-protein hybrid has been trapped inside the aqueous core of the liposome prepared by reversed phase evaporation (REV) method using oleic and linoleic acid which has been shown to be driven under magnetic field confirming the formation magnetic liposome (ML). Chemical characterization of stealth magnetic liposome has been performed by breaking the liposome and release of magnetic nanoparticles. The presence iron has been confirmed by colour complex formation with KSCN and UV-Vis study using spectrophotometer Cary 60, Agilent. This magnet driven liposome using nanoparticles-protein hybrid can be a smart vesicles for the targeted drug delivery.

Keywords: nanoparticles-protein hybrid, magnetic liposome, medical, pharmaceutical science

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Authors: Siti Aisya Gany, Swee Ching Tan, Sook Yee Gan

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Diminished antioxidant defense or increased production of reactive oxygen species in the biological system can result in oxidative stress which may lead to various neurodegenerative diseases including Alzheimer’s disease (AD). Microglial activation also contributes to the progression of AD by producing several pro-inflammatory cytokines, nitric oxide (NO), and prostaglandin E2 (PGE2). Oxidative stress and inflammation have been reported to be possible pathophysiological mechanisms underlying AD. In addition, the cholinergic hypothesis postulates that memory impairment in patient with AD is also associated with the deficit of cholinergic function in the brain. Although a number of drugs have been approved for the treatment of AD, most of these synthetic drugs have diverse side effects and yield relatively modest benefits. Marine algae have great potential in pharmaceutical and biomedical applications as they are valuable sources of bioactive properties such as anti-coagulation, anti-microbial, anti-oxidative, anti-cancer and anti-inflammatory. Hence, this study aimed to provide an overview of the properties of Malaysian seaweeds (Padina australis, Sargassum polycystum and Caulerpa racemosa) in inhibiting oxidative stress, neuroinflammation and cholinesterase enzymes. All tested samples significantly exhibit potent DPPH and moderate Superoxide anion radical scavenging ability (P<0.05). Hexane and methanol extracts of S. polycystum exhibited the most potent radical scavenging ability with IC50 values of 0.1572 ± 0.004 mg/ml and 0.8493 ± 0.02 for DPPH and ABTS assays, respectively. Hexane extract of C. racemosa gave the strongest superoxide radical inhibitory effect (IC50 of 0.3862± 0.01 mg/ml). Most seaweed extracts significantly inhibited the production of cytokine (IL-6, IL-1 β, TNFα) and NO in a concentration-dependent manner without causing significant cytotoxicity to the lipopolysaccharide (LPS)-stimulated microglia cells (P<0.05). All extracts suppressed cytokine and NO level by more than 80% at the concentration of 0.4mg/ml. In addition, C. racemosa and S. polycystum also showed anti-acetylcholinesterase activities with the IC50 values ranging from 0.086-0.115 mg/ml. Moreover, C. racemosa and P. australis were also found to be active against butyrylcholinesterase with IC50 values ranging from 0.118-0.287 mg/ml.

Keywords: anti-cholinesterase, anti-oxidative, neuroinflammation, seaweeds

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Authors: Khaled Alshammari

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Ciprofloxacin (CIP) is a common antibiotic drug used as a strudy electron donor that interacts with dynamic π -acceptors such as 2,3-dinitrosalsylic acid (HDNS) and Tetracyanoethylene (TCNE) for synthesizing a new model of charge transfer (CT) complexes. The synthesized complexes were identified using diverse analytical methods such as UV–vis spectra, photometric titration measurements, FT-IR, HNMR Spectroscopy, and thermogravimetric analysis techniques (TGA/DTA). The stoichiometries for all the formed complexes were found to be a 1:1 M ratio between the reactants. The characteristic spectroscopic properties such as transition dipole moment (µ), oscillator strength (f), formation constant (KCT), ionization potential (ID), standard free energy (∆G), and energy of interaction (ECT) for the CT-complexes were collected. The developed CT complexes were tested for their toxicity on main organs, antimicrobial activity, antioxidant activity, and biofilm formation.

Keywords: biological, biofilm, toxicity, thermal analysis, charge transfer, spectroscopy

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Authors: Nourhan Hussein Fanaki, Hoda Mohamed Gamal El-Din Omar, Nihal Kadry Moussa, Eva Adel Edward Farid

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The resistance of staphylococci to various antibiotics has become a major concern for health care professionals. The efficacy of the combinations of selected glycopeptides (vancomycin and teicoplanin) with gentamicin or rifampicin, as well as that of gentamicin/rifampicin combination, was studied against selected pathogenic staphylococcus isolated from Egypt. The molecular distribution of genes conferring resistance to these four antibiotics was detected among tested clinical isolates. Antibiotic combinations were studied using the checkerboard technique and the time-kill assay (in both the stationary and log phases). Induction of resistance to glycopeptides in staphylococci was tried in the absence and presence of diclofenac sodium as inducer. Transmission electron microscopy was used to study the effect of glycopeptides on the ultrastructure of the cell wall of staphylococci. Attempts were made to cure gentamicin resistance plasmids and to study the transfer of these plasmids by conjugation. Trials for the transformation of the successfully isolated gentamicin resistance plasmid to competent cells were carried out. The detection of genes conferring resistance to the tested antibiotics was performed using the polymerase chain reaction. The studied antibiotic combinations proved their efficacy, especially when tested during the log phase. Induction of resistance to glycopeptides in staphylococci was more promising in presence of diclofenac sodium, compared to its absence. Transmission electron microscopy revealed the thickening of bacterial cell wall in staphylococcus clinical isolates due to the presence of tested glycopeptides. Curing of gentamicin resistance plasmids was only successful in 2 out of 9 tested isolates, with a curing rate of 1 percent for each. Both isolates, when used as donors in conjugation experiments, yielded promising conjugation frequencies ranging between 5.4 X 10-2 and 7.48 X 10-2 colony forming unit/donor cells. Plasmid isolation was only successful in one out of the two tested isolates. However, low transformation efficiency (59.7 transformants/microgram plasmid DNA) of such plasmids was obtained. Negative regulators of autolysis, such as arlR, lytR and lrgB, as well as cell-wall associated genes, such as pbp4 and/or pbp2, were detected in staphylococcus isolates with reduced susceptibility to the tested glycopeptides. Concerning rifampicin resistance genes, rpoBstaph was detected in 75 percent of the tested staphylococcus isolates. It could be concluded that in vitro studies emphasized the usefulness of the combination of vancomycin or teicoplanin with gentamicin or rifampicin, as well as that of gentamicin with rifampicin, against staphylococci showing varying resistance patterns. However, further in vivo studies are required to ensure the safety and efficacy of such combinations. Diclofenac sodium can act as an inducer of resistance to glycopeptides in staphylococci. Cell-wall thickness is a major contributor to such resistance among them. Gentamicin resistance in these strains could be chromosomally or plasmid mediated. Multiple mutations in the rpoB gene could mediate staphylococcus resistance to rifampicin.

Keywords: glycopeptides, combinations, induction, diclofenac, transmission electron microscopy, polymerase chain reaction

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Authors: Priyanka Mokashi, Aparna Khanna, Nancy Pandita

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Diabetes mellitus is a chronic metabolic disorder which will be the 7th leading cause of death by 2030. The current line of treatment for the diabetes mellitus is oral antidiabetic drugs (biguanides, sulfonylureas, meglitinides, thiazolidinediones and alpha-glycosidase inhibitors) and insulin therapy depending upon the type 1 or type 2 diabetes mellitus. But, these treatments have their disadvantages, ranging from the developing of resistance to the drugs and adverse effects caused by them. Alternative to these synthetic agents, natural products provides a new insight for the development of more efficient and safe drugs due to their therapeutic values. Enicostema littorale blume (A. Raynal) is a traditional Indian plant belongs to the Gentianaceae family. It is widely distributed in Asia, Africa, and South America. There are few reports on Swrtiamarin, major component of this plant for its antidiabetic activity. However, the antidiabetic activity of flavonoids from E. littorale and their mechanism of action have not yet been elucidated. Flavonoids have a positive relationship with disease prevention and can act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, adipocytes, hepatocytes and skeletal myofibers. They may exert beneficial effects in diabetes by (i) improving hyperglycemia through regulation of glucose metabolism in hepatocytes; (ii) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells; (iii) increasing glucose uptake in hepatocytes, skeletal muscle and white adipose tissue (iv) reducing insulin resistance, inflammation and oxidative stress. Therefore, we have isolated four flavonoid rich fractions, Fraction A (FA), Fraction B (FB), Fraction C (FC), Fraction D (FD) from crude alcoholic hot (AH) extract from E. littorale, identified by LC/MS. Total eight flavonoids were identified on the basis of fragmentation pattern. Flavonoid FA showed the presence of swertisin, isovitexin, and saponarin; FB showed genkwanin, quercetin, isovitexin, FC showed apigenin, swertisin, quercetin, 5-O-glucosylswertisin and 5-O-glucosylisoswertisin whereas FD showed the presence of swertisin. Further, these fractions were assessed for their antidiabetic activity on stimulating glucose uptake in insulin-resistant HepG2 cell line model (IR/HepG2). The results showed that FD containing C-glycoside Swertisin has significantly increased the glucose uptake rate of IR/HepG2 cells at the concentration of 10 µg/ml as compared to positive control Metformin (0.5mM) which was determined by glucose oxidase- peroxidase method. It has been reported that enhancement of glucose uptake of cells occurs due the translocation of Glut4 vesicles to cell membrane through IR/IRS1/AKT pathway. Therefore, we have studied expressions of three genes IRS1, AKT and Glut4 by real-time PCR to evaluate whether they follow the same pathway or not. It was seen that the glucose uptake rate has increased in FD treated IR/HepG2 cells due to the activation of insulin receptor substrate-1 (IRS1) followed by protein kinase B (AKT) through phosphoinositide 3-kinase (PI3K) leading to translocation of Glut 4 vesicles to cell membrane, thereby enhancing glucose uptake and insulin sensitivity of insulin resistant HepG2 cells. Hence, the up-regulation indicated the mechanism of action through which FD (Swertisin) acts as antidiabetic candidate in the treatment of type 2 diabetes mellitus.

Keywords: E. littorale, glucose transporter, glucose uptake rate, insulin resistance

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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: Thippharat Wongsilarat, Parichat tuntilanon, Chonlakan Prataksitorn

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Recurrent adverse drug reactions are harmful to patients with mild to fatal illnesses, and affect not only patients but also their relatives, and organizations. To compare safe use of medicine among patients before and after using the recurrent adverse drug reaction prevention program . Quasi-experimental research with the target population of 598 patients with drug allergy history. Data were collected through an observation form tested for its validity by three experts (IOC = 0.87), and analyzed with a descriptive statistic (percentage). The research was conducted jointly with a multidisciplinary team to analyze and determine the weak points and strong points in the recurrent adverse drug reaction prevention system during the past three years, and 546, 329, and 498 incidences, respectively, were found. Of these, 379, 279, and 302 incidences, or 69.4; 84.80; and 60.64 percent of the patients with drug allergy history, respectively, were found to have caused by incomplete warning system. In addition, differences in practice in caring for patients with drug allergy history were found that did not cover all the steps of the patient care process, especially a lack of repeated checking, and a lack of communication between the multidisciplinary team members. Therefore, the recurrent adverse drug reaction prevention program was developed with complete warning points in the information technology system, the repeated checking step, and communication among related multidisciplinary team members starting from the hospital identity card room, patient history recording officers, nurses, physicians who prescribe the drugs, and pharmacists. Including in the system were surveillance, nursing, recording, and linking the data to referring units. There were also training concerning adverse drug reactions by pharmacists, monthly meetings to explain the process to practice personnel, creating safety culture, random checking of practice, motivational encouragement, supervising, controlling, following up, and evaluating the practice. The rate of prescribing drugs to which patients were allergic per 1,000 prescriptions was 0.08, and the incidence rate of recurrent drug reaction per 1,000 prescriptions was 0. Surveillance of recurrent adverse drug reactions covering all service providing points can ensure safe use of medicine for patients.

Keywords: recurrent drug, adverse reaction, safety, use of medicine

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Authors: Yohannes Kelifa, Gomathi Periasamy, Aman Karim

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Introduction: Diabetes mellitus has become a major public health and economical problem across the globe. Modern antidiabetic drugs have a number of limitations, and scientific investigation of traditional herbal remedies used for diabetes may provide novel leads for the development of new antidiabetic drugs that can be used as alternative or complementary to available antidiabetic allopathic medications. Though Myrica salicifolia Hochst. ex A. Rich. is used for the management of diabetes in Ethiopian traditional medicine, there was no previous scientific evidence about its antidiabetic effect to the authors’ knowledge. This study was undertaken to evaluate the antidiabetic activity the root extracts of Myrica salicifolia in streptozotocin (STZ)-induced diabetic mice. Methods: Experimental diabetes was induced by intraperitoneal administration of STZ (150 mg/kg) in male mice. Diabetic mice were treated with oral doses of M. salicifolia root extracts at 200, 400 and 600 mg/kg, and its fractions (chloroform, ethyl acetate, n-butanol and aqueous) at a dose of 400 mg/kg daily for 15 days. Fasting blood glucose level (BGL) was measured at 0, 5th,10th, and 15th day. The free radical scavenging activity of the crude extract was determined using in vitro by DPPH assay. The statistical significance was assessed by one-way ANOVA, followed by Tukey’s multiple comparison tests. Results were considered significant when p < 0.05. Results: Daily administration of the M. salicifolia 80% methanol root extracts (at three different doses (200, 400 and 600 mg/kg) significantly (p < 0.05, p < 0.01 and p < 0.001) reduced fasting BGL compared with diabetic control. The aqueous and butanol fractions at a dose of 400 mg/kg resulted in maximum reduction of fasting BGL by 42.39%, and 52.13%, respectively at the 15th day in STZ-induced diabetic mice. Free radical scavenging activity of the 80% methanol extract of M. salicifolia was comparable to ascorbic acid. The IC50 values of the crude extract and ascorbic acid (a reference compound) were found to be 4.54 μg/ml and 4.39 μg/ml, respectively. Conclusion: These findings demonstrated that the methanolic extracts of M. salicifolia root and its fractions (n-butanol and aqueous) exhibit a significant antihyperglycemic activity in STZ-induced diabetic mice. Furthermore, the result of the present study indicates that M. salicifolia root extract is a potential source of natural antioxidants.

Keywords: antidiabetic, diabetes mellitus, DPPH, mice, Myrica salicifolia, streptozotocin

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Authors: F. Boukli Hacene, W. Soufi, S. Ghalem

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Glaucoma disease is a progressive degenerative optic neuropathy, with irreversible visual field deficits and high eye pressure being one of the risk factors. Sulfonamides are carbonic anhydrase-II inhibitors that aim to decrease the secretion of aqueous humor by direct inhibition of this enzyme at the level of the ciliary processes. These drugs present undesirable effects that are difficult to accept by the patient. In our study, we are interested in the inhibition of carbonic anhydrase-II by different natural ligands (curcumin analogues) using molecular modeling methods using molecular operating environment (MOE) software to predict their interaction with this enzyme.

Keywords: carbonic anhydrase-II, curcumin analogues, drug research, molecular modeling

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Authors: Ana M. Prieto del Pino

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As is well known, UN Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances (1988) was a landmark regarding the seizure of proceeds of crime. Depriving criminals of the profits from their activity became a priority at an international level in the fight against organised crime. Enabling confiscation of proceeds of illicit traffic in narcotic drugs and psychotropic substances, criminalising money laundering and confiscating the proceeds thereof are the three measures taken in order to achieve that purpose. The beginning of 21st century brought the declaration of war on corruption and on the illicit enjoyment of the profits thereof onto the international scene. According to the UN Convention against Transnational Organised Crime (2000), States Parties should adopt the necessary measures to enable the confiscation of proceeds of crime derived from offences (or property of equivalent value) and property, equipment and other instrumentalities used in offences covered by that Convention. The UN Convention against Corruption (2003) states asset recovery explicitly as a fundamental principle and sets forth measures aiming at the direct recovery of property through international cooperation in confiscation. Furthermore, European legislation has made many significant strides forward in less than twenty years concerning money laundering, confiscation, and asset recovery. Crime does not pay, let there be no doubt about it. Nevertheless, we must be very careful not to sing out of tune with individual rights and legal guarantees. On the one hand, innocent individuals and businesses must be protected, since they should not pay for the guilty ones’ faults. On the other hand, the rule of law must be preserved and not be tossed aside regarding those who have carried out criminal activities. An in-depth analysis of judicial decisions on money laundering and confiscation of proceeds of crime issued by European national courts and by the European Court of Human Rights in the last decade has been carried out from a human rights, legal guarantees and criminal law basic principles’ perspective. The undertaken study has revealed the violation of the right to property, of the proportionality principle legal and the infringement of basic principles of states’ domestic substantive and procedural criminal law systems. The most relevant ones have to do with the punishment of money laundering committed through negligence, non-conviction based confiscation and a too-far reaching interpretation of the notion of ‘proceeds of crime’. Almost everything in life has a bright and a dark side. Confiscation of criminal proceeds and asset recovery are not an exception to this rule.

Keywords: confiscation, human rights, money laundering, organized crime

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Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi

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Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.

Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis

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Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

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Authors: R. Mickiene, A. Friese, U. Rosler, A. Maruska, O. Ragazinskiene

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This research focuses on phytochemistry and antimicrobial activities of compounds isolated and identified from three species of Eryngium. The antimicrobial activity of extracts from Eryngiumplanum L., Eryngium maritimum L., Eryngium campestre L. grown in Lithuania, were tested by the method of series dilutions, against different bacteria species: Escherichia coli, Proteus vulgaris and Staphylococcus aureus with and without antibiotic resistances, originating from livestock. The antimicrobial activity of extracts was described by determination of the minimal inhibitory concentration. Preliminary results show that the minimal inhibitory concentration range between 8.0 % and 17.0 % for the different Eryngium extracts and bacterial species.The total amounts ofphenolic compounds and total amounts of flavonoids were tested in the methanolic extracts of the plants. Identification and evaluation of the phenolic compounds were performed by liquid chromatography. The essential oils were analyzed by gas chromatography mass spectrometry.

Keywords: antimicrobial activities, Eryngium L. species, essential oils, gas chromatography mass spectrometry

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Authors: Ashti Morovati, Hushyar Azari, Bahram Pourghassem Gargari

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Objectives and goals: The prevalence of metabolic syndrome (MetS), as a major health burden for societies, is increasing. This clinical trial was conducted to evaluate the effects of CuEO supplementation on anthropometric indices, systolic and diastolic blood pressure, blood glucose level, insulin resistance and serum lipid level in patients suffering from MetS. Methods: This was a randomized, triple‐blind, placebo‐controlled clinical trial in which 56 patients with MetS aged 18–60 years who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Inclusion criteria for the study were comprised of diagnosis of MetS according to the new International Federation of Diabetes. The exclusion criteria were defined as: taking herbal supplements, use of drugs having evident interaction with cumin such as anti‐depressant drugs, vitamin D, omega 3, selenium, zinc, smoking, pregnancy, or breastfeeding, suffering from cancer, having any history of gastrointestinal and hepatic, cardiovascular, thyroid and kidney disorders, and menopause. 75 mg CuEO or placebo soft gels were administered three times daily to the participants for eight weeks. The soft gel consumption was checked by asking the participants to bring the medication containers in the follow‐up visits at the 4th and the 8th weeks of the study. Data pertaining to blood pressure, height, weight, waist circumference, hip circumference and BMI, as well as food consumption were collected at the beginning and end of the study. Fasting blood samples ( glucose, triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol) were obtained and biochemical measurements were assessed at the beginning and end of the study. Results: At eight weeks, a total of 44 patients completed this study. Except for diastolic blood pressure (DBP), the other assessed variables were not significantly different between the two groups. In intra group analysis, placebo and CuEO groups both had insignificant decrements in DBP (mean difference [MD] with 95% CI: −3.31 [−7.11, 0.47] and −1.77 [−5.95, 2.40] mmHg, respectively). However, DBP was significantly lower in CuEO compared with the placebo group at the end of study (81.41 ± 5.88 vs. 84.09 ± 5.54 mmHg, MD with 95% CI: −3.98 [−7.60, −0.35] mmHg, p < .05). Conclusions: The results of this study indicated that CuEO does not have any effect on MetS components, except for DBP in patients with MetS.

Keywords: blood pressure, fasting blood glucose, lipid profile, waist circumference

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Authors: Malahat Rezaee, Mahiran Basri, Abu Bakar Salleh, Raja Noor Zaliha Raja Abdul Rahman

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Sodium diclofenac is one of the most commonly used drugs of nonsteroidal anti-inflammatory drugs (NSAIDs). It is especially effective in the controlling the severe conditions of inflammation and pain, musculoskeletal disorders, arthritis, and dysmenorrhea. Formulation as nanoemulsions is one of the nanoscience approaches that has been progressively considered in pharmaceutical science for transdermal delivery of the drug. Nanoemulsions are a type of emulsion with particle sizes ranging from 20 nm to 200 nm. An emulsion is formed by the dispersion of one liquid, usually the oil phase in another immiscible liquid, water phase that is stabilized using the surfactant. Palm kernel oil esters (PKOEs), in comparison to other oils, contain higher amounts of shorter chain esters, which suitable to be applied in micro and nanoemulsion systems as a carrier for actives, with excellent wetting behavior without the oily feeling. This research aimed to study the effect of terpene type and concentration on sodium diclofenac permeation from palm kernel oil esters nanoemulsions and physicochemical properties of the nanoemulsions systems. The effect of various terpenes of geraniol, menthone, menthol, cineol and nerolidol at different concentrations of 0.5, 1.0, 2.0, and 4.0% on permeation of sodium diclofenac were evaluated using Franz diffusion cells and rat skin as permeation membrane. The results of this part demonstrated that all terpenes showed promoting effect on sodium diclofenac penetration. However, menthol and menthone at all concentrations showed significant effects (<0.05) on drug permeation. The most outstanding terpene was menthol with the most significant effect for skin permeability of sodium diclofenac. The effect of terpenes on physicochemical properties of nanoemulsion systems was investigated on the parameters of particle size, zeta potential, pH, viscosity and electrical conductivity. The result showed that all terpenes had the significant effect on particle size and non-significant effects on the zeta potential of the nanoemulsion systems. The effect of terpenes was significant on pH, excluding the menthone at concentrations of 0.5 and 1.0%, and cineol and nerolidol at the concentration of 2.0%. Terpenes also had significant effect on viscosity of nanoemulsions exception of menthone and cineol at the concentration of 0.5%. The result of conductivity measurements showed that all terpenes at all concentration except cineol at the concentration of 0.5% represented significant effect on electrical conductivity.

Keywords: nanoemulsions, palm kernel oil esters, sodium diclofenac, terpenes, skin permeation

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Authors: Boukli Hacene Faiza, Soufi Wassila, Ghalem Said

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The oral antidiabetics drugs such as alpha glucosidase inhibitors present undesirable effects like acarbose. Flavonoids are class of molecules widely distributed in plants, for this reason we are interested in our work to study the inhibition in silico of alpha glucosidase by natural ligands ( flavonoids analogues) using molecular modeling methods using MOE (Molecular Operating Environment) software to predict their interaction with this enzyme with score energy, ADME /T tests and druglikeness properties experiments. Two flavonoids Beicalein and Apigenin have high binding affinity with alpha glucosidase with lower IC50 supposed potent inhibitors.

Keywords: alpha glucosidase, flavonoides analogues, drug research, molecular modeling

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Authors: Philippa Saunders, Claire Fletcher

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INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive the expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signaling remains a key driver of growth. Androgen deprivation therapy (ADT) is, therefore, a first-line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signaling inhibitors, respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIAL AND METHOD: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.

Keywords: microRNA, androgen deprivation therapy, Enzalutamide, abiraterone, patient-derived xenograft

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Authors: Turban Kar, Maitree Bhattacharyya

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Curcumin, a dietary antioxidant has been identified as a wonder molecule to possess therapeutic properties protecting the cellular macromolecules from oxidative damage. In our experimental study, we have explored the effectiveness of curcumin in protecting the structural paradigm of Human Serum Albumin (HSA) when exposed to gamma irradiation. HSA, being an important transport protein of the circulatory system, is involved in binding of variety of metabolites, drugs, dyes and fatty acids due to the presence of hydrophobic pockets inside the structure. HSA is also actively involved in the transportation of drugs and metabolites to their targets, because of its long half-life and regulation of osmotic blood pressure. Gamma rays, in its increasing concentration, results in structural alteration of the protein and superoxide radical generation. Curcumin, on the other hand, mitigates the damage, which has been evidenced in the following experiments. Our study explores the possibility for protection by curcumin during the molecular and conformational changes of HSA when exposed to gamma irradiation. We used a combination of spectroscopic methods to probe the conformational ensemble of the irradiated HSA and finally evaluated the extent of restoration by curcumin. SDS - PAGE indicated the formation of cross linked aggregates as a consequence of increasing exposure of gamma radiation. CD and FTIR spectroscopy inferred significant decrease in alpha helix content of HSA from 57% to 15% with increasing radiation doses. Steady state and time resolved fluorescence studies complemented the spectroscopic measurements when lifetime decay was significantly reduced from 6.35 ns to 0.37 ns. Hydrophobic and bityrosine study showed the effectiveness of curcumin for protection against radiation induced free radical generation. Moreover, bityrosine and hydrophobic profiling of gamma irradiated HSA in presence and absence of curcumin provided light on the formation of ROS species generation and the protective (magical) role of curcumin. The molecular mechanism of curcumin protection to HSA from gamma irradiation is yet unknown, though a possible explanation has been proposed in this work using Thioflavin T assay. It was elucidated, that when HSA is irradiated at low dose of gamma radiation in presence of curcumin, it is capable of retaining the native characteristic properties to a greater extent indicating stabilization of molecular structure. Thus, curcumin may be utilized as a therapeutic strategy to protect cellular proteins.

Keywords: Bityrosine content, conformational change, curcumin, gamma radiation, human serum albumin

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Authors: Mehdi Soula, Yosra Mani, Estelle Saras, Antoine Drapeau, Raoudha Grami, Mahjoub Aouni, Jean-Yves Madec, Marisa Haenni, Wejdene Mansour

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Multi-resistance to antibiotics in gram-negative bacilli and particularly in enterobacteriaceae, has become frequent in hospitals in Tunisia. However, data on antibiotic resistant bacteria in aquatic products are scarce. The aims of this study are to estimate the proportion of ESBL- and carbapenemase-producing Enterobacterales in seafood (clams and fish) in Tunisia and to molecularly characterize the collected isolates. Two types of seafood were sampled in unrelated markets in four different regions in Tunisia (641 pieces of farmed fish and 1075 mediterranean clams divided into 215 pools, and each pool contained 5 pieces). Once purchased, all samples were incubated in tubes containing peptone salt broth for 24 to 48h at 37°C. After incubation, overnight cultures were isolated on selective MacConkey agar plates supplemented with either imipenem or cefotaxime, identified using API20E test strips (bioMérieux, Marcy-l’Étoile, France) and confirmed by Maldi-TOF MS. Antimicrobial susceptibility was determined by the disk diffusion method on Mueller-Hinton agar plates and results were interpreted according to CA-SFM 2021. ESBL-producing Enterobacterales were detected using the Double Disc Synergy Test (DDST). Carbapenem-resistance was detected using an ertapenem disk and was respectively confirmed using the ROSCO KPC/MBL and OXA-48 Confirm Kit (ROSCO Diagnostica, Taastrup, Denmark). DNA was extracted using a NucleoSpin Microbial DNA extraction kit (Macherey-Nagel, Hoerdt, France), according to the manufacturer’s instructions. Resistance genes were determined using the CGE online tools. The replicon content and plasmid formula were identified from the WGS data using PlasmidFinder 2.0.1 and pMLST 2.0. From farmed fishes, nine ESBL-producing strains (9/641, 1.4%) were isolated, which were identified as E. coli (n=6) and K. pneumoniae (n=3). Among the 215 pools of 5 clams analyzed, 18 ESBL-producing isolates were identified, including 14 E. coli and 4 K. pneumoniae. A low isolation rate of ESBL-producing Enterobacterales was detected 1.6% (18/1075) in clam pools. In fish, the ESBL phenotype was due to the presence of the blaCTX-M-15 gene in all nine isolates, but no carbapenemase gene was identified. In clams, the predominant ESBL phenotype was blaCTX-M-1 (n=6/18). blaCPE (NDM1, OXA48) was detected only in 3 isolates ‘K. pneumoniae isolates’. Replicon typing on the strains carring the ESBL and carbapenemase gene revelead that the major type plasmid carried ESBL were IncF (42.3%) [n=11/26]. In all, our results suggest that seafood can be a reservoir of multi-drug resistant bacteria, most probably of human origin but also by the selection pressure of antibiotic. Our findings raise concerns that seafood bought for consumption may serve as potential reservoirs of AMR genes and pose serious threat to public health.

Keywords: BLSE, carbapenemase, enterobacterales, tunisian seafood

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Authors: Mohammad Hossein Pazandeh, Monir Doudi, Sona Rostampour Yasouri

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Irregular consumption of current antibiotic makes increases of antibiotic resistance between urin pathogens on all worlds. This study selected based on this great community problem. The aim of this study was the biosynthesis of silver nanoparticles from Zataria multiflora extract and then to investigate its antibacterial effect on gram-negative bacilli common in Urinary Tract Infections (UTI) and MDR. The plant used in the present research was Zataria multiflora whose extract was prepared through Soxhlet extraction method. Green synthesis condition of silver nanoparticles was investigated in terms of three parameters including the extract amount, concentration of silver nitrate salt, and temperature. The seizes of nanoparticles were determined by Zetasizer. In order to identify synthesized silver nanoparticles Transmission Electron Microscopy (TEM) and X-ray Diffraction (XRD) methods were used. For evaluating the antibacterial effects of nanoparticles synthesized through biological method different concentrations of silver nanoparticles were studied on 140 cases of Muliple Drug Resistance (MDR) bacteria strains Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus vulgaris,Citrobacter freundii, Acinetobacter bumanii and Pseudomonas aeruginosa, (each genus of bacteria, 20 samples), which all were MDR and cause urinary tract infections , for identification of bacteria were used of Polymerase Chain Reaction (PCR) test and laboratory methods (Agar well diffusion and Microdilution methods) to assess their sensitivity to Nanoparticles. The data were analyzed using SPSS software by nonparametric Kruskal-Wallis and Mann-Whitney tests. Significant results were found about the effects of silver nitrate concentration, different amounts of Zataria multiflora extract, and temperature on nanoparticles; that is, by increasing the concentration of silver nitrate, extract amount, and temperature, the sizes of synthesized nanoparticles declined. However, the effect of above mentioned factors on particles diffusion index was not significant. Based on the TEM results, particles were mainly spherical shape with a diameter range of 25 to 50 nm. The results of XRD Analysis indicated the formation of Nanostructures and Nanocrystals of silver.. The obtained results of antibacterial effects of different concentrations of silver nanoparticles on according to agar well diffusion and microdilution method, biologically synthesized nanoparticles showed 1000 mg /ml highest and lowest mean inhibition zone diameter in E.coli , Acinetobacter bumanii 23 and 15mm, respectively. MIC was observed for all of bacteria 125mg/ml and for Acinetobacter bumanii 250mg/ml.Comparing the growth inhibitory effect of chemically synthesized Nanoparticles and biologically synthesized Nanoparticles showed that in the chemical method the highest growth inhibition belonged to the concentration of 62.5 mg /ml. The inhibitory effect on the growth all of bacteria causes of urine infection and MDR was observed and by increasing silver ion concentration in Nanoparticles, antibacterial activity increased. Generally, the biological synthesis can be considered an efficient way not only in making Nanoparticles but also for having anti-bacterial properties. It is more biocompatible and may be possess less toxicity than the Nanoparticles synthesized chemically.

Keywords: biosynthesis, MDR bacteria, silver nanoparticles, UTI

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Authors: Muhammad Tariq, Muhammad Waseem, Muhammad Hidayat Rasool

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Isolation and characterization of chromium tolerant Staphylococcus aureus from industrial wastewater and their potential use to bioremediate environmental chromium. Objectives: Chromium with its great economic importance in industrial use is major metal pollutant of the environment. Chromium are used in different industries for various applications such as textile, dyeing and pigmentation, wood preservation, manufacturing pulp and paper, chrome plating, steel and tanning. The release of untreated chromium in industrial effluents causes serious threat to environment and human health, therefore, the current study designed to isolate chromium tolerant Staphylococcus aureus for removal of chromium prior to their final discharge into the environment due to its cost effective and beneficial advantage over physical and chemical methods. Methods: Wastewater samples were collected from discharge point of different industries. Heavy metal analysis by atomic absorption spectrophotometer and microbiological analysis such as total viable count, total coliform, fecal coliform and Escherichia coli were conducted. Staphylococcus aureus was identified through gram’s staining, biomeriux vitek 2 microbial identification system and 16S rRNA gene amplification by polymerase chain reaction. Optimum growth conditions with respect to temperature, pH, salt concentrations and effect of chromium on the growth of bacteria, resistance to other heavy metal ions, minimum inhibitory concentration and chromium uptake ability of Staphylococcus aureus strain K1 was determined by spectrophotometer. Antibiotic sensitivity pattern was also determined by disc diffusion method. Furthermore, chromium uptake ability was confirmed by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope equipped with Oxford Energy Dipersive X-ray (EDX) micro analysis system. Results: The results presented that optimum temperature was 35ᵒC, pH was 8.0 and salt concentration was 0.5% for growth of Staphylococcus aureus K1. The maximum uptake ability of chromium by bacteria was 20mM than other heavy metal ions. The antibiotic sensitivity pattern revealed that Staphylococcus aureus was vancomycin and methicillin sensitive. Non hemolytic activity on blood agar and negative coagulase reaction showed that it was non-pathogenic. Furthermore, the growth of bacteria decreases in the presence of chromium and maximum chromium uptake by bacteria observed at optimum growth conditions. Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM) and Energy dispersive X-ray (EDX) analysis confirmed the presence of chromium uptake by Staphylococcus aureus K1. Conclusion: The study revealed that Staphylococcus aureus K1 have the potential to bio-remediate chromium toxicity from wastewater. Gradually, this biological treatment becomes more important due to its advantage over physical and chemical methods to protect environment and human health.

Keywords: wastewater, staphylococcus, chromium, bioremediation

Procedia PDF Downloads 156

Authors: Marianne D. M. Rendon, Sonia P. Acda, Veneranda A. Magpantay, Norma N. Fajardo, Amado A. Angeles

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The aim of this study is to evaluate the effect of supplementing broiler starter diet with different levels of an essential oil blend (EOB) containing capsaicin, carvacrol and cinnamaldehyde on the performance of broilers. A total of 300 day-old straight-run Cobb broiler chicks were randomly assigned to three treatments after 7-day group brooding following a completely randomized design (CRD). Birds assigned in treatment 1 were given starter basal diet while those in treatments 2 and 3 were given starter basal diet with 400 mg/kg antibiotic growth promoter (AGP) and 150 mg/kg EOB, respectively, until the 28th day. Basal finisher feed were given for all the treatments until harvest. Following 37 d feeding, body weight gain, feed consumption, feed efficiency, dressing percentage, livability and jejunal villi height were determined. Results showed no significant differences (P>0.05) in growth performance. However, villi height and crypt depth was significantly lower for birds fed EOB.

Keywords: broiler, capsaicin, carvacrol, cinnamaldehyde, essential oil

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Authors: Cleto J. Sauer Jr., Rita C. Sauer, Chaider G. Andrade, Doris F. Rabelo

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Introduction: Endotracheal Intubation (ETI) is a procedure for clinical management of patients with severe clinical presentation of COVID-19 disease. Realistic simulation (RS) is an active learning methodology utilized for clinical skill's improvement. To improve ETI skills of public health network's physicians from Recôncavo da Bahia region in Brazil, during COVID-19 outbreak, RS training was planned and carried out. Training scenario included the Nasco Lifeform realistic simulator, and three actions were simulated: ETI procedure, sedative drugs management, and bougie guide utilization. Training intervention occurred between May and June 2020, as an interinstitutional cooperation between the Health's Department of Bahia State and the Federal University from Recôncavo da Bahia. Objective: The main objective is to report the effects on participants' self-confidence perception for ETI procedure after RS based training. Methods: This is a descriptive study, with secondary data extracted from questionnaires applied throughout RS training. Priority workplace, time from last intubation, and knowledge about bougie were reported on a preparticipation questionnaire. Additionally, participants completed pre- and post-training qualitative self-assessment (10-point Likert scale) regarding self-confidence perception in performing each of simulated actions. Distribution analysis for qualitative data was performed with Wilcoxon Signed Rank Test, and self-confidence increase analysis in frequency contingency tables with Fisher's Exact Test. Results: 36 physicians participated of training, 25 (69%) from primary care setting, 25 (69%) performed ETI over a year ago, and only 4 (11%) had previous knowledge about the bougie guide utilization. There was an increase in self-confidence medians for all three simulated actions. Medians (variation) for self-confidence before and after training, for each simulated action were as follows: ETI [5 (1-9) vs. 8 (6-10) (p < 0.0001)]; Sedative drug management [5 (1-9) vs. 8 (4-10) (p < 0.0001)]; Bougie guide utilization [2.5 (1-7) vs. 8 (4-10) (p < 0.0001)]. Among those who performed ETI over a year ago (n = 25), an increase in self-confidence greater than 3 points for ETI was reported by 23 vs. 2 physicians (p = 0.0002), and by 21 vs. 4 (p = 0.03) for sedative drugs management. Conclusions: RS training contributed to self-confidence increase in performing ETI. Among participants who performed ETI over a year, there was a significant association between RS training and increase of more than 3 points in self-confidence, both for ETI and sedative drug management. Training with RS methodology is suitable for ETI confidence enhancement during COVID-19 outbreak.

Keywords: confidence, COVID-19, endotracheal intubation, realistic simulation

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Authors: Imran Muhammad

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The main cause of infectious disease in the modern world is Mycobacterium Tuberculosis (MT). To combat tuberculosis, new and efficient drugs are an urgent need in the modern world. Schif bases are potent for their biological pharmacophore activity. Thus we selected different Vanillin-based Schiff bases for their binding activity against target enzymes of Mycobacterium tuberculosis that is (DprE1 (decaprenyl phosphoryl-β-D-ribose 2′-epimerase), and DNA gyrase subunit-A), using molecular docking. We evaluate the inhibition potential, interaction, and binding mode of these compounds with the target enzymes.

Keywords: schiff bases, tuberculosis, DNA gyrase, DprE1, docking

Procedia PDF Downloads 61

Authors: José Ramón López-Mínguez, Estrella Suárez-Corchuelo, Sergio López-Tejero, Luis Nombela-Franco, Xavier Freixa-Rofastes, Guillermo Bastos-Fernández, Xavier Millán-Álvarez, Raúl Moreno-Gómez, José Antonio Fernández-Díaz, Ignacio Amat-Santos, Tomás Benito-González, Fernando Alfonso-Manterola, Pablo Salinas-Sanguino, Pedro Cepas-Guillén, Dabit Arzamendi, Ignacio Cruz-González, Juan Manuel Nogales-Asensio

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Background and objectives: The treatment of patients with non-valvular atrial fibrillation (NVAF) who need coronary stenting is challenging. The objective of the study was to determine whether left atrial appendage occlusion (LAAO) could be a feasible option and benefit these patients. To this end, we studied the impact of LAAO plus antiplatelet drugs vs oral anticoagulants (OAC) (including direct OAC) plus antiplatelet drugs in these patients’ long-term outcomes. Methods: The results of 207 consecutive patients with NVAF who underwent coronary stenting were analyzed. A total of 146 patients were treated with OAC (75 with acenocoumarol, 71 with direct OAC) while 61 underwent LAAO. The median follow-up was 35 months. Patients also received antiplatelet therapy as prescribed by their cardiologist. The study received the proper ethical oversight. Results: Age (mean 75.7 years), and the past medical history of stroke were similar in both groups. However, the LAAO group had more unfavorable characteristics (history of coronary artery disease [CHA2DS2-VASc], and significant bleeding [BARC ≥ 2] and HAS-BLED). The occurrence of major adverse events (death, stroke/transient ischemic events, major bleeding) and major cardiovascular events (cardiac death, stroke/transient ischemic attack, and myocardial infarction) were significantly higher in the OAC group compared to the LAAO group: 19.75% vs 9.06% (HR, 2.18; P = .008) and 6.37% vs 1.91% (HR, 3.34; P = .037), respectively. Conclusions: In patients with NVAF undergoing coronary stenting, LAAO plus antiplatelet therapy produced better long-term outcomes compared to treatment with OAC plus antiplatelet therapy despite the unfavorable baseline characteristics of the LAAO group.

Keywords: stents, atrial fibrillation, anticoagulants, left atrial appendage occlusion

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Authors: Janneth González, George Barreto, Ludis Morales, Angélica Sabogal

Abstract:

Sea anemone neurotoxins are peptides that interact with Na+ and K+ channels, resulting in specific alterations on their functions. Some of these neurotoxins (1ROO, 1BGK, 2K9E, 1BEI) are important for the treatment of nearly eighty autoimmune disorders due to their specificity for Kv1.3 channel. The aim of this study was to identify the common residues among these neurotoxins by computational methods, and establish whether there is a pattern useful for the future generation of a treatment for autoimmune diseases. Our results showed eight new key common residues between the studied neurotoxins interacting with a histidine ring and the selectivity filter of the receptor, thus showing a possible pattern of interaction. This knowledge may serve as an input for the design of more promising drugs for autoimmune treatments.

Keywords: neurotoxins, potassium channel, Kv1.3, computational methods, autoimmune diseases

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