Search results for: nanoparticle-based drug delivery

Authors: Huayang Yu, Nicola Ingram, David C. Green, Paul D. Thornton

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The dual stimuli-controlled release of doxorubicin from gel-embedded nanoparticles is reported. Non-cytotoxic polymer nanoparticles are formed from poly(ethylene glycol)-b-poly(benzyl glutamate) that, uniquely, contain a central ester link. This connection renders the nanoparticles pH-responsive, enabling extensive doxorubicin release in acidic solutions (pH 6.5), but not in solutions of physiological pH (pH 7.4). Doxorubicin loaded nanoparticles were found to be stable for at least 31 days and lethal against the three breast cancer cell lines tested. Furthermore, doxorubicin-loaded nanoparticles could be incorporated within a thermoresponsive poly(2-hydroxypropyl methacrylate) gel depot, which forms immediately upon injection of poly(2-hydroxypropyl methacrylate) into aqueous solution. The combination of the poly(2-hydroxypropyl methacrylate) gel and poly(ethylene glycol)-b-poly(benzyl glutamate) nanoparticles yields an injectable doxorubicin delivery system that facilities near-complete drug release when maintained at elevated temperatures (37 °C) in acidic solution (pH 6.5). In contrast, negligible payload release occurs when the material is stored at room temperature in a non-acidic solution (pH 7.4). The system has great potential as a vehicle for the prolonged, site-specific release of chemotherapeutics.

Keywords: biodegradable, nanoparticle, polymer, thermoresponsive

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Authors: Gail Louw, Helena Boshoff, Taeksun Song, Clifton Barry

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Drug resistance in Mycobacterium tuberculosis is primarily attributed to mutations in target genes. These mutations incur a fitness cost and result in bacterial generations that are less fit, which subsequently acquire compensatory mutations to restore fitness. We hypothesize that mutations in specific drug target genes influence bacterial metabolism and cellular function, which affects its ability to develop subsequent resistance to additional agents. We aim to determine whether the sequential acquisition of drug resistance and specific mutations in a well-defined clinical M. tuberculosis strain promotes or limits the development of additional resistance. In vitro mutants resistant to pretomanid, linezolid, moxifloxacin, rifampicin and kanamycin were generated from a pan-susceptible clinical strain from the Beijing lineage. The resistant phenotypes to the anti-TB agents were confirmed by the broth microdilution assay and genetic mutations were identified by targeted gene sequencing. Growth of mono-resistant mutants was done in enriched medium for 14 days to assess in vitro fitness. Double resistant mutants were generated against anti-TB drug combinations at concentrations 5x and 10x the minimum inhibitory concentration. Subsequently, mutation frequencies for these anti-TB drugs in the different mono-resistant backgrounds were determined. The initial level of resistance and the mutation frequencies observed for the mono-resistant mutants were comparable to those previously reported. Targeted gene sequencing revealed the presence of known and clinically relevant mutations in the mutants resistant to linezolid, rifampicin, kanamycin and moxifloxacin. Significant growth defects were observed for mutants grown under in vitro conditions compared to the sensitive progenitor. Mutation frequencies determination in the mono-resistant mutants revealed a significant increase in mutation frequency against rifampicin and kanamycin, but a significant decrease in mutation frequency against linezolid and sutezolid. This suggests that these mono-resistant mutants are more prone to develop resistance to rifampicin and kanamycin, but less prone to develop resistance against linezolid and sutezolid. Even though kanamycin and linezolid both inhibit protein synthesis, these compounds target different subunits of the ribosome, thereby leading to different outcomes in terms of fitness in the mutants with impaired cellular function. These observations showed that oxazolidinone treatment is instrumental in limiting the development of multi-drug resistance in M. tuberculosis in vitro.

Keywords: oxazolidinones, mutations, resistance, tuberculosis

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Authors: Bhumika Wadhwa, Fayaz Malik

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The serine/threonine protein kinase B (PKB) also known as Akt, is one of the multifaceted kinase in human kinome, existing in three isoforms. Akt plays a vital role in phosphoinositide 3-kinase (PI3K) mediated oncogenesis in various malignancies and is one of the attractive targets for cancer drug discovery. The functional significance of an individual isoform of Akt is not redundant in cancer cell proliferation and metastasis instead Akt isoforms play distinct roles during metastasis; thereby regulating EMT. This study aims to determine isoform specific functions of Akt in cancer. The results obtained suggest that Akt1 restrict tumor invasion, whereas Akt2 promotes cell migration and invasion by various techniques like MTT, wound healing and invasion assay. Similarly, qRT-PCR also revealed that Akt3 has shown promising results in promoting cancer cell migration. Contrary to pro-oncogenic properties attributed to Akt, it is to be understood how various isoforms of Akt compensates each other in the regulation of common pathways during cancer progression and drug resistance. In conclusion, this study aims to target selective isoforms which is essential to inhibit cancer. However, the question now is whether, and how much, Akt inhibition will be tolerated in the clinic remains to be answered and the experiments will have to address the question of which combinations of newly devised Akt isoform specific inhibitors exert a favourable therapeutic effect in in vivo models of cancer to provide the therapeutic window with minimal toxicity.

Keywords: Akt isoforms, cancer, drug resistance, epithelial mesenchymal transition

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Authors: Sarika Gupta, Harshika Khanna, Ajay K Verma, Surya Kant

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Background: Drug-resistant tuberculosis (DR-TB) is a growing health challenge to global TB control efforts. Pediatric DR-TB is one of the neglected infectious diseases. In our previously published report, we have notified an increased prevalence of DR-TB in the pediatric population at a tertiary health care centre in North India which was estimated as 17.4%, 15.1%, 18.4%, and 20.3% in (%) in the year 2018, 2019, 2020, and 2021. Limited evidence exists about a pattern of drug resistance, side effect profile and programmatic outcomes of Paediatric DR-TB treatment. Therefore, this study was done to find out the pattern of resistance, side effect profile and treatment outcome. Methodology: This was a prospective cohort study conducted at the nodal drug-resistant tuberculosis centre of a tertiary care hospital in North India from January 2021 to December 2022. Subjects included children aged between 0-18 years of age with a diagnosis of DR-TB, on the basis of GeneXpert (rifampicin [RIF] resistance detected), line probe assay and drug sensitivity testing (DST) of M. tuberculosis (MTB) grown on a culture of body fluids. Children were classified as monoresistant TB, polyresistant TB (resistance to more than 1 first-line anti-TB drug, other than both INH and RIF), MDR-TB, pre-XDR-TB and XDR-TB, as per the WHO classification. All the patients were prescribed DR TB treatment as per the standard guidelines, either shorter oral DR-TB regimen or a longer all-oral MDR/XDR-TB regimen (age below five years needed modification). All the patients were followed up for side effects of treatment once per month. The patient outcomes were categorized as good outcomes if they had completed treatment and cured or were improving during the course of treatment, while bad outcomes included death or not improving during the course of treatment. Results: Of the 50 pediatric patients included in the study, 34 were females (66.7%) and 16 were male (31.4%). Around 33 patients (64.7%) were suffering from pulmonary TB, while 17 (33.3%) were suffering from extrapulmonary TB. The proportions of monoresistant TB, polyresistant TB, MDR-TB, pre-XDR-TB and XDR-TB were 2.0%, 0%, 50.0%, 30.0% and 18.0%, respectively. Good outcome was reported in 40 patients (80.0%). The 10 bad outcomes were 7 deaths (14%) and 3 (6.0%) children who were not improving. Adverse events (single or multiple) were reported in all the patients, most of which were mild in nature. The most common adverse events were metallic taste 16(31.4%), rash and allergic reaction 15(29.4%), nausea and vomiting 13(26.0%), arthralgia 11 (21.6%) and alopecia 11 (21.6%). Serious adverse event of QTc prolongation was reported in 4 cases (7.8%), but neither arrhythmias nor symptomatic cardiac side effects occurred. Vestibular toxicity was reported in 2(3.9%), and psychotic symptoms in 4(7.8%). Hepatotoxicity, hypothyroidism, peripheral neuropathy, gynaecomastia, and amenorrhea were reported in 2 (4.0%), 4 (7.8%), 2 (3.9%), 1(2.0%), and 2 (3.9%) respectively. None of the drugs needed to be withdrawn due to uncontrolled adverse events. Conclusion: Paediatric DR TB treatment achieved favorable outcomes in a large proportion of children. DR TB treatment regimen drugs were overall well tolerated in this cohort.

Keywords: pediatric, drug-resistant, tuberculosis, adverse events, treatment

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Authors: Garzon V., Bustos R., Salvador J. P., Marco M. P., Pinacho D. G.

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Bacterial resistance to antimicrobial treatment has increased significantly in recent years, making it a public health problem. Large numbers of bacteria are resistant to all or nearly all known antimicrobials, creating the need for the development of new types of antimicrobials or the use of “last line” antimicrobial drug therapies for the treatment of multi-resistant bacteria. Some of the chemical groups of antimicrobials most used for the treatment of infections caused by multiresistant bacteria in the clinic are Glycopeptide (Vancomycin), Polymyxin (Colistin), Lipopeptide (Daptomycin) and Carbapenem (Meropenem). Molecules that require therapeutic drug monitoring (TDM). Due to the above, a methodology based on nanobiotechnology based on an optical and electrochemical biosensor is being developed, which allows the evaluation of the plasmatic levels of some antimicrobials such as glycopeptide, polymyxin, lipopeptide and carbapenem quickly, at a low cost, with a high specificity and sensitivity and that can be implemented in the future in public and private health hospitals. For this, the project was divided into five steps i) Design of specific anti-drug antibodies, produced in rabbits for each of the types of antimicrobials, evaluating the results by means of an immunoassay analysis (ELISA); ii) quantification by means of an electrochemical biosensor that allows quantification with high sensitivity and selectivity of the reference antimicrobials; iii) Comparison of antimicrobial quantification with an optical type biosensor; iv) Validation of the methodologies used with biosensor by means of an immunoassay. Finding as a result that it is possible to quantify antibiotics by means of the optical and electrochemical biosensor at concentrations on average of 1,000ng/mL, the antibodies being sensitive and specific for each of the antibiotic molecules, results that were compared with immunoassays and HPLC chromatography. Thus, contributing to the safe use of these drugs commonly used in clinical practice and new antimicrobial drugs.

Keywords: antibiotics, electrochemical biosensor, optical biosensor, therapeutic drug monitoring

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Authors: Akwu N. A., Naidoo Y., Salau V. F., Olofinsan K. A.

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Grewia lasiocarpa E. Mey. ex Harv. (Malvaceae) is a Southern African medicinal plant indigenously used with other plants for birthing problems. The anti-diabetic properties of the hexane, chloroform, and methanol extracts of Grewia lasiocarpa stem bark were assessed using in vitro α-glucosidase enzyme inhibition assay. The predictive in silico drug-likeness and toxicity properties of the phytocompounds were conducted using the pKCSM, ADMElab, and SwissADME computer-aided online tools. The highest α-glucosidase percentage inhibition was observed in the hexane extract (86.76%, IC50= 0.24 mg/mL), followed by chloroform (63.08%, IC50= 4.87 mg/mL) and methanol (53.22%, IC50= 9.41 mg/mL); while acarbose, the standard anti-diabetic drug was (84.54%, IC50= 1.96 mg/mL). The α-glucosidase assay revealed that the hexane extract exhibited the strongest carbohydrate inhibiting capacity and is a better inhibitor than the standard reference drug-acarbose. The computational studies also affirm the results observed in the in vitroα-glucosidaseassay. Thus, the extracts of G. lasiocarpa may be considered a potential plant-sourced compound for treating type 2 diabetes mellitus. This is the first study on the anti-diabetic properties of Grewia lasiocarpa hexane, chloroform, and methanol extracts using in vitro and in silico models.

Keywords: grewia lasiocarpa, α-glucosidase inhibition, anti-diabetes, ADMET

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Authors: Sunitha Sampathi, Pankaj Kumar Tiriya, Sonia Gera, Sravanthi Reddy Pailla, V. Likhitha, A. J. Maruthi

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Surgical site infections (SSIs) are the most common nosocomial infections localized at the incision site. With an estimated 27 million surgical procedures each year in USA, approximately 2-5% rate of SSIs are predicted to occur annually. SSIs are treated with antibiotic medication. Current trend suggest that the direct drug delivery from the suture to the scared tissue can improve patient comfort and wound recovery. For that reason coating the surface of the medical device such as suture and catguts with broad spectrum antibiotics can prevent the formation of bactierial colonies with out comprimising the mechanical properties of the sutures.Hence, the present study was aimed to develop and evaluate a surgical suture coated with an antibiotic Ciprofloxacin hydrochloride loaded on gold nanoparticles. Gold nanoparticles were synthesized by chemical reduction method and conjugated with ciprofloxacin using Polyvinylpyrolidone as stabilizer and gold as carrier. Ciprofloxacin conjugated gold nanoparticles were coated over an absorbable surgical suture made of Polyglactan using sodium alginate as an immobilising agent by slurry dipping technique. The average particle size and Polydispersity Index of drug conjugated gold NPs were found to be 129±2.35 nm and 0.243±0.36 respectively. Gold nanoparticles are characterized by UV-Vis absorption spectroscopy, Fourier Transform Infrared Spectroscopy (FT-IR), Scanning electron microscopy and Transmission electron microscopy. FT-IR revealed that there is no chemical interaction between drug and polymer. Antimicrobial activity for coated sutures was evaluated by disc diffusion method on culture plates of both gram negative (E-coli) and gram positive bacteria (Staphylococcus aureus) and results found to be satisfactory. In vivo studies for coated sutures was performed on Swiss albino mice and histological evaluation of intestinal wound healing parameters such as wound edges in mucosa, muscularis, presence of necrosis, exudates, granulation tissue, granulocytes, macrophages, restoration, and repair of mucosal epithelium and muscularis propria on day 7 after surgery were studied. The control animal group, sutured with plain suture (uncoated suture) showed signs of restoration and repair, but presence of necrosis, heamorraghic infiltration and granulation tissue was still noticed. Whereas the animal group treated with ciprofloxacin and ciprofloxacin gold nanoparticle coated sutures has shown promising decrease in terms of haemorraghic infiltration, granulation tissue, necrosis and better repaired muscularis layers on comparision with plain coated sutures indicating faster rate of repair and less chance of sepsis. Hence coating of sutures with broad spectrum antibiotics can be an alternate technique to reduce SSIs.

Keywords: ciprofloxacin hydrochloride, gold nanoparticles, surgical site infections, sutures

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Authors: Ilaria Manca, Ilaria Manca, Francesca Pettinau, Ignazia Mocci, Elisabetta M. Usai, Barbara Pittau

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Lamotrigine is a phenyltriazine used in the treatment of epilepsy and bipolar disorder type I. The purpose of this study was to test and compare various solid forms of immediate release (IR) lamotrigine products, at different strenghts, in order to study their disaggregation and dissolution behavior. IR products are designed to release their active substance promptly after administration. Concentration of hydrochloric acid in gastric juice is about 0.1-0.001 M, so FDA (Food and Drug Administration) recommends, for lamotrigine regular tablets, dissolution tests in HCl 0.1 M.Toinvestigate the pH dependency of drug release in the entire gastrointestinal tract, we worked at two additional media with different pH values (4.5 and 6.8), that reflect conditions in it. To afford acceptable dissolution rates, tablets must disintegrate. Disaggregation of constituent particles increases the surface area and substantially increases the dissolution rate. For this reason availability of an active substance from tablets depends on its ability to disintegrate fast in dissolution media. pH of gastrointestinal fluid affects drug absorption by conditioning its solubility and dissolution, but also tablet disintegration may be influenced by it. To obtain information about the quantitative relationship between different mixture components, Nuclear Magnetic Resonance (NMR) spectroscopy was used. We also investigate tablet hardness. The investigation carried out confirms pH 1.2 as the ideal environment for the immediate availability of the active substance.

Keywords: dissolution, disaggregation, Lamotrigine, bioequivalence

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Authors: Hari Bezwada, Michelle Cheon, Ryan Divan, Hannah Escritor, Michelle Kagramian, Isha Korgaonkar, Maya MacAdams, Udgita Pamidigantam, Richard Pilny, Eleanor Race, Angadh Singh, Nathan Zhang, LeeAnn Nguyen, Fina Liotta

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Malaria is a deadly disease caused by the Plasmodium parasite, which continues to develop resistance to current antimalarial drugs. In this research project, the effectiveness of numerous thiazole derivatives was explored in inhibiting the PfPKG, a crucial part of the Plasmodium life cycle. This study involved the synthesis of six thiazole-derived amides to inhibit the PfPKG pathway. Nuclear Magnetic Resonance (NMR) spectroscopy and Infrared (IR) spectroscopy were used to characterize these compounds. Furthermore, AutoDocking software was used to predict binding affinities of these thiazole-derived amides in silico. In silico, compound 6 exhibited the highest predicted binding affinity to PfPKG, while compound 5 had the lowest affinity. Compounds 1-4 displayed varying degrees of predicted binding affinity. In-vitro, it was found that compound 4 had the best percent inhibition, while compound 5 had the worst percent inhibition. Overall, all six compounds had weak inhibition (approximately 30-39% at 10 μM), but these results provide a foundation for future drug discovery experiments.

Keywords: Medicinal Chemistry, Malaria, drug discovery, PfPKG, Thiazole, Plasmodium

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Authors: A. V. Shrirao, N. I. Kochar, A. V. Chandewar

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The flower extract of Butea monosperma herb has been used traditionally in India for medicinal purposes. The plant has been reported to treat hyperglycemia and associated hyperlipidemia. Hyperlipidemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. The present work was undertaken to investigate the possible antihyperlipidemic and antioxidative effect of Butea monosperma flowers on hyperlipidemic rats. Hyperlipidemia was induced in rats by a single intraperitonial (i.p.) injection of Triton WR 1339 (400 mg/kg) and it showed sustained elevated levels of serum cholesterol and triglyceride. Ethanolic extract of Butea monosperma flowers (Et-BM) (250 and 500 mg/kg/day) was administered to normal and hyperlipidemic rats for 14 days. Serum and liver tissue were analyzed at three different time intervals for lipid profile and antioxidants enzymes and the activity were compared to the cholesterol-lowering drug, Atorvastatin (10 mg/kg). Parameters were altered during hyperlipidemia and reverted back to near normal values after Et-BM treatment or standard drug Atorvastatin. Lipid peroxidation decreased whereas the activities of superoxide dismutase, glutathione peroxidase and catalase increased in Et-BM treated rats. Pronounced changes were observed at 500 mg/kg of Et-BM for 2 weeks and it was comparable to the standard drug Atorvastatin. The current study provides strong evidence that Et-BM has a remarkable beneficial effect in treating hyperlipidemia and ROS without any side effects at the dosage and duration studied.

Keywords: antioxidant, butea monopserma, hyperlipidemia, triton WR 1339

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Authors: Si-Gwan Kim

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In Delay Tolerant Networks (DTN), there may not exist an end-to-end path between source and destination at the time of message transmission. Employing ‘Store Carry and Forward’ delivery mechanism for message transmission in such networks usually incurs long message delays. In this paper, we present the modified Binary Spray and Wait (BSW) routing protocol that enhances the performance of the original one. Our proposed algorithm adjusts the number of forward messages depending on the number of neighbor nodes. By using beacon messages periodically, the number of neighbor nodes can be managed. The simulation using ONE simulator results shows that our modified version gives higher delivery ratio and less latency as compared to BSW.

Keywords: delay tolerant networks, store carry and forward, one simulator, binary spray and wait

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Authors: Geetakshi Arora, Danish Malhotra

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Diabetic wounds are serious health issues and often fail to heal, leading to limb amputation that makes the life of the patient miserable. Delayed wound healing has been characterized by an increase in matrix metalloproteinase-9 (MMP-9). Thus research throughout the world has been going on to develop selective MMP-9 inhibitors for aiding diabetic wound healing. Bioactive constituents from natural sources always served as potential leads in drug development with high rates of success. Considering the need for novel selective MMP-9 inhibitors and the importance of natural bioactive compounds in drug development, we have screened a library of bioactive constituents from plant sources that were effective in diabetic wound healing on human MMP-9 (hMMP-9) using molecular docking studies. Screened constituents are ranked according to their dock score, ∆G value (binding affinity), and Ligand efficiency evaluated from FleXX docking and Hyde scoring modules available with drug designing platform LeadIT. Rhamnocitrin showed the highest correlation between dock score, ∆G value (binding affinity), and Ligand efficiency was further explored for binding interactions with hMMP-9. The overall study suggest that Rhamnocitrin is sufficiently decorated with both hydrophilic and hydrophobic substitutions that perfectly block hMMP-9 and act as a potential lead in the design and development of selective hMMP-9 inhibitors.

Keywords: MMP-9, diabetic wound, molecular docking, phytoconstituents

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Authors: Nihar Ranjan, Derrick Watkins, Dev P. Arya

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Current methods in the study of antibiotic activity of ribosome targeted antibiotics are dependent on cell based bacterial inhibition assays or various forms of ribosomal binding assays. These assays are typically independent of each other and little direct correlation between the ribosomal binding and bacterial inhibition is established with the complementary assay. We have developed novel high-throughput capable assays for ribosome targeted drug discovery. One such assay examines the compounds ability to bind to a model ribosomal RNA A-site. We have also coupled this assay to other functional orthogonal assays. Such analysis can provide valuable understanding of the relationships between two complementary drug screening methods and could be used as standard analysis to correlate the affinity of a compound for its target and the effect the compound has on a cell.

Keywords: bacterial resistance, aminoglycosides, screening, drugs

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Authors: Abubakar Sa’adatu Mohammed

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This paper reports on a study of problem solving differences between expert and novice Problem solvers for effective physics teaching. Significant differences were found both at the conceptual level and at the level of critical thinking, creative thinking and reasoning. It is suggested for a successful solution of a problem, conceptual knowledge alone may not be sufficient. There is the need of the knowledge of how the conceptual knowledge should be applied (problem solving skills). It is hoped that this research might contribute to efforts of exploring ways for students to acquire a powerful conceptual toolkit based on experts like problem solvers approach for effective teaching delivery.

Keywords: conceptual knowledge, procedural knowledge, critical thinking, creative thinking, reasoning ability

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Authors: Sahar Elsaleh, Ghada Farhat, Shaikha Al-Derham, Fasih Alam

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Background: Cesarean section (CS) delivery is one of the major concerns both in developing and developed countries. The rate of CS deliveries are on the rise globally, and especially in Qatar. Many socio-economic, demographic, clinical and institutional factors play an important role for cesarean sections. This study aims to investigate factors affecting the prevalence of CS among women in Qatar using the UNICEF’s Multiple Indicator Cluster Survey (MICS) 2012 database. Methods: The study has focused on the women’s questionnaire of the MICS, which was successfully distributed to 5699 participants. Following study inclusion and exclusion criteria, a final sample of 761 women aged 19- 49 years who had at least one delivery of giving birth in their lifetime before the survey were included. A number of socio-economic, demographic, clinical and institutional factors, identified through literature review and available in the data, were considered for the analyses. Bivariate and multivariate logistic regression models, along with a multi-level modeling to investigate clustering effect, were undertaken to identify the factors that affect CS prevalence in Qatar. Results: From the bivariate analyses the study has shown that, a number of categorical factors are statistically significantly associated with the dependent variable (CS). When identifying the factors from a multivariate logistic regression, the study found that only three categorical factors -‘age of women’, ‘place at delivery’ and ‘baby weight’ appeared to be significantly affecting the CS among women in Qatar. Although the MICS dataset is based on a cluster survey, an exploratory multi-level analysis did not show any clustering effect, i.e. no significant variation in results at higher level (households), suggesting that all analyses at lower level (individual respondent) are valid without any significant bias in results. Conclusion: The study found a statistically significant association between the dependent variable (CS delivery) and age of women, frequency of TV watching, assistance at birth and place of birth. These results need to be interpreted cautiously; however, it can be used as evidence-base for further research on cesarean section delivery in Qatar.

Keywords: cesarean section, factors, multiple indicator cluster survey, MICS database, Qatar

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Authors: Foluke Dada

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Prisons all over the world are set up by law to provide restraint and custody for individuals accused or convicted of crimes by the state. The Nigerian prison dates back to the colonial era and is modelled after the British system. It is a system that lays emphasis on punishment and deterrence. It emphasises retribution rather than reformation. These, it can be argued, results in the inhuman conditions of Nigerian prisons and the conscienceless treatment of convicts and awaiting trial inmates in Nigerian prisons. This paper attempts an examination of the challenges currently beguiling Nigerian prisons, the need for reforms in the prison systems and the imperative of these reforms to an efficient criminal justice delivery system in the country. This paper further postulates that rehabilitation should be favoured as against retribution f the development of the Nigerian criminal justice system in line with the shift towards reform.

Keywords: criminal justice, human rights, prison reforms, rehabilitation and retribution

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Authors: C. W. F. Che Wan Putra, M. Alshawi, M. S. Al Ahbabi, M. Jabakhanji

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Much of the waste that is generated throughout the life-cycle of a building is mainly related to project stakeholders not having access to information that others have created. This results in waste and high costs. Over the past decade, however, the industry reacted to these challenges by adopting effective procurement approaches, such as partnering and design and build, to improve collaboration and communication among projects’ stakeholders. Most recently, there is a focus on creating and reusing digital project information of stakeholders throughout the life-cycle to facilitate the exchange of information among partners. This shift is based around BIM (Building Information Modelling) and collaborative environment (IPD). The power of collaborative BIM goes beyond improving efficiency. Sustainability, perhaps the most important challenge for the design and construction community, is at the intersection of BIM and collaborative project delivery, drawing strength from both. Due to these benefits, a research study has been carried out to investigate the need of BIM and IPD, on a large scale construction project which is procured on a traditional approach, i.e. design-bid-build. A qualitative research work including a semi-structured interview with project partners was conducted on a typical project in the UAE, whereby the selected project suffered from severe delays and cost overrun. This paper aims to bring about clear evidence to what most likely to happen to a typical construction project in spite of employing very good consultants, project manager and contractors and how these problems could have been avoided if BIM and IPD were deployed.

Keywords: building information modelling (BIM), integrated project delivery (IPD), collaborative environment, case study

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Authors: R. M. Noah, N. M. Nasir, M. R. Jais, M. S. S. Wahab, M. H. Abdullah, A. S. S. Raj

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Infectious diseases are getting more difficult to treat due to the resistant strains of bacteria. Current generations of antibiotics are most likely ineffective against multi-drug resistant strains bacteria. Thus, there is an urgent need in search of natural antibiotics in particular from medicinal plants. One of the common medicinal plants, Melaleuca cajuputi, has been reported to possess antibacterial properties. The study was conducted to evaluate and justify the presence of antibacterial activity of Melaleuca cajuputi essential oil (EO) against the multi-drug resistant bacteria. Clinical isolates obtained from the teaching hospital were re-assessed to confirm the exact identity of the bacteria to be tested, namely methicillin-resistant staphylococcus aureus (MRSA), carbapenem-resistant enterobacteriaceae (CRE), and extended-spectrum beta-lactamases producer (ESBLs). A well diffusion method was done to observe the inhibition zones of the essential oil against the bacteria. Minimum inhibitory concentration (MIC) was determined using the microdilution method in 96-well flat microplate. The absorbance was measured using a microplate reader. Minimum bactericidal concentration (MBC) was performed using the agar medium method. The zones of inhibition produced by the EO against MRSA, CRE, and ESBL were comparable to that of generic antibiotics used, gentamicin and augmentin. The MIC and MBC results highlighted the antimicrobial efficacy of the EO. The outcome of this study indicated that the EO of Melaleuca cajuputi had antibacterial activity on the multi-drug resistant bacteria. This finding was eventually substantiated by electron microscopy work.

Keywords: melaleuca cajuputi, antibacterial, resistant bacteria, essential oil

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Authors: Linghua Kong, Xinxia Chen, Mika Gissler, Catharina Lavebratt

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Background: Prenatal exposure to preeclampsia has been associated with an increased risk of offspring attention-deficit/hyperactivity disorders (ADHD), autism spectrum disorder (ASD), and intellectual disability. However, little is known about the association between prenatal exposure to severe preeclampsia and neurodevelopmental and psychiatric disorders in offspring. Objective: This study aimed to assess the risk of maternal preeclampsia combined with perinatal problems, specifically low birth weight and prematurity, on offspring neuropsychiatric disorders. Methods: All singleton live births in Finland between 1996 and 2014 (n=1 012 723) were followed up in nation-wide registries until 2018. Main exposures included pre-eclampsia, small for gestational age, and delivery before 34 gestational weeks. Offspring neurodevelopmental and psychiatric disorders (ICD-10 codes) were examined as outcomes variables. Offspring birth year, sex, maternal age at delivery, parity, marital status at birth, mother's country of birth, maternal smoking, maternal gestational diabetes, maternal use of psychotropic medication during pregnancy, and maternal systemic inflammatory diseases were used as covariates. Risks for neurodevelopmental and psychiatric disorders were estimated using Cox proportional hazards modeling. Results: Of the 1 012 723 offspring, 25 901 (2.6%) were exposed to preeclampsia, and 93 281 (9.2%) were diagnosed with a neuropsychiatric disorder. Compared to births unexposed to preeclampsia, small for gestational age or delivery before 34 gestational weeks, those exposed to preeclampsia only had a 21% increase in the likelihood of any neuropsychiatric disorders after adjusting for potential confounding (adjusted HR=1.21, 95% CI: 1.15-1.26), while exposure to preeclampsia combined with small for gestational age or delivery before 34 gestational weeks had a more than twofold increased risk of having a child with neuropsychiatric disorders (adjusted HR=2.16, 95% CI: 2.02-2.32). The adjusted HR for neuropsychiatric disorders in offspring with small for gestational age or delivery before 34 gestational weeks only was 1.79 (95% CI: 1.73-1.83). In addition, the risk estimate in offspring exposed to both preeclampsia and perinatal problems was greater than those only exposed to preeclampsia for having personality disorders (adjusted HR=1.66; 95% CI: 1.07-2.57), intellectual disabilities (adjusted HR=3.47; 95% CI: 2.86-4.22), specific developmental disorders (adjusted HR=2.91; 95% CI: 2.69-3.15), ASD (adjusted HR=1.75; 95% CI: 1.42-2.17), ADHD and conduct disorders (adjusted HR=2.00; 95%CI: 1.76-2.27), and other behavioral and emotional disorders (adjusted HR=2.09; 95% CI: 1.84-2.37). Conclusion: In utero exposure to severe preeclampsia increased the risk of several neurodevelopmental and psychiatric disorders in offspring. Our findings are relevant to women with hypertensive disorders with regard to pregnancy consultation and management and may yield effective clues for the prevention of neurodevelopmental and psychiatric disorders in childhood.

Keywords: low birth weight, neurodevelopmental disorders, preeclampsia, prematurity, psychiatric disorders

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Authors: J. Punj, R. K. Pandey, V. Darlong, K. Thangavel

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Background: Dural puncture epidural (DPE) technique has been introduced recently for labour analgesia however, no study has compared ropivacaine and levobupivacaine for the same. Methods: The primary aim of the study was to compare time to onset of the Numerical Pain Rating Score (NPRS) ≤ 1 in labour analgesia with both drugs. After obtaining ethics and patient consent, ASA I and ASA II parturient with single foetus in vertex presentation and cervical dilatation <5.0 cm were included. DPE was performed with 16/ 26 G combined spinal epidural (CSE) technique, and parturients randomized into two groups. In Group R ( Ropivacaine) 20 ml 0.125% ropivacaine+ fentanyl 2µg/ml was injected to a maximum of 20 ml in 20 minutes and in Group L (Levobupivacaine), 20 ml 0.125% levobupivacaine + fentanyl 2µg/ml was injected. Outcomes were assessed at 0.5,2,4,6,8,10,12,14,16,18,20 and 30 minutes, then every 90 minutes until delivery. Appropriate statistical analysis was done, and p value of <0.05 was considered statistically significant. Results: The median time to onset of NPRS ≤1 in both groups was comparable (group R= 16 minutes vs group L= 18 minutes (p = 0.076). Volume of drug for NPR ≤1 in both groups was also comparable (Group R 15.95± 2.03 ml vs Group L 16.35 ± 1.34 ml (p=0.47). Conclusion: DPE with 16 G epidural needle and 26 gauge spinal needle with both 0.125% ropivacaine and 0.125% levobupivacaine results in similar efficacy of labour analgesia.

Keywords: dural puncture epidural, labour analgesia, obstetric analgesia, hypotension

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Authors: Sena Su, Burak Ozbek, Yesim M. Sahin, Sevil Yucel, Dilek Kazan, Faik N. Oktar, Nazmi Ekren, Oguzhan Gunduz

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In recent years, protein, lipid or polysaccharide-based polymers have been used in order to develop biodegradable materials and their chemical nature determines the physical properties of the resulting films. Among these polymers, proteins from different sources have been extensively employed because of their relative abundance, film forming ability, and nutritional qualities. In this study, the biodegradable composite nanofiber films based on fish sarcoplasmic protein (FSP) were prepared via electrospinning technique. Biodegradable polycaprolactone (PCL) was blended with the FSP to obtain hybrid FSP/PCL nanofiber mats with desirable physical properties. Mixture solutions of FSP and PCL were produced at different concentrations and their density, viscosity, electrical conductivity and surface tension were measured. Mechanical properties of electrospun nanofibers were evaluated. Morphology of composite nanofibers was observed using scanning electron microscopy (SEM). Moreover, Fourier transform infrared spectrometer (FTIR) studies were used for analysis chemical composition of composite nanofibers. This study revealed that the FSP based nanofibers have the potential to be used for different applications such as biodegradable packaging, drug delivery, and wound dressing, etc.

Keywords: edible film, electrospinning, fish sarcoplasmic protein, nanofiber

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Authors: Peter Yamoah, Frasia Oosthuizen

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Introduction: Reporting of Adverse Events Following Immunization continues to be a challenge. Pharmacovigilance centers throughout the world are mandated by the WHO to submit AEFI reports from various countries to a large pool of adverse drug reaction electronic database called Vigibase. Despite the relevant information of AEFI in Vigibase, it is unavailable to the general public. However, the WHO has an alternative website called VigiAccess which is an open access website serving as a repository of reported adverse drug reactions and AEFIs. The aim of the study was to ascertain the reporting pattern of a number of commonly used vaccines in VigiAccess. Methods: VigiAccess was thoroughly searched on the 5th of February 2018 for AEFI reports of measles vaccine, oral polio vaccine (OPV), yellow fever vaccine, pneumococcal vaccine, rotavirus vaccine, meningococcal vaccine, tetanus vaccine and tuberculosis (BCG) vaccine. These were reports from all pharmacovigilance centers in the world from the time they joined the WHO drug monitoring program. Results: After a thorough search in VigiAccess, there were 9,062 measles vaccine AEFIs, 185,829 OPV AEFIs, 24,577 yellow fever vaccine AEFIs, 317,208 pneumococcal vaccine AEFIs, 73,513 rotavirus vaccine AEFIs, 145,447 meningococcal vaccine AEFIs, 22,781 tetanus vaccine AEFIs and 35,556 BCG vaccine AEFIs. Conclusion: The study revealed that out of the eight vaccines studied, pneumococcal vaccines are associated with the highest number of AEFIs whilst measles vaccines were associated with the least AEFIs.

Keywords: vaccines, adverse reactions, VigiAccess, adverse event reporting

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Authors: Noora Al Muftah, Reda Rawi, Richard Thompson, Halima Bensmail

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Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. There is an urgent need to identify biomarkers that predict which patients with are most likely to respond to treatment. Systematic efforts to correlate tumor mutational data with biologic dependencies may facilitate the translation of somatic mutation catalogs into meaningful biomarkers for patient stratification. To identify genomic features associated with drug sensitivity and uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we have screened and integrated a panel of several hundred cancer cell lines from different databases, mutation, DNA copy number, and gene expression data for hundreds of cell lines with their responses to targeted and cytotoxic therapies with drugs under clinical and preclinical investigation. We found mutated cancer genes were associated with cellular response to most currently available Glioma cancer drugs and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Keywords: cancer, gene network, Lasso, penalized regression, P-values, unbiased estimator

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Authors: Rajesh S. Mony, Vaidyaratnam Oushadhasala

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An attempt is made in this study to evolve a drug development modality based on classical Ayurvedic knowledge base as well as on modern scientific methodology. The present study involves (a) identification of a specific ailment condition, (b) the selection of a polyherbal formulation, (c) deciding suitable extraction procedure, (d) confirming the efficacy of the combination by in-vitro trials and (e) fixing up the recommended dose. The ailment segment selected is arthritic condition. The selected herbal combination is Kunturushka, Vibhitaki, Guggulu, Haridra, Maricha and Nirgundi. They were selected as per Classical Ayurvedic references, Authentified as per API (Ayurvedic Pharmacopeia of India), Extraction of each drug was done by different ratios of Hydroalcoholic menstrums, Invitro assessment of each extract after removing residual solvent for anti-Inflammatory, anti-arthritic activities (by UV-Vis. Spectrophotometer with positive control), Invitro assessment of each extract for COX enzyme inhibition (by UV-Vis. Spectrophotometer with positive control), Selection of the extracts was made having good in-vitro activity, Performed the QC testing of each selected extract including HPTLC, that is the in process QC specifications, h. Decision of the single dose with mixtures of selected extracts was made as per the level of in-vitro activity and available toxicology data, Quantification of major groups like Phenolics, Flavonoids, Alkaloids and Bitters was done with both standard Spectrophotometric and Gravimetric methods, Method for Marker assay was developed and validated by HPTLC and a good resolved HPTLC finger print was developed for the single dosage API (Active Pharmaceutical Ingredient mixture of extracts), Three batches was prepared to fix the in process and API (Active Pharmaceutical Ingredient) QC specifications.

Keywords: drug development, antiinflammatory, quality stardardisation, planar chromatography

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Authors: Husham Bayazed

Abstract:

A growing number of studies indicate that atherosclerotic coronary artery disease (CAD) has a complex pathogenesis that extends beyond cholesterol intimal infiltration. The atherosclerosis process may involve an immune micro-environmental condition driven by local activation of the adaptive and innate immunity arrays, resulting in the formation of atherosclerotic plaques. Therefore, despite the wide usage of lipid-lowering agents, these devastating coronary diseases are not averted either at primary or secondary prevention levels. Many trials have recently shown an interest in the immune targeting of the inflammatory process of atherosclerotic plaques, with the promised improvement in atherosclerotic cardiovascular disease outcomes. This recently includes the immune-modulatory drug “Canakinumab” as an anti-interleukin-1 beta monoclonal antibody in addition to "Colchicine,” which's established as a broad-effect drug in the management of other inflammatory conditions. Recent trials and studies highlight the importance of inflammation and immune reactions in the pathogenesis of atherosclerosis and plaque formation. This provides an insight to discuss and extend the therapies from old lipid-lowering drugs (statins) to anti-inflammatory drugs (colchicine) and new targeted immune-modulatory therapies like inhibitors of IL-1 beta (canakinumab) currently under investigation.

Keywords: atherosclerotic plagues, immune microenvironment, lipid-lowering agents, and immunomodulatory drugs

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Authors: Temesgen Sidamo, Prakruti S. Rao, Eleni Akllilu, Workineh Shibeshi, Yumi Park, Yong-Soon Cho, Jae-Gook Shin, Scott K. Heysell, Stellah G. Mpagama, Ephrem Engidawork

Abstract:

The fluoroquinolones (FQs) are used off-label for the treatment of multidrug-resistant tuberculosis (MDR-TB), and for evaluation in shortening the duration of drug-susceptible TB in recently prioritized regimens. Within the class, levofloxacin (LFX) and moxifloxacin (MXF) play a substantial role in ensuring success in treatment outcomes. However, sub-therapeutic plasma concentrations of either LFX or MXF may drive unfavorable treatment outcomes. To the best of our knowledge, the pharmacokinetics of LFX and MXF in Ethiopian patients with MDR-TB have not yet been investigated. Therefore, the aim of this study was to develop a population pharmacokinetic (PopPK) model of levofloxacin (LFX) and moxifloxacin (MXF) and assess the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24-h (AUC0-24) and the in vitro minimum inhibitory concentration (MIC) (AUC0-24/MIC) in Ethiopian MDR-TB patients. Steady-state plasma was collected from 39 MDR-TB patients enrolled in the programmatic treatment course and the drug concentrations were determined using optimized liquid chromatography-tandem mass spectrometry. In addition, the in vitro MIC of the patients' pretreatment clinical isolates was determined. PopPK and simulations were run at various doses, and PK parameters were estimated. The effect of covariates on the PK parameters and the PTA for maximum mycobacterial kill and resistance prevention was also investigated. LFX and MXF both fit in a one-compartment model with adjustments. The apparent volume of distribution (V) and clearance (CL) of LFX were influenced by serum creatinine (Scr), whereas the absorption constant (Ka) and V of MXF were influenced by Scr and BMI, respectively. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L was 29%, 62%, and 95% with the simulated 750 mg, 1000 mg, and 1500 mg doses, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no difference in the PTA (94.4%) for maximum bacterial kill among the simulated doses of MXF (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention improved proportionately with dose. Standard LFX and MXF doses may not provide adequate drug exposure. LFX PopPK is more predictable for maximum mycobacterial kill, whereas MXF's resistance prevention target increases with dose. Scr and BMI are likely to be important covariates in dose optimization or therapeutic drug monitoring (TDM) studies in Ethiopian patients.

Keywords: population PK, PTA, moxifloxacin, levofloxacin, MDR-TB patients, ethiopia

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Authors: Maryamsadat Habibi

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Objective: pharmaceutical errors are avoidable occurrences that can result in inappropriate pharmaceutical use, patient harm, treatment failure, increased hospital costs and length of stay, and other outcomes that affect both the individual receiving treatment and the healthcare provider. This study aimed to perform a reconciliation of medications in the cardiovascular ward of Imam Reza Hospital in Mashhad, Iran, and evaluate the prevalence of medication discrepancies between the best medication list created for the patient by the pharmacist and the medication order of the treating physician there. Materials & Methods: The 97 patients in the cardiovascular ward of the Imam Reza Hospital in Mashhad were the subject of a cross-sectional study from June to September of 2021. After giving their informed consent and being admitted to the ward, all patients with at least one underlying condition and at least two medications being taken at home were included in the study. A medical reconciliation form was used to record patient demographics and medical histories during the first 24 hours of admission, and the information was contrasted with the doctors' orders. The doctor then discovered medication inconsistencies between the two lists and double-checked them to separate the intentional from the accidental anomalies. Finally, using SPSS software version 22, it was determined how common medical discrepancies are and how different sorts of discrepancies relate to various variables. Results: The average age of the participants in this study was 57.6915.84 years, with 57.7% of men and 42.3% of women. 95.9% of the patients among these people encountered at least one medication discrepancy, and 58.9% of them suffered at least one unintentional drug cessation. Out of the 659 medications registered in the study, 399 cases (60.54%) had inconsistencies, of which 161 cases (40.35%) involved the intentional stopping of a medication, 123 cases (30.82%) involved the stopping of a medication unintentionally, and 115 cases (28.82%) involved the continued use of a medication by adjusting the dose. Additionally, the category of cardiovascular pharmaceuticals and the category of gastrointestinal medications were found to have the highest medical inconsistencies in the current study. Furthermore, there was no correlation between the frequency of medical discrepancies and the following variables: age, ward, date of visit, type, and number of underlying diseases (P=0.13), P=0.61, P=0.72, P=0.82, P=0.44, and so forth. On the other hand, there was a statistically significant correlation between the number of medications taken at home (P=0.037) and the prevalence of medical discrepancies with gender (P=0.029). The results of this study revealed that 96% of patients admitted to the cardiovascular unit at Imam Reza Hospital had at least one medication error, which was typically an intentional drug discontinuance. According to the study's findings, patients admitted to Imam Reza Hospital's cardiovascular ward have a great potential for identifying and correcting various medication discrepancies as well as for avoiding prescription errors when the medication reconciliation method is used. As a result, it is essential to carry out a precise assessment to achieve the best treatment outcomes and avoid unintended medication discontinuation, unwanted drug-related events, and drug interactions between the patient's home medications and those prescribed in the hospital.

Keywords: drug combination, drug side effects, drug incompatibility, cardiovascular department

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Authors: Kwaku Damoah

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This study presents a comprehensive data-driven analysis to understand the evolution of adverse events (AEs) in pharmacovigilance. Utilizing data from the FDA Adverse Event Reporting System (FAERS), we employed three analytical methods: rank-based, frequency-based, and percentage change analyses. These methods assessed temporal trends and patterns in AE reporting, focusing on various drug-active ingredients and patient demographics. Our findings reveal significant trends in AE occurrences, with both increasing and decreasing patterns from 2000 to 2023. This research highlights the importance of continuous monitoring and advanced analysis in pharmacovigilance, offering valuable insights for healthcare professionals and policymakers to enhance drug safety.

Keywords: event analysis, FDA adverse event reporting system, pharmacovigilance, temporal trend analysis

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Authors: Rana Praween Kumar

Abstract:

Preterm-low birth weight delivery is a major cause of infant morbidity and mortality in developing countries and has been linked to poor periodontal health during pregnancy. Gingivitis and chronic periodontitis are highly prevalent chronic inflammatory oral diseases. The detection and diagnosis of these common diseases is a fundamentally important component of oral health care. This study is intended to investigate predisposing and enabling factors as determinants of oral health indicators in pregnancy as well as the association between periodontal problems during pregnancy with age and socio economic status of the individual. A community –based prospective cohort study will be conducted in Jamshedpur, Jharkhand, India among pregnant women using completed interviews and a full mouth oral clinical examination using the CPITN (Community Periodontal Index of Treatment Need) and OHI-S (Simplified Oral Hygiene) indices with adequate sample size and informed consent to the patient following proper inclusion and exclusion criteria. Multiple logistic regression analyses will be used to identify independent determinants of periodontal problems and use of dental services during pregnancy. Analysis of covariance (ANCOVA) will be used to investigate the relationship between periodontal problems with the age and socioeconomic status. The result will help in proper monitoring of periodontal health during pregnancy encouraging the delivery of healthy child and the maintenance of proper health of the mother.

Keywords: infant, periodontal problems, pregnancy, pre-term-low birth weight delivery

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Authors: Donna L. Roberts

Abstract:

2019 marked 23 years since Purdue Pharma launched its flagship drug, OxyContin, that unleashed an unprecedented epidemic touching both celebrities and common citizens, metropolitan, suburbia and rural areas and all levels of socioeconomic status. From rural Appalachia to East LA individuals, families and communities have been devastated by a trajectory of addiction that often began with the legitimate prescription of a pain killer for anything from a tooth extraction to a sports injury to recovery from surgery or chronic arthritis. Far from being a serendipitous progression of events, the proliferation of this new breed of 'miracle drug' was instead a carefully crafted marketing program aimed at both the medical community and common citizens. This research represents and in-depth investigation of the evolution of the marketing, distribution and promotion of prescription opioids by pharmaceutical companies and its relationship to the propagation of the opioid crisis. Specifically, key components of Purdue Pharma’s aggressive marketing campaign, including its bonus system and sales incentives, were analyzed in the context of the sociopolitical environment that essential created the proverbial 'perfect storm' for the changing manner in which pain is treated in the U.S. The analyses of these series of events clearly indicate their role in first, the increase in prescription of opioids for non-terminal pain relief and subsequently, the incidence of related addiction, overdose, and death. Through this examination of the conditions that facilitated and maintained this drug crisis, perhaps we can begin to chart a course toward its resolution.

Keywords: addiction, opioid, opioid crisis, Purdue Pharma

Procedia PDF Downloads 124