Search results for: adverse drugs reactions (ADR)

Authors: Arunas Burinskas, Aurelija Burinskiene

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On average, ten percent of drugs - commercial products are not available in pharmacies due to shortage. The shortage event disbalance sales and requires a recovery period, which is too long. Therefore, one of the critical issues that pharmacies do not record potential sales transactions during shortage and recovery periods. The authors suggest estimating outliers during shortage and recovery periods. To shorten the recovery period, the authors suggest using average sales per sales day prediction, which helps to protect the data from being downwards or upwards. Authors use the outlier’s visualization method across different drugs and apply the Grubbs test for significance evaluation. The researched sample is 100 drugs in a one-month time frame. The authors detected that high demand variability products had outliers. Among analyzed drugs, which are commercial products i) High demand variability drugs have a one-week shortage period, and the probability of facing a shortage is equal to 69.23%. ii) Mid demand variability drugs have three days shortage period, and the likelihood to fall into deficit is equal to 34.62%. To avoid shortage events and minimize the recovery period, real data must be set up. Even though there are some outlier detection methods for drug data cleaning, they have not been used for the minimization of recovery period once a shortage has occurred. The authors use Grubbs’ test real-life data cleaning method for outliers’ adjustment. In the paper, the outliers’ adjustment method is applied with a confidence level of 99%. In practice, the Grubbs’ test was used to detect outliers for cancer drugs and reported positive results. The application of the Grubbs’ test is used to detect outliers which exceed boundaries of normal distribution. The result is a probability that indicates the core data of actual sales. The application of the outliers’ test method helps to represent the difference of the mean of the sample and the most extreme data considering the standard deviation. The test detects one outlier at a time with different probabilities from a data set with an assumed normal distribution. Based on approximation data, the authors constructed a framework for scaling potential sales and estimating outliers with Grubbs’ test method. The suggested framework is applicable during the shortage event and recovery periods. The proposed framework has practical value and could be used for the minimization of the recovery period required after the shortage of event occurrence.

Keywords: drugs, Grubbs' test, outlier, shortage event

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Authors: Niyti, Aman Deep, Rajesh Kharab, Sahila Chopra, Raj. K. Gupta

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Relatively long-lived transactinide elements (i.e., elements with atomic number Z≥104) up to Z = 108 have been produced in nuclear reactions between low Z projectiles (C to Al) and actinide targets. Cross sections have been observed to decrease steeply with increasing Z. Recently, production cross sections of several picobarns have been reported for comparatively neutron-rich nuclides of 112 through 118 produced via hot fusion reactions with 48Ca and actinide targets. Some of those heavy nuclides are reported to have lifetimes on the order of seconds or longer. The relatively high cross sections in these hot fusion reactions are not fully understood and this has renewed interest in systematic studies of heavy-ion reactions with actinide targets. The main aim of this work is to understand the dynamics hot fusion reactions 18O+ 248Cm and 22Ne+244Pu (carried out at RIKEN and TASCA respectively) using the collective clusterization technique, carried out by undertaking the decay of the compound nucleus 266Rf∗ into 4n, 5n and 6n neutron evaporation channels. Here we extend our earlier study of the excitation functions (EFs) of 266Rf∗, formed in fusion reaction 18O+248Cm, based on Dynamical Cluster-decay Model (DCM) using the pocket formula for nuclear proximity potential, to the use of other nuclear interaction potentials derived from Skyrme energy density formalism (SEDF) based on semiclassical extended Thomas Fermi (ETF) approach and also study entrance channel effects by considering the synthesis of 266Rf* in 22Ne+244Pu reaction. The Skyrme forces used are the old force SIII, and new forces GSkI and KDE0(v1). Here, the EFs for the production of 260Rf, 261Rf and 262Rf isotope via 6n, 5n and 4n decay channel from the 266Rf∗ compound nucleus are studied at Elab = 88.2 to 125 MeV, including quadrupole deformations β2i and ‘hot-optimum’ orientations θi. The calculations are made within the DCM where the neck-length ∆R is the only parameter representing the relative separation distance between two fragments and/or clusters Ai which assimilates the neck formation effects.

Keywords: entrance channel effects, fusion reactions, skyrme force, superheavy nucleus

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Authors: Navid Kaboudi, Ali Shayanfar

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Introduction: Feeding infants with safe milk from the beginning of their life is an important issue. Drugs which are used by mothers can affect the composition of milk in a way that is not only unsuitable, but also toxic for infants. Consuming permeable drugs during that sensitive period by mother could lead to serious side effects to the infant. Due to the ethical restrictions of drug testing on humans, especially women, during their lactation period, computational approaches based on structural parameters could be useful. The aim of this study is to develop mechanistic models to predict the M/P ratio of drugs during breastfeeding period based on their structural descriptors. Methods: Two hundred and nine different chemicals with their M/P ratio were used in this study. All drugs were categorized into two groups based on their M/P value as Malone classification: 1: Drugs with M/P>1, which are considered as high risk 2: Drugs with M/P>1, which are considered as low risk Thirty eight chemical descriptors were calculated by ACD/labs 6.00 and Data warrior software in order to assess the penetration during breastfeeding period. Later on, four specific models based on the number of hydrogen bond acceptors, polar surface area, total surface area, and number of acidic oxygen were established for the prediction. The mentioned descriptors can predict the penetration with an acceptable accuracy. For the remaining compounds (N= 147, 158, 160, and 174 for models 1 to 4, respectively) of each model binary regression with SPSS 21 was done in order to give us a model to predict the penetration ratio of compounds. Only structural descriptors with p-value<0.1 remained in the final model. Results and discussion: Four different models based on the number of hydrogen bond acceptors, polar surface area, and total surface area were obtained in order to predict the penetration of drugs into human milk during breastfeeding period About 3-4% of milk consists of lipids, and the amount of lipid after parturition increases. Lipid soluble drugs diffuse alongside with fats from plasma to mammary glands. lipophilicity plays a vital role in predicting the penetration class of drugs during lactation period. It was shown in the logistic regression models that compounds with number of hydrogen bond acceptors, PSA and TSA above 5, 90 and 25 respectively, are less permeable to milk because they are less soluble in the amount of fats in milk. The pH of milk is acidic and due to that, basic compounds tend to be concentrated in milk than plasma while acidic compounds may consist lower concentrations in milk than plasma. Conclusion: In this study, we developed four regression-based models to predict the penetration class of drugs during the lactation period. The obtained models can lead to a higher speed in drug development process, saving energy, and costs. Milk/plasma ratio assessment of drugs requires multiple steps of animal testing, which has its own ethical issues. QSAR modeling could help scientist to reduce the amount of animal testing, and our models are also eligible to do that.

Keywords: logistic regression, breastfeeding, descriptors, penetration

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Authors: Simona Dostalova, Dita Munzova, Ana Maria Jimenez Jimenez, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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The boom of nanomedicine in recent years has led to the development of numerous new nanomaterials that can be used as nanocarriers in the drug delivery. These nanocarriers can either be synthetic or natural-based. The disadvantage of many synthetic nanocarriers is their toxicity in patient’s body. Protein cages that can naturally be found in human body do not exhibit such disadvantage. However, the release of cargo from some protein cages in target cells can be problematic. As a special type of protein cages can serve the capsid of many viruses, including phage. Phages infect bacterial cells; therefore they are not harmful to human cells. The targeting of phage particles to cancer cells can be solved by producing of empty phage capsids during which the targeting moieties (e.g. peptides) can be cloned into genes of phage capsid to decorate its surface. Moreover, the produced capsids do not contain viral nucleic acid and are therefore not infectious to beneficial bacteria in the patient’s body. The protein cage composed of viral capsid is larger than other frequently used apoferritin cage but its size is still small enough to benefit from passive targeting by Enhanced Permeability and Retention effect. In this work, bacteriophage λ was used, both whole and its empty capsid for delivery of different cytotoxic drugs (cisplatin, carboplatin, oxaliplatin, etoposide and doxorubicin). Large quantities of phage λ were obtained from phage λ-producing strain of E. coli cultivated in medium with 0.2 % maltose. After killing of E. coli with chloroform and its removal by centrifugation, the phage was concentrated by ultracentrifugation at 130 000 g and 4 °C for 3 h. The encapsulation of the drugs was performed by infusion method and four different concentrations of the drugs were encapsulated (200; 100; 50; 25 µg/ml). Free molecules of drugs were removed by dialysis. The encapsulation was verified using spectrophotometric and electrochemical methods. The amount of encapsulated drug linearly increased with the amount of applied drug (determination coefficient R2=0.8013). 76% of applied drug was encapsulated in phage λ particles (concentration of 10 µg/ml), even with the highest applied concentration of drugs, 200 µg/ml. Only 1% of encapsulated drug was detected in phage DNA. Similar results were obtained with encapsulation in phage empty capsid. Therefore, it can be concluded that the encapsulation of drugs into phage particles is efficient and mostly occurs by interaction of drugs with protein capsid.

Keywords: cytostatics, drug delivery, nanocarriers, phage capsid

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Authors: Zahid Hussain, Nayyab Sultan

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This study describes the preparation of zinc oxide nanoparticles and their anti-diabetic effect individually and with the combination of Momordica charantia plant extract. This plant is termed bitter melon, balsam pear, bitter gourd, or karela. Blood glucose levels in mice were monitored in their random state before and after the administration of zinc oxide nanoparticles and plant extract. The powdered form of nanoparticles and the selected plant were used as an oral treatment. Diabetes was induced in mice by using a chemical named as streptozotocin. It is an artificial diabetes-inducing chemical. In the case of zinc oxide nanoparticles (3mg/kg) and Momordica charantia plant extract (500mg/kg); the maximum anti-diabetic effect observed was 70% ± 1.6 and 75% ± 1.3, respectively. In the case of the combination of zinc oxide nanoparticles (3mg/kg) and Momordica charantia plant extract (500mg/kg), the maximum anti-diabetic effect observed was 86% ± 2.0. The results obtained were more effective as compared to standard drugs Amaryl (3mg/kg), having an effectiveness of 52% ± 2.4, and Glucophage (500mg/kg), having an effectiveness of 29% ± 2.1. Results indicate that zinc oxide nanoparticles and plant extract in combination are more helpful in treating diabetes as compared to their individual treatments. It is considered a natural treatment without any side effects rather than using standard drugs, which shows adverse side effects on health, and most probably detoxifies in liver and kidneys. More experimental work and extensive research procedures are still required in order to make them applicable to pharmaceutical industries.

Keywords: albino mice, amaryl, anti-diabetic effect, blood glucose level, Camellia sinensis, diabetes mellitus, Momordica charantia plant extract, streptozotocin, zinc oxide nanoparticles

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Authors: Pompa Marcello, Mauro Capocelli, Vincenzo Piemonte

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This work focuses on a mathematical model able to describe the gastro-intestinal physiology and providing a rational tool for the design of an artificial gastro-intestinal system. This latter is mainly devoted to analyse the absorption and bioavailability of drugs and nutrients through in vitro tests in order to overcome (or, at least, to partially replace) in vivo trials. The provided model realizes a conjunction ring (with extended prediction capability) between in vivo tests and mechanical-laboratory models emulating the human body. On this basis, no empirical equations controlling the gastric emptying are implemented in this model as frequent in the cited literature and all the sub-unit and the related system of equations are physiologically based. More in detail, the model structure consists of six compartments (stomach, duodenum, jejunum, ileum, colon and blood) interconnected through pipes and valves. Paracetamol, Ketoprofen, Irbesartan and Ketoconazole are considered and analysed in this work as reference drugs. The mathematical model has been validated against in vivo literature data. Results obtained show a very good model reliability and highlight the possibility to realize tailored simulations for different couples patient-drug, including food adsorption dynamics.

Keywords: gastro-intestinal model, drugs bioavailability, paracetamol, ketoprofen

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Authors: Veronika Lesáková, Silvia Slezáková, František Štěpánek

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Additive manufacturing technologies producing drug dosage forms aimed at personalized medicine applications are promising strategies with several advantages over the conventional production methods. One of the emerging technologies is 3D printing which reduces manufacturing steps and thus allows a significant drop in expenses. A decrease in material consumption is also a highly impactful benefit as the tested drugs are frequently expensive substances. In addition, 3D printed dosage forms enable increased patient compliance and prevent misdosing as the dosage forms are carefully designed according to the patient’s needs. The incorporation of multiple drugs into a single dosage form further increases the degree of personalization. Our research focuses on the development of 3D printed tablets incorporating multiple drugs (candesartan, losartan) and thermoplastic polymers (e.g., KlucelTM HPC EF). The filaments, an essential feed material for 3D printing,wereproduced via hot-melt extrusion. Subsequently, the extruded filaments of various formulations were 3D printed into tablets using an FDM 3D printer. Then, we have assessed the influence of the internal structure of 3D printed tablets and formulation on dissolution behaviour by obtaining the dissolution profiles of drugs present in the 3D printed tablets. In conclusion, we have developed tablets containing multiple drugs providing modified release profiles. The 3D printing experiments demonstrate the high tunability of 3D printing as each tablet compartment is constructed with a different formulation. Overall, the results suggest that the 3D printing technology is a promising manufacturing approach to dual tablet preparation for personalized medicine.

Keywords: 3D printing, drug delivery, hot-melt extrusion, dissolution kinetics

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Authors: Wei-Ju Huang, Hung-Pin Hsu

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[Background] In congestive heart failure (CHF), it has always been the principle of clinical treatment to control the water retention mechanism in the body to prevent excessive fluid retention. Early control of sympathetic nerves, Renin-Angiotensin-Aldosterone system (RAA system, RAAS), or strengthening of Atrial Natriuretic Peptide (ANP) was the point. In RAA system, related hormones, such as angiotensin, or enzymes in the pathway, such as ACE-I, can be used with corresponding inhibitors to reduce water content.[Aim] In recent years, clinical studies have pointed out that if different mechanisms are combined, the control effect seems to be better. For example, recent studies showed that ENTRESTO, a combination of Sacubitril and Valsartan, is a good new drug for CHF. Sacubitril is a prodrug. After activation, it can inhibit neprilysin and act as a neprilysin inhibitor (ARNI) to reduce the breakdown of natriuretic peptides(ANP). Valsartan is a kind of angiotensin receptor blocker (ARB), both of which are used to treat heart failure at the same time, have excellent curative effects.[Materials and Methods] Considering the side effects of this drug, coughing and a few cases of diarrhea were observed. However, the effect of this drug on the patient's intestinal tract has not been confirmed. On the other hand, studies have pointed out that ANP supplement can improve the CHF and increase the inhibitory effect on cancer cells. Therefore, the purpose of this study is to use a special microbial detection method to prove that whether oral drugs have an effect on microorganisms.The experimental method uses Nissui Compact Dry to observe the situation in different types of microorganisms. After the drug is dissolved in water, it is implanted in a petri dish, and the presence of different microorganisms is detected through different antibody reactions to confirm whether the drug has some toxicology in the gut.[Results and Discussion]From the above experimental results, it can be known that among the effects of Sacubitril and Valsartan on the basic microbial flora of the human body, low doses had no significant effect on Escherichia coli or intestinal bacteria. If Sacubitril or Valsartan with a high concentration of 3mg/ml is used alone or under the stimulation of a high concentration of the two drugs, it has a significant inhibitory effect on Escherichia coli. However, in terms of the effect on intestinal bacteria, high concentration of Sacubitril has a more significant inhibitory effect on intestinal bacteria, while high concentration of Valsartan has a less significant inhibitory effect on intestinal bacteria. The inhibitory effect of the combination of the two drugs on intestinal bacteria is also less significant.[Conclusion]The results of this study can be used as a further reference for the possible side effects of the clinical use of Sacubitril and Valsartan on the intestinal tract of patients,

Keywords: sacubitril, valsartan, entresto, congestive heart failure (CHF)

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Authors: Alejandra Betancur Sánchez, Carmen Elena Zapata Sánchez, Juan Bautista López Ortiz

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Adverse effects and increased air pollution has raised concerns about regulatory policies and has fostered the development of new air quality standards; this is due to the complexity of the composition and the poorly understood reactions in the atmospheric environment. Toxic compounds act as environmental agents having various effects, from irritation to death of cells and tissues. A toxic agent is defined an adverse response in a biological system. There is a particular class that produces some kind of alteration in the genetic material or associated components, so they are recognized as genotoxic agents. Within cells, they interact directly or indirectly with DNA, causing mutations or interfere with some enzymatic repair processes or in the genesis or polymerization of proteinaceous material involved in chromosome segregation. An air pollutant may cause or contribute to increased mortality or serious illness and even pose a potential danger to human health. The aim of this study was to evaluate the effect on the viability and the genotoxic potential on the cell lines CHO-K1 and Jurkat and peripheral blood of particulate matter PM T lymphocytes 2.5 obtained from filters collected three monitoring stations network air quality Aburrá Valley. Tests, reduction of MTT, trypan blue, NRU, comet assay, sister chromatid exchange (SCE) and chromosomal aberrations allowed evidence reduction in cell viability in cell lines CHO-K1 and Jurkat and damage to the DNA from cell line CHOK1, however, no significant effects were observed in the number of SCEs and chromosomal aberrations. The results suggest that PM2.5 material has genotoxic potential and can induce cancer development, as has been suggested in other studies.

Keywords: PM2.5, cell line Jurkat, cell line CHO-K1, cytotoxicity, genotoxicity

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Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

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Authors: Mustafa Al Sukar, Azzam Sleit, Abdullatif Abu-Dalhoum, Bassam Al-Kasasbeh

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Use and abuse of drugs by teens is very common and can have dangerous consequences. The drugs contribute to physical and sexual aggression such as assault or rape. Some teenagers regularly use drugs to compensate for depression, anxiety or a lack of positive social skills. Teen resort to smoking should not be minimized because it can be "gateway drugs" for other drugs (marijuana, cocaine, hallucinogens, inhalants, and heroin). The combination of teenagers' curiosity, risk taking behavior, and social pressure make it very difficult to say no. This leads most teenagers to the questions: "Will it hurt to try once?" Nowadays, technological advances are changing our lives very rapidly and adding a lot of technologies that help us to track the risk of drug abuse such as smart phones, Wireless Sensor Networks (WSNs), Internet of Things (IoT), etc. This technique may help us to early discovery of drug abuse in order to prevent an aggravation of the influence of drugs on the abuser. In this paper, we have developed a Decision Support System (DSS) for detecting the drug abuse using Artificial Neural Network (ANN); we used a Multilayer Perceptron (MLP) feed-forward neural network in developing the system. The input layer includes 50 variables while the output layer contains one neuron which indicates whether the person is a drug addict. An iterative process is used to determine the number of hidden layers and the number of neurons in each one. We used multiple experiment models that have been completed with Log-Sigmoid transfer function. Particularly, 10-fold cross validation schemes are used to access the generalization of the proposed system. The experiment results have obtained 98.42% classification accuracy for correct diagnosis in our system. The data had been taken from 184 cases in Jordan according to a set of questions compiled from Specialists, and data have been obtained through the families of drug abusers.

Keywords: drug addiction, artificial neural networks, multilayer perceptron (MLP), decision support system

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Authors: Hanjie Xie, Raphael Semiat, Ziyi Zhong

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It is well known that many oxidation reactions in nature are closely related to the origin and life activities. One of the features of these natural reactions is that they can proceed under mild conditions employing the oxidant of molecular oxygen (O₂) in the air and enzymes as catalysts. Catalysis is also a necessary part of life for human beings, as many chemical and pharmaceutical industrial processes need to use catalysts. However, most heterogeneous catalytic reactions must be run at high operational reaction temperatures and pressures. It is not strange that, in recent years, research interest has been redirected to green catalysis, e.g., trying to run catalytic reactions under relatively mild conditions as much as possible, which needs to employ green solvents, green oxidants such O₂, particularly air, and novel catalysts. This work reports the efficient binary Fe-Mn metal oxide catalysts for low-temperature formaldehyde (HCHO) oxidation, a toxic pollutant in the air, particularly in indoor environments. We prepared a series of nanosized FeMn oxide catalysts and found that when the molar ratio of Fe/Mn = 1:1, the catalyst exhibited the highest catalytic activity. At room temperature, we realized the complete oxidation of HCHO on this catalyst for 20 h with a high GHSV of 150 L g⁻¹ h⁻¹. After a systematic investigation of the catalyst structure and the reaction, we identified the reaction intermediates, including dioxymethylene, formate, carbonate, etc. It is found that the oxygen vacancies and the derived active oxygen species contributed to this high-low-temperature catalytic activity. These findings deepen the understanding of the catalysis of these binary Fe-Mn metal oxide catalysts.

Keywords: oxygen vacancy, catalytic oxidation, binary transition oxide, formaldehyde

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Authors: Londeka Ntuli, Frasia Oosthuizen

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Background: Tenefovir disiproxil fumarate (TDF) is a nephrotoxic drug and has been proven to contribute to renal insufficiency necessitating intensive monitoring and management of adverse effects arising from prolonged exposure to the drug. TDF is one of the preferred first-line drugs used in combination therapy in most regions. There are estimated 300 000 patients being initiated on the Efavirenz/TDF/Emtricitabine first-line regimen annually in South Africa. It is against this background that this study aims to investigate the effects of TDF on renal sufficiency of HIV positive patients. Methodology: A retrospective quantitative study was conducted, analysing clinical charts of HIV positive patient’s older than 18 years of age and on a TDF-containing regimen for more than 1 year. Data were obtained from the analysis of patient files and was transcribed into Microsoft® Excel® spreadsheet. Extracted data were coded, categorised and analysed using STATA®. Results: A total of 275 patient files were included in this study. Renal function started decreasing after 3 months of treatment (with 93.5% patients having a normal EGFR), and kept on decreasing as time progressed with only 39.6% normal renal function at year 4. Additional risk factors for renal insufficiency included age below 25, female gender, and additional medication. Conclusion: It is clear from this study that the use of TDF necessitates intensive monitoring and management of adverse effects arising from prolonged exposure to the drug. The findings from this study generated pertinent information on the safety profile of the drug TDF in a resource-limited setting of a public health institution. The appropriate management is of tremendous importance in the South African context where the majority of HIV positive individuals are on the TDF containing regimen; thus it is beneficial to ascertain the possible level of toxicities these patients may be experiencing.

Keywords: renal insufficiency, tenefovir, HIV, risk factors

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Authors: Halkiopoulos Constantinos, Gkintoni Evgenia, Koutsopoulou Ioanna, Antonopoulou Hera

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E-sports and e-gaming have emerged in recent years since the increase in internet use have become universal and e-gamers are the new reality in our homes. The excessive involvement of young adults with e-sports has already been revealed and the adverse consequences have been reported in researches in the past few years, but the issue has not been fully studied yet. The present research is conducted in Greece and studies the psychological profile of video game players and provides information on personality traits, habits and emotional status that affect online gamers’ behaviors in order to help professionals and policy makers address the problem. Three standardized self-report questionnaires were administered to participants who were young male and female adults aged from 19-26 years old. The Profile of Mood States (POMS) scale was used to evaluate people’s perceptions of their everyday life mood; the personality features that can trace back to people’s habits and anticipated reactions were measured by Eysenck Personality Questionnaire (EPQ), and the Trait Emotional Intelligence Questionnaire (TEIQue) was used to measure which cognitive (gamers’ beliefs) and emotional parameters (gamers’ emotional abilities) mainly affected/ predicted gamers’ behaviors and leisure time activities?/ gaming behaviors. Data mining techniques were used to analyze the data, which resulted in machine learning algorithms that were included in the software package R. The research findings attempt to designate the effect of personality traits, emotional status and emotional intelligence influence and correlation with e-sports, gamers’ behaviors and help policy makers and stakeholders take action, shape social policy and prevent the adverse consequences on young adults. The need for further research, prevention and treatment strategies is also addressed.

Keywords: e-sports, e-gamers, personality traits, POMS, emotional intelligence, data mining, R

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Authors: Kathryn L. Duncan, Charles A. Kuntz, Alessandra C. Santamaria, James O. Simcock

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Access to megavoltage radiation therapy for small animals is limited in many locations around the world. This can preclude the use of palliative radiation therapy for the treatment of appendicular osteosarcoma in dogs. The objective of this study was to retrospectively assess the adverse effects and survival times of dogs with appendicular osteosarcoma that were treated with hypofractionated orthovoltage radiation therapy and adjunctive carboplatin chemotherapy administered via a single subcutaneous infusion. Medical records were reviewed retrospectively to identify client-owned dogs with spontaneously occurring appendicular osteosarcoma that was treated with palliative orthovoltage radiation therapy and a single subcutaneous infusion of carboplatin. Data recorded included signalment, tumour location, results of diagnostic imaging, haematologic and serum biochemical analyses, adverse effects of radiation therapy and chemotherapy, and survival times. Kaplan-Meier survival analysis was performed, and log-rank analysis was used to determine the impact of specific patient variables on survival time. Twenty-three dogs were identified that met the inclusion criteria. Median survival time for dogs was 182 days. Eleven dogs had adverse haematologic effects, 3 had adverse gastrointestinal effects, 6 had adverse effects at the radiation site and 7 developed infections at the carboplatin infusion site. No statistically significant differences were identified in survival times based on sex, tumour location, development of infection, or pretreatment serum alkaline phosphatase. Median survival time and incidence of adverse effects were comparable to those previously reported in dogs undergoing palliative radiation therapy with megavoltage or cobalt radiation sources and conventional intravenous carboplatin chemotherapy. The use of orthovoltage palliative radiation therapy may be a reasonable alternative to megavoltage radiation in locations where access is limited.

Keywords: radiotherapy, veterinary oncology, chemotherapy, osteosarcoma

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Authors: Abhay Vir Singh Kanwar

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The pharmaceutical industry today is a multi-billion dollar business and yet disadvantages people in many corners of the globe who are still dying in large numbers from curable illnesses for lack of access to drugs. The astronomical prices of essential and life-saving drugs is not just an economic problem that can be settled through clever market strategies but is an ethical issue, given the accumulated wealth of today’s humanity and the sense of global justice that it increasingly comes to share. In this paper, I make a very practical argument for what I shall call ‘the ethical healthcare paradigm’, which, I propose, can replace the economistic paradigm that can still drive the healthcare sector without creating spillover effects on the market. Taking off from the ethical-philosophical argument for recognizing every individual’s right to capability to be healthy, I shall come to the focused practical proposal of the cost-rationalization and universal availability of essential, life-saving drugs through the undertaking of research and development funding for drug innovation by the business establishment as such in terms of the concept of CSR. The paper will first expose the concepts of basic and fundamental capabilities in relation to education and health, after which it will focus on the right to capability to be healthy of every person. In the third section, it will discuss the ‘ethical healthcare paradigm’ as opposed to the economistic health paradigm and will argue that the patient will have to be considered the primary stakeholder of this paradigm or the very ‘subject’ of healthcare. The next section will be on an ethical-historical critique of the pharmaceutical industry’s profit driven economism. The section after that will look at the business operation and the stages in the life cycle of a drug that comes to the market in order to understand the risks, strengths and problems of the pharmaceutical industry. Finally, the paper will discuss the concept of CSR in relation to the ethical healthcare paradigm in order to propose CSR funding in research and development for innovation on drugs so that life-saving drugs can be made available to every sick person cost-effectively.

Keywords: capability approach, healthcare, CSR, patient

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Authors: Raj Kumar, Prem Felix Siril

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The poor aqueous solubility of many pharmaceutical drugs and potential drug candidates is a big challenge in drug development. Nanoformulation of such candidates is one of the major solutions for the delivery of such drugs. We initially developed the evaporation assisted solvent-antisolvent interaction (EASAI) method. EASAI method is use full to prepared nanoparticles of poor water soluble drugs with spherical morphology and particles size below 100 nm. However, to further improve the effect formulation to reduce number of dose and side effect it is important to control the delivery of drugs. However, many drug delivery systems are available. Among the many nano-drug carrier systems, solid lipid nanoparticles (SLNs) have many advantages over the others such as high biocompatibility, stability, non-toxicity and ability to achieve controlled release of drugs and drug targeting. SLNs can be administered through all existing routes due to high biocompatibility of lipids. SLNs are usually composed of lipid, surfactant and drug were encapsulated in lipid matrix. A number of non-steroidal anti-inflammatory drugs (NSAIDs) have poor bioavailability resulting from their poor aqueous solubility. In the present work, SLNs loaded with NSAIDs such as Nabumetone (NBT), Ketoprofen (KP) and Ibuprofen (IBP) were successfully prepared using different lipids and surfactants. We studied and optimized experimental parameters using a number of lipids, surfactants and NSAIDs. The effect of different experimental parameters such as lipid to surfactant ratio, volume of water, temperature, drug concentration and sonication time on the particles size of SLNs during the preparation using hot-melt sonication was studied. It was found that particles size was directly proportional to drug concentration and inversely proportional to surfactant concentration, volume of water added and temperature of water. SLNs prepared at optimized condition were characterized thoroughly by using different techniques such as dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray diffraction (XRD) and differential scanning calorimetry and Fourier transform infrared spectroscopy (FTIR). We successfully prepared the SLN of below 220 nm using different lipids and surfactants combination. The drugs KP, NBT and IBP showed 74%, 69% and 53% percentage of entrapment efficiency with drug loading of 2%, 7% and 6% respectively in SLNs of Campul GMS 50K and Gelucire 50/13. In-vitro drug release profile of drug loaded SLNs is shown that nearly 100% of drug was release in 6 h.

Keywords: nanoparticles, delivery, solid lipid nanoparticles, hot-melt sonication, poor water soluble drugs, solubility, bioavailability

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Authors: Misbah Shahzadi

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The present study was conducted to identify the emotional and behavioral disturbances among the News Reporters covering Traumatic events. In the present study, a sample of 50 News Reporters belonging to the national and the local news agencies were selected from Rawalpindi and Islamabad who had covered any traumatic event in the past one year. Rotter’s Incomplete Sentence Blank (RISB) and Impact of Event Scale interpretations were used to assess a variety of emotional and behavioral patterns of News Reporters. Results showed that some of the frequent emotional and behavioral reactions exhibited by individuals like withdrawal, anxiety\depression, aggression, hyperarousal and avoidance behavior whereas gender-based comparisons indicated that there is no significant gender difference in the News Reporters in manifestations of behavioral and emotional disturbances. It is concluded that significant negative emotional and behavioral reactions are exhibited by the News Reporters who cover traumatic events. The study identifies the negative emotional and behavioral reactions/disturbances after trauma, which can be helpful for identifying problematic areas for counseling and therapeutic interventions for these News Reporters.

Keywords: behavioural disturbance, emotional disturbance, news reporters, traumatic events

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Authors: Artur Daniel Ramos Modolo

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Popular science magazines are an important way to communicate scientific information to lay audience in science. Since the popularization of social networking sites (SNSs) such as Facebook and Twitter, these magazines are trying to adapt their content to these new media. In this study, one hundred posts of popular science magazines on Facebook are analyzed regarding the use of genres of communication and readers’ reactions. The quantitative analysis of these features considers the variety of genres and how the users of Facebook answer to them (liking, sharing and commenting). The first hypothesis was that these magazines used the genres of communication posted on Facebook both to marketing and informational purposes and that these mixed intentions have an impact in the number of readers’ reactions. In order to analyze these features, twenty timeline posts published by five magazines: Cosmos, Galileu, New Scientist, Scientific American and Superinteressante were gathered during the period of three days (6th November 2015–8th November 2015). This research shows that the hyperlinks posted by these magazines created ways to diversify the communication genres used on their pages and, at the same time, revealed that, overall, readers react quantitatively different to these genres.

Keywords: Facebook, genres of communication, likes, popular science magazines, social networking sites

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Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Javaid Irfan, Andreas G. Schätzlein, Ijeoma F Uchegbeu

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Development of efficient delivery system for hydrophobic drugs remains a major concern in chemotherapy. The objective of the current study was to develop polymeric drug-delivery system for etoposide from amphiphilic derivatives of glycol chitosan, capable to improve the pharmacokinetics and to reduce the adverse effects of etoposide due to various organic solvents used in commercial formulations for solubilisation of etoposide. As a promising carrier, amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxy succinimide and quaternisation to glycol chitosan backbone. To this end a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternisation into 13 kDa. Nano sized micelles prepared from this amphiphilic polymer had the capability to encapsulate up to 3 mg/ml etoposide. The pharmacokinetic results indicated that GCPQ based etoposide formulation transformed the biodistribution pattern. AUC 0.5-24 hr 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. 30, p<0.05) and brain (19 vs. 9,p<0.001). Using the hydrophobic fluorescent dye Nile red, we showed that micelles efficiently delivered their payload to MCF7 and A2780 cancer cells in-vitro and to A431 xenograft tumor in-vivo, suggesting these systems could deliver hydrophobic anti- cancer drugs such as etoposide to tumors. The pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drug after intravenous administration. GCPQ based formulations not only reduced side effects associated with current available formulations but also increased their transport through the biological barriers, thus making it a good delivery system.

Keywords: glycol chitosan, Nile red, micelles, etoposide, A431 xenografts

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Authors: Nacira Mecheri, N. Boussid

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A new chemical mechanism designed to study the process of forming the first aromatic ring (benzene) and polycyclic aromatic hydrocarbons (PAH) from a flame of acetylene (C2H2) has been developed. The mechanism developed, contains 50 chemical species involved in 268 reversible elementary reactions. The comparison between the results from modelling and experimental measurements allowed us to test the validity of the postulated mechanism in specific experimental conditions. Kinetic analysis of the flame by calculating the maximum rates for each elementary reaction, allowed us to identify key reactions pathways of consumption and formation of main precursors of soot.

Keywords: benzene, PAH, acetylene, modeling, flame, soot

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Authors: Senem Avaz, Alpay Taralp

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Chitosan has been an attractive biopolymer for decades, but its processibility is lowered by its poor solubility, especially in physiological pH values. Freeze concentrated reactions of Chitosan with several organic acids including acrylic, citraconic, itaconic, and maleic acid revealed improved solubility and morphological properties. Solubility traits were assessed with a modified ninhydrin test. Chitosan derivatives were characterized by ATR-FTIR and morphological characteristics were determined by SEM. This study is a unique approach to chemically modify Chitosan to enhance water solubility.

Keywords: chitosan, freeze concentration, frozen reactions, ninhydrin test, water soluble chitosan

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Authors: Hüseyin Biçer

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The purpose of this study is an explanation of using and expectation traditional and complementary medicine in Turkey in terms of regionally, cultural and social. Due to geopolitics position, at the intersection of the Middle East, Africa and Europe, Turkey has historically hosted many civilizations and cultures, and hosts many religions at the same time and therefore is very open to intercultural interaction. For this reason, the traditional medicine of Turkey contains traces of many civilizations rather than a traditional medicine of its own. In Turkey, complementary and traditional medicine are used actively. The aim of the study is to measure whether the patients have ever taken traditional medicine as a caretaker or for the supportive treatment of their diseases, and as a result, their expectations. This cross-sectional, paper-based survey study was conducted in 27 state hospitals and 29 family medicine clinics in seven geographical regions of Turkey. Patients who had an appointment in the waiting rooms that day were included. 77.4% of the patients participating in the study stated that they used traditional medicine at least 5 times in their life, 27.6% stated that traditional medicine was sufficient in some diseases, and 36.8% stated that traditional treatment was a part of normal treatment. Both faith and cultural approaches in Turkey always keep traditional medicine close to drugs. Another danger, apart from traditional medicine drugs that can interact with drugs, is that patients find it sufficient to use traditional and complementary medicine alone.

Keywords: complementary medicine, traditional medicine, medicine in Turkey, alternative medicine

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Authors: Fahad Raj Khan, Suleman Khan

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There is a lack of consensus about the predictive value of raised blood glucose levels in terms of major adverse cardiac events (MACEs) in non-diabetic patients admitted for acute decompensated heart failure. The purpose of this research was to examine the long-term prognosis of acute decompensated heart failure (ADHF) in non-diabetic persons who had increased blood glucose levels, i.e., stress hyperglycemia, at the time of their ADHF hospitalization. The research involved 650 non-diabetic patients. Based on their admission stress hyperglycemia, they were divided into two groups.ie with and without (SHGL). The two groups' one-year outcomes for major adverse cardiac events (MACEs) were compared, and key predictors of MACEs were discovered. For statistical analysis, the two-tailed Mann-Whitney U test, Fisher's exact test, and binary logistic regression analysis were utilized. SHGL was found in 353 (54.3%) individuals. It was more frequent in men than in women. About 27% of patients with SHGL had previously been admitted for ADHF. Almost 62% were hypertensive, whereas 14 % had CKD. MACEs were significantly predicted by SHGL, HTN, prior hospitalization for ADHF, CKD, and cardiogenic shock upon admission. SHGL at the time of ADHF admission, independent of DM status, may be a predictive indication of MACEs.

Keywords: stress hyperglycemia, acute heart failure, major adverse cardiac events, MACEs

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Authors: Abraham J. Domb

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Nearly every eye disorder and treatment of post operated eyes evolve around ocular drug delivery. Most ocular diseases are treated with repeated topical applications administered as eye drops. Various attempts have been made to improve drug bioavailability by increasing both the retention of the drug in the pre-corneal area and the penetration of the drug through the cornea. However, currently marketed products are associated with vision blurring, irritability, patient discomfort, toxicity, low drug bioavailability, manufacturing difficulties and inadequate aqueous stability. It has been suggested to use iontophoresis for the non-invasive delivery of drugs. The iontophoretic device is composed of a control panel, two electrodes, a cylindrical well for the insertion of a disposable hydrogel, and a disposable hydrogel pellet. The drug-loaded hydrogel is attached to a cylindrical well at the edge of the electrode of the device and placed onto the eye. The device applies a variable electrical current that can vary from 0.1 mA to 1.5 mA for pre-set periods from 10 seconds to 300 seconds. The iontophoretic device developed in the lab was found to be effective in the delivery of the drugs: gentamicin, water-soluble steroids, and various anticancer agents. When testing in rabbits for safety, the device was considered to be non-toxic and effective.

Keywords: iontophoresis, eye disorder, drug delivery, hydrogel

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Authors: Fouzia Perveen, Rumana Qureshi

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The presently studied twelve anticancer drugs are the cytotoxic agents which inhibit the replication of DNA and activity of enzymes involved in DNA replication namely topoisomerase-II, polymerase and helicase and have shown remarkable anticancer activity in clinical trials. In this study, we performed molecular docking studies of twelve antitumor drugs against DNA and DNA enzymes in the presence and absence of ascorbic acid (AA) and developed the quantitative structure-activity relationship (QSAR) model for anticancer activity screening. A number of electronic and steric descriptors were calculated using MOE software package. QSAR was established showing a correlation of binding strength with various physicochemical descriptors. Out of these twelve, eight cytotoxic drugs were tested on Non-Small Cell Lung Cancer cell lines (H-157 and H-1299) in the absence and presence of ascorbic acid and experimental IC50 values were calculated. From the docking studies, binding constants were calculated indicating the strength of drug-DNA and drug-enzyme complex formation and it was correlated to the IC50 values (both experimental and theoretical). These results can offer useful references for directing the molecular design of DNA enzyme inhibitor with improved anticancer activity.

Keywords: ascorbic acid, binding constant, cytotoxic agents, cell culture, DNA, DNA enzymes, molecular docking

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Authors: Seyran Naghdi

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Background: Orphan drug development is limited by very high costs attributed to the research and development and small size market. How health policymakers address this challenge to consider both supply and demand sides need to be explored for directing the policies and plans in the right way. The price is an important signal for pharmaceutical companies’ profitability and the patients’ accessibility as well. Objective: This study aims to find out the orphan drugs' price-setting patterns and approaches in health systems through a systematic review of the available evidence. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach was used. MedLine, Embase, and Web of Sciences were searched via appropriate search strategies. Through Medical Subject Headings (MeSH), the appropriate terms for pricing were 'cost and cost analysis', and it was 'orphan drug production', and 'orphan drug', for orphan drugs. The critical appraisal was performed by the Joanna-Briggs tool. A Cochrane data extraction form was used to obtain the data about the studies' characteristics, results, and conclusions. Results: Totally, 1,197 records were found. It included 640 hits from Embase, 327 from Web of Sciences, and 230 MedLine. After removing the duplicates, 1,056 studies remained. Of them, 924 studies were removed in the primary screening phase. Of them, 26 studies were included for data extraction. The majority of the studies (>75%) are from developed countries, among them, approximately 80% of the studies are from European countries. Approximately 85% of evidence has been produced in the recent decade. Conclusions: There is a huge variation of price-setting among countries, and this is related to the specific pharmacological market structure and the thresholds that governments want to intervene in the process of pricing. On the other hand, there is some evidence on the availability of spaces to reduce the very high costs of orphan drugs development through an early agreement between pharmacological firms and governments. Further studies need to focus on how the governments could incentivize the companies to agree on providing the drugs at lower prices.

Keywords: orphan drugs, orphan drug production, pricing, costs, cost analysis

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Authors: M. A. Ferhat, M. N. Boukhatem, F. Chemat

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Since the available anti-inflammatory drugs exert an extensive variety of side effects, the search for new anti-inflammatory agents has been a priority of pharmaceutical industries. The aim of the present study was to assess the anti-inflammatory activities of the essential oil of rose geranium (RGEO). The chemical composition of the RGEO was investigated by gas chromatography. The major components were citronellol (29.13%), geraniol (12.62%), and citronellyl formate (8.06%). In the carrageenan induced paw edema, five different groups were established and RGEO was administered orally in three different doses. RGEO (100 mg/kg) was able to significantly reduce the paw edema with a comparable effect to that observed with diclofenac, the positive control. In addition, RGEO showed a potent anti-inflammatory activity by topical treatment in the method of croton oil-induced ear edema. When the dose was 5 or 10 ml of RGEO per ear, the inflammation was reduced by 73 and 88%, respectively. This is the first report to demonstrate a significant anti-inflammatory activity of Algerian RGEO. In addition, histological analysis confirmed that RGEO inhibited the inflammatory responses in the skin. Our results indicate that RGEO may have significant potential for the development of novel anti-inflammatory drugs with improved safety profile.

Keywords: anti-inflammatory effect, carrageenan, citronellol, histopathology, Rose geranium

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Authors: Meenu Mehta, Munish Garg

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The use of oral anticancer drugs from AYUSH system of medicine is widely increased among the society due to their low cost, enhanced efficacy, increased patient preference, lack of inconveniences related to infusion and they provide an opportunity to develop chronic treatment regimens. However, oral delivery of these drugs usually laid down by the limited bioavailability of the drug, which is associated with a wide variation. As most of the cytotoxic agents have a narrow therapeutic window and are dosed at or near the maximum tolerated dose, a wide variability in the bioavailability can negatively affect treatment result. It is estimated that 40% of active substances are poorly soluble in water. The improvement of bio-availability of drugs with such properties presents one of the greatest challenges in drug formulations. There are several techniques reported in literature. Among all these Self Emulsifying Drug Delivery System (SEDDS) has gained more attention due to enhanced oral bio-availability enabling a reduction in dose. Thus, SEDDS anticancer drugs will have the increased bioavailability and efficacy. These dosage form will provide societal benefit in a cost-effective manner as compared to other oral dosage forms. Present study reflects on the formulation strategies as SEDDS for oral anticancer agents of AYUSH system for enhanced bioavailability with proven efficacy by cancer cell lines.

Keywords: anticancer agents, AYUSH system, bioavailability, SEDDS

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Authors: S. Kurian, S. Satpathy, S. K. Gupta, S. Arya, D. K. Sharma

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Advances in the use of health care technology have resulted in increased adverse events (AEs) related to the use of medical devices. The study focused on the existing reporting systems. This study was conducted in a tertiary care public sector hospital. Devices included Syringe infusion pumps, Cardiac monitors, Pulse oximeters, Ventilators and Defibrillators. A total of 211 respondents were recruited. Interviews were held with 30 key informants. Medical records were scrutinized. Relevant statistical tests were used. Resident doctors reported maximum frequency of AEs, followed by nurses; and least by consultants. A significant association was found between the cadre of health care personnel and awareness that the patients and bystanders have a risk of sustaining AE. Awareness regarding reporting of AEs was low, and it was generally done verbally. Other critical findings are discussed in the light of the barriers to reporting, reasons for non-compliance, recording system, and so on.

Keywords: adverse events, health care technology, medical devices, public sector hospital, reporting systems

Procedia PDF Downloads 292