Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1116

World Academy of Science, Engineering and Technology

[Pharmacological and Pharmaceutical Sciences]

Online ISSN : 1307-6892

1116 Neurotoxic Effects Assessment of Metformin in Danio rerio

Authors: Gustavo Axel Elizalde-Velázquez


Metformin is the first line of oral therapy to treat type II diabetes and is also employed as a treatment for other indications, such as polycystic ovary syndrome, cancer, and COVID-19. Recent data suggest it is the aspirin of the 21st century due to its antioxidant and anti-aging effects. However, increasingly current articles indicate its long-term consumption generates mitochondrial impairment. Up to date, it is known metformin increases the biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription, but further information related to brain damage after its consumption is missing. Bearing in mind the above, this work aimed to establish whether or not chronic exposure to metformin may alter swimming behavior and induce neurotoxicity in Danio rerio adults. For this purpose, 250 Danio rerio grown-ups were assigned to six tanks of 50 L of capacity. Four of the six systems contained 50 fish, while the remaining two had 25 fish (≈1 male:1 female ratio). Every system with 50 fish was allocated one of the three metformin treatment concentrations (1, 20, and 40 μg/L), with one system as the control treatment. Systems with 25 fish, on the other hand, were used as positive controls for acetylcholinesterase (10 μg/L of Atrazine) and oxidative stress (3 μg/L of Atrazine). After four months of exposure, a mean of 32 fish (S.D. ± 2) per group of MET treatment survived, which were used for the evaluation of behavior with the Novel Tank test. Moreover, after the behavioral assessment, we aimed to collect the blood and brains of all fish from all treatment groups. For blood collection, fish were anesthetized with an MS-222 solution (150 mg/L), while for brain gathering, fish were euthanized using the hypothermic shock method (2–4 °C). Blood was employed to determine CASP3 activity and the percentage of apoptotic cells with the TUNEL assay, and brains were used to evaluate acetylcholinesterase activity, oxidative damage, and gene expression. After chronic exposure, MET-exposed fish exhibited less swimming activity when compared to control fish. Moreover, compared with the control group, MET significantly inhibited the activity of AChE and induced oxidative damage in the brain of fish. Concerning gene expression, MET significantly upregulated the expression of Nrf1, Nrf2, BAX, p53, BACE1, APP, PSEN1, and downregulated CASP3 and CASP9. Although MET did not overexpress the CASP3 gene, we saw a meaningful rise in the activity of this enzyme in the blood of fish exposed to MET compared to the control group, which we then confirmed by a high number of apoptotic cells in the TUNEL assay. To the best of our understanding, this is the first study that delivers evidence of oxidative impairment, apoptosis, AChE alteration, and overexpression of B- amyloid-related genes in the brain of fish exposed to metformin.

Keywords: AChE inhibition, CASP3 activity, NovelTank test, oxidative damage, TUNEL assay

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1115 From Herbal Medicine to Modern Medicine

Authors: Abanoub Refaat Mokhtar Henin


Forms of medicine such as Traditional Chinese Medicine, Traditional Korean Medicine, and Unani are practiced in parts of the world and have developed into ordered systems of medicine. This study aims to clarify the relationship between herbal products and modern medicine and examine possible concepts and methods based on natural products and traditional medicine to advance drug discovery. This article summarizes the unique features of the theory, applications, current role or status, and contemporary research on eight types of traditional medicine systems. Although only a small fraction of existing plant species has been scientifically tested for bioactivity since 1805, when the first pharmacologically active morphine compound was isolated from opium, natural products, and traditional medicines have already successfully contributed to modern medicine. In the development of new medicines, natural products and traditional medicines have their unmatched advantages, such as B. Rich clinical experience and unique variety of chemical structures and biological activities. Since prehistoric times, humans have used natural products such as plants, animals, microorganisms, and marine organisms in medicines to alleviate and treat diseases. According to the fossil record, human use of plants as medicine dates back at least 60,000 years. The use of natural products as medicine must obviously have been a great challenge for early humans. It is highly likely that early humans often ingested poisonous plants in their foraging activities, causing vomiting, diarrhea, coma, or other toxic reactions, and even death. In this way, however, the first humans were able to expand their knowledge of edible materials and natural medicines. Then humans invented fire, learned how to make alcohol, developed religions and made technological advances, and learned how to create new drugs.

Keywords: natural products, traditional medicines, drug discovery, traditional uses, chemo-diversity.

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1114 Therapeutic Potential of Cannabis in Cancer: Advances in Clinical Research and Pharmacogenomics Aspects

Authors: Bouchaïb Gazzaz, Hamid El Amri, Amal Taazit, Hind Dehbi


Medical cannabis has been cultivated and used in many countries around the world. The story of use of cannabis as therapeutic agent is difficult to trace, in particular because the laws regulating its production, distribution, possession and consumption are relatively recent. Nowadays, in countries where it is authorized, medical cannabis is used in a very wide variety of illnesses and pathologies, particularly in cancer cure. Presently, cannabinoid receptor agonists (like nabilone and dronabinol) are used for reducing the chemotherapy induced vomiting. This review aims to discuss a recent finding on use of therapeutic cannabis in patients with cancer. First, this work addresses progress made in the use of cannabinoids as a therapeutic agent and its application in the treatment of different types of cancer. Secondly, a detailed analysis of the pharmacogenetic aspect of cannabis will be discussed.

Keywords: cannabinoids, cancer treatment, cannabinoid receptors, pharmacogenomics

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1113 Enhanced Wound Healing Efficacy of Cordycepin-Melittin Nanoconjugate in Excised Wounds of Diabetic Rats

Authors: Mohammed Flaih Alotaibi, Rasheed Ahemad Shaik, Mohammed Z. Nasrullah


Diabetic foot ulcers are the foremost global healthcare burden. Hyperglycemia in diabetics is incriminating in impeding wound healing and it can allow for more severe medical issues. The study was intended to establish a nanoconjugate of cordycepin-melittin (COR-MEL) and evaluate its healing effects in wounded diabetic rats. Diabetes induced by injecting streptozotocin intraperitoneally (50 mg/kg, body weight). Therefore, animals were classified into various groups; diabetic untreated, vehicle-treated, COR alone, MEL alone, and COR-MEL nanoconjugate treated, respectively. Animals with diabetes were exposed to excision and treated with Vehicle, COR, MEL, or COR-MEL nanoconjugate topically. After 14 days, the wounded skin was sliced and subjected to histological and biochemical assessments. The formulated nanoconjugate has a particle size of 253.5± 17.4 nm by a polydispersity index of 0.36 ± 0.05, and a zeta potential of 1.72 ± 0.3 mV. The study demonstrated an accelerated wound contraction in COR-MEL-treated diabetic rats, which was further validated by histological analysis. The nanoconjugate further exhibited antioxidant activities by inhibiting the accumulation of malondialdehyde and exhaustion of superoxide dismutase and glutathione peroxidase enzymatic activities. The nanoconjugate further demonstrated an enhanced anti-inflammatory activity by retarding the expression of proinflammatory cytokines (IL-6 and TNF-α). Additionally, the nanoconjugate exhibits a strong expression of growth factors (TGF-β1, VEGF-A, and PDGFR-β), indicating enrichment of proliferation. Likewise, nanoconjugate increased the concentration of hydroxyproline as well as the mRNA expression of collagen, type I, alpha 1. Thus, it is concluded that the nanoconjugate possesses a potent wound-healing activity in diabetic rats via antioxidant, anti-inflammatory, and pro-angiogenetic mechanisms.

Keywords: diabetic wounds, cordycepin, melittin, nanoconjugate, wound healing

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1112 Network Pharmacological Evaluation of Holy Basil Bioactive Phytochemicals for Identifying Novel Potential Inhibitors Against Neurodegenerative Disorder

Authors: Bhuvanesh Baniya


Alzheimer disease is illnesses that are responsible for neuronal cell death and resulting in lifelong cognitive problems. Due to their unclear mechanism, there are no effective drugs available for the treatment. For a long time, herbal drugs have been used as a role model in the field of the drug discovery process. Holy basil in the Indian medicinal system (Ayurveda) is used for several neuronal disorders like insomnia and memory loss for decades. This study aims to identify active components of holy basil as potential inhibitors for the treatment of Alzheimer disease. To fulfill this objective, the Network pharmacology approach, gene ontology, pharmacokinetics analysis, molecular docking, and molecular dynamics simulation (MDS) studies were performed. A total of 7 active components in holy basil, 12 predicted neurodegenerative targets of holy basil, and 8063 Alzheimer-related targets were identified from different databases. The network analysis showed that the top ten targets APP, EGFR, MAPK1, ESR1, HSPA4, PRKCD, MAPK3, ABL1, JUN, and GSK3B were found as significant target related to Alzheimer disease. On the basis of gene ontology and topology analysis results, APP was found as a significant target related to Alzheimer’s disease pathways. Further, the molecular docking results to found that various compounds showed the best binding affinities. Further, MDS top results suggested could be used as potential inhibitors against APP protein and could be useful for the treatment of Alzheimer’s disease.

Keywords: holy basil, network pharmacology, neurodegeneration, active phytochemicals, molecular docking and simulation

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1111 Ethnobotanical Survey on the Use of Herbal Medicine at Children in Algeria

Authors: Metahri Leyla


Herbal medicine is one of the oldest medicines in the world. It constitutes an interesting alternative to treat and cure without creating new diseases. Despite the progress of medicine, the increase in the number of doctors, the creation of social security, many parents have resorted to herbal medicine for their children; they are increasingly asking for "natural remedies", "without risk" for their children. Herbal tea is a very accessible way to enjoy the benefits of herbal medicine. Accordingly; the objective of our study is to obtain detailed information on the composition and mode of administration of these herbal teas and to identify the different plants used; their beneficial effects, as well as their possible toxicity. The current research work represents an ethnobotanical survey spread over one month (from January 6, 2021, to February 19, 2021) carried out by means of an electronic questionnaire concerning 753 respondents involving single or multiparous mothers. The obtained results reveal that a total of 684 mothers used herbal teas for their infants, which revealed the use of 55 herbal remedies for several indications, the most sought after are the carminative effect and relief of colic, and which 9% of users noticed undesirable effects linked to the administration of herbal teas to their infants. As a conclusion, it has been asserted that the use of herbal teas as a natural remedy by Algerian mothers is a widely accepted practice, however, the "natural" nature of the plants does not mean that they are harmless.

Keywords: herbal medicine, herbal teas, children, mothers, medicinal plants

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1110 Clinical Pharmacology Throughout the World: A View from Global Health

Authors: Ragy Raafat Gaber Attaalla


Despite having the greatest rates of mortality and morbidity in the world, low- and middle-income (LMIC) nations trail high-income nations in terms of the number of clinical trials, the number of qualified researchers, and the amount of research information specific to their people. Health inequities and the use of precision medicine may be hampered by a lack of local genomic data, clinical pharmacology and pharmacometrics competence, and training opportunities. These issues can be solved by carrying out health care infrastructure development, which includes data gathering and well-designed clinical pharmacology training in LMICs. It will be advantageous if there is international cooperation focused at enhancing education and infrastructure and promoting locally motivated clinical trials and research. This paper outlines various instances where clinical pharmacology knowledge could be put to use, including pharmacogenomic opportunities that could lead to better clinical guideline recommendations. Examples of how clinical pharmacology training can be successfully implemented in LMICs are also provided, including clinical pharmacology and pharmacometrics training programmes in Africa and a Tanzanian researcher's personal experience while on a training sabbatical in the United States. These training initiatives will profit from advocacy for clinical pharmacologists' employment prospects and career development pathways, which are gradually becoming acknowledged and established in LMICs. The advancement of training and research infrastructure to increase clinical pharmacologists' knowledge in LMICs would be extremely beneficial because they have a significant role to play in global health.

Keywords: low- and middle-income, clinical pharmacology, pharmacometrics, career development pathways

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1109 Delivering Safer Clinical trials; Using Electronic Healthcare Records (EHR) to Monitor, Detect and Report Adverse Events in Clinical Trials

Authors: Claire Williams


Randomised controlled Trials (RCTs) of efficacy are still perceived as the gold standard for the generation of evidence, and whilst advances in data collection methods are well developed, this progress has not been matched for the reporting of adverse events (AEs). Assessment and reporting of AEs in clinical trials are fraught with human error and inefficiency and are extremely time and resource intensive. Recent research conducted into the quality of reporting of AEs during clinical trials concluded it is substandard and reporting is inconsistent. Investigators commonly send reports to sponsors who are incorrectly categorised and lacking in critical information, which can complicate the detection of valid safety signals. In our presentation, we will describe an electronic data capture system, which has been designed to support clinical trial processes by reducing the resource burden on investigators, improving overall trial efficiencies, and making trials safer for patients. This proprietary technology was developed using expertise proven in the delivery of the world’s first prospective, phase 3b real-world trial, ‘The Salford Lung Study, ’ which enabled robust safety monitoring and reporting processes to be accomplished by the remote monitoring of patients’ EHRs. This technology enables safety alerts that are pre-defined by the protocol to be detected from the data extracted directly from the patients EHR. Based on study-specific criteria, which are created from the standard definition of a serious adverse event (SAE) and the safety profile of the medicinal product, the system alerts the investigator or study team to the safety alert. Each safety alert will require a clinical review by the investigator or delegate; examples of the types of alerts include hospital admission, death, hepatotoxicity, neutropenia, and acute renal failure. This is achieved in near real-time; safety alerts can be reviewed along with any additional information available to determine whether they meet the protocol-defined criteria for reporting or withdrawal. This active surveillance technology helps reduce the resource burden of the more traditional methods of AE detection for the investigators and study teams and can help eliminate reporting bias. Integration of multiple healthcare data sources enables much more complete and accurate safety data to be collected as part of a trial and can also provide an opportunity to evaluate a drug’s safety profile long-term, in post-trial follow-up. By utilising this robust and proven method for safety monitoring and reporting, a much higher risk of patient cohorts can be enrolled into trials, thus promoting inclusivity and diversity. Broadening eligibility criteria and adopting more inclusive recruitment practices in the later stages of drug development will increase the ability to understand the medicinal products risk-benefit profile across the patient population that is likely to use the product in clinical practice. Furthermore, this ground-breaking approach to AE detection not only provides sponsors with better-quality safety data for their products, but it reduces the resource burden on the investigator and study teams. With the data taken directly from the source, trial costs are reduced, with minimal data validation required and near real-time reporting enables safety concerns and signals to be detected more quickly than in a traditional RCT.

Keywords: more comprehensive and accurate safety data, near real-time safety alerts, reduced resource burden, safer trials

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1108 Physico‑chemical Behavior and Microstructural Manipulation of Nanocomposites Containing Hydroxyapatite, Alumina, and Graphene Oxide

Authors: Reim A. Almotiri, Manal M. Alkhamisi


Ternary nanocomposites based on hydroxyapatite (HAP) and alumina (Al2O3) were embedded through graphene oxide (GO) nanosheets to be investigated for medical applications. The composition of the preparations has been confirmed by X-ray photoelectron spectroscopy, energy-dispersive X-ray analysis, and Fourier-Transform infrared spectroscopy. Scanning and transmission electron microscopy have shown the typical morphologies of the components of the nanocomposites with hydroxyapatite nanorods reaching an average diameter of 22.26±2 nm and an average length of 69.56±19.25 nm in the ternary nanocomposites. The ternary nanocomposite has a microhardness of 5.8±0.1 GPa and a higher average roughness of 6.5 nm compared to pure HAP preparation with an average roughness of 2.7 nm. All preparations have shown an acceptable cytotoxicity profile with a percent osteoblasts cell viability of 98.6±1.3% after culturing with the ternary nanocomposite. The TNC has also shown the highest antibacterial activity compared to preparations of each of its constituents and their nanocomposites, with a zone of inhibition’s diameter of 14.1±0.8 mm and 13.6±0.6 mm against Staphylococcus aureus and Escherichia coli, respectively, compared to no zone of inhibition for the pure hydroxyapatite preparation.

Keywords: hydroxypatite, cytotoxicity, nanocomposites, X-ray analysis

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1107 Pharmacogenetics of P2Y12 Receptor Inhibitors

Authors: Ragy Raafat Gaber Attaalla


For cardiovascular illness, oral P2Y12 inhibitors including clopidogrel, prasugrel, and ticagrelor are frequently recommended. Each of these medications has advantages and disadvantages. In the absence of genotyping, it has been demonstrated that the stronger platelet aggregation inhibitors prasugrel and ticagrelor are superior than clopidogrel at preventing significant adverse cardiovascular events following an acute coronary syndrome and percutaneous coronary intervention (PCI). Both, nevertheless, come with a higher risk of bleeding unrelated to a coronary artery bypass. As a prodrug, clopidogrel needs to be bioactivated, principally by the CYP2C19 enzyme. A CYP2C19 no function allele and diminished or absent CYP2C19 enzyme activity are present in about 30% of people. The reduced exposure to the active metabolite of clopidogrel and reduced inhibition of platelet aggregation among clopidogrel-treated carriers of a CYP2C19 no function allele likely contributed to the reduced efficacy of clopidogrel in clinical trials. Clopidogrel's pharmacogenetic results are strongest when used in conjunction with PCI, but evidence for other indications is growing. One of the most typical examples of clinical pharmacogenetic application is CYP2C19 genotype-guided antiplatelet medication following PCI. Guidance is available from expert consensus groups and regulatory bodies to assist with incorporating genetic information into P2Y12 inhibitor prescribing decisions. Here, we examine the data supporting genotype-guided P2Y12 inhibitor selection's effects on clopidogrel response and outcomes and discuss tips for pharmacogenetic implementation. We also discuss procedures for using genotype data to choose P2Y12 inhibitor therapies as well as any unmet research needs. Finally, choosing a P2Y12 inhibitor medication that optimally balances the atherothrombotic and bleeding risks may be influenced by both clinical and genetic factors.

Keywords: inhibitors, cardiovascular events, coronary intervention, pharmacogenetic implementation

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1106 Antibacterial and Antifungal Activities of the Essential Oil of Pulicaria jaubertii Leaves

Authors: Methaq Algabr, Nabil Al-Hajj, Ameerh Jaber, Amtellah Alshotobi, Shaima'a Al-suryhi, Gadah Whaban, Nawal Alshehari


Steam distillation of the essential oil of P. jaubertii was performed using a Clevenger apparatus. Essential oils were analyzed by gas chromatography-flame ionization detector (GC-FID) and gas chromatography coupled to chromatography–mass spectrometry (GC-MS). The major chemical components identified in P. jaubertii essential oil include carvotanacetone (63.975%), 1-methyl-1,2-propanedione (5.887%), 2,5-dimethoxy-para-cymene (3.303%) and ar-curcumene (3.276%). The antimicrobial activity of the essential oil of P. jaubertii was evaluated against all tested microorganisms. P. jaubertii essential oil inhibited all tested microorganisms except Escherichia coli with a minimum inhibitory concentration (MIC) of 5.0 μg/mL against Staphylococcus aureus.

Keywords: Pulicaria jaubertii, essential oil, antimicrobial, Carvotancetone

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1105 The Pharmacology and Physiology of Steroid Oral Contraceptives

Authors: Ragy Raafat Gaber Attaalla


PIP: This review, based on 2 large-scale studies, discusses the pharmacology and physiology of oral steroid contraceptives (OCs). The pharmacological distinction between synthetic and naturally occurring steroids centers on changes in biological activity dependent on compound formulation and an individual's metabolism. OC mechanism of action is explained as the main prevention of ovulation by interference with gonadotropin-releasing hormone. Since some 52 metabolic alterations have been reported in OC users, these phenomena are dealt with in 3 categories: 1) effects on the primary target organs of the female reproductive tract (ovary, myometrium, endometrium, cervix, vagina, breasts, and hypothalamus), 2) general metabolic effects (serum proteins, carbohydrate metabolism, lipid metabolism, water and electrolyte metabolism, body weight, tryptophan metabolism, and vitamins and minerals), and 3) effects on other organ systems (liver, central nervous system, skin, genitourinary, gastrointestinal tract, eye, immune phenomena, and effect on subsequent fertility). The choice of the proper OC formulation and use of OCs by adolescents are discussed. Assessment of OC safety, contraindications, and patient monitoring are provided.

Keywords: steroid oral contraceptives, ovulation, female reproductive tract, metabolic effects

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1104 Leveraging the HDAC Inhibitory Pharmacophore to Construct Deoxyvasicinone Based Tractable Anti-Lung Cancer Agent and pH-Responsive Nanocarrier

Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali


A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

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1103 Investigation of Antidepressant Activity of Dracaena Trifasciata in Rats

Authors: Samiah Rehman, Kashmira J. Gohil


Objective: Dracaena trifascaita extract (DTE) possesses strong antioxidant and anti-inflammatory properties that play a vital role in the treatment of mental disorders like depression. The present study was designed to evaluate the antidepressant effects of hydroalcoholic extracts of DT on behavioral models of depression. Methodology: Animals were randomly divided into 6 groups of 5 each: Group 1 and 2 received distilled water and standard drug, imipramine: 25mg/kg, respectively. Groups 4, 5 and 6 received DTE treatment orally at doses of 200 ,400 and 600mg/ kg, respectively, for 14 days. Time of immobility was noted by force swimming test (FST)and tail suspension test (TST) on the 1st,7th and 14th days. Results: The time of immobility was reduced in the treatment group as compared to the control and standard. DTE600 mg/kg showed the highest and most significant antidepressant effects as compared to the standard drug imipramine. (25mg/kg). Conclusion: DTE has good potential as an alternative therapy for depression.

Keywords: Dracaena trifasciata, antidepressants, force swimming test, tail suspension test, herbal drug of depression

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1102 Central Nervous System Delivery Device to Effectively Control Cerebral Spinal Fluid Flow for Optimized Delivery of Therapeutics

Authors: M. A. Glicksman, H. R. Benatti, T. Taghian, S. Nagpal, W. Gormley, W. C. Baker, R. Patel, E. Brown, H. Gray-Edwards


BACKGROUND: Appropriate drug distribution is needed for the effective treatment of brain metastases and leptomeningeal carcinomatosis. Lack of proper drug bioavailability in the CNS contributes to poor outcomes in these patients. EnClear Therapies has developed a device delivering intrathecal therapeutics utilizing the active control of CSF flow through an external pump. Herein, we look at intrathecal drug delivery of methotrexate with EnClear’s system and its impact on drug concentration in sheep and non-human primates. METHODS: The EnClear device utilizes two implantable catheters (intracranial in the ventricular system and lumbar thecal sac) and an extracorporeal pump that controls the speed and direction of CSF flow. The software monitors the output from sensor arrays for pressure, respiration, and heart rate. Gadolinium and MRI were used to determine the CSF flow characteristics. Administration of Methotrexate via the EnClear system was compared to the current two standards of delivery, intracerebroventricular or lumbar intrathecal administration. Methotrexate levels were measured with Liquid Chromatography/Mass Spectrometry in CSF, blood, and multiple CNS and peripheral tissues. RESULTS: There was a two-fold increase in methotrexate levels in multiple regions of the brain, including deeper brain structures, including the striatum, using EnClear's system, compared to traditional lumbar intrathecal and intracerebroventricular delivery. Higher peak levels of methotrexate were reached in the CSF with the use of EnClear’s system, with a simultaneous reduction in the peripheral nerves and systemic tissues – a potential source of toxicity. CONCLUSIONS: In large animal studies, the EnClear device has, for the first time, demonstrated increased brain parenchymal drug levels via intrathecal delivery. In addition to the drug parenchyma, drug delivery with this novel device has shown improved distribution throughout CNS and leptomeninges as compared to traditional intrathecal drug delivery and decreased peripheral distribution.

Keywords: brain drug delivery, brain metastases, cerebral spinal fluid, CNS, CSF, distribution

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1101 Antibiogram Profile of Antibacterial Multidrug Resistance in Democratic Republic of Congo: Situation in Bukavu City Hospitals

Authors: Justin Ntokamunda Kadima, Christian Ahadi Irenge, Patient Birindwa Mulashe, Félicien Mushagalusa Kasali, Patient Wimba


Background: Bacterial strains carrying multidrug resistance traits are gaining ground worldwide, especially in countries with limited resources. This study aimed to evaluate the spreading of multidrug-resistant bacteria strains in Bukavu city hospitals in the Democratic Republic of Congo. Methods: We analyzed 758 antibiogram data recorded in files of patients consulted between January 2016 and December 2017 at three reference hospitals selected as sentinel sites, namely the Panzi General Reference Hospital (HGP), BIO -PHARM hospital (HBP), and Saint Luc Clinic (CSL). Results: Of 758 isolates tested, the laboratories identified 12 bacterial strains in 712 isolates, of which 223 (29.42%) presented MDR profile, including Escherichia coli (11.48%), Klebsiella pneumonia (6.07%), Enterobacter (5.8%), Staphylococcus aureus and coagulase-negative Staphylococci (1.58%), Proteus mirabilis (1.85%), Salmonella enterica (1.19%), Pseudomonas aeruginosa (0.53%), Streptococcus pneumonia (0.4%)), Citrobacter (0.13%), Neisseria gonorrhea (0.13%), Enterococcus faecalis (0.13%), and Morganella morganii (0.13%). Infected patients were significantly more adults (73.1% vs. 21.5%) compared to children and mainly women (63.7% vs. 30.9%; p = 0.001). Conclusion: The observed expansion requires that hospital therapeutic committees set up an effective clinical management system and define the right combinations of antibiotics.

Keywords: multidrug resistance, bacteria, antibiogram, Bukavu

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1100 Conformal Coating Technology Applicable to Cell Therapeutics Using Click-Reactive Biocompatible Polymers

Authors: Venkat Garigapati


Cell-based therapies are limited due to underlying host immune system activity. Microencapsulation of living cells to overcome this issue has some serious drawbacks, such as limitations of nutrient and oxygen diffusion, which pose a threat to the function and longevity of cells. The conformal coating could overcome the issues which are generally involved in traditional microencapsulation. Some of the theoretical advantages of conformal coating include superior nutrient and oxygen supply to cells, prolonged lifespan, improved drug-secreting cell functionality and an opportunity to load high cell doses in small volumes. Despite several advantages to the conformal coating, there are no suitable methods available to apply to living cells. The ultra-thin conformal coating was achieved utilizing click-reactive methacryloyloxyethyl phosphorylcholine (MPC) polymers, which are capable of specifically reacting one polymer to another at neutral pH in the aqueous isotonic system at the desired temperature suitable for living cells without the need of deleterious initiators. ARPE-19 (Adult Retinal Pigment Epithelial cell line-19) cell-spheroids and rat pancreatic islets were used in the formulation studies. The in vitro studies of coated ARPE-19 cell-spheroids and rat islets indicate that the coat was intact; cells were viable and functioning. The in vitro study results revealed that the conformal coating technology seems promising and in vivo studies are being planned.

Keywords: cells, hydrogel, conformal coating, microencapsulation, insulin

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1099 Molluscicidal Activity of Some Aqueous and Organic Extract from Some Asteraceae

Authors: Lineda Rouissat-Dahane, Abdelkrim Cheriti, Abbderazak Marouf, Reddy Kandappa H., Govender Patrick


Natural phytochemicals extracted from folk herbal have drawn much attention in complementary and alternative medicine, and the plant kingdom is considered for developing new molluscicide. The aqueous and acetone extract of the aerial parts of some Asteraceae (Anvillea radiata, Bubonium graveolens, Launaea arborescens, Launaea nudicaulis and Warionia saharae) were investigated for its molluscicidal activity against Lymnaea acuminata showed significant molluscicidal activity with a median lethal concentration (LC50) of aqueous extract (8,178mg/ml) and organic extract 0.002μg/mL, which was indicated higher potency than the positive control, (LC50=100mg /mL for aqueous extract ; LC50=11.6 μg/mL for organic extract). Among the extract and their fractions, those of aerial parts of Launaea nudicaulis and Warionia saharae were found to exhibit significant molluscicidal activities. Among different solvent fractions of the acetone extract of Warionia saharae, the dichloromethane (DCM) soluble fraction showed the most potent molluscicidal activity against Lymnaea acuminata. Plants in species Anvillea radiata, Bubonium graveolens, Launaea arborescens, Launaea nudicaulis, and Warionia saharae produce a great variety of Flavonoids, Glucoside flavonoids, and Saponins that confer natural resistance against several pests. Most extracts were found to exhibit significant molluscicidal activity.

Keywords: acetone extract, aqueous extract, Asteraceae, molluscicidal activity, Lymnaea acuminata

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1098 Six Years Antimicrobial Resistance Trends among Bacterial Isolates in Amhara National Regional State, Ethiopia

Authors: Asrat Agalu Abejew


Background: Antimicrobial resistance (AMR) is a silent tsunami and one of the top global threats to health care and public health. It is one of the common agendas globally and in Ethiopia. Emerging AMR will be a double burden to Ethiopia, which is facing a series of problems from infectious disease morbidity and mortality. In Ethiopia, although there are attempts to document AMR in healthcare institutions, comprehensive and all-inclusive analysis is still lacking. Thus, this study is aimed to determine trends in AMR from 2016-2021. Methods: A retrospective analysis of secondary data recorded in the Amhara Public Health Institute (APHI) from 2016 to 2021 G.C was conducted. Blood, Urine, Stool, Swabs, Discharge, body effusions, and other Microbiological specimens were collected from each study participants, and Bacteria identification and Resistance tests were done using the standard microbiologic procedure. Data was extracted from excel in August 2022, Trends in AMR were analyzed, and the results were described. In addition, the chi-square (X2) test and binary logistic regression were used, and a P. value < 0.05 was used to determine a significant association. Results: During 6 years period, there were 25143 culture and susceptibility tests. Overall, 265 (46.2%) bacteria were resistant to 2-4 antibiotics, 253 (44.2%) to 5-7 antibiotics, and 56 (9.7%) to >=8 antibiotics. The gram-negative bacteria were 166 (43.9%), 155 (41.5%), and 55 (14.6%) resistant to 2-4, 5-7, and ≥8 antibiotics, respectively, whereas 99(50.8%), 96(49.2% and 1 (0.5%) of gram-positive bacteria were resistant to 2-4, 5-7 and ≥8 antibiotics respectively. K. pneumonia 3783 (15.67%) and E. coli 3199 (13.25%) were the most commonly isolated bacteria, and the overall prevalence of AMR was 2605 (59.9%), where K. pneumonia 743 (80.24%), E. cloacae 196 (74.81%), A. baumannii 213 (66.56%) being the most common resistant bacteria for antibiotics tested. Except for a slight decline during 2020 (6469 (25.4%)), the overall trend of AMR is rising from year to year, with a peak in 2019 (8480 (33.7%)) and in 2021 (7508 (29.9%). If left un-intervened, the trend in AMR will increase by 78% of variation from the study period, as explained by the differences in years (R2=0.7799). Ampicillin, Augmentin, ciprofloxacin, cotrimoxazole, tetracycline, and Tobramycin were almost resistant to common bacteria they were tested. Conclusion: AMR is linearly increasing during the last 6 years. If left as it is without appropriate intervention after 15 years (2030 E.C), AMR will increase by 338.7%. A growing number of multi-drug resistant bacteria is an alarm to awake policymakers and those who do have the concern to intervene before it is too late. This calls for a periodic, integrated, and continuous system to determine the prevalence of AMR in commonly used antibiotics.

Keywords: AMR, trend, pattern, MDR

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1097 Distribution of HLA-DQA1 and HLA-DQB1 Alleles in Thais: Genetics Database Insight for COVID-19 Severity

Authors: Jinu Phonamontham, Jina Phonamontham


Coronavirus, also referred to as COVID-19, is a virus caused by the SARS-Cov-2 virus. The pandemic has caused over 10 million cases and 500,000 deaths worldwide through the end of June 2020. In a previous study, HLA-DQA1*01:02 allele was associated with COVID-19 disease (p-value = 0.0121). Furthermore, there was a statistical significance between HLA- DQB1*06:02 and COVID-19 in the Italian population by Bonferroni’s correction (p-value = 0.0016). Nevertheless, there is no data describing the distribution of HLA alleles as a valid marker for prediction of COVID-19 in the Thai population. We want to investigate the prevalence of HLA-DQA1*01:02 and HLA-DQB1*06:02 alleles that are associated with severe COVID-19 in the Thai population. In this study, we recruited 200 healthy Thai individuals. Genomic DNA samples were isolated from EDTA blood using Genomic DNA Mini Kit. HLA genotyping was conducted using the Lifecodes HLA SSO typing kits (Immucor, West Avenue, Stamford, USA). The frequency of HLA-DQA1 alleles in Thai population, consisting of HLA-DQA1*01:01 (27.75%), HLA-DQA1*01:02 (24.50%), HLA-DQA1*03:03 (13.00%), HLA-DQA1*06:01 (10.25%) and HLA-DQA1*02:01 (6.75%). Furthermore, the distributions of HLA-DQB1 alleles were HLA-DQB1*05:02 (21.50%), HLA-DQB1*03:01 (15.75%), HLA-DQB1*05:01 (14.50%), HLA-DQB1*03:03 (11.00%) and HLA-DQB1*02:02 (8.25%). Particularly, HLA- DQA1*01:02 (29.00%) allele was the highest frequency in the NorthEast group, but there was not significant difference when compared with the other regions in Thais (p-value = 0.4202). HLA-DQB1*06:02 allele was similarly distributed in Thai population and there was no significant difference between Thais and China (3.8%) and South Korea (6.4%) and Japan (8.2%) with p-value > 0.05. Whereas, South Africa (15.7%) has a significance with Thais by p-value of 0.0013. This study supports the specific genotyping of the HLA-DQA1*01:02 and HLA-DQB1*06:02 alleles to screen severe COVID-19 in Thai and many populations.

Keywords: HLA-DQA1*01:02, HLA-DQB1*06:02, Asian, Thai population

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1096 Drug Therapy Problems and Associated Factors among Patients with Heart Failure in the Medical Ward of Arba Minch General Hospital, Ethiopia

Authors: Debalke Dale, Bezabh Geneta, Yohannes Amene, Yordanos Bergene, Mohammed Yimam


Background: A drug therapy problem (DTP) is an event or circumstance that involves drug therapies that actually or potentially interfere with the desired outcome and requires professional judgment to resolve. Heart failure is an emerging worldwide threat whose prevalence and health loss burden constantly increase, especially in the young and in low-to-middle-income countries. There is a lack of population-based incidence and prevalence of heart failure (HF) studies in sub-Saharan African countries, including Ethiopia. Objective: The aim of this study was designed to assess drug therapy problems and associated factors among patients with HF in the medical ward of Arba Minch General Hospital(AGH), Ethiopia, from June 5 to August 20, 2022. Methods: A retrospective cross-sectional study was conducted among 180 patients with HF who were admitted to the medical ward of AGH. Data were collected from patients' cards by using questionnaires. The data were categorized and analyzed by using SPSS version 25.0 software, and data were presented in tables and words based on the nature of the data. Result: Out of the total, 85 (57.6%) were females, and 113 (75.3%) patients were aged over fifty years. Of the 150 study participants, 86 (57.3%) patients had at least one DTP identified, and a total of 116 DTPs were identified, which is 0.77 DTPs per patient. The most common types of DTP were unnecessary drug therapy (32%), followed by the need for additional drug therapy (36%), and dose too low (15%). Patients who used polypharmacy were 5.86 (AOR) times more likely to develop DTPs than those who did not (95% CI = 1.625–16.536, P = 0.005), and patients with more co-morbid conditions developed 3.68 (AOR) times more DTPs than those who had fewer co-morbidities (95% CI = 1.28–10.5, P = 0.015). Conclusion: The results of this study indicated that drug therapy problems were common among medical ward patients with heart failure. These problems are adversely affecting the treatment outcomes of patients, so it requires the special attention of healthcare professionals to optimize them.

Keywords: heart failure, drug therapy problems, Arba Minch general hospital, Ethiopia

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1095 Pharmaceutical Innovation in Jordan: KAP Analysis

Authors: Abdel Qader Al Bawab, Mohannad Odeh, Rami Amer


Recently, there has been an increasing interest in innovative business development. Nevertheless, in the pharmacy practice field, there seems to be a gap in perceptions, attitudes, and knowledge about innovation between practicing pharmacists and academia. This study explores this gap and aspects of pharmaceutical innovation in Jordan, comparing pharmacists and last-year pharmacy students. A validated (r2 = 0.74) and reliable (Pearson’s r = 0.88) online questionnaire was designed to assess and compare knowledge, attitude, and perceptions about pharmaceutical innovation. A total of 397 participants (215 pharmacy students and 182 pharmaceutical professionals) responded. Compared with 50% of the pharmacists, only 32.1% of the students claimed that they knew the differences between pharmaceutical innovation, discovery, invention, and entrepreneurship [x2 (2) = 14.238, p = 0.001; Cramer’s V = 0.189]. Pharmacists demonstrated a higher level of trust in the innovative website design for their institution compared with students (25.3% vs. 16.3%, p < 0.001, Cramer’s V = 0.327). However, 60% of the students did not know the innovative design standards for websites, while the corresponding percentage was 37% for the pharmacists (p < 0.001; Cramer’s V = 0.327). The majority of the students were interested in pharmaceutical innovation (81.9%). Unfortunately, 76.3% never studied innovation in their pharmacy curricula. Similarly, most pharmacists (76.4%) considered adopting innovation, but only 30% had a concrete plan. For the field where pharmacists aim to innovate in the next 5 years, new pharmaceutical services were the dominant field (34.6%). Despite a positive attitude and perception, pharmacists and pharmacy students expressed poor knowledge about innovation. Policies to enhance awareness about innovation and professional educational tools should be implemented.

Keywords: pharmacy, innovation, knowledge, attitude, practice

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1094 Trace Analysis of Genotoxic Impurity Pyridine in Sitagliptin Drug Material Using UHPLC-MS

Authors: Bashar Al-Sabti, Jehad Harbali


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

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

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1093 Assessment of Spatial and Vertical Distribution of Heavy Metals in the Mid Sand Bars of Brahmaputra River in Assam, India

Authors: Vijay Meena, Arup Kumar Sarma, Chandan Mahanta


The environment has been getting contaminated by anthropogenic processes including those that discharge heavy metals to air, soil and water. The present work emphasizes the spatial distribution and vertical profile of six heavy metals (Cu, Zn, Mn, Ni, Fe, Cr) in three layers of mid sand bars (bed surface layer, 50 cm and 100 cm depth) at 42 sampling stations covering around 600 km stretch of the Brahmaputra River, India. Heavy metal analysis was conducted on the sample collected from mid-sand bars in the river stretch to examine the impact of dredging for various hydrological operations in the future. Sediment quality was assessed by calculating six different indices viz., EF, CF, CD, PLI, Igeo, and PERI. In all sediment layers, heavy metal concentrations have been observed to be the same as listed, Fe > Mn > Zn > Ni > Cr > Cu in μg/g. The average concentration of Cu, Mn, and Fe was found in the middle layer while Zn, Ni, and Cr were in the Surface layer. EF indicates higher enrichment in reach 2 which is likely to be due to anthropogenic sources of industrial and urbanized effluents. The sediment of the mid-sand bar was generally found moderately polluted possessing low risk to aquatic lives and the environment. Suggesting, Dredging can be possible in the future. An examination of correlation matrices, principal components analysis, and cluster analyses indicated that these heavy metals possess similar anthropogenic origins for their enrichment.

Keywords: heavy metal contamination, risk assessment, anthropogenic impacts, sediment

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1092 Inventory of Aromatic and Medicinal Plants Used in Natural Cosmetics in Western Algeria

Authors: Faiza Chaib, Yasmina-Nadia Bendahmane, Fatima Zohra Ghanemi


In order to know the traditional use of aromatic and medicinal plants in natural cosmetics, we carried out an ethnobotanical study using an online quiz among the Algerian population residing mainly in western Algeria (Oran, Tlemcen, and Mostaganem). Our study identified 37 plant species used as cosmetic plants, divided into 9 botanical families. The families mainly used and the richest in species are the lamiaceae, the apiecea, and the rutaceae. Our study states that the 5 species with the highest frequency of use and highest citation value are lemon, chamomile, turmeric, garlic, and lavender. Lemon takes first place in the order of frequency. The plants listed have been listed in tables grouping the identification of plants by their scientific and vernacular names, frequency of use, parts used, parts of the body concerned, desired action, as well as the main traditional recipes. This study allowed us to highlight the importance of aromatic plants and to appreciate their traditional practices in natural cosmetics.

Keywords: aromatic plants, ethnobotanical survey, traditional use, natural cosmetics, questionnaire, western Algeria

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1091 Descriptive Study of Adverse Drug Reactions in a Paediatric Hospital in Mongolia from 2015 to 2019

Authors: Khaliun Nyambayar, Nomindari Azzaya, Batkhuyag Purevjav


Pharmacovigilance was officially introduced in Mongolia in 2003, in accordance with the Health Minister Order 183 for the registry of adverse drug reactions (ADR), approved in 2006 and was reviewed in 2010. This study was designed to evaluate the incidence and common types of adverse drug reactions among hospitalized children, the frequency of adverse drug reaction reported by health care providers, and the follow-up processes resulting from adverse drug reactions. A retrospective study of paediatric patients who experienced an adverse drug reaction from 2015 to 2019, extracted from the “yellow” card at the State Research Center for Maternal and Child Health, (city). A total of 417 adverse drug reactions were reported with an overall incidence was 80 (21.5%). Adverse reactions resulting from the use of antibiotics (particularly gentamycin, cephalosporins, and vancomycin) were usually mild. ADR’s were reported by physicians and nurses (93.8%), pharmacists (6.25%). Although documentation of physician notification occurred for 93% of adverse drug reactions, only 29% of cases were documented in the patient's medical chart, 13% included follow-up education for individuals involved, and 10% were updated in the allergy profile of the hospital computer system. Measures to improve the detection and reporting of adverse drug reactions by all health care professionals should be improved, to enhance our understanding of the nature and impact of these reactions in children.

Keywords: adverse drug reaction, pediatric, yellow card, Mongolia

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1090 An Insight into the Interaction Study of a WhiB Protein and its Binding Partner

Authors: Sonam Kumari


Tuberculosis is the deadliest disease worldwide. Millions of people lose their lives every year due to this disease. It has turned lethal due to the erratic nature of its causative organism, Mycobacterium tuberculosis (Mtb). Mtb tends to enter into an inactive, dormant state and emerge to replicating state upon encountering favorable conditions. The mechanism by which Mtb switches from the dormant state to the replicative form is still poorly characterized. Proteome studies have given us an insight into the role of certain proteins in giving stupendous virulence to Mtb, but numerous dotsremain unconnected and unaccounted. The WhiB family of proteins is one such protein that is associated with developmental processes in actinomycetes. Mtb has seven such proteins (WhiB1 to WhiB7). WhiB proteins are transcriptional regulators; they regulate various essential genes of Mtbby binding to their promoter DNA. Biophysical parameters of the effect of DNA binding on WhiB proteins has not yet been appropriately characterized. Interaction with DNA induces conformational changes in the WhiB proteins, confirmed by steady-state fluorescence and circular dichroism spectroscopy. ITC has deduced thermodynamic parameters and the binding affinity of the interaction. Since these transcription factors are highly unstable in vitro, their stability and solubility were enhanced by the co-expression of molecular chaperones. The present study findings help determine the conditions under which the WhiB proteins interact with their interacting partner and the factors that influence their binding affinity. This is crucial in understanding their role in regulating gene expression in Mtbandin targeting WhiB proteins as a drug target to cure TB.

Keywords: mycobacterium tuberculosis, TB, whiB proteins, ITC

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1089 Curcumin-Loaded Phenethyl Isothiocyanate Nano-Spheres: Preparation, Stability Study, and Its Implication for Cataract Prevention

Authors: Pankaj Dinesh Baviskar


This study examines the impact of curcumin-loaded nano-spheres in the form of emulsions on fish eye cataracts. Curcumin nanoemulsions were prepared by using phenethyl isothiocyanate. Nanoemulsions were synthesized by ultrasound-assisted method at 150 Watt. A zeta potential measurement for curcumin-loaded nanoemulsions was found to be -30.7eV, -13.4eV, and -9.55eV, and particle size was found to be 149.3 nm, 245.3 and nm 403.5 nm using particle size analyzer respectively for different conditions. The surface morphology of nano-spheres was examined by FE-SEM analysis. The zeta potential measured indicates its stability for corresponding nano-spheres. The anti-cataract application was studied by using isolated fish eye lenses. The cataract was induced using high glucose concentrated solution. The biochemical parameters in the form of reduced glutathione were measured to interpret the anti-cataract ability of curcumin-loaded nanoemulsions.

Keywords: curcumin, nano, cataract, nanoemulsion

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1088 Chitosan-Whey Protein Isolate Core-Shell Nanoparticles as Delivery Systems

Authors: Zahra Yadollahi, Marjan Motiei, Natalia Kazantseva, Petr Saha


Chitosan (CS)-whey protein isolate (WPI) core-shell nanoparticles were synthesized through self-assembly of whey protein isolated polyanions and chitosan polycations in the presence of tripolyphosphate (TPP) as a crosslinker. The formation of this type of nanostructures with narrow particle size distribution is crucial for developing delivery systems since the functional characteristics highly depend on their sizes. To achieve this goal, the nanostructure was optimized by varying the concentrations of WPI, CS, and TPP in the reaction mixture. The chemical characteristics, surface morphology, and particle size of the nanoparticles were evaluated.

Keywords: whey protein isolated, chitosan, nanoparticles, delivery system

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1087 The European Pharmacy Market: The Density and its Influencing Factors

Authors: Selina Schwaabe


Community pharmacies deliver high-quality health care and are responsible for medication safety. During the pandemic, accessibility to the nearest pharmacy became more essential to get vaccinated against Covid-19 and to get medical aid. The government's goal is to ensure nationwide, reachable, and affordable medical health care services by pharmacies. Therefore, the density of community pharmacies matters. Overall, the density of community pharmacies is fluctuating, with slightly decreasing tendencies in some countries. So far, the literature has shown that changes in the system affect prices and density. However, a European overview of the development of the density of community pharmacies and its triggers is still missing. This research is essential to counteract against decreasing density consulting in a lack of professional health care through pharmacies. The analysis focuses on liberal versus regulated market structures, mail-order prescription drug regulation, and third-party ownership consequences. In a panel analysis, the relative influence of the measures is examined across 27 European countries over the last 21 years. In addition, the paper examines seven selected countries in depth, selected for the substantial variance in their pharmacy system: Germany, Austria, Portugal, Denmark, Sweden, Finland and Poland. Overall, the results show that regulated pharmacy markets have over 10.75 pharmacies/100.000 inhabitants more than liberal markets. Further, mail-order prescription drugs decrease the density by -17.98 pharmacies/100.000 inhabitants. Countries allowing third-party ownership have 7.67 pharmacies/100.000 inhabitants more. The results are statistically significant at a 0.001 level. The output of this analysis recommends regulated pharmacy markets, with a ban on mail-order prescription drugs allowing third-party ownership to support nationwide medical health care through community pharmacies.

Keywords: community pharmacy, market conditions, pharmacy, pharmacy market, pharmacy lobby, prescription, e-prescription, ownership structures

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