Search results for: drug discovery

Authors: Neelma Ashraf

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Actinomycetes, particularly genus Streptomyces is of great importance due to their role in the discovery of new natural products, particularly antimicrobial secondary metabolites in the medicinal science and biotechnology industry. Different Streptomyces strains were isolated from Helianthus annuus plants and tested for antibacterial and antifungal activities. The most promising five strains were chosen for further investigation, and growth conditions for antibiotic synthesis were optimised. The supernatants were extracted in different solvents, and the extracted products were analyzed using liquid chromatography-mass spectrometry (LC-MS) and biological testing. From one of the potent strains Streptomyces globusus sp. BR123, a compound lavendamycin was identified using these analytical techniques. In addition, this potent strain also produces a strong antifungal polyene compound with a quasimolecular ion of 2072. Streptomyces sp. BR123 was genome sequenced because of its promising antimicrobial potential in order to identify the gene cluster responsible for analyzed compound “lavendamycin”. The genome analysis yielded candidate genes responsible for the production of this potent compound. The genome sequence of 8.15 Mb of Streptomyces sp. isolate BR123 with a GC content of 72.63% and 8103 protein coding genes was attained. Many antimicrobial, antiparasitic, and anticancerous compounds were detected through multiple biosynthetic gene clusters predicted by in-Silico analysis. Though, the novelty of metabolites was determined through the insignificant resemblance with known biosynthetic gene clusters. The current study gives insight into the bioactive potential of Streptomyces sp. isolate BR123 with respect to the synthesis of bioactive secondary metabolites through genomic and spectrometric analysis. Moreover, the comparative genome study revealed the connection of isolate BR123 with other Streptomyces strains, which could expand the knowledge of this genus and the mechanism involved in the discovery of new antimicrobial metabolites.

Keywords: streptomyces, secondary metabolites, genome, biosynthetic gene clusters, high performance liquid chromatography, mass spectrometry

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Authors: Tayyaba Zahra, Shehla Gul Bokhari, Asim Khalid Mahmood, Raheela Akhtar, Khizar Matloob

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In Pakistan, dogs are commonly infested with ticks, especially in summers, causing not only dermatological issues but also systemic problems. Persistence of tick infestation often leads to heavy losses. Different acaricides are locally available with variable efficacy; however, recurrence of infestation is commonly reported. The present study was thus designed to compare the efficacy of a novel drug Fluralaner and conventionally used Ivermectin against tick infestation. Dogs positive for tick infestation were randomly divided into 2 groups viz, Groups A and B having 8 dogs each. Ticks were enumerated manually from the whole body of dogs at day 0 before the administration of drugs Dogs in Group A were treated with Fluralaner at day 0, and dogs in Group B were treated with Ivermectin. Post-treatment, ticks were counted again at days 7, 14, 21, 28, and 35. At day 07 of the study, no tick was found on the dogs treated with Fluralaner, while many ticks were present on the dogs treated with Ivermectin showing an efficacy up to 50%. On the consecutive follow-up evaluations, similar results were found for Fluralaner while the efficacy of Ivermectin was further reduced to less than 50%. Furthermore, Fluralaner treated dogs had better RBC counts, PCV, Hgb concentration, LFTs, RFTs post-treatment than the dogs treated with Ivermectin. Statistically, oral Fluralaner proved a more effective drug (P≤0.05)than oral Ivermectin against tick infestation in dogs.

Keywords: fluralaner, ivermectin, dogs, tick infestations

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Authors: Jackson Ishara, Ariel Buzera, Gustave N. Mushagalusa, Ahmed R. A. Hammam, Judith Munga, Paul Karanja, John Kinyuru

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Numerous mushroom bioactive metabolites, including polysaccharides, eritadenine, lignin, chitosan, mevinolin, and astrakurkurone have been studied in life-threatening conditions and diseases such as diabetes, cardiovascular, hypertension, cancer, DNA damage, hypercholesterolemia, and obesity attempting to identify natural therapies. These bioactive metabolites have shown potential as antiviral and immune system strengthener natural agents through diverse cellular and physiological pathways modulation with no toxicity evidence, widely available, and affordable. In light of the emerging literature, this paper compiles the most recent information describing the molecular mechanisms that underlie the nutraceutical potentials of these mushroom metabolites suggesting their effectiveness if combined with existing drug therapies. The findings raise hope that these mushroom bioactive metabolites may be utilized as natural therapies considering their therapeutic potential while anticipating further research designing clinical trials and developing new drug therapies while encouraging their consumption as a natural adjuvant in preventing and controlling life-threatening conditions and diseases.

Keywords: bioactive metabolites, food functionality, health-threatening conditions, mushrooms, nutraceutical

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Authors: Md. Alauddin, Md. Ruhul Amin, Md. Omar Faruque, Muhammad Ali Siddiquee, Zakir Hossain Howlader, Mohammad Asaduzzaman

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Diabetes and hypertension are the major lifestyle related diseases. The α-amylase and angiotensin converting enzymes (ACE) are the key enzymes that regulate diabetes and hypertension. The aim was to develop a drug for the treatment of diabetes and hypertension. The Rice Bran (RB) sample (Oryza sativa; BRRI-Dhan-84) was collected from the Bangladesh Rice Research Institute (BRRI), and rice bran proteins were isolated and hydrolyzed by hydrolyzing enzyme alcalase and trypsin. In vivo experiment suggested that rice bran bioactives has an effect on regulating the expression of several key gluconeogenesis and lipogenesis-regulating genes, such as glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, and fatty acid synthase. The above genes have a connection of regulating the glucose level, lipids profile as well as act as an anti-inflammatory agent. A molecular docking, bioinformatics and in vitro experiments were performed. We found rice bran protein hydrolysates significantly (<0.05) influence the peptide concentration in the case of trypsin, alcalase, and (trypsin + alcalase) digestion. The in vitro analysis found that protein hydrolysate significantly (<0.05) reduced diabetic and hypertension as well as oxidative stress. A molecular docking study showed that the YY and IP peptide have a significantly strong binding affinity to the active site of the ACE enzyme and α-amylase with -7.8Kcal/mol and -6.2Kcal/mol, respectively. The Molecular dynamics (MD) simulation and Swiss ADME data analysis showed that less toxicity risk, good physicochemical properties, pharmacokinetics, and drug-likeness with drug scores 0.45 and 0.55 of YY and IP peptides, respectively. Thus, rice bran bioactive could be a good candidate for the treatment of diabetes and hypertension.

Keywords: anti-hypertensive and anti-hyperglycemic, anti-oxidative, bioinformatics, in vitro study, rice bran proteins and peptides

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Authors: Amber Dhoot, Tarush Gupta, Andrea Gurr, William Jenkins, Sandro Pietrunti, Alexis Tang

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Background: The COVID-19 pandemic has driven pharmacovigilance towards a new paradigm. Nowadays, more people than ever before are recognising and reporting adverse reactions from medications, treatments, and vaccines. In the modern era, with over 3.8 billion users, social media has become the most accessible medium for people to voice their opinions and so provides an opportunity to engage with more patient-centric and accessible pharmacovigilance. However, the pharmaceutical industry has been slow to incorporate social media into its modern pharmacovigilance strategy. This project aims to make social media a more effective tool in pharmacovigilance, and so reduce drug costs, improve drug safety and improve patient outcomes. This will be achieved by firstly uncovering and categorising the barriers facing the widespread adoption of social media in pharmacovigilance. Following this, the potential opportunities of social media will be explored. We will then propose realistic, practical recommendations to make social media a more effective tool for pharmacovigilance. Methodology: A comprehensive systematic literature review was conducted to produce a categorised summary of these barriers. This was followed by conducting 11 semi-structured interviews with pharmacovigilance experts to confirm the literature review findings whilst also exploring the unpublished and real-life challenges faced by those in the pharmaceutical industry. Finally, a survey of the general public (n = 112) ascertained public knowledge, perception, and opinion regarding the use of their social media data for pharmacovigilance purposes. This project stands out by offering perspectives from the public and pharmaceutical industry that fill the research gaps identified in the literature review. Results: Our results gave rise to several key analysis points. Firstly, inadequacies of current Natural Language Processing algorithms hinder effective pharmacovigilance data extraction from social media, and where data extraction is possible, there are significant questions over its quality. Social media also contains a variety of biases towards common drugs, mild adverse drug reactions, and the younger generation. Additionally, outdated regulations for social media pharmacovigilance do not align with new, modern General Data Protection Regulations (GDPR), creating ethical ambiguity about data privacy and level of access. This leads to an underlying mindset of avoidance within the pharmaceutical industry, as firms are disincentivised by the legal, financial, and reputational risks associated with breaking ambiguous regulations. Conclusion: Our project uncovered several barriers that prevent effective pharmacovigilance on social media. As such, social media should be used to complement traditional sources of pharmacovigilance rather than as a sole source of pharmacovigilance data. However, this project adds further value by proposing five practical recommendations that improve the effectiveness of social media pharmacovigilance. These include: prioritising health-orientated social media; improving technical capabilities through investment and strategic partnerships; setting clear regulatory guidelines using multi-stakeholder processes; creating an adverse drug reaction reporting interface inbuilt into social media platforms; and, finally, developing educational campaigns to raise awareness of the use of social media in pharmacovigilance. Implementation of these recommendations would speed up the efficient, ethical, and systematic adoption of social media in pharmacovigilance.

Keywords: adverse drug reaction, drug safety, pharmacovigilance, social media

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Authors: Rama Devi Kyatham, D. Ashok, K. S. K. Rao Patnaik, Raju Bathula

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We have shown the importance of pyrazoles as anti-microbial chemical entities. These compounds have generally been considered significant due to their wide range of pharmacological acivities and their discovery motivates new avenues of research.The proposed pyrazoles were synthesized and evaluated for their anti-microbial activities. The Synthesized compounds were analyzed by different spectroscopic methods.

Keywords: pyrazoles, validation, resistant microbial strains, anti-microbial activities

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Authors: Shekoufeh Behdad, Amirhossein Yadegari, Leila Ghodrati, Saman Yadegari

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Context: Preoperative anxiety is a common psychological reaction experienced by all patients undergoing surgery. It can have negative effects on the patient's well-being and even impact surgical outcomes. Therefore, finding effective interventions to reduce preoperative anxiety is important in improving patient care. Research Aim: The aim of this study is to compare the effects of oral administration of zaleplon (5 mg) and alprazolam (0.5 mg) on preoperative anxiety levels in women undergoing gynecological abdominal surgery. Methodology: This study is a double-blind, randomized clinical trial conducted after receiving approval from the university's ethics committee and obtaining written informed consent from the patients. The night before the surgery, patients were randomly assigned to receive either 0.5 mg of alprazolam or 5 mg of zaleplon orally. Anxiety levels, measured using a 10-cm visual analog scale, and hemodynamic variables (blood pressure and heart rate) were assessed before drug administration and on the morning of the operation after the patient entered the pre-operation room. Findings: The study found that there were no significant differences in mean anxiety levels or hemodynamic variables before and after administration of either drug in both groups (P value > 0.05). This suggests that both 0.5 mg of alprazolam and 5 mg of zaleplon effectively reduce preoperative anxiety in women undergoing abdominal surgery without serious side effects. Theoretical Importance: This study contributes to the understanding of the effectiveness of alprazolam and zaleplon in reducing preoperative anxiety. It adds to the existing literature on pharmacological interventions for anxiety management, specifically in the context of gynecological abdominal surgery. Data Collection: Data for this study were collected through the assessment of anxiety levels using a visual analog scale and measuring hemodynamic variables, including systolic, diastolic, and mean arterial blood pressures, as well as heart rate. These measurements were taken before drug administration and on the morning of the surgery. Analysis Procedures: Statistical analysis was performed to compare the mean anxiety levels and hemodynamic variables before and after drug administration in the two groups. The significance of the differences was determined using appropriate statistical tests. Questions Addressed: This study aimed to answer the question of whether there are differences in the effects of alprazolam and zaleplon on preoperative anxiety levels in women undergoing gynecological abdominal surgery. Conclusion: The oral administration of both 0.5 mg of alprazolam and 5 mg of zaleplon the night before surgery effectively reduces preoperative anxiety in women undergoing abdominal surgery. These findings have important implications for the management of preoperative anxiety and can contribute to improving the overall surgical experience for patients.

Keywords: zaleplon, alprazolam, premedication, abdominal surgery

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Authors: Rima A. Ajlouni

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The discovery of quasi-periodic structures in material science is revealing an exciting new class of symmetries, which has never been explored before. Due to their unique structural and visual properties, these symmetries are drawing interest from many scientific and design disciplines. Especially, in art and architecture, these symmetries can provide a rich source of geometry for exploring new patterns, forms, systems, and structures. However, the structural systems of these complicated symmetries are still posing a perplexing challenge. While much of their local order has been explored, the global governing system is still unresolved. Understanding their unique global long-range order is essential to their generation and application. The recent discovery of dodecagonal quasi-periodic patterns in historical Islamic architecture is generating a renewed interest into understanding the mathematical principles of traditional Islamic geometry. Astonishingly, many centuries before its description in the modern science, ancient artists, by using the most primitive tools (a compass and a straight edge), were able to construct patterns with quasi-periodic formations. These ancient patterns can be found all over the ancient Islamic world, many of which exhibit formations with 5, 8, 10 and 12 quasi-periodic symmetries. Based on the examination of these historical patterns and derived from the generating principles of Islamic geometry, a global multi-level structural model is presented that is able to describe the global long-range order of dodecagonal quasi-periodic formations in Islamic Architecture. Furthermore, this method is used to construct new quasi-periodic tiling systems as well as generating their deflation and inflation rules. This method can be used as a general guiding principle for constructing infinite patches of dodecagon-based quasi-periodic formations, without the need for local strategies (tiling, matching, grid, substitution, etc.) or complicated mathematics; providing an easy tool for scientists, mathematicians, teachers, designers and artists, to generate and study a wide range of dodecagonal quasi-periodic formations.

Keywords: dodecagonal, Islamic architecture, long-range order, quasi-periodi

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Authors: Yaw Opoku-Damoah, Run Zhang, Hang Thu Ta, Zhi Ping Xu

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Gas therapy is still at an early stage of research and development. Even though most gasotransmitters have proven their therapeutic potential, their handling, delivery, and controlled release have been extremely challenging. This research work employs a versatile nanosystem that is capable of delivering a gasotransmitter in the form of a photo-responsive carbon monoxide-releasing molecule (CORM) for targeted cancer therapy. The therapeutic action was mediated by upconversion nanoparticles (UCNPs) designed to transfer bio-friendly low energy near-infrared (NIR) light to ultraviolet (UV) light capable of triggering carbon monoxide (CO) from a water-soluble amphiphilic manganese carbonyl complex CORM incorporated into a carefully designed lipid drug delivery system. Herein, gaseous CO that plays a role as a gasotransmitter with cytotoxic and homeostatic properties was investigated to instigate cellular apoptosis. After successfully synthesizing the drug delivery system, the ability of the system to encapsulate and mediate the sustained release of CO after light excitation was demonstrated. CO fluorescence probe (COFP) was successfully employed to determine the in vitro drug release profile upon NIR light irradiation. The uptake of nanoparticles enhanced by folates and its receptor interaction was also studied for cellular uptake purposes. The anticancer potential of the final lipid nanoparticle Lipid/UCNPs/CORM/FA (LUCF) was also determined by cell viability assay. Intracellular CO release and a subsequent therapeutic action involving ROS production, mitochondrial damage, and CO production was also evaluated. In all, this current project aims to use in vitro studies to determine the potency and efficiency of a NIR-mediated CORM prodrug delivery system.

Keywords: carbon monoxide-releasing molecule, upconversion nanoparticles, site-specific delivery, amphiphilic manganese carbonyl complex, prodrug delivery system.

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Authors: P. Behera, K. K. Singh, D. K. Saini, M. De

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Implementation of 2D materials in the detection of bio analytes is highly advantageous in the field of sensing because of its high surface to volume ratio. We have designed our sensor array with different cationic two-dimensional MoS₂, where surface modification was achieved by cationic thiol ligands with different functionality. Green fluorescent protein (GFP) was chosen as signal transducers for its biocompatibility and anionic nature, which can bind to the cationic MoS₂ surface easily, followed by fluorescence quenching. The addition of bio-analyte to the sensor can decomplex the cationic MoS₂ and GFP conjugates, followed by the regeneration of GFP fluorescence. The fluorescence response pattern belongs to various analytes collected and transformed to linear discriminant analysis (LDA) for classification. At first, 15 different proteins having wide range of molecular weight and isoelectric points were successfully discriminated at 50 nM with detection limit of 1 nM. The sensor system was also executed in biofluids such as serum, where 10 different proteins at 2.5 μM were well separated. After successful discrimination of protein analytes, the sensor array was implemented for bacteria sensing. Six different bacteria were successfully classified at OD = 0.05 with a detection limit corresponding to OD = 0.005. The optimized sensor array was able to classify uropathogens from non-uropathogens in urine medium. Further, the technique was applied for discrimination of bacteria possessing resistance to different types and amounts of drugs. We found out the mechanism of sensing through optical and electrodynamic studies, which indicates the interaction between bacteria with the sensor system was mainly due to electrostatic force of interactions, but the separation of native bacteria from their drug resistant variant was due to Van der Waals forces. There are two ways bacteria can be detected, i.e., through bacterial cells and lysates. The bacterial lysates contain intracellular information and also safe to analysis as it does not contain live cells. Lysates of different drug resistant bacteria were patterned effectively from the native strain. From unknown sample analysis, we found that discrimination of bacterial cells is more sensitive than that of lysates. But the analyst can prefer bacterial lysates over live cells for safer analysis.

Keywords: array-based sensing, drug resistant bacteria, linear discriminant analysis, two-dimensional MoS₂

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Authors: Rasha Saad, Jean Frederic Weber, Fatimah Bebe, Sadia Sultan

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The goal of study was to screen the effects of candesartan and four endophytic fungi for their potential in microbial biotransformation. In this experiment, four types of unidentified fungi with the codes of TH2L1, TH2R10, TH1P35 and TH1S46 were used in screening process by MECFUS (Microtiter plate, Elicitors, Combination, Freeze-drying, UHPLC, Statistical analysis) protocol. The experiment was carried out by using 96-well microtiter plate (MTP) with different media and elicitors. Various media with two concentrations of Potato Dextrose Broth (PDB) and elicitors used were to induce the production of secondary metabolites from the fungi as well as the biotransformation of the drug compound. After incubation, cultures were extracted by freeze drying method and finally analyzed by ultra-High performance Liquid Chromatography (uHPLC). The extracts analyzed by uHPLC followed by LC/Ms, demonstrated the presence of biotransformation products from the drug compound and elicitation of the secondary metabolism from the fungi by the occurrence of the additional peaks. From the four fungi, TH1S46 showed highly potential produced secondary metabolites as well as the biotransformation of candesartan. For other fungi, they responded when candesartan was introduced. Moreover, the additional peaks produced in uHPLC need to be further investigation by using LC-MS or NMR.

Keywords: biotransformation, candesartan, endophytes, secondary metabolites

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Authors: M. Kumpugdee-Vollrath, M. Tabatabaeifar, M. Helmis

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Shellac is a natural polyester resin secreted by insects. Pectins are natural, non-toxic and water-soluble polysaccharides extracted from the peels of citrus fruits or the leftovers of apples. Both polymers are allowed for the use in the pharmaceutical industry and as a food additive. SSB Aquagold® is the aqueous solution of shellac and can be used for a coating process as an enteric or controlled drug release polymer. In this study, tablets containing 10 mg methylene blue as a model drug were prepared with a rotary press. Those tablets were coated with mixtures of shellac and one of the pectin different types (i.e. CU 201, CU 501, CU 701 and CU 020) mostly in a 2:1 ratio or with pure shellac in a small scale fluidized bed apparatus. A stable, simple and reproducible three-stage coating process was successfully developed. The drug contents of the coated tablets were determined using UV-VIS spectrophotometer. The characterization of the surface and the film thickness were performed with the scanning electron microscopy (SEM) and the light microscopy. Release studies were performed in a dissolution apparatus with a basket. Most of the formulations were enteric coated. The dissolution profiles showed a delayed or sustained release with a lagtime of at least 4 h. Dissolution profiles of coated tablets with pure shellac had a very long lagtime ranging from 13 to 17.5 h and the slopes were quite high. The duration of the lagtime and the slope of the dissolution profiles could be adjusted by adding the proper type of pectin to the shellac formulation and by variation of the coating amount. In order to apply a coating formulation as a colon delivery system, the prepared film should be resistant against gastric fluid for at least 2 h and against intestinal fluid for 4-6 h. The required delay time was gained with most of the shellac-pectin polymer mixtures. The release profiles were fitted with the modified model of the Korsmeyer-Peppas equation and the Hixson-Crowell model. A correlation coefficient (R²) > 0.99 was obtained by Korsmeyer-Peppas equation.

Keywords: shellac, pectin, coating, fluidized bed, release, colon delivery system, kinetic, SEM, methylene blue

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Authors: Tayaba Dastgeer, Farhan Rasheed, Muhammad Saeed, Maqsood Ahmad, Zia Ashraf, Abdul Waheed, Muhammad Kamran, Mohsin Khurshid

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Objectives: The study aimed to determine the efficacy of linezolid against clinical isolates of methicillin-resistant staphylococcus aureus (MRSA). Methodology: This cross-sectional study was conducted in the microbiology department of Allama Iqbal Medical College Lahore from August 2017 to September 2019. Isolates were confirmed as MRSA via the presence of the mec-A gene. Confirmed MRSA isolates were processed for susceptibility testing against different antimicrobials, especially linezolid, via the disc diffusion method. Zone sizes were interpreted according to CLSI guidelines. Results: Various types of clinical samples were included in the study; however, the highest frequency of MRSA isolates was found in pus samples, followed by other clinical samples. Among hospitalized patients, most MRSA isolates were obtained from patients in the surgical ward. Of 243 mec-A gene detected isolates, Vancomycin and linezolid showed 100% susceptibility, chloramphenicol showed declining resistance 78 (32.09%), and emerging sensitivity 165 (67.90%) against MRSA. Conclusion: Linezolid is a very efficient drug against MRSA, but the use of this novel drug must be conserved for vancomycin-resistant Staphylococcus aureus or when more resistant pathogens are suspected.

Keywords: MRSA, chloramphenicol, linezolid, nosocomial infections

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Authors: Puntarikorn Rungrattanakasin

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Objectives: To develop the trigger tool to warn about the risk of bleeding as an adverse event from warfarin drug usage during admission in Medical Wards of Chumphae Hospital. Methods: A retrospective study was performed by reviewing the medical records for the patients admitted between June 1st,2020- May 31st, 2021. ADEs were evaluated by Naranjo’s algorithm. The international normalized ratio (INR) and events of bleeding during admissions were collected. Statistical analyses, including Chi-square test and Reciever Operating Characteristic (ROC) curve for optimal INR threshold, were used for the study. Results: Among the 139 admissions, the INR range was found to vary between 0.86-14.91, there was a total of 15 bleeding events, out of which 9 were mild, and 6 were severe. The occurrence of bleeding started whenever the INR was greater than 2.5 and reached the statistical significance (p <0.05), which was in concordance with the ROC curve and yielded 100 % sensitivity and 60% specificity in the detection of a bleeding event. In this regard, the INR greater than 2.5 was considered to be an optimal threshold to alert promptly for bleeding tendency. Conclusions: The INR value of greater than 2.5 (>2.5) would be an appropriate trigger tool to warn of the risk of bleeding for patients taking warfarin in Chumphae Hospital.

Keywords: trigger tool, warfarin, risk of bleeding, medical wards

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Authors: Salome Labeh

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Diverse Languages that exist in Nigeria, gave rise to the need to choose among these languages, which one or ones to be used as the National Language(s) in Nigeria. The Multilingual Nature of Nigeria has been examined, in relation to the provisional result of 1991 census conducted in Nigeria and the status of language policy in the country, which eventually led to the discovery of the fact that Hausa, Igbo, Yoruba languages have the highest speaker in terms of population, and are already made co-official languages in Nigeria, alongside with English language. Then, these languages should be considered as the National Languages, if eventually a language policy emerges in Nigeria.

Keywords: multilingual, languages, culture, Nigeria

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Authors: Shiva Shakori Poshteh

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Lung cancer is a highly prevalent and devastating disease, representing a significant global health concern with profound implications for healthcare systems and society. Its high incidence, mortality rates, and late-stage diagnosis contribute to its formidable nature. To address these challenges, nanoparticle-based drug delivery has emerged as a promising therapeutic strategy. Curcumin (CUR), a natural compound derived from turmeric, has garnered attention as a potential nanomedicine for lung cancer treatment. Nanoparticle formulations of CUR offer several advantages, including improved drug delivery efficiency, enhanced stability, controlled release kinetics, and targeted delivery to lung cancer cells. CUR exhibits a diverse array of effects on cancer cells. It induces apoptosis by upregulating pro-apoptotic proteins, such as Bax and Bak, and downregulating anti-apoptotic proteins, such as Bcl-2. Additionally, CUR inhibits cell proliferation by modulating key signaling pathways involved in cancer progression. It suppresses the PI3K/Akt pathway, crucial for cell survival and growth, and attenuates the mTOR pathway, which regulates protein synthesis and cell proliferation. CUR also interferes with the MAPK pathway, which controls cell proliferation and survival, and modulates the Wnt/β-catenin pathway, which plays a role in cell proliferation and tumor development. Moreover, CUR exhibits potent antioxidant activity, reducing oxidative stress and protecting cells from DNA damage. Utilizing CUR as a standalone treatment is limited by poor bioavailability, lack of targeting, and degradation susceptibility. Nanoparticle-based delivery systems can overcome these challenges. They enhance CUR’s bioavailability, protect it from degradation, and improve absorption. Further, Nanoparticles enable targeted delivery to lung cancer cells through surface modifications or ligand-based targeting, ensuring sustained release of CUR to prolong therapeutic effects, reduce administration frequency, and facilitate penetration through the tumor microenvironment, thereby enhancing CUR’s access to cancer cells. Thus, nanoparticle-based CUR delivery systems promise to improve lung cancer treatment outcomes. This article provides an overview of lung cancer, explores CUR nanoparticles as a treatment approach, discusses the benefits and challenges of nanoparticle-based drug delivery, and highlights prospects for CUR nanoparticles in lung cancer treatment. Future research aims to optimize these delivery systems for improved efficacy and patient prognosis in lung cancer.

Keywords: lung cancer, curcumin, nanomedicine, nanoparticle-based drug delivery

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Authors: Zayed Alsulami, Asma Aldosseri, Ahmed Ezziden, Abdulrahman Alonazi

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Children are more susceptible to medication errors than adults. Medication administration process is the last stage in the medication treatment process and most of the errors detected in this stage. Little research has been undertaken about medication errors in children in the Middle East countries. This study was aimed to evaluate how the paediatric nurses adhere to the medication administration policy and also to identify any medication preparation and administration errors or any risk factors. An observational, prospective study of medication administration process from when the nurses preparing patient medication until administration stage (May to August 2014) was conducted in Saudi Arabia. Twelve paediatric nurses serving 90 paediatric patients were observed. 456 drug administered doses were evaluated. Adherence rate was variable in 7 steps out of 16 steps. Patient allergy information, dose calculation, drug expiry date were the steps in medication administration with lowest adherence rates. 63 medication preparation and administration errors were identified with error rate 13.8% of medication administrations. No potentially life-threating errors were witnessed. Few logistic and administrative factors were reported. The results showed that the medication administration policy and procedure need an urgent revision to be more sensible for nurses in practice. Nurses’ knowledge and skills regarding the medication administration process should be improved.

Keywords: medication sasfety, paediatric, medication errors, paediatric ward

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Authors: Vasudha Devi, Arul Amuthan, K. Narayanan, Praveen KS, Venkata Rao J

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Background: Siddha Medicine is one of the Indian traditional medical systems, in which the cancer disease is mentioned as 'putrunoi' which literally means the disease of growth like termite mound. There are number of formulations available for the treatment of cancer disease. Neeradi muthu vallathymezugu (NMV) and thamira kattu chendooram (TKC) are two drugs commonly prescribed by Siddha physicians. These drugs have been clinically reported to be safe and effective when given orally. Though these formulations are in practice for centuries, no efforts have been made to standardize them and explore their anti-cancer potential systematically. Objective: To compare the cytotoxic activity of NMV and TKC with doxorubicin using cancer cell lines. Materials and methods: For this study, ethanol extract of NMV was taken, whereas TKC was used as such. In vitro cytotoxic activity was evaluated by sulphorhodamine (SRB) assay against human hepatic cancer cells (HepG2), human breast cancer cells (MCF-7) and human cervical cancer cells [KeLa]. Doxorubicin was used as the standard. The SRB assay is based on the ability of cellular proteins to bind with sulphorhodamine-B. The number of live cells in drug treated cell lines directly affects the color formation in the assay, which is estimated calorimetrically by measuring the absorbance at 540 nm to calculate the cytotoxicity (inhibitory concentration - IC50 value) of the drug. Results: The IC50values of NMV, TKC and doxorubicin against HepG2 were 3.08 µg/ml, 20.21 µg/ml and 1.21µg/ml respectively. In MCF-7, it was 11.75 µg/ml, 17.67 µg/ml and 2.8µg/ml. In HeLa, the values were 24.76 µg/ml, 73.35 µg/ml and 1.12µg/ml. Conclusions: The study proves the possible anti-cancer potential of these two formulations. Compared to TKC, NMV showed good cytotoxic effect even at low dose. Human hepatic cancer cells responded well even at very low dose, when compared to other cancer cells. Though, cytotoxic potential of these compounds was found to be less compared to doxorubicin, the isolated lead compound may have the potential to be used as an anticancer drug clinically.

Keywords: Neeradi muthu vallathymezugu (Hydnocarpus laurifolia), thamira kattu chendooram, cytotoxicity, in-vitro, Siddha Medicine

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Authors: Yulistiani, Muhammad Amin, Fasich

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A surface charge of the nanoparticle is a very important consideration in pulmonal drug delivery system. The zeta potential (ZP) is related to the surface charge which can predict stability of nanoparticles as nebules of liposomal amikacin. Anionic lipid such as 1,2-dipalmitoyl-sn-glycero-3-phosphatidylglycerol (DPPG) is expected to contribute to the physical stability of liposomal amikacin and the optimal ZP value. Suitable ZP can improve drug release profiles at specific sites in alveoli as well as their stability in dosage form. This study aimed to analyze the effect of DPPG on ZP values and physical stability of liposomal amikacin. Liposomes were prepared by using the reserved phase evaporation method. Liposomes consisting of DPPG, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), cholesterol and amikacin were formulated in five different compositions 0/150/5/100, 10//150/5/100, 20/150/5/100, 30/150/5/100 and 40/150/5/100 (w/v) respectively. A chloroform/methanol mixture in the ratio of 1 : 1 (v/v) was used as solvent to dissolve lipids. These systems were adjusted in the phosphate buffer at pH 7.4. Nebules of liposomal amikacin were produced by using the vibrating nebulizer and then characterized by the X-ray diffraction, differential scanning calorimetry, particle size and zeta potential analyzer, and scanning electron microscope. Amikacin concentration from liposome leakage was determined by the immunoassay method. The study revealed that presence of DPPG could increase the ZP value. The addition of 10 mg DPPG in the composition resulted in increasing of ZP value to 3.70 mV (negatively charged). The optimum ZP value was reached at -28.780 ± 0.70 mV and particle size of nebules 461.70 ± 21.79 nm. Nebulizing process altered parameters such as particle size, conformation of lipid components and the amount of surface charges of nanoparticles which could influence the ZP value. These parameters might have profound effects on the application of nebules in the alveoli; however, negatively charge nanoparticles were unexpected to have a high ZP value in this system due to increased macrophage uptake and pulmonal clearance. Therefore, the ratio of liposome 20/150/5/100 (w/v) resulted in the most stable colloidal system and might be applicable to pulmonal drug delivery system.

Keywords: anionic lipid, dipalmitoylphosphatidylglycerol, liposomal amikacin, stability, zeta potential

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Authors: Sarah Gounden, Mukesh Dheda, Boikhutso Tlou, Elizabeth Ojewole, Frasia Oosthuizen

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Background: Antiretroviral therapy (ART) has been effective in the reduction of mortality and resulted in an improvement in the prognosis of HIV-infected patients. However, treatment with antiretrovirals (ARVs) has led to the development of many adverse drug reactions (ADRs). It is, therefore, necessary to determine the safety profile of these medicines in a South African population in order to ensure safe and optimal medicine use. Objectives: The aim of this study was to quantify ADRs experienced with the different ARVs currently used in South Africa, to determine the safety profile of ARV medicine in South Africa based on reported ADRs, and to determine the ARVs with the lowest risk profile based on specific patient populations. Methodology: This was a quantitative study. Individual case safety reports for the period January 2010 – December 2013 were obtained from the National Pharmacovigilance Center; these reports contained information on ADRs, ARV medicine, and patient demographics. Data was analysed to find associations that may exist between ADRs experienced, ARV medicines used and patient demographics. Results: A total of 1916 patient reports were received of which 1534 met the inclusion criteria for the study. The ARV with the lowest risk of ADRs were found to be lamivudine (0.51%, n=12), followed by lopinavir/ritonavir combination (0.8%, n=19) and abacavir (0.64%, n=15). A higher incidence of ADRs was observed in females compared to males. The age group 31–50 years and the weight group 61–80 kg had the highest incidence of ADRs reported. Conclusion: This study found that the safest ARVs to be used in a South African population are lamivudine, abacavir, and the lopinavir/ritonavir combination. Gender differences play a significant role in the occurrence of ADRs and both anatomical and physiological differences account for this. An increased BMI (body mass index) in both men and women showed an increase in the incidence of ADRs associated with ARV therapy.

Keywords: adverse drug reaction, antiretrovirals, HIV/AIDS, pharmacovigilance, South Africa

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Authors: T. Hojageldiyev, Y. Bolmammedov, S. Gurbanaliyev

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It is known that drugs used in the treatment of tuberculosis show toxic effect to organism especially to liver besides its therapeutic effect. Because of ineffectiveness of drugs used in the treatment regimen of tuberculosis against multidrug resistance (MDR) and extensively drug-resistance (XDR) tuberculosis requires the development of new treatment methods and new, novel drugs. Considering the usage of Artemisia absinthium in traditional medicine in treatment of wounds which suggests its antibacterial activity it seems that, also it may have significant antimycobacterial activity. The objective of present study was to evaluate antibacterial activity of ethanolic extract of A. absinthium against M. tuberculosis. In this study, the effect of ethanolic extract of A. absinthium was tested against tuberculosis and pharmaco-toxicological properties evaluated on laboratory animals. The 20%, 40%, 70% and 96% ethanolic extracts of A. absinthium prepared then its bacteriostatic and bactericidal activities were evaluated by validated methods. Data were analyzed by GraphPad Prism 7.0 at the level P < 0.05. Results showed that ethanolic extracts of A. absinthium show no toxicological properties with having high LD50. All concentrations of extract show high bacteriostatic activity on M. tuberculosis. 96% ethanolic extract has highest bactericidal effect among other concentrations. By conducting further studies, as a result of our study, antimycobacterial drug can be prepared from A. absinthium.

Keywords: Artemisia absinthium, antimycobacterial, ethanolic extract, Mycobacteria tuberculosis

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Authors: Rachel Fanelwa Ajayi, Anovuyo Jonnas, Emmanuel I. Iwuoha

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Tuberculosis (TB) is an infectious disease caused by the bacterium (Mycobacterium tuberculosis) which has a predilection for lung tissue due to its rich oxygen supply. The mycobacterial cell has a unique innate characteristic which allows it to resist human immune systems and drug treatments; hence, it is one of the most difficult of all bacterial infections to treat, let alone to cure. At the same time, multi-drug resistance TB (MDR-TB) caused by poorly managed TB treatment, is a growing problem and requires the administration of expensive and less effective second line drugs which take much longer treatment duration than fist line drugs. Therefore, to acknowledge the issues of patients falling ill as a result of inappropriate dosing of treatment and inadequate treatment administration, a device with a fast response time coupled with enhanced performance and increased sensitivity is essential. This study involved the synthesis of electroactive platforms for application in the development of nano-biosensors suitable for the appropriate dosing of clinically diagnosed patients by promptly quantifying the levels of the TB drug; Isonaizid. These nano-biosensors systems were developed on gold surfaces using the enzyme N-acetyletransferase 2 coupled to the cysteamine modified poly(8-anilino-1-napthalene sulphonic acid)/zinc oxide nanocomposites. The morphology of ZnO nanoparticles, PANSA/ZnO nano-composite and nano-biosensors platforms were characterized using High-Resolution Transmission Electron Microscopy (HRTEM) and High-Resolution Scanning Electron Microscopy (HRSEM). On the other hand, the elemental composition of the developed nanocomposites and nano-biosensors were studied using Fourier Transform Infra-Red Spectroscopy (FTIR) and Energy Dispersive X-Ray (EDX). The electrochemical studies showed an increase in electron conductivity for the PANSA/ZnO nanocomposite which was an indication that it was suitable as a platform towards biosensor development.

Keywords: N-acetyletransferase 2, isonaizid, tuberculosis, zinc oxide

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Authors: Tigabu Dagne Akal

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While advances in computer and communications technology have made the network ubiquitous, they have also rendered networked systems vulnerable to malicious attacks devised from a distance. These attacks or intrusions start with attackers infiltrating a network through a vulnerable host and then launching further attacks on the local network or Intranet. Nowadays, system administrators and network professionals can attempt to prevent such attacks by developing intrusion detection tools and systems using data mining technology. In this study, the experiments were conducted following the Knowledge Discovery in Database Process Model. The Knowledge Discovery in Database Process Model starts from selection of the datasets. The dataset used in this study has been taken from Massachusetts Institute of Technology Lincoln Laboratory. After taking the data, it has been pre-processed. The major pre-processing activities include fill in missed values, remove outliers; resolve inconsistencies, integration of data that contains both labelled and unlabelled datasets, dimensionality reduction, size reduction and data transformation activity like discretization tasks were done for this study. A total of 21,533 intrusion records are used for training the models. For validating the performance of the selected model a separate 3,397 records are used as a testing set. For building a predictive model for intrusion detection J48 decision tree and the Naïve Bayes algorithms have been tested as a classification approach for both with and without feature selection approaches. The model that was created using 10-fold cross validation using the J48 decision tree algorithm with the default parameter values showed the best classification accuracy. The model has a prediction accuracy of 96.11% on the training datasets and 93.2% on the test dataset to classify the new instances as normal, DOS, U2R, R2L and probe classes. The findings of this study have shown that the data mining methods generates interesting rules that are crucial for intrusion detection and prevention in the networking industry. Future research directions are forwarded to come up an applicable system in the area of the study.

Keywords: intrusion detection, data mining, computer science, data mining

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Authors: Ricardo Avila, Gabriel Lopes, Vania Vidal, Jose Macedo

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This article offers a approach to the automatic discovery of semantic concepts and links in the domain of Oil Exploration and Production (E&P). Machine learning methods combined with textual pre-processing techniques were used to detect local patterns in texts and, thus, generate new concepts and new semantic links. Even using more specific vocabularies within the oil domain, our approach has achieved satisfactory results, suggesting that the proposal can be applied in other domains and languages, requiring only minor adjustments.

Keywords: semantic links, data mining, linked data, SKOS

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Authors: Iddrisu Ibrahim, Joseph Atia Ayariga, Junhuan Xu, Daniel A. Abugri, Robertson K. Boakai, Olufemi S. Ajayi

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The recalcitrance of pathogenic bacteria indicates that millions of people who are at risk of infection arising from chronic diseases, surgery, organ transplant, diabetes, and several other debilitating diseases present an aura of potentially untreatable illness due to resistance development. Antimicrobial resistance has successfully become a global health menace, and resistances are often acquired by bacteria through health-care-related incidence (HRI) orchestrated by multi-drug resistant (MDR) and extended drug-resistant pathogens (EDRP). To understand the mechanisms S. Typhimurium uses to resist CDB, we study the abundance of LPS modification, Ergosterols, Mysristic palmitic resistance, Oleic acid resistance of susceptible and resistant S. Typhimurium. Using qPCR, we also analyzed the expression of selected genes known for enabling resistance in S. Typhimurium. We found high abundance of LPS, Ergosterols, Mysristic palmitic resistance, Oleic acid resistance of and high expression of resistant genes in S. Typhimurium compared to the susceptible strain. LPS modification, Ergosterols, Mysristic palmitic resistance, Oleic acid and genes such as Fims, integrons, blaTEM are important indicators of resistance development of S. typhimurium.

Keywords: antimicrobials, resistance, Cannabidiol, Salmonella, blaTEM, fimA, Lipopolysaccharide, Ergosterols

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Authors: Melissa Langevin, Natalie Ward, Colleen Fitzgibbons, Christa Ramsey, Melanie Hogue, Anna Theresa Lobos

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Description: Root Cause Analysis (RCA) is used by health care teams to examine adverse events (AEs) to identify causes which then leads to recommendations for prevention Despite widespread use, RCA has limitations. Best practices have not been established for implementing recommendations or tracking the impact of interventions after AEs. During phase 1 of this study, we used simulation to analyze two fictionalized AEs that occurred in hospitalized paediatric patients to identify and understand how the errors occurred and generated recommendations to mitigate and prevent recurrences. Scenario A involved an error of commission (inpatient drug error), and Scenario B involved detecting an error that already occurred (critical care drug infusion error). Recommendations generated were: improved drug labeling, specialized drug kids, alert signs and clinical checklists. Aim: Use simulation to optimize interventions recommended post critical event analysis prior to implementation in the clinical environment. Methods: Suggested interventions from Phase 1 were designed and tested through scenario simulation in the clinical environment (medicine ward or pediatric intensive care unit). Each scenario was simulated 8 times. Recommendations were tested using different, voluntary teams and each scenario was debriefed to understand why the error was repeated despite interventions and how interventions could be improved. Interventions were modified with subsequent simulations until recommendations were felt to have an optimal effect and data saturation was achieved. Along with concrete suggestions for design and process change, qualitative data pertaining to employee communication and hospital standard work was collected and analyzed. Results: Each scenario had a total of three interventions to test. In, scenario 1, the error was reproduced in the initial two iterations and mitigated following key intervention changes. In scenario 2, the error was identified immediately in all cases where the intervention checklist was utilized properly. Independently of intervention changes and improvements, the simulation was beneficial to identify which of these should be prioritized for implementation and highlighted that even the potential solutions most frequently suggested by participants did not always translate into error prevention in the clinical environment. Conclusion: We conclude that interventions that help to change process (epinephrine kit or mandatory checklist) were more successful at preventing errors than passive interventions (signage, change in memory aids). Given that even the most successful interventions needed modifications and subsequent re-testing, simulation is key to optimizing suggested changes. Simulation is a safe, practice changing modality for institutions to use prior to implementing recommendations from RCA following AE reviews.

Keywords: adverse events, patient safety, pediatrics, root cause analysis, simulation

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Authors: Faisal O. Al-Otaibi, Arthur T. Tucker, Richard M. Langford, Stuart Ratcliffe, Atholl Johnston, Terry D. Lee, Kenneth B. Kirby, Chandan A. Alam

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The Transdermal Delivery System (TDS®) is a proprietary liquid formulation that can be applied to intact skin via a metered pump spray to facilitate drug delivery to the circulation. The aim of this study was to assess the ability of the TDS preparation to deliver diazepam systemically, and to characterize the pharmacokinetic profile of the drug in healthy adult subjects. We conducted a randomized, single-dose, two-period, crossover phase I (pharmacokinetic) comparative study in twelve healthy volunteers. All volunteers received both 10 mg TDS-diazepam topically to the upper chest and 10 mg of the rectal diazepam preparation (Diastat®, 10 mg diazepam gel), with a minimum washout of 14 days between dosing episodes. Both formulations were well tolerated in all volunteers. Following topical application of TDS-diazepam, the mean AUC0-72h was 1241 ng/mL.h and the Cmax 34 ng/mL. The values for rectal Diastat were 4109 ng/mL.h and 300 ng/mL respectively. This proof of concept study demonstrates that the TDS preparation successfully delivered diazepam systemically to adults. As expected, the concentration of diazepam following the TDS application was lower and not bioequivalent to rectal gel. Future development of this unique system is required.

Keywords: transdermal delivery system, diazepam, seizure, bioequivalence, pharmacokinetic

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Authors: Donna L. Roberts

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Heroin has appeared on the drug scene before. Yet the current opioid crisis differs in significant ways. In order to address the grave challenges, this epidemic poses, the unique precipitating and sustaining conditions must be thoroughly examined. This research explored the various aspects of the political, economic, and social conditions that created a 'perfect storm' for the evolution and maintenance of the current opioid crisis. Specifically, the epidemiology, demographics, and progression of addiction inherent in the current crisis were compared to the patterns of past opioid use. Additionally, the role of pharmaceutical companies and prescribing physicians, the nature and pharmaceutical properties of the available substances and the changing socioeconomic climate were considered. Results indicated that the current crisis differs significantly with respect to its evolution, magnitude, prevalence, and widespread societal effects. Precipitated by a proliferation of prescription medication and sustained by the availability of cheaper, more potent street drugs, including new versions of synthetic opioids, the current crisis presents unprecedented challenges affecting a wider and more diverse segment of society. The unique aspects of this epidemic demand unique approaches to addressing the problem. Understanding these differences is a key step in working toward a practical and enduring solution.

Keywords: addiction, drug abuse, opioids, opioid crisis

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Authors: Kye Gilder, Kevin Shan, Amy Halseth, Steve Smith

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This study assessed the effect of prolonged-release naltrexone 32 mg/bupropion 360 mg (NB) on cardiovascular (CV) events in overweight/obese participants at elevated CV risk. Participants must lose ≥2% body weight at 16 wks, without a sustained increase in blood pressure, to continue drug. Only serious adverse events (SAE) and adverse events leading to discontinuation of study drug (AELDSD) were collected. The study was terminated early after second interim analysis with 50% of all CV events. Data on CV endpoints has been published. Current analyses focused on AEs in participants on antidepressants at baseline, as these individuals were excluded from Phase 3 trials. Intent-to-treat (ITT) population (placebo [PBO] N=4450, NB N=4455) was 54.5% female, 83.5% white, mean age of 61 yrs, mean BMI 37.3 kg/m2, 22.8% with a history of depression, 23.1% on antidepressants, including 15.4% on an SSRI. SAEs in participants receiving antidepressants was similar between NB (10.7%) and PBO (9.9%) and also similar to overall population (9.5% NB, 8.1% PBO). SAEs in those on SSRIs were similar, 10.1% NB and PBO 9.4%. For those on SSRIs or other antidepressants, AELDSDs were similar to overall population and were primarily GI disorders. Obesity increases the risk of developing depression. For participants taking NB and antidepressants, including SSRIs, there is a similar AE profile as the overall population and data revealed no evidence of an additional health risk with combined use.

Keywords: antidepressant, Contrave, Mysimba, obesity, pharmacotherapy

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Authors: Indu Lata Kanwar, Preeti K. Suresh

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The aim of this study is to fabricate hydroxyapatite based nanocomposites for local drug delivery in periodontal pockets. Hydroxyapatite is chemically similar to the mineral component of bones and hard tissues in mammals. Synthetic biocompatibility and bioactivity with human teeth and bone, making it very attractive for biomedical applications. Nanocomposite is a multiphase solid material where one of the phases has one, two or three dimensions of less than 100 nanometres (nm), or structures having nano­scale repeat distances between the different phases that make up the material. Nanostructured calcium phosphate materials play an important role in the formation of hard tissues in nature. It is reported that calcium phosphates materials in nano-size can mimic the dimensions of constituent components of calcified tissues. Nano-sized materials offer improved performances compared with conventional materials due to their large surface-to-volume ratios. The specific biological properties of the nanocomposites, as well as their interaction with cells, include the use of bioactive molecules. The approach of periodontal tissue engineering is considered promising to restore bone defect through the use of engineered materials with the aim that they will prohibit the invasion of fibrous connective tissue and help repair the function during bone regeneration.

Keywords: bioactive, hydroxyapatite, nanocomposities, periondontal

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