World Academy of Science, Engineering and Technology

Authors: Catherine Mae C. Cuya, Sofia Antonienne Allarde, Kent Vinzcent R., De Castro, Ma. Alysson C. Dedell, Amerah M. Maruhom, Marielle Jazmin A. Sebastian, Omar A. Villalobos, Irish Mhel C. Mitra, Mary Jho-Anne T. Corpuz

Abstract:

The increasing demand for safer and eco-friendly dermatological treatments has driven interest in natural alternatives for skin disorders. This study explored the potential of ethanolic seed extract from Swietenia macrophylla as an anti-melanogenic agent, with the goal of developing a preformulated dosage form. The extract underwent physicochemical evaluation and organoleptic assessments to determine its stability and suitability for formulation. To confirm its anti-melanogenic activity, zebrafish (Danio rerio) embryos were used as an in vivo model, where imaging techniques assessed melanin inhibition. Additionally, toxicity classification, survival, and mortality rates, and ocular melanin content were analyzed across three replicates. Data were subjected to one-way analysis of variance (ANOVA) and post-hoc Tukey test, with results expressed as mean ± standard deviation. Furthermore, excipient compatibility and stability testing under controlled conditions were conducted to ensure the formulation’s stability and efficacy. The findings demonstrated the potential of S. macrophylla as a natural anti-melanogenic agent, paving the way for its application in cosmetic and dermatological formulations.

Keywords: Swietenia macrophylla, anti-melanogenic, zebrafish, ethanolic extract, excipient compatibility, stability testing, cosmetic formulation

Procedia PDF Downloads 10

Authors: Sara Alhassan

Abstract:

The Saudi Food and Drug Authority (SFDA) sets pricing rules for pharmaceutical products to promote fair pricing and ensure equitable access to essential drugs. The registration of pharmaceutical products is valid for five years for each concentration, medicinal formula, or package and the price is revised at the renewal phase based on the common pricing criteria outlined in the pricing guidelines. Revising the product price will determine the pricing department's recommendation if the product price will be reduced or remain at the same current price. The previous practice (2019-2021) for repricing medicines was based on reviewing all pharmaceutical products according to criteria specified in the previous pricing guidelines. After establishing the new pricing guidelines in the year 2021, which aimed to ensure fairness and equitable access to essential medicines by regulating the prices. The prices of pharmaceutical products should be set at an affordable level for all stakeholders, including patients, healthcare providers, and governments. This study aims to examine the impact of the new regulation of pharmaceutical pricing on the practice of the pharmaceutical renewal registration phase at SFDA. By Measuring and comparing different variables as the number of applications submitted for renewal reversion to the number of applications closed without price reductions versus the number of applications eligible for price reductions and the number of appeals to the approved prices after the revision. These findings will provide valuable insights into the effectiveness and efficiency of the new pricing practice established by the SFDA.

Keywords: pricing regulations, price revision, pharmaceutical products, renewal phase

Procedia PDF Downloads 8

Authors: Ramy Reda Morgan Kamel

Abstract:

The idea of myocardial injury, despite the fact that first identified from animal studies, is now identified as a clinical phenomenon which can bring about microvascular harm, no-reflow phenomenon, myocardial lovely, myocardial hibernation and ischemic preconditioning. The final result of this occasion is left ventricular (LV) systolic disorder main to elevated morbidity and mortality. the standard scientific case of reperfusion damage takes place in acute myocardial infarction (MI) with ST segment elevation wherein an occlusion of a major epicardial coronary artery is accompanied through recanalization of the artery. this will arise either spontaneously or by thrombolysis and/or by means of number one percutaneous coronary intervention (PCI) with green platelet inhibition by using aspirin (acetylsalicylic acid), clopidogrel and glycoprotein IIb/IIIa inhibitors. In latest years, percutaneous coronary intervention (PCI) has emerge as a well-mounted approach for the remedy of coronary artery ailment. PCI improves symptoms in patients with coronary artery disorder and it's been increasing the safety of strategies. but, peri- and submit-procedural myocardial harm, including angiographical sluggish coronary float, microvascular embolization, and extended degrees of cardiac enzyme, along with creatine kinase and troponin-T and -I, has additionally been mentioned even in non-compulsory instances. moreover, myocardial reperfusion harm at the start of myocardial reperfusion, which reasons tissue damage and cardiac disorder, can also occur in cases of the acute coronary syndrome. due to the fact patients with myocardial damage is related to larger myocardial infarction and have a worse long-time period analysis than those without myocardial damage, it's far important to prevent myocardial harm throughout and/or after PCI in sufferers with coronary artery ailment. thus far, many studies have proven that adjunctive pharmacological treatment suppresses myocardial damage and increases coronary blood go with the flow throughout PCI strategies. in this evaluation, we spotlight the usefulness of pharmacological treatment in mixture with PCI in attenuating myocardial harm in sufferers with coronary artery disease.

Keywords: electromagnetic solar system, nano-material, nano pharmacology, pharmacovigilance, quantum theoryclinical simulation, education, pharmacology, simulation, clinical pharmacology, pharmacometrics, career development pathways

Procedia PDF Downloads 7

Authors: Titus Emmanuel Onugba, Joseph. C. Oguegbulu

Abstract:

The reduced efficacy of metronidazole in the treatment of diarrheal diseases is mainly due to lower concentrations of the drug reaching the colonic site of action. Biopolymers like locust bean gum (LBG) and chitosan have been useful biopolymers in developing controlled-release matrices for drugs. In this work, efforts were made to develop a biopolymer composite of chitosan and LBG as coating films on metronidazole for improved colon-specific delivery of metronidazole. A ratio of 1:2 Chitoas/LBG was used to prepare four coating levels of biopolymer coating solution, F1, F2, F3, and F4, corresponding to 10%, 20%, 30%, and 40%, respectively, of average tablet weight. A dip-coating method was used to coat metronidazole tablets in triplicates. KH₂PO₄ and NaOH were used to prepare simulated colonic fluid USP (pH 6.8), while 0.1N HCl was used as simulated gastric fluid (pH 1.2) without enzyme. In vitro drug release studies showed that F4-coated tablets had the maximum drug release of 48% after I hr. in SGF. In SCF on the other hand, F4-coated tablets showed the lowest drug release of 60.3% after 30 minutes, with F3-coated tablets showing maximum drug release. Overall, our coated tablets show higher drug release in colonic medium compared to the gastric medium, suggesting that our developed pharmaceutical system may be capable of controlled release of metronidazole to the colonic site of action. These findings present an opportunity for modifications in the pharmaceutical formulation of metronidazole to improve its efficacy in the treatment of diarrheal infections, as well as larger implications for other drug formulations.

Keywords: biopolymer composites, chitosan, dissolution studies, drug delivery, locust bean gum

Procedia PDF Downloads 7

Authors: Md. Suman

Abstract:

Objective: The main objective of this study was to evaluate the knowledge of antibiotic resistant among Bangladeshi pharmacy customers.Methods: Study was conducted among Bangladesh pharmacy customers different area in the Dhaka city. The questionnaire covered 1) Patients age-15 year to 50 years & sex are both male & female 2) knowledge of antibiotics and antibiotic resistance 3) Antibiotics use with or without registered doctor’s prescriptionResults: Among 524 participants, 60.4% (n=317) male & 39.5% (n=207) female, 40.2 %( n=211) had initial knowledge of antibiotics resistant in general and 59.7 %( n=313) had don’t have knowledge of antibiotic resistance. Simultaneously, more than 60.6 %( n=318) patient’s/Participant’s take antibiotics without doctor’s prescription from pharmacy as per dispenser advice they are always suggested antibiotics to the pharmacy customers when patient’s sufferer colds, influenza, cough & fever. Only 35.69% (n=187) patient’s take antibiotics with registered doctor’s prescription. Total number of participant 45.42% (n=238) patient’s take antibiotics Without registered doctor’s prescription as well as only 18.89% (n=99) take medicines without antibiotics. On the other hand prescription dispense by registered pharmacist 29.20 %( n=153) and prescription dispense by without pharmacist 70.80 %( n=371). Conclusions: High level of knowledge of antibiotics and antibiotic resistance among Bangladesh pharmacy customers, there are obvious knowledge gaps. We suggest that action is taken to increase the knowledge level, and particularly target people in vocational, male dominated occupations outside the health service.

Keywords: antibiotics, antibiotics resistant, knowledge of antibiotics, miss use of antibiotics

Procedia PDF Downloads 12

Authors: Olivier Ndogo Eteme, Victorine Ezami Meyomesse

Abstract:

Objectives: Bacterial resistance to conventional antibiotics is a serious public health problem. Over the past decade, small proteins known as antimicrobial peptides (AMPs), natural compounds produced by all prokaryotic and eukaryotic cells, have shown promising results in overcoming the growing problems of antibiotic resistance. There are nowadays several cysteine-rich peptides of plant origin that have shown very good antimicrobial activities. The research of molecules with bactericidal activity with a lack of multi-resistance is always a current event. The present study was undertaken to investigate the in vitro antibacterial activities of four synthesized peptides obtained in 97% yield. Method: This reaction, by solid phase synthesis method was monitored by combining HPLC and LC/MS methods. The antibacterial test was performed using microdilution method. Results: The conformity and effectiveness of the synthesis of the peptides was carried out by LC/MS with an average yield of 97%. Both synthesized peptides were bactericidal on all tested strains, unless Neo1 which is bacteriostatic on E. coli ATCC 25922 strain. The biofilm eradication capacity test was carried out on two ATCC strains of S. epidermidis. Strain ATCC 35984 is a good biofilm-forming strain, while strain ATCC 12228 is considered a poor biofilm former. Comparison of the presence of biofilm between them showed a significant difference with p<0.05, showing that the controls used are significantly different in all cases. In addition, both synthesized peptides do not present hemolytic properties, therefore making them good drug candidates. Conclusion: Antimicrobial peptides are a good alternative today to fight against microbial resistance. So, new Neo synthesized peptides (Neo1, Neo2, Neo3 and Neo4) could serve as a basis for preclinical approaches to potential new active ingredients to combat certain microbial resistance.

Keywords: solid phase synthesis, peptides, antibacterial activity, microbial resistance, protease stability

Procedia PDF Downloads 7

Authors: Priyanka Shinde, Mukesh Bansal, Yeganeh Donyanavard, Sreekanth Pentlavalli, Adrian Kelly, Anant Paradkar

Abstract:

This study aimed to investigate the feasibility of utilizing ionic liquid for the development of solid oral dosage forms of ibuprofen as conventional tablets. As Ionic liquids (ILs) are organic salts that contain anions and cations with melting points (Tm) and glass transition (Tg) below 100°C. Holding desirable properties such as high ionic conductivity, excellent solvents, low volatility, and thermal stability, for improving solubility and bioavailability of ibuprofen. Considering these properties, the research mainly focuses on creating a polymeric ionic mixture suitable for tablet production and investigating different formulation techniques to optimize the process. For preparation of Ibu-Ionic Liquid, API (Ibuprofen), Triethanolamine (Tea), Di iso propanolamine (Dipa) were used, followed by Polymers; PVA, PEO, PVP, HPMC-AS were used to create Polymeric Ionic liquid in various ratios such as (IL (TEA): HPMCA-AS 1:2.5, 1:3, 1:4, IL (TEA): PVA 1:2.5,1:3,1:4 and same with ionic liquid (DIPA) etc. The formed product then subjected to direct compression along with bulking agents and lubricant (Lactose, Calcium phosphate, Magnesium Stearate etc.) having varied concentration of each ingredient to optimize the formulation. Additionally, Different analytical tests were performed to support this finding such as thermal gravimetric analysis (TGA), Differential scanning colorimetry (DSC), Fourier transfer infra-red (FTIR), to check the composition of the formed Ionic Liquids and ILs polymeric mixture. The drug release profiles of the final formulations were assessed via dissolution studies. Conclusion: The generated ILs exhibited promising disintegration and dissolution profiles which can be used to formulate conventional oral tablets.

Keywords: ibuprofen, Ils ionic liquids, ILs polymeric mixture, solubility, bioavailability

Procedia PDF Downloads 6

Authors: Tayba Akram

Abstract:

The transdermal drug delivery is now a promising route for drug delivery systems. This route has the potential advantage of avoiding hepatic first-pass metabolism, decreasing side effects gastrointestinal effects, improving patient compliance and increasing bioavailability. The major limitation of this route is the difficulty of permeating the drug through the skin. The formulation is carried out to develop matrix-type transdermal patches containing Amlodepine besylate and polymer Eudragit by solvent casting method. Different ratios of Propylene glycol are used as plasticizers & Tween 80 is used as a permeation enhancer appropriate ratio of two solvents, ethanol and methanol, is used for effective mixing. The possible drug-polymer interactions were studied. Formulated transdermal patches were evaluated with regard to physicochemical characteristics, in-vitro permeation studies and stability studies. All the prepared formulations showed good physical stability. The in-vitro permeation studies were performed using the Franz diffusion cell. Out of all the formulated patches, F 8 showed good permeation in 24 hrs. So, these two formulations were selected as the best formulations.

Keywords: drug delivery, gastrointestinal effect, Amlodepine besylate, Eudragit

Procedia PDF Downloads 11

Authors: Giulia Di Prima, Maria Elena Mauceri, Giovanna Giuliana, Viviana De Caro

Abstract:

Oral Lichen Planus (OLP) is a chronic, non-infectious inflammatory disease of the oral cavity characterized by symmetrical and bilateral lesions or multiple lesions affecting the buccal mucosa, the tongue, and the gingiva, causing severe pain and impairing patients’ quality of life. The conventional OLP treatment involves the topical administration of corticosteroids and clobetasol-17-propionate (CLB) remain the primary therapeutic option, even if there are no commercially available pharmaceutical forms intended for oromucosal application. An underestimated aspect of OLP pathogenesis is the role of oxidative stress. During inflammation, the generation of ROS is significantly enhanced. The latter can cause damage to several cellular components as protein, membrane lipids, nucleic acids, etc., inducing genetic mutations and playing a critical role in the potential malignant degeneration. A recent systematic review of over 1154 studies has demonstrated that antioxidants might not only effectively reduce pain but also increase the disease resolution rate and prevent potentially malignant outcomes. Among natural antioxidants resveratrol (RSV) is a polyphenol that was recently focused by researchers due to its biological actions by which it could be useful in the management of OLP in co-administration with conventional corticosteroids. However, both RSV and CLB suffer from several drawback related to their formulation and administration. Based on these considerations, the aim of this work was to develop novel, personalizable and patient-friendly drug delivery systems for the loco-regional clinical administration of CLB or co-administration of CLB+RSV to treat OLP lesions in order to evaluate both i) the clinical efficacy of stand-alone CLB when administered through a standardizable and innovative formulation instead of the conventionally used ones and ii) the clinical efficacy of the co-administration of the two selected active molecules, in terms of healing rate respect the control group (administration of a conventional CLB-loaded semisolid formulation). To address this issue while also overcoming the limitations of the chosen drugs a microcomposite patch was designed and characterized. Lipid-based microparticles (LMPs) as solid lipid microparticles (SLM) and microstructured lipid carriers (MLC) were then optimized to encapsulate CLB and RSV, respectively. The LMPs were prepared according to a patented technique and were accurately designed to be applied into the oral cavity. They thus resulted suitable in terms of melting temperature range (compliant with the oral temperature) and particle size (<450 μm). Moreover, in view of their next use for the preparation of the final dosage forms, they were further investigated as pharmaceutical intermediate in terms of particle shape and flow properties. Subsequently, two different buccal patches were prepared by dispersing the LMPs into a mucoadhesive hydrophilic gel then subjected to solvent casting: the CLB series patches were loaded only with the SLM-CLB, while the CLB+RSV series patches contained both SLM-CLB and MLC-RSV. Both formulations resulted soft, deformable, homogeneous, reproducible, mucoadhesive, low swellable and potentially comfortable for patients. Finally, their ex vivo ability to promote actives entry into the buccal tissue was also demonstrated, making them promising drug delivery systems for a further clinical trial actually in progress (Oral Medicine Unit, Palermo University Hospital Policlinico “P. Giaccone”).

Keywords: buccal patch, clobetasol-17-propionate, lipid microparticles, oral lichen planus, resveratrol

Procedia PDF Downloads 24

Authors: Susan Sarhadi, Seyedeh Alia Moosavian, Mohammad Mashreghi, Niloufar Rahiman, Shiva Golmohamadzadeh, Kayvan Sadri, Jamshidkhan Chamani, Mahmoud Reza Jaafari

Abstract:

Orally administered Insulin has to survive the harsh gastrointestinal tract condition, penetrate the enteric epithelial barrier, and bypass the first pass effect before reaching the bloodstream. To address this problem, PEGylated liposomal insulin was prepared and modified with B12 to improve the stability and absorption of insulin in the gastrointestinal environment. Liposomes were prepared by film method plus extrusion, linked to B12, and characterized for their particle size, zeta potential, and encapsulation efficiency (EE%). The release profile in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were evaluated. The results indicated that B12-targeted PEGylated liposomes were more stable than non-functionalized Lip-PEG in SGF and SIF. In vitro, results showed significantly enhanced cellular uptake of B12-targeted PEGylated liposomes in Caco-2 cells compared to non-targeted liposomes. In the meantime, they had no toxicity on Caco-2 cells. In BALB/c mice, B12-targeted PEGylated liposomes showed higher insulin accumulation in the intestine and liver. In diabetic rats B12 targeted PEGylated liposomes provided higher insulin bioavailability compared with other formulations. These findings suggest that B12-targeted liposomes could be an effective formulation for oral delivery of insulin and merits further investigations.

Keywords: insulin, liposomes, vitamin B12, oral delivery

Procedia PDF Downloads 18

Authors: Sajad Khaliq Dar, Dipanjan Goswami, Arshad H. Khuroo, Mohd. Akhtar, Pulak Kumar Metia, Sudershan Kumar

Abstract:

Background: Development of modified-release oral dosage formulations (OSD) like tacrolimus in narrow therapeutic categories, together with high levels of intra-individual variability, impose greater challenges. The risk assessment for bioequivalence studies requires developing a suitable design through pilot studies involving the comparison of multiple formulations of the same product with a marketed product to understand the in-vivo behaviour. These formulations could have varying coating levels and other minor quantitative differences to achieve the desired release rate for the final product. Although small-scale studies are critical before the conduct of full-scale Pharmacokinetic (PK) studies, regulatory agencies evaluate critical bioavailability attributes (CBA) before approving the submitted dossiers. Since Tacrolimus is a BCS Class II drug, therefore developing the extended-release formulation, in addition to associated challenges, provides an opportunity to present the In vitro-in vivo correlations (IVIVC) to regulatory agencies, not only to exhibit product quality but also to reduce the burden of additional human trials and cost involved to them for bringing the product to market. Objective: The objective of this study was to develop a Level-A In vitro - In vivo Correlation (IVIVC) model for Sun Pharma’s test formulation Tacrolimus ER tablet 4mg and extend its application to a widened dissolution window of 25% at 2.5 hours (critical release time) sampling time point. Experimental Procedure: Post the conduct of two in-vivo studies, a pilot study evaluating two test prototypes on 24 subjects (under fasting) and a pivotal study having 50 subjects (under fasting), the observed pharmacokinetic profile was used for IVIVC model development. The dissolution media used was 0.005% HPC + 0.25% SLS in Water 900 mL at pH 4.50 using USP II (Paddle) apparatus with alternative sinkers operated at 100 RPM. The sampling time points were chosen to mimic the drug absorption in vivo. The dissolution best fit to data was obtained using Makoid Banakar kinetics. Then deconvolution, anchoring to concepts of the single compartment by Wagner Nelson method was applied for tacrolimus slow-release formulation batch with film coating weight build-up of 5.4% (used in pilot bio study), medium release with Hypromellose (retard-release exhibit batch used in the pivotal study) and fast release formulation batch with film coating weight build-up of 5.05% (used in pilot bio study). Results and Conclusion: The results were deemed acceptable as prediction errors for internal and external validation were < 3% depicting in-vitro drug release mimics in-vivo absorption. Moreover, the prediction result for the Test/Reference ratio was <15% for all test formulations and widening dissolution (i.e., 39%-64% drug release at 2.5hrs) predictions were well within 80-125% when compared against Envarsus XR (reference drug). This IVIVC-validated model can be used in the futuristic exploration of dose titration with 1mg tacrolimus ER OSD as a surrogate for In-vivo bioequivalence trials.

Keywords: pharmacokinetics, BCS, oral dosage form, Bioavailability, intra-individual variability

Procedia PDF Downloads 22

Authors: Patcharaporn Sudchada, Nuntika Prommee

Abstract:

Background: Herbal medicines constitute a vital component of Thailand's healthcare system and possess significant potential for international recognition. However, the absence of standardized clinical research guidelines aligned with international standards, coupled with unique local challenges, has hindered the development and registration of Thai herbal medicines in the global market. Objective: To establish comprehensive research and development guidelines for herbal medicine formulations that comply with international standards, with particular emphasis on enhancing research quality, scientific credibility, and facilitating both domestic registration and international market acceptance. Methods: The research methodology comprised eight sequential phases: (1) systematic collection and review of relevant documentation and regulatory frameworks; (2) development of preliminary content structure and template designs; (3) systematic analysis and synthesis of scientific evidence and regulatory data; (4) creation of detailed research guidelines and accompanying templates; (5) execution of domestic and international consultation meetings and study visits involving nine stakeholder groups; (6) systematic expert review of the draft guidelines; (7) incorporation of feedback from relevant regulatory and research agencies; and (8) finalization and validation of the comprehensive guidelines. Results: The study produced comprehensive research and development guidelines for herbal medicines that meet international standards, encompassing the complete development pathway from initial concept through pre-clinical studies, product development, preparation protocols, clinical trial conduct, and product registration procedures. The guidelines include standardized templates and forms specifically designed for clinical research documentation. Conclusion: The established guidelines represent a significant advancement in standardizing clinical research for Thai herbal medicines, enhancing their scientific credibility and potential for international acceptance. Nevertheless, Thailand continues to face specific challenges, including insufficient specialized personnel in herbal research (particularly in clinical trials), challenges in integrating traditional Thai medicine principles with modern scientific methodology, limited research infrastructure, inadequate funding mechanisms, complex registration procedures, and public skepticism toward herbal products. The policy recommendations outlined in this research provide a strategic framework for addressing these challenges and promoting sustainable development of Thai herbal medicines within the national context.

Keywords: herbal medicine, clinical research, international standards, research guidelines, drug development, traditional thai medicine, regulatory compliance

Procedia PDF Downloads 29

Authors: Marwan Abdel Baset, Sally A. El Awdan, Marwa S. Khattab, Salma A. El-Marasy

Abstract:

Rivaroxaban (RVX) id used to treat thrombosis however its effect on testicular IR hasnot been investigated yet. This study investigates the effect of RVX on testicular ischemia-reperfusion in rats. Rats were randomly allocated into 4 groups. The sham group, testicular ischemia-reperfusion (IR) group, the remaining 2 groups were treated with RVX in doses of7 and 14 mg/kg, respectively for a week prior IR. Then biochemical parameters were carried out in addition to western blot analysis. RVX-treated groups showed significant reduction in protein expression of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF) associated with elevation in testosterone level, reduction in malondialdehyde (MDA), elevation in glutathione peroxidase (GPX), reduction in nuclear factor kappa-B p65 (NF-ĸb p65), reduction in Bax (Bcl2-associated X protein) and elevation in BCL2 (B-cell lymphoma 2), content. Moreover, RVX reduced caspase-3 protein expression. It can be concluded that HIF-1α mediated RVX’s anti-oxidant, anti-inflammatory and, anti-apoptotic effect in rats subjected to testicular IR.

Keywords: HIF-1α, rats, rivaroxaban, testicular ischemia-reperfusion

Procedia PDF Downloads 23

Authors: Ramy Reda Morgan Kamel

Abstract:

generation-greater education gear are being unexpectedly included into health packages globally. these gadget provide an interactive platform for students and may be used to deliver topics in various modes which include video games and simulations. Simulations are of particular hobby to healthcare education, wherein they are hired to enhance clinical know-how and help to bridge the distance among precept and exercise. Simulations will regularly test talents for practical responsibilities, but restrained research examines the effects of simulation on student perceptions of their getting to know. The aim of this observe become to determine the effects of an interactive virtual patient simulation for pharmacology schooling and clinical workout on scholar know-how, skills and confidence. Ethics popularity of the examine end up received from Griffith college studies Ethics Committee (PHM/eleven/14/HREC). The simulation became intended to duplicate the pharmacy surroundings and affected man or woman interaction. The content material material come to be designed to beautify know-how of proton-pump inhibitor pharmacology, role in therapeutics and secure deliver to sufferers. The tool changed into deployed into a 3rd-year scientific pharmacology and therapeutics course. a number of core exercise regions were examined along with the competency domains of wondering, counselling, referral and product provision. Baseline measures of pupil self-stated knowledge, capabilities and self warranty were taken preceding to the simulation using a especially designed questionnaire. A greater substantial questionnaire became deployed following the virtual affected character simulation, which moreover blanketed measures of scholar engagement with the hobby. A quiz assessing scholar proper and conceptual understanding of proton-pump inhibitor pharmacology and associated counselling statistics changed into also included in both questionnaires.

Keywords: electromagnetic solar system, nano-material, nano pharmacology, pharmacovigilance, quantum theoryclinical simulation, education, pharmacology, simulation, clinical pharmacology, pharmacometrics, career development pathways

Procedia PDF Downloads 30

Authors: Nguyen Dang Duc, Nguyen Phuong Sinh, Lam Nguyen Hong Anh

Abstract:

Superior mesenteric artery (SMA) syndrome is a rare cause of high-section intestinal obstruction. SMA syndrome is characterized by compression of the third segment of the duodenum due to the narrowing of the distance between the superior mesenteric artery and the abdominal aorta. The main clinical signs of SMA syndrome are high intestinal obstruction, such as postprandial vomiting, epigastric pain, early feeling of abdominal fullness, and indigestion. Abdominal computed tomography plays an important role in diagnosis. There are two main methods of treating SMA syndrome that are conservative and surgical treatment. We report a clinical case of an 18-year-old male patient admitted to the hospital because of a Bungarus snake bit in the second hour, to the twelfth day of treatment, the patient developed diarrhea that lasted until the twenty-fourth day of treatment. On the twenty-fifth day of treatment, the patient lost 16 kilograms (from 56 down to 40). The patient had symptoms of vomiting after eating, indigestion, and epigastric pain. On abdominal computed tomography, the angle created by the superior mesenteric artery and the abdominal aorta was 17 degrees, the distance between the two arteries was 3.8 millimeters, light dilation and stagnation of the D1 and D2 segment of the duodenum with gas and watery level inside segment D3 and D4 of the duodenum and this segment was constricted. This patient was diagnosed with superior mesenteric artery syndrome with the Bungarus snake bites. Currently, the patient was treated with feeding through a jejunal tube each other intravenous nutrition. Finally, The patient was discharged and returned to his house on the forty-fifth day of treatment. We reported this clinical case to introduce clinical and paraclinical signs, diagnose, and methods treated for patient having SMA syndrome.

Keywords: superior mesenteric artery syndrome, Bungarus snake bites, loss weight

Procedia PDF Downloads 25

Authors: Ragy Raafat Gaber Attaalla

Abstract:

Background: The research begins with a summary of the state of pharmacy practice research, both now and in the future. The concerns that are relevant to practice research are then covered in this research to set the stage. These concerns include shifts in the demography of the population, technological advancements, the institutional function of pharmacies, consumer behavior, and the pharmacy profession itself. It also describes the significant changes in pharmacy practice research, such as interprofessional collaboration and patient teaming, the description and measurement of intervention results, and the cultural diversity of patients. Methods: It would be most frequently employed in the next pharmacy practice research are highlighted in the conclusion. They cover the cultural diversity of patients, documenting and assessing the results of interventions, and interdisciplinary communication and partnership with patients. Results: The rise of large and complicated data sets, the handling of electronic health records, and the use of a wide range of mixed techniques by pharmacy practice researchers are a few potential future methodological obstacles.

Keywords: pharmacy, practice, research, significant changes

Procedia PDF Downloads 24

Authors: Rania Awad, Avi Avital, Alejandro Sosnik

Abstract:

Neurodevelopmental disorders, including autism spectrum disorder (ASD), affect 5.9% of the global population. Recently, research indicated the potential therapeutic use of cannabidiol (CBD) to treat different neurodevelopmental disorders, including ASD. Intranasal drug delivery (IN) is a non-invasive and painless administration route that enhances drug bioavailability in the brain by bypassing the blood-brain barrier. However, IN has limited bioavailability due to the low nasal mucosa permeability. Various polymeric nanoparticles (NPs) have been investigated for IN delivery with different successes. In this study, we investigate the nanoencapsulation of CBD within self-assembled polymeric NPs for nose-to-brain delivery in ASD to increase the bioavailability of CBD in the brain. The nanoencapsulation of CBD within self-assembled polymeric NPs, namely poly (ethylene oxide)-b-poly (propylene oxide)-b-poly (ethylene oxide) (PEO-PPO-PEO) polymeric micelles, was assessed. The CBD-loaded system was characterized by different methods. The compatibility was assessed in the nasal septum epithelium cell line Rpmi 2650. In vitro, permeability studies were conducted using Rpmi2650 cell monolayers cultured in semipermeable membranes 2650. The accumulation of CBD-loaded NPs labeled with near-infra-red fluorescent dye in the brain was measured after IN and oral administration after 20 and 45 min using IVIS spectrum CT imaging (IVIS-CT). Pharmacokinetic (PK) studies were conducted to assess the CBD concentration in rat plasma and brain tissues at different time points, PK parameters were measured and analyzed. Then, the effect of IN and oral administration of CBD-loaded NPs on a social cooperation test, which is a relevant behavioral test in the ASD model in rats, was investigated. Initially, we produced Pluronic® F127 polymeric micelles loaded with 25% w/w of CBD, with a size of 23 ± 1 nm, with suitable physical properties for IN administration. Then, Pluronic® F127 nanoparticles (F127 NPs) in the medium showed good compatibility and permeability in Rpmi 2650 cells. In the IVIS-CT study, the accumulation of IN administration of CBD-loaded F127 in the rat's brains was higher than the oral. Pharmacokinetic analysis of rat brain tissues revealed that, 20 minutes after administration, the concentration of CBD was higher following a 5 mg/kg nasal administration compared to a 15 mg/kg oral administration of CBD-loaded F127. Followed by IN administration of CBD-loaded F127 improved the social cooperation performance of the ASD model in rats as compared to oral and control groups.

Keywords: drug delivery to the brain, Intranasal drug delivery, nanoencapsulation, neurodevelopmental disorders, polymeric nanoparticles.

Procedia PDF Downloads 24

Authors: Fatima Zohra Belghait, Nawal Cheikh, Oscar Palacios, Ramon Barnadas, Pau Bayon

Abstract:

Metalloporphyrin and its derivatives play an important role in different scientific areas due to its tetradentate vacant site in the center that is suitable for metal coordination. Metalosomes (MTS) are supramolecular aggregates (similar to liposomes) generated by the self-assembly of compounds similar to phospholipids (with a polar and a hydrophobic part), but incorporating, as part of their membrane, molecules that contain bound metals. The aim of our work is to synthesise metalosomes containing catioinc amphiphilic porphyrin and their complexes with Fe and Cu to study their therapeutical applications. All synthesized compounds were confirmed with Dynamic Light Scattering; elemental analysis, Ultraviolet–visible spectroscopy

Keywords: metalloporphyrin, amphiphilique porphyrin, metalosomes, supramolecular

Procedia PDF Downloads 24

Authors: Katie M. Clark, Adriana A. Tienda, Krista C. Paffenroth, Lindsey N. Brigante, Daniel C. Colvin, Jose Maldonado, Erin S. Calipari, Fiona E. Harrison

Abstract:

Manganese (Mn) is an essential trace element required for human health and is important in antioxidant defenses, as well as in the development and function of dopaminergic neurons. However, chronic low-level Mn exposure, such as through contaminated drinking water, poses risks that may contribute to neurodevelopmental and neurodegenerative conditions, including attention deficit hyperactivity disorder (ADHD). Pharmacological inhibition of the dopamine transporter (DAT) blocks reuptake, elevates synaptic dopamine, and alleviates ADHD symptoms. This study aimed to determine whether Mn exposure in juvenile mice modifies their response to DAT blockers, amphetamine, and methylphenidate and utilize neuroimaging methods to visualize and quantify Mn distribution across dopaminergic brain regions. Male and female heterozygous DATᵀ³⁵⁶ᴹ and wild-type littermates were randomly assigned to receive control (2.5% Stevia) or high Manganese (2.5 mg/ml Mn + 2.5% Stevia) via water ad libitum from weaning (21-28 days) for 4-5 weeks. Mice underwent repeated testing in locomotor activity chambers for three consecutive days (60 mins.) to ensure that they were fully habituated to the environments. On the fourth day, a 3-hour activity session was conducted following treatment with amphetamine (3 mg/kg) or methylphenidate (5 mg/kg). The second drug was administered in a second 3-hour activity session following a 1-week washout period. Following the washout, the mice were given one last injection of amphetamine and euthanized one hour later. Using the ex-vivo brains, magnetic resonance relaxometry (MRR) was performed on a 7Telsa imaging system to map T1- and T2-weighted (T1W, T2W) relaxation times. Mn inherent paramagnetic properties shorten both T1W and T2W times, which enhances the signal intensity and contrast, enabling effective visualization of Mn accumulation in the entire brain. A subset of mice was treated with amphetamine 1 hour before euthanasia. SmartSPIM light sheet microscopy with cleared whole brains and cFos and tyrosine hydroxylase (TH) labeling enabled an unbiased automated counting and densitometric analysis of TH and cFos positive cells. Immunohistochemistry was conducted to measure synaptic protein markers and quantify changes in neurotransmitter regulation. Mn exposure elevated Mn brain levels and potentiated stimulant effects in males. The globus pallidus, substantia nigra, thalamus, and striatum exhibited more pronounced T1W shortening, indicating regional susceptibility to Mn accumulation (p<0.0001, 2-Way ANOVA). In the cleared whole brains, initial analyses suggest that TH and c-Fos co-staining mirrors behavioral data with decreased co-staining in DATT356M+/- mice. Ongoing studies will identify the molecular basis of the effect of Mn, including changes to DAergic metabolism and transport and post-translational modification to the DAT. These findings demonstrate that alterations in T1W relaxation times, as measured by MRR, may serve as an early biomarker for Mn neurotoxicity. This neuroimaging approach exhibits remarkable accuracy in identifying Mn-susceptible brain regions, with a spatial resolution and sensitivity that surpasses current conventional dissection and mass spectrometry approaches. The capability to label and map TH and cFos expression across the entire brain provides insights into whole-brain neuronal activation and its connections to functional neural circuits and behavior following amphetamine and methylphenidate administration.

Keywords: manganese, environmental toxicology, dopamine dysfunction, biomarkers, drinking water, light sheet microscopy, magnetic resonance relaxometry (MRR)

Procedia PDF Downloads 37

Authors: Raquel R. Soares-Santos, Daniel P. Machado, Thiago L. Romero, Igor D. G. Duarte

Abstract:

Tramadol, an analgesic classified as an 'atypical opioid,' exhibits both opioid and non-opioid mechanisms of action. This study aimed to explore these mechanisms, specifically the opioid-, cannabinoid-, nitric oxide-, and potassium channel-based mechanisms, which contribute to the peripheral antinociception effect of tramadol, in an experimental rat model. The nociceptive threshold was determined using paw pressure withdrawal. To examine the mechanisms of action, several substances were administered intraplantarly: naloxone, a non-selective opioid antagonist (50 μg/paw); AM251 (80 μg/paw) and AM630 (100 μg/paw) as the selective antagonists for type 1 and type 2 cannabinoid receptors, respectively; nitric oxide synthase inhibitors L-NOArg, L-NIO, L-NPA, and L-NIL (24 μg/paw); and the enzyme inhibitors of guanylatocyclase and phosphodiesterase of cGMP, ODQ and zaprinast. Additionally, potassium channel blockers glibenclamide, tetraethylammonium, dequalinium, and paxillin were used. The results showed that opioid and cannabinoid receptor antagonists did not reverse tramadol’s effects. L-NOarg, L-NIO, and L-NPA partially reversed antinociception, while ODQ completely reversed, and zaprinast enhanced tramadol’s antinociception effect. Notably, glibenclamide blocked tramadol’s antinociception in a dose-dependent manner. These findings suggest that tramadol’s peripheral antinociception effect is likely mediated by the nitrergic pathway and sensitive ATP potassium channels, rather than the opioid and cannabinoid pathways.

Keywords: tramadol, nitric oxide, potassium channels, peripheral analgesia, opioid

Procedia PDF Downloads 27

Authors: Sibghat Mansoor Rana, Muhammad Islam, Hamid Saeed, Hummera Rafique, Muhammad Majid, Muhammad Tahir Aqeel, Fariha Imtiaz, Zaman Ashraf

Abstract:

The 1,3,4-oxadiazole derivatives Ox-6a-f have been synthesized by incorporating flur- biprofen moiety with the aim to explore the potential of target molecules to decrease the oxidative stress. The title compounds Ox-6a-f were prepared by simple reactions in which a flurbiprofen –COOH group was esterified with methanol in an acid-catalyzed medium, which was then reacted with hydrazine to afford the corresponding hydrazide. The acid hydrazide was then cyclized into 1,3,4-oxadiazole-2-thiol by reacting with CS2 in the presence of KOH. The title compounds Ox-6a-f were synthesized by the reaction of an –SH group with various alkyl/aryl chlorides, which involves an S-alkylation reaction. The structures of the synthesized Ox-6a-f derivatives were ascer- tained by spectroscopic data. The in silico molecular docking was performed against target proteins cyclooxygenase-2 COX-2 (PDBID 5KIR) and cyclooxygenase-1 COX-1 (PDBID 6Y3C) to determine the binding affinity of the synthesized compounds with these structures. It has been inferred that most of the synthesized compounds bind well with an active binding site of 5KIR compared to 6Y3C, and especially compound Ox-6f showed excellent binding affinity (7.70 kcal/mol) among all synthesized compounds Ox-6a-f. The molecular dynamic (MD) simulation has also been performed to check the stability of docking complexes of ligands with COX-2 by determining their root mean square deviation and root mean square fluctuation. Little fluctuation was observed in case of Ox-6f, which forms the most stable complex with COX-2. The comprehensive antioxidant potential of the synthesized compounds has been evaluated by determining their free radical scavenging activity, including DPPH, OH, nitric oxide (NO), and iron chelation assay. The derivative Ox-6f showed promising results with 80.23% radical scavenging potential at a dose of 100 μg/mL while ascorbic acid exhibited 87.72% inhibition at the same dose. The anti-inflammatory activity of the final products has also been performed, and inflammatory markers were assayed, such as a thiobarbituric acid-reducing substance, nitric oxide, interleukin-6 (IL-6), and COX-2. The derivatives Ox-6d and Ox-6f displayed higher anti-inflammatory activity, exhibiting 70.56% and 74.16% activity, respectively. The results were compared with standard ibuprofen, which showed 84.31% activity at the same dose, 200 μg/mL. The anti-inflammatory potential has been performed by following the carrageen-induced hind paw edema model, and results showed that derivative Ox-6f exhibited 79.83% reduction in edema volume compared to standard ibuprofen, which reduced 84.31% edema volume. As dry lab and wet lab results confirm each other, it has been deduced that derivative Ox-6f may serve as the lead structure to design potent compounds to address oxidative stress.

Keywords: synthetic chemistry, pharmaceutical chemistry, oxadiazole derivatives, anti-inflammatory, anti-cancer compounds

Procedia PDF Downloads 33

Authors: Juliette Begin, Juliano Colapelle, Andrea Taratanu, Daniel Thirion, Amelie Marsot, Bryan A. Ross

Abstract:

Chronic obstructive pulmonary disease (COPD), a leading cause of death globally, is characterized by chronic airflow obstruction and acute exacerbations (AECOPDs) that are often triggered by respiratory infections. Pseudomonas aeruginosa (P. aeruginosa), a potentially serious bacterial cause of AECOPDs, is treated with targeted anti-pseudomonal antibiotics. These select few antimicrobials are often used as first-line therapy in patients who are clinically unwell and/or in those suspected of P. aeruginosa-related infection prior to confirmation, potentially contributing to antimicrobial resistance. The present study evaluates prescribing practices in patients with a confirmed sputum history of P. aeruginosa admitted for AECOPD at the McGill University Health Centre (MUHC) and treated with anti-pseudomonal antibiotics. Serum antibiotic concentrations were measured from the same-day peak, trough, and mid-dose blood sampling intervals after reaching steady-state (on or after day 3) and were quantified using ultra-high-performance liquid chromatography (UHPLC). Demographic, clinical, and treatment outcomes were extracted from patient medical charts. Treatment failure was defined by respiratory-related death or mechanical ventilation after ≥3 days of antibiotics; antibiotic therapy extended beyond 2 weeks or a new antibiotic regimen started; or urgent care readmission within 30 days for AECOPD. To date, 9 of 30 planned participants have completed testing: seven received ciprofloxacin, one received meropenem, and one received piperacillin-tazobactam. Due to serum sample batching requirements, the serum ciprofloxacin concentration results for the first 2/8 participants are presented at the time of writing. The first participant had serum levels of 5.45mg/L (T₀), 4.74mg/L (T₅₀), and 4.49mg/L (T₁₀₀), while the second had serum levels of 5mg/L (T₀), 2.6mg/L (T₅₀), and 2.51mg/L (T₁₀₀). Pharmacokinetic parameters Cmax (5.18±0.43mg/L), T₁/₂ (23.56±18.94hours), and AUC (181.9±155.95mg*h/l) were higher than reported monograph values and met target AUC-to-MIC ratio of >125. The patients treated with meropenem and with piperacillin-tazobactam experienced treatment failure. Preliminary results suggest that standard ciprofloxacin dosing in patients experiencing an AECOPD and colonized with P. aeruginosa appears to achieve effective serum concentrations. Final cohort results will inform the pharmacokinetic appropriateness and clinical sufficiency of current AECOPD antimicrobial strategies in P. aeruginosa-colonized patients. This study will guide clinicians in determining the appropriate dosing for AECOPD treatment to achieve therapeutic levels, optimizing outcomes, and minimizing adverse effects. It could also highlight the value of routine antibiotic level monitoring in patients with treatment failure to ensure optimal serum concentrations.

Keywords: acute exacerbation, antimicrobial resistance, chronic obstructive pulmonary disease, pharmacokinetics/pharmacodynamics, Pseudomonas aeruginosa

Procedia PDF Downloads 36

Authors: Mulugeta Gurum Gerechal

Abstract:

In this piece of study, food safety questions and potential health risks make this as one of the most serious environmental concerns. Then, the levels of essential and non-essential heavy metals concentration were studied in Onion, Carrot, Swiss chard and Lettuce vegetables and compared the permissible levels with international guidelines for safe food. The concentration of Fe was found in the higher concentrations compared to other metals analyzed or significantly different at 95% confidence level than the rest metals studied in this study. However, the levels of the concentration of Cd and Pb exceeded the permissible level set by WHO specifications in water samples, Cd and Pb exceeded the permissible level set by FAO/WHO specifications in all vegetable samples collected from Adiahferom River Fe and Cu were also found below the recommended levels. The higher concentration of Pb and Cd above the permissible level in vegetables used for human food may pose health risk to consumer. However, the Fe hasn’t any health effect they take on from the Adiahferom body River. Mostly, the levels of metals in similar vegetable samples differed between the three sampling site, that may be due to variation in sources and processes of contaminations.

Keywords: Adiahferom, turbidity, temperature, physico-chemical, assessment

Procedia PDF Downloads 27

Authors: Farahnaz Motamedi Sedeh, Homayoon Mahravani, Parvin Shawrang, Mehdi Behgar

Abstract:

Most countries use inactivated binary ethylenimine (BEI) vaccines to control and prevent Foot-and-Mouth Disease (FMD). However, this vaccine induces a short-term humoral immune response in animals. This study investigated the cellular and humoral immune responses in homologous and prime-boost (PB) groups in the BALB/c mouse model. FMDV strain O/IRN/1/2007 was propagated in the BHK-21 cell line and inactivated by three methods, including a chemical with BEI to produce a conventional vaccine (CV), a gamma irradiation vaccine (GIV), and an electron irradiated vaccine (EIV). Three vaccines were formulated with the adjuvant aluminum hydroxide gel. In addition, a DNA vaccine was prepared by amplifying the virus VP1 gene pcDNA3.1 plasmid. In addition, the plasmid encoding the granulocyte-macrophage colony-stimulating factor gene (GM-CSF) was used as a molecular adjuvant. Eleven groups of five mice each were selected, and the vaccines were administered as homologous and heterologous strategy prime-boost (PB) in three doses two weeks apart. After the evaluation of neutralizing antibodies, interleukin (IL)-2, IL-4, IL-10, interferon-gamma (INF-γ), and MTT assays were compared in the different groups. The pcDNA3.1+VP1 cassette was prepared and confirmed as a DNA vaccine. The virus was inactivated by gamma rays and electron beams at 50 and 55 kGy as GIV and EIV, respectively. Splenic lymphocyte proliferation in the inactivated vaccinated homologous groups was significantly lower (P≤0.05) compared with the heterologous prime-boosts (PB1, PB2, PB3) and DNA + GM-CSF groups (P≤0.05). The highest SNT titer was observed in the inactivated vaccine groups. IFN-γ and IL-2 were higher in the vaccinated groups. It was found that although there was a protective humoral immune response in the groups with inactivated vaccine, there was adequate cellular immunity in the group with the DNA vaccine. However, the strongest cellular and humoral immunity was observed in the PB groups. The primary injection was accompanied by DNA vaccine + GM-CSF and boosted injection with GIV or CV.

Keywords: foot and mouth disease, irradiated vaccine, immune responses, DNA vaccine, prime boost strategy

Procedia PDF Downloads 30

Authors: Tayba Akram

Abstract:

our main objective of this study is to work on the etiology of liver cirrhosis, to find basic reasons and causes of liver damage, and to find the pattern of liver cirrhosis in hepatic patients either suffering from hepatitis B/C or simple jaundice. We can evaluate medical treatment and the latest trends in patients suffering from liver cirrhosis. We can evaluate the side effects and adverse effects induced by drug therapy used to treat liver cirrhosis. The conclusion is based on the etiology of liver cirrhosis. The most common cause of liver cirrhosis is the viral Hepatitis C virus. Other common causes of liver cirrhosis that are estimated from our research are Hepatitis B virus, Diabetes Mellitus, Ascites, and very rarely found Hepatitis D virus.

Keywords: etiology, liver, cirrhosis, co-morbid diseases

Procedia PDF Downloads 28

Authors: Mazen AlGharsan

Abstract:

Objective: The Carbopol Microsphere of Linezolid, a drug used to treat lung disease (pulmonary disease), was prepared using Buchi B-90 nano spray-drier. Methods: Production yield, drug content, external morphology, particle size, and in vitro release pattern were performed. Results: The work was 79.35%, and the drug content was 66.84%. The surface of the particles was shriveled in shape, with particle size distribution with a mean diameter of 9.6 µm; the drug was released in a biphasic manner with an initial release of 25.2 ± 5.7% at 60 minutes. It later prolonged the release by 95.5 ± 2.5% up to 12 hours. Differential scanning calorimetry (DSC) revealed no change in the melting point of the formulation. Fourier-transform infrared (FT-IR) studies showed no polymer-drug interaction in the prepared nanoparticles.

Keywords: nanotechnology, drug delivery, Linezolid, lung disease

Procedia PDF Downloads 28

Authors: Abdullah Ijaz Hussain

Abstract:

The purpose of this study was to explore the cardioprotective and anti-inflammatory effects of polyphenol-rich extracts from cucurbitaceae family members, including Cucurbita pepo, C. moschata, and C. maxima, on rat models. The initial crude extracts from these cucurbits were further separated into hexane, chloroform, ethyl acetate, butanol, and aqueous ethanol fractions, labeled as HEF, CHF, EAF, BUF, and AEF, respectively. Of these, AEF yielded the highest amount, followed by BUF, HEF, EAF, and CHF in descending order. Notably, EAF contained the greatest concentration of total phenolics, flavonoids, and flavonols. In terms of antioxidant activity, EAF demonstrated the most potent DPPH radical scavenging capability, succeeded by CHF, BUF, AEF, and HEF. EAF also exhibited the strongest reducing potential among the fractions. RP-HPLC analysis identified various phenolic acids and flavonoids across the cucurbita fractions, including ferulic acid, vanillic acid, p-coumeric acid, gallic acid, p-hydroxybenzoic acid, chlorogenic acid, catechin, rutin, quercetin, myricetin, and kaempferol. Doses of 250 and 500 mg/kg body weight of cucurbita fractions were administered orally to male WKY rats daily for 21 days. The rats' body weight, heart rate, and blood pressure were monitored bi-weekly. Oxidative status assessments were conducted using plasma samples to measure levels of malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), nitric oxide (NO), and total antioxidant capacity (TAC). At the study's conclusion, surgical assessments, including blood pressure, pulse wave velocity (PWV), and echocardiograms (ECG) were performed. The findings indicated that EAF from cucurbita significantly enhanced antihypertensive and antioxidant activities in the SHR rat group.

Keywords: polyphenols, chlorogenic acid, antihypertensive activity, oxidative stress, lcms

Procedia PDF Downloads 41

Authors: Janet Joy, Shri Shailesh Amarkhed, Pradeep M. Kulkarni

Abstract:

Introduction: Ureteral stent-related symptoms significantly impact patients' quality of life. This study compared the efficacy of Mirabegron, Tolterodine, and Fesoterodine in managing these symptoms. Methodology: In this prospective, randomized, placebo-controlled trial, two hundred patients undergoing ureteral stenting were randomly assigned to receive Mirabegron, Tolterodine, Fesoterodine, or placebo for two weeks. Symptoms were assessed using the Ureteral Stent Symptom Questionnaire (USSQ) at stent removal. Results: 200 patients completed the study. Mirabegron demonstrated the lowest mean USSQ score (31.6 ± 6.4), followed by Fesoterodine (34.0 ± 6.9) and Tolterodine (35.0 ± 7.2), all significantly lower than placebo (48.6 ± 8.7, p<0.001). Mirabegron showed superior efficacy in reducing urinary symptoms (score: 16.5 ± 3.9) compared to Fesoterodine (17.8 ± 4.1) and Tolterodine (18.2 ± 4.3). Side effects, such as parched mouth, were less frequent with Mirabegron (6%) than with Tolterodine (28%) and Fesoterodine (24%). Conclusion: All three medications significantly improved stent-related symptoms compared to placebo. Mirabegron demonstrated a trend toward superior efficacy and fewer side effects, suggesting its potential as a first-line treatment for stent-related discomfort.

Keywords: ureteral stent, mirabegron, tolterodine, fesoterodine, USSQ, stent-related symptoms

Procedia PDF Downloads 34

Authors: Asif Mahmood, Shama Shama, Hao Ni, Hao Wang, Yu Ling, Hui Xu, Shixing Yang, Qais Ahmad Naseer, Wen Zhang

Abstract:

Cardiovirus is a genus of viruses belonging to the family Picornaviridae. Here, we used viral metagenomic techniques to detect the viral nucleic acid in the fecal samples from wild rats in Zhenjiang city in China. Fecal samples were collected from 20 wild rats and pooled into four sample pools and then subjected to libraries construction which were then sequenced on Illumina MiSeq platform. The sequenced reads were analyzed using viral metagenomic analysis pipeline. A novel cardiovirus from feces of a wild rat was identified, named amzj-2018, of which the complete genome was acquired. Phylogenetic analysis based on the complete amino acid sequence of polyprotein revealed that amzj-2018 formed a separate branch located between clusters of Saffold virus and Rat Theilovirus 1 (RTV-1). Phylogenetic analysis based on different regions of the polyproteins, including P1, P2, P3, and P2+P3, respectively, showed discordant trees, where the tree based on P3 region indicated that amzj-2018 clustered separately between Theiler's murine encephalomyelitis virus and RTV-1. The complete genome of a cardiovirus was determined from the feces of wild rats which belonged to a novel type of cardiovirus based on phylogenetic analysis. Whether it is associated with disease needs further investigation.

Keywords: cardiovirus, viral metagenomics, genomic organization, phylogenetic analysis

Procedia PDF Downloads 33

Authors: Amandeep Thakur, Yi-Hsuan Chu, Chun-Hsu Pan, Kunal Nepali

Abstract:

The transfer of ADP-ribose residues onto target substrates from nicotinamide adenine dinucleotide (NAD) (PARylation) is catalyzed by Poly (ADP-ribose) polymerases (PARPs). Amongst the PARP family members, the DNA damage response in cancer is majorly regulated by PARP1 and PARP2. The blockade of DNA repair by PARP inhibitors leads to the progression of DNA single-strand breaks (induced by some triggering factors) to double-strand breaks. Notably, PARP inhibitors are remarkably effective in cancers with defective homologous recombination repair (HRR). In particular, cancer cells with BRCA mutations are responsive to therapy with PARP inhibitors. The aforementioned requirement for PARP inhibitors to be effective confers a narrow activity spectrum to PARP inhibitors, which hinders their clinical applicability. Thus, the quest to expand the application horizons of PARP inhibitors beyond BRCA mutations is the need of the hour. Literature precedents reveal that HDAC inhibition induces BRCAness in cancer cells and can broaden the therapeutic scope of PARP inhibitors. Driven by such disclosures, dual inhibitors targeting both PARP and HDAC enzymes were designed by our research group to extend the efficacy of PARP inhibitors beyond BRCA-mutated cancers to cancers with induced BRCAness. The design strategy involved the installation of Veliparib, an investigational PARP inhibitor, as a surface recognition part in the HDAC inhibitor pharmacophore model. The chemical architecture of veliparib was deemed appropriate as a starting point for the generation of dual inhibitors by virtue of its size and structural flexibility. A validatory docking study was conducted at the outset to predict the binding mode of the designed dual modulatory chemical architectures. Subsequently, the designed chemical architectures were synthesized via a multistep synthetic route and evaluated for antitumor efficacy. Delightfully, one compound manifested impressive anti-leukemic effects (HL-60 cell lines) mediated via dual inhibition of PARP and class I HDACs. The outcome of the western blot analysis revealed that the compound could downregulate the expression levels of PARP1 and PARP2 and the HDAC isoforms (HDAC1, 2, and 3). Also, the dual PARP-HDAC inhibitor upregulated the protein expression of the acetyl histone H3, confirming its abrogation potential for class I HDACs. In addition, the dual modulator could arrest the cell cycle at the G0/G1 phase and induce autophagy. Further, polymer-based nanoformulation of the dual inhibitor was furnished to afford targeted delivery of the dual inhibitor at the cancer site. Transmission electron microscopy (TEM) results indicate that the nanoparticles were monodispersed and spherical. Moreover, the polymeric nanoformulation exhibited an appropriate particle size. Delightfully, pH-sensitive behavior was manifested by the polymeric nanoformulation that led to selective antitumor effects towards the HL-60 cell lines. In light of the magnificent anti-leukemic profile of the identified dual PARP-HDAC inhibitor, in-vivo studies (pharmacokinetics and pharmacodynamics) are currently being conducted. Notably, the optimistic findings of the aforementioned study have spurred our research group to initiate several medicinal chemistry campaigns to create bifunctional small molecule inhibitors addressing PARP as the primary target.

Keywords: PARP inhibitors, HDAC inhibitors, BRCA mutations, leukemia

Procedia PDF Downloads 39