Search results for: adverse drug reactions

Authors: Muhammet Baldan, Emel Timuçin

Abstract:

Generally, absorption and bioavailability increase if solubility increases; therefore, it is crucial to predict them in drug discovery applications. Molecular descriptors and Molecular properties are traditionally used for the prediction of water solubility. There are various key descriptors that are used for this purpose, namely Drogan Descriptors, Morgan Descriptors, Maccs keys, etc., and each has different prediction capabilities with differentiating successes between different data sets. Another source for the prediction of solubility is structural features; they are commonly used for the prediction of solubility. However, there are little to no studies that combine three or more properties or descriptors for prediction to produce a more powerful prediction model. Unlike available models, we used a combination of those features in a random forest machine learning model for improved solubility prediction to better predict and, therefore, contribute to drug discovery systems.

Keywords: solubility, random forest, molecular descriptors, maccs keys

Procedia PDF Downloads 29

Authors: Kedar J. Mahadeshwar

Abstract:

Concept introduction: This paper talks about how an innovative cloud based analytics enabled solution that could address a major industry challenge that is approaching all of us globally faster than what one would think. The world of supply chain for drugs and devices is changing today at a rapid speed. In the US, the Drug Supply Chain Security Act (DSCSA) is a new law for Tracing, Verification and Serialization phasing in starting Jan 1, 2015 for manufacturers, repackagers, wholesalers and pharmacies / clinics. Similarly we are seeing pressures building up in Europe, China and many countries that would require an absolute traceability of every drug and device end to end. Companies (both manufacturers and distributors) can use this opportunity not only to be compliant but to differentiate themselves over competition. And moreover a country such as UAE can be the leader in coming up with a global solution that brings innovation in this industry. Problem definition and timing: The problem of counterfeit drug market, recognized by FDA, causes billions of dollars loss every year. Even in UAE, the concerns over prevalence of counterfeit drugs, which enter through ports such as Dubai remains a big concern, as per UAE pharma and healthcare report, Q1 2015. Distribution of drugs and devices involves multiple processes and systems that do not talk to each other. Consumer confidence is at risk due to this lack of traceability and any leading provider is at risk of losing its reputation. Globally there is an increasing pressure by government and regulatory bodies to trace serial numbers and lot numbers of every drug and medical devices throughout a supply chain. Though many of large corporations use some form of ERP (enterprise resource planning) software, it is far from having a capability to trace a lot and serial number beyond the enterprise and making this information easily available real time. Solution: The solution here talks about a service provider that allows all subscribers to take advantage of this service. The solution allows a service provider regardless of its physical location, to host this cloud based traceability and analytics solution of millions of distribution transactions that capture lots of each drug and device. The solution platform will capture a movement of every medical device and drug end to end from its manufacturer to a hospital or a doctor through a series of distributor or retail network. The platform also provides advanced analytics solution to do some intelligent reporting online. Why Dubai? Opportunity exists with huge investment done in Dubai healthcare city also with using technology and infrastructure to attract more FDI to provide such a service. UAE and countries similar will be facing this pressure from regulators globally in near future. But more interestingly, Dubai can attract such innovators/companies to run and host such a cloud based solution and become a hub of such traceability globally.

Keywords: cloud, pharmaceutical, supply chain, tracking

Procedia PDF Downloads 517

Authors: Ahlam Ali, Katrina Lappin, Jaine Blayney, Ken Mills

Abstract:

Leukaemia is the most frequently (30%) occurring type of paediatric cancer. Of these, approximately 80% are acute lymphoblastic leukaemia (ALL) with acute myeloid leukaemia (AML) cases making up the remaining 20% alongside other leukaemias. Unfortunately, children with AML do not have promising prognosis with only 60% surviving 5 years or longer. It has been highlighted recently the need for age-specific therapies for AML patients, with paediatric AML cases having a different mutational landscape compared with AML diagnosed in adult patients. Drug Repurposing is a recognized strategy in drug discovery and development where an already approved drug is used for diseases other than originally indicated. We aim to identify novel combination therapies with the promise of providing alternative more effective and less toxic induction therapy options. Our in-silico analysis highlighted ‘cell death and survival’ as an aberrant, potentially targetable pathway in paediatric AML patients. On this basis, 83 apoptotic inducing compounds were screened. A preliminary single agent screen was also performed to eliminate potentially toxic chemicals, then drugs were constructed into a pooled library with 10 drugs per well over 160 wells, with 45 possible pairs and 120 triples in each well. Seven cell lines were used during this study to represent the clonality of AML in paediatric patients (Kasumi-1, CMK, CMS, MV11-14, PL21, THP1, MOLM-13). Cytotoxicity was assessed up to 72 hours using CellTox™ Green reagent. Fluorescence readings were normalized to a DMSO control. Z-Score was assigned to each well based on the mean and standard deviation of all the data. Combinations with a Z-Score <2 were eliminated and the remaining wells were taken forward for further analysis. A well was considered ‘successful’ if each drug individually demonstrated a Z-Score <2, while the combination exhibited a Z-Score >2. Each of the ten compounds in one well (155) had minimal or no effect as single agents on cell viability however, a combination of two or more of the compounds resulted in a substantial increase in cell death, therefore the ten compounds were de-convoluted to identify a possible synergistic pair/triple combinations. The screen identified two possible ‘novel’ drug pairing, with BCL2 inhibitor ABT-737, combined with either a CDK inhibitor Purvalanol A, or AKT/ PI3K inhibitor LY294002. (ABT-737- 100 nM+ Purvalanol A- 1 µM) (ABT-737- 100 nM+ LY294002- 2 µM). Three possible triple combinations were identified (LY2409881+Akti-1/2+Purvalanol A, SU9516+Akti-1/2+Purvalanol A, and ABT-737+LY2409881+Purvalanol A), which will be taken forward for examining their efficacy at varying concentrations and dosing schedules, across multiple paediatric AML cell lines for optimisation of maximum synergy. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.

Keywords: AML, drug repurposing, ABT-737, apoptosis

Procedia PDF Downloads 187

Authors: Zineb Ouahdi

Abstract:

Spirocyclic compound derivatives, with their unique heterocyclic motifs, serve as a continual source of inspiration in the pursuit of developing potential therapeutic agents. These compounds are diverse in their chemical structures; some have fully saturated skeletons, while others are partially unsaturated. Nevertheless, these compounds share a characteristic feature with natural products - the presence of at least one heteroatom in one of their rings. The inclusion of a C = O dipolarophile in pyridazinones imparts an exciting aspect for 1,3-dipolar cycloaddition reactions, the focal point of our study. Our research has involved a detailed theoretical investigation of the reaction between ethyl (Z)-2-bromo-2-(2-(p-tolyl)hydrazono)acetate and 6-methyl-4,5-dihydropyridazine-3(2H)-one. This has been accomplished using the DFT/B3LYP/6-31g(d,p) method, intending to illuminate the chemical pathway of this reaction. The chemical reactivity theories we used for this purpose included FMO, TS, and local and global indices derived from conceptual DFT. The theoretical framework outlined in this study allowed us to propose a reaction mechanism for cycloaddition reactions. It also enabled the identification of the potential activities of the analyzed compounds (P1, P2, P3, P4, P5, and P6) against the major protease of the coronavirus disease (COVID-19). This was achieved using various computational tools, including AutoDock Tools, Autodock Vina, Autodock 4, and PYRX.

Keywords: MEDT, pyridazin, cycloaddition, FMO, DFT, docking

Procedia PDF Downloads 86

Authors: Syed Beenish Rufai, Sarman Singh

Abstract:

Background: Performance of Genotype MTBDRsl (Hain Life science GmbH Germany) for detection of mutations associated with second-line drug resistance is well known. However, less evidence regarding the association of mutations and genetic background of strains is known which, in the future, is essential for clinical management of anti-tuberculosis drugs in those settings where the probability of particular genotype is predominant. Material and Methods: During this retrospective study, a total of 259 MDR-TB isolates obtained from pulmonary TB patients were tested for second-line drug susceptibility testing (DST) using Genotype MTBDRsl VER 1.0 and compared with BACTEC MGIT-960 as a reference standard. All isolates were further characterized using spoligotyping. The spoligo patterns obtained were compared and analyzed using SITVIT_WEB. Results: Of total 259 MDR-TB isolates which were screened for second-line DST by Genotype MTBDRsl, mutations were found to be associated with gyrA, rrs and emb genes in 82 (31.6%), 2 (0.8%) and 90 (34.7%) isolates respectively. 16 (6.1%) isolates detected mutations associated with both FQ as well as to AG/CP drugs (XDR-TB). No mutations were detected in 159 (61.4%) isolates for corresponding gyrA and rrs genes. Genotype MTBDRsl showed a concordance of 96.4% for detection of sensitive isolates in comparison with second-line DST by BACTEC MGIT-960 and 94.1%, 93.5%, 60.5% and 50% for detection of XDR-TB, FQ, EMB, and AMK/CAP respectively. D94G was the most prevalent mutation found among (38 (46.4%)) OFXR isolates (37 FQ mono-resistant and 1 XDR-TB) followed by A90V (23 (28.1%)) (17 FQ mono-resistant and 6 XDR-TB). Among AG/CP resistant isolates A1401G was the most frequent mutation observed among (11 (61.1%)) isolates (2 AG/CP mono-resistant isolates and 9 XDR-TB isolates) followed by WT+A1401G (6 (33.3%)) and G1484T (1 (5.5%)) respectively. On spoligotyping analysis, Beijing strain (46%) was found to be the most predominant strain among pre-XDR and XDR TB isolates followed by CAS (30%), X (6%), Unique (5%), EAI and T each of 4%, Manu (3%) and Ural (2%) respectively. Beijing strain was found to be strongly associated with D94G (47.3%) and A90V mutations by (47.3%) and 34.8% followed by CAS strain by (31.6%) and 30.4% respectively. However, among AG/CP resistant isolates, only Beijing strain was found to be strongly associated with A1401G and WT+A1401G mutations by 54.5% and 50% respectively. Conclusion: Beijing strain was found to be strongly associated with the most prevalent mutations among pre-XDR and XDR TB isolates. Acknowledgments: Study was supported with Grant by All India Institute of Medical Sciences, New Delhi reference No. P-2012/12452.

Keywords: tuberculosis, line probe assay, XDR TB, drug susceptibility

Procedia PDF Downloads 129

Authors: Ramesh Subramani, Mathivanan Narayanasamy, William Aalbersberg

Abstract:

It is well accepted by last 35 years of research and on-going programmes that marine environment harbours abundant and unique biodiversity, which is currently playing as an important source in bioprospecting. It has become apparent that marine microorganisms are lead in the biodiscovery. Among marine organisms, actinobacteria are a target phylum for discovering novel antibiotics against increasing the multi-drug resistant human pathogens because of these taxa representing for novel genera and species. Marine actinomycetes are a proven source of new antibiotic leads and novel enzymes with important industrial applications. A total of 183 streptomycete and 25 non-streptomycete strains were isolated from different marine samples collected from north-eastern part of the Indian Ocean. Among them, 111 isolates displayed antibacterial activity against human pathogens and 151 exhibited antifungal activity against phytopathogens. Importantly, most of them produced various extracellular enzymes and 58 of them produced exopolysaccharides. Totally eight small bioactive compounds and a thermostable alkaline protease have been purified from a selected strain, Streptomyces fungicidicus. Besides, our on-going studies on non-streptomycete strains (rare actinomycetes) are most likely promising resource for new and unique compounds against current emerging drug-resistant pathogens. We have just recognised the chemical diversity in marine microorganisms. Therefore it is worthwhile to continue the exploration of marine microorganisms for new drug leads, novel enzymes and other bioprospecting research.

Keywords: bioactive compounds, industrial enzymes, marine actinobacteria, microbial metabolites, marine natural products

Procedia PDF Downloads 266

Authors: Richa Mardianingrum, Srie R. N. Endah

Abstract:

In this research, we have designed four isoniazid derivatives i.e., isonicotinohydrazide (1-isonicotinoyl semicarbazide, 1-thiosemi isonicotinoyl carbazide, N '-(1,3-dimethyl-1 h-pyrazole-5-carbonyl) isonicotino hydrazide, and N '-(1,2,3- 4-thiadiazole-carbonyl) isonicotinohydrazide. The docking and molecular dynamic have performed to them in order to study its interaction with Mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (InhA). Based on this research, all of the compounds were predicted to have a stable interaction with Mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (INHA) receptor, so they could be used as an anti-tuberculosis drug candidate.

Keywords: anti-tuberculosis, docking, Inhibin alpha subunit, InhA, inhibition, synthesis, isonicotinohydrazide

Procedia PDF Downloads 167

Authors: Sutapa Som Chaudhury, Chitrangada Das Mukhopadhyay

Abstract:

Alzheimer’s disease is a well-known form of dementia since its discovery in 1906. Current Food and Drug Administration approved medications e.g. cholinesterase inhibitors, memantine offer modest symptomatic relief but do not play any role in disease modification or recovery. In last three decades many small molecules, chaperons, synthetic peptides, partial β-secretase enzyme blocker have been tested for the development of a drug against Alzheimer though did not pass the 3rd clinical phase trials. Here in this study, we designed a PEGylated, aminogenic, tripeptidic polymer with two different molecular weights based on the aggregation prone amino acid sequence 17-20 in amyloid beta (Aβ) 1-42. Being conjugated with poly-ethylene glycol (PEG) which self-assembles into hydrophilic nanoparticles, these PEGylated tripeptides constitute a very good drug delivery system crossing the blood brain barrier while the peptide remains protected from proteolytic degradation and non-specific protein interactions. Moreover, being completely aminogenic they would not raise any side effects. These peptide inhibitors were evaluated for their effectiveness against Aβ42 fibrillation at an early stage of oligomer to fibril formation as well as preformed fibril clearance via Thioflavin T (ThT) assay, dynamic light scattering analyses, atomic force microscopy and scanning electron microscopy. The inhibitors were proved to be safe at a higher concentration of 20µM by the reduction assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. Moreover, SHSY5Y neuroblastoma cells have shown a greater survivability when treated with the inhibitors following Aβ42 fibril and oligomer treatment as compared with the control Aβ42 fibril and/or oligomer treated neuroblastoma cells. These make the peptidic inhibitors a promising compound in the aspect of the discovery of alternative medication for Alzheimer’s disease.

Keywords: Alzheimer’s disease, alternative medication, amyloid beta, PEGylated peptide

Procedia PDF Downloads 199

Authors: Leila Fozouni, Anahita Mazandarani

Abstract:

Background: Maternal infections are the most common cause of infections in infants, and the level of infection and its severity highly depends on the degree of colonization of the bacteria in the mother; so, the occurrence of aggressive diseases is not unpredictable in mothers with very high colonization. Group B Streptococcus is part of the normal flora of the gastrointestinal and genital tracts in women and is the leading cause of septicemia and meningitis in newborns. Today Zinc oxide nanoparticle is regarded as one of the most commonly used and safest nanoparticles for defeating Gram-positive and Gram-negative bacteria. This study aims to determine the antibacterial effects of Zinc oxide on the growth of drug-resistant group B Streptococcus strains isolated from pregnant women. Materials and Methods: This cross-sectional study was conducted on 150 pregnant women of 28–37 weeks admitted to seven hospitals and maternity wards in Golestan province, northeast of Iran. For bacterial identification, rectovaginal swabs were firstly inoculated to the Todd-Hewitt Broth and cultured in blood agar (containing 5% sheep blood). Then microbiologic and PCR methods were performed to detect group B Streptococci. Disk diffusion and broth microdilution tests were used to determine the bacterial susceptibility to antibiotics according to CLSI M100(2021) criteria. The antibacterial properties of Zinc oxide nanoparticles were evaluated using the agar well-diffusion method. Results: The prevalence of group B Streptococcus was 18% in pregnant women. Out of twenty-seven positive cultures, 62.96% were higher than thirty years old. Ninety percent and 45% of isolates were resistant to clindamycin and erythromycin, respectively, and susceptibility to cefazolin was 71%. In addition, susceptibility to ampicillin and penicillin were 74% and 55%, respectively. The results showed that 82% of erythromycin-resistant, 92% clindamycin-resistant, and 78% of cefazolin-resistant isolates were eliminated by zinc oxide nanoparticles at a concentration of 100 mg/L of the nanoparticle. Furthermore, ZnONPs could inhibit all drug-resistant isolates at a concentration of 200 mg/mL (MIC90 ≥ 200). Conclusion: Since the drug resistance of group B streptococci against various antibiotics is increasing, determining and investigating the drug-resistance pattern of this bacterium to different antibiotics in order to prevent arbitrary consumption of antibiotics by pregnant women and ultimately prevent Infant mortality seems necessary. Generally, ZnONPs showed a high antimicrobial effect, and it was revealed that the bactericide effect increases upon the increase in the concentration of the nanoparticle.

Keywords: group B beta-hemolytic streptococcus, pregnant women, zinc oxide nanoparticles, drug resistance

Procedia PDF Downloads 78

Authors: Eslam Dabbish, Fortuna Ponte, Stefano Scoditti, Emilia Sicilia, Gloria Mazzone

Abstract:

The medical techniques based on the use of light for activating the drug are occupying a prominent place in the cancer treatment due to their selectivity that contributes to reduce undesirable side effects of conventional chemotherapy. Among these therapeutic treatments, photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) are emerging as complementary approaches for selective destruction of neoplastic tissue through direct cellular damage. Both techniques rely on the employment of a molecule, photosensitizer (PS), able to absorb within the so-called therapeutic window. Thus, the exposure to light of otherwise inert molecules promotes the population of excited states of the drug, that in PDT are able to produce the cytotoxic species, such as 1O2 and other ROS, in PACT can be responsible of the active species release or formation. Following the success of cisplatin in conventional treatments, many other transition metal complexes were explored as anticancer agents for applications in different medical approaches, including PDT and PACT, in order to improve their chemical, biological and photophysical properties. In this field, several crucial characteristics of candidate PSs can be accurately predicted from first principle calculations, especially in the framework of density functional theory and its time-dependent formulation, contributing to the understanding of the entire photochemical pathways involved which can ultimately help in improving the efficiency of a drug. A brief overview of the outcomes on some platinum and ruthenium-based PSs proposed for the application in the two phototherapies will be provided.

Keywords: TDDFT, metal complexes, PACT, PDT

Procedia PDF Downloads 86

Authors: Sara Assi, Berthe Hayar, Claudio Pisano, Nadine Darwiche, Walid Saad

Abstract:

Nanomedicine, the application of nanotechnology to medicine, is an emerging discipline that has gained significant attention in recent years. Current breakthroughs in nanomedicine have paved the way to develop effective drug delivery systems that can be used to target cancer. The use of nanotechnology provides effective drug delivery, enhanced stability, bioavailability, and permeability, thereby minimizing drug dosage and toxicity. As such, the use of nanoparticle (NP) formulations in drug delivery has been applied in various cancer models and have shown to improve the ability of drugs to reach specific targeted sites in a controlled manner. Cancer is one of the major causes of death worldwide; in particular, colorectal cancer (CRC) is the third most common type of cancer diagnosed amongst men and women and the second leading cause of cancer related deaths, highlighting the need for novel therapies. Retinoids, consisting of natural and synthetic derivatives, are a class of chemical compounds that have shown promise in preclinical and clinical cancer settings. However, retinoids are limited by their toxicity and resistance to treatment. To overcome this resistance, various synthetic retinoids have been developed, including the adamantyl retinoid ST1926, which is a potent anti-cancer agent. However, due to its limited bioavailability, the development of ST1926 has been restricted in phase I clinical trials. We have previously investigated the preclinical efficacy of ST1926 in CRC models. ST1926 displayed potent inhibitory and apoptotic effects in CRC cell lines by inducing early DNA damage and apoptosis. ST1926 significantly reduced the tumor doubling time and tumor burden in a xenograft CRC model. Therefore, we developed ST1926-NPs and assessed their efficacy in CRC models. ST1926-NPs were produced using Flash NanoPrecipitation with the amphiphilic diblock copolymer polystyrene-b-ethylene oxide and cholesterol as a co-stabilizer. ST1926 was formulated into NPs with a drug to polymer mass ratio of 1:2, providing a stable formulation for one week. The contin ST1926-NP diameter was 100 nm, with a polydispersity index of 0.245. Using the MTT cell viability assay, ST1926-NP exhibited potent anti-growth activities as naked ST1926 in HCT116 cells, at pharmacologically achievable concentrations. Future studies will be performed to study the anti-tumor activities and mechanism of action of ST1926-NPs in a xenograft mouse model and to detect the compound and its glucuroconjugated form in the plasma of mice. Ultimately, our studies will support the use of ST1926-NP formulations in enhancing the stability and bioavailability of ST1926 in CRC.

Keywords: nanoparticles, drug delivery, colorectal cancer, retinoids

Procedia PDF Downloads 90

Authors: Itze Coronel Salomon

Abstract:

The rise of organized crime and violence related to drug cartels in Mexico has created serious challenges for the authorities to provide security to those who live within its borders. However, to achieve a significant improvement in security is absolute respect for fundamental human rights by the authorities. Irregular migrants in Mexico are at serious risk of abuse. Research by Amnesty International as well as reports of the NHRC (National Human Rights) in Mexico, have indicated the major humanitarian crisis faced by thousands of migrants traveling in the shadows. However, the true extent of the problem remains invisible to the general population. The fact that federal and state governments leave no proper record of abuse and do not publish reliable data contributes to ignorance and misinformation, often spread by the media that portray migrants as the source of crime rather than their victims. Discrimination and intolerance against irregular migrants can generate greater hostility and exclusion. According to the modus operandi that has been recorded criminal organizations and criminal groups linked to drug trafficking structures deprive migrants of their liberty for forced labor and illegal activities related to drug trafficking, even some have been kidnapped for be trained as murderers . If the victim or their family cannot pay the ransom, the kidnapped person may suffer torture, mutilation and amputation of limbs or death. Migrant women are victims of sexual abuse during her abduction as well. In 2011, at least 177 bodies were identified in the largest mass grave found in Mexico, located in the town of San Fernando, in the border state of Tamaulipas, most of the victims were killed by blunt instruments, and most seemed to be immigrants and travelers passing through the country. With dozens of small graves discovered in northern Mexico, this may suggest a change in tactics between organized crime groups to the different means of obtaining revenue and reduce murder profile methods. Competition and conflict over territorial control drug trafficking can provide strong incentives for organized crime groups send signals of violence to the authorities and rival groups. However, as some Mexican organized crime groups are increasingly looking to take advantage of income and vulnerable groups, such as Central American migrants seem less interested in advertising his work to authorities and others, and more interested in evading detection and confrontation. This paper pretends to analyze the introduction of this new trend of kidnapping migrants for forced labors by drug cartels in Mexico into the forms of contemporary slavery and its implications.

Keywords: international law, migration, transnational organized crime

Procedia PDF Downloads 406

Authors: Hannah Gutmann, Rick Richardson, Richard Bryant

Abstract:

Intrusive memories following a traumatic event are not uncommon. However, in some individuals, these memories become maladaptive and lead to prolonged stress reactions. A seminal model of PTSD explains that aberrant processing during trauma may lead to prolonged stress reactions and intrusive memories. This model explains that elevated arousal at the time of the trauma promotes data driven processing, leading to fragmented and intrusive memories. This study investigated the role of elevated arousal on the development of intrusive memories. We measured salivary markers of arousal and investigated what impact this had on data driven processing, memory fragmentation, and subsequently, the development of intrusive memories. We assessed 100 healthy participants to understand their processing style, arousal, and experience of intrusive memories. Participants were randomised to a control or experimental condition, the latter of which was designed to increase their arousal. Based on current theory, participants in the experimental condition were expected to engage in more data driven processing and experience more intrusive memories than participants in the control condition. This research aims to shed light on the mechanisms underlying the development of intrusive memories to illustrate ways in which therapeutic approaches for PTSD may be augmented for greater efficacy.

Keywords: stress, cortisol, SAA, PTSD, intrusive memories

Procedia PDF Downloads 186

Authors: Trina Isabel D. Santiago, Juan Raphael M. Perez, Maria Angelica O. Soriano, Teresita B. Suing, Jumee F. Tayaban

Abstract:

To achieve universal healthcare for everyone, the World Health Organization has emphasized the importance of National Medicines Policies for increased accessibility and utilization of high-quality and affordable medications. In the Philippines, significant challenges have been identified surrounding the sustainability of essential medicines, resulting in limited access such as high cost and dominance and market dominance and monopoly of multinational companies (MNCs) in the Philippine pharmaceutical industry. These identified challenges have been addressed by several initiatives, such as the Philippine National Drug Policy and Generics Act of 1988 (Republic Act 6675), to attempt to reduce drug prices. Despite these efforts, the concerns with drug accessibility and affordability continue to persist; hence, Republic Act 9502 was enacted. This paper attempts to review RA 9502 in the pursuit of making medicines more affordable for Filipinos, analyze and critique the problems and challenges associated with the law, and provide recommendations to address identified problems and challenges. A literature search and review, as well as an analysis of the law, has been done to evaluate the policy. RA 9502 recognizes the importance of market competition in drug price reduction and quality medicine accessibility. Contentious issues prior to enactment of the law include 1) parallel importation, pointing out that the drug price will depend on the global market price, 2) contrasting approaches in the drafting of the law as the House version focused on medicine price control while the Senate version prioritized market competition, and 3) MNCs opposing the amendments with concerns on discrimination, constitutional violations, and noncompliance with international treaty obligations. There are also criticisms and challenges with the implementation of the law in terms of content or modeling, interpretation and implementation, and other external factors or hindrances. The law has been criticized for its narrow scope as it only covers specific essential medicines with no cooperation with the national health insurance program. Moreover, the law has sections taking advantage of the TRIPS flexibilities, which disallow smaller countries to reap the benefits of flexibilities. The sanctions and penalties have an insignificant role in implementation as they only ask for a small portion of the income of MNCs. Proposed recommendations for policy improvement include aligning existing legislation through strengthened price regulation and expanded law coverage, strengthening penalties to promote law adherence, and promoting research and development to encourage and support local initiatives. Through these comprehensive recommendations, the issues surrounding the policy can be addressed, and the goal of enhancing the affordability and accessibility of medicines in the country can be achieved.

Keywords: drug accessibility, drug affordability, price regulation, Republic Act 9502

Procedia PDF Downloads 33

Authors: Rady A., Elsheshai A., Eltawel M.

Abstract:

Introduction and Aim of work: Literature suggest that antipsychotic medications may decrease cortisol level, an effect that seems to be more present with second generation antipsychotic. Our study aims at assessing effect of long term use of antipsychotics on cortisol level Subjects and Methods: 30 chronic schizophrenic patients on antipsychotics compared to 20 drug naive schizophrenic patients as regards serum cortisol level Results: Cortisol level was significantly lower in chronic schizophrenic patients receiving antipsychotics compared to drug naive patients (P=0.002 <0.05) Conclusion: Antipsychotic medications seem to have the potential to decrease cortisol level in blood. Among hypothesis proposed in literature is the good control of pseudo stress due to psychotic features.

Keywords: schizophrenia, antipsychotic, cortisol, HPA

Procedia PDF Downloads 511

Authors: Zoe Goldberger, Priscilla S. Briquez, Jeffrey A. Hubbell

Abstract:

Tumor cells have mutations resulting from genetic instability that the immune system can actively recognize. Immune checkpoint immunotherapy (ICI) is commonly used in the clinic to re-activate immune reactions against mutated proteins, called neoantigens, resulting in tumor remission in cancer patients. However, only around 20% of patients show durable response to ICI. While tumor mutational burden (TMB) has been approved by the Food and Drug Administration (FDA) as a criterion for ICI therapy, the relevance of the subcellular localizations of the mutated proteins within the tumor cell has not been investigated. Here, we hypothesized that localization of mutations impacts the effect of immune responsiveness to ICI. We analyzed publicly available tumor mutation sequencing data of ICI treated patients from 3 independent datasets. We extracted the subcellular localization from the UniProtKB/Swiss-Prot database and quantified the proportion of membrane, cytoplasmic, nuclear, or secreted mutations per patient. We analyzed this information in relation to response to ICI treatment and overall survival of patients showing with 1722 ICI-treated patients that high mutational burden localized at the membrane (mTMB), correlate with ICI responsiveness, and improved overall survival in multiple cancer types. We anticipate that our results will ameliorate predictability of cancer patient response to ICI with potential implications in clinical guidelines to tailor ICI treatment. This would not only increase patient survival for those receiving ICI, but also patients’ quality of life by reducing the number of patients enduring non-effective ICI treatments.

Keywords: cancer, immunotherapy, membrane neoantigens, efficacy prediction, biomarkers

Procedia PDF Downloads 100

Authors: Leandra Prempeh, Emily Malugen

Abstract:

Prenatal drug exposure can have a molecular impact on the hypothalamic and reward genes that regulate feeding behavior. This can impact feeding regulation, resulting in feeding difficulties and growth failure. This was potentially seen in “McKayla,” a 19- month old girl with a history of in-utero drug exposure, patent ductus arteriosus, and gastroesophageal reflux disease who presented for intensive day treatment feeding therapy. She was diagnosed with Avoidant Restrictive Food Intake Disorder, described as total food refusal and meeting 100% of her caloric needs from a gastrostomy tube. The primary goals during intensive feeding therapy were to increase her oral intake and decrease her reliance on supplementation with formula. Several behavioral antecedent manipulations were implemented to establish consistent responding and make progress towards treatment goals. This included multiple modified bolus placements (using underloaded and Nuk brush), reinforcement contingencies, and variety fading before stability was finally achieved. Following, increasing retention of bites then increasing volume and variety were goals targeted. From treatment onset to the last 3 days of treatment, McKayla's rate of rapid acceptance of bite presentations increased significantly from 33.33% to 93.13%, rapid swallowing went from 0.00% to 92.32%, and her percentage of inappropriate mealtime behavior and expels decreased from 58.33% and 100% to 2.31% and 7.68%, respectively. Overall, the treatment team successfully introduced and increased the bite size of 7 pureed foods, generalize the treatment to caregivers with high integrity, and began facilitating tube weaning. She was receiving about 33.42% of her needs by mouth at the time of discharge. Other nutritional concerns addressed during treatment included drinking a nutritionally complete drink out of an open cup and age appropriate growth. McKayla continued to have emesis almost daily, as was her baseline before starting treatment; however, the frequency during mealtime decreased. Overall, McKayla responded well to treatment. She had a very slow response to treatment and required a lot of antecedent manipulations to establish consistent responding. As the literature suggests, [drug]-exposed neonates, like McKayla, may be at increased risk for nutritional and growth challenges that may persist throughout development. This supports the need for longterm follow-up of infant growth.

Keywords: behavioral intervention, feeding problems, in-utero drug exposure, intensive multidisciplinary intervention

Procedia PDF Downloads 54

Authors: Maryam Beiranvand

Abstract:

Multi-drug resistance in various microorganisms has increased globally in many healthcare facilities. Less effective antimicrobial activity of drug therapies for infection control becomes trouble. Since 1980, no new type of antimicrobial drug has been identified, even though combinations of antibiotic drugs have been discovered almost every decade. Between 1981 and 2006, over 70% of novel pharmaceuticals and chemical agents came from natural sources. Microorganisms have yielded almost 22,000 natural compounds. The identification of antimicrobial components from endophytes bacteria could help overcome the threat posed by multi-drug resistant strains. The project aims to analyze and identify antimicrobial peptides isolated from entophytic bacteria and their activity against multidrug-resistant Gram-negative bacteria in South Korea. Endophytic Paenibacillus polymyxa. 4G3 isolated from the plant, Gynura procumbery exhibited considerable antimicrobial activity against Methicillin-resistant Staphylococcus aureus, and Escherichia coli. The Rapid Annotations using Subsystems Technology showed that the total size of the draft genome was 5,739,603bp, containing 5178 genes with 45.8% G+C content. Genome annotation using antiSMASH version 6.0.0 was performed, which predicted the most common types of non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS). In this study, diethyl aminoethyl cellulose (DEAEC) resin was used as the first step in purifying for unknown peptides, and then the target protein was identified using hydrophilic and hydrophobic solutions, optimal pH, and step-by-step tests for antimicrobial activity. This crude was subjected to C18 chromatography and elution with 0, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100% methanol, respectively. Only the fraction eluted with 20% -60% methanol demonstrated good antimicrobial activity against MDR E. coli. The concentration of the active fragment was measured by the Brad-ford test, and Protein A280 - Thermo Fisher Scientific at the end by examining the SDS PAGE Resolving Gel, 10% Acrylamide and purity were confirmed. Our study showed that, based on the combined results of the analysis and purification. P polymyxa. 4G3 has a high potential exists for producing novel functions of polymyxin E and bacitracin against bacterial pathogens.

Keywords: endophytic bacteria, antimicrobial activity, antimicrobial peptide, whole genome sequencing analysis, multi -drug resistance gram negative bacteria

Procedia PDF Downloads 59

Authors: Alemu Tadesse Feroche

Abstract:

In this study, some 2, 3 distributed quinazoline -4 (3H) - one derivative were synthesized using a three-step synthetic route. They were obtained in a good yield (59.5-85%) by applying different chemical reactions like cyclization and condensation reactions. The chemical structure of the final compounds was also verified by spectroscopic methods (IR, ¹HNMR) and elemental microanalysis. The in vivo antimalarial activity of these compounds on P. berghei infected mice was found to be moderate to high at an oral dose of 0.04846 mmol/kg /day. This is equal to 25 mg/kg of chloroquine phosphate, which causes 100% inhibition of the parasite. It is worth mentioning that most active compounds (E) -3 Phenyl -2- [2- (pyridine -4- yl) vinyl] -4 (3H) -quinazolinone IVa (64.02%, (E)-2-[2-(4 - Hydroxy-3 - methoxystyryl) - vinyl) -3 - phenyl -4 (3H ) - quinazolinone IVc (77.25%) and (E)-2 –[2 –(Pyridin -4-yl) –vinyl] -3 phenenylamine -4(3H) quinazolinone IVe (73.54%) showed a dose-dependent increase in present suppression in antimalarial activities. Furthermore, the synthesized compounds were screened for their in vitro antileishmanial activity against L. aethiopica isolate (CL/039/09). All tested compounds (IVa (0.03766 ug/ml), IVb (0.00538 ug/ml, IVc (0.00412 ug/ml, IVd (0.00110 ug/ml), IVe (0.03017 ug/ml) and IVf (0.03894 ug/ml)) showed excellent potency that is much better than amphotericin B (IC50 = 0,04359 ug/ml). The results of acute toxicity indicated that all test compounds (IVa –IVf) proved to be nontoxic and well tolerated by the experimental animals up to 300 mg/kg in oral and 140 mg/kg in parental studies.

Keywords: 4(3H)-quinazolinone, in vivo antimalarial activity, in vitro antileishmanial activity, acute toxicity

Procedia PDF Downloads 90

Authors: Sarah Crawford, Gerry Lesley

Abstract:

This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

Procedia PDF Downloads 57

Authors: Sudhir Kumar, V. R. Sinha

Abstract:

Background: The topical and systemic toxicity associated with present nonmelanoma skin cancer (NMSC) treatment therapy using 5-Fluorouracil (5-FU) make it necessary to develop a novel delivery system having lesser toxicity and better control over drug release. Solid lipid nanoparticles offer many advantages like: controlled and localized release of entrapped actives, nontoxicity, and better tolerance. Aim:-To investigate safety and efficacy of 5-FU loaded solid lipid nanoparticles as a topical delivery system for the treatment of nonmelanoma skin cancer. Method: Topical solid lipid nanoparticles of 5-FU were prepared using Compritol 888 ATO (Glyceryl behenate) as lipid component and pluronic F68 (Poloxamer 188), Tween 80 (Polysorbate 80), Tyloxapol (4-(1,1,3,3-Tetramethylbutyl) phenol polymer with formaldehyde and oxirane) as surfactants. The SLNs were prepared with emulsification method. Different formulation parameters viz. type and ratio of surfactant, ratio of lipid and ratio of surfactant:lipid were investigated on particle size and drug entrapment efficiency. Results: Characterization of SLNs like–Transmission Electron Microscopy (TEM), Differential Scannig calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Particle size determination, Polydispersity index, Entrapment efficiency, Drug loading, ex vivo skin permeation and skin retention studies, skin irritation and histopathology studies were performed. TEM results showed that shape of SLNs was spherical with size range 200-500nm. Higher encapsulation efficiency was obtained for batches having higher concentration of surfactant and lipid. It was found maximum 64.3% for SLN-6 batch with size of 400.1±9.22 nm and PDI 0.221±0.031. Optimized SLN batches and marketed 5-FU cream were compared for flux across rat skin and skin drug retention. The lesser flux and higher skin retention was obtained for SLN formulation in comparison to topical 5-FU cream, which ensures less systemic toxicity and better control of drug release across skin. Chronic skin irritation studies lacks serious erythema or inflammation and histopathology studies showed no significant change in physiology of epidermal layers of rat skin. So, these studies suggest that the optimized SLN formulation is efficient then marketed cream and safer for long term NMSC treatment regimens. Conclusion: Topical and systemic toxicity associated with long-term use of 5-FU, in the treatment of NMSC, can be minimized with its controlled release with significant drug retention with minimal flux across skin. The study may provide a better alternate for effective NMSC treatment.

Keywords: 5-FU, topical formulation, solid lipid nanoparticles, non melanoma skin cancer

Procedia PDF Downloads 504

Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Mehboob Alam

Abstract:

The development of efficient delivery systems remains a major concern in cancer chemotherapy as many efficacious anticancer drugs are hydrophobic and difficult to formulate. Nanomedicines based on drug-loaded amphiphilic glycol chitosan micelles offer potential advantages for the formulation of drugs such as etoposide that may improve the pharmacokinetics and reduce the formulation-related adverse effects observed with current formulations. Amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxysuccinimide and quaternization to glycol chitosan backbone. To this end, a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternization, yielding a 13 kDa amphiphilic polymer. Micelles prepared from this amphiphilic polymer had a size of 162nm and were able to encapsulate up to 3 mg/ml etoposide. Pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drugs after intravenous administration. AUC 0.5-24h showed statistically significant difference in ETP-GCPQ vs. Commercial preparation in liver (25 vs.70, p<0.001), spleen (27 vs.36, p<0.05), lungs (42 vs.136,p<0.001),kidneys(25 vs.70,p< 0.05),and brain(19 vs.9,p<0.001). ETP-GCPQ crossed the blood-brain barrier, and 4, 3.5, 2.6, 1.8, 1.7, 1.5, and 2.5 fold higher levels of etoposide were observed at 0.5, 1, 2, 4, 6, 12, and 24hrs; respectively suggesting these systems could deliver hydrophobic anticancer drugs such as etoposide to tumors but also increased their transport through the biological barriers, thus making it a good delivery system

Keywords: glycol chitosan, micelles, pharmacokinetics, tissue distribution

Procedia PDF Downloads 93

Authors: Ranjot Kaur, Om P. Katare, Anupama Sharma, Sarah R. Dennison, Kamalinder K. Singh, Bhupinder Singh

Abstract:

Respiratory microbial infections being among the top leading cause of death worldwide are difficult to treat as the microbes reside deep inside the airways, where only a small fraction of drug can access after traditional oral or parenteral routes. As a result, high doses of drugs are required to maintain drug levels above minimum inhibitory concentrations (MIC) at the infection site, unfortunately leading to severe systemic side-effects. Therefore, delivering antimicrobials directly to the respiratory tract provides an attractive way out in such situations. In this context, current study embarks on the systematic development of lung lia pid-modified chitosan nanoparticles for inhalation of voriconazole. Following the principles of quality by design, the chitosan nanoparticles were prepared by ionic gelation method and further coated with major lung lipid by precipitation method. The factor screening studies were performed by fractional factorial design, followed by optimization of the nanoparticles by Box-Behnken Design. The optimized formulation has a particle size range of 170-180nm, PDI 0.3-0.4, zeta potential 14-17, entrapment efficiency 45-50% and drug loading of 3-5%. The presence of a lipid coating was confirmed by FESEM, FTIR, and X-RD. Furthermore, the nanoparticles were found to be safe upto 40µg/ml on A549 and Calu-3 cell lines. The quantitative and qualitative uptake studies also revealed the uptake of nanoparticles in lung epithelial cells. Moreover, the data from Spraytec and next-generation impactor studies confirmed the deposition of nanoparticles in lower airways. Also, the interaction of nanoparticles with DPPC monolayers signifies its biocompatibility with lungs. Overall, the study describes the methodology and potential of lipid-coated chitosan nanoparticles in futuristic inhalation nanomedicine for the management of pulmonary aspergillosis.

Keywords: dipalmitoylphosphatidylcholine, nebulization, DPPC monolayers, quality-by-design

Procedia PDF Downloads 132

Authors: Shazia Mannan, Zunera Khalid, Hammad-Ul-Mubeen

Abstract:

Wingless type Mouse mammary tumor virus (MMTV) Integration site-10B (Wnt10B) is an important member of the Wnt protein family that functions as cellular messenger in paracrine manner. Aberrant Wnt10B activity is the cause of several abnormalities including cancers of breast, cervix, liver, gastric tract, esophagus, pancreas as well as physiological problems like obesity, and osteoporosis. The objective of this study was to determine the possible inhibitors against aberrant expression of Wnt10B in order to prevent and treat the physiological disorders associated with it. Wnt10B3D structure was predicted by using comparative modeling and then analyzed by PROCHECK, Verify3D, and Errat. The model having 84.54% quality value was selected and acylated to satisfy the hydrophobic nature of Wnt10B. For search of inhibitors, virtual screening was performed on Natural Products (NP) database. The compounds were filtered and ligand-based screening was performed using the antagonist for mouse Wnt-3A. This resulted in a library of 272 unique compounds having most potent drug like activities for Wnt-4. Out of the 271 molecules analyzed three small molecules ZINC35442871, ZINC85876388, and ZINC00754234 having activity against Wnt4 abbarent expression were found common through docking experiment of Wnt10B. It is concluded that the three molecules ZINC35442871, ZINC85876388, and ZINC00754234 can be considered as lead compounds for performing further drug designing experiments against aberrant Wnt expressions.

Keywords: Wnt10B inhibitors, comparative computational studies, proto-oncogene, molecular docking

Procedia PDF Downloads 144

Authors: Rosa Tsegaye Aga, Xuan Jiang, Pavel Vazquez Faci, Siqing Liu, Simon Rayner, Endalkachew Alemu, Markos Abebe

Abstract:

Tuberculosis (TB) is a major cause of disease globally. In most cases, TB is treatable and curable, but only with the proper treatment. There is a time when drug-resistant TB occurs when bacteria become resistant to the drugs that are used to treat TB. Current strategies to identify drug-resistant TB bacteria are laboratory-based, and it takes a longer time to identify the drug-resistant bacteria and treat the patient accordingly. But machine learning (ML) and data science approaches can offer new approaches to the problem. In this study, we propose to develop an ML-based model to predict the antibiotic resistance phenotypes of TB isolates in minutes and give the right treatment to the patient immediately. The study has been using the whole genome sequence (WGS) of TB isolates as training data that have been extracted from the NCBI repository and contain different countries’ samples to build the ML models. The reason that different countries’ samples have been included is to generalize the large group of TB isolates from different regions in the world. This supports the model to train different behaviors of the TB bacteria and makes the model robust. The model training has been considering three pieces of information that have been extracted from the WGS data to train the model. These are all variants that have been found within the candidate genes (F1), predetermined resistance-associated variants (F2), and only resistance-associated gene information for the particular drug. Two major datasets have been constructed using these three information. F1 and F2 information have been considered as two independent datasets, and the third information is used as a class to label the two datasets. Five machine learning algorithms have been considered to train the model. These are Support Vector Machine (SVM), Random forest (RF), Logistic regression (LR), Gradient Boosting, and Ada boost algorithms. The models have been trained on the datasets F1, F2, and F1F2 that is the F1 and the F2 dataset merged. Additionally, an ensemble approach has been used to train the model. The ensemble approach has been considered to run F1 and F2 datasets on gradient boosting algorithm and use the output as one dataset that is called F1F2 ensemble dataset and train a model using this dataset on the five algorithms. As the experiment shows, the ensemble approach model that has been trained on the Gradient Boosting algorithm outperformed the rest of the models. In conclusion, this study suggests the ensemble approach, that is, the RF + Gradient boosting model, to predict the antibiotic resistance phenotypes of TB isolates by outperforming the rest of the models.

Keywords: machine learning, MTB, WGS, drug resistant TB

Procedia PDF Downloads 36

Authors: Veronika Solilová, Danuše Nerudová

Abstract:

The paper examines the interaction between the environmental taxation, size of government spending on environmental protection and greenhouse gas emissions and gross inland energy consumption. The aim is to analyze the effects of environmental taxation and government spending on environmental protection as an environmental policy instruments on greenhouse gas emissions and gross inland energy consumption in the EU15. The empirical study is performed using a VAR approach with the application of aggregated data of EU15 over the period 1995 to 2012. The results provide the evidence that the reactions of greenhouse gas emission and gross inland energy consumption to the shocks of environmental policy instruments are strong, mainly in the short term and decay to zero after about 8 years. Further, the reactions of the environmental policy instruments to the shocks of greenhouse gas emission and gross inland energy consumption are also strong in the short term, however with the deferred effects. In addition, the results show that government spending on environmental protection together with gross inland energy consumption has stronger effect on greenhouse gas emissions than environmental taxes in EU15 over the examined period.

Keywords: VAR analysis, greenhouse gas emissions, environmental taxation, government spending

Procedia PDF Downloads 282

Authors: Mostafa Sefidgar, Sohrab Zendehboudi, Hossein Bazmara, Madjid Soltani

Abstract:

Based on findings from clinical applications, most drug treatments fail to eliminate malignant tumors completely even though drug delivery through systemic administration may inhibit their growth. Therefore, better understanding of tumor formation is crucial in developing more effective therapeutics. For this purpose, nowadays, solid tumor modeling and simulation results are used to predict how therapeutic drugs are transported to tumor cells by blood flow through capillaries and tissues. A solid tumor is investigated as a porous media for fluid flow simulation. Most of the studies use Darcy model for porous media. In Darcy model, the fluid friction is neglected and a few simplified assumptions are implemented. In this study, the effect of these assumptions is studied by considering Brinkman model. A multi scale mathematical method which calculates fluid flow to a solid tumor is used in this study to investigate how neglecting fluid friction affects the solid tumor simulation. In this work, the mathematical model in our previous studies is developed by considering two model of momentum equation for porous media: Darcy and Brinkman. The mathematical method involves processes such as fluid flow through solid tumor as porous media, extravasation of blood flow from vessels, blood flow through vessels and solute diffusion, convective transport in extracellular matrix. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network. Finally, the two models of porous media are used for modeling fluid flow in normal and tumor tissues in three different shapes of tumors. Simulations of interstitial fluid transport in a solid tumor demonstrate that the simplifications used in Darcy model affect the interstitial velocity and Brinkman model predicts a lower value for interstitial velocity than the values that Darcy model does.

Keywords: solid tumor, porous media, Darcy model, Brinkman model, drug delivery

Procedia PDF Downloads 287

Authors: X. Li, J. Sundquist, C. Sjöstedt, M. Winkleby, K. S. Kendler, K. Sundquist

Abstract:

Aims: This study examines the association between the incidence of drug abuse (DA) and linking (communal) social capital, a theoretical concept describing the amount of trust between individuals and societal institutions. Methods: We present results from an 8-year population-based cohort study that followed all residents in Sweden, aged 15-44, from 2003 through 2010, for a total of 1,700,896 men and 1,642,798 women. Social capital was conceptualized as the proportion of people in a geographically defined neighborhood who voted in local government elections. Multilevel logistic regression was used to estimate odds ratios (ORs) and between-neighborhood variance. Results: We found robust associations between linking social capital (scored as a three level variable) and DA in men and women. For men, the OR for DA in the crude model was 2.11 [95% confidence interval (CI) 2.02-2.21] for those living in areas with the lowest vs. highest level of social capital. After accounting for neighborhood-level deprivation, the OR fell to 1.59 (1.51-1-68), indicating that neighborhood deprivation lies in the pathway between linking social capital and DA. The ORs remained significant after accounting for age, sex, family income, marital status, country of birth, education level, and region of residence, and after further accounting for comorbidities and family history of comorbidities and family history of DA. For women, the OR decreased from 2.15 (2.03-2.27) in the crude model to 1.31 (1.22-1.40) in the final model, adjusted for multiple neighborhood-level and individual-level variables. Conclusions: Our study suggests that low linking social capital may have important independent effects on DA.

Keywords: drug abuse, social linking capital, environment, family

Procedia PDF Downloads 464

Authors: Laurisa Peters, Usha Barahmand, Maria Stalias-Mantzikos, Naila Shamsina, Kerry Aguero

Abstract:

In the current study, the authors sought to examine whether the links between moral and sexual disgust and misophonia are mediated by mental contamination. An internationally diverse sample of 283 adults (193 females, 76 males, and 14 non-binary individuals) ranging in age from 18 to 60 years old was recruited from online social media platforms and survey recruitment sites. The sample completed an online battery of scales that consisted of the New York Misophonia Scale, State Mental Contamination Scale, and the Three-Domain Disgust Scale. The hypotheses were evaluated using a series of mediations performed using the PROCESS add-on in SPSS. Correlations were found between emotional and aggressive-avoidant reactions in misophonia, mental contamination, pathogen disgust, and sexual disgust. Moral disgust and non-aggressive reactions in misophonia failed to correlate significantly with any of the other constructs. Sexual disgust had direct and indirect effects, while pathogen disgust had only direct effects on aspects of misophonia. These findings partially support our hypothesis that mental contamination mediates the link between disgust propensity and misophonia while also confirming that pathogen-based disgust is not associated with mental contamination. Findings imply that misophonia is distinct from obsessive-compulsive disorder. Further research into the conceptualization of moral disgust is warranted.

Keywords: misophonia, moral disgust, pathogen disgust, sexual disgust, mental contamination

Procedia PDF Downloads 83

Authors: Nureni A. Yekini, Isaac T. Babalola, Edwin E. Aighokhan, Agnes K. Akinwole, N. Stephen Igwe

Abstract:

Survey was conducted to gather information on potential adverse health effects of Mobile Phones, and Telecommunication Tower Base Stations in Nigeria. Data was sourced from two sampled populations. Firstly from the people living in close proximity to base stations, and secondly from cell phone users. Questionnaire was used to gathered information from 574 people on thirteen non-specific health symptoms. Data obtained was presented and analyzed. The analysis shows that people living close to the based stations over a long period of time with or without cell phone, and also the heavy phone users with close proximity to the base stations are liable to have some potential health hazards, such as fatigue, sleep disturbances, headaches, feeling of discomfort, difficulty in concentrating, depression, memory loss, visual disruptions, irritability, hearing disruptions, skin problems, cardiovascular disorders, and dizziness.

Keywords: health hazards, wireless base stations, phone users, mobile phones, Nigeria

Procedia PDF Downloads 306